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[ "Wrestling at the 2012 Summer Olympics – Men's Greco-Roman 84 kg\n\nMen's Greco-Roman 84 kg competition at the 2012 Summer Olympics in London, United Kingdom, took place on 6 August at ExCeL London.", "\nThis Greco-Roman wrestling competition consists of a single-elimination tournament, with a repechage used to determine the winner of two bronze medals. ", "The two finalists face off for gold and silver medals. ", "Each wrestler who loses to one of the two finalists moves into the repechage, culminating in a pair of bronze medal matches featuring the semifinal losers each facing the remaining repechage opponent from their half of the bracket.", "\n\nEach bout consists of up to three rounds, lasting two minutes apiece. ", "The wrestler who scores more points in each round is the winner of that rounds; the bout ends when one wrestler has won two rounds (and thus the match).", "\n\nSchedule\nAll times are British Summer Time (UTC+01:00)\n\nResults\nLegend\nF — Won by fall\n\nFinal\n\nTop half\n\nBottom half\n\nRepechage\n\nFinal standing\n\nReferences\n\nPage 75\n\nCategory:Wrestling at the 2012 Summer Olympics" ]
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[ "Q:\n\nPublish Q/A statistics over the years: is Stack Overflow quality deteriorating?", "\n\nIt would be interesting to see the public statistics of (un) answered questions on Stack Overflow during last 2-3-4 years. ", "How many questions are being answered, per period of time? ", "Which percent of them were answered by topic starter? ", "And so on.", "\nI judge by my own participation. ", "I rarely use Stack Overflow, only if I'm completely stuck with the problem. ", "Back in 2012-2014 most of my questions at least attracted attention and users were really helpful. ", "It encouraged to help other people as well. ", "Nowadays among 20 last questions only one was answered correctly by other user, several questions were answered by myself, the rest just left without attention.", "\nHave I become a more boring person since 2012 so that I can't clearly explain my problem, or has the Stack Overflow community changed?", "\nI know Stack Overflow had Data Mining team, it would be interesting to see some data on public.", "\n\nA:\n\nLet's look at (one way to measure) how posts are received: what percentage of posts had positive, negative or zero scores:\n\nFor questions only it looks similar, but worse:\n\nWe should also look at the number of posts, because the number of questions can affect how people vote (very directly in terms of the number of zero-scored posts, but also elsewhere). ", "But considering the fact that the number of posts per year hasn't changed that much since 2013, this isn't all that relevant. ", "Although that might raise the question of why it hasn't changed much, which may or may not have something to do with quality.", "\n\nThe pretty constant decline in upvoted posts and increase in downvoted posts leads me to conclude that either (or both):\n\nPeople are more critical\nQuality is on the decline\n\nMy own anecdotal evidence is in line with this (that both of the above are true).", "\nNote, however, that this doesn't mean Stack Overflow will go up in flames any time soon - these trends could keep going for many years before things would get particularly bad, or they could very well start naturally evening out at some point, not to mention that Stack Overflow staff could make changes to address this.", "\n\nThere are many other factors one can look at. ", "This one seemed to provide a reasonable amount of insight while being quite simple to analyse.", "\nNote that these are just a count of posts, not a sum of scores - the latter would heavily favour older posts, while one might assume the former would not change much over time.", "\nThe above are taken from the PostsWithDeleted table, so should include deleted posts, although I can't comment on whether or not there might be some posts that are excluded from this.", "\n\n" ]
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[ "Russian in Bashkortostan\n\nRussian in Bashkortostan - Russian population of Bashkortostan, which numbered in the 2010 census - 1,432,906 people (35.19% of the population). ", "The non-Russian population of the Republic is 64.81%. ", "It is 10th place among the regions of Russia (following Chechnya, Ingushetia, Dagestan, Kabardino-Balkaria, Karachay-Cherkessia, North Ossetia, Kalmykia, Tuva and Chuvashia).", "\n\nHistory \nThe first Russian settlements in the Urals were: \n1586, Ufa, \n1591 Osa \n1645, Menzelinsk \n1667 Birsk \nAround these points began to appear all the villages of Russian peasants.", "\n\nRussian nationalism in Bashkortostan \nIn Bashkortostan, manifested in different forms Russian nationalism. ", "\n\nThe most terrible tragedy in the history of Russian colonization of the republic is Seyantus tragedy. ", "When in 1736 in Seyantus f the government team A. I. Tevkelev was shot and slaughtered with spears and bayonets about 1 thousand residents of the village, and 105 men were burned in the barn.", "\n\nImplication: \n The country is not implemented Self-determination: no training in the Bashkir language in high school, there is no scientific apparatus in the Bashkir language. ", "Given that all the nations of Europe with a population over one million people have realized this right. ", "\n Failure to study the Bashkir language, as a form of nationalism \n Refusal of registration plates, pointers to official languages (in Vol. ", "H. President of Russia in Ufa) \n Carrying Russian marches. ", "\n Representation of the Russian people as the most disadvantaged in their rights: \"Now we see that the Bashkir people have their own national republic and the Russian people have nothing». ", "\n Failure to state awards of the Republic \nSo the head of Sobor Russian Bashkortostan Timothy Azarov in 2012 publicly renounced the main state awards of the Republic - Order Salavat Yulaev:\n\nReferences \n\n Kuzeev RG 'peoples of the Middle Volga and Southern Urals. ", "Ethnogenetic view of history. - ", "M., 1992. ", "\n Russian Bashkortostan. ", "History and culture. - ", "Ufa, 2003. ", "\n Murzabulatov MV 'Russian Bashkortostan Bashkortostan // Panorama. - ", "Ufa, 2008.", "\n\nExternal links \nhttp://www.vatandash.ru/index.php?article=2084\n\nCategory:Ethnic groups in Russia" ]
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[ "A few months ago a paper by Jim Houston and Bob Dean in the Journal of Coastal Research (JCR) cast doubt on whether global sea level rise has accelerated over the past century or so. ", "As things go these days, ‘climate sceptics’ websites immediately heralded this as a “bombshell”. ", "A rebuttal by myself and Martin Vermeer has now been published in JCR.", "\n\n\n\nThe keystone of the argument by Houston & Dean is the fact that a prominent global sea level reconstruction (Church & White 2006) shows no acceleration since 1930. ", "Which raises the question: why 1930, given the sea level data set starts in 1870? ", "The reason becomes immediately evident when looking at the acceleration starting from any arbitrary date (Fig. ", "1).", "\n\n\n\nFigure 1. ", "Acceleration of sea-level rise (i.e., twice the quadratic coefficient) from different starting years up to 2001 in the global tide gauge data set of Church and White (2006; red line with uncertainty band). ", "Note that after ~1960 the calculation gets excessively ‘noisy’ because the time interval gets too short to robustly compute acceleration. ", "I graphed this right away after reading the Houston & Dean paper, and a few days later Tamino independently came up with a similar plot – it’s the obvious thing to do. ", "The blue line shows the same quantity from the sea-level hindcast of Vermeer & Rahmstorf (2009) computed from global temperature data.", "\n\nAround 1930 we see a unique minimum in the acceleration curve – I will explain the cause of this shortly. ", "Other start dates either before or after this minimum show positive acceleration. ", "Picking 1930 for this analysis is thus a classic cherry-pick, and according to the authors that is no accident. ", "They write in the paper: ‘Since the worldwide data of Church and White (2006)…appear to have a linear rise since around 1930, we analyzed the period 1930 to 2010.’ ", "The interval was thus hand-picked to show a linear rise rather than acceleration.", "\n\nConnection to temperature\n\nHouston & Dean use their result to question the future acceleration of sea level rise predicted by Vermeer & Rahmstorf (2009) for the 21st Century as a consequence of global warming. ", "They argue that the 1930s acceleration minimum calls into question the semi-empirical link between global temperature and global sea level proposed by us in that paper. ", "However, it is clear they never bothered to check this, because quite the opposite is the case: our semi-empirical formula predicts this acceleration minimum, as the graph above shows. ", "As it turns out, this is an expected outcome of the mid-20th-Century plateau in global temperature.", "\n\nIf one subtracts out the non-climatic sea level change due to water stored in artificial reservoirs on land, as we did in Vermeer & Rahmstorf (2009), then the agreement between the acceleration curve predicted from global temperature with the actually observed curve is even better (graph below). ", "Thus, the 1930s acceleration minimum pointed out by Houston & Dean supports our approach and projections rather than challenging them.", "\n\n\n\nFigure 2. ", "The same as Figure 1, but here the sea-level data are corrected for water storage in artificial reservoirs (Chao, Wu, and Li, 2008).", "\n\nRegarding our projections of future sea level rise, Houston & Dean write:\n\nit is not clear that the acceleration necessary to achieve these comparatively large projected rises in mean sea level over the course of the 21st century is evident in tide-gauge records.", "\n\nThat is a puzzling statement. ", "Why would the acceleration we expect only for the 21st Century already show up in tide gauge records of the 20th? ", "Since we expect a temperature rise to cause an acceleration of sea level rise, the acceleration in the 20th Century (which has seen only 0.7 ºC of global warming) must obviously be much smaller than that expected for the 21st Century, for scenarios of a many times greater warming.", "\n\nFurther issues raised by Houston & Dean\n\nHouston and Dean raise a number of further points (beyond the Church & White global data set) on which we just cite the brief summary statements and refer the readers to our journal comment for more detail:\n\nMany U.S. tide gauges show a deceleration; since 1930, most of them do.", "\n\nHowever, again, 1930 is a special choice, and U.S. tide gauges only provide a regional signal, not a global one.", "\n\nThe authors’ extension of the Douglas (1992) sea-level compilation shows a sea-level deceleration for 1905–2010.", "\n\nBut this data set is not a properly area-weighted global average but is instead highly biased to the Northern Hemisphere. ", "It is known that the twentieth-century acceleration is largely found in the Southern Hemisphere (Merrifield, Merrifield, and Mitchum, 2009), and the only two Southern Hemisphere groups in the extended Douglas data set indeed show acceleration.", "\n\nDecadal trends in tide gauge compilations show large variations over the full record, and the most recent decadal trends are not unusual.", "\n\nHowever, these variations in decadal tide gauge trends are not a climate signal but rather are dominated by sampling noise due to the inadequate number of tide gauges.", "\n\n\n\nThe satellite altimeter record shows a slight deceleration since 1993.", "\n\nBut this time interval is far too short to draw any conclusions.", "\n\n\n\nIn our comment we conclude:\n\nNone of this supports a lack of acceleration in global sea-level rise, as compared to what is expected from global warming. ", "Outside a few starting years around 1930, global sea-level reconstructions robustly show a modern acceleration of sea-level rise in conjunction with global warming.", "\n\nFor the evidence, just have a look at some of the references listed below.", "\n\np.s. ", "I just see that JCR also carries a reply by Houston & Dean to our comment. ", "This largely focuses on our supposedly “selective” use of data, because we show the acceleration of sea level rise ‘only’ for starting years from 1870 (the start of the data set) to 1970 (after which the computation is too noisy to be meaningful by anyone’s standard). ", "This is slightly ironic given that Houston & Dean focused only on the rather unique start year 1930. ", "Houston and Dean further argue that the data already become too noisy around 1940 because “decadal fluctuations begin to dominate records shorter than about 60 years, and accelerations become increasingly meaningless for starting years in Figure 1 greater than about 1940”. ", "We disagree: while this may be true for individual records it is not true for the global sea level reconstruction shown. ", "The 2-sigma range and the fact that the curve is smooth until then shows it is meaningful up to about 1960; we continued the graph up to 1970 in order to show (rather than just claim in the text) how the uncertainty explodes after 1960. ", "In any case, by showing the plot until 1970, we allow readers to see the full potentially meaningful range and judge for themselves whether they see any significant difference between the data and our model. ", "That our model is somehow called into question by the observed sea level acceleration was, after all, a key claim in Houston & Dean’s original paper.", "\n\nHouston & Dean excuse the strong northern-hemisphere bias introduced by their simple averaging by saying that “this criticism would apply to any study of sea-level rise”. ", "That is not true; the sea level data set we use (Church and White 2006) and also the temperatures (GISS) use an area-weighted averaging scheme that makes sure the northern and southern hemispheres are properly represented in proportion to their surface areas, regardless of the data density.", "\n\nBut at least on one thing we agree. ", "As Houston & Dean state in their final sentence, we indeed predict a much larger acceleration of sea level rise in the 21st Century than is observed in the 20th Century. ", "That is a direct logical consequence of the fact that we expect much larger warming in the 21st than in the 20th.", "\n\nUpdate 24 July: A related case of “lack of acceleration” – also from the Journal of Coastal Research – is expertly treated by Tamino here: How Not to Analyze Tide Gauge Data. ", "It does raise some questions about the quality of peer review at JCR.", "\n\nLink\n\nPIK sea level pages\n\nReferences\n\nChurch, J. A., N. J. White, 2006: A 20th century acceleration in global sea-level rise. ", "Geophysical Research Letters, 33, L01602.", "\n\nDouglas, B. C., 1992: Global sea level acceleration. ", "journal of Geophysical Research-Oceans, 97, 12699-12706.", "\n\nHouston, J., R. Dean, 2011: Sea-level acceleration based on US tide gauges and extensions of previous global-gauge analysis. ", "Journal of Coastal Research.", "\n\nMerrifield, M. A., S. T. Merrifield, and G. T. Mitchum, 2009: An Anomalous Recent Acceleration of Global Sea Level Rise. ", "Journal of Climate, 22, 5772-5781.", "\n\nRahmstorf, S. and M. Vermeer, 2011: Discussion of: Houston, J.R. and Dean, R.G., 2011. ", "Sea-Level Acceleration Based on U.S. Tide Gauges and Extensions of Previous Global-Gauge Analyses. ", "Journal of Coastal Research 27, 784–787.", "\n\nVermeer, M., S. Rahmstorf, 2009: Global Sea Level Linked to Global Temperature. ", "Proceedings of the National Academy of Science of the USA, 106, 21527-21532." ]
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[ "//\n// Copyright 2017, Sander van Harmelen\n//\n// Licensed under the Apache License, Version 2.0 (the \"License\");\n// you may not use this file except in compliance with the License.", "\n// You may obtain a copy of the License at\n//\n// http://www.apache.org/licenses/LICENSE-2.0\n//\n// Unless required by applicable law or agreed to in writing, software\n// distributed under the License is distributed on an \"AS IS\" BASIS,\n// WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n// See the License for the specific language governing permissions and\n// limitations under the License.", "\n//\n\npackage gitlab\n\nimport (\n\t\"bytes\"\n\t\"fmt\"\n\t\"time\"\n)\n\n// SnippetsService handles communication with the snippets\n// related methods of the GitLab API.", "\n//\n// GitLab API docs: https://docs.gitlab.com/ce/api/snippets.html\ntype SnippetsService struct {\n\tclient *Client\n}\n\n// Snippet represents a GitLab snippet.", "\n//\n// GitLab API docs: https://docs.gitlab.com/ce/api/snippets.html\ntype Snippet struct {\n\tID int `json:\"id\"`\n\tTitle string `json:\"title\"`\n\tFileName string `json:\"file_name\"`\n\tDescription string `json:\"description\"`\n\tAuthor struct {\n\t\tID int `json:\"id\"`\n\t\tUsername string `json:\"username\"`\n\t\tEmail string `json:\"email\"`\n\t\tName string `json:\"name\"`\n\t\tState string `json:\"state\"`\n\t\tCreatedAt *time.", "Time `json:\"created_at\"`\n\t} `json:\"author\"`\n\tUpdatedAt *time.", "Time `json:\"updated_at\"`\n\tCreatedAt *time.", "Time `json:\"created_at\"`\n\tWebURL string `json:\"web_url\"`\n\tRawURL string `json:\"raw_url\"`\n}\n\nfunc (s Snippet) String() string {\n\treturn Stringify(s)\n}\n\n// ListSnippetsOptions represents the available ListSnippets() options.", "\n//\n// GitLab API docs: https://docs.gitlab.com/ce/api/snippets.html#list-snippets\ntype ListSnippetsOptions ListOptions\n\n// ListSnippets gets a list of snippets.", "\n//\n// GitLab API docs: https://docs.gitlab.com/ce/api/snippets.html#list-snippets\nfunc (s *SnippetsService) ListSnippets(opt *ListSnippetsOptions, options ...RequestOptionFunc) ([]*Snippet, *Response, error) {\n\treq, err := s.client.", "NewRequest(\"GET\", \"snippets\", opt, options)\n\tif err !", "= nil {\n\t\treturn nil, nil, err\n\t}\n\n\tvar ps []*Snippet\n\tresp, err := s.client.", "Do(req, &ps)\n\tif err !", "= nil {\n\t\treturn nil, resp, err\n\t}\n\n\treturn ps, resp, err\n}\n\n// GetSnippet gets a single snippet\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#single-snippet\nfunc (s *SnippetsService) GetSnippet(snippet int, options ...RequestOptionFunc) (*Snippet, *Response, error) {\n\tu := fmt.", "Sprintf(\"snippets/%d\", snippet)\n\n\treq, err := s.client.", "NewRequest(\"GET\", u, nil, options)\n\tif err !", "= nil {\n\t\treturn nil, nil, err\n\t}\n\n\tps := new(Snippet)\n\tresp, err := s.client.", "Do(req, ps)\n\tif err !", "= nil {\n\t\treturn nil, resp, err\n\t}\n\n\treturn ps, resp, err\n}\n\n// CreateSnippetOptions represents the available CreateSnippet() options.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#create-new-snippet\ntype CreateSnippetOptions struct {\n\tTitle *string `url:\"title,omitempty\" json:\"title,omitempty\"`\n\tFileName *string `url:\"file_name,omitempty\" json:\"file_name,omitempty\"`\n\tDescription *string `url:\"description,omitempty\" json:\"description,omitempty\"`\n\tContent *string `url:\"content,omitempty\" json:\"content,omitempty\"`\n\tVisibility *VisibilityValue `url:\"visibility,omitempty\" json:\"visibility,omitempty\"`\n}\n\n// CreateSnippet creates a new snippet. ", "The user must have permission\n// to create new snippets.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#create-new-snippet\nfunc (s *SnippetsService) CreateSnippet(opt *CreateSnippetOptions, options ...RequestOptionFunc) (*Snippet, *Response, error) {\n\treq, err := s.client.", "NewRequest(\"POST\", \"snippets\", opt, options)\n\tif err !", "= nil {\n\t\treturn nil, nil, err\n\t}\n\n\tps := new(Snippet)\n\tresp, err := s.client.", "Do(req, ps)\n\tif err !", "= nil {\n\t\treturn nil, resp, err\n\t}\n\n\treturn ps, resp, err\n}\n\n// UpdateSnippetOptions represents the available UpdateSnippet() options.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#update-snippet\ntype UpdateSnippetOptions struct {\n\tTitle *string `url:\"title,omitempty\" json:\"title,omitempty\"`\n\tFileName *string `url:\"file_name,omitempty\" json:\"file_name,omitempty\"`\n\tDescription *string `url:\"description,omitempty\" json:\"description,omitempty\"`\n\tContent *string `url:\"content,omitempty\" json:\"content,omitempty\"`\n\tVisibility *VisibilityValue `url:\"visibility,omitempty\" json:\"visibility,omitempty\"`\n}\n\n// UpdateSnippet updates an existing snippet. ", "The user must have\n// permission to change an existing snippet.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#update-snippet\nfunc (s *SnippetsService) UpdateSnippet(snippet int, opt *UpdateSnippetOptions, options ...RequestOptionFunc) (*Snippet, *Response, error) {\n\tu := fmt.", "Sprintf(\"snippets/%d\", snippet)\n\n\treq, err := s.client.", "NewRequest(\"PUT\", u, opt, options)\n\tif err !", "= nil {\n\t\treturn nil, nil, err\n\t}\n\n\tps := new(Snippet)\n\tresp, err := s.client.", "Do(req, ps)\n\tif err !", "= nil {\n\t\treturn nil, resp, err\n\t}\n\n\treturn ps, resp, err\n}\n\n// DeleteSnippet deletes an existing snippet. ", "This is an idempotent\n// function and deleting a non-existent snippet still returns a 200 OK status\n// code.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#delete-snippet\nfunc (s *SnippetsService) DeleteSnippet(snippet int, options ...RequestOptionFunc) (*Response, error) {\n\tu := fmt.", "Sprintf(\"snippets/%d\", snippet)\n\n\treq, err := s.client.", "NewRequest(\"DELETE\", u, nil, options)\n\tif err !", "= nil {\n\t\treturn nil, err\n\t}\n\n\treturn s.client.", "Do(req, nil)\n}\n\n// SnippetContent returns the raw snippet as plain text.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#snippet-content\nfunc (s *SnippetsService) SnippetContent(snippet int, options ...RequestOptionFunc) ([]byte, *Response, error) {\n\tu := fmt.", "Sprintf(\"snippets/%d/raw\", snippet)\n\n\treq, err := s.client.", "NewRequest(\"GET\", u, nil, options)\n\tif err !", "= nil {\n\t\treturn nil, nil, err\n\t}\n\n\tvar b bytes.", "Buffer\n\tresp, err := s.client.", "Do(req, &b)\n\tif err !", "= nil {\n\t\treturn nil, resp, err\n\t}\n\n\treturn b.Bytes(), resp, err\n}\n\n// ExploreSnippetsOptions represents the available ExploreSnippets() options.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#explore-all-public-snippets\ntype ExploreSnippetsOptions ListOptions\n\n// ExploreSnippets gets the list of public snippets.", "\n//\n// GitLab API docs:\n// https://docs.gitlab.com/ce/api/snippets.html#explore-all-public-snippets\nfunc (s *SnippetsService) ExploreSnippets(opt *ExploreSnippetsOptions, options ...RequestOptionFunc) ([]*Snippet, *Response, error) {\n\treq, err := s.client.", "NewRequest(\"GET\", \"snippets/public\", nil, options)\n\tif err !", "= nil {\n\t\treturn nil, nil, err\n\t}\n\n\tvar ps []*Snippet\n\tresp, err := s.client.", "Do(req, &ps)\n\tif err !", "= nil {\n\t\treturn nil, resp, err\n\t}\n\n\treturn ps, resp, err\n}\n" ]
{ "pile_set_name": "Github" }
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[ "Q:\n\nConfusion about the nature, defininition, and subject of study of Epistemology, Gnosiology and Phillosophy of Science\n\nI am confused with the terms and the branches of phillosophy.", "\nHere is an example where all 3 terms were used.", "\nI always though phillosophy of science and epistemology were the exact same thing while gnosiology was the more idiomatic term used in Greek. ", "As in it would be unidiomatic to say Epistemology instead of Gnosiology in the Greek language.", "\nGnosiology would be simply the \"translation\" of Epistemology.", "\nAll 3 terms would be equivalent with absolutely no difference in nuance.", "\nWhat is the difference between Epistemology, Gnosiology, and Phillosophy of Science?", "\n\nA:\n\nEpistemology is the study of what can be known and how, in a truly abstract sense, not so much tied to practices, but to foundations. ", " It is an ordinary subfield of basic philosophy.", "\nPhilosophy of Science as a noted discipline is very new, arising after the Scientific Revolution in Europe. ", " In modern study it is often merged with History of Science, following the dictum that, particularly in this case, 'history without philosophy is blind and philosophy without history is empty'. ", " It is dedicated to how people actually do science in particular, often as contrasted with how science describes itself and recounts its own history, and is generally not about theoretical foundations.", "\nGnosiology is theoretically a broader term, but not so much any more. ", " It was introduced by Orthodox Christians as form of traditional epistemology with a provision for revealed knowledge. ", " This sense is sometimes used purposely today by commentators like Quakers who place high regard upon inspiration (or 'experiment' in the archaic form) as a form of knowledge. ", " (But also because we just love to be quaint and quirky.)", "\nThe root moved from 'episteme', 'certain', related to 'ascertain', to 'gnosis', a more general term for 'knowing', because revealed knowledge can, almost by definition, not be 'ascertained' -- it must be validated in different ways, through pedigree or mystical experience.", "\nAttempts have been made to revive it to apply to fields like aesthetics, which also lack the kind of standards that can be 'ascertained' but where things can still be known. ", " But few Western writers adopted the term.", "\nEvidently this move from Epistemology to Gnosiology stuck in the East and Gnosiology is the popular Greek term for Epistemology among Soviet and post-Soviet philosophical writers. ", " This usage has drifted back to the West as a synonym and not as something distinct from Epistemology.", "\n\n" ]
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[ "1. ", "Field of the Invention\nThe present invention relates to an ink jet printing head adapted for use in an ink jet printer and a method for producing the same, and more particularly to an ink jet printing head in which, in forming nozzles and liquid chamber, the frame of the liquid chamber is constituted by the combination of walls having a width substantially equal to that of the nozzle wall, thereby improving adhesion of a heater board and a top plate and also improving the stability of manufacture, and a method for producing such ink jet printing head.", "\n2. ", "Related Background Art\nFor use in the ink jet printing head there have been proposed nozzles of various shapes, one of which will be explained with reference to FIG. ", "6.", "\nReferring to FIG. ", "6, a top plate 101 is formed from a silicon wafer which is cut and polished in such a manner that the upper face is constituted by the (110) crystalline plane. ", "There are also shown a penetrating hole 102 constituting a liquid chamber or an ink reservoir, and a groove 103 for an ink discharging nozzle.", "\nA silicon chip 108 is provided with a plurality of heat generating members (heaters) 109 and will be hereinafter called a heater board. ", "The top plate 101 and the heater board 108 are adhered in a direction shown in FIG. ", "6 to form oblong nozzles between nozzles 103 and the surface of the heater board 108. ", "In such adhering operation, the positions of both components are precisely adjusted in such a manner that a heater 109 is contained in each nozzle. ", "Ink is supplied from an unrepresented ink tank, then guided to an ink liquid chamber 102 and reaches the interior of the nozzles 103. ", "The heater board 108 is controlled by an unrepresented control circuit and each heater 109 is energized according to the print data. ", "The above-mentioned control circuit may be provided on the heater board or formed on another substrate, and will not be explained further as it is not related to the principle of the present invention.", "\nThe heater 109 energized according to the print data generates heat, thereby heating the ink in the corresponding nozzle. ", "The heated ink boils above a certain critical temperature, thus generating a bubble. ", "The generated bubble grows within a short time of several microseconds and gives an impact force to the ink, whereby a part of the ink is strongly pushed out and lands on a printing medium such as paper. ", "A printed image is obtained by repeating this process.", "\nIn the following there will be explained the method of producing the top plate, with reference to FIGS. ", "7A to 7H. In these drawings, the views at the right-hand side are those of the top plate 101 seen from the lower side (nozzle side) while those at the left-hand side are cross-sectional views of the top plate cut along a plane in the discharging direction.", "\nFIG. ", "7A illustrates a silicon wafer. ", "FIG. ", "7B shows the formation of an oxide film. ", "FIG. ", "7C shows patterning of SiO.sub.2. ", "FIG. ", "7D shows formation of a SiN film. ", "FIG. ", "7E shows the patterning of SiN. FIG. ", "7F shows anisotropic etching of Si, wherein a numeral 102 indicates a liquid chamber. ", "FIG. ", "7G shows elimination of SiN. FIG. ", "7H shows anisotropic etching of Si, wherein a numeral 103 indicates a nozzle.", "\nFIG. ", "7A shows a silicon (Si) wafer 105 used as the material for forming the nozzle members, having a crystalline orientation <110> on the surface and <111> in the longitudinal direction of the nozzle. ", "Both sides of the silicon wafer 105 are subjected to the formation of a thin silicon dioxide film 106 of a thickness of about 1 .mu.m as shown in FIG. ", "7B, by thermal oxidation or CVD (chemical vapor deposition). ", "The silicon dioxide layer 106 serves as a mask layer in anisotropic etching of silicon. ", "Then, with the ordinary photolithographic process, the silicon dioxide layer 106 is patterned into the shape of nozzles and liquid chamber on one side (lower face in the illustration) and into the shape of the liquid chamber on the other side (FIG. ", "7C). ", "Then, on the nozzle forming side, a silicon nitride layer 107 is formed for example by CVD (FIG. ", "7D) and is patterned into the shape of the liquid chamber (FIG. ", "7E).", "\nThe wafer is then subjected to anisotropic wet etching by immersion in etching liquid such as 22% solution of TMAH (tetramethylammonium hydride) whereby the etching proceeds in exposed areas of silicon on both sides of the wafer, namely according to the shape of the liquid chamber and the etched portions from both sides are eventually connected to form penetrating holes. ", "Then the silicon nitride layer on the nozzle face is eliminated by etching (FIG. ", "7G) to expose the nozzle pattern formed in the silicon dioxide layer 106 in the step shown in FIG. ", "7C, and anisotropic etching is executed again with TMAH whereby a portion corresponding to the nozzle is etched. ", "In this operation, the liquid chamber etched in the step shown in FIG. ", "7F is also further etched, but the shape of the liquid chamber is little affected because the etching time for the nozzle is shorter than that for the liquid chamber. ", "Otherwise it is also possible to shorten the etching time for the liquid chamber in consideration of the etching time required for nozzle etching, thereby eventually obtaining the liquid chamber of the desired shape.", "\nHowever, with the anisotropic etching of the present invention, there can be obtained a nozzle with a rectangular cross section because the <111> plane perpendicular to the wafer surface is present in the ink discharging direction, but, in the longitudinal direction of the nozzle, there is no crystalline plane capable of stopping the etching, so that the wall between the nozzles is overetched in the longitudinal direction to form an acute angle shape. ", "Consequently, in such overetched portion, there inevitably remains the thin silicon dioxide film constituting the mask layer. ", "Such silicon dioxide film alone is removed, without damaging silicon, by blowing pressurized air, eventually containing water, to the wafer. ", "For removing the film of about 1 .mu.m by blowing water with pressurized air, there is only required a pressure of 1 to 20 kgf/cm.sup.2. ", "Otherwise the entire silicon dioxide film may be removed by wet etching employing the mixture of ammonium fluoride and hydrofluoric acid.", "\nThe top plate 108 prepared by the above-described process is shown in FIG. ", "8. ", "In the patterning process for forming the liquid chamber, the both surfaces of the top plate chip are formed in similar shapes, but the pattern at the ink supply side, at the upper surface in FIG. ", "6, may be made smaller at such a level that the penetrating hole is formed by anisotropic etching. ", "In fact a pattern smaller than at the nozzle side is preferred in order to ensure the connection with the unrepresented ink supply member or the strength of the wafer in forming the top plate.", "\nAs explained in the foregoing, anisotropic etching of silicon can be utilized in forming the structure of the top plate, providing high mass producibility since the top plate can be prepared in the state of a wafer. ", "Also the nozzle preparation by photolithographic technology allows to obtain nozzles of a high density with a high precision.", "\nHowever, the conventional method of preparing the top plate has been associated with the following drawbacks because the nozzle walls and the liquid chamber frames are significantly different in width.", "\nIn forming the nozzles by adhering the top plate, principally comprising of silicon, with the heater board, the adhesion is most simply achieved by spraying an adhesive material. ", "This is achieved by spraying, on the surface of the top plate, mist of a resinous adhesive material adjusted in viscosity with diluting liquid and mixed with compressed air. ", "The adhesive comprises a material of high chemical resistance such as polyether amide resin (for example HIMAL supplied by Hitachi Chemical Co.), and is to form a protective film on the inner wall of the nozzle simultaneously with the coating of the adhesive material on the bottom faces of the nozzle walls of the top plate.", "\nHowever, with the progress of the ink jet printer toward the higher image quality with a nozzle density of 360 dpi or higher, the width of the nozzle wall becomes as small as 40 .mu.m or even smaller, and, for a nozzle density of 600 dpi, the width of the nozzle wall becomes as small as 10 .mu.m, which is much smaller than the wall width of the liquid chamber frame. ", "If the adhesive material is spray coated as explained above in such structure, the coated thickness of the adhesive material may fluctuate as shown in FIG. ", "9, depending on the width of the lateral walls constituting the nozzle and that of the lateral walls constituting the liquid chamber. ", "More specifically the thickness d1 of the adhesive material on the nozzle walls becomes smaller than the thickness d2 of the adhesive on the liquid chamber walls because the latter is larger. ", "For example, in case of coating the adhesive material with a thickness of 10 .mu.m on the liquid chamber frame of the larger width, the adhesive can only be coated with a thickness of 2 to 5 .mu.m on the nozzle wall of a width of 10 .mu.m though this value depends to a certain extent on the viscosity of the adhesive. ", "Also if the thickness of the adhesive is reduced, matching the width of the nozzle wall, the thickness becomes relatively difficult to control and may show fluctuation.", "\nSuch fluctuation in the coating thickness of the adhesive results in a fluctuation in the overflowing amount at the adhesion of the substrate. ", "FIG. ", "12A schematically shows the state of adhesion in case the wall width fluctuates. ", "Since the frame wall of the liquid chamber 2 is wider than the nozzle wall 104, a larger amount of the adhesive 110 overflows into the nozzle 103 at the adhering operation. ", "Such overflowing adhesive 110 deforms the shape inside the nozzle 103, thereby deteriorating the ink flow therein or the ink discharging direction therefrom and, if the adhesive sticks on the heat generating member, the heat generating state for ink discharge may be varied to disable the desired ink discharge.", "\nOn the other hand, such fluctuation in the thickness of the adhesive may result in insufficient adhesion on the lateral walls of the nozzle in adhering the top plate and the heater board. ", "Such insufficient adhesion may lead to a crosstalk between the nozzles at the ink discharge or color mixing between the liquid chamber of different colors in case of a color printing head.", "\nFor adhering the substrate, the Japanese Patent Application Laid-open No. ", "60-206657 discloses a technology of forming the nozzle walls and the liquid chamber walls with photosensitive resin on the heater board and adhering the top plate thereon. ", "In order to prevent formation of a closed space at the adhering face between the top plate and the wall, the wall is so formed as to form a space open to the exterior.", "\nIn such configuration, however, since the top plate is coated on its entire surface with the adhesive material and is then adhered onto the walls, the surface of the adhesive is exposed in a part of the nozzle. ", "The surface of the adhesive material is difficult to control and may deform the cross-sectional shape of each nozzle, thus eventually affecting the ink flow therein." ]
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[ "Rectal compliance as a routine measurement: extreme volumes have direct clinical impact and normal volumes exclude rectum as a problem.", "\nThe clinical impact of rectal compliance and sensitivity measurement is not clear. ", "The aim of this study was to measure the rectal compliance in different patient groups compared with controls and to establish the clinical effect of rectal compliance. ", "Anorectal function tests were performed in 974 consecutive patients (284 men). ", "Normal values were obtained from 24 controls. ", "Rectal compliance measurement was performed by filling a latex rectal balloon with water at a rate of 60 ml per minute. ", "Volume and intraballoon pressure were measured. ", "Volume and pressure at three sensitivity thresholds were recorded for analysis: first sensation, urge, and maximal toleration. ", "At maximal toleration, the rectal compliance (volume/pressure) was calculated. ", "Proctoscopy, anal manometry, anal mucosal sensitivity, and anal endosonography were also performed as part of our anorectal function tests. ", "No effect of age or gender was observed in either controls or patients. ", "Patients with fecal incontinence had a higher volume at first sensation and a higher pressure at maximal toleration (P = 0.03), the presence of a sphincter defect or low or normal anal pressures made no difference. ", "Patients with constipation had a larger volume at first sensation and urge (P < 0.0001 and P < 0.01). ", "Patients with a rectocele had a larger volume at first sensation (P = 0.004). ", "Patients with rectal prolapse did not differ from controls; after rectopexy, rectal compliance decreased (P < 0.0003). ", "Patients with inflammatory bowel disease had a lower rectal compliance, most pronounced in active proctitis (P = 0.003). ", "Patients with ileoanal pouches also had a lower compliance (P < 0.0001). ", "In the 17 patients where a maximal toleration volume < 60 ml was found, 11 had complaints of fecal incontinence, and 6 had a stoma. ", "In 31 patients a maximal toleration volume between 60 and 100 ml was found; 12 patients had complaints of fecal incontinence, and 6 had a stoma. ", "Proctitis or pouchitis was the main cause for a small compliance. ", "All 29 patients who had a maximal toleration volume > 500 ml had complaints of constipation. ", "No correlation between rectal and anal mucosal sensitivity was found. ", "Rectal compliance measurement with a latex balloon is easily feasible. ", "In this series of 974 patients, some patient groups showed an abnormal rectal visceral sensitivity and compliance, but there was an overlap with controls. ", "Rectal compliance measurement gave a good clinical impression about the contribution of the rectum to the anorectal problem. ", "Patients with proctitis and pouchitis had the smallest rectal compliance. ", "A maximal toleration volume < 60 ml always led to fecal incontinence, and stomas should be considered for such patients. ", "A maximal toleration volume > 500 ml was only seen in constipated patients, and therapy should be given to prevent further damage to the pelvic floor. ", "Values close to or within the normal range rule out the rectum as an important factor in the anorectal problem of the patient." ]
{ "pile_set_name": "PubMed Abstracts" }
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[ "---\nabstract: 'We report on implementing graph grammars for intelligence analysis in OCaml. ", "Graph grammars are represented as elements of an algebraic data type in OCaml. ", "In addition to algebraic data types, we use other concepts from functional programming languages to implement features of graph grammars. ", "We use type checking to perform graph pattern matching. ", "Graph transformations are defined as implicit coercions derived from structural subtyping proofs, subset types, lambda abstractions, and analytics. ", "An analytic is a general-purpose OCaml function whose output is required to match a graph pattern described by an element of an algebraic data type. ", "By using a strongly-typed language for representing graphs, we can ensure graphs produced from a graph transformation will match a specific schema. ", "This is a high priority requirement for intelligence analysis.'", "\nauthor:\n- |\n [Rod Moten]{}\\\n [Datanova Scientfic, LLC]{}\\\n- |\n [Kemafor Anyanwu-Ogan]{}\\\n [North Carolina State University]{}\\\n- |\n [Sahibi Miranshah]{}\\\n [North Carolina State University]{}\\\nbibliography:\n- '../my-library.bib'\ndate: 'March 19, 2016'\ntitle: Implementing graph grammars for intelligence analysis in OCaml\n---\n\nIntroduction\n============\n\n[10]{}(3.5,14.5)\n\nDISTRIBUTION A. Approved for public release: distribution unlimited.", "\n\n©Datanova Scientific 2016.", "\n\nIntelligence analysis is the process of analyzing known facts about entities, events, and their relationships in order to predict future events and facts about entities. ", "There are many methods and practices for performing intelligence analysis. ", "In the past decade, *link analysis*  has risen as a valuable method for performing intelligence analysis over large-scale heterogeneous data sets. ", "Link analysis is the process of identifying new relationships between entities and events based on existing facts about the entities and events. ", "In link analysis, the intelligence data is often represented as a graph. ", "Edges between nodes represent semantic relationships between nodes. ", "Visually, an analysis performs link analysis by drawing a new edge between two nodes or creating a new node by combining nodes. ", "In other words, the analyst performs transforms on the existing graph to reflect the discovery of new information. ", "A program can use information about the topology or features of the graph to infer new information automatically. ", "For example, an analytic could infer two person nodes are close associates if 85% of their friends-of edges point to the same node. ", "The newly discovered relationship could be represented as a new close-associate-of edge between the two person nodes.", "\n\n*Object-based production* (OBP) is a methodology for treating intelligence data produced from multiple sources as objects in a common language . ", "An object represents an entity or event. ", "The objects could be extracted from data sources of various modalities, such as still imagery, motion imagery, audio, unstructured text, and structured data. ", "Performing link analysis over objects usually requires representing the objects and the relationships between objects as a graph.", "\n\nA graph created from objects represents a knowledge base of all known facts obtained from multiple sources of intelligence. ", "Usually an analyst only needs a portion of these facts when performing an investigation. ", "We call the subgraph containing these facts the *mission graph*. ", "The mission graph may be a transformation of a subgraph of the main graph. ", "The transformation often entails removing edges and attributes that aren’t needed in the mission and condensing multiple relationships into a single relationship.", "\n\nIn this paper, we report on a graph database we created to support extraction of mission graphs using graph grammars. ", "To represent graph grammars, we created a strongly-typed language, called *Flutes*, that we implemented in OCaml. ", "The terms in Flutes represent graphs and the types represent specifications of graphs with the same topology. ", "Graph grammar rules are defined using subset types, lambda abstractions, and analytics. ", "The body of a lambda abstraction is a Flutes term. ", "An analytic is a lambda abstraction whose body can be any OCaml expression that evaluates to a Flutes term.", "\n\nWe demonstrate the value of using concepts from strongly-typed functional programming by showing the following. ", "In , we show how we implemented a graph database for OBP in OCaml. ", "In , we show how constructs from Flutes are used to define graph grammar rules. ", "In , we show how queries over large graphs can be performed efficiently by representing graphs symbolically.", "\n\nFlutes DB {#flutes-section}\n=========\n\nGraphs used in OBP have a specific topology. ", "We call the topology the *linked-object topology*. ", "In the linked-object topology, objects are represented as DAGs. ", "Relationships between objects are represented as DAGs where the root node is the name of the relation and the children are the related objects. ", "A knowledge graph that has the linked-object topology does not have any cycles. ", "Researchers who primarily work with RDF have trouble grasping this concept because cycles are common in RDF graphs. ", "For example, consider the graph in a representing a man named Joe and a woman named Sue who are siblings. ", "This is the common way to present relationships. ", "The edge is used as the relation. ", "As a result, inverse relations will form cycles. ", "Inverse relations can be represented without cycles using the linked-object topology as depicted in b. In b, the blue edge and the red edge represent the first argument and the second argument of the relation, respectively.", "\n\nAnother feature of the linked-object topology not exploited by the RDF community is classifying an edge as an *essential property* or as an *accidental property*. ", "An essential property represents a feature all objects of a specific type must have. ", "However, the value of an essential property may be unknown. ", "For example, birth date is an essential property of every person. ", "Accidental properties may exist for only some objects of a specific type. ", "For example, having a brother is an accidental property of people.", "\n\nSince graphs with the linked-object topology do not have cycles, we can represent them as terms in a strongly-typed language. ", "More specifically, an object and its essential properties can be represented as a record and accidental properties can be represented as $n$-ary predicates. ", "We implemented such a language, which we call Flutes, in OCaml. ", "contains a portion of the definition of Flutes’ abstract syntax as algebraic data type in OCaml. ", "We only show the definition of a fragment of the abstract syntax due to space limitations.", "\n\n type flutes_term =\n | Num of float | Str of string\n | Atom of Taxonomy.concept\n | Record of (Taxonomy.concept * flutes_term) list\n | List of flutes_term list\n | Bottom of Taxonomy.concept\n | Field_Selection of flutes_term * Taxonomy.concept\n | Var_Term of string\n | Term_Alias of string\n \n and flutes_built_in_pred =\n | LessThan | LessThanEqualTo| GreaterThan\n | GreaterThanEqualTo | EqualTo\n \n and flutes_prop_type =\n | Builtin_Pred of flutes_built_in_pred \n * flutes_term list\n | And of flutes_prop_type * flutes_prop_type\n | Or of flutes_prop_type * flutes_prop_type\n | Not of flutes_prop_type\n | Exists_Term of string * flutes_type \n * flutes_prop_type\n | TRUE | FALSE\n | InSequence of flutes_term* flutes_term list\n \n and flutes_type=\n | NumTy | StrTy | ListTy of flutes_type\n | RecordTy of (Ontology.concept * flutes_type) list\n | EnumTy of Ontology.concept list\n | VoidTy\n | SubsetTy of flutes_term * flutes_type \n * flutes_prop_type\n | TyAlias of string\n\nObjects are represented as records in Flutes, that is expressions created with the constructor . ", "Records are terms with a list of fields. ", "The labels of the fields are concepts from a taxonomy. ", "The module encapsulates the taxonomy. ", "The modules defines a method for creating a concepts from a string.", "\n\n mk_concept : string -> concept\n\nalso maintains a total-ordering, an equivalence relation and a join semi-lattice. ", "The equivalence relation and the join semi-lattice can be used to define semantic relationships between concepts. ", "For example, the equivalence relationship can be used to define synonyms of concepts and the join semi-lattice can be used to define hypernyms and hyponyms of concepts. ", "These relations are used in type subsumption, which we describe later in the paper. ", "contains functions for adding pairs to the relations. ", "We omit describing them in detail due to space limitation.", "\n\nPredicates are implemented as records with special labels. ", "These labels indicate the argument position. ", "For example, the logical expression $\\mathrm{nickname}(\\mathrm{``joe\"},\\mathrm{``joseph\"})$ is defined as the record in .", "\n\n\\[predicate-record-eg\\]\n\n Record [(\"nickname\", \n [(Positional_Concept 0, Str \"joe\");\n (Positional_Concept 1, Str \"joseph\")]\n )]\n\nThe elements constructed with are used to create references to terms. ", "In Flutes, terms can be assigned names. ", "These names are used at the arguments of .", "\n\nAssignment of names to terms is performed using a term declaration. ", "Term declarations are performed using the Flutes concrete syntax. ", "We created a parser for the concrete syntax using menhir. ", "Here’s an example term definition.", "\n\n sue_grafton := {\"name\" : \"Sue Grafton\", \n \"dob\" : \"1941-12-07\",\n \"birth-place\" = Kentucky};\n\nThe expression on the left of is the term name. ", "If a term definition is parsed successfully, it stores an S-expression of the term defined by the right of in MongoDB . ", "The term name will be the key of the term in MongoDB.", "\n\nMongoDB is the persistent storage layer of Flutes DB. ", "Flutes DB is the combination of MongoDB, a library for the OCaml top-level and an OCaml standalone program for managing the Flutes terms in MongoDB.", "\n\nThe library for the OCaml top-level environment contains a module named . ", "This modules contains functions for defining Flutes terms and types and for retrieving terms and types from MongoDB. ", "In addition, contains functions for issuing commands to perform type checking, for applying lambda abstractions, and for running analytics.", "\n\nThe module hides the definition of the constructors of the algebraic data types in to ensure Flutes terms and types are well–formed. ", "contains the signatures of some of these functions. ", "For instance, the functions and construct records representing the application of a predicate to term. ", "We can create the term in using as follows.", "\n\n triple (str \"joe\") (str \"joseph\")\n\nThe creates a predicate application term for predicates with various arity. ", "We will use these functions when constructing Flutes terms and Flutes types in the rest of this paper instead of the constructors in .", "\n\n (******* FLUTES TERM FUNCTIONS **************)\n type flutes_term\n val str : string -> flutes_term\n val num : int -> flutes_term val num_f : float -> flutes_term\n val list : flutes_term list -> flutes_term\n val record : (string * flutes_term) list -> flutes_term\n val atom : string -> flutes_term\n val pred_app : string -> flutes_term list -> flutes_term\n val triple : string -> flutes_term -> flutes_term -> flutes_term\n val record_select : flutes_term -> string -> flutes_term\n val pred_arg_select : flutes_term -> int -> flutes_term\n val var : string -> flutes_term\n val term_name : string -> flutes_term\n (******* FLUTES TYPE FUNCTIONS **************)\n type flutes_type type flutes_prop_type\n val str_ty : flutes_type \n val num_ty : flutes_type\n val type_name : string -> flutes_type\n val record_ty : (string * flutes_type) list -> flutes_type\n val pred_ty : string -> flutes_type list -> flutes_type\n val triple_ty : string -> flutes_type * flutes_type -> flutes_type\n val subset_ty : flutes_term -> flutes_type -> flutes_prop_type\n -> flutes_type\n\n (**INFIX OPERATORS FOR BUILT-IN PREDICATES *)\n val ( === ) : flutes_term -> flutes_term -> flutes_prop_type \n (***** INFIX OPERATORS FOR PROP TYPES ********)\n (* and prop type *)\n val ( ^^ ) : flutes_prop_type -> flutes_prop_type -> flutes_prop_type\n (* or prop type *)\n val ( ||| ) : flutes_prop_type -> flutes_prop_type -> flutes_prop_type\n (* exists prop type *)\n val ( ?? ) : ", "string -> flutes_type -> flutes_prop_type -> flutes_prop_type\n (******* FLUTES DB FUNCTIONS **************)\n val abox_insert : string -> flutes_term -> unit\n val find_members : unit -> unit\n val mk_kb_class :string -> flutes_type -> unit\n\nTerms in MongoDB are partitioned into two collections, untyped terms and typed terms. ", "Newly inserted terms are added to the untyped terms collection. ", "Terms are inserted via the concrete syntax parser or using the function from the module. ", "A term is moved to the typed terms collection if a Flutes type can be inferred from it. ", "All well-formed Flutes terms have a Flutes type except those that reference terms that do not have a Flutes type. ", "If a term alias refers to a term not in the typed terms collection, then the term will not have a type.", "\n\nIn our current implementation of Flutes DB, type inference will only infer *static types*. ", "A static type is any `flutes_type` created with any function in other than or . ", "Therefore, types created with the functions and will be static types. ", "Both of these functions use the constructor . ", "The main difference between the two is  creates a record type whose members are records representing predicate applications. ", "The function is a convenience version of . ", "Types created with represent references to types whose definitions are stored in MongoDB. ", "Types whose definitions are stored in MongoDB are called *classes*. ", "Types created with represent sets of terms that satisfy a condition defined by a . ", "We describe subset types in more detail in .", "\n\nDetermining membership of subset types and classes is performed by a separate task we call *finding class members*. ", "Finding class members involves detecting which typed terms belong to classes. ", "In Flutes DB, we create a collection in MongoDB for each class. ", "Finding class members copies typed terms that belong to the class to the class’ collection. ", "The class collections serve as indexes for graphs that have similar topology and characteristics. ", "Subset types represent sets of graphs whose membership can change as new facts are added. ", "For example, we use a subset type to represent people who have a financial transaction with the author Sue Grafton. ", "As new financial transactions are added, new members may be added to this type.", "\n\nFinding class members is performed when a user evaluates the expression in the top–level environment. ", "Evaluating this expression causes the top-level environment to send a message to running instances of a standalone OCaml program called *Abox Manager*. ", "The running instances of ABox Manager search the typed terms for members of classes.", "\n\nWe describe how works via an example. ", "Suppose we evaluated the code in in the top-level environment. ", "The code in will result in four classes being defined: , , , and . ", "Running the parser on the concrete syntax in will define a person named Sue and a person named Joe.", "\n\n joe := {\"name\"=\"Joe\", \"birth_date\"=\"1984-06-27\"};\n sue := {\"name\"=\"Sue\", \"dob\"=\"1941-12-07\"};\n t1 := {\"amount\" = 500.0, \"type\"=check()};\n o1 := orig-of(joe, t1);\n r1 := recv-of(sue, t2);\n\nIn addition, it defines a \\$500 financial transaction involving Sue and Joe. ", "All of these terms have Flutes static types, so ABox Manager will add all of these terms to the typed terms collection in MongoDB. ", "Next, if the user evaluates in the OCaml top-level, then ABox Manager instances will determine the classes each of the members belong to and add each member to the collection corresponding to the class in MongoDB. ", "Both and would be added to ’s collection. ", "Here is the type inferred from .", "\n\n\\[joes-type-eq\\]\n\n record_ty [(\"name\", str_ty); \n (\"birth_date\", str_ty)]\n\nThis type is a subtype of because we added and to the equivalence relation on the last line of the code in . ", "In Flutes, structural subtyping of record types use the equivalence relation and the lattice defined in the module to pair fields. ", "Normally, strict identity is used to pair fields. [", "Under our definition of subtyping, it is possible for there to be multiple proofs of the same subtyping judgment. ", "We made our prover deterministic by requiring the fields of a record type to be ordered under the total ordering of labels defined in the module . ", "The prover finds pairs by looking to match the first field in the super type, with a field in the subtype. ", "The prover scans the fields of the subtype in order. ]{}", "\n\nThe term in the collection for bound to has its renamed to . ", "In other words, is the following term in .", "\n\n record [(\"name\", \"Joe\"); (\"dob\", \"1984-06-27\")]\n\nThe result of proving a type is subtype of another type produces a coercion. ", "When ABox Manager detects a term’s inferred type is a subtype of a class, ABox Manager uses the coercion to convert the term to a term that belongs to the class. ", "This is how type subsumption is implemented to support semantics relationship of attribute names.", "\n\n let _ = mk_kb_class \"person\" \n (record_ty [(\"name\", str_ty); \n (\"dob\", str_ty)])\n let _ = mk_kb_class \"trans\" \n (record_ty \n [(\"amount\", str_ty); \n (\"type\", enum_ty [\"check\", \"cc\"])])\n \n let _ = mk_kb_class \"orig_of\" \n (triple_ty \"orig-of\" (type_name \"person\") \n (type_name \"person\")\n\n let _ = mk_kb_class \"recv_of \n (triple_ty \"recv-of\" (type_name \"person\") \n (type_name \"person\")\n \n let _ = same_as \"dob\" \"birth_date\" /* last line */\n\nGrammar Rules in FlutesDB {#grammar-rules-in-flutes-section}\n=========================\n\nInformally, a graph grammar production rule could be expressed as the logic formula $\\forall g.P(g)\\implies \\exists g'.", "Q(g')$. In the formula, $\\forall g.P(g)$ is the left-hand side of the production rule and $\\exists g'.", "Q(g')$ is the right-hand side of the production rule. ", "The predicate $P$ defines the conditions a matching graph must have in order to apply the rule. ", "The predicate $Q$ defines the conditions the output graph $g'$ will have after the rule has been applied to the matching graph. ", "The graph $g'$ is produced by performing some transformations to the graph containing $g$.\n\nFlutes contains three constructs for representing grammar rules, subset types, lambda abstractions and analytics. ", "Subset types are created with the function . ", "This function takes three arguments, the binding term, the binding type, and the proposition type. ", "The first two arguments, the binding term and the binding type, determine the the structure of the terms that belong to the subset type. ", "The third argument, the proposition type, indicates the properties each member of the subset type have. ", "The code in contains an example of using a subset type as a grammar rule. ", "It defines a rule to transform a five-node four-edge subgraph into a three-node two-edge subgraph. ", "contains a drawing of the transformation. ", "The code in can be read logically as make person $p$ financially related to person $q$ if there exists a transaction $t$ where $p$ is the originator of $t$ and $q$ is the receiver of $t$. Notice the binding term contains two variables, and , that occur free in the proposition type.", "\n\n\\[mission-set-type-eq\\]\n\n let [p;q;r;s;t] = map var [\"p\";\"q\";\"r\";\"s\";\"t\"]\n in\n subset_ty \n (triple \"fi-related\" p q) \n ((triple_ty \"fi-related\" \n (type_name \"person\", \n type_name \"person\"))) \n ((??) \"", "t\" (type_name \"trans\")\n ((??) \"", "s\" (type_name \"orig_of\") \n ((??) \"", "r\" (type_name \"recv_of\")\n (((triple \"orig-of\" p t\n === s) \n ^^ \n ((triple \"recv-of\" q t) \n === r)))))\n\n![", "Transformation of a financial transaction graph to a financially related graph.[]{data-label=\"financial-subgraphs\"}](graph-trans-Picture1.png){height=\"1.5in\" width=\"5in\"}\n\nFinding members of the subset type involves finding terms that produce a substitution that meets the following criteria. ", "The application of the substitution to the binding term produce a term that belongs to the binding type and the application of the substitution to the proposition type produces a provable proposition.", "\n\nLambda abstractions and analytics are used to define graph grammars rules whose right-hand side use a functional graph transformation. ", "These rules can be expressed informally as the logic formula $\\forall g.S(g,I)\\implies \\exists g'.\\kappa(g)=g' \\wedge(S(f(g'),O)$. In this formula, $S$ is the predicate subsumed by. ", "In other words, $S(x,C)$ means $x$ is subsumed by type $C$ or class $C$ . ", "$f$ is the graph transformation. ", "$g'$ is the coerced term produced from the coercion $\\kappa$ derived from the proof of the subtyping judgment of $g$’s inferred type and $I$. In the case of lambda abstraction, $I$ is the class of the binding variable and $O$ is the type of the body, and $f(g')$ is the application of the lambda abstraction to $g'$. In the case of an analytic, f is an OCaml function of type . ", "In this case, it is possible for $f(g')$ to not evaluate to a term subsumed by $O$. If this occurs, the grammar rule fails.", "\n\nThe module contains functions for defining grammar rules using lambda abstractions and analytics. ", "Due to space limitation we omit the signatures and provide a short example of their use later in the paper.", "\n\nLarge graphs in FlutesDB\\\n {#unification-in-flutes-section}\n=========================\n\nWe conducted experiments to demonstrate FlutesDB can be used as a 5GL for mission extraction. ", "In the experiments, we used subset types to extract a small low-dimensional mission set from a large high-dimensional data set. ", "For the large high-dimensional data set, we used DBpedia and randomly generated financial data for people in DBpedia. ", "The mission set are people who are financially related.", "\n\nWe represent financially related people as terms of the form\n\n triple \"fi-related\" (term_name \"x\", term_name \"y\").", "\n\nThese terms have to be constructed from collections of terms representing a financial transaction. ", "The concrete syntax in contains the definition of a financial transaction. ", "The randomly generated terms for financial transactions may be incomplete. ", "In other words, the transaction may not have an originator or a receiver. ", "We did this to make the data set more realistic because intelligence data is often incomplete.", "\n\nIn addition to demonstrating mission set extraction, we show the ability to extract a mission target. ", "A mission target represents the objects an analyst is trying to discover using existing and newly collected intelligence data. ", "In our experiment, the newly collected intelligence data is represented as data added to FlutesDB after the mission set has been created.", "\n\nTo demonstrate our approach based on FlutesDB is feasible for mission extraction, we have to show it meets the following criteria.", "\n\n1. ", " \\[safety-criteria\\] An analyst can create a mission set and a mission target without having to write any special programming logic to ensure the transformation is safe.", "\n\n2. ", " \\[query-criteria\\] Queries and updates to the DB are performed without the analyst’s knowledge.", "\n\n3. ", " \\[performance-criteria\\] The amount of time to extract the mission set should be reasonable with respect to the size of the data set.", "\n\nTo meet Criteria \\[safety-criteria\\] a solution needs to prevent the execution of a transformation that will corrupt the integrity of data. ", "Criteria \\[query-criteria\\] means an analyst only specifies what they want in the mission set and the mission target opposed to specifying how to get the data using queries and API calls to retrieve it from the DB.", "\n\nIn Criteria \\[performance-criteria\\], reasonable depends on the frequency of extracting mission sets. ", "If an analyst only needs to extract a mission set once a week, then two or three hours is a reasonable amount of time to extract a mission set. ", "If an analyst needs to extract several mission sets in a single eight-hour work day, then a few minutes is a reasonable amount of time.", "\n\nDetecting members of a mission target should always be fast. ", "Detecting whether a new term is a member of mission target should be on the order of one millisecond for high-dimensional terms and ten microseconds for low-dimensional terms. ", "High-dimensional terms are objects such as people that may have 100s of attributes. ", "Low-dimensional terms are objects such as net-flow records or tracks of a moving vehicle with fewer than 20 attributes. ", "This means if one million people are added, it should take less than 20 minutes to determine if those terms belong to a mission target. ", "This is suitable for investigations tracking the behaviors of people or other entities with many features. ", "If the new terms represent one million net-flow records or one million new air tracks, it should take about 10 seconds to determine if they belong to a mission target. ", "A typical PC generates less than 1000 net-flow records per second and GMTI sensors produce less than 1000 tracks per second. ", "Therefore, 10 seconds is a reasonable amount of time for these cases.", "\n\nFor the experiment, we used 238,287,247 Flutes terms. ", "These terms were created by converting 378,547,908 DBpedia triples into terms in Flutes’ concrete syntax and from approximately 17 million financial transaction terms for people in DBpedia. ", "The graphs containing the transactions and the attributes of the people graphs have high dimensionality. [ ", "illustrates the dimensionality pictorially.]{}", "\n\nConversion of DBpedia was performed by adapting an algorithm for automatically detecting objects in an RDF graph. ", "The objects detected are trees of depth one. ", "We treated the edges as essential properties. ", "Therefore each of these trees were converted into a record whose fields corresponded to the edges of the tree. ", "Any property in the RDF graph not detected as an essential property we considered to be an accidental property. ", "We represented these edges as predicate applications, that is terms created using the function .", "\n\n![", "Sue Grafton in financial transactions with two other people.[]{data-label=\"people-transaction-graph-full\"}](sue_grafton_graph_full.png){height=\"4in\" width=\"5in\"}\n\nFor the experiment, we made the mission set all financially related people. ", "This type is defined in . ", "This mission set only needs to contain links between people who have at least one financial transaction in common. ", "We don’t need to include the financial transaction in the mission set. ", "In addition, we don’t need to include most of the attributes of a person. ", "We only need the person’s name and date of birth.", "\n\ngraphically depicts a portion of the mission extracted from the graph in .", "\n\n![", "People financially related to Sue Grafton from .[]{data-label=\"sue-grafton-financially-related\"}](sue_grafton_graph_financially_related.png){height=\"3in\" width=\"5in\"}\n\nFlutesDB uses unification to find members of subset types. ", "FlutesDB creates a collection of disjunctive skolemized clauses from the subset type. ", "FlutesDB determines the skolem variables based on variables bound by the existential quantifier `??", "`. ", "In , FlutesDB creates two skolem variables for `s` and `r`. ", "FlutesDB scans the typed terms for instances to replace the skolem variables in the clauses. ", "Then it performs unification to determine bindings for the free variables in the binding term of the subset type. ", "In the variables are and . ", "If the substitution of the free variables produces a term that belongs to or is subsumed by the binding type, then the term or its coercion is made a member of the class represented by the subset type.", "\n\n[|l|c|]{} & elapsed time\\\norig\\_of & 24.53m\\\nrecv\\_of & 32.26m\\\nfi\\_related & 45.23m\\\nmission set (total)$^\\mathrm{a}$ & 102.02m\\\nm\\_target (initial)$^\\mathrm{b}$ & 6.23239m\\\nm\\_target (new. ", "per term)$^\\mathrm{c}$ & 1.17703s\\\n\\\n\\\n\\\n\\\n\nTo make FlutesDB efficient, all the typed terms aren’t scanned. ", "Only a subset of the terms belonging to the type of the skolem variables are scanned. ", "In the case of the mission set in , we only scan terms from and . ", "However, we do scan $n^m$ terms where $n$ is the number of terms in and $m$ is the number of terms in . ", "When using a member of as a skolem variable, we only need to scan the set of members of that contains the same term of type as the member of . ", "FlutesDB creates an adjacency list that maps each term to all the terms it contains. ", "FlutesDB uses this adjacency list to create the set of terms to scan for members of recv\\_of. ", "This set only contains two terms for our data set. ", "Therefore, we only scan $n^{2}$ terms. ", "Once we find this transaction, unification will produce a substitution for the two arguments of .", "\n\nBefore performing this process, FlutesDB has to find the members of and . ", "FlutesDB detects the dependency of the mission set has on and when it creates the clauses from . ", "FlutesDB will only use newly added typed terms as candidates of and . ", "shows the running times to find members of , and .", "\n\nIn the experiment, we made finding people related to Sue Grafton the mission target. ", "We define the mission target as the class using the type in .", "\n\n\\[mission-target-eq\\]\n\n let target = term_name \n \"http://dbpedia.org/resource/sue_grafton\"\n in let p;f = var \"p\"; var\"f\"\n in\n subset_ty \"p\" (type_name \"person\") \n ((??) \"", "f\" (type_name \"fi_related\")\n ((triple \"fi-related\" p target === f) \n ||| \n (triple \"fi-related\" target p === f)))\n\nalso contains the elapsed time to find members of . ", "The elapsed time show that in a little more than one second, we can type five new financial transaction (20 terms), add new terms to the mission set, and add new terms to the target set. ", "This is within the range specified by Criteria \\[performance-criteria\\].", "\n\nWe can use an analytic to do something more dynamic than the subset type, such as determining membership of a class based on whether a term is near a member of a class of money laundering suspects. ", "Finding the nearest neighbor needs the ability to traverse the adjacency list. ", "We have an OCaml module, called for traversing the accidental properties of the graph. ", "Due to space limitation, we don’t provide it here. ", "This module allows programmers to traverse the entire graph, so it supports the ability to write nearest neighbor and other graph algorithms. ", "This module will also have a function to return the names of the classes a term belongs to.", "\n\nAssume a programmer created a nearest neighbor function using the module. ", "Given a term $t$, a class name $c$, and a path length $k$, it returns the names of the terms on a path no longer than length $k$ that belong to or subsumed by the class $c$. Then an analyst could use this function to define an analytic to find all people financially related to Sue Grafton who are associated with a person in a criminal organization. ", "Here is the OCaml code to create the analytic.", "\n\n mk_analytic \"find_criminal\" \"m_target\" \n \"criminal_org\" \n (fun t -> nearest 3 t \"criminal_org\") \n \n\nWhen Flutes DB runs analytics, it take all terms in the analytic’s input class and passes it as an argument to the code representing the body of the analytic. ", "If the code doesn’t raise an exception during its execution, then FlutesDB checks if the output term can be subsumed by the output type. ", "If it can be, then its coerced term is returned as the result of the evaluation.", "\n\nConclusion\n==========\n\nWe demonstrated the benefits of using concepts from functional programming to create a language for extracting mission graphs from large graphs of linked objects. ", "The proof-of-concept we presented in this paper, FlutesDB, can be used to create an end-user language for analysts because the user can focus on what needs to be solved and not on how to solve it. ", "For example, the end-user does not have to provide the programming logic to perform graph transformations to extract mission graphs. ", "The end-user only has to specify the characteristics of the mission graph. ", "In cases where programming logic is needed, our proof-of-concept demonstrates programmers can easily provide analytics that analysts could incorporate into their specifications.", "\n\nRelated Work\n------------\n\nResearchers have created approaches using SPARUL that can be used creating graph transformations. ", "However, these approaches have a fundamental problem they make them undesirable for intelligence analysis. ", "The SPARUL and RDF type system is too weak for preventing careless mistakes that could be catastrophic for intelligence analysis. ", "In particular, analyst can specify an object belongs to a type, but whose structure does not match the type. ", "This weakness could lead to data integrity issues that could cause analysts to make incorrect predictions.", "\n\nFlutes is related to attributed type graphs with node type inheritance . ", "We know of no existing work on attributed type graphs with node type inheritance that supports semantic relationships between attribute names. ", "Attributed type graphs are defined as set-theoretic functions or using categories. ", "Therefore, it is possible we can use attributed type graphs as a denotational model of Flutes.", "\n\nFlutes is also related to declarative graph grammars. ", "However we know of no declarative graph grammars that support node type inheritance.", "\n\nAcknowledgement {#acknowledgement .unnumbered}\n===============\n\nThe research presented in this paper was funded in part by ONR  contract N00014-15-P-1172.", "\n\n[10]{}(3.5,14.5)\n\nDISTRIBUTION A. Approved for public release: distribution unlimited.", "\n\n©Datanova Scientific 2016.", "\n" ]
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[ "Q:\n\nStrings to class in Ruby\n\nI have a class in Ruby (on Rails) as follows: \nclass Good\n include MongoMapper::Document\n has_many :offers, :dependent => :destroy\n\n key :name, String\n key :description, String\n key :email, String\n key :offers, Array\n key :type, String\nend\n\nI am parsing a JSON object from an external URL and retrieve only a partial set of the types in this class, ie, I can retrieve only name, description, and type. ", "On my server, I already have a page and data that can be displayed. ", "I would like to display the data from the external URL on the page as well. ", "How can I do this without making too many changes to the code? ", "One thing I thought of was to make the strings I retrieve a part of the class Good, but I have no idea of how I can do it. ", "\nIn other words, the retrieved name, description and type will be cast into the type Good and then will use the existing page, created to display our goods to display both, our, and the retrieved goods. ", "How can I do this? ", "Is this the right way of going about it?", "\n\nA:\n\nYour question is pretty unclear, but I'll take a shot. ", "You could have a Struct like\nArbitraryGood = Struct.new(:name, :description, :type)\n\nYou could then map a collection of Good instances to this\n@arbitrary_goods = Good.all.map { |g| ArbitraryGood.new(g.name, g.description, g.type) }\n\nThen you can gather your JSON response and append new ArbitraryGood instances to it.", "\nobjects_from_json = ... # for you to implement\n@arbitrary_goods += objects_from_json.map { |o| ArbitraryGood.new(o.name, o.description, o.type) }\n\nNow @arbitrary_goods contains a single listing mixed with data from both Good instances and the parsed external JSON for use within your view.", "\n\n" ]
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[ "Q:\n\nHow to populate html input element with Ajax callback data\n\nI am trying to populate an html field with some text being queried using jQuery Ajax. ", "The data being sent to the function view is received back on page load. ", "The callback data can be seen in the console. ", "However the data value itself is not populated in the input field.", "\nWhy my code below is failing:\n$('.clsSomeTxt input').val(data.recdValue);\n\nWhereas in the console it shows:\nconsole.log('The value received back is: ' + data.recdValue);\n\nI have tried using form's id also, without success.", "\nEdit\n<table id=\"xHeader\">\n\n {% for fieldX in form.visible_fields %}\n <tr>\n <th>{{ fieldX.label_tag }}</th>\n <td>\n {{ fieldX.errors }}\n\n {% if fieldX.name == \"model_id\" %}\n {{ fieldX }}<input type=\"text\" class=\"clsSomeTxt\" id=\"clsSomeTxt\" readonly style=\"background: lightgrey; width: 320px\">\n {% else %}\n {{ fieldX }}\n {% endif %}\n\n </td>\n </tr>\n {% endfor %}\n</table>\n\nA:\n\nAs I mentioned in comment you are using wrong selector, input already has clsSomeTxt class, your selector is totally wrong; you select an input inside of clsSomeTxt, but this is class of input. ", "So the right selector is:\n$('input.clsSomeTxt').val(data.recdValue);\n\nOr just:\n$('.clsSomeTxt').val(data.recdValue);\n\n" ]
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[ "Premature sentiments.", "\nWhile I found myself nodding in agreement with the sentiments of your editorial (Nursing Standard August 20, 1988), aren't you 'jumpinq the qun' just a little?" ]
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[ "Healthy Living\n\nHealthy Living\n\nHealthy living is about preventing and managing chronic diseases so you can live the best life possible.", "\n\nOur experts focus on preventing and managing diabetes, heart disease, cancer, and asthma, but our trained health educators can help anyone with a variety of health-related topics, from information about proper nutrition for your family to finding physical activity that works for you." ]
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[ "This isn't your average election year video of celebrities asking you to vote...instead it's regular folks, asking you to vote for celebrities who can't. ", "If you can't bring yourself to vote in the midterm elections for yourself and your future this November 2nd. ", "Then do it, for Bieber. ", "This video is a Campus Progress submission to the Vote Again 2010 Video Contest (http://www.voteagain2010.com)\n\nVideo by Sara Haile-Mariam and Tara Kutz" ]
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[ "package ThreeSum\n\nimport (\n\t\"testing\"\n\t\"reflect\"\n)\n\nfunc TestThreeSum(t *testing.", "T) {\n\n\tif reflect.", "DeepEqual(threeSum([]int{-1, 0}), [][]int{}) {\n\t\tt.Log(\"pass\")\n\t} else {\n\t\tt.Error(\"failed\")\n\t}\n\n\tif reflect.", "DeepEqual(threeSum([]int{-1, 0, 1, 2, -1, -4}),\n\t\t[][]int{{-1, -1, 2}, {-1, 0, 1},}) {\n\t\tt.Log(\"pass\")\n\t} else {\n\t\tt.Error(\"failed\")\n\t}\n\n\tif reflect.", "DeepEqual(threeSum([]int{0, 0, 0}),\n\t\t[][]int{{0, 0, 0}}) {\n\t\tt.Log(\"pass\")\n\t} else {\n\t\tt.Error(\"failed\")\n\t}\n\n\tif reflect.", "DeepEqual(threeSum([]int{-4, -2, -2, -2, 0, 1, 2, 2, 2, 3, 3, 4, 4, 6, 6}),\n\t\t[][]int{{-4, -2, 6}, {-4, 0, 4}, {-4, 1, 3}, {-4, 2, 2}, {-2, -2, 4}, {-2, 0, 2}}) {\n\t\tt.Log(\"pass\")\n\t} else {\n\t\tt.Error(\"failed\")\n\t}\n\n}\n" ]
{ "pile_set_name": "Github" }
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[ "Armand Niccolai\n\nArmand Niccolai (November 8, 1911 – December 2, 1988) was a guard who played nine seasons in the National Football League. ", "Niccolai attended Duquesne University.", "\n\nArmand Niccolai played nine seasons for the Pittsburgh Pirates/Steelers after attending nearby Duquesne University. ", "He led the team in scoring in four years, including posting a personal-best 28 points in both 1935 and 1936. ", "He booted a Steelers'-best seven field goals in 1936, which that mark would not be broken for the next 14 years.", "\n\nNiccolai died in Monessen, Pennsylvania.", "\n\nExternal links\n\nCategory:1911 births\nCategory:1988 deaths\nCategory:Players of American football from Pennsylvania\nCategory:American football offensive linemen\nCategory:American football placekickers\nCategory:Pittsburgh Pirates (football) players\nCategory:Pittsburgh Steelers players\nCategory:Duquesne University alumni\nCategory:Burials at Monongahela Cemetery (Monongahela, Pennsylvania)" ]
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[ "// Special functions -*- C++ -*-\n\n// Copyright (C) 2006, 2007, 2008, 2009, 2010\n// Free Software Foundation, Inc.\n//\n// This file is part of the GNU ISO C++ Library. ", " This library is free\n// software; you can redistribute it and/or modify it under the\n// terms of the GNU General Public License as published by the\n// Free Software Foundation; either version 3, or (at your option)\n// any later version.", "\n//\n// This library is distributed in the hope that it will be useful,\n// but WITHOUT ANY WARRANTY; without even the implied warranty of\n// MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the\n// GNU General Public License for more details.", "\n//\n// Under Section 7 of GPL version 3, you are granted additional\n// permissions described in the GCC Runtime Library Exception, version\n// 3.1, as published by the Free Software Foundation.", "\n\n// You should have received a copy of the GNU General Public License and\n// a copy of the GCC Runtime Library Exception along with this program;\n// see the files COPYING3 and COPYING.RUNTIME respectively. ", " If not, see\n// <http://www.gnu.org/licenses/>.", "\n\n/** @file tr1/exp_integral.tcc\n * This is an internal header file, included by other library headers.", "\n * Do not attempt to use it directly. ", "@headername{tr1/cmath}\n */\n\n//\n// ISO C++ 14882 TR1: 5.2 Special functions\n//\n\n// Written by Edward Smith-Rowland based on:\n//\n// (1) Handbook of Mathematical Functions,\n// Ed. ", "by Milton Abramowitz and Irene A. Stegun,\n// Dover Publications, New-York, Section 5, pp. ", "228-251.", "\n// (2) The Gnu Scientific Library, http://www.gnu.org/software/gsl\n// (3) Numerical Recipes in C, by W. H. Press, S. A. Teukolsky,\n// W. T. Vetterling, B. P. Flannery, Cambridge University Press (1992),\n// 2nd ed, pp. ", "222-225.", "\n//\n\n#ifndef _GLIBCXX_TR1_EXP_INTEGRAL_TCC\n#define _GLIBCXX_TR1_EXP_INTEGRAL_TCC 1\n\n#include \"special_function_util.h\"\n\nnamespace std _GLIBCXX_VISIBILITY(default)\n{\nnamespace tr1\n{\n // [5.2] Special functions\n\n // Implementation-space details.", "\n namespace __detail\n {\n _GLIBCXX_BEGIN_NAMESPACE_VERSION\n\n template<typename _Tp> _Tp __expint_E1(const _Tp);\n\n /**\n * @brief Return the exponential integral @f$ E_1(x) @f$\n * by series summation. ", " This should be good\n * for @f$ x < 1 @f$.\n * \n * The exponential integral is given by\n * \\f[\n * E_1(x) = \\int_{1}^{\\infty} \\frac{e^{-xt}}{t} dt\n * \\f]\n * \n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_E1_series(const _Tp __x)\n {\n const _Tp __eps = std::numeric_limits<_Tp>::epsilon();\n _Tp __term = _Tp(1);\n _Tp __esum = _Tp(0);\n _Tp __osum = _Tp(0);\n const unsigned int __max_iter = 100;\n for (unsigned int __i = 1; __i < __max_iter; ++__i)\n {\n __term *= - __x / __i;\n if (std::abs(__term) < __eps)\n break;\n if (__term >= _Tp(0))\n __esum += __term / __i;\n else\n __osum += __term / __i;\n }\n\n return - __esum - __osum\n - __numeric_constants<_Tp>::__gamma_e() - std::log(__x);\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_1(x) @f$\n * by asymptotic expansion.", "\n * \n * The exponential integral is given by\n * \\f[\n * E_1(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t} dt\n * \\f]\n * \n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_E1_asymp(const _Tp __x)\n {\n _Tp __term = _Tp(1);\n _Tp __esum = _Tp(1);\n _Tp __osum = _Tp(0);\n const unsigned int __max_iter = 1000;\n for (unsigned int __i = 1; __i < __max_iter; ++__i)\n {\n _Tp __prev = __term;\n __term *= - __i / __x;\n if (std::abs(__term) > std::abs(__prev))\n break;\n if (__term >= _Tp(0))\n __esum += __term;\n else\n __osum += __term;\n }\n\n return std::exp(- __x) * (__esum + __osum) / __x;\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_n(x) @f$\n * by series summation.", "\n * \n * The exponential integral is given by\n * \\f[\n * E_n(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t^n} dt\n * \\f]\n * \n * @param __n The order of the exponential integral function.", "\n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_En_series(const unsigned int __n, const _Tp __x)\n {\n const unsigned int __max_iter = 100;\n const _Tp __eps = std::numeric_limits<_Tp>::epsilon();\n const int __nm1 = __n - 1;\n _Tp __ans = (__nm1 !", "= 0\n ? _", "Tp(1) / __nm1 : -std::log(__x)\n - __numeric_constants<_Tp>::__gamma_e());\n _Tp __fact = _Tp(1);\n for (int __i = 1; __i <= __max_iter; ++__i)\n {\n __fact *= -__x / _Tp(__i);\n _Tp __del;\n if ( __i !", "= __nm1 )\n __del = -__fact / _Tp(__i - __nm1);\n else\n {\n _Tp __psi = -__numeric_constants<_Tp>::gamma_e();\n for (int __ii = 1; __ii <= __nm1; ++__ii)\n __psi += _Tp(1) / _Tp(__ii);\n __del = __fact * (__psi - std::log(__x)); \n }\n __ans += __del;\n if (std::abs(__del) < __eps * std::abs(__ans))\n return __ans;\n }\n std::__throw_runtime_error(__N(\"Series summation failed \"\n \"in __expint_En_series.\"));", "\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_n(x) @f$\n * by continued fractions.", "\n * \n * The exponential integral is given by\n * \\f[\n * E_n(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t^n} dt\n * \\f]\n * \n * @param __n The order of the exponential integral function.", "\n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_En_cont_frac(const unsigned int __n, const _Tp __x)\n {\n const unsigned int __max_iter = 100;\n const _Tp __eps = std::numeric_limits<_Tp>::epsilon();\n const _Tp __fp_min = std::numeric_limits<_Tp>::min();\n const int __nm1 = __n - 1;\n _Tp __b = __x + _Tp(__n);\n _Tp __c = _Tp(1) / __fp_min;\n _Tp __d = _Tp(1) / __b;\n _Tp __h = __d;\n for ( unsigned int __i = 1; __i <= __max_iter; ++__i )\n {\n _Tp __a = -_Tp(__i * (__nm1 + __i));\n __b += _Tp(2);\n __d = _Tp(1) / (__a * __d + __b);\n __c = __b + __a / __c;\n const _Tp __del = __c * __d;\n __h *= __del;\n if (std::abs(__del - _Tp(1)) < __eps)\n {\n const _Tp __ans = __h * std::exp(-__x);\n return __ans;\n }\n }\n std::__throw_runtime_error(__N(\"Continued fraction failed \"\n \"in __expint_En_cont_frac.\"));", "\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_n(x) @f$\n * by recursion. ", " Use upward recursion for @f$ x < n @f$\n * and downward recursion (Miller's algorithm) otherwise.", "\n * \n * The exponential integral is given by\n * \\f[\n * E_n(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t^n} dt\n * \\f]\n * \n * @param __n The order of the exponential integral function.", "\n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_En_recursion(const unsigned int __n, const _Tp __x)\n {\n _Tp __En;\n _Tp __E1 = __expint_E1(__x);\n if (__x < _Tp(__n))\n {\n // Forward recursion is stable only for n < x.\n __En = __E1;\n for (unsigned int __j = 2; __j < __n; ++__j)\n __En = (std::exp(-__x) - __x * __En) / _Tp(__j - 1);\n }\n else\n {\n // Backward recursion is stable only for n >= x.\n __En = _Tp(1);\n const int __N = __n + 20; // TODO: Check this starting number.", "\n _Tp __save = _Tp(0);\n for (int __j = __N; __j > 0; --__j)\n {\n __En = (std::exp(-__x) - __j * __En) / __x;\n if (__j == __n)\n __save = __En;\n }\n _Tp __norm = __En / __E1;\n __En /= __norm;\n }\n\n return __En;\n }\n\n /**\n * @brief Return the exponential integral @f$ Ei(x) @f$\n * by series summation.", "\n * \n * The exponential integral is given by\n * \\f[\n * Ei(x) = -\\int_{-x}^\\infty \\frac{e^t}{t} dt\n * \\f]\n * \n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_Ei_series(const _Tp __x)\n {\n _Tp __term = _Tp(1);\n _Tp __sum = _Tp(0);\n const unsigned int __max_iter = 1000;\n for (unsigned int __i = 1; __i < __max_iter; ++__i)\n {\n __term *= __x / __i;\n __sum += __term / __i;\n if (__term < std::numeric_limits<_Tp>::epsilon() * __sum)\n break;\n }\n\n return __numeric_constants<_Tp>::__gamma_e() + __sum + std::log(__x);\n }\n\n\n /**\n * @brief Return the exponential integral @f$ Ei(x) @f$\n * by asymptotic expansion.", "\n * \n * The exponential integral is given by\n * \\f[\n * Ei(x) = -\\int_{-x}^\\infty \\frac{e^t}{t} dt\n * \\f]\n * \n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_Ei_asymp(const _Tp __x)\n {\n _Tp __term = _Tp(1);\n _Tp __sum = _Tp(1);\n const unsigned int __max_iter = 1000;\n for (unsigned int __i = 1; __i < __max_iter; ++__i)\n {\n _Tp __prev = __term;\n __term *= __i / __x;\n if (__term < std::numeric_limits<_Tp>::epsilon())\n break;\n if (__term >= __prev)\n break;\n __sum += __term;\n }\n\n return std::exp(__x) * __sum / __x;\n }\n\n\n /**\n * @brief Return the exponential integral @f$ Ei(x) @f$.\n * \n * The exponential integral is given by\n * \\f[\n * Ei(x) = -\\int_{-x}^\\infty \\frac{e^t}{t} dt\n * \\f]\n * \n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_Ei(const _Tp __x)\n {\n if (__x < _Tp(0))\n return -__expint_E1(-__x);\n else if (__x < -std::log(std::numeric_limits<_Tp>::epsilon()))\n return __expint_Ei_series(__x);\n else\n return __expint_Ei_asymp(__x);\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_1(x) @f$.\n * \n * The exponential integral is given by\n * \\f[\n * E_1(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t} dt\n * \\f]\n * \n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_E1(const _Tp __x)\n {\n if (__x < _Tp(0))\n return -__expint_Ei(-__x);\n else if (__x < _Tp(1))\n return __expint_E1_series(__x);\n else if (__x < _Tp(100)) // TODO: Find a good asymptotic switch point.", "\n return __expint_En_cont_frac(1, __x);\n else\n return __expint_E1_asymp(__x);\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_n(x) @f$\n * for large argument.", "\n * \n * The exponential integral is given by\n * \\f[\n * E_n(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t^n} dt\n * \\f]\n * \n * This is something of an extension.", "\n * \n * @param __n The order of the exponential integral function.", "\n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_asymp(const unsigned int __n, const _Tp __x)\n {\n _Tp __term = _Tp(1);\n _Tp __sum = _Tp(1);\n for (unsigned int __i = 1; __i <= __n; ++__i)\n {\n _Tp __prev = __term;\n __term *= -(__n - __i + 1) / __x;\n if (std::abs(__term) > std::abs(__prev))\n break;\n __sum += __term;\n }\n\n return std::exp(-__x) * __sum / __x;\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_n(x) @f$\n * for large order.", "\n * \n * The exponential integral is given by\n * \\f[\n * E_n(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t^n} dt\n * \\f]\n * \n * This is something of an extension.", "\n * \n * @param __n The order of the exponential integral function.", "\n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint_large_n(const unsigned int __n, const _Tp __x)\n {\n const _Tp __xpn = __x + __n;\n const _Tp __xpn2 = __xpn * __xpn;\n _Tp __term = _Tp(1);\n _Tp __sum = _Tp(1);\n for (unsigned int __i = 1; __i <= __n; ++__i)\n {\n _Tp __prev = __term;\n __term *= (__n - 2 * (__i - 1) * __x) / __xpn2;\n if (std::abs(__term) < std::numeric_limits<_Tp>::epsilon())\n break;\n __sum += __term;\n }\n\n return std::exp(-__x) * __sum / __xpn;\n }\n\n\n /**\n * @brief Return the exponential integral @f$ E_n(x) @f$.\n * \n * The exponential integral is given by\n * \\f[\n * E_n(x) = \\int_{1}^\\infty \\frac{e^{-xt}}{t^n} dt\n * \\f]\n * This is something of an extension.", "\n * \n * @param __n The order of the exponential integral function.", "\n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n _Tp\n __expint(const unsigned int __n, const _Tp __x)\n {\n // Return NaN on NaN input.", "\n if (__isnan(__x))\n return std::numeric_limits<_Tp>::quiet_NaN();\n else if (__n <= 1 && __x == _Tp(0))\n return std::numeric_limits<_Tp>::infinity();\n else\n {\n _Tp __E0 = std::exp(__x) / __x;\n if (__n == 0)\n return __E0;\n\n _Tp __E1 = __expint_E1(__x);\n if (__n == 1)\n return __E1;\n\n if (__x == _Tp(0))\n return _Tp(1) / static_cast<_Tp>(__n - 1);\n\n _Tp __En = __expint_En_recursion(__n, __x);\n\n return __En;\n }\n }\n\n\n /**\n * @brief Return the exponential integral @f$ Ei(x) @f$.\n * \n * The exponential integral is given by\n * \\f[\n * Ei(x) = -\\int_{-x}^\\infty \\frac{e^t}{t} dt\n * \\f]\n * \n * @param __x The argument of the exponential integral function.", "\n * @return The exponential integral.", "\n */\n template<typename _Tp>\n inline _Tp\n __expint(const _Tp __x)\n {\n if (__isnan(__x))\n return std::numeric_limits<_Tp>::quiet_NaN();\n else\n return __expint_Ei(__x);\n }\n\n _GLIBCXX_END_NAMESPACE_VERSION\n } // namespace std::tr1::__detail\n}\n}\n\n#endif // _GLIBCXX_TR1_EXP_INTEGRAL_TCC\n" ]
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[ "Q:\n\nHandling Facebook access token expiry in Javascript SDK\n\nI am using Facebook Javascript SDK http://developers.facebook.com/docs/reference/javascript/ to authenticate and approve my Facebook app.", "\nMy SDK code will be as follows:\nwindow.fbAsyncInit = function() \n{\n FB.init({\n appId : 'MY_APP_ID', \n status : true, // check login status\n cookie : true, // enable cookies to allow the server to access the session\n xfbml : true, // parse XFBML\n oauth : true\n });\n\n FB.login(function(response) \n {\n if (response.authResponse) \n {\n var userFBAccessToken = response.authResponse.accessToken;\n console.log('userFBAccessToken: ' + userFBAccessToken);\n FB.api('/me', function(response) \n {\n console.log('Good to see you, ' + response.name + '.');", "\n FB.logout(function(response) {\n console.log('Logged out.');", "\n });\n });\n } else {\n console.log('User cancelled login or did not fully authorize.');", "\n }\n }, {scope: 'user_activities,user_notes,user_photos,user_videos,user_status,offline_access'});\n}; \n\n// Load the SDK Asynchronously\n(function() {\n var e = document.createElement('script'); e.async = true;\n e.src = document.location.protocol + '//connect.facebook.net/en_US/all.js';\n document.getElementById('fb-root').appendChild(e);\n}());\n\nI am confused with offline_access deprecation. ", "My questions here are, if I enable the 'Deprecate offline access' option in my App Advanced settings page:\n\nWhat will be the expiry time of the access token which I received from response.authResponse.accessToken. ", "Whether its 2 hours or 60 days? (", "what will be the duration for now and after May 1st 2012)\nIf its only 2 hours, how can I extend it to 60 days?", "\nWhether the retrieved access token will be valid only when users are in online or it will be valid even when they are offline?", "\n\nThank you.", "\n\nA:\n\n1+2. ", "The expiry will be 2 hours. ", "You will need to extend it after it expires. ", "The request for extension is explained here under 'Client-side OAuth and Extending Access_Token Expiration Time through New Endpoint':\nhttps://developers.facebook.com/roadmap/offline-access-removal/\n\nShould be valid at all times.", "\n\n" ]
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[ "Annonay\n\nAnnonay (; ) is a French commune in the north of the Ardèche department in the Auvergne-Rhône-Alpes region of southern France. ", "It is the most populous commune in the Ardèche department although it is not the capital which is the smaller town of Privas.", "\n\nGeography\nThe commune consists of the city of Annonay and the hamlets of Vissenty, Chatinais, and Boucieu. ", "With residential development, these four entities have merged into one today. ", "Further away is the hamlet of Toissieu.", "\n\nAnnonay was built over several small hills at the confluence of the rivers Cance (Canse) and Deûme (Deôme). ", "Annonay is a crossroads of trade routes: from the Rhône Valley to the region of Saint-Étienne (east-west) and from Lyon to south of the Massif Central (north-south). ", "It is located south of Lyon, south-west of Saint-Rambert-d'Albon, and north-west of Saint-Vallier at the foot of the mountains of Vivarais just west of the river Rhône. ", "Access to the commune is by the D121 from Davezieux in the north-east passing through the commune and the city and continuing to Villevocance in the south-west. ", "There is also the D578 from the city to Quintenas in the south and the D206 to Saint-Marcel-les-Annonay in the north. ", "There are also the D371 and the D370 in the east of the commune.", "\n\nThe geology consists mainly of grey or light orange leucogranite and orthogneiss rich in biotite, sillimanite and cordierite with alternating bands of felsic and mafic material. ", "The escarpment of Annonay is surrounded by plateaux and gentle hills used for cultivating cherries, apricots, apples, pears, and other crops. ", "A reservoir created by damming the Ternay River north-west of the town provides water for industrial and domestic use. ", "The highest point of the town at is located near a place called \"Sagne Ronde\"; the lowest point at is the bed of the Cance near the ruins of the \"Mill Baru\". ", "The Montmiandon overlooking the city, rises to above sea level.", "\n\nName\nThe origin of the name of the town has numerous hypotheses. ", "One of these suggests that Annonay comes from meaning the domain of an \"Annonius\", a rich Roman who lived there. ", "Another explanation is that Annonay came from the presence of a food store of the . ", "In any case, the site of the city has been occupied since antiquity. ", "Roman coins and medals were found during the digging of the Rue Malleval in 1851.", "\n\nHistory\n\nMiddle Ages\n\nThe first written mention of Annonay dates from 403. ", "A chronicle of archives in Vienne characterized the city as a small town \"built by poor unclothed workers lost in the mountains of Haut-Vivarais\".", "\n\nA manuscript which has now disappeared, History of Annonay by P. Bartholomew Popon stated that Evance, Bishop of Vienne, had built on the site of Liberty Square a church dedicated to Saint-Mary or Our Lady in 584.", "\n\nA charter of 790 (\"The statutes of the Church of Vienne\"), confirmed in 805, extracted from the cartulary of the Church of Vienne and quoted Annonay as the seat of a rural archpriest.", "\n\nIn the 13th and early 14th centuries the small town of Annonay was an important step on the road of pilgrimage to the Virgin of Puy-en-Velay. ", "In witness to this hostelries for pilgrims, five monasteries including the Saint-Clair Convent, one Cordelier, and two priories one of which was the Chapel of Trachin.", "\n\nThe family de Roussillon dominated the region. ", "One of its members, Guillaume de Roussillon, participated in the Crusades. ", "From 1288 a charter was signed between the city and the Lord of Annonay. ", "This granted some autonomy to the city: in particular the right to levy taxes.", "\n\nIn 1342 or 1347 Annonay suffered the Black Death which raged in Europe. ", "A large part of the population was decimated. ", "From 1365 two consuls were responsible for the city.", "\n\nDuring the 15th century, Annonay affirmed itself as a commercial crossroads: exporting its wine, trading between the valley of the Rhône, the Dauphiné and the mountain by mule, the tannery developed using the waters of the Deume. ", "The city, built on a rocky outcrop located between two rivers, was defended by the castle of Roussillon in the south and two fortified houses: in the north Maleton and in the west Du Peloux. ", "A line of ramparts ringed all. ", "The suburbs grew towards the Champ de Mars along the banks of the Cance and Deume. ", "The relative prosperity however attracted thieves, highwaymen, and mercenaries. ", "During the Hundred Years War the city strengthened its fortifications with watchtowers, such as the so-called Martyrs Tower. ", "The walls were pierced by gates to control the entrance and exit to the city. ", "There are written references to the Deume, Cance, and Champ entrances, to mention only the most important.", "\n\nIn 1487 the city had fourteen churches or chapels for about two thousand inhabitants. ", "At the center of town was the parish Church of Notre Dame to which was attached a college of canons of the order of Saint-Ruf. ", "Until the Wars of Religion clerics represented up to half of the population.", "\n\nModern times (16th and 17th centuries)\n\nIn 1524 Annonay was attached to the domain of the King of France in the wake of the revolt by the Constable of Bourbon: his property, which included Annonay, was confiscated. ", "The country was then dominated by the Lévis-Ventadour, the Rohan-Soubises etc.", "\n\nWars of Religion\n\nDuring this period Annonay had 3,500 inhabitants. ", "The districts of Cance and Deume were neglected by the wealthy in favor of the Place Vielle (Old Square – now the Place de la Liberté or Liberty Square), Place Grenette, Rue des Forges (formerly Main Street and today Rue Franki Kramer).", "\n\nAnnonay adopted Protestantism before Geneva. ", "From 1528 a Franciscan friar, Etienne Machopolis – who had heard Martin Luther preach in Saxony, spread the new ideas. ", "In 1539 two merchants from Annonay were burned alive for spreading the ideas of Luther. ", "It was the excesses of the clergy that pushed people into the arms of the Reformation. ", "Moreover, in the region Protestants such as the Benay family had developed the culture of silkworms and protected the Italian artisans who came to develop the silk mills.", "\n\nAnnonay, when in the hands of Protestants, was taken for the first time in 1562 by the Catholic troops of Christophe of Saint-Chamond, Lord of Thorrenc and Andance. ", "The city was retaken at the end of 1562 by the Protestants led by Jean de Saint-Romain, his own brother. ", "Saint-Romain and his troops destroyed the Catholic places of worship in Annonay except for the Trachin Chapel which became a Protestant temple. ", "On 10 January 1563 three thousand Catholics commanded by Saint-Chamond dislodged them from Annonay. ", "The city was sacked in five days. ", "The Edict of Amboise (March 1563) restored peace by giving Protestants freedom of worship in bailiwicks such as Annonay. ", "To this misfortune was added another: plague broke out in 1564.", "\n\nIn 1568 the Protestants of Saint-Romain seized Annonay and slaughtered the college of Notre Dame. ", "A few months later, in September, Catholics, under the command of Saint-Chamond, retook the city again. ", "The troops of Saint-Romain reverted to the masters of Annonay on 17 July 1574. ", "The houses of Cance and Bourgville districts were razed and the ramparts ruined, college and various Annonay chapels were completely destroyed except the Trachin Chapel. ", "From 1574 the Protestant Lord Jean de Fay of Virieu was sent by Henry III to negotiate peace between Catholics and Protestants. ", "A compromise was found in the castle of La Condamine: the Protestant lord was responsible for controlling the locations in the region which were disarmed. ", "An edict of pacification was granted in 1577. ", "The city then had a long period of peace but in the short term trade and industry were destroyed. ", "The city, in ruins, had only 300 fires or about 1500 inhabitants. ", "Religious orders were expelled. ", "In 1583, 1584, and 1585, poor harvests caused inflation, food shortages, and famine. ", "Plague wreaked havoc in Upper Vivarais.", "\n\nWith the signing of the Edict of Nantes the city regained prosperity. ", "At the end of the 16th century thirty tanneries were located on the banks of the Deume and Cance, attracted by the quality of their waters and the prosperous farms nearby. ", "The tanneries grew. ", "There were 11 Tanners and 4 Dressers in 1590; there were 20 and 37 respectively in 1704.", "\n\n17th–18th centuries\n\nCatholicism became the new majority in the capital of Upper Vivarais due to the massive influx of foreign population. ", "Reconstruction of the Church of Notre Dame was undertaken with a constrained budget. ", "Meanwhile, the Trachin Chapel, the only intact religious building, became the parish church. ", "A Protestant church was built in the district of the Place Saint-Ursula. ", "In September 1601 Annonay received a visit by the future Saint Francis de Sales and a little later from the future Saint John Francis Regis. ", "The reconstruction of the city was characterized by the arrival of new religious communities and the creation of educational institutions such as the Convent of Santa Maria. ", "A new hospital, joining the medieval structures of Notre-Dame La Belle and Notre-Dame de l'Aumône was created on 16 March 1686 at the Champ-de-Mars.", "\n\nIn 1685 the revocation of the Edict of Nantes affected Annonay. ", "Protestants who were at that time 50% of the population had to choose between exile, abjuration, or to continue practicing their religion in secret. ", "The Protestants were mostly artisans, manufacturers, wine-growers, and traders. ", "A century later a census showed that there were only 7% Protestants mostly from the upper classes.", "\n\nThe paper industry was started in Annonay in the 17th century with the Montgolfiers, papermakers originating from Auvergne, installed at Vidalon-lès-Annonay (today a hamlet in the commune of Davézieux). ", "The Johannot, another Auvergne family, had been settled in Faya since 1634. ", "Attracted to the water quality, the driving force of the rivers, and the abundance of raw materials (rags), they imported technological innovations from Holland: e.g. the Dutch pile.", "\n\nIn the maze of streets and small squares of Annonay, there was progress with the commissioning in 1726 of four public fountains fed by captive water sources.", "\n\nIn 1780 industrial production was booming: 25,000 cow hides and 500,000 sheep skins were processed by the tanneries. ", "Paper mills produced 300 tons of paper. ", "This success did not go smoothly: the employment in great numbers of the best workers by Montgolfier caused a scarcity of labor and demands for wage increases. ", "There was a strike for two months in the Vidalon Workshop in late 1781 after a long period of tension between the employer and his employees, the first lost the best of his workforce through his intransigent attitude at a time when fights between gavots and journeymen were common.", "\n\nIn 1781, the term Bailiage was changed to Sénéchaussée.", "\n\nOn 14 December 1782, thanks to Etienne and Joseph Montgolfier, the first balloon rose above Vidalon-lès-Annonay. ", "It consisted of a large paper bag lined with cloth placed over a fire of wet straw and wool. ", "It remained however a private experience: the first public official flight in a hot air balloon took place on 4 June 1783 at Annonay, or precisely from the Place des Cordeliers – in front of a chosen public: the Members of State particularly of Vivarais. ", "Several other inventions are credited to Joseph Montgolfier: the hydraulic ram, the method of manufacture of Wove paper and filter paper, called joseph paper.", "\n\nAnnonay developed through trade. ", "It benefited from an improved road network (even if it was as a result of the revolt of camisards). ", "In 1787 Annonay had 130 merchants for about 7,000 inhabitants. ", "Among them: 11 drapers, 11 clothiers, 26 grocers, 3 goldsmiths, 26 shoe merchants, and 28 tailors. ", "At the same time, the Catholic parish of the city was headed by a priest-archpriest, and vicars. ", "The college of canons was composed of the prior and twelve canons. ", "The monastery of the Poor Clares had twelve nuns and two lay sisters, the Convent of Santa Maria had thirty nuns and four lay sisters. ", "Adding to this religious presence was the pastor of the Protestant community.", "\n\nFrench Revolution\nThe French Revolution started down this organization. ", "The region was characterized by a wave of dechristianization which caused a certain spirit of resistance among the Catholic and Protestant populations. ", "The Terror made victims such as Pierre-François Dulau-Dallemand, the pastor of Saint-Julien-Vocance; Bartholomew Montblanc, Vicar at Givors hidden around Annonay, and the priests of Rouville, Bac-et-Guards, and former Jesuits. ", "To them must be added the three Sisters of Saint-Joseph from the community of Vernosc-lès-Annonay.", "\n\nThe representatives of Annonay, while being very favorable to the new order, adopted a moderate attitude. ", "This moderation was well illustrated by the personality of the lawyer Boissy d'Anglas, closely linked to the Girondins. ", "André Joseph Abrial, a native of Annonay, became Minister of Justice and was an author of the Civil Code (Code Napoleon).", "\n\n19th century\n\nDuring the first half of the 19th century, the need for an industrial workforce for paper-making and leather at Annonay attracted population from the surrounding countryside. ", "The number of inhabitants doubled from 5,550 in 1801 to 11,398 in 1846 (it would reach 18,445 inhabitants in 1866). ", "The physiognomy of the city changed with the rapid development or opening of new shopping streets (Rues Sadi Carnot, Montgolfier, Boissy d'Anglas, Tournon, Melchior de Vogue). ", "A new city hall was built in a developing area.", "\n\nIn 1822, the Congregation of St. Basil, a Catholic order of priests was founded in the town.", "\n\nOn 26 February 1848, the city workers violently showed their support for the revolutionary Parisians (during February 1848), including the stoning of houses belonging to notable people. ", "The army maintained order.", "\n\nWith demographic pressure, the size of the existing infrastructure including the sole Catholic church did not allow proper welcoming of new residents to the faith. ", "Two new churches were built: Saint-Francis and Saint-Joseph. ", "Around the city, about a kilometer or two new town houses were built in the image of the Domain of Marc Seguin or Déomas Castle constituting a \"sunbelt\".", "\n\nThe tannery rode the industrial prosperity of Annonay. ", "High-end gloves were made in Grenoble but the best skins came from Annonay. ", "In 1870 the Annonay tannery processed 8 million skins and employed 50% of the workers in the city. ", "Three thousand of them were working at the time in this industry.", "\n\nImproving the road network and creating the first lines of railway put an end to Annonay's role as a commercial center for the mountainous hinterland. ", "The latter was now in direct contact with Saint-Étienne. ", "The east-west trade that were advantageous to Annonay were replaced by north-south trade particularly following the valley of the Rhône. ", "From now on Annonay, although the hometown of Marc Seguin, would be connected to the railway network by a branch line.", "\n\nThe Franco-Prussian War of 1870 blocked exports: the stocks of the Annonay works were blocked for a time in Paris. ", "This crisis began the decline of the tanneries in Annonay compounded by weak industrial investment. ", "More than 2,000 employees were laid off to go and find work in other areas.", "\n\nBarthélémy Baru Canson married the daughter of Étienne de Montgolfier. ", "New processes of papermaking were established and production became specialized. ", "The paper mill employed 1,500 people around 1875. ", "Such activity requires a lot of water which was supplied by the Ternay reservoir from 1867. ", "Its water was also distributed to residents through standpipes positioned in each district.", "\n\nWhile modern community life was started with the creation of the first sports clubs such as Annonéenne, a company gym which still exists; the nascent local press reported on events such as celebrations marking the centenary of the first flight of a balloon. ", "Annonay improved its main entrance by creating a new road connecting the PLM station to the center of town: the Boulevard of the Republic (1883–1888).", "\n\nThe 20th century\n\nIn the early 20th century, the city still retained its appearance after the Wars of religion except for the Station district. ", "Construction works were mainly concentrated in the industrial valleys of Cance and Deume. ", "The historic center saw the building of Annonay's first department store \"Les Galeries Modernes\" (currently Public Service offices) and reconstruction on another site of the historic church of Notre-Dame. ", "At this time the magic of electricity came (1910). ", "The telephone was known and used. ", "The national news with the laws on religious congregations and the separation of church and state was a passion in Annonay and in its surroundings. ", "There were expulsions of monks and nuns with the Querelle des inventaires particularly active during violent protests motivated by the fear of a return to the excesses of 1793–1794.", "\n\nThe First World War with its refugees, its wounded, its mutilated, and its dead (552 from Annonay) put an end to the protests.", "\n\nThe period between the two wars was marked by the presidential visit of Alexandre Millerand in 1923 on the occasion of the inauguration of the monument in honor of Marc Seguin and by the 150th anniversary of the first flight of the balloon (1933). ", "The appearance of the city remained the same: dirty, dark streets, few new buildings like the \"Vanaude\" house. ", "The \"sunbelt\" of castles contrast with the city center of slums and polluting industries. ", "On the economic front mechanical industries grew: machines for the tannery of the Mercier brothers and especially for the manufacturing of buses. ", "The old craft business of Jean-Joseph Besset became Renault then Irisbus, who manufacture its entire range of buses and coaches for France. ", "These entrepreneurs invented the concept of the industrial zone. ", "The descendants of the Montgolfier brothers, B. and E. de Canson invented tracing paper and photographic paper. ", "Weaving experiencing strong growth.", "\n\nDuring the Second World War Annonay was the site of the last battles of 1940. ", "On 6 June 1944 the local resistance of the Secret Army were the first to liberate their own city. ", "These facts earned the city the Croix de Guerre 1939–1945 and a citation at the order of the nation.", "\n\nWhen peace returned, industrial sectors developed in Annonay such as food processing and pharmaceutical production. ", "Other industries declined following the marginalisation of the work of leather and textile after great social conflict. ", "The face of the city changed. ", "From 1949 near the Besset factory a new district was created from scratch on farmland. ", "It contains large housing subdivisions, schools, sports facilities and shops. ", "Catholics built their fourth church in the city. ", "Urbanization moved towards Boulieu-lès-Annonay, Roiffieux, and especially Davézieux with its industrial and commercial area. ", "In the center, renovation of the old town, reconstruction of the banks of the Deume and the hillsides of Cance are scheduled. ", "From a city with black façades, slums, and industrial wastelands, Annonay has become a colorful city made of new or rehabilitated buildings. ", "The Deume has been covered for more than one kilometer and a new axis conveys traffic: the Avenue de l'Europe.", "\n\nThe Annonay people celebrated with great pomp the centenary of the railway line (1970), Marc Seguin (1975 and 1986), and the bicentennial of the first flight of the hot air balloon (1983).", "\n\nThe 21st century\n\nThe city bore the brunt of deindustrialisation. ", "Economic jewels disappeared causing job losses (industrial weaving, manufacture and paper production). ", "At the same time new companies emerged bringing hope in the fields of food and cleaning equipment.", "\n\nAlthough more discreet in a secular society religious life remains. ", "The Catholic community created the parish of Sainte-Claire by merging the parishes of the city of Annonay, Roiffieux, Vocance, Villevocance, Vanosc, Saint-Julien-Vocance, Monestier, and the hamlet of Toissieu. ", "The Protestant community is shared between the Evangelical Church and the United Protestant Church of France. ", "The Muslim community built the House of the Orient, a building which includes the first mosque in Annonay.", "\n\nOn 8 March 2001, an ETA suspect was arrested at a local roadblock.", "\n\nAssociative and cultural life is rich. ", "The people of Annonay celebrated the centennial of the opening of the new Church of Notre Dame (2012) and the establishment of the Joseph Besset factory (2013).", "\n\nHeraldry\n\nAdministration\nList of Successive Mayors\n\nMayors from 1942\n\n(Not all data is known)\n\nTwinning\n\nAnnonay has twinning associations with:\n Backnang (Germany) since 1966. ", "\n Barge (Italy) since 2001. ", "\n Chelmsford (UK) since 1999.", "\n\nPopulation\n\nDistribution of age groups\nThe population of the town is relatively old. ", "The proportion of people above the age of 60 years (28%) is higher than the national rate (21.8%) and the county rate (26.8%). ", "Like the national and departmental proportions, the female population of the commune is higher than the male population. ", "The rate (54%) is higher by more than two points than the national rate (51.9%).", "\n\nPercentage distribution of age groups in Annonay and Ardèche Department in 2009\n\nSources:\nEvolution and Structure of the population of the Commune in 2009, INSEE.", "\nEvolution and Structure of the population of the Department in 2009, INSEE.", "\n\nEconomy\nAnnonay has a strong industrial tradition, originally powered by the water flowing through the deep gorges around the town. ", "In the 19th century, it was connected to the Paris-Lyon Railway and was famed for the best paper in France. ", "It also produced glove leather and cotton, woolen, and silk goods. ", "A modern dam was constructed across the Ternay, an affluent of the Deûme northwest of town, which expanded the power available to local factories. ", "By the First World War, the leather industry had become predominant, while the economy expanded to include more raw silk, flour, chemical manures, glue, gelatine, brushes, chocolates, and candles. ", "Although the leather industry has since declined, the Tannerie d'Annonay (\"Annonay Tannery\") continues the tradition under the Grison brand.", "\n\nIrisbus (a Renault Vehicles Industries and Fiat Iveco joint venture) builds buses and is the largest single employer with around 2,000 staff with several associated businesses.", "\n\nThe multinational paper company Arjo Wiggins subsidiary Papeteries Canson et Montgolfier SA, which dates back to 1557 owns three of the several paper factories in the town.", "\n\nOther industries in or close to the town include plastics, textiles, and pharmaceutical companies including Ciba, Aguettant and Tetra Médical.", "\n\nThere are a number of vineyards near the town.", "\n\nThe average salary in the area is 23,300 euro.", "\n\nCulture and heritage\n\nCivil heritage\n\nThe Montgolfier brothers\n\nA Statue of the brothers Joseph and Etienne de Montgolfier located in the Place de Liberation. ", "A work by the sculptor Henri Cordier, it was inaugurated on 5 June 1888.", "\nThe Pyramid stone obelisk, the work of Étienne-François Imbard located on the Boulevard de la République. ", "Built between 1819 and 1822, it commemorates the first ballooning experience of the Montgolfier brothers.", "\nThe Montgolfier-Canson Paper Mill (18th century) is registered as an historical monument.", "\n\nMarc Seguin\n\nA Monument to Marc Seguin, Place de la Liberté ( 1923 ). ", "This bronze statue, the work of François Clémencin, was removed by the German army in 1942 then was replaced by a statue by the same sculptor which was inaugurated on 1 June 1947.", "\nThe Domain of Marc Seguin at Varagnes (19th century) is registered as a historical monument.", "\n\nBoissy d'Anglas\nA Statue of François-Antoine de Boissy d'Anglas located at the Champ de Mars. ", "The work of the sculptor Pierre Hébert, it was inaugurated on 5 October 1862. ", "The base is decorated with a bas-relief bronze (also the work of Pierre Hébert) representing the meeting on 1 Prairial Year III of the National Convention.", "\nA Painting: Boissy d'Anglas at the National Convention, 1 Prairial Year III, the work of Auguste Jean-Baptiste Vinchon, displayed in the wedding hall of the Town Hall.", "\n\nFountains\n\nThe Jean-Baptiste Béchetoille fountain (1900). ", "The work of the architect Millefaud.", "\nThe Fountain in the Place Grenette (1726).", "\nThe Fountain in the Place de la Liberté opened in 1923.", "\n\nOther sites of interest\n\nThe City Hall of neoclassical inspiration (1835), rebuilt twice after fires (1870 and 1926).", "\nThe Fortified house of Nicolas du Peloux in Rue de la Postern (Governor in 1577).", "\nBourgeois mansions in Rue de Trachin from the 17th and 18th centuries.", "\nThe Valgelas Bridge (14th century), a former city gate.", "\nThe La Vanaude House at 33 Avenue Marc-Seguin (1930) is registered as an historical monument. ", "It is the work of the architects Hugues Gosselin and Maurice Frappa.", "\nThe César Filhol Museum in Rue Bechetoille (1700), formerly the royal bailiwick house. ", "The museum contains two items that are registered as historical objects:\nA Group Sculpture: Virgin of Pity (16th century)\nA Statue: Christ (17th century) possibly by Veyrines.", "\nThe Place Mayol (16th century) with a door of glazing beads.", "\nThe Château of Déomas (1876) illustration of the \"Sun Belt of Annonay\".", "\nSubstantial remains of the railway line between Firminy, Bourg-Argental, and Saint-Rambert-d'Albon:\nVidalon Tunnel, a passage on a ledge above the Deûme (covered in vegetation in 2013);\nRetaining walls with characteristic stone-setting of the \"Station district\" (in the Place de la Gare in Annonay); Sacré-Cœur tunnel;\nthe Vissenty cutting.", "\n\nReligious heritage\n\nThe Church Our Lady of the Assumption, in the neo-Byzantine Roman style, built between 1904 and 1912. ", "Its bell tower contains a Carillon of five bells with a weight more than . ", "It replaced a church of the same patronage located on the Place de la Liberté. ", "The work of the architects Rey, Allengry, and Joly. ", "Its interior decoration (paste paintings) is inspired by the Litanies of the Blessed Virgin, the Litany of Loreto, the Bible, hagiography, and the history of Annonay. ", "Consecrated in 1954, it contains many items that are registered as historical objects:\n2 Statues: Adoring Angels (18th century)\nA Statue: Virgin and child (18th century)\nA Gallery Organ (1880) signed Cavaillé-Coll.", "\nA Choir Organ (1848)\n2 Statues: Acolyte Angels (17th century)\n2 Statues: Cherubs (17th century)\nA Bust-Reliquary: Saint John of the Cross (17th century)\nA Bust-Reliquary: Saint Peter of Alcantara (17th century)\nThe Church of Saint Francis of Assisi, in neo-Gothic style (1863–1866).", "\nThe Church of Saint Joseph of Cance, in neo-Gothic style (1870–1872).", "\nThe Church of the Holy Family of Perrières, in modern style (1957–1958).", "\nThe Church of Saint Maurice of Toissieu, in neo-Gothic style (1876–1878).", "\nThe Chapel of the Evangelical Free Church, Boulevard de la République (1900).", "\nThe Temple of the Reformed Church, Rue Franki Kramer, portal from the 18th century.", "\nOrient House, Muslim cultural and religious center (2008–2013).", "\nThe Chapel of the Hospital, dating from the 17th century. ", "The chapel contains many items that are registered as historical objects:\nA Sideboard (19th century)\n2 Apothecary Jars (19th century)\nA Venetian Wall lamp mirror (18th century)\nA Chest of Drawers with diamond corners (18th century)\nA Painting: Christ on the Cross (17th century)\nA Painting: The Martyrdom of Saint Sebastian (17th century)\nA Painting with gold frame: Pope Clement VI (18th century)\nA Painting with gold frame: Saint Jerome (17th century)\nA Painting with gold frame: Adoration of the Trinity (17th century)\n24 Apothecary Jars (19th century)\nA Mortar and pestle (1654)\nA Mortar and pestle with chopping block (13th century)\nThe Chapel of the Convent of Saint Mary (1633) is registered as an historical monument. ", "The convent was built on the foundations of a castle called Malatour in 1630 with the Chapel built later in 1633. ", "The chapel contains several items that are registered as historical objects:\nA Triptyche: 3 paintings of the life of Saint Francis Regis (1888)\nA Retable (17th century)\nA framed Painting: Raphael Sara and Tobie (17th century)\nWood panelling and Paintings (17th century)\n\nThe Vierge des Fouines Statue (Nosy Virgin Statue) or Our Lady of Faith Statue placed on the rocks of Saint-Denis. ", "5.22 metres tall and the work of Bachini from Lyon. ", "It was blessed on 26 September 1943.", "\nThe Chapel of Trachin or Trachi is in Gothic style with an octagonal bell tower, with remains of a priory dating from 1320. ", "The chapel contains several items that are registered as historical objects:\nA Decorative ceiling painting (19th century)\nA Bust of Saint François-de-Sales (17th century)\nA Painting: the Nativity of the Virgin (18th century)\nA Painting: Saints Jacques and Philippe (1658)\nA Statue: Virgin and child (18th century)\nThe Chapel of Vidalon-les-Annonay contains a Gallery Organ (1818) that is registered as an historical object.", "\nThe former Chapel of Saint-Clair in Rue Sadi Carnot (14th century) is registered as an historical monument. ", "It was built in Gothic style from 1348 to 1356.", "\nThe Cemetery chapel at Toissieu.", "\n\nMilitary Heritage\nThe War Memorial (1914–1918, 1939–1945, and subsequent wars). ", "Designed by architect Maurice Luquet, the statues The pensive soldier and The Stricken Woman were sculpted by Paul Landowski. ", "It was inaugurated on 25 June 1922.", "\nThe Monument of Mobiles (1907) at the cemetery. ", "Designed by architect Theodore Joly and sculptor Aimé Millet.", "\nAn Old door from the castle dating from the 12th century.", "\nThe Soubises Vaults, remnants of the walls with a covered path around (12th–13th centuries).", "\nThe Tower of Martyrs, from the 12th century, the remains of the ramparts of the city, this tower is located above the Deume. ", "It is said that the condemned were thrown to their death in the shallow river. ", "It is also believed that the name may come from the Martins ford which it defended.", "\n\nCultural heritage\n\nThe \"Italian\" Theatre (1887), in the Place des Cordeliers, built on the site of the chapel of the former Franciscan convent.", "\n\nNotable people linked to the commune\nFrançois-Antoine de Boissy d'Anglas\nGuillaume de Roussillon, Lord of Annonay from 1271 to 1277. ", "Sent by the king of France, Philippe III the Bold and Pope Gregory X to Saint Jean d'Acre which, in 1275, was the capital of the Kingdom of Jerusalem. ", "Victim of a plot by Charles of Anjou and Guillaume de Beaujeu, Grand Master of the Knights Templar: he did not return and his son Artaud took the succession of the \"old castle\".", "\nPierre Bertrand (1280–1349): cardinal, Jurist who defended the jurisdiction of the church at the conferences of Vincennes (1329).", "\nCharles Francis of Aviau of the Woods of Sanzay (1736–1826), Archbishop of Vienne and founder, during the Revolution, of a clandestine seminar on the site of the town college (College of the Sacred Heart).", "\nLouis de Beaudine Romanet de Lestranges (1749–1815), general of the armies of the Republic, born in Saint-Félicien and died at Annonay.", "\nCount Abrial (1750–1826): politician and magistrate who played an important role under the Consulate, the Empire, and the Restoration.", "\nAndré Barthélémy Boissonnet (born 24 August 1765 at Annonay, died 26 May 1839 at Sézanne), French general and politician of the 19th century.", "\nBarthélémy de Canson (1774–1859): Peer of France and famous papermaker for his creation of Canson art paper.", "\nThe Monneron brothers, founders of the Monneron Bank (1791–1792): Paul Mérault Monneron, Chief Engineer of the La Perouse expedition, Joseph François Augustin Monneron, Pierre Antoine Monneron, Louis Monneron, and Charles Claude Ange Monneron.", "\nThe Montgolfier Brothers\nMarc Seguin (1786–1875), engineer, inventor of the wire-cable suspension bridge and the fire-tube boiler.", "\nAuguste Bravais (1811–1863), physicist who created the mathematical models of crystal structures known as Bravais lattices. ", "He made one of the first scientific ascents of Mont Blanc (1844).", "\nMarie-Joseph Canteloube de Malaret (born at Annonay on 21 October 1879, died in Paris on 4 November 1957): composer, a pupil of Vincent d'Indy, a specialist in folk songs of the French provinces and in particular \"Chants d'Auvergne\". ", "He also wrote operas.", "\nVital Chomel (born on 24 August 1922 at Annonay): curator then Director of the Archives of Isère (1958–1988), author of important books on his specialty and the Dauphiné in general.", "\nJacques Trémolin: known as a storyteller on animals, this aristocratic resistance fighter and communist organized, under the pseudonym Loyola (a reference to his education with the Jesuits), the liberation of the city in June 1944 where he proclaimed a republic and was mayor until its recovery by the Germans.", "\nThe Bechetoille family, merchant-drapers and bankers.", "\nThe Johannot family, a Protestant family who created the first paper mill in Annonay in 1634. (", "The \"Jo\" in Arjomari: a group of four large French papermills) (Jean-Baptiste Johannot, Jean-Joseph Johannot)\nThe Binet family, of Protestant origin, cousins of Johnannot and known for their manufacture of felt and baize with the same name used for drying the paper pulp. ", "This technique is still used today for the production of banknotes.", "\nOlivier Dussopt (1978–), politician\nMaurice Grimaud (1913–2009), chief of police of Paris in May 1968 and was the grandson of Antoine Grimaud (1852–1926), Mayor of Annonay from 1904 to 1919.", "\nFred (1924–) and René Mella (1926–), tenors of Les Compagnons de la chanson.", "\nRoger Dumas (1932–2016) comedian and French author, born in the commune.", "\nFrançois Joseph Clozel (1860–1918), governor of French West Africa.", "\nAbou Lagraa (1970–) dancer and contemporary choreographer, born in Annonay.", "\nDavy Mourier (1976–), actor, writer, director, designer, and French animator, born in the commune.", "\nJacques Rouviere (1938–), writer, verbicruciste, and former director of the Bank of France. ", "Member of the Academy of Letters Pyrenees.", "\nPaul Desgrand (1799–1878), cousin of the Montgolfiers and the Seguin brothers, he was a great merchant of French textiles and played an important role at Creusot before the Schneiders then at Lyon as a silk merchant where he finished his career in Tassin-la-demi-lune.", "\nClément Grenier (1991–), football player of Olympique Lyonnais and champion of Europe U19.", "\n\nCulture\nArchives: Parish and Civil Records, genealogical analysis, municipal Proceedings\nMuseum of the Canson & Montgolfier paper-makers: traces the history of the cottage industry of paper. ", "It is the only museum to present a large working paper machine.", "\nVivarois Municipal Museum César Filhol: presents local ethnology, collections, and traces the history of local inventions by the Montgolfiers and Seguins.", "\nOccitan culture still holds a significant place\nJean-Pierre Mocky used the town as the setting for his film Litan (1982).", "\nThe 2003 part-British funded movie L'homme du train (The Man on the Train) was filmed in Annonay.", "\n\nCulinary specialities\nAngel wings (Bugnes)\nPantins\nPogne of Annonay\n\nLocal press\nThe regional newspaper Le Dauphiné Libéré is available in Annonay. ", "It also hosts the headquarters of the weekly Le Reveil du Vivarais. ", "Another weekly L'Hebdo de l'Ardèche also covers the territory. ", "Since the early 2000s a free monthly made its appearance, L'Indispensable is distributed among traders in the Annonay basin. ", "It informs readers about cultural events taking place around the region.", "\n\nFestivals\nEach year\nIn February:\nThe Premier International Festival of Film\nIn June:\nThe Festival of Hot air Ballooning (1st weekend).", "\nThe Festi'roc 07, a Christian modern music festival, it is organized by the Catholic parishes of the Annonay Basin.", "\nIn November:\nThe Love of good food of Ardèche and Upper Vivarais, (3rd weekend). ", "This is organized by the association of the same name. ", "During a weekend, the Place des Cordeliers becomes a showcase of Ardèche products. ", "Sixty exhibitors and many activities punctuate this event.", "\nThe Championship of France for Hot air Ballooning\n\nPicture gallery\n\nHistorical bibliography\n\nFrançois Chomel, Annonay pas à pas, pierre à pierre, Édition du Vivarais, Annonay, 1995, 250 p.\nPierre Fanget, Annonay ma ville, Annonay, 1971.", "\nAbbé Filhol, Histoire religieuse et civile d'Annonay et du Haut–Vivarais depuis l'origine de cette ville jusqu'à nos jours, Tomes 1, 2, 3 et 4, Moussy ainé, 1882.", "\nEmmanuelle Faure, Claude Osset, Annonay, Mémoire en images, Éditions Alan Sutton, Saint-Cyr-sur-Loire, 127 pages, 2004.", "\nEmmanuelle Faure, Bernard Faure, Claude Osset, Annonay en Fêtes, 1860–2000, Jean Pierre Huguet Editeur, Saint-Julien-Molin-Molette, 2002, 283 p.\nLa Gazette d'Annonay, Hebdomadaire local paraissant entre 1889 et 1944.", "\nAntoine Grimaud, Annonay, la vie municipale de 1870 à 1920, Imprimerie Hervé, Annonay, 1926, 540 p.\nGaston Grimaud, Mon vieil Annonay, Decombe frères, Annonay, 1948, 48 p.\nLe Journal d'Annonay, Hebdomadaire local paraissant entre 1865 et 1944.", "\nAbbé Léorat Picansel, Annonay pendant la Terreur, Tomes 1 et 2, Amis du Fonds Vivarois, 1988.", "\nRémy Bernard, Histoire d'Annonay et sa région, Horvath, Roanne, 1981, 149 p.\nLe Réveil du Vivarais et de la vallée du Rhône, Hebdomadaire local paraissant depuis 1944.", "\n\nSee also\n Communes of the Ardèche department\n History\n Parlement of Toulouse\n Languedoc\n Estates of Languedoc\n Vivarais\n Pays d'états\n\nNotes\n\nReferences\n\nExternal links\n Annonay Official website \n Chamber of Commerce and Industry of Ardèche \nAnnonay on Lion1906\nAnnonay on Google Maps\nAnnonay on Géoportail, National Geographic Institute (IGN) website \nAnnonay on the 1750 Cassini Map\nAnnonay on the INSEE website \nINSEE \n\nCategory:Communes of Ardèche" ]
{ "pile_set_name": "Wikipedia (en)" }
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[ "/*\n * Copyright 2002-2019 the original author or authors.", "\n *\n * Licensed under the Apache License, Version 2.0 (the \"License\");\n * you may not use this file except in compliance with the License.", "\n * You may obtain a copy of the License at\n *\n * https://www.apache.org/licenses/LICENSE-2.0\n *\n * Unless required by applicable law or agreed to in writing, software\n * distributed under the License is distributed on an \"AS IS\" BASIS,\n * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n * See the License for the specific language governing permissions and\n * limitations under the License.", "\n */\n\npackage org.springframework.context.annotation\n\nimport org.junit.", "Assert.assertEquals\nimport org.junit.", "Test\nimport org.springframework.beans.factory.getBean\nimport org.springframework.beans.factory.parsing.", "BeanDefinitionParsingException\n\nclass KotlinConfigurationClassTests {\n\n\t@Test(expected = BeanDefinitionParsingException::class)\n\tfun `Final configuration with default proxyBeanMethods value`() {\n\t\tAnnotationConfigApplicationContext(FinalConfigurationWithProxy::class.java)\n\t}\n\n\t@Test\n\tfun `Final configuration with proxyBeanMethods set to false`() {\n\t\tval context = AnnotationConfigApplicationContext(FinalConfigurationWithoutProxy::class.java)\n\t\tval foo = context.getBean<Foo>()\n\t\tassertEquals(foo, context.getBean<Bar>().foo)\n\t}\n\n\n\t@Configuration\n\tclass FinalConfigurationWithProxy {\n\n\t\t@Bean\n\t\tfun foo() = Foo()\n\n\t\t@Bean\n\t\tfun bar(foo: Foo) = Bar(foo)\n\t}\n\n\t@Configuration(proxyBeanMethods = false)\n\tclass FinalConfigurationWithoutProxy {\n\n\t\t@Bean\n\t\tfun foo() = Foo()\n\n\t\t@Bean\n\t\tfun bar(foo: Foo) = Bar(foo)\n\t}\n\n\tclass Foo\n\n\tclass Bar(val foo: Foo)\n}\n" ]
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[ "#include <linux/module.h>\n#include <linux/vermagic.h>\n#include <linux/compiler.h>\n\nMODULE_INFO(vermagic, VERMAGIC_STRING);\n\nstruct module __this_module\n__attribute__((section(\".gnu.linkonce.this_module\"))) = {\n .name = KBUILD_MODNAME,\n .init = init_module,\n#ifdef CONFIG_MODULE_UNLOAD\n .exit = cleanup_module,\n#endif\n .arch = MODULE_ARCH_INIT,\n};\n\nstatic const char __module_depends[]\n__used\n__attribute__((section(\".modinfo\"))) =\n\"depends=x_tables\";\n\n" ]
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[ "1. ", "Field of the Invention\nThe present invention relates to a hydraulic orifice, and more particularly to a hydraulic orifice which reduces pulsation of an oil supplied to a variable valve apparatus of an engine.", "\n2. ", "Description of Related Art\nGenerally, oil pressurized at a hydraulic pump passes through a hydraulic line in a cylinder block and is supplied to a cylinder head. ", "Finally, the oil is supplied to various variable valve apparatuses through an oil control valve.", "\nA head oil journal is formed between the cylinder block and the cylinder head of the engine, and a hydraulic orifice is mounted at the head oil journal such that a flow direction, a pressure, and a pulsation of the oil received from the hydraulic pump are controlled and the controlled oil is supplied to the oil control valve.", "\nA conventional hydraulic orifice is mounted at a head oil journal formed in a cylinder head, and supplies oil received from a hydraulic pump to a supply line.", "\nThe hydraulic orifice includes an outer case and an inner case, the outer case is pressed on the head oil journal, and the inner case is pressed on an interior circumference of the outer case. ", "At this time, a forming portion formed at the outer case is bent toward the inner case so as to assemble the inner case to the outer case.", "\nAn inner chamber is formed in the inner case. ", "In addition, an oil hydraulic line for connecting the inner chamber with the supply line is formed at an exterior circumference of the inner case. ", "The oil hydraulic line has spiral shape.", "\nAccording to a conventional hydraulic orifice, however, pulsation of the oil is reduced when passing through the oil hydraulic line. ", "Therefore, the oil hydraulic line having suitable length should be formed. ", "For this purpose, the oil hydraulic line of spiral shape should be formed and it may be difficult to form the oil hydraulic line.", "\nIn addition, since the outer case and the inner case are assembled by bending the forming portion formed at the outer case toward the inner case, a diameter difference between both ends of the outer case cannot be controlled within a predetermined error range. ", "Since the oil hydraulic line is formed at the exterior circumference of the inner case, a part of the oil hydraulic line may be blocked when the forming portion is bent.", "\nFurther, when pressing the outer case on the head oil journal, an oil passage flowing the oil received from the hydraulic pump into the cylinder head and a supply hole of the outer case should be aligned. ", "For this purpose, an additional tool should be necessary and it may be hard to assemble.", "\nThe information disclosed in this Background of the Invention section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art." ]
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[ "Tag: Camer\n\nShe came, she saw and she certainly rapped her voice out last night during her performance at the second day of the 4th edition of Douala Hiphop Festival at Stade Soppo Priso in Bonapriso, Douala.", "\n\nAnd going by the reviews, CIANA proved how versatile and comfortable she can be on stage as she performed to Bangwa Sense wrapping it up with Ozeile Nchiengo her popular 2014 single. ", "A few first images below.", "\n\nAnd there you have it!", "\n\nCredits: Afroziky | @DoulHiphopFest\n\nTwitter/Instagram follow: @bestciana\n\nFacebook: Miss Ciana\n\nAdvertisements\n\nShare this:\n\nLike this:\n\nA well placed marriage of talent and sound made from Cameroon. “", "Jusqu’au Matin” a CamerFranAnglais afropop new track by UK based La Bizu and Belgium based Miss Lena is that perfect song that gets you out of your chair and onto the dance floor to shake all night long.", "\n\nShare this:\n\nLike this:\n\nIt’s about that time in their movie cycle where they themselves get to seat back and watch the show unfold. ", "After all the hard work is done, the buzz is created and all the attention gotten, the cast and crew of the revolutionary movie VIRI are warming up for the première.", "\n\nSometime in October we were approached with the idea of a potential collaboration between MMPR and a new project we saw had the desire to create a difference and be different. ", "It was jam packed with uniqueness and a promise to portray outstanding unconventionalities. ", "Though conflicted on the acceptance of this unlikely project to our market, we went ahead and took a risk as the project was not yet at a phase where we could see to make a judgement for ourselves as is customary to our work procedure. ", "Today we are being celebrated for celebrating this work of art.", "\n\nLet’s go through some spectacular moments we shared on VIRI shall we?", "\n\nOur online promo kicked off with an intro of the project and we did our very first profiling with the producer and actor Nkanya Nkwai. ", "Here is a link for recap.", "\n\nAs we went on we spoke to other cast and crew members, we had one spectacular chat with one of the cast members, find out who that is on this link.", "\n\nAs we progressed we had the pages of VIRI, MMPR and personal accounts flooded with VIRI pictures and articles. ", "Here are pages you can catch on Facebook to bring you up to speed for the première… go here and here.", "\n\nWe had some fabulous bloggers share in the VIRI spirit; they took out their time to blog on and promote VIRI so a big S/O goes to Muke Alison, Yefon Mainsah, Tina Monique & Partner, TipTop Stars. ", "Check out a few links here and here\n\nWhen we celebrated the life and experiences of Tata Nelson Mandela and found out the similarities he shared with the characters in VIRI, it was such an honour for us. ", "Rest in perfect peace our Tata.", "\n\nThen we got what seemed like a feasible existence of VIRI for the first time, the teaser poster and the teaser to the trailer. ", "Then it became so real even in the eyes of you all.", "\n\nThe day we felt most lucky came as we unveiled the first ever VIRI movie poster. ", "What was going to be its CD jackets and we had online reach of over 400.000 views and support.", "\n\nSince then support has continuously been amazing. ", "We even got mentioned on GMC Cameroon as the trending thing online, we couldn’t be more blessed.", "\n\nIn under a few days leading to the première, the producer with a German engine Nkanya Nkwai has been able to tour almost every relevant radio and TV stations around the Littoral; South West and Centre provinces for promo talks – from STV, Canal2 Internationale to CRTV. ", "Radio includes likes of FM 105, Sweet FM just to name a few.", "\n\nThe runners are almost at the finished line, the race is almost won, and we must not despair or doubt our dreams. ", "Nkanya said “My goal is to reach 500people at least for the première night, it could still be more but I won’t be happy with less.” ", "Well, well Nkanya seems you are going to beat that after all. ", "It’s been amazing growing this baby of yours together and come March 22nd we will all celebrate a victory like no other.", "\n\nLet’s all keep the VIRI dream alive and be there at Hotel La Falaise on Saturday March 22nd at 7.00pm prompt. ", "For more information about ticket sale, please call: 71674948 or 70615687.", "\n\nKudos to DreamsAlive Productions, the cast and crew of VIRI for a spectacular job. ", "Catch the teaser trailer which received a huge cheer from our MMPR One guests below…\n\nFollow Nkanya on Twitter: @NkanyaNkwai\n\nFollow us on Twitter: @ModeMaisonPR\n\nShare this:\n\nLike this:\n\nMaison d’Afie by Sarah Divine-Garba is a womenswear brand launched a couple of years ago in the UK. ", "Life took over Sarah’s life and this venture was put on hold. ", "With a relocation back to Cameroon, a wedding, a daughter and a relocation to Switzerland done through the time the brand was on hold, Sarah is back!!", "\n\nThe new collection dubbed “Mami Nyanga” is a subtle romance between “street couture” and tropical flavours giving rise to a few essential classic items. ", "The collection is made of 8 interchangeable pieces suitable for any occasion. ", "The idea here is to achieve much with less.", "\n\nThey remained true to themselves by infusing tribal accents into the designs with the use of colour and embroidery of tribal art. ", "Most of the work is artisanal with a lot of attention put into the cut.", "\n\nQuality and practicality were the key drivers in their thought process. ", "The collection features customized prints in silks, and polyester and there is indeed a pick for every lady." ]
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[ "Richard Kaner and Maher El-Kady in Kaner's office. ", "Kaner is holding a replica of a new energy storage and conversion device they developed. ", "Credit: Reed Hutchinson/UCLA\n\nUCLA researchers have designed a device that can use solar energy to inexpensively and efficiently create and store energy, which could be used to power electronic devices, and to create hydrogen fuel for eco-friendly cars.", "\n\nThe device could make hydrogen cars affordable for many more consumers because it produces hydrogen using nickel, iron and cobalt—elements that are much more abundant and less expensive than the platinum and other precious metals that are currently used to produce hydrogen fuel.", "\n\n\"Hydrogen is a great fuel for vehicles: It is the cleanest fuel known, it's cheap and it puts no pollutants into the air—just water,\" said Richard Kaner, the study's senior author and a UCLA distinguished professor of chemistry and biochemistry, and of materials science and engineering. \"", "And this could dramatically lower the cost of hydrogen cars.\"", "\n\nThe technology, described in a paper in the journal Energy Storage Materials, could be especially useful in rural areas, or to military units serving in remote locations.", "\n\n\"People need fuel to run their vehicles and electricity to run their devices,\" Kaner said. \"", "Now you can make both electricity and fuel with a single device.\"", "\n\nIt could also be part of a solution for large cities that need ways to store surplus electricity from their electrical grids.", "\n\n\"If you could convert electricity to hydrogen, you could store it indefinitely,\" said Kaner, who also is a member of UCLA's California NanoSystems Institute.", "\n\nTraditional hydrogen fuel cells and supercapacitors have two electrodes: one positive and one negative. ", "The device developed at UCLA has a third electrode that acts as both a supercapacitor, which stores energy, and as a device for splitting water into hydrogen and oxygen, a process called water electrolysis. ", "All three electrodes connect to a single solar cell that serves as the device's power source, and the electrical energy harvested by the solar cell can be stored in one of two ways: electrochemically in the supercapacitor or chemically as hydrogen.", "\n\nThe device also is a step forward because it produces hydrogen fuel in an environmentally friendly way. ", "Currently, about 95 percent of hydrogen production worldwide comes from converting fossil fuels such as natural gas into hydrogen—a process that releases large quantities of carbon dioxide into the air, said Maher El-Kady, a UCLA postdoctoral researcher and a co-author of the research.", "\n\n\"Hydrogen energy is not 'green' unless it is produced from renewable sources,\" El-Kady said. ", "He added that using solar cells and abundantly available elements to split water into hydrogen and oxygen has enormous potential for reducing the cost of hydrogen production and that the approach could eventually replace the current method, which relies on fossil fuels.", "\n\nCombining a supercapacitor and the water-splitting technology into a single unit, Kaner said, is an advance similar to the first time a phone, web browser and camera were combined on a smartphone. ", "The new technology may eventually lead to new applications that even the researchers haven't considered yet, Kaner said.", "\n\nThe researchers designed the electrodes at the nanoscale—thousands of times thinner than the thickness of a human hair—to ensure the greatest surface area would be exposed to water, which increases the amount of hydrogen the device can produce and also stores more charge in the supercapacitor. ", "Although the device the researchers made would fit in the palm of your hand, Kaner said it would be possible to make larger versions because the components are inexpensive.", "\n\n\"For hydrogen cars to be widely used, there remains a need for a technology that safely stores large quantities of hydrogen at normal pressure and temperature, instead of the pressurized cylinders that are currently in use,\" said Mir Mousavi, a co-author of the paper and a professor of chemistry at Iran's Tarbiat Modares University.", "\n\nExplore further Hydrogen power moves a step closer\n\nMore information: Yasin Shabangoli et al. ", "An integrated electrochemical device based on earth-abundant metals for both energy storage and conversion, Energy Storage Materials (2017). ", "Yasin Shabangoli et al. ", "An integrated electrochemical device based on earth-abundant metals for both energy storage and conversion,(2017). ", "DOI: 10.1016/j.ensm.2017.09.010" ]
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[ "Crew still working on main break at Flamingo near Strip — and traffic’s still slow\n\nTraffic is still a hassle on westbound Flamingo Road near the Strip after a water main broke late Sunday.", "\n\nBy RICARDO TORRES LAS VEGAS REVIEW-JOURNAL\n\nMay 5, 2015 - 1:53 pm\n\nCrews work on containing a water main break on Flamingo Road outside of Bally's and The Cromwell hotel-casinos, near Las Vegas Boulevard South, on Monday morning, May 4, 2015. (", "Chase Stevens/Las Vegas Review-Journal)\n\nCrews work on containing a water main break on Flamingo Road outside of Bally's and The Cromwell hotel-casinos, near Las Vegas Boulevard South, on Monday morning, May 4, 2015. (", "Chase Stevens/Las Vegas Review-Journal)\n\nCrews work on containing a water main break on Flamingo Road outside of Bally's and The Cromwell hotel-casinos, near Las Vegas Boulevard South, on Monday morning, May 4, 2015. (", "Chase Stevens/Las Vegas Review-Journal)" ]
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[ "Q:\n\nistream_iterator read values from file into set\n\nI am having difficulty using the istream_iterator for the purpose I need. ", "I have a file that I want to read line by line into a set. ", "I have to use the iterator and I was wondering if there's something wrong with my code or my approach. ", "\nThe help is much appreciated. ", "Here's a simplified version of the code I'm writing:\nmain.cpp\n#include <iostream>\n#include <fstream>\n#include <string>\n#include <set>\n\nusing namespace std;\n\nint main() {\n\n ifstream file(\"fruits.txt\");\n\n set<string> M;\n\n copy(istream_iterator<string>(file),\n istream_iterator<string>(),\n [](string & s){ M.insert(s); });\n\n for( auto val : M ) {\n cout << val << \", \";\n }\n\n return 0;\n}\n\nfruits.txt\nbanana\napple\npear\nstrawberry\nblueberry\npeach\npear\napple\n\nErrors:\nmain.cpp:16:26: Variable 'M' cannot be implicitly\ncaptured in a lambda with no capture-default specified\n\n/Applications/Xcode.app/Contents/Developer/Toolchains/XcodeDefault.xctoolchain/usr\n/include/c++/v1/algorithm:1750:49: Cannot increment value of type '(lambda at \n/Users/cnapoli22/Downloads/TEST SHIT/TEST SHIT/main.cpp:16:10)'\n\nA:\n\nThe last argument to copy needs to be an iterator, not a lambda:\n#include <algorithm>\n#include <fstream>\n#include <iostream>\n#include <iterator>\n#include <set>\n#include <string>\n\nusing namespace std;\n\nint main()\n{\n ifstream file(\"fruits.txt\");\n\n set<string> M;\n\n copy(istream_iterator<string>(file),\n istream_iterator<string>(),\n inserter(M, M.end()));\n\n for (auto const& val : M)\n {\n cout << val << \", \";\n }\n}\n\n" ]
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[ "Overall guest ratings\n\nReview highlights\n\nGood to know\n\nNearby\n\nAbout\n\nYou cannot find a better combination of value and convenience in Charleston South Carolina than the Holiday Inn Express®. ", "Located off Highway 17 near I-526 the Holiday Inn Express is just five miles from the historic Holy City peninsula and six miles from Charleston International Airport. ", "Our hotel is also just minutes from Boeing Charleston Naval Base and the U.S. Department of Agriculture. ", "Business travelers can take advantage of our modern business center and free high-speed wireless internet. ", "For those traveling on holiday we’ll gladly arrange for you to be picked up and taken to the historic downtown scene where you can stroll along the Battery peruse the old City Market or go boutique-hopping on the famed King Street shopping district. ", "Some of Charleston’s most beautiful plantations—including Magnolia Gardens and Middleton Place—are just a short drive away. ", "And don’t forget to check out Charleston’s much-loved family destinations like the South Carolina Aquarium Charles Towne Landing Patriots Point Naval & Maritime Museum and Tanger Outlet Mall. ", "You may want to save time to relax in our outdoor pool or break a sweat in our well-equipped fitness center. ", "And of course at Holiday Inn Express everyone starts the day off right with our complimentary breakfast bar featuring piping hot cinnamon rolls and robust Arabica coffee. ", "See you soon!" ]
{ "pile_set_name": "Pile-CC" }
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0.006036
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[ "# ----------------------------------------------------\n# This file is generated by the Qt Visual Studio Add-in.", "\n# ------------------------------------------------------\n\nTEMPLATE = lib\nTARGET = lomox\nRelease:DESTDIR = ../Release\nDebug:DESTDIR = ../Debug\nQT += core sql network xml script webkit widgets webkitwidgets printsupport\nCONFIG += debug\n\nmacx:QMAKE_MACOSX_DEPLOYMENT_TARGET = 10.10.5\nmacx:QMAKE_MAC_SDK=macosx10.11\n\nDEFINES += QT_LARGEFILE_SUPPORT QT_XML_LIB QT_SQL_LIB QT_NETWORK_LIB QT_WEBKIT_LIB QT_PHONON_LIB LOMOX_LIB\nRelease:INCLUDEPATH += ./GeneratedFiles/Release \nDebug:INCLUDEPATH += ./GeneratedFiles/Debug\nINCLUDEPATH += ./GeneratedFiles \\\n . \\", "\n ./include \\\n ./implement\nDEPENDPATH += .", "\nRelease:MOC_DIR += ./GeneratedFiles/Release\nDebug:MOC_DIR += ./GeneratedFiles/Debug\nRelease:OBJECTS_DIR += Release\nDebug:OBJECTS_DIR += Debug\nUI_DIR += ./GeneratedFiles\nRCC_DIR += ./GeneratedFiles\ninclude(lomox.pri)\n\nmac {\n target.path = /usr/lib\n INSTALLS += target\n}\nunix {\n target.path = /usr/lib\n INSTALLS += target\n}\n" ]
{ "pile_set_name": "Github" }
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[ "---\nauthor:\n- |\n Armand Comas Massagué\\\n [College of Electrical and Computer Engineering]{}\\\n `comasmassague.a@northeastern.edu` Chi Zhang\\\n [Khoury College of Computer Sciences]{}\\\n `zhang.chi13@northeastern.edu` Zlatan Feric\\\n [Khoury College of Computer Sciences]{}\\\n `feric.z@northeastern.edu` Octavia Camps\\\n [College of Electrical and Computer Engineering]{}\\\n `camps@coe.neu.edu` Rose Yu\\\n [Khoury College of Computer Sciences]{}\\\n `roseyu@northeastern.edu`\nbibliography:\n- 'biblio.bib'\ntitle: |\n Learning Disentangled Representations of\\\n Video with Missing Data\n---\n\n=1\n\nIntroduction\n============\n\nRelated Work\n============\n\nDisentangled-Imputed-Video-autoEncoder (DIVE)\n=============================================\n\nExperiments\n===========\n\nConclusion and Discussion\n=========================\n\nBroader Impact {#broader-impact .unnumbered}\n==============\n\nVideos provide a window into the physics of the world we live in. ", "They contain abundant visual information of what objects are, how they move, and what happens when cameras move against the scene. ", "Being able to learn a representation that disentangles these factors is fundamental to AI that can understand and act in spatiotemporal environment. ", "Despite the wealth of methods for video prediction, state-of-the-art approaches are sensitive to missing data, which are very common in real-world videos. ", "Our proposed model significantly improves the robustness of video prediction methods against missing data, and thereby increasing the practical values of video prediction techniques and our trust in AI. ", "Video surveillance systems can be potentially abused for discriminatory targeting, and we remained cognizant of the bias in our training data. ", "To reduce the potential risk of this, we pre-processed the MOTSChallenge videos to greyscale.", "\n" ]
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[ "21 F.3d 1120\nNOTICE: Although citation of unpublished opinions remains unfavored, unpublished opinions may now be cited if the opinion has persuasive value on a material issue, and a copy is attached to the citing document or, if cited in oral argument, copies are furnished to the Court and all parties. ", " See General Order of November 29, 1993, suspending 10th Cir. ", "Rule 36.3 until December 31, 1995, or further order.", "\nSidney J. CLARK, Jr., Plaintiff-Appellant,v.Michael A. NELSON, Warden; Debra Wheaton, Head of Nursing,Defendants-Appellees.", "\nNo. ", "93-3233.", "\nUnited States Court of Appeals, Tenth Circuit.", "\nApril 5, 1994.", "\n\nBefore SEYMOUR, Chief Judge, McKAY and BALDOCK, Circuit Judges.", "\nORDER AND JUDGMENT1\nMCKAY, Circuit Judge.", "\n\n\n1\nThe appellees in this appeal from the district court's dismissal of a petition for habeas corpus did not file a brief. ", " Appellant has agreed that this case may be submitted for decision on the briefs. ", " See Fed. ", " R.App. ", "P. 34(f); 10th Cir. ", " R. 34.1.2. ", " The case is therefore ordered submitted without oral argument.", "\n\n\n2\nThis matter is before the court on appellant's application for a certificate of probable cause and request for leave to proceed in forma pauperis. ", " We issue a certificate of probable cause, grant appellant's request to proceed in forma pauperis, and proceed to the merits of the appeal. ", " After reviewing the record on appeal and appellant's brief, we AFFIRM for substantially the reasons set forth in the district court's Memorandum and Order of July 15, 1993.", "\n\n\n3\nAFFIRMED.", "\n\n\n\n1\n This order and judgment is not binding precedent, except under the doctrines of law of the case, res judicata, and collateral estoppel. ", " The court generally disfavors the citation of orders and judgments; nevertheless, an order and judgment may be cited under the terms and conditions of the court's General Order filed November 29, 1993. ", " 151 F.R.D. 470\n\n\n" ]
{ "pile_set_name": "FreeLaw" }
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[ "# libGammu translation.", "\n# Copyright (C) 2003 - 2009 Michal Čihař <michal@cihar.com>\n# This file is distributed under the same license as the libGammu package.", "\n# Automatically generated, 2009.", "\n#\nmsgid \"\"\nmsgstr \"\"\n\"Project-Id-Version: libgammu 1.22.93\\n\"\n\"Report-Msgid-Bugs-To: gammu-users@lists.sourceforge.net\\n\"\n\"POT-Creation-Date: 2019-02-14 14:57+0100\\n\"\n\"PO-Revision-Date: 2020-03-02 16:32+0000\\n\"\n\"Last-Translator: Wellington Terumi Uemura <wellingtonuemura@gmail.com>\\n\"\n\"Language-Team: Portuguese (Brazil) <https://hosted.weblate.org/projects/\"\n\"gammu/libgammu/pt_BR/>\\n\"\n\"Language: pt_BR\\n\"\n\"MIME-Version: 1.0\\n\"\n\"Content-Type: text/plain; charset=UTF-8\\n\"\n\"Content-Transfer-Encoding: 8bit\\n\"\n\"Plural-Forms: nplurals=2; plural=n > 1;\\n\"\n\"X-Generator: Weblate 4.0-dev\\n\"\n\n#: libgammu/gsmcomon.c:84\nmsgid \"No error.\"", "\nmsgstr \"Sem erro.\"", "\n\n#: libgammu/gsmcomon.c:85\nmsgid \"Error opening device. ", "Unknown, busy or no permissions.\"", "\nmsgstr \"Erro abrindo dispositivo. ", "Desconhecido, ocupado ou sem permissões.\"", "\n\n#: libgammu/gsmcomon.c:86\nmsgid \"Error opening device, it is locked.\"", "\nmsgstr \"Erro abrindo dispositivo, está travado.\"", "\n\n#: libgammu/gsmcomon.c:87\nmsgid \"Error opening device, it doesn't exist.\"", "\nmsgstr \"Erro abrindo dispositivo, não existe.\"", "\n\n#: libgammu/gsmcomon.c:88\nmsgid \"Error opening device, it is already opened by another app.\"", "\nmsgstr \"Erro ao abrir o dispositivo, ele já está em uso por outra aplicação.\"", "\n\n#: libgammu/gsmcomon.c:89\nmsgid \"Error opening device, you don't have the required permission.\"", "\nmsgstr \"Erro ao abrir o dispositivo, você não tem as permissões necessárias.\"", "\n\n#: libgammu/gsmcomon.c:90\nmsgid \"Error opening device. ", "No required driver in operating system.\"", "\nmsgstr \"\"\n\"Erro abrindo dispositivo. ", "Não há drivers requeridos no sistema operacional.\"", "\n\n#: libgammu/gsmcomon.c:91\nmsgid \"Error opening device. ", "Some hardware not connected/wrongly configured.\"", "\nmsgstr \"\"\n\"Erro abrindo dispositivo. ", "Equipamento não conectado ou configurado \"\n\"inadequadamente.\"", "\n\n#: libgammu/gsmcomon.c:92\nmsgid \"Error setting device DTR or RTS.\"", "\nmsgstr \"Erro configurando dispositivo DTR ou RTS.\"", "\n\n#: libgammu/gsmcomon.c:93\nmsgid \"Error setting device speed. ", "Maybe the speed is not supported?\"", "\nmsgstr \"\"\n\"Erro ao configurar a velocidade do dispositivo. ", "Talvez a velocidade não seja \"\n\"compatível?\"", "\n\n#: libgammu/gsmcomon.c:94\nmsgid \"Error writing to the device.\"", "\nmsgstr \"Erro ao gravar no dispositivo.\"", "\n\n#: libgammu/gsmcomon.c:95\nmsgid \"Error during reading from the device.\"", "\nmsgstr \"Erro durante leitura do dispositivo.\"", "\n\n#: libgammu/gsmcomon.c:96\nmsgid \"Can't set parity on the device.\"", "\nmsgstr \"Não foi possível configurar a paridade do dispositivo.\"", "\n\n#: libgammu/gsmcomon.c:97\nmsgid \"No response in specified timeout. ", "Probably the phone is not connected.\"", "\nmsgstr \"\"\n\"Não houve resposta no tempo especificado. ", "Provavelmente o telefone esteja \"\n\"desconectado.\"", "\n\n#: libgammu/gsmcomon.c:98\nmsgid \"\"\n\"Frame not requested right now. ", "See <https://wammu.eu/support/bugs/> for \"\n\"information on how to report it.\"", "\nmsgstr \"\"\n\"Quadro não solicitado neste momento. ", "Veja mais informações em <https://wammu.\"", "\n\"eu/support/bugs/> para saber como relatar o problema.\"", "\n\n#: libgammu/gsmcomon.c:99\nmsgid \"\"\n\"Unknown response from phone. ", "See <https://wammu.eu/support/bugs/> for \"\n\"information on how to report it.\"", "\nmsgstr \"\"\n\"Resposta desconhecida do telefone. ", "Veja mais informações em <https://wammu.\"", "\n\"eu/support/bugs/> para saber como relatar o problema.\"", "\n\n#: libgammu/gsmcomon.c:100\nmsgid \"\"\n\"Unknown frame. ", "See <https://wammu.eu/support/bugs/> for information on how \"\n\"to report it.\"", "\nmsgstr \"\"\n\"Quadro Desconhecido. ", "Veja mais informações em <https://wammu.eu/support/bugs/\"\n\"> para saber como relatar o problema.\"", "\n\n#: libgammu/gsmcomon.c:101\nmsgid \"Unknown connection type string. ", "Check config file.\"", "\nmsgstr \"\"\n\"String do tipo de Conexão desconhecida. ", "Veja arquivo configuração gammurc.\"", "\n\n#: libgammu/gsmcomon.c:102\nmsgid \"Unknown model type string. ", "Check config file.\"", "\nmsgstr \"String de Modelo desconhecido. ", "Veja arquivo configuração gammurc.\"", "\n\n#: libgammu/gsmcomon.c:103\nmsgid \"\"\n\"Some functions are not available for your system (disabled in config or not \"\n\"implemented).\"", "\nmsgstr \"\"\n\"Algumas funções não estão disponíveis para o seu sistema (desativadas no \"\n\"config ou não implementadas).\"", "\n\n#: libgammu/gsmcomon.c:104\nmsgid \"Function not supported by phone.\"", "\nmsgstr \"Função não suportada pelo celular.\"", "\n\n#: libgammu/gsmcomon.c:105\nmsgid \"Empty entry.\"", "\nmsgstr \"Entrada está vazia.\"", "\n\n#: libgammu/gsmcomon.c:106\nmsgid \"Security error. ", "Maybe no PIN?\"", "\nmsgstr \"Erro Segurança. ", "Pode ser ausência do PIN?\"", "\n\n#: libgammu/gsmcomon.c:107\nmsgid \"Invalid location. ", "Maybe too high?\"", "\nmsgstr \"Localização inválida. ", "Pode ser muito alta?\"", "\n\n#: libgammu/gsmcomon.c:108\nmsgid \"Functionality not implemented. ", "You are welcome to help.\"", "\nmsgstr \"\"\n\"Funcionalidade ainda não implementada. ", "Você é bem vindo caso queira ajudar.\"", "\n\n#: libgammu/gsmcomon.c:109\nmsgid \"Memory full.\"", "\nmsgstr \"Memória cheia.\"", "\n\n#: libgammu/gsmcomon.c:110\nmsgid \"Unknown error.\"", "\nmsgstr \"Erro desconhecido.\"", "\n\n#: libgammu/gsmcomon.c:111\nmsgid \"Can not open specified file.\"", "\nmsgstr \"Não foi possível abrir o arquivo especificado.\"", "\n\n#: libgammu/gsmcomon.c:112\nmsgid \"More memory required…\"\nmsgstr \"É preciso mais memória…\"\n\n#: libgammu/gsmcomon.c:113\nmsgid \"Operation not allowed by phone.\"", "\nmsgstr \"Operação não permitida pelo celular.\"", "\n\n#: libgammu/gsmcomon.c:114\nmsgid \"\"\n\"No SMSC number given. ", "Provide it manually or use the one configured on the \"\n\"phone.\"", "\nmsgstr \"\"\n\"Nenhum número SMSC foi informado. ", "Providencie manualmente ou utilize um já \"\n\"configurado no telefone.\"", "\n\n#: libgammu/gsmcomon.c:115\nmsgid \"You're inside the phone menu (maybe editing?). ", "Exit it and try again.\"", "\nmsgstr \"\"\n\"Você está dentro do menu telefone (editando talvez?). ", "Encerre e tente \"\n\"novamente.\"", "\n\n#: libgammu/gsmcomon.c:116\nmsgid \"Phone not connected.\"", "\nmsgstr \"O telefone não está conectado.\"", "\n\n#: libgammu/gsmcomon.c:117\nmsgid \"\"\n\"Function is currently being implemented. ", "If you want to help, please contact \"\n\"authors.\"", "\nmsgstr \"Função sendo implementada... Por favor contate os desenvolvedores.\"", "\n\n#: libgammu/gsmcomon.c:118\nmsgid \"Phone disabled and connected to charger.\"", "\nmsgstr \"O telefone está desativado e conectado ao carregador.\"", "\n\n#: libgammu/gsmcomon.c:119\nmsgid \"File format not supported by Gammu.\"", "\nmsgstr \"Formato de arquivo não suportado pelo Gammu.\"", "\n\n#: libgammu/gsmcomon.c:120\nmsgid \"\"\n\"Nobody is perfect, some bug appeared in protocol implementation. ", "Please \"\n\"contact authors.\"", "\nmsgstr \"\"\n\"Erro indeterminado na utiliza do protocolo. ", "Por favor contactar \"\n\"desenvolvedores.\"", "\n\n#: libgammu/gsmcomon.c:121\nmsgid \"Transfer canceled by phone, maybe you pressed \\\"Cancel\\\" on the phone.\"", "\nmsgstr \"\"\n\"A transferência foi cancelada pelo telefone, talvez a tecla \\\"Cancelar\\\" \"\n\"tenha sido pressionada no telefone.\"", "\n\n#: libgammu/gsmcomon.c:122\nmsgid \"Phone module need to send another answer frame.\"", "\nmsgstr \"Módulo do telefone precisa enviar outro frame de resposta.\"", "\n\n#: libgammu/gsmcomon.c:123\nmsgid \"Current connection type doesn't support called function.\"", "\nmsgstr \"Conexão atual não suporta função chamada.\"", "\n\n#: libgammu/gsmcomon.c:124\nmsgid \"CRC error.\"", "\nmsgstr \"Erro no CRC.\"", "\n\n#: libgammu/gsmcomon.c:125\nmsgid \"Invalid date or time specified.\"", "\nmsgstr \"Data ou hora especificada é inválida.\"", "\n\n#: libgammu/gsmcomon.c:126\nmsgid \"Phone memory error, maybe it is read only?\"", "\nmsgstr \"Erro de memória do telefone, talvez seja uma memória de leitura apenas?\"", "\n\n#: libgammu/gsmcomon.c:127\nmsgid \"Invalid data given to phone.\"", "\nmsgstr \"Dados inválidos fornecidos para o celular.\"", "\n\n#: libgammu/gsmcomon.c:128\nmsgid \"File with specified name already exists.\"", "\nmsgstr \"Arquivo com o nome especificado já existe.\"", "\n\n#: libgammu/gsmcomon.c:129\nmsgid \"File with specified name doesn't exist.\"", "\nmsgstr \"Nome arquivo especificado não existe.\"", "\n\n#: libgammu/gsmcomon.c:130\nmsgid \"You have to supply folder name and not filename.\"", "\nmsgstr \"Você deve informar o nome da pasta e não o nome do arquivo.\"", "\n\n#: libgammu/gsmcomon.c:131\nmsgid \"You have to supply filename and not folder name.\"", "\nmsgstr \"Você deve informar o nome do arquivo e não o nome da pasta.\"", "\n\n#: libgammu/gsmcomon.c:132\nmsgid \"Can not access SIM card.\"", "\nmsgstr \"Não pode acessar cartão SIM.\"", "\n\n#: libgammu/gsmcomon.c:133\nmsgid \"\"\n\"Wrong GNAPPLET version in use on phone. ", "Use version from currently used \"\n\"Gammu.\"", "\nmsgstr \"\"\n\"A versão em uso do GNAPPLET no celular está errada. ", "Utilize a versão atual \"\n\"do Gammu.\"", "\n\n#: libgammu/gsmcomon.c:134\nmsgid \"Only part of folder has been listed.\"", "\nmsgstr \"Só parte da pasta foi listada!.\"", "\n\n#: libgammu/gsmcomon.c:135\nmsgid \"Folder must be empty.\"", "\nmsgstr \"Pasta precisa estar vazia.\"", "\n\n#: libgammu/gsmcomon.c:136\nmsgid \"Data converted.\"", "\nmsgstr \"Dado convertido.\"", "\n\n#: libgammu/gsmcomon.c:137\nmsgid \"Gammu is not configured.\"", "\nmsgstr \"Gammu não foi configurado.\"", "\n\n#: libgammu/gsmcomon.c:138\nmsgid \"Wrong folder used.\"", "\nmsgstr \"Pasta Informada está errada.\"", "\n\n#: libgammu/gsmcomon.c:139\nmsgid \"Internal phone error.\"", "\nmsgstr \"Erro interno do celular.\"", "\n\n#: libgammu/gsmcomon.c:140\nmsgid \"Error writing file to disk.\"", "\nmsgstr \"Erro ao gravar no disco.\"", "\n\n#: libgammu/gsmcomon.c:141\nmsgid \"No such section exists.\"", "\nmsgstr \"Seção inexistente.\"", "\n\n#: libgammu/gsmcomon.c:142\nmsgid \"Using default values.\"", "\nmsgstr \"Usando valores padrões.\"", "\n\n#: libgammu/gsmcomon.c:143\nmsgid \"Corrupted data returned by phone.\"", "\nmsgstr \"Dados corrompidos retornaram do celular.\"", "\n\n#: libgammu/gsmcomon.c:144\nmsgid \"Bad feature string in configuration.\"", "\nmsgstr \"String de Configuração de funcionalidade errada.\"", "\n\n#: libgammu/gsmcomon.c:145\nmsgid \"Desired functionality has been disabled on compile time.\"", "\nmsgstr \"Funcionalidade desejada foi desabilitada na compilação.\"", "\n\n#: libgammu/gsmcomon.c:146\nmsgid \"Bluetooth configuration requires channel option.\"", "\nmsgstr \"Configuração Bluetooth requer opção canal.\"", "\n\n#: libgammu/gsmcomon.c:147\nmsgid \"Service is not running.\"", "\nmsgstr \"Serviço não está rodando.\"", "\n\n#: libgammu/gsmcomon.c:148\nmsgid \"Service configuration is missing.\"", "\nmsgstr \"Configuração do Serviço inexistente.\"", "\n\n#: libgammu/gsmcomon.c:149\nmsgid \"Command rejected because device was busy. ", "Wait and restart.\"", "\nmsgstr \"\"\n\"Comando rejeitado porque o dispositivo esta ocupado. ", "Aguarde e tente \"\n\"novamente.\"", "\n\n#: libgammu/gsmcomon.c:150\nmsgid \"Could not connect to the server.\"", "\nmsgstr \"Não foi possível conectar com o servidor.\"", "\n\n#: libgammu/gsmcomon.c:151\nmsgid \"Could not resolve the host name.\"", "\nmsgstr \"Não conseguiu resolver nome host.\"", "\n\n#: libgammu/gsmcomon.c:152\nmsgid \"Failed to get SMSC number from phone.\"", "\nmsgstr \"Falhou em obter o número SMSC do celular.\"", "\n\n#: libgammu/gsmcomon.c:153\nmsgid \"Operation aborted.\"", "\nmsgstr \"Operação cancelada.\"", "\n\n#: libgammu/gsmcomon.c:154\nmsgid \"\"\n\"Installation data not found, please consult debug log and/or documentation \"\n\"for more details.\"", "\nmsgstr \"\"\n\"Dados da Instalação não encontrados, por favor consulte o registro de \"\n\"depuração (debug/log) e/ou a documentação para mais detalhes.\"", "\n\n#: libgammu/gsmcomon.c:155\nmsgid \"Entry is read only.\"", "\nmsgstr \"Entrada só para leitura.\"", "\n\n#: libgammu/gsmcomon.c:156\nmsgid \"Network error.\"", "\nmsgstr \"Erro de rede.\"", "\n\n#: libgammu/gsmcomon.c:157\nmsgid \"Invalid database version.\"", "\nmsgstr \"Versão invalida do banco de dados.\"", "\n\n#: libgammu/gsmcomon.c:158\nmsgid \"Failed to initialize DB driver.\"", "\nmsgstr \"Falha ao inicializar o driver do banco de dados.\"", "\n\n#: libgammu/gsmcomon.c:159\nmsgid \"Failed to configure DB driver.\"", "\nmsgstr \"Falhou ao configurar o driver do banco de dados.\"", "\n\n#: libgammu/gsmcomon.c:160\nmsgid \"Failed to connect to database.\"", "\nmsgstr \"Falhou ao conectar-se com o banco de dados.\"", "\n\n#: libgammu/gsmcomon.c:161\nmsgid \"Database connection timeout.\"", "\nmsgstr \"Conexão com o banco de dados excedida.\"", "\n\n#: libgammu/gsmcomon.c:162\nmsgid \"Error in executing SQL query.\"", "\nmsgstr \"Erro ao executar a pesquisa de SQL.\"", "\n\n#: libgammu/gsmcomon.c:163\nmsgid \"The type of memory is not available or has been disabled.\"", "\nmsgstr \"O tipo da memória não está disponível ou foi desativada.\"", "\n\n#: libgammu/gsmcomon.c:164\nmsgid \"The operation cannot be performed.\"", "\nmsgstr \"Operação não pode ser executada.\"", "\n\n#: libgammu/gsmcomon.c:197\nmsgid \"Unknown error description.\"", "\nmsgstr \"Descrição do erro desconhecida.\"", "\n\n#: libgammu/phone/dummy/dummy.c:610\nmsgid \"Templates\"\nmsgstr \"Modelos\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1969\nmsgid \"Personal\"\nmsgstr \"Pessoal\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1971 libgammu/phone/nokia/nfunc.c:1156\nmsgid \"Car\"\nmsgstr \"Automóvel\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1973 libgammu/phone/nokia/nfunc.c:1158\nmsgid \"Headset\"\nmsgstr \"Fone Ouvido\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1979 libgammu/phone/nokia/nfunc.c:1146\nmsgid \"General\"\nmsgstr \"Geral\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1981 libgammu/phone/nokia/nfunc.c:1148\nmsgid \"Silent\"\nmsgstr \"Silencioso\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1983\nmsgid \"Discreet\"\nmsgstr \"Discreto\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1985\nmsgid \"Loud\"\nmsgstr \"Alto\"\n\n#: libgammu/phone/nokia/dct3/n6110.c:1987\nmsgid \"My style\"\nmsgstr \"Meu estilo\"\n\n#: libgammu/phone/nokia/dct4s40/6510/n6510.c:578\nmsgid \"SIM\"\nmsgstr \"SIM\"\n\n#: libgammu/phone/nokia/dct4s40/6510/n6510.c:579 libgammu/phone/pfunc.c:41\n#: libgammu/phone/s60/s60phone.c:1779\nmsgid \"Inbox\"\nmsgstr \"Caixa Postal Entrada\"\n\n#: libgammu/phone/nokia/dct4s40/6510/n6510.c:580\nmsgid \"Sent items\"\nmsgstr \"Itens Enviados\"\n\n#: libgammu/phone/nokia/dct4s40/6510/n6510.c:581\nmsgid \"Saved items\"\nmsgstr \"Itens Salvos\"\n\n#: libgammu/phone/nokia/nfunc.c:962\nmsgid \"Family\"\nmsgstr \"Família\"\n\n#: libgammu/phone/nokia/nfunc.c:964\nmsgid \"VIP\"\nmsgstr \"VIP\"\n\n#: libgammu/phone/nokia/nfunc.c:966\nmsgid \"Friends\"\nmsgstr \"Amigos\"\n\n#: libgammu/phone/nokia/nfunc.c:968\nmsgid \"Colleagues\"\nmsgstr \"Colegas\"\n\n#: libgammu/phone/nokia/nfunc.c:970\nmsgid \"Other\"\nmsgstr \"Outro\"\n\n#: libgammu/phone/nokia/nfunc.c:1150\nmsgid \"Meeting\"\nmsgstr \"Reunião\"\n\n#: libgammu/phone/nokia/nfunc.c:1152\nmsgid \"Outdoor\"\nmsgstr \"Externo\"\n\n#: libgammu/phone/nokia/nfunc.c:1154\nmsgid \"Pager\"\nmsgstr \"Pager\"\n\n#: libgammu/phone/pfunc.c:42 libgammu/phone/s60/s60phone.c:1780\nmsgid \"Outbox\"\nmsgstr \"Caixa Postal Saída\"\n" ]
{ "pile_set_name": "Github" }
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[ { "analysis_explanation": null, "end": 82, "entity_type": "EMAIL_ADDRESS", "recognition_metadata": { "recognizer_identifier": "EmailRecognizer_140094861343664", "recognizer_name": "EmailRecognizer" }, "score": 1, "start": 66 }, { "analysis_explanation": null, "end": 310, "entity_type": "EMAIL_ADDRESS", "recognition_metadata": { "recognizer_identifier": "EmailRecognizer_140094861343664", "recognizer_name": "EmailRecognizer" }, "score": 1, "start": 277 }, { "analysis_explanation": null, "end": 473, "entity_type": "EMAIL_ADDRESS", "recognition_metadata": { "recognizer_identifier": "EmailRecognizer_140094861343664", "recognizer_name": "EmailRecognizer" }, "score": 1, "start": 447 }, { "analysis_explanation": null, "end": 344, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "DateRecognizer_140094861343904", "recognizer_name": "DateRecognizer" }, "score": 0.95, "start": 334 }, { "analysis_explanation": null, "end": 388, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "DateRecognizer_140094861343904", "recognizer_name": "DateRecognizer" }, "score": 0.95, "start": 378 }, { "analysis_explanation": null, "end": 51, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 40 }, { "analysis_explanation": null, "end": 83, "entity_type": "PERSON", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 52 }, { "analysis_explanation": null, "end": 190, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 186 }, { "analysis_explanation": null, "end": 395, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", 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[ "Bay Area demonstrations by right-wing groups scheduled over the weekend fizzled in face of massive opposition protests, defusing fears that Charlottesville-like violence could erupt in San Francisco and Berkeley. ", "Indeed, protests in San Francisco were peaceful, and the few scuffles that did occur in Berkeley seemed instigated by black-garbed Black Bloc protestors, according to many reports.", "\n\nBut people and groups associated with the “alt-right”—an amalgam of neo-Nazis, white supremacists, “citizen” militias, and hyper-conservative prayer groups—have vowed ongoing demonstrations in other American cities in coming months. ", "And that’s led to profound public safety concerns.", "\n\nCharlottesville, after all, wasn’t marked solely by the murder of a young woman by an ISIS-like car attack. ", "Some of the most enduring and disturbing images of the event were of right-wing protestors openly toting assault-style long guns and semi-automatic pistols (including this video of a white supremacist who was arrested yesterday for discharging his pistol in the direction of counter-protestors). ", "It takes no great stretch of the imagination to contemplate the horrors that might have resulted if wholesale gunfire had erupted.", "\n\nAnd though no firearms were in evidence at the weekend’s Bay Area demonstrations, some media have reported concerns that other elements may be arming themselves in fears of gun-crazed and goose-stepping hordes of neo-Nazis and white supremacists invading their neighborhoods.", "\n\nThe Second Amendment gives you the right to bear arms, but really, that’s the beginning point of the conversation…the intent is not totally clear.", "\n\nAuthorities in Charlottesville allowed demonstrators to display firearms because of the state’s “open carry” law. ", "California’s firearm regulations are much stricter, but the basic right to carry guns in public remains murky. ", "The language of the Second Amendment, which assures the right of citizens to keep and bear arms, is simultaneously explicit and opaque.", "\n\n“The Second Amendment gives you the right to bear arms,” says Jesse Choper, a UC Berkeley Law professor emeritus and the former Berkeley Law dean. “", "But really, that’s the beginning point of the conversation. ", "As is true with most of the Bill of Rights, the intent is not totally clear, and in fact, the language in the Second Amendment is particularly confusing.”", "\n\nThat confusion, of course, is largely due to this line: “…A well-regulated militia, being necessary to the security of a free state, the right of the people to keep and bear arms, shall not be infringed.”", "\n\nFor decades, legal scholars and advocates on both sides of the gun control issue have differed over the intended meaning of the Founding Fathers. ", "Did they mean that only those citizens who are organized into official militias by local or regional jurisdictions have the right to bear arms? ", "Or that anyone can keep arms because they might eventually join a “well-regulated” militia? ", "And what about the storage of the arms themselves? ", "Can citizens keep them in their homes, or only in armories that supply the cited well-regulated militias? ", "Further, even assuming that every law-abiding citizen can own firearms, does that right extend to locked-and-loaded open carry in public?", "\n\nChoper observes the U.S. Supreme Court tacked the issue in the 2008 landmark case, District of Columbia v Heller, and that the justices’ ruling defines basic gun rights today. ", "The majority opinion for that case was written by the late Antonin Scalia, a fervent Constitutional “originalist” and ardent gun enthusiast.", "\n\n“The interesting thing about District of Columbia v Heller is that Scalia had to accommodate the other four justices who ultimately sided with him, ” Choper says. “", "As a consequence, it provides a very limited interpretation of the Second Amendment. ", "It stipulates that a person has the right to own a gun to protect himself or herself, family, and property. ", "That’s it. ", "The decision does not imply the right to carry a weapon in public, including public buildings.”", "\n\nJust as it would be hard to punish cities in an open carry state for allowing open carry during demonstrations, it would also be difficult to challenge authorities trying to stop trouble before it starts by banning firearms.", "\n\nWhen it comes to applying District of Columbia v Heller in the streets, continues Choper, “[Cities] can find themselves between a rock and a hard place. ", "They want to respect the right of free speech, and they need to protect public safety. ", "Given that [public carry] currently is not protected by the Constitution, cities have the right to enforce ‘no gun’ rules.”", "\n\nBut municipalities located in open carry states may choose not to invoke gun strictures; and that’s what appears to have happened in Charlottesville. ", "It raises the question: are cities that refuse to ban guns at public demonstrations liable if anyone gets hurt or killed?", "\n\n“It would be an uphill battle to make liability stick for any [gun-related death] if the city is in an open carry state,” Choper says. “", "That isn’t to say authorities shouldn’t or couldn’t try to stop [people carrying guns during demonstrations]. ", "So just as it would be hard to punish cities in an open carry state for allowing open carry during demonstrations, it would also be difficult to challenge authorities trying to stop trouble before it starts by banning firearms. ", "All rules and laws have exceptions under extraordinary circumstances. ", "No right, including the right to bear arms, is absolute.”", "\n\nCalifornia cities, at least, are unlikely to face the dilemma of Charlottesville. ", "Though the weekend demonstration planned by Patriot Prayer for Crissy Field was cancelled, San Francisco authorities had moved decisively to ban firearms from the event. ", "Comments provided by John Coté, the spokesman for City Attorney Dennis J. Herrera, confirmed that state law prohibits the open carry of both long guns and handguns in urban and suburban areas, with some exceptions for counties with fewer than 200,000 people (not San Francisco County, obviously).", "\n\n“Someone with a concealed carry weapons permit issued by a sheriff or police chief in California (not any other state) can carry a concealed handgun in parts of San Francisco, but San Francisco bars possession of all firearms, even with a concealed weapons permit, on city property, including city-owned parks,” Coté wrote.", "\n\nCrissy Field, the site for the planned Patriot Prayer demonstration, is part of the federal Golden Gate National Recreational Area, and it conforms to all California state gun control laws. ", "The open carry of firearms in public is illegal in GGNRA. ", "Concealed firearms carried by people with licenses issued by California police chiefs or county sheriffs are allowed under some circumstances. ", "However, the permit conditions for the Patriot Prayer event at Crissy Field prohibited all firearms, Coté stated.", "\n\nSo as things stand, it’s clear that officials and police have the right to curtail the open carry of firearms at public events and demonstrations. ", "District of Columbia v Heller confirms that authority, however obliquely. ", "But the law is fluid, Choper observes, and that protean quality applies in particular to the Second Amendment.", "\n\n“I once read it 20 times for a case, and I still have no clear understanding of it,” says Choper, “and I know something about constitutional law. ", "And I’m not alone: remember, the Court split 5-4 on Heller. ", "And [Neil] Gorsuch [recently appointed to SCOTUS by Trump] believes the Second Amendment should be interpreted as a strong defense of the right to bear arms. ", "So things could change. ", "But even Gorsuch can’t ignore the context of a regulation enforced under exceptional circumstances, such as those that could lead to injury or the loss of life.”", "\n\nCircumstances, in other words, that involve inflamed partisans facing each other in public venues." ]
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[ "As tax season rolls on, scams are picking up, hurting last-minute filers. ", "And Microsoft is offering advice to help steer clear of them.", "\n\nIn February, there was an average of 300,000 phishing attempts per day across Microsoft's browsers, the company said in an advisory. ", "The company's security experts expect these scams to grow as tax day approaches.", "\n\nIn the two weeks before the April 15 deadline, 20 to 25 percent of Americans file taxes, according to the Internal Revenue Service. ", "And with about a month until the filing deadline, Microsoft is urging Windows 10 users to take the following steps to avoid tax scams.", "\n\nGOOGLE IS TRYING TO KEEP YOUR PASSWORD SAFE FROM HACKERS\n\nPasswords are not enough\n\n“Don’t rely on passwords alone. ", "When possible, always use multi-factor authentication,” Holly Stewart, Principal Research Lead for the Windows Defender Antivirus Research team at Microsoft, wrote in the note.", "\n\nWith multi-factor authentication, a user gets access to a feature or device only after providing two or more pieces of identification. ", "So instead of just providing a password, a user is also asked to provide a temporary passcode and/or a biometric ID, like a fingerprint or face scan.", "\n\nNewer Windows 10 laptops from manufacturers like Hewlett-Packard and Dell now often come with “Windows Hello” face ID or fingerprint ID or both. ", "Microsoft also offers a Microsoft Authenticator app for managing account logins on other devices, including Apple and Google products.", "\n\nBe very wary of email\n\nThe company also said that users should be suspicious of all links, especially when the email seems “off” or unexpected – like an email from your credit card company, or financial institution.", "\n\nThere are also preventative measures users can take, such as checking directly with the sender before opening or downloading an attachment, Microsoft added.", "\n\nAnd tax-related URLs should be scrutinized too. ", "For example, users should hover over links to make sure the URL goes to a legitimate website. ", "If you’re not sure, rather than clicking on the link, bring up the tax site via a search engine and log in from there, Microsoft said.", "\n\nAnd more wary of attachments\n\nAttachments are notorious places for malware to get at your personal data. ", "An email with a fake invoice from a tax preparation company is one of the top methods criminals use to trick people into opening a malicious attachment that could, in turn, execute malware on your computer, Microsoft said.", "\n\n“We’ve seen PDFs that contain innocuous-looking links that lead to users accidentally downloading malicious software designed to steal their credentials,” the company wrote in the advisory.", "\n\nCLICK HERE TO GET THE FOX NEWS APP\n\nKeep software up-to-date\n\nLastly, users should keep their software current. ", "If you’re running Windows 10, make sure it has the latest security and feature updates and you have virus protection running, such as Windows Defender Antivirus." ]
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[ "1. ", "Introduction {#sec1-molecules-23-01975}\n===============\n\nTraditional Chinese medicines (TCMs) are in widespread use around the world as complementary therapy, increasingly concerned in Western nations \\[[@B1-molecules-23-01975],[@B2-molecules-23-01975]\\]. ", "In recent years, the stability of active compounds from TCMs has attracted especially extensive attention, having a vital influence on their quality, safety, and efficacy (QSE) \\[[@B3-molecules-23-01975],[@B4-molecules-23-01975],[@B5-molecules-23-01975],[@B6-molecules-23-01975],[@B7-molecules-23-01975]\\]. ", "Drug regulatory agencies around the world have drafted guidelines for manufacturing and controlling the QSE of drugs. ", "Drug stability and degradation studies are an integral part of drug development. ", "Stability testing is an important approach to evaluate the quality of drug substances and products, which may vary with time under the influence of temperature, humidity, light, etc. ", "\\[[@B8-molecules-23-01975]\\]. ", "The International Conference on Harmonization (ICH) has released a series of guidelines on stability studies of pharmaceuticals \\[[@B9-molecules-23-01975]\\]. ", "In order to comply with the stringent requirements of regulatory guidelines, quality control and stability studies have taken a front seat in the TCM development process. ", "Unlike synthetic drugs, it is well known that TCMs and their preparations generally exert their therapeutic effects through the synergic effects of multiple active ingredients \\[[@B5-molecules-23-01975],[@B10-molecules-23-01975],[@B11-molecules-23-01975]\\]. ", "Therefore, it is much more complicated to guarantee QSE under the influence of various storage conditions for a TCM product. ", "The major challenges, namely the chemical complexity and variability in the chemical composition of the raw material, have posed an impediment for the stability testing of TCM products \\[[@B12-molecules-23-01975]\\]. ", "Consequently, the systematic study of active compounds and their stability has become an indispensable and urgent task, which would contribute to improvements in manufacturing and controlling the quality of TCMs.", "\n\nThe nearly ripe fruits of *Euodia rutaecarpa* (Juss.) ", "Benth., *", "Euodia rutaecarpa* (Juss.) ", "Benth. ", "var. *", "officinalis* (Dode) Huang, and *Euodia rutaecarpa* (Juss.) ", "Benth. ", "var. *", "bodinieri* (Dode) Huang, known as Wuzhuyu, have been used to treat headache, gastrointestinal disorders, abdominal pain during menstruation, vomiting, and diarrhea \\[[@B13-molecules-23-01975]\\]. ", "Previous studies focused on the fat-soluble substances of these fruits, yet the water-soluble substances were not paid enough attention. ", "However, patients usually take a decoction of Fructus Euodiae (FE) for clinical use. ", "In our previous study, a large quantity of phenolic acids, including caffeoylgluconic, feruloylgluconic, and chlorogenic acid derivatives, were identified from the aqueous extract of FE using the UPLC-Q-TOF MS technique. ", "Three caffeoylgluconic acid derivatives, *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-gluconic acid (CGA), *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-gluconic acid methyl ester (CGA-ME), and *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-glucono-*γ*-lactone (CGA-LT) ([Figure S1](#app1-molecules-23-01975){ref-type=\"app\"}), were isolated from the aqueous extract of FE with the guidance of UPLC-Q-TOF MS analytical results \\[[@B14-molecules-23-01975]\\]. ", "Caffeoylgluconic acid derivatives, which belong to phenolic acids, were rarely reported in the literature \\[[@B14-molecules-23-01975],[@B15-molecules-23-01975]\\]. ", "Modern research suggested that phenolic acids have many pharmacological effects, such as dilating blood vessels, antioxidant and anti-inflammatory activity, analgesia, and antibiosis \\[[@B16-molecules-23-01975],[@B17-molecules-23-01975],[@B18-molecules-23-01975]\\]. ", "During the process of isolating the three caffeoylgluconic acid derivatives, it was found that the compounds were unstable to temperature and pH extremes and could convert to each other; thus, a long and arduous journey was followed to obtain the pure compounds. ", "Since there were numerous caffeoylgluconic acid derivatives in the aqueous extract of FE, it was necessary to investigate their stability to guide the separation and further pharmaceutical study of these compounds.", "\n\nDifferent analytical techniques, such as thin layer chromatography (TLC), high performance liquid chromatography (HPLC), HPLC based on hydrophilic interaction chromatography-electrospray ionization-mass spectrometry (HILIC-ESI-MS), electrospray ionization Fourier transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS), liquid chromatography coupled with mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR), have been established to evaluate the stability of the characteristic ingredients of TCMs and track the possible degradation products to clarify the degradation pathways \\[[@B19-molecules-23-01975],[@B20-molecules-23-01975],[@B21-molecules-23-01975],[@B22-molecules-23-01975],[@B23-molecules-23-01975],[@B24-molecules-23-01975],[@B25-molecules-23-01975],[@B26-molecules-23-01975]\\]. ", "Among these techniques, UPLC-UV is the most comprehensive method with low cost, high sensitivity, and favorable separating power that can be employed to detect the targeted compounds using UV absorption. ", "In addition, UPLC-MS provides a powerful supplementary tool for profiling the targeted compounds and degradation products, which can afford accurate information of quasi-molecular and fragment ions for the identification of the compounds of interest \\[[@B27-molecules-23-01975],[@B28-molecules-23-01975],[@B29-molecules-23-01975]\\].", "\n\nIn the present study, the stability of caffeoylgluconic acid derivatives in aqueous solutions at different temperatures and pH values was studied by UPLC analysis. ", "Furthermore, a UPLC-DAD/ESI-Q-TOF MS method was established to study the degradation products of the three caffeoylgluconic acids derivatives. ", "The structures of the degradation products and formation mechanisms were deduced according to the mass information of the quasi-molecular and fragment ions of the degradation products.", "\n\n2. ", "Results and Discussion {#sec2-molecules-23-01975}\n=========================\n\n2.1. ", "Effect of Temperature and pH on Stability of CGA, CGA-ME, and CGA-LT {#sec2dot1-molecules-23-01975}\n-------------------------------------------------------------------------\n\nCGA, CGA-ME (methyl-esterified derivative of CGA), and CGA-LT (lactonized derivative of CGA), were the representative compounds existing in FE. ", "A stability study of these compounds was systematically undertaken. ", "Shown in [Figure 1](#molecules-23-01975-f001){ref-type=\"fig\"}, [Figure 2](#molecules-23-01975-f002){ref-type=\"fig\"} and [Figure 3](#molecules-23-01975-f003){ref-type=\"fig\"} are the representative chromatograms and variation curves of concentration with time.", "\n\nAs for the stability of CGA, CGA-ME, and CGA-LT exposed to different temperatures (20, 40, 60, and 80 °C), with increasing temperature, CGA-ME and CGA-LT were degraded and converted into CGA at an accelerating speed; this was not applicable to CGA, which was relatively stable and inert to temperature variations. ", "Especially surprising was that CGA-ME and CGA-LT rapidly converted into CGA in alkaline medium rather than in acidic medium, which is displayed in [Figure 2](#molecules-23-01975-f002){ref-type=\"fig\"}D and [Figure 3](#molecules-23-01975-f003){ref-type=\"fig\"}D. Different to CGA-ME and CGA-LT, CGA was slightly degraded in alkaline medium. ", "Regardless of the temperature or pH, with time, the conversion from CGA-ME and CGA-LT to CGA was aggravated, which was mediated by a hydrolysis reaction \\[[@B30-molecules-23-01975],[@B31-molecules-23-01975],[@B32-molecules-23-01975]\\].", "\n\n2.2. ", "Evaluation of Stability Index (StI) and Sensitivity Index (SeI) of CGA, CGA-ME, and CGA-LT {#sec2dot2-molecules-23-01975}\n-----------------------------------------------------------------------------------------------\n\nIn order to comprehensively evaluate the degradation susceptibility and integrated stability of CGA, CGA-ME, and CGA-LT under different temperatures and pH values, the sensitivity index (SeI) and stability index (StI) were established and applied in this study.", "\n\nCGA is taken as an example to introduce the data processing as displayed in [Figure 4](#molecules-23-01975-f004){ref-type=\"fig\"}; the relative concentrations at the different temperatures and pH values were obtained by dividing the CGA concentrations at 12 h of exposure to the different temperatures and pH values by the prepared concentration of CGA. ", "The area under the relative concentration--temperature curve (AUC~RcT~) and the area under the relative concentration--pH curve (AUC~RcP~) were calculated; these were respectively divided by the ideal AUC~RcT~ and AUC~RcP~, and the results were nominated as AUC'~RcT~ and AUC'~RcP~, respectively. ", "The computational formulae for SeI and StI are listed as follows. ", "$${{SeI} = \\frac{{{AUC}\\prime}_{RcT}}{{{AUC}\\prime}_{RcP}}}\\ $$ $${{StI} = {{AUC}\\prime}_{RcT} \\times {{{AUC}\\prime}_{RcP}/2}}\\ $$\n\nDisplayed in [Figure 5](#molecules-23-01975-f005){ref-type=\"fig\"} are the SeI and StI results of CGA, CGA-ME, and CGA-LT. ", "The SeI values of CGA, CGA-ME, and CGA-LT were 0.9926 (±0.059), 0.4883 (±0.018), and 0.5900 (±0.042), respectively. ", "When the SeI of a compound was above 1, it was speculated that the tested compound was more sensitive to the variation of pH than that of temperature, and vice versa. ", "The StI values of CGA, CGA-ME, and CGA-LT were 0.4679 (±0.024), 0.1134 (±0.004), and 0.1819 (±0.010), respectively. ", "The larger the StI of a compound was, the higher the comprehensive stability was.", "\n\n2.3. ", "Identification of Degradation Products of CGA, CGA-ME, and CGA-LT {#sec2dot3-molecules-23-01975}\n----------------------------------------------------------------------\n\nSuffering at high temperatures and in alkaline mediums, CGA, CGA-ME, and CGA-LT were subject to similar degradation pathways. ", "Therefore, based on accurate mass information, the degradation products of CGA, CGA-ME, and CGA-LT were characterized by employing the exposed samples of CGA at 80 °C and those of CGA-ME and CGA-LT at pH 8, respectively. ", "Inorganic salt in buffer solution would contaminate MS and deteriorate the MS sensitivity; therefore, ammonia was employed to adjust the pH of the processed sample solution. ", "Given the perfect MS signal of CGA derivatives and degradation products, the negative detection mode was selected. ", "In order to obtain a satisfactory separation of the targeted compounds and their degraded compounds, different column temperatures were employed for the reacted solution of CGA (40 °C), and CGA-ME and CGA-LT (48 °C); therefore, the retention time of CGA in [Figure 6](#molecules-23-01975-f006){ref-type=\"fig\"} was longer than that in [Figure 7](#molecules-23-01975-f007){ref-type=\"fig\"} and [Figure 8](#molecules-23-01975-f008){ref-type=\"fig\"}.", "\n\nCGA showed a quasi-molecular ion at *m*/*z* 357.0839 \\[M − H\\]^−^, and its characteristic fragment ions were detected at *m*/*z* 195.0509 \\[M − H−caffeoyl\\]^−^, 179.0345 \\[M − H−gluconic acid residue\\]^−^, 135.0446 \\[M − H−gluconic acid residue−CO~2~\\]^−^, and 129.0189 \\[M − H−caffeoyl−2H~2~O−CH~2~O\\]^−^. The detailed MS information of CGA is listed in [Table S1](#app1-molecules-23-01975){ref-type=\"app\"}. ", "The representative MS and MS^2^ spectra and proposed fragmentation pathways are shown in [Figure S2](#app1-molecules-23-01975){ref-type=\"app\"}. ", "The main degradation products derived from CGA, CGA-d~1~ to CGA-d~4~, were detected. ", "They had similar MS data and fragment pathways to those of CGA and were identified as isomers of CGA. ", "It can be proposed that CGA underwent a hydrolytic reaction to form caffeic acid and gluconic acid, leading to the production of isomers of CGA by esterification via caffeic acid and one of other four alcohol hydroxyls of gluconic acid \\[[@B30-molecules-23-01975],[@B32-molecules-23-01975]\\]. ", "The chromatogram of the sample solution and proposed degradation pathways of CGA are shown in [Figure 6](#molecules-23-01975-f006){ref-type=\"fig\"}.", "\n\nAs a methyl-esterified derivative of CGA, CGA-ME indicted a quasi-molecular ion at *m*/*z* 371.0984 \\[M − H\\]^−^, whose mass weight was 14 Da larger than that of CGA. ", "The characteristic neutral loss produced ions at *m*/*z* 339.0717 \\[M − H−CH~3~OH\\]^−^, 179.0343 \\[M − H−methyl gluconic acid residue\\]^−^, 177.0399 \\[M − H−CH~3~OH−caffeoyl\\]^−^, and 161.0239 \\[M − H−methyl gluconic acid\\]^−^. Then, the consecutive loss of CO~2~ from the ion at *m*/*z* 179.0343 generated an ion at *m*/*z* 135.0446. ", "In [Table S1](#app1-molecules-23-01975){ref-type=\"app\"}, the detailed MS information of CGA-ME is supplied. ", "Displayed in [Figure S3](#app1-molecules-23-01975){ref-type=\"app\"} are the representative MS and MS^2^ spectra and proposed fragmentation pathways. ", "Based on the MS data in [Table S1](#app1-molecules-23-01975){ref-type=\"app\"}, it was proposed that CGA-ME was degraded into caffeic acid, CGA, and isomers of CGA-ME through a hydrolytic reaction. ", "Further, the lactonized gluconic acid of CGA produced CGA-LT and its isomer. ", "Shown in [Figure 7](#molecules-23-01975-f007){ref-type=\"fig\"} are the chromatogram of the sample solution and proposed degradation pathways of CGA-ME.", "\n\nCGA-LT, the lactonized derivative of CGA, exhibited a quasi-molecular ion at *m/z* 339.0715 \\[M − H\\]^−^, and its characteristic fragment ions were detected at *m/z* 179.0341, 177.0397, and 161.0236 in the negative ion mode, corresponding to the loss of glucono-*γ*-lactone residue, caffeoyl, and glucono-*γ*-lactone, respectively. ", "Furthermore, the consecutive loss of CO~2~ from the ion at *m/z* 179.0341 generated an ion at *m/z* 135.0443. ", "The detailed MS information of CGA-LT is listed in [Table S1](#app1-molecules-23-01975){ref-type=\"app\"}. ", "The representative MS and MS^2^ spectra and proposed fragmentation pathways are shown in [Figure S4](#app1-molecules-23-01975){ref-type=\"app\"}. ", "According to the MS data, it can be deduced that CGA-LT was transformed into isomers of CGA-LT via a hydrolytic reaction or decomposed into CGA through an opening-ring reaction. ", "The chromatogram of the sample solution and proposed degradation pathways of CGA-LT are shown in [Figure 8](#molecules-23-01975-f008){ref-type=\"fig\"}.", "\n\n3. ", "Materials and Methods {#sec3-molecules-23-01975}\n========================\n\n3.1. ", "Reagents and Materials {#sec3dot1-molecules-23-01975}\n---------------------------\n\nCGA, CGA-ME, and CGA-LT were purified by us using D101 macroporous resin, Sephadex LH-20 and ODS column chromatography, and preparative HPLC from the aqueous extract of FE; the compounds were identified by UV, IR, MS, and NMR technologies \\[[@B14-molecules-23-01975]\\]. ", "Their purities above 95% were determined by UPLC analysis. ", "LC-grade acetonitrile was purchased from Sigma-Aldrich (St. Louis, MO, USA). ", "LC-grade water was produced by a Milli-Q water purification system (Millipore, Massachusetts, MA, USA). ", "Formic acid was bought from Meridian Medical Technologies (MREDA, New York, NY, USA). ", "Phosphoric acid, disodium hydrogen phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate were bought from DAMAO Chemical Reagent Factory (Tianjin, China).", "\n\nThe phosphate buffer solution at pH 2, 4, 6, and 8 was prepared according to the guidelines released by Chinese pharmacopoeia.", "\n\n3.2. ", "UPLC Analysis {#sec3dot2-molecules-23-01975}\n------------------\n\nComposed of a column heater, a sample manager, a binary solvent manager, and a photo-diode array (PDA) detector, a Waters Acquity UPLC system (Waters, Milford, MA, USA) was employed to undertake the chromatographic separation on an Acquity UPLC BEH C18 column (3.0 mm × 100 mm, 1.7 μm) with the column heater fixed at 40 °C. ", "The mobile phase was acetonitrile (A) and 0.1% formic acid aqueous solution (B) with an isocratic elution at 8% acetonitrile. ", "The flow rate was 0.3 mL/min. ", "The detection wavelength was 320 nm and the injection volume was 4 μL.\n\n3.3. ", "UPLC-Q/TOF MS Analysis {#sec3dot3-molecules-23-01975}\n---------------------------\n\nAnalysis was performed on a Waters ACQUITY UPLC tandem Xevo G2-S spectrometer (Waters, Milford, MA, USA). ", "The chromatographic condition of UPLC was employed as described in [Section 3.2](#sec3dot2-molecules-23-01975){ref-type=\"sec\"}. ", "However, the column temperatures were maintained at 40 °C for CGA analysis and at 48 °C for CGA-ME and CGA-LT. ", "For the MS analysis, nitrogen was used as desolvation gas at a flow rate of 600 L/h for ESI (−). ", "The flow rate of the cone gas was set at 50 L/h. The source and desolvation temperature were fixed at 100 °C and 450 °C, respectively. ", "The capillary voltage was −2.0 kV. The collision energy was 10--60 eV. The spectra were recorded in the range of *m/z* 100--1200 for a full scan.", "\n\n3.4. ", "Stability Study of Tested Compounds under Different Temperatures and pH Values {#sec3dot4-molecules-23-01975}\n-----------------------------------------------------------------------------------\n\nCGA, CGA-ME, and CGA-LT (about 1.5 mg) were dissolved in 10 mL of water, respectively. ", "The sample solution (2.5 mL) was incubated at the different temperatures (20, 40, 60, and 80 °C) for 12 h and analyzed following the established UPLC-DAD method to record the concentrations of the tested compounds once per hour.", "\n\nCGA, CGA-ME, and CGA-LT (about 3 mg) were each dissolved in 2 mL of water. ", "The sample solution (0.5 mL) was separately mixed with 4.5 mL of buffer solution with a pH of 2, 4, 6, and 8, incubated at 4 °C for 12 h, and analyzed to track the concentration variations of the tested compounds once per hour. ", "In order to guarantee the reliability of results, the stability study of each compound was repeated three times.", "\n\nCGA, CGA-ME, and CGA-LT (about 0.5 mg) were dissolved in 2 mL of water, respectively. ", "Ammonia solution was added to the solution to adjust the pH at 8. ", "CGA, CGA-ME, and CGA-LT (about 0.5 mg) were each dissolved in 2 mL of water and incubated for 10 h at 80 °C. ", "The processed sample solution was diluted five times with water for UPLC-DAD/ESI-Q-TOF MS analysis.", "\n\n3.5. ", "Statistical Analysis {#sec3dot5-molecules-23-01975}\n-------------------------\n\nThe plotting and curve fitting were performed using GraphPad Prism 5.01 software (Graphpad software Inc., La Jolla, CA, USA).", "\n\n4. ", "Conclusions {#sec4-molecules-23-01975}\n==============\n\nAccording to the time--concentration curves as well as SeI and StI of the tested compounds, it was concluded that the integrated stability of CGA was better than that of CGA-ME and CGA-LT. ", "CGA-ME was proved to be the most unstable. ", "Moreover, CGA was inert to the variation of temperature and pH, while CGA-ME and CGA-LT were more susceptible to the variation of temperature. ", "The degradation products and pathways of CGA, CGA-ME, and CGA-LT were identified, as they were characterized by the formation of isomers of the tested compounds via a hydrolytic reaction. ", "Consequently, this study sheds light on the stability of the tested compounds and contributes to improving the manufacturing and quality control of FE and its preparation.", "\n\nThe authors gratefully acknowledge Harmonia Testing Technology (Tianjin) Limited Company for the UV, IR, and NMR measurements of CGA, CGA-ME, and CGA-LT.", "\n\n**Sample Availability:** Samples of the compounds *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-gluconic acid (CGA), *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-gluconic acid methyl ester (CGA-ME), and *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-glucono-*γ*-lactone (CGA-LT) are available from the authors.", "\n\nThe following are available online. ", "Figure S1: Chemical structural formula of CGA, CGA-ME, and CGA-LT; Figure S2: MS (A) and MS^2^ (B) spectra and proposed fragmentation pattern (C) of CGA; Figure S3: MS (A) and MS^2^ (B) spectra and proposed fragmentation pattern (C) of CGA-ME; Figure S4: MS (A) and MS^2^ (B) spectra and proposed fragmentation pattern (C) of CGA-LT; Table S1: Characterization of the degradation products of CGA, CGA-ME, and CGA-LT by UPLC-DAD/ESI-Q-TOF MS.", "\n\n###### \n\nClick here for additional data file.", "\n\nFormal Analysis, J.Y. and Y.W.; Software, J.D. and Z.J.; Supervision, X.C.; Writing---Original Draft, H.Y. and Y.H.; Writing---Review and Editing, H.Y.\n\nThis research was funded by Tianjin Support Plans for Top of the Notch Youth Talents, National Basic Scientific and Technological Project (2014FY111100), and National Science and Technology Major Projects for \"Major New Drugs Innovation and Development\" (2015ZX09J15102-004-004).", "\n\nThe authors declare no conflict of interest.", "\n\n![", "UPLC representative chromatograms of *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-gluconic acid (CGA) in the exposed solution at 80 °C (**A**) and pH 8 (**B**) after 12 h; Time--concentration curves of CGA at different temperatures (**C**) and pH values (**D**).](molecules-23-01975-g001){#molecules-23-01975-f001}\n\n![", "Representative UPLC chromatograms of *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-gluconic acid methyl ester (CGA-ME) in the exposed solution at 40 °C (**A**) and pH 8 (**B**) after 12 h; Time--concentration curves of CGA-ME and CGA at different temperatures (**C**) and pH values (**D**).](molecules-23-01975-g002){#molecules-23-01975-f002}\n\n![", "Representative UPLC chromatograms of *trans*-caffeoyl-6-*O*-[d]{.smallcaps}-glucono-*γ*-lactone (CGA-LT) in the exposed solution at 40 °C (**A**) and pH 8 (**B**) after 12 h; Time--concentration curves of CGA-LT and CGA at different temperatures (**C**) and pH values (**D**).](molecules-23-01975-g003){#molecules-23-01975-f003}\n\n![", "Relative concentration--temperature curve of CGA (**A**); relative concentration--pH curve of CGA (**B**); calculation model of sensitivity index (SeI) and stability index (StI) for CGA (**C**).](molecules-23-01975-g004){#molecules-23-01975-f004}\n\n![", "SeI (**A**) and StI (**B**) of CGA, CGA-ME, and CGA-LT (*n* = 3).](molecules-23-01975-g005){#molecules-23-01975-f005}\n\n![", "Representative total ion current (TIC) chromatogram of the reacted solution of CGA in the negative ion mode (**A**) and proposed pathways of degradation for CGA (**B**).](molecules-23-01975-g006){#molecules-23-01975-f006}\n\n![", "Representative TIC chromatogram of the reacted solution of CGA-ME in the negative ion mode (**A**) and proposed pathways of degradation for CGA-ME (**B**).](molecules-23-01975-g007){#molecules-23-01975-f007}\n\n![", "Representative TIC chromatogram of the reacted solution of CGA-LT in the negative ion mode (**A**) and proposed pathways of degradation for CGA-LT (**B**).](molecules-23-01975-g008){#molecules-23-01975-f008}\n\n[^1]: These authors contributed equally to this work.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Summary*FASTR* protocol was designed to provide a compact treatment for high-risk prostate cancer patients but was discontinued because of excess toxicity. ", "FASTR-2 employed lower prostate dose, smaller PTV margins and omission of nodal irradiation. ", "FASTR-2 allowed for safe, fiducial-less delivery of ultra-hypofractionated radiotherapy to the prostate and seminal vesicles with early biochemical control; however, long-term follow-up is required to ensure disease control and toxicity outcomes are comparable to conventional treatment paradigms.", "\n\nIntroduction {#sec1}\n============\n\nBiochemical control and disease-free survival in high-risk prostate cancer are improved with radical radiation combined with adjuvant androgen deprivation compared with either treatment alone.[@bib1], [@bib2] Although effective, this regimen can be very demanding, especially on elderly or frail patients. ", "Growing evidence suggests that prostate cancer has a lower α-to-β ratio than most solid tumors and may benefit from hypofractionation.[@bib3] Ultra-hypofractionation in the form of stereotactic ablative radiation (SABR) has been shown to be tolerable in the low- and intermediate-risk groups;[@bib4], [@bib5], [@bib6], [@bib7], [@bib8] however, the optimal protocol for treating high-risk prostate cancer with SABR has yet to be established.", "\n\nShort course radiation combined with androgen deprivation therapy (ADT) was explored in the FASTR trial,[@bib9] where patients received 12 months of ADT along with radiation to the prostate (40 Gy/5 fractions delivered weekly) and pelvic lymph nodes (25 Gy/5 fractions delivered weekly). ", "This study was discontinued after accrual of 16 patients owing to an unacceptable rate of acute and late toxicities including one grade 4 gastrointestinal (GI) toxicity. ", "It was thought that the rate of toxicity likely reflected the high rectal, small bowel, and bladder doses secondary to the large prescription dose to prostate and the inclusion of pelvic nodal irradiation.", "\n\nThe present study was designed with consideration of these previous toxicities and used a lower dose to the prostate (35 Gy/5 weekly fractions). ", "Given the uncertainty in survival benefit of pelvic nodal irradiation in prostate cancer,[@bib10], [@bib11] it was decided to omit pelvic lymph node irradiation. ", "Furthermore, recent evidence has shown equivalence of 18 months compared with 36 months of ADT,[@bib12] and we decided to lengthen the duration of ADT to 18 months.", "\n\nThe aim of this phase I/II study is to prospectively establish the safety and side effect profile of a novel stereotactic, ultra-hypofractionated radiotherapy approach to the prostate alone combined with 18 months of ADT for the treatment of high-risk prostate cancer. ", "The secondary outcome of biochemical disease-free survival is also examined.", "\n\nMethods and Materials {#sec2}\n=====================\n\nPatients were eligible for the study if they had at least 1 high-risk feature as described by the National Comprehensive Cancer Network criteria for high-risk prostate cancer (cT3/4, prostate-specific antigen \\[PSA\\] \\>20 or Gleason Score ≥ 8 based on transrectal ultrasound guided biopsy), no evidence of metastatic disease on computed tomographic (CT) scan of the pelvis or on bone scan, and were willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. ", "Patients were considered for the trial if they met the aforementioned criteria and were over the age of 70 years or declined standard treatment, with standard treatment being defined as 70 Gy in 28 fractions to the prostate and proximal seminal vesicles plus 48 Gy in 28 fractions to the pelvic nodes or 44 Gy in 22 fractions to the prostate, seminal vesicles, and pelvic nodes with a high-dose rate brachytherapy boost of 15 Gy to the prostate. ", "Patients were excluded from the study if they did not meet the eligibility criteria outlined earlier; had received prior pelvic radiotherapy or brachytherapy; were taking anticoagulation; had a history of inflammatory bowel disease, diverticulitis, or collagen vascular disease (other than rheumatoid arthritis); had previous treatment for malignancy (other than basal or squamous cell skin cancer) within 3 years of prostate cancer diagnosis; or were on ADT for \\>2 months before study enrollment.", "\n\nPatients consenting for treatment received 18 months of ADT. ", "The preferred regimen was 3, 6-month luteinizing hormone-releasing hormone (LHRH) agonist depot injections (3- or 4-month depots also allowed). ", "Four weeks of antiandrogen therapy was given contemporaneously with the initiation of LHRH agonist. ", "Radiation therapy began 2 months after ADT was initiated.", "\n\nPatients were instructed on appropriate bowel and bladder preparation for simulation and each treatment to ensure an empty rectum and full bladder. ", "Rectal spacers were not utilized in this study. ", "CT simulation allowed for acquisition of images with a 3-mm slice thickness from L4 superiorly to the ischial tuberosities inferiorly. ", "Resimulation was allowed in the case of unrepresentative anatomy (full rectum or empty bladder). ", "The clinical target volume (CTV) was defined as the prostate plus the proximal 1 cm of the seminal vesicles (at a minimum, entire seminal vesicles could be included if clinically involved). ", "The PTV was a nonuniform expansion around the CTV of 4 mm posteriorly and 5 mm in all other directions. ", "Magnetic resonance imaging was not used for target delineation. ", "The following organs at risk were contoured in keeping with the Radiation Therapy Oncology Group guidelines ([www.rtog.org](http://www.rtog.org){#intref0010}): anus (as a solid organ); rectum (as a solid organ); bladder (as a solid organ); bilateral femoral heads and proximal femurs to the level of the ischial tuberosities; penile bulb; and small bowel. ", "Volumetric-modulated arc therapy was planned with the dose volume histogram (DVH) constraints outlined in [Table 1](#tbl1){ref-type=\"table\"}, where the DVH constraints from the original FASTR trial were also listed for comparison. ", "As shown in [Table 1](#tbl1){ref-type=\"table\"}, the DVH constraints for organs at risk (OARs) are more restrictive in the FASTR-2 trial than those in the FASTR trial. ", "The tighter DVH constraints for OARs were the results of lower prescription dose (35 Gy instead of 40 Gy), smaller target volume (not including pelvic nodes), smaller posterior PTV margin (4 mm instead of 5 mm), and the analysis of the previous FASTR trial.[@bib13]Table 1Planning dose constraints for FASTR-2 and FASTRVolumeDose constraintFASTR-2FASTR[@bib9]PTV prostate and seminal vesicleD95 = 35 GyD95 = 40 GyD5 = 33 GyD5 = 42 GyDmax = 38 GyDmax = 43 GyPTV nodesD95 = 25 GyD5 = 28 GyDmax = 41 Gy (within 1 cm of high dose volume)Dmax = 28 Gy (outside 1 cm of high dose volume)BladderV26 ≤ 50%V29 ≤ 50%V31 ≤ 30%V35 ≤ 30%RectumV20 ≤ 60%V27 ≤ 50%V24 ≤ 50%V35 ≤ 20%V32 ≤ 10%V35 ≤ 2 mLSmall bowelV27.5 ≤ 2 mLV27.5 ≤ 2 mLV25 ≤ 190 mLV25 ≤ 190 mL\n\nTreatments were delivered in 5 fractions, 1 fraction per week for 5 weeks. ", "All plans were verified in phantom before the first treatment fraction with a tolerance of 95% passing rate using gamma parameters, 3% in dose difference, and 3 mm for distance to agreement.", "\n\nPatients received treatment on a linear accelerator with cone beam CT (CBCT) capabilities. ", "CBCT was obtained before each treatment with automatic and manual soft tissue registration to the prostate. ", "The attending radiation oncologist was responsible for viewing and approving the registration for the first fraction of treatment.", "\n\nPatients were assessed at baseline and at 6 weeks after treatment. ", "They were assessed at 6 monthly intervals thereafter until 3 years, then yearly. ", "Assessments included measurements of toxicity using the Common Toxicity Criteria version 4.0. ", "Measurements of prostate-specific antigen (PSA) and testosterone were checked at baseline and at each of the postradiotherapy visits. ", "Liver function tests were checked at baseline, 6 weeks, and 6 months after treatment. ", "The study was approved by the university Research Ethics Board.", "\n\nThe primary outcome was the incidence of grade 3 genitourinary (GU) and GI toxicity at 6 weeks, 6 months, and 1 year. ", "Secondary endpoints were biochemical disease-free survival at 1, 2, and 3 years.", "\n\nAn independent data safety monitoring committee reviewed the toxicity data for the initial 15 patients enrolled after 6 months of follow-up.", "\n\nDose-volume histogram (DVH) values for FASTR and FASTR-2 were compared using the Wilcoxon signed-rank test. ", "All analyses were performed using R Studio (version 3.4.1). *", "P* values \\< .05 were considered statistically significant.", "\n\nResults {#sec3}\n=======\n\nThirty patients were enrolled in the study between March 2015 and August 2017. ", "Two patients were withdrawn from the study before treatment: 1 patient was found to have pelvic nodal involvement after enrollment and 1 patient had significant stool burden resulting in poor reproducibility of anatomy. ", "Of the 30 patients enrolled, 26 were ≥70 years and 4 were \\<70 years but declined standard therapy. ", "All patients had high-risk prostate cancer with a PSA \\>20 ng/mL (*n* = 12), Gleason grade ≥ 8 (*n* = 17), or clinical T3 or T4 disease (*n* = 6). ", "Baseline characteristics are summarized in [Table 2](#tbl2){ref-type=\"table\"}. ", "All 28 patients that received treatment were treated according to protocol. ", "Median follow-up was 28 months (range, 12-44) from the start of radiation.", "Table 2Baseline patient characteristicsVariableTotal (*n* = 30)Age at baseline76.6 (61-89)Clinical stage T1c7 (23.3%) T217 (56.7%) T35 (16.7%) T41 (3.3%)PSA at baseline25.56 (6.58-98.4)Gleason score 64 (13.3%) 79 (30.0%) 89 (30.0%) 9-108 (26.7%)Risk category (based on NCCN criteria) High23 (76.6%) Very high7 (23.3%)[^1]\n\nIn addition, 27 patients were available for toxicity analysis at 6 weeks, 28 patients were available for analysis at 6 months, and 23 patients were available for analysis at 1 year. ", "No grade 3 or higher toxicities were reported at any time point. ", "At baseline, 1 patient (3.5%) had moderate to severe nocturia and no patients had moderate or severe gastrointestinal symptoms. ", "Five patients (18.5%) experienced grade 2 toxicity at 6 weeks after completion of radiation treatment (4 GU and 1 GI). ", "Five patients (17.9%) experienced grade 2 GU toxicity at 6 months, and 5 patients (21.7%) experienced grade 2 GU toxicity at 1 year. ", "There were no instances of grade 2 or higher GI toxicity at 6 months or 1 year. ", "Toxicity data is summarized in [Table 3](#tbl3){ref-type=\"table\"}. ", "The most common toxicities experienced were nocturia and urinary frequency or urgency. ", "There were no reported episodes of rectal bleeding at any time point. ", "Of the 23 patients seen at 1-year follow-up, there were no cases of biochemical failure (mean PSA 0.05, maximum PSA 0.23).Table 3Summary of GU and GI toxicitiesBaseline (*n* = 28)6 weeks (*n* = 27)6 months (*n* = 28)1 year (*n* = 23)Grade 1 GU10 (35.7%)15 (55.5%)17 (60.7%)15 (65.2%)Grade 2 GU1 (3.6%)4 (14.8%)5 (17.9%)5 (21.7%)Grade 1 GI3 (10.7%)8 (29.6%)12 (42.9%)9 (39.1%)Grade 2 GI01 (3.7%)00[^2]\n\nDosimetric constraints to OARs were met in all patients. ", "The rectal maximum dose (D1), D20, and D50, decreased from 40.7 Gy, 29.6 Gy, and 20.8 Gy in FASTR to 35.0 Gy, 22.2 Gy and 11.1 Gy in FASTR-2 (*P* \\< .001), respectively. ", "The bladder maximum dose (D1), D20 and D50, decreased from 40.9 Gy, 28.1 Gy, and 21.5 Gy in FASTR to 35.7 Gy, 15.7 Gy, and 6.3 Gy in FASTR-2 (*P* \\< .001), respectively. ", "Dosimetric results are compared in [Table 4](#tbl4){ref-type=\"table\"} between the FASTR-2 and the FASTR trials.", "Table 4Dosimetric outcomes for FASTR-2 and FASTRFASTR-2FASTR[@bib9]MeanRangeMeanRange*P* ValueD95 prostate and proximal SV35.2 Gy33.7-35.9 Gy40.2 Gy40.0-40.7 Gy\\<.001V100 prostate and proximal SV96.4%83.8-101.7%96.3%95.0-100.0%.376D95 nodes25.2 Gy24.7-25.4 Gyn/aV100 nodes96.8%85.1-100.0%n/aD1 rectum35.0 Gy31.2-36.1 Gy40.7 Gy39.7-41.5 Gy\\<.001D20 rectum22.2 Gy9.4-32.9 Gy29.6 Gy24.1-39.2 Gy\\<.001D50 rectum11.1 Gy4.0-22.4 Gy20.8 Gy15.3-25.2 Gy\\<.001D1 bladder35.7 Gy30.8-36.4 Gy40.9 Gy37.6-42.0 Gy\\<.001D20 bladder15.7 Gy2.5-33.3 Gy28.1 Gy23.5-36.5 Gy\\<.001D50 bladder6.3 Gy0.7-22.2 Gy21.5 Gy15.3-26.2 Gy\\<.001[^3]\n\nDiscussion {#sec4}\n==========\n\nFASTR-2 was well tolerated, with no reported grade 3 or higher toxicities. ", "This is in keeping with expectations based on our analysis of the FASTR trial where it was found that higher relative dose volumes to the rectum (V20-40 Gy) was most strongly associated with rectal bleeding.[@bib13] The FASTR-2 protocol was created with stricter dosimetric constraints to the rectum and bladder compared with the original FASTR protocol, in addition to a lower prescribed dose to the PTV and elimination of nodal irradiation. ", "With the implementation of these changes, there were no reported instances of rectal bleeding or of intermediate or late grade 2 or higher GI toxicities and only 1 reported instance of early grade 2 GI toxicity.", "\n\nThe majority of prostate SABR studies have looked at the role of ultra-hypofractionation in low or intermediate risk prostate cancer; only a few studies have looked at the role of SABR in patients with high-risk prostate cancer. ", "The recently published results from the phase 3, randomized HYPO-RT-PC trial[@bib14] show noninferiority of ultra-hypofractionated radiation compared with conventional fractionation for patients with intermediate and high-risk prostate cancer.[@bib14] Patients in the conventional fractionation arm (*n* = 602) received 78 Gy in 39 fractions and patients in the ultra-hypofractionated arm (*n* = 598) received 42.7 Gy in 7 fractions delivered every other day. ", "Treatment in both arms was prescribed to the prostate only with a 7-mm PTV expansion using fiducial markers for image guidance. ", "Five year biochemical and clinical control rates were 83.8% and 83.7% for the conventional fractionation and ultra-hypofractionation arms, respectively. ", "Furthermore, physician reported late grade 2 or higher toxicity was not significantly different between the 2 arms.", "\n\nTwo previous prospective phase I/II trials have explored the role of SABR to prostate and elective nodal volumes. ", "Both the SATURN (Stereotactic Ablative Radiotherapy Including Regional Lymph Node Irradiation) and FASTR trials prescribed 40 Gy in 5 fractions to the prostate and 25 Gy in 5 fractions to the regional lymph nodes; however, these 2 studies had very different toxicity outcomes.[@bib9], [@bib15] FASTR was terminated during phase I owing to excess late GI toxicities; whereas within SATURN, minimal GI toxicities were noted. ", "A detailed dosimetric analysis of the 2 studies allowed for identification of a correlation between higher dose (≥20 Gy/5 fractions) volumes to the rectum and GI toxicity.[@bib13] FASTR defined the high-dose volume to include the prostate and the proximal 1 cm of seminal vesicle, with a 5-mm expansion from CTV to PTV. ", "SATURN, on the other hand, defined their high dose volume to include only the prostate and used fiducial markers to allow for a 3-mm expansion from CTV to PTV. ", "Furthermore, in FASTR, radiation was prescribed such that 95% of the high-dose PTV received at least 40 Gy; whereas in SATURN, radiation was prescribed such that 99% of the high-dose PTV received at least 33.25 Gy. ", "These variations in protocol are thought to explain the increased rectal dose and increased rectal toxicity experienced in the FASTR trial.", "\n\nOther prospective trials have explored the role of SABR for localized high-risk prostate cancer either as monotherapy or in combination with external beam radiotherapy to pelvic nodes.[@bib16], [@bib17], [@bib18], [@bib19] Only one of these trials had any reported grade 3 or higher toxicity, with 2 of 18 patients with high-risk prostate cancer treated with EBRT to the pelvic nodes in addition to SBRT boost to the prostate experiencing grade 3 GU toxicity.[@bib17] The 2 studies with the longest follow-up reported biochemical disease free survival of 65% at 8 years[@bib16] and 91.9% at 4 years.[@bib18] In all of these studies, fiducial markers were used for image guidance.", "\n\nThe role of ADT in combination with SABR has not been well established. ", "Extrapolation from ablative dosing with brachytherapy for high-risk prostate cancer does indicate that there may be less benefit to ADT than conventional radiotherapy.[@bib20] Current guidelines continue to recommend ADT in addition to radiation for patients with high-risk prostate cancer, although it is unclear whether this should apply.[@bib21] It should be acknowledged that ADT may increase late GI toxicities.[@bib22]\n\nLimitations of this study include small sample size and lack of randomized control data. ", "The dose prescription used in this study was 35 Gy in 5 fractions prescribed to 95% of the PTV. ", "Although this is a lower dose than reported in similar trials, this dose is in keeping with the recently published American Society for Radiation Oncology (ASTRO)/American Society of Clinical Oncology (ASCO)/American Urological Association (AUA) guidelines on hypofractionated radiotherapy for localized prostate cancer, which recommends 35 to 36.25 Gy in 5 fractions for ultra-hypofractionated EBRT regimens as doses higher than this are associated with increased risk of late toxicity.[@bib23] Pelvic nodes were not included in the treatment field in this study; however, the role of nodal irradiation in high-risk prostate cancer is controversial. ", "The long-term results of the GETUG-01 and RTOG-9413 trials did not show benefit of pelvic nodal irradiation for high-risk prostate cancer patients who were also receiving adjuvant ADT.[@bib10], [@bib11] This protocol uses a larger PTV expansion than some similar trials because image guidance was achieved using CBCT without the use of fiducial markers. ", "Fiducial markers have been used in the vast majority of trials studying the use of SABR for prostate cancer; however, it has a number of limitations, including the requirement for local expertise in placing the markers, risks of infection associated with the transperineal procedure, and possibility of marker migration resulting in unreliable image registration and, as such, are not necessarily feasible for all centers or all patients. ", "Biochemical control was achieved in all patients at 1-year follow-up; however, all patients remained on ADT at this timepoint, and therefore longer follow-up is required to determine whether the efficacy of this treatment regimen is comparable to standard treatment for high-risk prostate cancer.", "\n\nBenefits of the FASTR-2 protocol include a weekly fractionation schedule with only 5 fractions, making this regimen especially appealing for frail patients or patients travelling a long distance for treatment. ", "Prostate directed radical radiation has been shown to improve overall survival in men with low-volume metastatic disease treated with concurrent ADT.[@bib24], [@bib25] The FASTR-2 treatment regimen should be similarly well tolerated in this patient population, and the small number of fractions would be desirable in a patient population with known metastatic disease.", "\n\nConclusion {#sec5}\n==========\n\nThe FASTR-2 protocol allows for safe delivery of ultra-hypofractionated radiotherapy to the prostate and seminal vesicles in patients with high-risk prostate cancer without the use of fiducial markers and using a weekly treatment schedule, which is more convenient for some patients. ", "Long term follow-up is required to ensure disease control and toxicity outcomes are comparable to conventional high-risk treatment paradigms.", "\n\nThe authors wish to thank K. Sebborn, C. Johnson, and A. O\\'Connell for clinical trial coordination. ", "Clinical Trials Group identifier: NCT02229734.", "\n\nSources of support: This work was supported by an unrestricted research grant from Sanofi-Aventis.", "\n\nDisclosures: The authors declare that there is no conflict of interest.", "\n\n[^1]: *Abbreviations:* NCCN = National Comprehensive Cancer Network; PSA = prostate-specific antigen.", "\n\n[^2]: *Abbreviations:* GI = gastrointestinal; GU = genitourinary.", "\n\n[^3]: SV = Seminal vesicles.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Our CRASSH network on International Black Radicalism came about by pulling together several streams. ", "Firstly, a group of us realised that there were/are many people researching multiple dimensions of racialisation, racism, and anti-racism across the University from a variety of disciplinary perspectives – sociology, politics, education, psychology, philosophy, history, English, African studies and Latin American studies, to mention a few. ", "Our CRASSH network brings these people together into a collaborative dialogue. ", "Secondly, the network engages with recent student-led activism to ‘decolonise’ the University. ", "We pushed for this CRASSH network so that we could examine intellectuals, and intellectual systems of thought, that are traditionally excluded from the academy. ", "Lastly, as organising members, each of us cares deeply about racism and all seek transformative justice, and we think a comprehensive examination of Black radicalism is important for this social project.", "\n\nQ. By definition, a CRASSH Research Network has an interdisciplinary question at its core. ", "What's yours?", "\n\nWhat is 'international Black radicalism' and how has it been changed in a digital age? ", "Black radicalism has always been inter, or trans, disciplinary. ", "To think of one story, CLR James (an historian who is also co-opted as the pioneer of cultural studies, with sociologists also owing a lot to him), gave a copy of his Black Jacobins to Martin Luther King Jr (a theologian, civil rights activist), via Louis Armstrong (a musician) – so we have the transmission of Black radical knowledge stretching across and influencing multiple disciplines, travelling across a network of Black radicals all of whom also came from different disciplinary backgrounds and brought a particular disciplinary perspective to issues of Black liberation. ", "MLK Jr himself claimed that ‘Injustice anywhere is a threat to justice everywhere’ – Black struggle for liberation in one place is inherently connected to Black struggle globally. ", "How has the digital age accelerated the internationalism of Black radicalism, as we have seen in Twitter revolutions against police brutality such as #BlackLivesMatter and #SayHerName? ", "This question itself requires that trans-disciplinary network that Black radicalism has always relied upon.", "\n\nQ. Could you tell us a bit more about this year's convenors, speakers and attendees and the perspectives they bring to the discussion?", "\n\nConvenors: The convenors represent three departments at the University of Cambridge: the Department of Sociology (Dr Ali Meghji and Tanisha Pratt), the Department of Latin American Studies (Rachell Sanchez Rivera) and the Faculty of Education (Daphne Martschenko and Sharon Walker). ", "Their research addresses a range of issues including race and class, intersectionality theory, decolonial theory, race and medical sociology, the processes of racialised beauty, race, ‘biomedicine’ and biopolitics, and race and educational policy. ", "This collaboration builds on past work to support the establishment of reading groups focused on theories of race and racism in their respective departments.", "\n\nSpeakers: The programme is supported by a range of speakers. ", "Michaelmas term saw contributions from Dr Brian Alleyne (Senior Lecturer, Department of Sociology, Goldsmiths University) and Professor Hakim Adi (University of Chichester). ", "In Lent and Easter term, planned contributions include Rachell Sanchez Rivera (Centre of Latin American Studies, Cambridge), Alicia Garza (Leader of the BlackLivesMatter group) and Journey to Justice (Volunteer led UK human rights education charity). ", "When inviting speakers, the network has aimed to draw on intellectual contributions from academia (both well established and emerging), as well as from grassroot and activist social movements and organisations.", "\n\nAttendees: We have been pleased to host attendees in Michaelmas 2018 from a range of disciplinary backgrounds. ", "This has greatly enriched the groups discussions and sources of expertise. ", "We have also been pleased to see participation from undergraduate students through to University research fellows. ", "We hope to continue this rich exchange of ideas over the coming terms.", "\n\nQ. What can we expect from International Black Radicalism in 2019?", "\n\nWe have a number of exciting discussions planned for 2019. ", "In the first week PhD student Rachell Sanchez Rivera (Centre of Latin American Studies, University of Cambridge) will discuss performances of Black radicalism in a 'colourblind' era. ", "This session will explore the global emergence of colourblind ideology, and how Black radicalism has countered transnational political discourses of post-racialism, post-racism, and mixed-ness. ", "It will focus on the Latin American emergence of ‘mixed-ness,’ and how Black radicals sought to resist this colourblind racial rule. ", "The second session, An Exception to Colourblindness: Black Consciousness in Apartheid South Africa, will focus on the question of how Black radical thinkers in South Africa – including Steve Biko and Nelson Madela – drew upon the thought of contemporary and past Black radicals, including Frantz Fanon, W. E. B Du Bois, and Angela Davis. ", "In the third session we will discuss the role of international Black radicalism in international music. ", "We will consider how Black radical thought from the 1970s emerged in the cultural sphere, particularly in music. ", "By selecting four songs, two from the 1970s (Bob Marley’s 'Slave Driver' [1973] and G. Scott-Heron’s 'The Revolution Will Not Be Televised' [1970]) and two from the present day (Beyonće’s 'Formation' [2016] and Kendrick Lamar’s 'The Blacker the Berry' [2015]), we will discuss how each reflects on similar messages and connections to Black radical thought. ", "In the final session, The Suppression of Black Radicalism: In Memory of Marielle Franco, we will consider how contemporary Black radicals are threatened by their political states and the police. ", "Specifically, we will focus on how Black radicalism often leads to aggressive reactions from racial regimes, as highlighted by the recent murder of Afro-feminist activist Marielle Franco in Brazil.", "\n\nInternational Black Radicalism: Term Card, Lent 2019\n\nQ. How can people learn more about your network?", "\n\nWe welcome anyone and everyone to come join our network and discuss and learn more about international Black radicalism. ", "We are an interdisciplinary group and our door is open to any members from any faculty and those outside of the university.", "\n\nWe meet alternative weeks during term time on Wednesdays from 12:00-14:00. ", "You can follow along on our webpage to get further details on sessions, reading materials, and meeting location.", "\n\nSharon Walker is a PhD Candidate in the Faculty of Education, University of Cambridge. ", "Her research focuses on race and educational policy in the UK, and in particular the widening participation policy agenda in higher education.", "\n\nAli Meghji is a Research Fellow at Sidney Sussex College, and will join the Department of Sociology as Lecturer in Social Inequalities in September, 2019. ", "He is a cultural, critical race sociologist of race and class.", "\n\nTanisha Spratt is a PhD Candidate in the Department of Sociology, University of Cambridge. ", "Her research centres questions of (in)visibility in the lives of US patients with one of two chronic diseases (alkaptonuria and vitiligo). ", "Specifically, she explores the role that social (in)visibility plays in the lives of patients from both disease groups who experience their disease in relation to other social identities that they simultaneously occupy (including race, class and gender).", "\n\nDaphne Martschenko holds a PhD from the Faculty of Education, University of Cambridge. ", "Her scholarship explores the social and ethical dilemmas of behavioural genetics research for the American education system, focusing in particular on how it engages with teacher perceptions of intelligence, race, and socioeconomic status.", "\n\nRachell Sanchez Rivera is a PhD candidate in the Centre of Latin American Studies, specializing in gender, race and eugenics in Latin America and the Caribbean. ", "Before starting her PhD in Cambridge, she did her B.A. in Political Science and History from the University of Puerto Rico, Río Piedras Campus and a M.A. in Regional Studies – Latin America and the Caribbean from Columbia University in the City of New York.", "\n\nAbout CRASSH Research Networks\n\nThe CRASSH Research Networks Programme supports groups of Cambridge graduate students and faculty members with a common interdisciplinary research interest, bringing together early-career researchers, established academics and guest speakers on particular research topics for a year of collaborative work. ", "The groups run bi-weekly events which are free and open to all." ]
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[ "Sergiu Juric\n\nSergiu Juric is a Moldovan professional footballer who plays as a goalkeeper.", "\n\nExternal links\n\nProfil at FC SHERIFF\n\nCategory:1984 births\nCategory:Living people\nCategory:Sportspeople from Chișinău\nCategory:Moldovan footballers\nCategory:Association football goalkeepers\nCategory:Moldova international footballers\nCategory:Moldovan National Division players\nCategory:FC Sheriff Tiraspol players\nCategory:FC Tiraspol players" ]
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[ "Always the cop, Kamala Harris is threatening to disarm Americans caught with contraband plastic straws and hamburgers, but polluters will also have to look over their shoulders for her Environmental Justice Unit:\n\nKamala creates \"Environmental Justice Unit\" to arrest climate change https://t.co/VZQHzzTJJo — Siraj Hashmi (@SirajAHashmi) September 5, 2019\n\nSen. Kamala Harris on why she created Environmental Justice Unit: \"No community should be dumped on. ", "No community should be less than.\" ", "pic.twitter.com/8hTGelaoP2 — The Hill (@thehill) September 5, 2019\n\n\"No community should be dumped on\" Interesting words — Lime & Coconut (@UnmixedCoco) September 5, 2019\n\nHas she been back to her home state recently?", "\n\nBut what about all the people dumping on the streets of San Francisco? ? — ", "Reagan & Maverick (@AngleOfAttack1) September 5, 2019\n\nI’d say there is a lot of California communities that in Harris’ words have been dumped on. — ", "Chris Campbell (@ChrisCampbell32) September 5, 2019\n\nSpeaking of dump taking, has she ridden BART lately? ", "The elevators are a hobo dumping grounds. ", "FECES — RebeccaThrockmorton (@RebeccaThrockm9) September 5, 2019\n\npic.twitter.com/5xWL8pyX5d — That is One Bad Take (@ItsTheArrow) September 5, 2019\n\nCompanies were dumping illegally and only Kamala was there to stop them? ", "In the bay area? ", "Oh hahahahahaha.", "\n\nWhat a whopper this is. — ", "CageyBee (@CageyBee33) September 5, 2019\n\nShe’ll walk it back in 5, 4, 3, 2,…. — ", "Make Greenland Great Again!! (", "@Sports_fan20) September 5, 2019\n\nWatching this with the sound off is the most entertaining thing you'll see all day — Katie Thulin (@katiet121) September 5, 2019\n\nLive look-in on the Environmental Justice Unit. ", "pic.twitter.com/LQVtYNUGPo — Unagi (@brownrobin64) September 5, 2019\n\n“In the criminal justice system, the people are represented two separate but equally important groups: the EJU which investigates pollution and the presidential candidate who prosecuted the offenders for possession of marijuana. ", "These are their stories.” — ", "Thomas Adamson (@tomthecamel2093) September 5, 2019\n\nWe thought this forum was about the climate crisis, not pollution.", "\n\nWas does this even mean? ", "Anyone out there who can speak Gibberish? ", "Translation, please. — ", "Jeff (@jeff_karr) September 5, 2019\n\nIs she going to arrest the weather? ", "Another useless agency that will suck up tax dollars and help precisely .00000001% of the people it’s aimed at, while those running it rake in the $ and live in big houses in gated communities. — ", "Gargle My Balls (@somethi79963647) September 5, 2019\n\nKamala thinking she can handcuff climate change — Dave Coleman (@dave_onion) September 5, 2019\n\nI hope Climate doesn't drop the soap in prison — 1.21 G1GAZ0CKS (@d0c_z1ck) September 5, 2019\n\nShe makes me laugh. — ", "Willie V (@MSU69889966) September 5, 2019\n\nRelated:" ]
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[ "Q:\n\nLeast-squares solution to a linear matrix equation\n\nLet $\\\\A$ be a matrix of size $\\\\(m, n)$, $\\\\b$ a column vector of size $\\\\m$, $\\\\x$ a column vector of size $\\\\n$ and $\\\\a$ a real number.", "\nIf $\\begin{bmatrix}\nx \\\\ \na\n\\end{bmatrix}$ is the least-squares solution to the linear matrix equation:\n$$\n\\begin{bmatrix}\nA & \\begin{matrix}\n-1 \\\\ \n-1 \\\\\n... \\\\ \n-1 \n\\end{matrix}\n\\end{bmatrix}\n\\begin{bmatrix}\nx \\\\ \na\n\\end{bmatrix} = b\n$$\ndoes it mean that the arithmetic mean of $\\\\A x - b$ equals $\\\\a$?", "\nAs background information, I used that result to answer this post on stackoverflow.", "\n\nA:\n\nYes, this is actually a restatement of the following well-known fact: if the design matrix contains a column of all ones (or equivalently, all negative-ones), then the sum of the residuals is zero. ", "For a short proof, \nlet $e$ denote the column of all ones, $X = [A, -e]$, by the nature of least squares, the residual vector $b - (Ax - ae)$ is perpendicular to the linear space spanned by the columns of $X$. In particular, it is perpendicular to the vector $e$, thus,\n$$0 = e^T(b - Ax + ae) = an - e^T(Ax - b)$$\nor $a = e^T(Ax - b)/n$, which is your assertion.", "\n\n" ]
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[ "Right ventricular pulmonary hypertension.", "\nIn heart failure (HF) syndrome, the development of pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure are ominous prognostic signs. ", "Pathophysiology, clinical interest and targeted therapeutic approaches for left-sided PH and its consequences on RV function have been traditionally confined to advanced HF stages. ", "Community- and population-based studies have clearly indicated that PH is frequent even in HF patients with preserved ejection fraction, and may carry important prognostic implications in normal ageing as well. ", "HF guidelines are inconclusive on both preventive and curative strategies for left-sided PH and its consequences on RV function. ", "The search for new therapeutic opportunities targeted on pulmonary vascular and right heart remodeling are an important challenge for the future." ]
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[ "In the past decades, two known zoonotic coronaviruses, severe acute respiratory syndromes coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), have been reported to damage the respiratory tract and cause severe outbreaks ([@r1][@r2]--[@r3]). ", "Severe acute respiratory syndrome coronavirus 2 ([@r4]) is a newly discovered coronavirus, which was first discovered in Wuhan, China in December 2019. ", "The disease was officially named coronavirus disease 2019 (COVID-19) on 11 February 2020 ([@r5]). ", "Epidemiological data have basically determined the route of person-to-person transmission in COVID-19 ([@r6], [@r7]), which spread rapidly and has become a worldwide public health challenge. ", "Most of the patients developed pneumonia, which can worsen rapidly into respiratory failure ([@r8]). ", "The elderly and patients with low immune function have a higher susceptibility and mortality ([@r1]). ", "One study reported that patients usually have pneumonia with abnormal findings on chest computerized tomography (CT) scan ([@r9]). ", "Common symptoms at onset include fever, cough, and myalgia or fatigue. ", "A large number of patients experienced severe complications including acute respiratory distress syndrome (ARDS; 29%); 32% of patients needed an intensive care unit (ICU) admission, and six (15%) died ([@r9]). ", "In another report of 99 cases, 17 (17%) patients developed ARDS, of which 11 (11%) worsened within a few days and died ([@r7]). ", "According to a new report, the mortality for critical cases reached 60.5% ([@r10]). ", "Unfortunately, the pathogenesis of COVID-19 still remains unclear, and there are no efficient therapeutics.", "\n\nStudy demonstrated that in the pathogenesis of severe acute respiratory syndrome (SARS), a cytokine storm occurred, involving a considerable release of proinflammatory cytokine including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-12 ([@r11]). ", "In the research of Middle East respiratory syndrome (MERS), caused by another coronavirus (MERS-CoV), cytokine genes of IL-6, IL-1β, and IL-8 can be markedly high. ", "A delayed proinflammatory cytokine induction by MERS-CoV was also confirmed ([@r12]). ", "Similar to the changes in SARS and MERS, in COVID-19, higher plasma levels of cytokines including IL-6, IL-2, IL-7, IL-10, granulocyte-colony stimulating factor, interferon-γ (IFN-γ)--inducible protein, monocyte chemoattractant protein, macrophage inflammatory protein 1α, and TNF-α were found in ICU patients, which implied that a cytokine storm occurred ([@r7], [@r9]) and related to the severity and prognosis of the disease. ", "In the biopsy samples at autopsy from a patient who died from the severe infection with COVID-19, histological examination showed bilateral diffuse alveolar damage with cellular fibromyxoid exudates. ", "Mononuclear inflammatory lymphocytes were seen in both lungs ([@r13]). ", "These studies suggested that an inflammatory factor or a cytokine storm had occurred. ", "In our previous research, after analyzing the immune characteristics of patients with COVID-19, we have found that aberrant pathogenic T cells and inflammatory monocytes with a large number of cytokines secreting may incite an inflammatory storm. ", "This research has found flow cytometric profiles of increased IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF), and IFN-γ in these severe patients, whereas TNF-α was not significantly up-regulated in CD4^+^ T cells from COVID-19 patients ([@r14]). ", "So, we believe that IL-6 and GM-CSF are the key cytokines leading to inflammatory storm, which may result in increased alveolar--capillary blood--gas exchange dysfunction, especially impaired oxygen diffusion, and eventually lead to pulmonary fibrosis and organ failure. ", "Therefore, we suggested that IL-6 might play a key role in the cytokine storm, and interfering of IL-6 might be a potentially therapeutic for severe and critical COVID-19.", "\n\nIL-6 receptor (IL-6R) has two forms: membrane-bound interleukin-6 receptor (mIL-6R) and soluble interleukin-6 receptor (sIL-6R). ", "IL-6 binds to sIL-6R to form a complex, which then binds to gp130 on the cell membrane to complete transsignal transduction and play a proinflammatory role ([@r15][@r16][@r17]--[@r18]). ", "As a recombinant humanized anti-human IL-6 receptor monoclonal antibody, tocilizumab can specifically bind sIL-6R and mIL-6R and inhibit signal transduction. ", "It is currently used mainly for rheumatoid arthritis ([@r18]). ", "The results of long-term toxicity tests on animals showed that tocilizumab was well tolerated, and no significant abnormalities were observed in other clinicopathological studies or histopathological evaluations ([@r18][@r19]--[@r20]). ", "In this study, we prospectively observed tocilizumab in treating severe or critical COVID-19 patients using historical data to see if IL-6 plays a pivot role in the pathogenesis and the efficacy of the tocilizumab interference of IL-6 in order to provide a therapeutic strategy for this fatal disease.", "\n\nResults {#s1}\n=======\n\nDemographic Characteristics. {#", "s2}\n----------------------------\n\nThe average age of the subjects was 56.8 ± 16.5 y and ranged from 25 to 88 y ([Table 1](#t01){ref-type=\"table\"}). ", "Of the 21 patients, 18 were males (85.7%), and 3 were females (14.3%); 17 patients (81.0%) were assessed as severe, and 4 (19.0%) were critical. ", "Among them, five patients (23.8%) had a history of exposure to Wuhan, and six (28.6%) had exposure to patients who had confirmed COVID-19. ", "Others had no epidemiological history when questioned. ", "Eighteen patients (85.7%) received tocilizumab once, and 3 patients (14.3%) had another one at the same dose due to fever within 12 h.\n\n###### \n\nDemographic characteristics of the patients on presentation\n\n Characteristic Patients (*n* = 21)\n ---------------------------------------------------------------------- ----------------------------------------------------------------\n Age (range), y 56.8 ± 16.5 (25--88)[\\*](#tfn1){ref-type=\"table-fn\"}\n Gender \n  Male 18/21 (85.7%)\n  Female 3/21 (14.3%)\n Chronic medical illness \n  Hypertension 9/21 (42.9%)\n  Diabetes 5/21 (23.8%)\n  CHD 2/21 (9.5%)\n  COPD 1/21 (4.8%)\n  Brain infarction 1/21 (4.8%)\n  Bronchiectasis 1/21 (4.8%)\n  Auricular fibrillation 1/21 (4.8%)\n  CKD 1/21 (4.8%)\n Exposure \n  Exposure to Wuhan 5/21 (23.8%)\n  Exposure to patients[^†^](#tfn2){ref-type=\"table-fn\"} 6/21 (28.6%)\n Symptoms \n  Fever 21/21 (100%)\n  Cough 14/21 (66.7%)\n  Phlegm 9/21 (42.9%)\n  Fatigue 6/21 (28.6%)\n  Chest tightness 6/21 (28.6%)\n  Nausea 4/21(19.0%)\n  Rhinorrhea 1/21 (4.8%)\n  Chest pain 1/21 (4.8%)\n Body temperature, °C 38.8 ± 0.6 (37.6--40.6)\n  37.6--38.6 11/21 (52.4%)\n  38.6--39.6 8/21 (38.1%)\n  39.6--40.6 2/21 (9.5%)\n Time to progression, d 5.6 ± 2.8 (2--14)[\\*](#tfn1){ref-type=\"table-fn\"}\n Laboratory tests before tocilizumab[^‡^](#tfn3){ref-type=\"table-fn\"} \n  Neutrophils percentage (%, 40--75) 82.28 ± 9.14 (16/20, 80.0%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Platelet count (×10^9^/L, 125--350) 170.35 ± 58.26 (4/20, 20.0%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Erythrocyte sedimentation rate (mm/h, 0--15) 42.42 ± 27.82 (10/12, 83.3%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  [d]{.smallcaps}-dimer (μg/mL, 0--1.10) 0.80 ± 0.92 (2/19, 10.5%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Prothrombin time (s, 10.5--14.5) 12.39 ± 2.12 (4/19, 21.1%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Alanine aminotransferase (IU/L, 0--50) 29.55 ± 14.44 (1/20, 5.0%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Aspartate aminotransferase (IU/L, 15--40) 31.15 ± 9.25 (1/20, 5.0%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Creatine kinase (IU/L, 50--310) 162.41 ± 74.77 (1/19, 5.3%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Lactate dehydrogenase (U/L, 120--250) 370.70 ± 140.21 (17/20, 85.0%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Creatinine (μmol/L, 35--115) 78.20 ± 26.46 (2/20, 10.0%)[\\*](#tfn1){ref-type=\"table-fn\"}\n  Blood urea nitrogen (mmol/L, 3.1--8.0) 5.64 ± 2.75 (2/20, 10.0%)[\\*](#tfn1){ref-type=\"table-fn\"}\n State of illness \n  Severe 17/21 (81.0%)\n  Critical 4/21 (19.0%)\n Oxygen therapy \n  High-flow oxygen 9/20 (45.0%)\n  Nasal cannula 7/20 (35.0%)\n  Invasive ventilation 2/20 (10.0%)\n  Noninvasive ventilation 1/20 (5.0%)\n  Mask oxygen 1/20 (5.0%)\n Tocilizumab adverse events 0\n Clinical outcome \n  Discharge from hospital 21/21 (100%)\n Hospitalization days (range), d[^§^](#tfn4){ref-type=\"table-fn\"} 15.1 ± 5.8 (10--31)[\\*](#tfn1){ref-type=\"table-fn\"}\n  ≤14 13/21 (61.9%)\n  14--21 6/21 (28.6%)\n  ≥21 2/21 (9.5%)\n\nData are *n*/*N* (%) unless specified otherwise. ", "CHD, coronary heart disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease.", "\n\nPlus--minus values are means ± SD.", "\n\nPatients who have confirmed COVID-19.", "\n\nNot all patients received all relevant laboratory tests.", "\n\nHospitalization days after the treatment with tocilizumab.", "\n\nClinical Presentations. {#", "s3}\n-----------------------\n\nAll patients presented with fever as the first symptom followed by dry cough (14/21, 66.7%), a small amount of white phlegm (9/21, 42.9%), fatigue (6/21, 28.6%), and chest tightness (6/21, 28.6%). ", "Four (19.0%) patients had nausea. ", "Other symptoms, including rhinorrhea and chest pain, were rare (4.8%). ", "Among all patients, there was a mean time of 5.6 ± 2.8 d (range, 2 to 14) from the onset of fever to the occurrence of dyspnea. ", "Twenty patients were treated with an oxygen therapy, including high-flow oxygen therapy in 9 patients (45.0%), nasal cannula in 7 patients (35.0%), mask oxygen in 1 patient (5.0%), noninvasive ventilation in 1 patient (5.0%), and invasive ventilation in 2 patients (10.0%). ", "Also, one patient refused oxygen therapy. ([", "Table 1](#t01){ref-type=\"table\"})\n\nLaboratory Examinations. {#", "s4}\n------------------------\n\n[Tables 1](#t01){ref-type=\"table\"} and [2](#t02){ref-type=\"table\"} show the results of baseline laboratory tests before tocilizumab. ", "White blood cell count showed that four patients (4/20, 20.0%) have an abnormal value (mean, 6.30 ± 2.77 × 10^9^/L) in peripheral blood. ", "The percentage of lymphocytes was decreased in 85.0% of patients (17/20; mean, 15.52 ± 8.89%); 80.0% of patients (16/20) have elevated percentage of neutrophils (mean, 82.28 ± 9.14%). ", "Ten of 12 patients (83.3%) had elevated erythrocyte sedimentation rate (mean, 42.42 ± 27.82 mm/h). ", "The mean of [d]{.smallcaps}-dimer was 0.80 ± 0.92 μg/mL, and prothrombin time was 12.39 ± 2.12 s. C-reactive protein (CRP) levels increased in all 20 patients (mean, 75.06 ± 66.80 mg/L). ", "The mean of procalcitonin (PCT) value was 0.33 ± 0.78 ng/mL, and only 2 of 20 patients (10.0%) presented an abnormal value. ", "One patient (1/19, 5.3%) had an elevated creatine kinase with a mean of 162.41 ± 74.77 IU/L. Lactate dehydrogenase levels increased in 85.0% of patients (17/20; mean, 370.70 ± 140.21 U/L). ", "Only 1 of 20 patients (5.0%) had slightly elevated alanine aminotransferase and aspartate aminotransferase (means, 29.55 ± 14.44 and 31.15 ± 9.25 IU/L, respectively). ", "Creatinine and blood urea nitrogen increased slightly in two patients (2/20, 10%), with mean values of 78.20 ± 26.46 μmol/L and 5.64 ± 2.75 mmol/L, respectively.", "\n\n###### \n\nLaboratory tests before and after tocilizumab\n\n Normal range Before tocilizumab After tocilizumab \n ---------------------------- -------------- ------------------------------- ------------------------------- ------------------------------- -------------------------------\n White cell count, ×10^9^/L 3.5--9.5 6.30 ± 2.77 (4/20, 20.0%) 8.05 ± 4.39 (8/18, 44.4%) 6.02 ± 3.05 (9/21, 42.9%) 5.25 ± 2.11 (2/19, 10.5%)\n Lymphocyte percentage, % 20--50 15.52 ± 8.89 (17/20, 85.0%) 11.78 ± 11.36 (16/18, 88.9%) 16.93 ± 13.59 (14/21, 66.7%) 22.62 ± 13.48 (9/19, 47.4%)\n CRP, mg/L 0--5 75.06 ± 66.80 (20/20, 100%) 38.13 ± 54.21 (17/18, 94.4%) 10.61 ± 13.79 (10/20, 50.0%) 2.72 ± 3.60 (3/19, 15.8%)\n Procalcitonin, ng/mL 0--0.5 0.33 ± 0.78 (2/20, 10.0%) 0.21 ± 0.35 (2/16, 12.5%) 0.09 ± 0.13 (1/19, 5.3%) 0.12 ± 0.15 (1/18,5.6%)\n IL-6, pg/mL 0--7 153.44 ± 296.63 (18/18, 100%) 129.18 ± 131.79 (13/13, 100%) 300.98 ± 341.90 (17/17, 100%) 274.90 ± 414.08 (12/12, 100%)\n\nData are means ± SD (abnormal no./total no., %). ", "D, day after tocilizumab.", "\n\nAdditionally, all patients had been analyzed for IL-6 expression levels before tocilizumab. ", "The mean of 18 patients tested by electrochemical luminescence method was 153.44 ± 296.63 pg/mL. The remaining three patients from Anhui Provincial Hospital have analyzed their IL-6 expression in peripheral blood lymphocyte with 6.95, 7.40, and 7.72% IL-6^+^ cells of CD4^+^ T cells. ", "Both methods have shown IL-6 up-regulation in these severe and critical COVID-19 patients.", "\n\nImaging Features. {#", "s5}\n-----------------\n\nAll patients had abnormal chest CT on presentation. ", "The primary abnormality on the initial chest CT was plaque-like, ground glass opacities and focal consolidation, mainly distributed in the peripheral, especially the subpleural region ([Fig. ", "1 *A*--*C*](#fig01){ref-type=\"fig\"}). ", "The ground glass opacities increased in size, extent, and severity in 21 patients within the first 7 d after admission before receiving tocilizumab. ", "No pleural effusions, mediastinal nodes, or central pulmonary emboli were found.", "\n\n![", "Chest CT scans showed significant remission in both lungs in patients after the treatment with tocilizumab. (*", "A*--*C*) Computerized tomography (CT) showed plaque-like and ground glass opacities before the treatment with tocilizumab. (*", "D*--*F*) Chest CT showed diffuse infiltration in both lungs, but the lesions were clearly absorbed after the treatment with tocilizumab.](pnas.2005615117fig01){#fig01}\n\nTreatment Outcomes. {#", "s6}\n-------------------\n\nThe body temperature of all patients dramatically returned to normal on the first day after receiving tocilizumab and remained stable thereafter ([Fig. ", "2*B*](#fig02){ref-type=\"fig\"}). ", "Clinical symptoms were significantly relieved synchronously in the following days. ", "The peripheral oxygen saturation improved remarkably ([Fig. ", "2 *C* and *D*](#fig02){ref-type=\"fig\"}). ", "Fifteen patients (15/20, 75.0%) had lowered their oxygen intake within 5 d after the treatment with tocilizumab. ", "Among these patients, one patient did not need further oxygen therapy. ", "Among the three patients who used ventilator, one patient was taken off the noninvasive ventilator on the first day after tocilizumab, one patient had tracheal extubated and regained consciousness on the fifth day and another one on the eleventh day.", "\n\n![", "The values of CRP, body temperature, concentration of oxygen inhalation, and oxygen saturation before and after the treatment with tocilizumab for the 21 patients with COVID-19. (*", "A*) CRP decreased significantly after the treatment with tocilizumab and returned to normal in the majority of the patients. (*", "B*) The fever returned to normal in all 21 patients after tocilizumab. (*", "C* and *D*) Before the treatment, 20 patients needed oxygen therapy except 1 who refused. ", "After tocilizumab, 15 patients had lowered their oxygen intake, and the oxygen saturation remained stable. ", "Among them, one patient did not need further oxygen therapy on the third day. ", "Therefore, the concentration of his oxygen inhalation during D3-D5 has marked as 21%, similar as oxygen content in normal air. (*", "B*--*D*) \\**P* \\< 0.05, \\*\\**P* \\< 0.01, \\*\\*\\**P* \\< 0.005, \\*\\*\\*\\**P* \\< 0.0001. ", "D, day after tocilizumab; SpO2, percutaneous blood oxygen saturation.](pnas.2005615117fig02){#fig02}\n\nA significant change of the percentage of lymphocytes and CRP levels was observed after tocilizumab treatment, as shown in [Fig. ", "2*A*](#fig02){ref-type=\"fig\"} and [Table 2](#t02){ref-type=\"table\"}. ", "On the fifth day after treatment, only two patients (2/19, 10.5%) had an abnormal value in white blood cell count with a mean of 5.25 ± 2.11 × 10^9^/L. The percentage of lymphocytes in 10 patients (10/19, 52.6%) returned to normal (mean, 22.62 ± 13.48%). ", "CRP decreased significantly and returned to normal in 84.2% of patients (16/19; mean, 2.72 ± 3.60 mg/L) after treatment on the fifth day. ", "The value of IL-6 did not decrease significantly in the short term after treatment with tocilizumab ([Table 2](#t02){ref-type=\"table\"}). ", "After treatment, CT scans showed that the lesions were absorbed in 19 (90.5%) patients and a little improvement in the others ([Fig. ", "1 *D*--*F*](#fig01){ref-type=\"fig\"}). ", "All patients have been discharged including critical ones. ", "Two consecutive negative viral qualitative tests with a time interval of 24 h have indicated that the viral load was completely cleared. ", "The mean hospitalization time was 15.1 ± 5.8 d after the treatment with tocilizumab. ", "Among them, 13 (61.9%) patients were discharged within 2 wk after tocilizumab, and 6 were discharged within 3 wk ([Table 1](#t01){ref-type=\"table\"}).", "\n\nSafety. {#", "s7}\n-------\n\nAll reported adverse events of patients were recorded. ", "In our study, there were no serious events caused by tocilizumab. ", "Adverse drug reactions, including elevated transaminase, neutropenia, infection, etc., ", "were not reported. ", "No emerging bacterial, fungal, or viral infections were observed during the treatment.", "\n\nDiscussion {#s8}\n==========\n\nIn this study, we retrospectively observed tocilizumab, an IL6R inhibitor, in treatment of 21 patients with severe and critical COVID-19. ", "Clinical data showed that the symptoms, hypoxygenmia, and CT opacity changes were improved immediately after the treatment with tocilizumab in most of the patients, suggesting that tocilizumab could be an efficient therapeutic for the treatment of COVID-19.", "\n\nCOVID-19 is a newly occurred infectious respiratory disease with mild symptoms in the early stages of infection. ", "However, in a considerable number of patients, the symptoms deteriorate rapidly and are manifested as chest tightness, shortness of breath, and even respiratory failure. ", "CT scans often show rapid enlarged opacities. ", "These patients usually need oxygen therapy and even assistant ventilation in the ICU. ", "Unfortunately, 4.3 to 11% of them died even after recommended standard treatment ([@r7], [@r8]), as no effective therapeutics could be achieved. ", "Additionally, the mortality for critical cases reached as high as 60.5% ([@r10]). ", "In this research, all 21 patients had a history of routine treatment for a week before tocilizumab but deteriorated with sustained fever, hypoxygenmia, and CT image worsening. ", "After the treatment with tocilizumab, in addition to the improvement of body temperature, the respiratory function was improved to some degree in most of the patients. ", "Chest tightness was relieved. ", "Most patients lowered their oxygen intake flow, and the oxygen saturation remained stable. ", "Two patients were taken off the ventilator within 5 d. Therefore, it is necessary to start tocilizumab treatment as soon as possible when the following conditions occurred, including persistent fever, the condition changes from mild to severe (including high-risk factor for severe cases), diffuse lung opacities on CT scans, and elevated level of IL-6. ", "Early treatment can effectively control the deterioration of symptoms.", "\n\nThe decrease of the percentage of lymphocytes has been considered an important indicator for diagnosis and severity judgment in COVID-19 patients ([@r8]). ", "In our study, a lower percentage of lymphocytes was found in 85.0% of patients (17/20) and returned to normal in 52.6% of patients (10/19) within 5 d when tocilizumab was given. ", "At the same time, elevated CRP also returned to normal. ", "The level of IL-6 increased in all patients before treatment. ", "After the treatment, the IL-6 levels will be temporarily increased in serum in the next few days, for its receptors have been blocked by tocilizumab. ", "Similar conditions can be observed in chimeric antigen receptor T cell treatment ([@r21]). ", "The lung opacities on CT scans were absorbed in 19 (90.5%) patients. ", "Considering that the lung tissue damage needs sufficient time for repairing, remission delay in CT scan can be anticipated. ", "During the treatment, no adverse drug reactions and subsequent pulmonary infections were reported. ", "Clinical symptoms of all patients improved remarkably with good prognosis after the treatment. ", "All patients have been discharged, and most of them were within 2 wk after tocilizumab. ", "Therefore, tocilizumab can effectively treat severe patients of COVID-19, which might be explained by the blocking of IL-6--associated febrile and inflammatory storm response.", "\n\nNevertheless, there are several shortcomings in this study. ", "The number of patients was rather limited. ", "It was a single observation study, and a significant bias could have possibly existed. ", "Apparently, the evidence strength needs to be enhanced. ", "To get more evidence, a randomized, controlled trial and a study on the mechanism of IL-6 in COVID-19 are being under performing.", "\n\nConclusion {#s9}\n==========\n\nIn summary, tocilizumab effectively improve clinical symptoms and represses the deterioration of severe COVID-19 patients. ", "Therefore, tocilizumab is an effective treatment in severe patients of COVID-19, which provided a therapeutic strategy for this fatal infectious disease.", "\n\nMethods {#s10}\n=======\n\nPatients. {#", "s11}\n---------\n\nA total of 21 patients met the study conditions and were treated with tocilizumab between 5 and 14 February 2020. ", "Seven of the patients were treated in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), and 14 patients were treated in Anhui Fuyang Second People's Hospital. ", "All patients enrolled met the severe or critical criteria defined by the \"Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (7th Interim Edition)\" sponsored by the National Health Commission of the People's Republic of China ([@r22]). ", "For diagnosis, specimens were obtained by throat swabs under aseptic operation and tested with real-time RT-PCR assay that was developed from the publicly released virus sequence. ", "The diagnosis of severity was defined if any of the following conditions were met: 1) respiratory rate ≥30 breaths per 1 min, 2) SpO2 ≤ 93% while breathing room air, 3) PaO~2~/FiO~2~ ≤ 300 mm Hg. ", "A critical case was diagnosed if any of the following conditions were met: 1) respiratory failure, which requiring mechanical ventilation; 2) shock; 3) combined with other organ failure, need to be admitted to the ICU. ", "Also, patients with active pulmonary tuberculosis combined with clear bacterial infection and fungal infection were excluded.", "\n\nThe Medical Research Ethics Committee of the Anhui Provincial Hospital approved the study. ", "All patients signed informed consent before using tocilizumab and agreed to publish this case series. ", "We are committed to protecting patient privacy and complying with the Helsinki Declaration \\[approval no. ", "2020-XG(H)-015\\].", "\n\nIL-6 Test. {#", "s12}\n----------\n\nThe value of IL-6 was measured by electrochemical luminescence method (Roche Diagnostics GmbH) in 18 patients or fluorescence-activated cell sorting analysis in 3 patients. ", "Intracellular staining of IL-6 was performed without adding any restimulation. ", "The cells were then collected, washed, and blocked according to the instructions of eBioscience. ", "The normal range of IL-6 in peripheral blood is less than 7 pg/mL.\n\nTreatment and Observation. {#", "s13}\n--------------------------\n\nAll patients received standard care as follows according to the \"Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (7th Interim Edition)\" ([@r22]): 1) antiviral therapy of lopinavir/ritonavir (200/50 mg per tablet for adults twice a day, two tablets each time, and the course of treatment does not exceed 10 d), IFN-α (5 million U each time for adults or equivalent dissolved in 2 mL of sterilized water and aerosol inhalation twice a day), and ribavirin (recommended for use with IFN or lopinavir/ritonavir, 500 mg per dose for adults, intravenous \\[i.v.\\] drip two to three times a day, and the course of treatment does not exceed 10 d); 2) glucocorticoid (use for a short period of time, range 3 to 5 d, as appropriate, at a dose not exceeding the equivalent of 1 to 2 mg/kg per day methylprednisolone for patients with rapid progress in respiratory function and imaging and excessive activation of the inflammatory response); 3) other symptom relievers and oxygen therapy.", "\n\nAlso, they were treated with tocilizumab (Roche Pharma \\[Schweiz\\] Ltd; B2084B21).The first dose was 4--8 mg/kg body weight, and the recommended dose was 400 mg through an i.v. ", "drip up to a maximum of 800 mg. ", "Dilution was to 100 mL with 0.9% normal saline, and the infusion time was more than 1 h. In case of fever within 12 h, an additional dose was given (same as before), and the cumulative dose could not be more than two times.", "\n\nClinical features including body temperature, concentration of oxygen inhalation, and oxygen saturations were recorded daily before and after treatment. ", "A whole-blood white cell count was performed repeatedly. ", "All patients had been spiral CT scanned on admission and a week later after the beginning of tocilizumab treatment using a 64-row spiral Optima CT680 scanner (GE Healthcare) in a whole-lung, low-dosage exposure, scanning with 5-mm slices.", "\n\nData Collection. {#", "s14}\n----------------\n\nClinical data were retrospectively analyzed by searching the information archived and coded by The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People's Hospital, including gender, age, coexisting diseases, epidemiology, clinical symptoms, and peripheral oxygen saturations. ", "Not all patients received relevant laboratory tests at a particular time, and we put emphasis on white blood cell count, lymphocytes percentage, CRP, and PCT. ", "This study focused on the changes in body temperature, respiratory function, and CT findings before and after treatment with tocilizumab.", "\n\nStatistical Analysis. {#", "s15}\n---------------------\n\nAll statistical data were analyzed by IBM SPSS software v.16.0 and are expressed as means ± SD. ", "Paired *t* tests analyses have been used in [Fig. ", "2 *B*--*D*](#fig02){ref-type=\"fig\"}. ", "Data Sharing.", "\n\nRequests for materials should be addressed to the corresponding authors.", "\n\nThis work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province Grant 202004a07020001 and China National Center for Biotechnology Development 175 Grant 2020YFC0843800.", "\n\nThe authors declare no competing interest.", "\n\nThis article is a PNAS Direct Submission.", "\n\n[^1]: Edited by Zhu Chen, Shanghai Jiao Tong University, Shanghai, China, and approved April 14, 2020 (received for review March 25, 2020)\n\n[^2]: Author contributions: X.X. and H.W. designed research; M.H., W.S., D.W., Y.Z., X. Zheng, Y.Y., X.L., X. Zhang, and A.P. performed research; X.X., T.L., B.F., and H.W. analyzed data; and X.X., T.L., B.F., and H.W. wrote the paper.", "\n\n[^3]: ^1^X.X. and M.H. contributed equally to this work.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "[Mathematical kinetic model of dual-frequency ultrasound assisted extraction of effective components traditional Chinese medicine].", "\nTo establish the mathematical kinetic model of the components extracted from the Salvia miltiorrhiza. ", "In the conditions of ultrasound extracting the course of traditional Chinese medicine, the role of ultrasound intensity is large enough, the proliferation of boundary layer can be infinitesimal, as well as the solute upon the surface of medicine quickly into the main solution, we can assume that the whole process of extraction from the control of proliferation. ", "A mathematical model of dual-frequency ultrasound extraction kinetics based on Fick's second diffusion law was established for traditional Chinese medicine. ", "Based on material size and solid/liquid ratio significant factors. ", "We adopt Origin software to carry out a mathematics simulation, the result showed: simulation graphics and experiment value are very fitting. ", "This proves that S. miltiorrhiza extraction course accords with ordinary extraction dynamics equation at the dual-frequency ultrasound." ]
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[ "News Archive, 2009\n\nIIS Scholar Presents Paper at a Conference on FatimidsJanuary 2009\n\nDrs. ", "Farhad Daftary and Shainool Jiwa participated in a conference on ‘The Fatimids and the Mediterranean’ organised by the Universita degli Studi di Palermo. ", "The proceedings focussed on the social, cultural and political frameworks and institutions in the Muslim world as well as in the broader Mediterranean region during the Fatimid era.", "\n\nHeld from 3-6 December, 2008, the conference was organised under the patronage of the Ministry of Foreign Affairs for the Sicilian Region, The Institute of Ismaili Studies, and Fondazione Universitaria Italo-Libica (Italian-Libyan University Foundation). ", "Dr Daftary delivered introductory remarks in the opening session and presided over the first session.", "\n\nDuring the next session, Dr Shainool Jiwa delivered a paper on the ‘Historical representations of a Fatimid Imam-caliph: Exploring al-Maqrizi’s and Idris’ writings on Imam-caliph al-Mu‘izz li Din Allah’. ", "She noted that although Taqi al-Din Ahmad b. Ali al-Maqrizi (845 AH/1449 CE) and ‘Imad al-Din Idris (d. 872 AH/1468 CE) were writing in the 15th century, almost three centuries after the Fatimid empire had waned, their writings assume primary source significance as, in constructing their narrative, they draw upon a spectrum of earlier North African, Egyptian and Iraqi sources, Sunni and Ismaili, which have not survived the vagaries of time and circumstance. ", "Though contemporaneous, both authors, the first an Egyptian Sunni Shafi‘i jurist, the second a Yemeni, Tayyibi Ismaili Chief Da‘i, have significantly different interests and motivations when writing about the Fatimid era. ", "This provided a relatively rare opportunity to study two discrete perspectives from which to understand and examine Fatimid historiography. ", "An examination of their notions, purposes and expressions of history formed the focus of this paper.", "\n\nThe reign of the fourth Fatimid Imam-caliph, al-Mu‘izz li Din Allah [953-975 AH], in whose era Egypt was brought under Fatimid sway, thus transforming their North African state into a Mediterranean empire, has received significant attention from both al-Maqrizi and Idris. ", "Thus, their writings on the life and times of Imam-caliph al-Mu‘izz provide an instructive case-study on the focus, scope, purpose and perimeters of what constitutes historical narratives in Fatimid historiography and, by extension, in formative Muslim historical writings. ", "Dr Jiwa postulated that al-Maqrizi strives to present what he considers to be accurate knowledge, through a reasoned examination of the source materials available to him. ", "Adopting what would today be considered an empiricist, Rankean approach; he notes an expressed preference for sources that are in close spatial and geographic proximity to the events they are describing. ", "For ‘Imad al-Din Idris, on the other hand, the purpose of recording terrestrial history is to faithfully understand and document the unfolding of a primordial divine purpose within the Tayyibi Ismaili doctrinal and cosmological structure of the universe. ", "Hence, while the recording of human engagements is necessary and important, essentially it serves a larger, symbolic ethos and function. ", "The paper, therefore, argued that for Idris the defining paradigm of the acceptability of a source was whether it resonated with this worldview, regardless of its eastern or western, Sunni or Shi‘i provenance. ", "Consequently, the Itti‘az of al-Maqrizi and the Uyun of Idris complement and supplement each other in providing as historically accurate and as symbolically representative a rendering of the Fatimid weltenschaung as is possible within our current purview of primary sources.", "\n\nThe Institute of Ismaili Studies - IIS Scholar Presents Paper at a Conference on Fatimids" ]
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[ "One of the benefits of home video is that you can enjoy\nadult films in the privacy of your home, and not in the\npresence of rather questionable patrons at some downtown dive\nmasquerading as a movie theatre. ", "A stalwart of such porn\nhouses, 8 and 16mm loops were the equivalent of \"B\" movies;\nshot very quickly and on the cheap. ", "As the adult video market\nexpanse, most of these old loops have become readily\navailable, allowing us to see now popular stars in\nless-than-glamorous productions.", "\n\nAs one of the best compilations of old loops this reviewer\nhas seen, the first volume of the Erotica Collection\nfeatures five stags of surprisingly good quality. ", "The first\none, Desiree's Dilemma, has not only Desiree\n(Pretty Peaches) Cousteau, but a young John Leslie, to\nboot. ", "In this segment (the tape's best), Desiree gets\ncollared, chained, and basically dominated, all in a rather\nrough twenty minutes. ", "Unfortunately, she does not get an\nenema.", "\n\nAs for the other loops, there is an emphasis on oral sex and\nthreesomes. ", "While not up to the quality of Desiree's\nDilemma, they all have a fast and furious physical play.", "\nThose searching for plot line and character development are\ndirected elsewhere. ", "But, for anyone who likes their sex films\nminus studs and nymphos straining to be Meryl Street, old\nloops and the Erotica Collection won't let you down." ]
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[ "Q:\n\nHow to loop through an associative array in PHP?", "\n\nLets assume I have the following:\n$times = array();\n for($month = $current_month; $month <= $end_month; $month++) {\n $first_minute = mktime(0, 0, 0, $month, 1);\n $last_minute = mktime(23, 59, 0, $month, date('t', $first_minute));\n $times[$month] = array($first_minute, $last_minute);\n }\n\nI now need to loop through all the $months but I am not sure how I can achieve this.", "\nI have tried foreach() but that requires I enter a value for $month. ", "We are assuming the value is not clear.", "\n\nA:\n\nDo you mean you need to loop through $times?", "\nA simple foreach will do...\nforeach ($times as $month => $mins) {\n // $month = the month\n // $mins[0] = first minute\n // $mins[1] = last minute\n}\n\n" ]
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[ 0.019230769230769232, 0.004987531172069825, 0, 0, 0, 0 ]
0.004036
5
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[ "package templates\n\n// ClientEncodeTemplate is the template for generating the client-side encoding\n// function for a particular Binding.", "\nvar ClientEncodeTemplate = `\n{{- with $binding := . -}}", "\n\t// EncodeHTTP{{$binding.", "Label}}Request is a transport/http.", "EncodeRequestFunc\n\t// that encodes a {{ToLower $binding.", "Parent.", "Name}} request into the various portions of\n\t// the http request (path, query, and body).", "\n\tfunc EncodeHTTP{{$binding.", "Label}}Request(_ context.", "Context, r *http.", "Request, request interface{}) error {\n\t\tstrval := \"\"\n\t\t_ = strval\n\t\treq := request.(*pb.{{GoName $binding.", "Parent.", "RequestType}})\n\t\t_ = req\n\n\t\tr.Header.", "Set(\"transport\", \"HTTPJSON\")\n\t\tr.Header.", "Set(\"request-url\", r.URL.Path)\n\n\t\t// Set the path parameters\n\t\tpath := strings.", "Join([]string{\n\t\t{{- range $section := $binding.", "PathSections}}\n\t\t\t{{$section}},\n\t\t{{- end}}\n\t\t}, \"/\")\n\t\tu, err := url.", "Parse(path)\n\t\tif err !", "= nil {\n\t\t\treturn errors.", "Wrapf(err, \"couldn't unmarshal path %q\", path)\n\t\t}\n\t\tr.URL.RawPath = u.RawPath\n\t\tr.URL.Path = u.Path\n\n\t\t// Set the query parameters\n\t\tvalues := r.URL.Query()\n\t\tvar tmp []byte\n\t\t_ = tmp\n\t\t{{- range $field := $binding.", "Fields }}\n\t\t\t{{- if eq $field.", "Location \"query\"}}\n\t\t\t\t{{if and $field.", "Repeated $field.", "IsBaseType}}\n\t\t\t\t\t{{- if (Contains $field.", "GoType \"[]string\")}}\n\t\t\t\t\tvalues[\"{{$field.", "QueryParamName}}\"] = req.{{$field.", "CamelName}}\n\t\t\t\t\t{{- else}}\n\t\t\t\t\tfor _, v := range req.{{$field.", "CamelName}} {\n\t\t\t\t\t\tvalues.", "Add(\"{{$field.", "QueryParamName}}\", fmt.", "Sprint(v))\n\t\t\t\t\t}\n\t\t\t\t\t{{- end}}\n\t\t\t\t{{else if or (not $field.", "IsBaseType) $field.", "Repeated}}\n\t\t\t\t\ttmp, err = json.", "Marshal(req.{{$field.", "CamelName}})\n\t\t\t\t\tif err !", "= nil {\n\t\t\t\t\t\treturn errors.", "Wrap(err, \"failed to marshal req.{{$field.", "CamelName}}\")\n\t\t\t\t\t}\n\t\t\t\t\tstrval = string(tmp)\n\t\t\t\t\tvalues.", "Add(\"{{$field.", "QueryParamName}}\", strval)\n\t\t\t\t{{else}}\n\t\t\t\t\tvalues.", "Add(\"{{$field.", "QueryParamName}}\", fmt.", "Sprint(req.{{$field.", "CamelName}}))\n\t\t\t\t{{- end }}\n\t\t\t{{- end }}\n\t\t{{- end}}\n\t\t{{- range $oneof := $binding.", "OneofFields }}\n\t\t\t{{- if eq $oneof.", "Location \"query\"}}\n\t\t\t\t{{- range $option := $oneof.", "Options }}\n\t\t\t\t\t{{if or (not $option.", "IsBaseType) $option.", "Repeated}}\n\t\t\t\t\t\tif val := req.", "Get{{$option.", "Name}}(); val !", "= {{$option.", "ZeroValue}} {\n\t\t\t\t\t\t\ttmp, err = json.", "Marshal(req.", "Get{{$option.", "Name}}())\n\t\t\t\t\t\t\tif err !", "= nil {\n\t\t\t\t\t\t\t\treturn errors.", "Wrap(err, \"failed to marshal req.", "Get{{$option.", "Name}}()\")\n\t\t\t\t\t\t\t}\n\t\t\t\t\t\t\tstrval = string(tmp)\n\t\t\t\t\t\t\tvalues.", "Add(\"{{$option.", "QueryParamName}}\", strval)\n\t\t\t\t\t\t}\n\t\t\t\t\t{{else}}\n\t\t\t\t\t\tif val := req.", "Get{{$option.", "Name}}(); val !", "= {{$option.", "ZeroValue}} {\n\t\t\t\t\t\t\tvalues.", "Add(\"{{$option.", "QueryParamName}}\", fmt.", "Sprint(val))\n\t\t\t\t\t\t}\n\t\t\t\t\t{{- end }}\n\t\t\t\t{{- end }}\n\t\t\t{{- end }}\n\t\t{{- end}}\n\n\t\tr.URL.RawQuery = values.", "Encode()\n\n\t\t{{- if ne $binding.", "Verb \"get\" }}\n\t\t// Set the body parameters\n\t\tvar buf bytes.", "Buffer\n\t\ttoRet := request.(*pb.{{GoName $binding.", "Parent.", "RequestType}})\n\t\t{{- range $field := $binding.", "Fields -}}\n\t\t\t{{if eq $field.", "Location \"body\"}}\n\t\t\t\t{{/* Only set the fields which should be in the body, so all\n\t\t\t\tothers will be omitted due to emptiness */}}\n\t\t\t\ttoRet.{{$field.", "CamelName}} = req.{{$field.", "CamelName}}\n\t\t\t{{end}}\n\t\t{{- end }}\n\t\tencoder := json.", "NewEncoder(&buf)\n\t\tencoder.", "SetEscapeHTML(false)\n\t\tif err := encoder.", "Encode(toRet); err !", "= nil {\n\t\t\treturn errors.", "Wrapf(err, \"couldn't encode body as json %v\", toRet)\n\t\t}\n\t\tr.Body = ioutil.", "NopCloser(&buf)\n\t\t{{- end }}\n\t\treturn nil\n\t}\n{{- end -}}\n`\n\nvar ClientTemplate = `\n// Code generated by truss. ", "DO NOT EDIT.", "\n// Rerunning truss will overwrite this file.", "\n// Version: {{.Version}}\n// Version Date: {{.VersionDate}}\n\n// Package http provides an HTTP client for the {{.Service.", "Name}} service.", "\npackage http\n\nimport (\n\t\"bytes\"\n\t\"encoding/json\"\n\t\"fmt\"\n\t\"io\"\n\t\"io/ioutil\"\n\t\"net/http\"\n\t\"net/url\"\n\t\"strings\"\n\t\"context\"\n\n\t{{ if len .HTTPHelper.", "Methods -}}\n\t\t\"github.com/gogo/protobuf/jsonpb\"\n\t{{- end }}\n\n\t\"github.com/go-kit/kit/endpoint\"\n\thttptransport \"github.com/go-kit/kit/transport/http\"\n\t\"github.com/pkg/errors\"\n\n\t// This Service\n\t\"{{.ImportPath -}} /svc\"\n\tpb \"{{.PBImportPath -}}\"\n)\n\nvar (\n\t_ = endpoint.", "Chain\n\t_ = httptransport.", "NewClient\n\t_ = fmt.", "Sprint\n\t_ = bytes.", "Compare\n\t_ = ioutil.", "NopCloser\n)\n\n// New returns a service backed by an HTTP server living at the remote\n// instance. ", "We expect instance to come from a service discovery system, so\n// likely of the form \"host:port\".", "\nfunc New(instance string, options ...httptransport.", "ClientOption) (pb.{{.Service.", "Name}}Server, error) {\n\n\tif !", "strings.", "HasPrefix(instance, \"http\") {\n\t\tinstance = \"http://\" + instance\n\t}\n\tu, err := url.", "Parse(instance)\n\tif err !", "= nil {\n\t\treturn nil, err\n\t}\n\t_ = u\n\n\t{{if not .HTTPHelper.", "Methods -}}\n\t\tpanic(\"No HTTP Endpoints, this client will not work, define bindings in your proto definition\")\n\t{{- end}}\n\n\t{{range $method := .HTTPHelper.", "Methods}}\n\t\t{{ if $method.", "Bindings -}}\n\t\t\t{{ with $binding := index $method.", "Bindings 0 -}}\n\t\t\t\tvar {{$binding.", "Label}}Endpoint endpoint.", "Endpoint\n\t\t\t\t{\n\t\t\t\t\t{{$binding.", "Label}}Endpoint = httptransport.", "NewClient(\n\t\t\t\t\t\t\"{{$binding.", "Verb | ToUpper}}\",\n\t\t\t\t\t\tcopyURL(u, \"{{$binding.", "BasePath}}\"),\n\t\t\t\t\t\tEncodeHTTP{{$binding.", "Label}}Request,\n\t\t\t\t\t\tDecodeHTTP{{$method.", "Name}}Response,\n\t\t\t\t\t\toptions...,\n\t\t\t\t\t).Endpoint()\n\t\t\t\t}\n\t\t\t{{- end}}\n\t\t{{- end}}\n\t{{- end}}\n\n\treturn svc.", "Endpoints{\n\t{{range $method := .HTTPHelper.", "Methods -}}\n\t\t{{ if $method.", "Bindings -}}\n\t\t\t{{ with $binding := index $method.", "Bindings 0 -}}\n\t\t\t\t{{$method.", "Name}}Endpoint: {{$binding.", "Label}}Endpoint,\n\t\t\t{{end}}\n\t\t{{- end}}\n\t{{- end}}\n\t}, nil\n}\n\nfunc copyURL(base *url.", "URL, path string) *url.", "URL {\n\tnext := *base\n\tnext.", "Path = path\n\treturn &next\n}\n\n// CtxValuesToSend configures the http client to pull the specified keys out of\n// the context and add them to the http request as headers. ", " Note that keys\n// will have net/http.", "CanonicalHeaderKey called on them before being send over\n// the wire and that is the form they will be available in the server context.", "\nfunc CtxValuesToSend(keys ...string) httptransport.", "ClientOption {\n\treturn httptransport.", "ClientBefore(func(ctx context.", "Context, r *http.", "Request) context.", "Context {\n\t\tfor _, k := range keys {\n\t\t\tif v, ok := ctx.", "Value(k).(string); ok {\n\t\t\t\tr.Header.", "Set(k, v)\n\t\t\t}\n\t\t}\n\t\treturn ctx\n\t})\n}\n\n\n// HTTP Client Decode\n{{range $method := .HTTPHelper.", "Methods}}\n\t// DecodeHTTP{{$method.", "Name}}Response is a transport/http.", "DecodeResponseFunc that decodes\n\t// a JSON-encoded {{GoName $method.", "ResponseType}} response from the HTTP response body.", "\n\t// If the response has a non-200 status code, we will interpret that as an\n\t// error and attempt to decode the specific error message from the response\n\t// body. ", "Primarily useful in a client.", "\n\tfunc DecodeHTTP{{$method.", "Name}}Response(_ context.", "Context, r *http.", "Response) (interface{}, error) {\n\t\tdefer r.Body.", "Close()\n\t\tbuf, err := ioutil.", "ReadAll(r.", "Body)\n\t\tif err == io.", "EOF {\n\t\t\treturn nil, errors.", "New(\"response http body empty\")\n\t\t}\n\t\tif err !", "= nil {\n\t\t\treturn nil, errors.", "Wrap(err, \"cannot read http body\")\n\t\t}\n\n\t\tif r.StatusCode !", "= http.", "StatusOK {\n\t\t\treturn nil, errors.", "Wrapf(errorDecoder(buf), \"status code: '%d'\", r.StatusCode)\n\t\t}\n\n\t\tvar resp pb.{{GoName $method.", "ResponseType}}\n\t\tif err = jsonpb.", "UnmarshalString(string(buf), &resp); err !", "= nil {\n\t\t\treturn nil, errorDecoder(buf)\n\t\t}\n\n\t\treturn &resp, nil\n\t}\n{{end}}\n\n// HTTP Client Encode\n{{range $method := .HTTPHelper.", "Methods}}\n\t{{range $binding := $method.", "Bindings}}\n\t\t{{$binding.", "GenClientEncode}}\n\t{{end}}\n{{end}}\n\nfunc errorDecoder(buf []byte) error {\n\tvar w errorWrapper\n\tif err := json.", "Unmarshal(buf, &w); err !", "= nil {\n\t\tconst size = 8196\n\t\tif len(buf) > size {\n\t\t\tbuf = buf[:size]\n\t\t}\n\t\treturn fmt.", "Errorf(\"response body '%s': cannot parse non-json request body\", buf)\n\t}\n\n\treturn errors.", "New(w.", "Error)\n}\n\ntype errorWrapper struct {\n\tError string ` + \"`\" + `json:\"error\"` + \"`\" + `\n}\n`\n" ]
{ "pile_set_name": "Github" }
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[ "This invention relates to a rotor for a permanent magnet-type dynamoelectric machine, and more particularly to a dynamoelectric machine rotor having a plurality of permanent magnet segments.", "\nFIG. ", "1 illustrates, in a sectional side view, one example of a permanent magnet-type dynamoelectric machine 10 with the conventional rotor having a segmented rotor magnet assembly. ", "The dynamoelectric machine 10 comprises a housing 11 and a stator 12 mounted to the housing 11 and including a stator core 13 and stator coils 14 wound around the core 13. ", "The dynamoelectric machine 10 also comprises a rotor 15 rotatably supported within the housing 11 by a pair of bearings 16 and 17. ", "The rotor 15 comprises a rotary shaft 18 rotatably supported by the bearings 16 and 17, a tubular cylindrical rotor core 19 press-fitted onto the shaft 18 and a rotor magnet assembly 20. ", "The rotor magnet assembly 20 comprises a plurality of permanent magnet segments 21 attached to a circumferential surface 22 of the rotor core 19 to form a substantially tubular assembly as best seen in FIG. ", "2. ", "In the illustrated example, the assembly 20 comprises four magnet segments 21 made of a ferrite magnetic material. ", "As shown in FIG. ", "3, each magnet segment 21 has an inner cylindrical surface 23 extending along the outer circumference 22 of the rotor core 19, an outer cylindrical surface 24, two end surfaces 25, two side surfaces 26 extending axially in a plane containing the axis of the rotor 15, and two axially extending chamferred surfaces 27 at the outer axial side edges or corners of the magnet segment 21. ", "The chamferred surfaces 27 of the magnet segments 21 are provided for reducing the cogging torque and the magnetic noise. ", "The magnet segments 21 are attached to the outer surface 22 of the rotor core 19 by a suitable bonding agent 28. ", "When associated, each of the chamferred axially-extending outer side edges 27 defines, together with the chamferred outer side edge 27 of the adjacent magnet segment 21, a plurality of axial recesses 29 of a V-shaped cross section.", "\nThe permanent magnet segments 21 of the rotor magnet assembly 20 of the conventional design are attached only by the bonding agent 28 applied between the inner cylindrical surface 23 of the segments 21 and the outer cylindrical surface 22 of the rotor core 19. ", "Therefore, a massive centrifugal force is exerted on the segments 21, causing a tremendous amount of separating force to be applied to the bonding agent 28. ", "Also, at the time of acceleration or deceleration during the period of starting or stopping, a massive shearing force applies to the bonding agent 28 between the magnet segments 21 and the outer cylindrical surface 22 of the rotor core 19.", "\nTherefore, the dynamoelectric rotor assembly of this type utilizing magnet segments bonded to the rotor core is not suitable to be operated at a relatively high speed rotation or with a repeated stopping and starting operation. ", "If the magnet segment or the fragment thereof is separated due to the centrifugal force during a high-speed rotation, the separated segment is very dangerous as it flies at a great speed. ", "Also the magnet segment or the fragment which is separated from the assembly may be caught between the stator and the rotor, halting or damaging the dynamoelectric machine." ]
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[ "Introduction {#Sec1}\n============\n\nWorldwide, prostate cancer is the second most commonly diagnosed cancer in men accounting for 7% of male cancer deaths \\[[@CR1]\\]. ", "In 2012, approximately 134,000 new prostate cancer cases and 43,000 deaths from prostate cancer were estimated in Central and South America, accounting for 12% of all cancer cases and 14% of male cancer deaths. ", "Across this region, prostate cancer was the most common male cancer diagnosis and one of the leading causes of cancer death in men in most countries \\[[@CR2]\\]. ", "Incidence rates varied sixfold between countries and varied between registries within some countries, such as Brazil (threefold--sixfold). ", "Mortality rates varied fourfold between countries. ", "Reasons for geographical and temporal variation in prostate cancer incidence and mortality rates include differences in diagnostic and registration practices, healthcare access, treatment and death certification, and public awareness. ", "By 2030, the burden from prostate cancer is expected to nearly double in this region, mainly due to the simultaneous expansion and age distribution of the male population.", "\n\nFor appropriate patients, androgen deprivation therapy (ADT) may be achieved through either surgical or medical castration. ", "Unfortunately, despite ADT, disease will invariably progress to castration-resistant prostate cancer (CRPC). ", "Approximately 90% of patients with CRPC develop bone metastases (mCRPC), which may account for significant morbidity and mortality associated with the disease \\[[@CR3], [@CR4]\\].", "\n\nIn 2004, docetaxel (taxane chemotherapy) was the first survival-prolonging treatment to be approved for mCRPC \\[[@CR5], [@CR6]\\]. ", "Since then, five new agents have been approved in this setting including sipuleucel-T (immunotherapy, only in the United States, \\[US\\]) \\[[@CR7]\\], cabazitaxel (taxane chemotherapy) \\[[@CR8]\\], abiraterone \\[[@CR9]--[@CR12]\\] and enzalutamide (androgen receptor \\[AR\\] axis-targeted therapies) \\[[@CR13], [@CR14]\\], and radium-223 (targeted alpha therapy) \\[[@CR15]\\]. ", "All of these agents have significantly improved overall survival for patients with mCRPC, with median survival times of 35 months reported in chemonaive patients treated with AR axis-targeted agents (supplementary table S1). ", "Despite regulatory approvals by the US Food and Drug Administration, European Medicines Agency or individual Latin American agencies, accessibility is not universal for all of these agents.", "\n\nThe strength of recommendation from treatment guidelines varies \\[[@CR16]--[@CR19]\\] (supplementary table S2). ", "The Prostate Cancer Clinical Trials Working Group (PCWG) provides recommendations in relation to trial design in this setting \\[[@CR20]\\], and consensus recommendations from experts treating patients in current clinical practice are available \\[[@CR21]--[@CR24]\\]. ", "However, level 1 data for optimal patient selection, treatment combinations or sequencing are limited. ", "These choices are currently influenced by clinical judgment, therapeutic experience and availability. ", "Access to life-extending yet costly new therapies varies globally, with limited public reimbursement being of particular concern to patients and to physicians treating mCRPC in Latin America.", "\n\nThe Latin American mCRPC treatment committee, comprising a multidisciplinary group of 14 uro-oncology experts from Argentina, Brazil, Colombia, Mexico and the USA, was convened in 2016 in Bogotá, Colombia. ", "These Latin American counties were selected as they currently have the highest adoption of the approved life-prolonging treatments for mCRPC. ", "In addition, clinical expertise from these countries has contributed to developing current treatment guidelines (e.g., Brazil and Argentina for NCCN guidelines). ", "A representative from the USA, experienced in the clinical development of treatment therapies and guidelines for mCRPC, was included to moderate discussion. ", "The expert committee reviewed the current evidence and guidance for treating mCRPC, considering factors influencing patient selection, the timing of treatment and best methods for treatment monitoring. ", "Participants provided their clinical opinion and experience that might inform such decisions to develop consensus recommendations that may assist other Latin American physicians in clinical decision making (Table [1](#Tab1){ref-type=\"table\"}).Table 1Summary of treatment recommendations for approved agents in mCRPC in Latin AmericaAgentInitiationSwitch/stopMonitoring treatmentChemotherapy Docetaxel^a^Patients with rapidly progressive (symptomatic) and/or high burden of diseaseClinical indication/radiographic progressionRadiographic methodology depends on availability. ", "Bone and CT scans are standard imaging techniques for diagnosing new bone lesions. ", "CT scan is useful for monitoring extra-skeletal progression whilst on treatment CabazitaxelPatients progressing (who do not respond or have a short response) on docetaxelAR axis therapy^b^ Abiraterone acetateFirst-line for mildly symptomatic/asymptomatic patients\\\nPatients progressing on chemotherapy\\\nPatients progressing on radium-223 if a AR axis-targeted therapy has not been previously usedClinical indication/radiographic progression\\\nSwitching from abiraterone to enzalutamide and vice versa is not recommendedMRI and PET with new molecular tracers may prove useful in the future for monitoring disease progression but require validation.\\\nThere are currently no new validated biomarkers for monitoring and treatment decisions. ", "Clinical biomarker studies are ongoing.\\\nPSA values alone should be interpreted with caution. ", "Biomarker information should be used with patient clinical parameters EnzalutamideAs above\\\nPreference for enzalutamide for patients with visceral metastasesTargeted alpha therapy Radium-223^c^In patients with symptomatic bone metastases\\\nIdeally in patients with bone metastases progressing on first-line abiraterone or enzalutamide (earlier in the course of mCRPC)\\\nCan be used prior to chemotherapy (patients unfit/unwilling for chemotherapy)\\\nCan be used in patients progressing on chemotherapyClinical indication/radiographic progression (evidence of visceral metastases)\\\nPatients with a rising PSA during radium-223 therapy and no visceral disease, adding a corticosteroid or an older hormone therapy are viable optionsIn the future, ALP may be validated as a more suitable marker than PSA for monitoring response to radium-223*ALP* alkaline phosphatase, *CT* computed tomography, *mCRPC* metastatic castration-resistant prostate cancer, *MRI* magnetic resonance imaging, *PET* positron emission tomography, *PSA* prostate-specific antigen^a^Docetaxel + androgen depravation therapy is also preferred for high-volume, metastatic hormone-sensitive disease^b^Bicalutamide was recommended as a treatment alternative in cases where access to new hormone therapy is restricted or the aim is to expose patients to an additional line of therapy; however, results are expected to be worse than those with abiraterone or enzalutamide^c^For the purpose of prolonging survival (not pain palliation) in patients with bone-predominant disease (no visceral metastases). ", "Symptoms should be carefully assessed. ", "Giving earlier in the course increases likelihood of receiving all six treatment cycles of life-prolonging therapy\n\nMethods {#Sec2}\n=======\n\nThe multidisciplinary expert panel from Latin America reviewed the current recommendation for the use of chemotherapy (docetaxel and cabazitaxel), AR axis-targeted agents (abiraterone and enzalutamide) and targeted alpha therapy (radium-223) in the treatment of patients with mCRPC. ", "Treatment guidelines reviewed were ESMO, NCCN, AUA and ASCO. ", "Level 1 recommendations from these treatment guidelines were discussed in the context of the participants own clinical experience to develop clinical consensus, with consideration given to factors influencing patient selection and treatment monitoring. ", "Voting was coordinated by Professor Sade; consensus recommendations were agreed on a majority vote. ", "Dr Shore moderated discussion but did not contribute a vote.", "\n\nCurrent treatment options for mCRPC {#Sec3}\n-----------------------------------\n\nCurrent treatment options for mCRPC are summarized (supplementary table S1). ", "The integration of available agents for the optimal management of patients in Latin America was discussed.", "\n\nChemotherapy {#Sec4}\n------------\n\nThe TAX 327 \\[[@CR5]\\] and SWOG 9916 \\[[@CR6]\\] studies showed a survival benefit for patients with mCRPC treated with docetaxel-based chemotherapy compared with mitoxantrone-based control. ", "The TROPIC study \\[[@CR8]\\] demonstrated cabazitaxel (25 mg/m^2^) as a chemotherapeutic treatment option post-docetaxel. ", "Subsequently, cabazitaxel 20 mg/m^2^ demonstrated non-inferiority for overall survival with an improved safety profile compared with 25 mg/m^2^ cabazitaxel in patients progressing on docetaxel \\[[@CR25]\\]. ", "However, both 20 and 25 mg/m^2^ cabazitaxel did not demonstrate superiority for survival compared with docetaxel in chemotherapy-naïve patients \\[[@CR26]\\].", "\n\nUS and European guidelines recommend docetaxel for the treatment of patients with mCRPC and cabazitaxel in patients progressing on docetaxel \\[[@CR16], [@CR18]\\], and in some guidelines chemotherapy is recommended particularly in symptomatic patients, or in asymptomatic patients showing signs of rapid progression or visceral metastases \\[[@CR16]\\]. ", "There is consensus for taxane use (second-line) in patients with symptomatic disease progressing on AR axis-targeted agents, and many clinicians would use third-line cabazitaxel in patients progressing on AR axis-targeted agents (e.g., abiraterone and enzalutamide) and docetaxel \\[[@CR22]\\]. ", "Small retrospective studies suggest that prior treatment with AR axis-targeted agents may negatively impact on the activity of subsequent docetaxel treatment \\[[@CR27], [@CR28]\\].\"The panel agreed that docetaxel should be recommended in patients with symptomatic mCRPC with rapidly progressive and/or high-burden disease. ", "Cabazitaxel (20 mg/m^2^) was recommended for patients progressing on docetaxel.\"", "\n\nAR axis-targeted agents {#Sec5}\n-----------------------\n\nThe addition of the CYP17 inhibitor abiraterone to prednisone improved overall survival both in mCRPC patients progressing on docetaxel \\[[@CR9], [@CR10]\\], and first-line in asymptomatic or mildly symptomatic chemotherapy-naive patients (without visceral metastases) \\[[@CR11], [@CR12]\\].", "\n\nIn patients with mCRPC who had previously received chemotherapy, survival was longer in those treated with the AR inhibitor enzalutamide compared with placebo \\[[@CR13]\\]. ", "In chemotherapy-naïve patients, those who received enzalutamide showed benefit for radiological progression and overall survival compared with patients who received placebo \\[[@CR14]\\]. ", "Radiological progression was also improved in patients with visceral metastases.", "\n\nAbiraterone and enzalutamide are approved for the first-line treatment of mCRPC, and in patients who have previously received docetaxel \\[[@CR16]--[@CR19]\\]. ", "There was consensus for the first-line use of AR axis-targeted agents in patients with asymptomatic mCRPC \\[[@CR22]\\]; treatment in patients with mCRPC leads to prostate-specific antigen (PSA) decline in 90% of cases. ", "However after a PSA nadir, the majority of patients will experience a PSA rise. ", "Switching from abiraterone to enzalutamide or vice versa on progression does not appear to be effective due to the development of resistance mechanisms \\[[@CR21], [@CR29], [@CR30]\\].\"The panel agreed that abiraterone and enzalutamide should be recommended as first-line treatment options for asymptomatic or mildly symptomatic patients with a rising PSA or low-volume mCRPC following ADT alone. ", "Switching between the two agents for second-line treatment was not recommended. ", "Enzalutamide was recommended as the hormone therapy of choice for patients with visceral metastases. ", "Both agents were considered appropriate options for patients progressing on chemotherapy.\"", "\n\nIn some Latin American countries, the use of bicalutamide is considered as a viable first-line option for chemotherapy-naive patients progressing slowly after ADT alone, particularly for those with low burden of disease and slowly rising PSA. ", "However, abiraterone or enzalutamide is considered to be more active than bicalutamide in this setting and should be preferred, if available, considering their survival-prolonging effects \\[[@CR31], [@CR32]\\].\"The panel agreed to recommend bicalutamide as a treatment alternative in cases where access to abiraterone or enzalutamide is restricted, or where the aim is to expose patients to an additional line of therapy.\"", "\n\nTargeted alpha therapy {#Sec6}\n----------------------\n\nRadium-223 is incorporated into new bone in areas of increased bone turnover around prostate cancer metastases \\[[@CR33]\\]. ", "Radium-223 emits high-energy alpha particles over a short range (\\< 0.1 mm) resulting in a localized antitumor effect and minimal toxicity to normal bone marrow \\[[@CR33]--[@CR35]\\].", "\n\nIn the phase 3 ALSYMPCA study in patients with mCRPC who had ≥ 2 symptomatic bone metastases (no visceral or bulky nodal disease), overall survival was longer, time to first on-treatment symptomatic skeletal event (SSE) was delayed, and a meaningful improvement in patient quality of life (QoL) was reported, in those receiving radium-223 compared with placebo \\[[@CR15]\\]. ", "Patients in both arms also received best standard of care (BSoC). ", "Radium-223 is recommended for patients with symptomatic bone-predominant mCRPC without visceral metastases \\[[@CR16]--[@CR19]\\]. ", "Whilst radium-223 reduced pain in this study, this was not a primary measure of treatment response and was not observed in all patients. ", "Failure to reduce pain should not lead to discontinuation of radium-223. ", "Administering analgesics or external beam radiation therapy should be considered, and radium-223 can be safely and effectively combined with these and other agents in BSoC \\[[@CR15], [@CR36], [@CR37]\\].\"The panel recommend that radium-223 should be administered primarily for the purpose of prolonging overall survival and not for pain palliation.\"", "\n\nRadium-223 is considered easy to administer with a good safety profile \\[[@CR15]\\]. ", "Administration should be performed by physicians and health technicians certified to use radioisotopes, with appropriate radiation safety precautions taken. ", "The importance of educating both patients and staff on radium-223 use is emphasized; it is safe for appropriately trained healthcare workers \\[[@CR38]\\].", "\n\nThe timing of the administration of radium-223 prior to the onset of visceral disease is important. ", "Approximately 90% of patients with a life expectancy of \\> 1 year will have bone metastases and no visceral disease \\[[@CR39]\\] and are potential candidates for radium-223. ", "In the USA and Europe, some clinicians suggest that radium-223 may be given following early signs of progression after first-line abiraterone or enzalutamide \\[[@CR22], [@CR23]\\]. ", "Exploratory analyses suggest that patients with less advanced mCRPC are more likely to complete the full six cycles of radium-223 \\[[@CR40], [@CR41]\\]. ", "Post hoc analyses reported the combination of radium-223 with abiraterone or enzalutamide was tolerable and may lead to longer survival \\[[@CR37], [@CR42]\\]. ", "Phase 3 clinical trials including ERA-223 (NCT02043678) and PEACE-3 (NCT02194842) in asymptomatic/mildly symptomatic patients should provide level 1 evidence for the combination of radium-223 with AR axis-targeted agents.", "\n\nData from the phase 3 study showed radium-223 was effective when administered to patients with or without previous docetaxel use \\[[@CR43]\\]. ", "In further exploratory analyses in patients who received docetaxel after radium-223, it was shown that docetaxel was feasible and well tolerated \\[[@CR44]\\]. ", "With the potential for additive myelosuppression, radium-223 is not recommended for use in combination with chemotherapy outside of a clinical trial \\[[@CR45]\\].\"There was consensus that the number of bone metastases should not influence decisions on whether to administer radium-223. ", "In the absence of level 1 evidence, for guidance, use of radium-223 early in the disease course in patients with CRPC and bone metastases (no visceral disease) progressing on first-line abiraterone or enzalutamide may be considered. ", "Radium-223 can also be used for patients progressing on chemotherapy (with no visceral metastases), but should not be used in combination with chemotherapy. ", "Chemotherapy can be safely administered after radium-223.\"", "\n\nIn instances when PSA is rising during radium-223 therapy, and in the absence of radiological progression, or clinical indication (no visceral metastases), some physicians suggest the addition of abiraterone or enzalutamide. ", "Due to lack of reimbursement for this combination in Latin America, adding a corticosteroid (e.g., low-dose dexamethasone) here would be an option with a view to starting abiraterone or enzalutamide after six cycles of radium-223 therapy. ", "An alternative option would be to add an older antihormone therapy (bicalutamide, diethylstilbestrol and ketoconazole) in line with BSoC use in the radium-223 phase 3 study \\[[@CR15]\\]. ", "This approach is used in some countries including Mexico and Argentina.", "\"The panel agreed that for patients with a rising PSA during radium-223 therapy and no visceral disease, adding a corticosteroid or an older anti-hormone therapy are viable options. ", "If the patient has not received abiraterone or enzalutamide, starting either of those after radium-223 (6 cycles) is also an option.\"", "\n\nPatient selection and treatment monitoring {#Sec7}\n------------------------------------------\n\nOptimal disease management relies on selecting patients who will benefit most from a particular agent, and knowing when best to change treatment. ", "The PCWG3 have introduced the concept of 'no longer clinically benefiting' to underscore the distinction between first evidence of progression and the clinical need to terminate treatment in clinical trials \\[[@CR20]\\]. ", "In addition, two out of three criteria consisting of PSA progression, radiographic progression and clinical deterioration are recommended requirements in order to stop treatment \\[[@CR21]\\]. ", "In this context, factors important for patient selection and treatment monitoring were discussed.", "\n\nPatient symptoms {#Sec8}\n----------------\n\nDisease symptoms are important considerations in treatment selection \\[[@CR15], [@CR22]\\], although accurate symptom evaluation is problematic. ", "The symptom definition used in the ALSYMPCA study is regarded as standard for symptomatic patient identification (regular use of analgesic medication or treatment with EBRT required for cancer-related bone pain within the previous 12 weeks). ", "However, patients treated with abiraterone or enzalutamide may complain of fatigue, muscle pain, sarcopenia amongst other symptoms, making it difficult to ascertain symptoms associated with metastatic bone disease, medication or other non-cancer-related conditions. ", "Furthermore, reporting of pain varies widely according to patient age, cultural background and socioeconomic factors. ", "Also patients taking over-the-counter drugs may consider themselves asymptomatic. ", "Other important factors for consideration during symptom assessments include difficulty in sleeping, changes in daily activities, depression and weakness \\[[@CR46]\\].\"The panel recommend that in addition to assessing pain, clinicians should screen for the presence of other symptoms including depression, sarcopenia, weakness and changes to daily life. ", "It was advised that including a caregiver (family member, close friend or professional caregiver) during the consultation process is very useful for the evaluation of patient symptoms \\[[@CR46]\\].\"", "\n\nPrevious treatment history {#Sec9}\n--------------------------\n\nPatient history of previous use of anticancer agents is important in treatment selection. ", "This information in the hormone-sensitive setting may be important when considering treatment in patients who have progressed to mCRPC. ", "The STAMPEDE \\[[@CR47]\\] and CHAARTED \\[[@CR48]\\] trials support the combination of chemotherapy with ADT in newly diagnosed patients with high-volume metastatic hormone-sensitive disease, which is now considered to be the standard of care for these patients. ", "However, chemotherapy use in metastatic hormone-sensitive disease varies worldwide. ", "In the USA, chemotherapy with ADT is predominantly given to patients with high-volume metastatic disease \\[[@CR48]\\] although in the UK it is also provided to patients with low-volume disease \\[[@CR47]\\]. ", "Some variation is found across countries in Latin America, but predominantly chemotherapy is combined with ADT in patients with high-volume disease. ", "In these cases, many clinicians will typically wait 1--2 months after the start of ADT before administering docetaxel. ", "Approaches will vary depending on whether physicians are working in university- or community-based centers.", "\"The panel agreed that the combined use of docetaxel and ADT in high-volume, metastatic, hormone-sensitive disease is recommended.\"", "\n\nRecent data have demonstrated that adding abiraterone to ADT in patients with newly diagnosed high-risk metastatic 'hormone-naïve' prostate cancer significantly prolonged survival \\[[@CR49], [@CR50]\\]. ", "Thus, where access is available in Latin American countries, the use of abiraterone in the hormone-sensitive setting may also influence the subsequent choice of agents in patients progressing to mCRPC.", "\n\nBiomarkers {#Sec10}\n----------\n\nCurrently, there are no validated biomarkers for predicting which patients might benefit from a specific treatment. ", "Recent data suggest that screening for AR gene alterations may identify patients unlikely to respond to AR axis-targeted therapies. ", "Indeed, the presence of AR splice variant-7 (AR-V7) mRNA in circulating tumor cells from patients with mCRPC was associated with resistance to enzalutamide and abiraterone \\[[@CR51]\\]. ", "Furthermore, a gain in tumor AR copy number was associated with worse patient outcome following treatment with enzalutamide or abiraterone \\[[@CR52]\\]. ", "However, such potential diagnostic approaches require further clinical validation before their routine implementation in the community setting/clinical practice. ", "Clinical studies investigating biomarkers in mCRPC (AR-V7) are ongoing (e.g., NCT03103724 and NCT02429193). ", "Recently, data from several clinical trials have been shared in the DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge, which reported novel prognostic models (based on patient demographics, laboratory values, medical history, lesion sites and previous treatments) for predicting overall survival in patients with mCRPC \\[[@CR53]\\]. ", "Such approaches may be useful for identifying predictive markers for response to treatment in this setting.", "\n\nRising PSA levels and short PSA doubling times during treatment may indicate tumor progression. ", "However, in clinical practice, PSA progression alone requires cautious interpretation and is not recommended as a trigger to stop or switch a treatment \\[[@CR21], [@CR22]\\]. ", "In particular, a PSA flare phenomenon has been described following the initiation (first 2--3 months) of chemotherapy and treatment with AR axis-targeted agents. ", "Rapidly rising serum ALP levels (a marker of osteoblast activity) is an indication of disease progression in bone. ", "Serum ALP levels may therefore be a more clinically relevant biomarker than PSA in patients with bone metastases \\[[@CR21], [@CR22]\\]. ", "Biomarker analysis from the ALSYMPCA study showed that radium-223 treatment led to a significant decrease in total (t)ALP levels compared with placebo, and patients receiving radium-223 who experienced a tALP decline at week 12 had longer overall survival than those who did not \\[[@CR15], [@CR54]\\]. ", "By contrast, radium-223 had a relatively modest effect on PSA kinetics which was not a good surrogate for response \\[[@CR54]\\].\"The panel agreed that currently there are no validated biomarkers for predicting patients that might respond to therapy, and no new validated biomarkers for measuring on-treatment progression, although clinical biomarker studies are ongoing. ", "Changes in PSA levels should be interpreted with caution and treatment should not be changed/stopped based on PSA alone. ", "Imaging and clinical indicators of progression are also important. ", "ALP may prove to be a more suitable marker of response to radium-223.\"", "\n\nImaging {#Sec11}\n-------\n\nGuidelines for imaging metastatic disease are available \\[[@CR20], [@CR55]\\]. ", "Imaging methods for patients with mCRPC and bone metastases are summarized (supplementary table S3).", "\n\nBone scintigraphy and computed tomography (CT) scans of the chest--thorax and abdomen--pelvis are recommended for patients with mCRPC before a new line of treatment is started \\[[@CR21], [@CR23]\\]. ", "Data suggest that automated bone scan index (aBSI) at baseline is prognostic for survival, radiological progression-free survival and SSEs \\[[@CR56]\\]. ", "The use of magnetic resonance imaging (MRI), positron emission tomography (PET)/CT with labeled tracers (including prostate-specific membrane antigen \\[PMSA\\]) and single-photon emission CT bone scans (SPECT) combined with CT in the baseline staging and monitoring of treatment requires further investigation \\[[@CR16], [@CR20], [@CR21]\\].", "\n\nAccess to different imaging methodologies varies across Latin America, and availability may be limited to academic centers. ", "The standard imaging in Latin America for patients with rising PSA is a bone scan, and CT for the diagnosis of visceral metastases. ", "However, where a PSA rise is measured, it was agreed that in the absence of clinical or radiographic progression, current treatment should continue.", "\"The panel agree that bone scans and CT are the standard imaging tests in Latin America for detecting bone and visceral lesions. ", "In patients with a rising PSA during ADT alone, and for patients with de novo metastatic disease, the panel recommends against imaging in the absence of laboratory abnormalities or patient complaints.\"", "\n\nThere is a lack of data on the use of imaging techniques for monitoring treatment response in clinical trials. ", "Agreement on the frequency of use of imaging during treatment varies with some clinicians recommending imaging only when clinically indicated \\[[@CR21]--[@CR23]\\].", "\n\nMonitoring of disease progression and treatment response in the bone is problematic, with bone lesion flare occurring on bone scans (scintigraphy using technetium-99 m-methyldiphosphate) \\[[@CR57], [@CR58]\\]. ", "Whilst bone scans can detect new metastatic lesions, it is difficult to differentiate between tumor activity and the healing processes in the bone, making the distinction between spread of metastases and successful treatment difficult \\[[@CR58]\\]. ", "Frequent bone scintigraphy is therefore unlikely to be helpful. ", "Further studies are necessary to confirm the role of systematic disease monitoring using more advanced techniques including MRI (whole body) or PSMA PET/CT in monitoring and characterizing early response to treatment \\[[@CR59]\\]. ", "The use of molecular imaging techniques including hyperpolarized carbon-13 MRI (NCT02844647), diffusion weighted MRI and PET/CT using novel tracers is under development (supplementary table S3).\"For patients with mCRPC undergoing treatment with life-prolonging agents, the panel recommend that imaging should be prompted where symptomatic decline and/or significant worsening of laboratory evaluations are reported, or where a course of therapy has been successfully completed and another antineoplastic agent is under consideration. ", "Where indicated, CT and bone scans are the standard imaging tests for patients with a rising PSA. ", "Imaging should not be used to measure treatment response; a CT scan is recommended only if clinically indicated to check for signs of progression (visceral disease). ", "Newly developed molecular imaging techniques may be useful in monitoring disease progression in bone and to detect extra-skeletal lesions, however these techniques require validation in prospective studies.\"", "\n\nTreatment cost and access to agents in Latin America {#Sec12}\n----------------------------------------------------\n\nUnequal access to life-prolonging agents and to the newer technologies for monitoring treatment is a major limitation to successfully treating patients with mCRPC across different countries in Latin America. ", "Treatment cost is a primary factor for limiting access to cancer agents. ", "This may in part be due to the rise in the incidence of chronic diseases including cancer, which now compete for resources previously predominantly allocated to treating infectious diseases \\[[@CR60]\\].", "\n\nObtaining adequate financing for cancer treatment is a challenge for many Latin American countries. ", "The budget percentage spent for health in Latin America is generally lower than that of developed countries, although there are clear disparities between countries in Latin America; for example, Argentina spends 8.1% of its gross domestic product on health, whereas Brazil, the most populous country of the region, spends only 6.3% \\[[@CR60]\\]. ", "In the majority of these cases, however, health expenditures are concentrated in the private sector. ", "For example in Mexico in 2008, of the total spent on health, 52% was for the private sector, which covers only 5% of the entire population \\[[@CR60]\\].", "\n\nOther factors influencing the optimal treatment of patients include: a fragmented structure and organization of healthcare systems in some countries, and unequal distribution of resources which are concentrated primarily in urban areas \\[[@CR60], [@CR61]\\]. ", "In addition, in some regions, provision of education on the handling and administration of the use of radiotracers and alpha-targeted therapies may be required to improve knowledge of these agents.", "\n\nWith the treatment landscape for prostate cancer dramatically changing in the last decade, it is important to consider the added value regarding improved clinical outcome and QoL, and reduced morbidity to the patient, in addition to the cost of these new drugs. ", "For example, continued use of older hormone therapies, whilst an option, may not be as effective as using newer AR axis-targeted agents. ", "It is therefore important that there is dialogue between prostate cancer specialists and hospital and government decision makers, to educate on the clinical and economic value for preventing disease progression and the associated morbidities and complications (emergency room visits, hospital resource utilization), and to improve awareness of the importance of allocating funding in line with new evidenced-based (level 1) findings.", "\n\nConclusions {#Sec13}\n===========\n\nTreatment options for patients with metastatic prostate cancer are increasing. ", "Patients should have the opportunity to receive as many of the available life-prolonging therapies as possible. ", "The recommendation for use of chemohormonal therapy for patients with metastatic hormone-sensitive prostate cancer may affect subsequent treatment selection and sequence in patients progressing to mCRPC. ", "The thorough assessment of symptoms in patients with mCRPC prior to treatment was considered to be important and should not be limited to the reporting of pain alone. ", "Taxane-based chemotherapy was recommended for patients with rapidly progressive (symptomatic) and/or high burden of disease. ", "First-line treatment with AR axis-targeted therapies was recommended for patients with asymptomatic or mildly symptomatic disease and could also be considered for patients progressing on chemotherapy. ", "It was recommended that radium-223 should be administered primarily for the purpose of prolonging survival, and not for pain palliation. ", "Use of radium-223 early in the disease course in patients with CRPC and bone metastases (no visceral disease) who are progressing on first-line abiraterone or enzalutamide may be considered. ", "PSA was not considered to be a reliable biomarker for monitoring response to radium-223. ", "Biomarker information was considered to be best used in the context of other assessments to establish clinical progression. ", "CT and bone scans were considered to be the current standard imaging tests for baseline staging and treatment monitoring (with respect to detecting new lesions) of patients with mCRPC in Latin America. ", "Repeated radiological assessments were not recommended, and unless otherwise indicated by clinical assessment, imaging was recommended at the beginning and end of treatment to establish a baseline for further treatments.", "\n\nElectronic supplementary material\n=================================\n\n {#Sec14}\n\nBelow is the link to the electronic supplementary material. ", "Supplementary material 1 (DOCX 34 kb) Supplementary material 2 (DOCX 32 kb) Supplementary material 3 (DOCX 34 kb)\n\n**Electronic supplementary material**\n\nThe online version of this article (10.1007/s12032-018-1105-8) contains supplementary material, which is available to authorized users.", "\n\nMedical writing assistance was provided by Dr Paul Hoban, Cancer Communications and Consultancy Ltd. (Knutsford, UK) and was funded by Bayer. ", "The authors are fully responsible for the content of this manuscript.", "\n\nAuthor contribution {#FPar1}\n===================\n\nJPS was the Co-Chair of the expert panel meeting and was involved in collection, presentation and discussion of data, and manuscript reviewing/editing; CV participated in expert panel discussion and manuscript reviewing; MG participated in expert panel discussion and manuscript reviewing; CM participated in expert panel discussion and manuscript reviewing/editing; MÁ participated in expert panel discussion and manuscript reviewing; CP participated in expert panel discussion and manuscript reviewing/editing; NH participated in expert panel discussion and manuscript reviewing; PIB participated in expert panel discussion and manuscript reviewing/editing; DB participated in expert panel discussion and manuscript reviewing/editing; FS participated in expert panel discussion and manuscript reviewing; SB participated in expert panel discussion and manuscript reviewing/editing; LN participated in expert panel discussion and manuscript reviewing/editing; NDS was the Co-Chair of the expert panel meeting and was involved in collection, presentation and discussion of data, project development and manuscript writing/reviewing/editing.", "\n\nFunding {#FPar2}\n=======\n\nThe consensus recommendations described in this report are the outcome of the deliberations of the members of an expert panel convened at a meeting funded by Bayer.", "\n\nConflict of interest {#FPar3}\n====================\n\nP Bernal, Consultant for Bayer, is indirectly related to the work submitted; L Nogueira, Advisory board member for Bayer, Astellas and Janssen, is indirectly related to the work submitted; D Bastos plays Consultant and advisory roles for Janssen, Astellas, Bayer, Merck and Roche; Research funding to his institution is from Janssen Astellas and Pfizer; S Bella, Consultant for Bayer, is directly related to the work submitted; ND Shore is a Consultant for Astellas, Bayer, Ferring, Janssen, Medivation, Sanofi, Tolmar and Valeant. ", "All other authors have no potential conflicts of interest to declare.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Photograph of the funeral of Fred Hampton, which was attended by over 5,000 people mourning his killing by members of the Chicago Police Department. (", "Photo: Paul Sequeira)On this very day, as the Army Corps of Engineers and police forces from Morton County North Dakota and nine surrounding states gather their collective forces and fearsome weaponry in an effort to evict the proud and peaceful Indigenous Water Protectors from their sacred land at Standing Rock, and thousands of veterans gather to protect them from concussion grenades, water hoses, rubber bullets and God knows what else, it is profoundly appropriate to reflect on the courage and leadership of Chicago Black Panther leader Fred Hampton and revisit the sordid history of his assassination at the hand of a conspiracy between local law enforcement and the FBI 47 years ago.", "\n\nOn December 4, 1969, 47 years ago today, a select unit of Chicago police officers executed a predawn raid that left Illinois Black Panther Party (BPP) leaders Fred Hampton and Mark Clark dead and several other young Panthers wounded. ", "The seven survivors of the raid were arrested on fraudulent attempted murder charges. ", "The officers who committed the execution were specially assigned to Cook County State’s Attorney Edward Hanrahan. ", "The claims of a “shootout” that were made by Hanrahan and his men were soon exposed as bald-faced lies: the physical evidence definitively established that the raiders fired nearly 100 shots at the sleeping Panthers, while only one shot could be linked to a Panther weapon.", "\n\nHowever, as was painstakingly proved over the next eight years, the false official claim of a violent confrontation was only one layer of a massive conspiracy that was also designed to cover up the central role of the Federal Bureau of Investigation and its COINTELPRO program in the murderous raid.", "\n\nThe headstone of slain Black Panther leader Fred Hampton in Haynesville, Louisiana, has been riddled by a barrage of bullets from unidentified night riders. ", "Flint Taylor — one of the lawyers for Hampton’s family — recently journeyed to Haynesville to eulogize Fred Hampton’s mother, Iberia, a devoted mother and courageous activist who passed away in October 2016. ", "He discovered this desecration of Hampton’s grave at that time. (", "Credit: Flint Taylor)\n\nJust after the raid that killed Fred Hampton and Mark Clark, the Minister of Defense for the Illinois Chapter of the Black Panther Party, Bobby Rush, declared that J. Edgar Hoover and the FBI were responsible for the raid. ", "However, at that time there was no hard proof. ", "The first documentation that supported Rush’s claim came in 1971 when activists broke into an FBI office in Media, Pennsylvania, and liberated a trove of FBI documents. ", "These documents outlined the FBI’s super-secret and highly illegal COINTELPRO program and its focus in the 1960s on the Black liberation movement and its leaders. ", "Using Malcolm X as an example, Hoover directed all of the Bureau’s offices to “disrupt, misdirect, and otherwise neutralize” African American organizations and leaders including the Southern Christian Leadership Conference, the Student Nonviolent Coordinating Committee, the Nation of Islam, Dr. Martin Luther King Jr., Stokely Carmichael and H. Rap Brown.", "\n\nIn Chicago, a major breakthrough came in 1973 when it was revealed that Chicago BPP Chief of Security William O’Neal was a paid informant for the FBI. ", "Lawyers at the People’s Law Office (full disclosure: I was one of those lawyers) had filed a civil rights lawsuit on behalf of the Hampton and Clark families and the raid survivors shortly after the raid, and they subpoenaed the Chicago FBI’s files on O’Neal. ", "While the FBI only produced a tiny fraction of the relevant files, an honest Assistant US Attorney produced an FBI memorandum that included a detailed floor plan of the interior of Fred Hampton’s apartment that specifically identified the bed on which Hampton slept. ", "The memo, on its face, showed that the floor plan, together with other important information designed to be utilized in a police raid, was based on information communicated by O’Neal to his FBI control agent, and that the agent supplied this information to State’s Attorney Hanrahan’s office before the raid.", "\n\nThe lawyers then focused on discovering more details about the FBI’s involvement in the conspiracy. ", "We sought the Chicago office’s COINTELPRO file in order to establish a direct link between the FBI’s illegal program and the raid on December 4. ", "At the same time, Idaho Senator Frank Church’s Select Committee to Study Governmental Operations (Church Committee), which was created in the wake of the Watergate scandal, was investigating rampant abuses by all US intelligence agencies, including the FBI. ", "In late 1975 a Church Committee attorney informed the People’s Law Office lawyers that the Committee had obtained several Chicago documents that definitively established the link. ", "Armed with the content of the still secret documents, the lawyers were able to convince the judge, who had previously refused to compel the FBI to produce the Chicago COINELPRO file, to order the FBI to do so. ", "In the file that was subsequently produced were several documents that revealed the FBI’s efforts to foment gang violence against Hampton and the Chicago Panthers, and one dated December 3, 1969, that claimed the impending raid as part of the COINTEPRO program.", "\n\nIn January 1976 the trial of the Fred Hampton civil case began in Federal Court. ", "Two months into what would turn out to be the longest trial in federal court history, O’Neal’s FBI control agent inadvertently revealed that the FBI had not produced all of its files on Hampton, O’Neal, the raid survivors and the Chicago BPP. ", "The judge reluctantly ordered that they do so, and the next day a government lawyer wheeled in on shopping carts nearly 200 volumes of FBI files that had been suppressed since they were first requested three years before. ", "The government produced several redacted volumes of these files each day over the next month. ", "The files contained directives to destroy the Panther’s Breakfast for Children Program and disrupt the distribution of the BPP newspaper; reports showing that the dynamic and charismatic 21-year-old Fred Hampton was a targeted BPP leader; materials demonstrating that O’Neal was an agent provocateur; and massive wiretap “overhears” (logs that included conversations between BPP members and their attorneys).", "\n\nAmong the government’s documentation was O’Neal’s control file. ", "In it was yet another smoking gun: memos to and from FBI headquarters and the Chicago office requesting and approving payment of a $300 bonus — 30 pieces of silver — to reward O’Neal for his role in the raid. ", "According to the memos, O’Neal’s information was of “tremendous value” and, in the words of O’Neal’s COINTELRO supervisor, made the raid a “success.”", "\n\nThat same month, on April 23, 1976, the Church Committee released its final staff report, which devoted an entire chapter to the “FBI’s Covert Action Plan to Destroy the Black Panther Party.” ", "The chapter concluded by highlighting the Hampton raid as a COINTELPRO operation and quoting from the recently uncovered “bonus” documents.", "\n\nThe judge, an unabashed supporter of the FBI, exonerated the FBI and its DOJ lawyers of any wrongdoing in suppressing the documents. ", "A year later, he dismissed O’Neal and the other FBI defendants from the case. ", "On April 23, 1979, the Seventh Circuit Court of Appeals, in a landmark 2-1 decision, overturned the trial judge, finding that the FBI and their government lawyers “obstructed justice” by suppressing documents. ", "The Court of Appeals also concluded that there was “serious evidence” to support the conclusion that the FBI, Hanrahan and his police unit had participated in a “conspiracy designed to subvert and eliminate the Black Panther Party and its members” in planning and executing the raid, thereby suppressing a “vital radical Black political organization.” ", "The Court of Appeals further found that the evidence additionally supported the conclusion that these same defendants also participated in a post-raid conspiracy to “cover up evidence” regarding the raid, “to conceal the true character of their pre-raid and raid activities,” to “harass the survivors of the raid” and to “frustrate any legal redress the survivors might seek.” ", "This decision survived a challenge in the US Supreme Court, and stands to this day as a unique judicial recognition of outrageous federal and local conspiratorial criminality and cover-up.", "\n\nAs we enter the uncharted waters of a volatile Trump presidency, with an unrepentant Ku Klux Klan sympathizer slated to head up the Justice Department, it is important not to relegate the Hampton assassination and COINTELPRO to the annals of history. ", "Particularly in an era of officially sanctioned drone assassinations, government provocateurs running wild, and a presidential election in which the “winner” appears to have benefited from international and FBI COINTELPRO-like actions, while the “loser” used similar tactics against her opponent in the primaries, it is well to remember a quote from a 1964 COINTELPRO directive:\n\nOver the years, our approach to investigative problems in the intelligence field has given rise to a number of new programs, some of which have been most revolutionary, and it can be presumed that with a continued aggressive approach to these programs, new and productive ideas will be forthcoming. ", "These ideas will not be increased in number or improved upon from the standpoint of accomplishments merely through the institution of a program such as COINTELPRO which is given another name and in fact, only encompasses everything that has been done in the past or will be done in the future.", "\n\nFor Black Lives Matter, the Water Protectors at Standing Rock, undocumented workers, Muslims, environmental activists, and a multitude of other people and organizations, the future, as contemplated in the 1964 COINTELRO memo and implemented in its most violent and racist form on December 4, 1969, may well be upon us again. ", "The only answer now, as it was then, is to organize, educate and resist. ", "And, as Fred Hampton would say, “All Power to the People.”", "\n\nNote: For more information on the Hampton/Clark case, the history of the Black Panther Party and the FBI’s program to destroy it, visit peopleslawoffice.com." ]
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[ "Some state vaccination laws contribute to greater exemption rates and disease outbreaks in the United States.", "\nHealth officials attest that immunizations are among the most successful interventions in public health. ", "However, there remains a substantial unvaccinated population in the United States. ", "We analyzed how state-level vaccination exemption laws affect immunization rates and the incidence of preventable disease. ", "We measured the association between each component of state kindergarten vaccination exemption laws and state vaccination exemption rates from 2002 to 2012, using the Centers for Disease Control and Prevention's annual school assessment reports. ", "We found that policies such as requiring health department approval of nonmedical exemptions, requiring a physician to sign an exemption application, and having criminal or civil punishments for noncompliance with immunization requirements had a significant effect in reducing vaccine exemptions. ", "Our exemption law effectiveness index identified eighteen states with the most effective laws and nine states with the least effective ones. ", "The most effective states had lower incidences of pertussis, compared to other states. ", "For policy makers interested in decreasing the number of vaccine exemptions in their state, our findings are of particular interest." ]
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[ "We can professionally translate all types of legal, technical, medical, financial and other documents. ", "All translations are done by expert specialist translators." ]
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[ "Q:\n\nVBScript to export all members of multiple Active Directory groups?", "\n\nIs there a way of exporting all the members of multiple Active Directory groups at once using a VBScript? ", " Preferably the output would be the usernames listed under the group they are a member of.", "\nI have the following which allows me to export the members of 1 AD Group at a time, but I am at a loss as to how to modify it to look at multiple groups.", "\nOn Error Resume Next\nSet fso = CreateObject(\"Scripting.", "FileSystemObject\")\nSet outfile = fso.", "CreateTextFile(\"Members.csv\")\nSet objGroup = GetObject(\"LDAP://cn=*GROUPNAME*,OU=Groups,DC=domain,DC=local\")\nobjGroup.", "GetInfo\n\narrMembersOf = objGroup.", "GetEx(\"member\")\n\nFor Each GetObject in ObjGroup\n outfile.", "WriteLine objGroup.", "Name\nNext\n\nFor Each strMember in arrMembersOf\n outfile.", "WriteLine strMember\nNext\n\nAny ideas?", "\n\nA:\n\nYeah, this is possible, but I think you might need to change your approach slightly. ", "You need to write an LDAP query to query two groups at once, rather than just setting your scope to a particular group.", "\nSo, try reworking your script like this:\n Set objRootDSE = GetObject(\"LDAP://RootDSE\")\n strDNSDomain = objRootDSE.Get(\"defaultNamingContext\")\n Set objRootDSE = Nothing\n Set ad = CreateObject(\"ADODB.Command\")\n Set adoConnection = CreateObject(\"ADODB.Connection\")\n adoConnection.", "Provider = \"ADsDSOObject\"\n adoConnection.", "Open \"Active Directory Provider\"\n ad.", "ActiveConnection = adoConnection\n\n'Put the distinguishedname of your two groups here:\nstrFilter = \"(|(memberof=CN=Group Name,OU=....)(memberof=CN=Group Name 2,OU=....))\"\n\n'Chose what you want to return here:\nstrAttributes = \"samaccountname,cn\"\n\nstrQuery = \"<LDAP://\" & strDNSDomain & \">\" & \";\" & strFilter & \";\" & strAttributes & \";subtree\"\n\n ad.", "CommandText = strQuery\n ad.", "Properties(\"SearchScope\") = 2 \n ad.", "Properties(\"Page Size\") = 1000\n ad.", "Properties(\"Cache Results\") = False\nSet objRS = ad.", "Execute\n\nNow you've got all the results in a recordset, you can work your way through them writing each one to a file or whatever you want to do. ", "So something like:\nDo Until objRS.EOF\n\n 'Do something with each value\n objRS.Fields(\"samaccountname\")\n\nobjRS.MoveNext\nLoop\n\nAny use? ", "I'm assuming here you know a little bit about writing LDAP queries\n\n" ]
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[ "*New* Madeira Flat Sheet\n\nTop quality MicroCotton is the base cloth for our Madeira collection; a contemporary take on the traditional embroidered bed. ", "Certainly worthy of the master bedroom; but can easily be styled in a guest room as well…" ]
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[ "Wiqu (Lima)\n\nWiqu (Quechua twisted, bent, crooked, also spelled Hueco) is a mountain in the Paryaqaqa or Waruchiri mountain range in the Andes of Peru, about high. ", "It is located in the Lima Region, Huarochirí Province, Quinti District, and in the Yauyos Province, Tanta District. ", "Wiqu lies southwest of Paryaqaqa and northeast of Parya Chaka.", "\n\nReferences\n\nCategory:Mountains of Peru\nCategory:Mountains of Lima Region" ]
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[ "Stretch-mediated responses of osteoblast-like cells cultured on titanium-coated substrates in vitro.", "\nCyclic stretching experiments on osteoblast-like cells have proven to be a useful tool in understanding the underlying mechanisms of load transduction at the bone-implant surface. ", "However, most experimental setups use silicone rubber substrates, which are atypical for orthopedic and dental implant materials. ", "Therefore, we investigated the responses of osteoblast-like cells to loading on titanium (Ti)-coated versus plain silicone substrates. ", "Ti-coated substrates were made by a radio-frequency magnetron sputtering process, and characterized using Rutherford backscattering spectrometry, X-ray photoelectron spectroscopy, and contact-angle measurements. ", "Osteoblast-like cells cultured from rat bone marrow were seeded on both types of substrates and stretched for 1 h continuously. ", "Subsequently, cell proliferation, alkaline phosphatase activity, and calcium content were measured for up to 24 days after seeding. ", "In addition light-, scanning electron-, and confocal laser scanning micrographs were made. ", "The results showed that our Ti coating had a thickness of 50 nm and contained Ti/oxygen as 1:1. ", "However, further characterization proved that the silicone material had a tendency to resurface through the coating. ", "Osteoblast-like cells proliferated faster on the Ti-coated substrates, but differentiation was slower compared with the silicone substrates. ", "It was concluded that that there was a definitive influence of the substrate material in mechanical stress models. ", "Therefore, extrapolation of results obtained using silicone substrates cannot be translated directly toward the situation of metallic implant materials." ]
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[ "Get In Touch\n\nProspective Students\n\nIt's Time to Think about Your Future\n\nIs your high school graduation in sight? ", "Are you looking for a more career-focused education, or for professional development that fits your unique and busy lifestyle? ", "Are you passionate about advancing in your field through graduate studies? ", "Whether you're a high school student ready to jumpstart your future, a military veteran looking to incorporate your leadership skills into your professional life, or an international student looking for an American education, your professional life starts at Champlain College." ]
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[ "Notodoris minor\n\nNotodoris minor is a species of sea slug. ", "It is a dorid nudibranch, a shell-less marine gastropod mollusc in the family Aegiridae.", "\n\nTaxonomy\nThis species was known as Notodoris minor, but a 2004 paper considered Notodoris to be a junior synonym of the genus Aegires. ", "This decision was reversed in 2015.", "\n\nDescription\n\nNotodoris minor can grow to 14 cm in length. ", "The skin is toughened with tiny spicules. ", "The upper surfaces have a few irregular pustules, while the small rhinophores are smooth and simple. ", "The branched gills are located midway along the body and are partially hidden by three large lobes. ", "The Notodoris minor has a yellow background colour and a pattern of diagonal and transverse black lines arranged in a network covering the entire body. ", "The gills and rhinophores are yellow, but in younger specimens and with some adults, there may be some black pigmentation.", "\n\nDistribution \nNotodoris minor lives in the Indo-west Pacific area. ", "It has been found in the Philippines, Vanuatu, Solomon Islands, Mauritius, Tanzania, Oman, Indonesia, Okinawa, Papua New Guinea, and the Great Barrier Reef.", "\n\nDiet\nNotodoris minor feeds on calcareous sponges belonging to the family Leucettidae. ", "In the Indo-West Pacific, specimens have been recorded eating Leucetta primigenia.", "\n\nReferences\n\nFurther reading \n Gosliner, T.M. Behrens, D.W. & Williams, G.C. (1996). ", "Coral reef animals of the Indo-Pacific. ", "Sea Challengers, Monterey, California. ", "314 pp.", "\n Marshall, J.G. & Willan, R.C. (1999). ", "Nudibranchs of Heron Island, Great Barrier Reef. ", "A survey of the Opisthobranchia (Sea Slugs) of Heron and Wistari Reefs. ", "Backhuys Publishers, Leiden, The Netherlands, 257 pp.", "\n\nCategory:Aegiridae\nCategory:Gastropods described in 1904" ]
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[ "Escherichia coli heat-stable enterotoxin-mediated colonic Cl- secretion is absent in cystic fibrosis.", "\nCalcium- and adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretions in the human colon are abnormal in cystic fibrosis, but the effect of guanosine 3',5'-cyclic monophosphate (cGMP) is unknown. ", "This study examined the effects of the cGMP activator Escherichia coli heat-stable enterotoxin (STa) on rectal ion transport of controls and subjects with cystic fibrosis. ", "In vivo rectal potential difference (PD) was measured in response to 10(-7) mol/L STa in adult cystic fibrosis (n = 6) and control subjects (n = 7). ", "Cl- transport was also evaluated in 24-hour primary cultures of human colonocytes using 6-methoxy-quinolyl-acetoethyl ester in response to STa (1 mumol/L) and 8-bromo-cGMP (100 mumol/L) with or without Cl- transport inhibitors. ", "Whereas STa increased rectal potential difference in controls, there was no effect in cystic fibrosis subjects. ", "STa stimulated the cGMP concentration in rectal biopsy specimens from both control and cystic fibrosis subjects approximately twofold. ", "In vitro Cl- transport in non-cystic fibrosis colonocytes increased threefold and fivefold with STa and 8-bromo-cGMP, respectively. ", "These transport increases were inhibited by furosemide and the Cl- channel blocker diphenylamine-2-carboxylate. ", "Human colonocytes secrete Cl- in response to STa and cGMP in normal subjects, but this response is absent in cystic fibrosis." ]
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[ "Q:\n\nQuoteName not giving result\n\nI am trying this code \nCREATE TABLE #t \n( \n nam Varchar(100) \n) \nINSERT INTO #t(nam)VALUES('abc[]def') \nSELECT * FROM #t Where Quotename(nam) like Quotename('abc[]def') \ndrop table #t \n\nand not giving me any result.... Am I missing something?", "\n\nA:\n\nCREATE TABLE #t \n( \n nam Varchar(100) \n); \nINSERT INTO #t(nam)VALUES('abc[]def'); \nSELECT * FROM #t Where Quotename(nam) = Quotename('abc[]def');\ndrop table #t;\n\nIts not returning anything because Brackets [ ] are know as Wildcard alphabets with LIKE. ", "\nThe set of characters specified between brackets wildcard which will match any one characters in the specified position (the location of the wildcard). ", "\nhttp://msdn.microsoft.com/en-us/library/ms179859.aspx\nPlease open the link and search the following text.", "\nUsing the [ ] wildcard characters\n\n" ]
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[ "The Life of Anne Frank\n\n#1 What year was Anne Frank born?", "\n\n#2 Where did the Frank family go into hiding?", "\n\nThe back room of the father's friend's officeThe attic of the father's friend's homeThe attic above the father's officeThe basement of a neighbor's home\n\n#3 Which Frank family member received the call-up that forced the family to immediately leave for their hiding place?", "\n*Note: call-ups were notices that rounded up Jewish people to send them to work camps in Germany.", "\n\nAnneMargotEdithOtto\n\n#4 What year did Anne begin her diary?", "\n\n1939194119301942\n\n#5 What was the real name of the dentist who joined the Frank and van Pels family while in hiding?", "\n\nMr. DusselJoop ter HeulFritz PfefferMiep Gies\n\n#6 Who was the person that betrayed those in hiding by calling the Security Police?", "\n\nVan MaarenLena Hartog-Van BladerenTony AhlersNo one knows\n\n#7 What was the name of the concentration camp that all of those in hiding were first sent to?", "\n\nAuschwitz-BirkenauBergen-BelsenWesterborkSachsenhausen\n\n#8 Anne and Margot both died only a few weeks before the concentration camp was liberated. ", "What did they die of?", "\n\nThey were killed in the gas chamber.", "They died from dysentery.", "They died from exhaustion and starvation.", "They died from typhus.", "\n\n#9 Who was the only surviving member of those in hiding?", "\n\nPeter van PelsOtto FrankEdith FrankAnne Frank\n\n#10 What was the name of the female that helped hide the family and who also is credited for saving Anne's diary?" ]
{ "pile_set_name": "Pile-CC" }
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[ "the prime factors of 14213442?", "\n2, 3, 2368907\nWhat are the prime factors of 301836?", "\n2, 3, 25153\nList the prime factors of 1762845.", "\n3, 5, 7, 103, 163\nWhat are the prime factors of 95183?", "\n11, 17, 509\nWhat are the prime factors of 1373394?", "\n2, 3, 11, 20809\nWhat are the prime factors of 3526259?", "\n11, 17, 109, 173\nWhat are the prime factors of 13926384?", "\n2, 3, 32237\nList the prime factors of 276100.", "\n2, 5, 11, 251\nWhat are the prime factors of 771913?", "\n19, 40627\nList the prime factors of 4132618.", "\n2, 7, 295187\nList the prime factors of 35601.", "\n3, 11867\nWhat are the prime factors of 106666?", "\n2, 7, 19, 401\nWhat are the prime factors of 9274?", "\n2, 4637\nList the prime factors of 981254.", "\n2, 490627\nList the prime factors of 11858040.", "\n2, 3, 5, 32939\nList the prime factors of 444534.", "\n2, 3, 43, 1723\nWhat are the prime factors of 5134?", "\n2, 17, 151\nList the prime factors of 959378.", "\n2, 7, 17, 29, 139\nWhat are the prime factors of 1453974?", "\n2, 3, 242329\nWhat are the prime factors of 723569?", "\n7, 11, 9397\nList the prime factors of 8647958.", "\n2, 11, 67, 5867\nList the prime factors of 1244281.", "\n17, 53, 1381\nList the prime factors of 16091.", "\n16091\nWhat are the prime factors of 9746641?", "\n23, 61, 6947\nList the prime factors of 4181604.", "\n2, 3, 7, 67, 743\nList the prime factors of 1309048.", "\n2, 13, 41, 307\nList the prime factors of 65436.", "\n2, 3, 7, 19, 41\nWhat are the prime factors of 32229788?", "\n2, 29, 79, 3517\nList the prime factors of 170446.", "\n2, 85223\nList the prime factors of 808594.", "\n2, 461, 877\nWhat are the prime factors of 915021?", "\n3, 19, 5351\nList the prime factors of 1339215.", "\n3, 5, 19, 37, 127\nWhat are the prime factors of 101068?", "\n2, 11, 2297\nWhat are the prime factors of 5376053?", "\n151, 35603\nList the prime factors of 2453051.", "\n2453051\nList the prime factors of 8398135.", "\n5, 1679627\nWhat are the prime factors of 21638830?", "\n2, 5, 2163883\nWhat are the prime factors of 2643821?", "\n2643821\nList the prime factors of 11590853.", "\n11590853\nWhat are the prime factors of 240629?", "\n41, 5869\nWhat are the prime factors of 683984?", "\n2, 7, 31, 197\nWhat are the prime factors of 728590?", "\n2, 5, 72859\nList the prime factors of 4365422.", "\n2, 101, 21611\nWhat are the prime factors of 12518742?", "\n2, 3, 2086457\nList the prime factors of 1169011.", "\n1169011\nWhat are the prime factors of 7646555?", "\n5, 7, 197, 1109\nList the prime factors of 280.", "\n2, 5, 7\nList the prime factors of 439361.", "\n13, 33797\nList the prime factors of 47862.", "\n2, 3, 2659\nList the prime factors of 12164392.", "\n2, 1520549\nList the prime factors of 944715.", "\n3, 5, 62981\nWhat are the prime factors of 2783801?", "\n17, 163753\nWhat are the prime factors of 162336?", "\n2, 3, 19, 89\nWhat are the prime factors of 2350901?", "\n7, 335843\nWhat are the prime factors of 30798187?", "\n7, 503, 8747\nWhat are the prime factors of 6933048?", "\n2, 3, 288877\nWhat are the prime factors of 190158?", "\n2, 3, 41, 773\nList the prime factors of 192897.", "\n3, 21433\nWhat are the prime factors of 1654096?", "\n2, 67, 1543\nWhat are the prime factors of 4409824?", "\n2, 19, 7253\nWhat are the prime factors of 32324842?", "\n2, 11, 1469311\nWhat are the prime factors of 10555559?", "\n7, 241, 6257\nWhat are the prime factors of 611536?", "\n2, 37, 1033\nWhat are the prime factors of 629668?", "\n2, 13, 12109\nList the prime factors of 275359.", "\n7, 139, 283\nWhat are the prime factors of 181735?", "\n5, 19, 1913\nWhat are the prime factors of 14336954?", "\n2, 7168477\nWhat are the prime factors of 980526?", "\n2, 3, 17, 9613\nList the prime factors of 1468926.", "\n2, 3, 79, 1033\nList the prime factors of 80591.", "\n7, 29, 397\nWhat are the prime factors of 545833?", "\n41, 13313\nWhat are the prime factors of 437776?", "\n2, 27361\nList the prime factors of 186919.", "\n41, 47, 97\nList the prime factors of 617262.", "\n2, 3, 102877\nList the prime factors of 12845.", "\n5, 7, 367\nList the prime factors of 279899.", "\n31, 9029\nList the prime factors of 12582.", "\n2, 3, 233\nWhat are the prime factors of 1846?", "\n2, 13, 71\nWhat are the prime factors of 1440282?", "\n2, 3, 240047\nWhat are the prime factors of 1631629?", "\n1631629\nWhat are the prime factors of 9796126?", "\n2, 1453, 3371\nWhat are the prime factors of 6289815?", "\n3, 5, 7, 37, 1619\nList the prime factors of 575105.", "\n5, 115021\nWhat are the prime factors of 422098?", "\n2, 211049\nList the prime factors of 26160419.", "\n41, 638059\nList the prime factors of 1398020.", "\n2, 5, 13, 19, 283\nList the prime factors of 5820945.", "\n3, 5, 13, 29851\nWhat are the prime factors of 292865?", "\n5, 58573\nList the prime factors of 2899755.", "\n3, 5, 64439\nWhat are the prime factors of 325548?", "\n2, 3, 9043\nList the prime factors of 660429.", "\n3, 7, 11, 953\nWhat are the prime factors of 5828396?", "\n2, 7, 41, 5077\nWhat are the prime factors of 663766?", "\n2, 331883\nList the prime factors of 9096463.", "\n1777, 5119\nList the prime factors of 404390.", "\n2, 5, 7, 53, 109\nList the prime factors of 172028.", "\n2, 29, 1483\nList the prime factors of 59545.", "\n5, 11909\nList the prime factors of 325968.", "\n2, 3, 6791\nList the prime factors of 825460.", "\n2, 5, 149, 277\nList the prime factors of 27028610.", "\n2, 5, 7, 101, 3823\nWhat are the prime factors of 459534?", "\n2, 3, 19, 29, 139\nList the prime factors of 1001332.", "\n2, 167, 1499\nList the prime factors of 3996636.", "\n2, 3, 7, 971\nList the prime factors of 843321.", "\n3, 47, 5981\nWhat are the prime factors of 1559230?", "\n2, 5, 41, 3803\nList the prime factors of 306083.", "\n306083\nWhat are the prime factors of 386459?", "\n223, 1733\nList the prime factors of 1436685.", "\n3, 5, 19, 71\nWhat are the prime factors of 15239643?", "\n3, 443, 11467\nWhat are the prime factors of 44997?", "\n3, 53, 283\nList the prime factors of 1909625.", "\n5, 15277\nWhat are the prime factors of 9392?", "\n2, 587\nWhat are the prime factors of 73078?", "\n2, 61, 599\nWhat are the prime factors of 18465423?", "\n3, 73, 84317\nWhat are the prime factors of 207124?", "\n2, 53, 977\nWhat are the prime factors of 908649?", "\n3, 7, 14423\nList the prime factors of 246302.", "\n2, 7, 73, 241\nList the prime factors of 645338.", "\n2, 322669\nWhat are the prime factors of 398674?", "\n2, 199337\nWhat are the prime factors of 9260632?", "\n2, 1157579\nList the prime factors of 3954768.", "\n2, 3, 47, 1753\nWhat are the prime factors of 585306?", "\n2, 3, 3613\nWhat are the prime factors of 221233?", "\n221233\nWhat are the prime factors of 33108484?", "\n2, 41, 201881\nList the prime factors of 5840053.", "\n199, 29347\nWhat are the prime factors of 51086?", "\n2, 7, 41, 89\nList the prime factors of 1335232.", "\n2, 31, 673\nWhat are the prime factors of 1387143?", "\n3, 154127\nList the prime factors of 2474650.", "\n2, 5, 43, 1151\nWhat are the prime factors of 2275572?", "\n2, 3, 13, 29, 503\nWhat are the prime factors of 897526?", "\n2, 7, 64109\nList the prime factors of 11488871.", "\n1453, 7907\nList the prime factors of 36453242.", "\n2, 7, 1277, 2039\nWhat are the prime factors of 651916?", "\n2, 17, 9587\nWhat are the prime factors of 628523?", "\n7, 101, 127\nList the prime factors of 354193.", "\n7, 50599\nList the prime factors of 341460.", "\n2, 3, 5, 7, 271\nWhat are the prime factors of 259281?", "\n3, 11, 97\nList the prime factors of 885262.", "\n2, 7, 37, 1709\nWhat are the prime factors of 20311632?", "\n2, 3, 11, 12823\nWhat are the prime factors of 251692?", "\n2, 7, 89, 101\nList the prime factors of 423076.", "\n2, 105769\nWhat are the prime factors of 1397064?", "\n2, 3, 58211\nList the prime factors of 28850398.", "\n2, 19, 31, 1289\nWhat are the prime factors of 123220?", "\n2, 5, 61, 101\nWhat are the prime factors of 1105059?", "\n3, 19, 19387\nWhat are the prime factors of 47574?", "\n2, 3, 881\nWhat are the prime factors of 1135759?", "\n43, 61, 433\nWhat are the prime factors of 55990?", "\n2, 5, 11, 509\nWhat are the prime factors of 1854400?", "\n2, 5, 19, 61\nList the prime factors of 2364040.", "\n2, 5, 7, 8443\nList the prime factors of 1636821.", "\n3, 60623\nList the prime factors of 1813444.", "\n2, 37, 12253\nWhat are the prime factors of 29204888?", "\n2, 751, 4861\nWhat are the prime factors of 4949927?", "\n107, 46261\nList the prime factors of 72325.", "\n5, 11, 263\nWhat are the prime factors of 94280?", "\n2, 5, 2357\nWhat are the prime factors of 9538273?", "\n739, 12907\nWhat are the prime factors of 21443870?", "\n2, 5, 7, 107, 409\nWhat are the prime factors of 28819621?", "\n23, 1253027\nWhat are the prime factors of 2481009?", "\n3, 59, 107, 131\nList the prime factors of 36611492.", "\n2, 23, 397951\nWhat are the prime factors of 3883957?", "\n7, 11, 50441\nList the prime factors of 187843.", "\n187843\nWhat are the prime factors of 16286108?", "\n2, 4071527\nWhat are the prime factors of 18010230?", "\n2, 3, 5, 7, 139, 617\nWhat are the prime factors of 893400?", "\n2, 3, 5, " ]
{ "pile_set_name": "DM Mathematics" }
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[ "Q:\n\nCannot find Enable Attachments in ArcCatalog 10.1\n\nI am using ArcCatalog 10.1 but I cannot find the option \"Enable Attachments\" when I right click on a shapefile. ", "Please see the picture below too.", "\n\nThere was another question similar to this in this forum but the solution proposed was to convert shapefile to GDB. ", "Can anyone guide me how to do that? ", "Or is there another way to enable attachments.?", "\nI also converted the shapefile to shapefile stored under geodatabase. ", "See the picture below\n\nHowever my TestingB.shp also doesnot have the attachments option on right click same as TestingA file.", "\n\nA:\n\nAttachments can be enabled only on feature classes stored within a geodatabase (this can be any type of geodatabase - personal, file, or enterprise). ", "You cannot attach your files to a shapefile because there is no container the data can be stored in.", "\nTo convert your shapefile to a geodatabase, you can use a GP tool Feature Class To Feature Class (Conversion) or just right-click the shapefile and choose Export > To Geodatabase (which will start the GP tool dialog box).", "\n\nA:\n\nI've attached an image showing what you need to do for the first step. ", "Namely, turn the Shapefile into a Featureclass. ", "A Featureclass can only reside inside a Geodatabase (aka GDB).", "\nAlternately you can create a GDB and import your Shapefile into it by R-click, etc. ", "See this image below. ", "\n\nAs Alex Tereshenkov said - You can only enable attachments to a Featureclass, which by definition will reside inside a GDB. ", "Shapefiles with attachments are disallowed. ", "\nNow you can enable attachments as per normal.", "\n\n" ]
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[ "Morosaphycita oculiferella\n\nMorosaphycita oculiferella is a moth of the family Pyralidae described by Edward Meyrick in 1879. ", "It is known from Australia (including Queensland and the Australian Capital Territory) and New Zealand.", "\n\nThe wingspan is about 20 mm. ", "Adults have dark brown forewings with various dark lines, each having a white mark near the base of the inner margin. ", "The hindwings are off white, with narrow dark margins.", "\n\nReferences\n\nCategory:Phycitinae\nCategory:Moths of New Zealand\nCategory:Taxa named by Edward Meyrick\nCategory:Moths of Australia\nCategory:Moths described in 1879" ]
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[ "Referral Program\n\nWant a £100 Amazon Gift Card for FREE?", "\n\nIntroducing the SWATT Books Referral Program\n\nWith the SWATT Books Referral Program, for every referral you give to me who signs up for a design & publishing package, I will give you a £100 Amazon.co.uk Gift Card. ", "PLUS, I will give your referee £100 off their package!!!", "\n\nSo if you know someone who is writing a book, send them to my Publishing page for more information on how I can help them make their dream of becoming a published author a reality.", "\n\nNuts & Bolts\n\nTo qualify, simply send an email to sam@swatt-books.co.uk with your name, email address, and contact telephone number, as well as your referrals name, email address, and contact telephone number. ", "If your referral signs up to an all inclusive Design & Publishing packages or a bespoke design & publishing package, I will contact you to arrange delivery of your gift card. ", "It’s that simple!!" ]
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[ "Youth League President Accused Of Stealing Fees\n\nCounty police have charged the president of the Anne Arundel County Youth Soccer League with felony theft of more than $12,000 in registration fees owed the Department of Recreation and Parks.", "\n\nDale C. Adams Sr., ", "42, of the 1100 block Neptune Place in Annapolis, was charged Dec. 10 with cashing an unauthorized check for $12,434.50 on the league's account at a branch of Citizens Bank of Maryland in Linthicum.", "\n\nThe league check was cashed Sept. 7, and Adams used the money to pay off a foreclosure on his Annapolis home, according to the police statement of charges.", "\n\n\"Adams reported the checks stolen (to police) and then they turned up a couple of weeks later,\" Recreation and Parks Director Joseph McCann said yesterday. \"", "The next thing you know, this check turned up.\"", "\n\nAdams could not be reached for comment.", "\n\nThe county will seek to collect the money from Citizens Bank, McCann said, because it cashed the check on Adams' authority alone in violation of the league's requirement for a second official's signature.", "\n\nIf convicted of the felony theft charge, Adams could face 15 years in prison and a fine up to $1,000.", "\n\nMcCann said he ordered an audit of the league's finances but found no other problems.", "\n\n\"Apparently, Adams was well thought of,\" he said. \"", "They've been a good organization. ", "They've been a big help to the Recreation and Parks Department.\"", "\n\nThe department routinely entrusts volunteer organizations with collecting about $2.5 million each year owed the county for use of fields and other sports facilities.", "\n\n\"The arrangement we have with the volunteer organizations is that they collect the money for the soccer teams and then they pass along fees to us,\" McCann said. \"", "They cut us one check to cover the number of teams registered for the season.\"", "\n\nThe missing money was the bulk of the fees the league had collected for this season, he said.", "\n\nAlthough the citizens groups follow cash control guidelines recommended by the county, they are managed independently, McCann said.", "\n\n\"In these volunteer organizations, there are isolated reports of theft but they go to the police and don't involve us,\" he said. \"", "The people at fault here -- beside the person who allegedly committed the theft -- is the bank.\"" ]
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[ "Cephalons come in all shapes and sizes. ", "Some assist their Operators in navigation and the maintenance of complex tools, while others are more curious beings, spreading vast networks across the Solar System in the pursuit of knowledge. ", "Cephalon Cordylon's task is much simpler.", "\n\nIt is Cordylon's responsibility to sort and file knowledge obtained by the Lotus. ", "Although the acquisition of such data occupies most of the AI's time, there are moments where Cordylon can be inclined to share the fruits of its labor with others. ", "On those rare occasions, its massive databanks open and offer those deemed worthy insight.", "\n\nMost of the time, Tenno just ask for Mods.", "\n\nBut! ", "Every now and then some approach Cephalon Cordylon with questions that only a being of such vast intellect could answer. ", "These are the responses:\n\nZephyrzay Asks: How does a Cephalon celebrate the festive season?", "\n\nCephalon have no need for celebration, but it is understood that organic life forms frequently enjoy distracting themselves from their mortality and eminent demise with a wide range of celebratory occasions. ", "As participation in these events helps improve morale, I always stay prepared for any potential celebrations by keeping appropriate festive subroutines on standby.", "\n\nThese celebratory statements and actions include:\n\n· \"Congratulations on another year of existence.\"", "\n\n· \"A reminder: excessive consumption of mood-altering substances can lead to intense sickness.\"", "\n\n· \"Please enjoy this seasonally-correct and visually accurate representation of festive imagery.\"", "\n\nThe final statement is normally followed by a holographic image of confetti, streamers, and flashing lights. ", "I have learned not to perform such an action around Tenno that feel particularly attached to Mirage, as it has encouraged an unintended response in the past.", "\n\nMorec0 Asks: I'm certain that the Colonists have attempted, and likely continue to attempt, self-defence against the Grineer or Corpus throughout their history. ", "What sort of weapons have they used or even made to defend themselves?", "\n\nEven well-prepared Colonists likely do not have an appropriate defense that could withstand a premeditated Grineer or Corpus invasion, but there have been reports of some colonies surviving such attacks through unconventional means.", "\n\nThe most frequent come from Colonists that have enlisted the help of freelance mercenaries or Syndicates such as Steel Meridian. ", "These deadly firefights still see causalities, but raids are expected on settlements unfortunate enough to catch the attention of the Grineer Empire. ", "Corpus engagements can often be negotiated before coming to violence, but these contracts are rarely mutually beneficial for both parties.", "\n\nA rare exception is the reported instance of a Corpus Hostile Investigation Unit that was held back by a single juvenile colonist. ", "Description of the incident from HIU informants is unclear, but the core of the report focuses around several hand-made booby-traps that caused serious injuries preventing the team from performing a full sweep of the area.", "\n\nSnowmotion Asks: Knowledgeable Cordylon, were you in possession of the capability to physically taste, of the various dishes and desserts on offer across our solar system, could you share the ones you believe would be most agreeable to you?", "\n\nThere are many dishes across our Solar System that could fall under the definition of `Agreeable` due to either the general appreciation for their base ingredients. ", "Many of these prepared meals range widely depending on local tastes, but there are a few that stand out:\n\n· Boiled Martian Oasis Jellyfish, dusted with blend of Earth spices served over the finest solar-enriched vegetation.", "\n\n· The Corpus-created Nutritional Flavor Bar is well known amongst Crewmen for its marketing slogan: 'Sustain yourself with nourishment.'", "\n\n· Kubrow Flank, fried or burned. ", "This is one of two 'recipes' that can be found in Grineer logs under 'edible objects.'", "\n\nAn Avid Fisherman Asks: Where can I purchase a weapon that's both practical in combat, but also excellent for catching the occasional wild carp on Earth.", "\n\nAny tool that can serve multiple purposes reliably is one to be admired, and I am pleased to announce that Tenno should have access to such a weapon within the next lunar cycle. ", "While effective against wildlife I am inclined to warn Operators against using such a weapon for hunting wildlife larger than the size of a regulation Landing Craft." ]
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[ "Quebec started legalization with only a dozen cannabis stores to serve the whole province — or one for every 700,000 people.", "\n\nSo Quebecers who wanted to buy legal weed had a choice.", "\n\nThey could try to use the few stores, lining up in the cold and sometimes travelling long distances. (", "Major centres like Gatineau and Sherbrooke still don’t have stores.)", "\n\nOr they could order from home online, in their pyjamas if they wanted to.", "\n\n– Read the entire article at Global News." ]
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[ "Q:\n\nUrl navigation in a WebApp built with ExtJS\n\nwhen you develop a web application using ExtJS (with its MVC and a Viewport), generally there's no possibility to navigate: every item into the page (buttons, textfields, textareas, ...) is bound to a specific method of the view's controller.", "\nSo, when you 'travel' through the application, the original URL is always the same and it doesn't change.", "\nNow, take as example an application with a header menu bar filled with these following buttons:\nHome | Setup | Archive\n\nAnd the original URL of the application take the following: \nhttp://www.mydomain.com/webapp\n\nAt this point, when someone click Home or Setup or Archive menu a certain view is displayed into the center region and the URL should change in \nhttp://www.mydomain.com/webapp/[home|setup|archive]\n\nSo, if I click Setup menu the following URL should be displayed in the address bar: \nhttp://www.mydomain.com/webapp/setup\n\nFurther more, the same page should be shown if I type the same URL into the address bar from another URL.", "\nBut currently my webapp still remains into 'http://www.mydomain.com/webapp' showing the requested view. (", "MyApp.view.", "Setup, for instance).", "\nThat's the point: how can I develop a webapp (with ExtJS, MVC and Viewport) with URL navigation? ", "Is it possible to do without nesting javascript/html code into other PHP/Ruby/Python/$RANDOM_SERVER_LANGUAGE? (", "I want to split client by server side)\nAn implementation of this already exists: it's the ExtJS API Documentation. ", "If I'm right, there's no server-side application or .htaccess that provide the page requested.", "\nIn fact, there's a folder called 'source' into the main directory that contains an HTML file for each class.", "\nHow they do that?", "\nThanks in advance.", "\nWilk\n\nA:\n\nOk, I found the solution by myself :P\nWell, this kind of thing could be done by the following way:\nHTML part\n<!", "DOCTYPE html>\n<html>\n<head>\n <title>Stackoverflow</title>\n <link rel=\"stylesheet\" type=\"text/css\" href=\"../extjs-4.1.0/resources/css/ext-all.css\"/>\n <script type=\"text/javascript\" src=\"../extjs-4.1.0/ext-all.js\"> </script>\n <script type=\"text/javascript\" src=\"sof.js\"> </script>\n</head>\n<body>\n <a href=\"#!photos.html\">Photos</a>\n <a href=\"#!info.html\">Info</a>\n <a href=\"#!aboutme.html\">About Me</a>\n\n <div id=\"results\"></div>\n</body>\n\nJavascript part, done with ExtJS framework (sof.js)\n// Loads each HTML part with an AJAX request\nfunction loadAnchor (url) {\n Ext.Ajax.request ({\n url: url ,\n success: function (res) {\n // Edits results div with the new HTML part\n var r = Ext.get ('results');\n r.dom.innerHTML = res.responseText;\n }\n });\n}\n\nExt.onReady (function () {\n var anchors = document.getElementsByTagName ('a');\n\n Ext.each (anchors, function (a) {\n a = Ext.get (a);\n // Attaches to each anchor the following function on click event\n a.on ('click', function (ev, anchor) {\n // Splits the hash, keeping the HTML requested\n var url = anchor.getAttribute('href').split('#!')[1];\n loadAnchor (url);\n });\n });\n\n // This is done without clicking an anchor, but by inserting directly the full URI\n // E.g.: http://www.mydomain.com/webapp/index.html#!info.html instead of clicking the anchor Info\n var url = document.location.hash.split('#!')[1];\n loadAnchor (url);\n});\n\nAs you can see, each anchor is bound with a javascript function that loads the requested resource by an AJAX request.", "\nThen, a certain container (a div, for example) is modified with the response (maybe HTML code or JSON, XML, etc...).", "\nHowever, this thing has to be done with a server web like Apache but without a server application: in fact, each resource can be a pure HTML file and no server app is needed to serve those file.", "\nFor further details, see:\n\nAnchored based URL navigation\nMaking AJAX Applications Crawlable\n\n" ]
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[ "S2 Games\n\nS2 Games was a video game development company which was founded by Marc \"Maliken\" DeForest, Jesse Hayes, and Sam McGrath, based in Rohnert Park, California. ", "They also have a development location in Kalamazoo, Michigan.", "\n\nThe company slogan was Dedicated employees serving dedicated gamers. ", "Continuous development. ", "Never-ending improvement.", "\n\nHistory\nTheir first project (a real-time strategy, third-person shooter and role-playing game hybrid), Savage: The Battle for Newerth, was released in the Summer of 2003. ", "They released its sequel, Savage 2: A Tortured Soul, on January 16, 2008, and are independently publishing and distributing it. ", "Their latest installment in the Newerth series, Heroes of Newerth, based heavily around Defense of the Ancients, was released on May 12, 2010.", "\n\nIn 2015 S2 Games sold the rights to Heroes of Newerth to Garena to focus on Strife, their second-generation MOBA.", "\n\nGarena subsequently moved Heroes of Newerth to Frostburn Studios, a Kalamazoo, Michigan based subsidiary of Garena.", "\n\nTitles\nSavage: The Battle for Newerth (2003) (Windows, Macintosh, Linux)\nSavage 2: A Tortured Soul (2008) (Windows, Macintosh, Linux)\nHeroes of Newerth (2010) (Windows, Macintosh, Linux)\nStrife (2015) (Windows, Macintosh, Linux)\nSavage Resurrection (2016) (Windows)\nBrawl of Ages (2017) (Windows)\n\nKey events\nIn 2003, S2 Games released Savage: The Battle for Newerth, their first commercial game.", "\nIn 2004, three former S2 Games employees left the company to form Offset Software.", "\nIn 2006, S2 Games re-released Savage: The Battle for Newerth, as freeware.", "\nIn 2008, S2 Games released Savage 2: A Tortured Soul.", "\nIn 2009, S2 Games re-released Savage 2: A Tortured Soul as freeware.", "\nIn 2010, S2 Games released Heroes of Newerth.", "\nIn 2011, S2 Games re-released Heroes of Newerth as freeware/free-to-play.", "\nIn 2012, S2 Games made all heroes in Heroes of Newerth completely free for online play.", "\nIn 2012, over 10,000,000 Heroes of Newerth user accounts had been registered.", "\nIn 2013, S2 Games announced Strife an upcoming \"second generation MOBA\".", "\nIn 2015, S2 Games released Heroes of Newerth from its label into the hands of Frostburn Studios.", "\nIn 2017, Savage Resurrection was re-released under a free-to-play model.", "\nIn 2018, Strife and Brawl of Ages servers were shut down and S2 Games was quietly closed.", "\n\nReferences\n\nExternal links\n\n \nCategory:Video game companies of the United States\nCategory:Video game companies based in California\nCategory:Video game development companies\nCategory:Software companies based in the San Francisco Bay Area\nCategory:Companies based in Sonoma County, California\nCategory:Rohnert Park, California\nCategory:Video game companies established in 2003\nCategory:Video game companies disestablished in 2018\nCategory:Defunct video game companies\nCategory:Defunct companies based in the San Francisco Bay Area\nCategory:2003 establishments in California\nCategory:2018 disestablishments in California\nCategory:Companies based in Kalamazoo, Michigan" ]
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[ "How does inflammation cause Barrett's metaplasia?", "\nOesophageal adenocarcinoma conveys a poor prognosis and has a rapidly increasing incidence. ", "Similarly, Barrett's metaplasia (a precursor lesion for oesophageal adenocarcinoma) has an increasing incidence. ", "Both oesophageal adenocarcinoma and Barrett's metaplasia are more common in the context of inflammation as a result of acid and bile reflux. ", "The cytokine profile of Barrett's metaplasia is predominantly a T-helper 2 response that contrasts with the T-helper 1 response in normal and inflamed oesophagus and normal intestine. ", "A key transcription factor in the development of Barrett's metaplasia, CDX2, has recently been shown to be induced in response to inflammatory mediators. ", "The mechanism for induction of CDX2 is dependent on nuclear factor kappa B, a crucial transcription factor in the inflammatory response. ", "Understanding the role of oesophageal inflammation will provide important insight into the development of Barrett's metaplasia and oesophageal cancer." ]
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[ "# Copyright 2018 The TensorFlow Authors. ", "All Rights Reserved.", "\n#\n# Licensed under the Apache License, Version 2.0 (the \"License\");\n# you may not use this file except in compliance with the License.", "\n# You may obtain a copy of the License at\n#\n# http://www.apache.org/licenses/LICENSE-2.0\n#\n# Unless required by applicable law or agreed to in writing, software\n# distributed under the License is distributed on an \"AS IS\" BASIS,\n# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n# See the License for the specific language governing permissions and\n# limitations under the License.", "\n# ==============================================================================\n\"\"\"Implementation of fully connected network.\"\"\"", "\n\nfrom __future__ import absolute_import\nfrom __future__ import division\nfrom __future__ import print_function\n\nimport tensorflow as tf\n\n\nclass FeedFowardNetwork(tf.layers.", "Layer):\n \"\"\"Fully connected feedforward network.\"\"\"", "\n\n def __init__(\n self, hidden_size, filter_size, relu_dropout, train, allow_pad\n ):\n super(FeedFowardNetwork, self).__init__()\n self.hidden_size = hidden_size\n self.filter_size = filter_size\n self.relu_dropout = relu_dropout\n self.train = train\n self.allow_pad = allow_pad\n\n self.filter_dense_layer = tf.layers.", "Dense(\n filter_size,\n use_bias = True,\n activation = tf.nn.relu,\n name = 'filter_layer',\n )\n self.output_dense_layer = tf.layers.", "Dense(\n hidden_size, use_bias = True, name = 'output_layer'\n )\n\n def call(self, x, padding = None):\n \"\"\"Return outputs of the feedforward network.", "\n\n Args:\n x: tensor with shape [batch_size, length, hidden_size]\n padding: (optional) If set, the padding values are temporarily removed\n from x (provided self.allow_pad is set). ", "The padding values are placed\n back in the output tensor in the same locations.", "\n shape [batch_size, length]\n\n Returns:\n Output of the feedforward network.", "\n tensor with shape [batch_size, length, hidden_size]\n \"\"\"\n padding = None if not self.allow_pad else padding\n\n # Retrieve dynamically known shapes\n batch_size = tf.shape(x)[0]\n length = tf.shape(x)[1]\n\n if padding is not None:\n with tf.name_scope('remove_padding'):\n # Flatten padding to [batch_size*length]\n pad_mask = tf.reshape(padding, [-1])\n\n nonpad_ids = tf.to_int32(tf.where(pad_mask < 1e-9))\n\n # Reshape x to [batch_size*length, hidden_size] to remove padding\n x = tf.reshape(x, [-1, self.hidden_size])\n x = tf.gather_nd(x, indices = nonpad_ids)\n\n # Reshape x from 2 dimensions to 3 dimensions.", "\n x.set_shape([None, self.hidden_size])\n x = tf.expand_dims(x, axis = 0)\n\n output = self.filter_dense_layer(x)\n if self.train:\n output = tf.nn.dropout(output, 1.0 - self.relu_dropout)\n output = self.output_dense_layer(output)\n\n if padding is not None:\n with tf.name_scope('re_add_padding'):\n output = tf.squeeze(output, axis = 0)\n output = tf.scatter_nd(\n indices = nonpad_ids,\n updates = output,\n shape = [batch_size * length, self.hidden_size],\n )\n output = tf.reshape(\n output, [batch_size, length, self.hidden_size]\n )\n return output\n" ]
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[ "Justin Gimelstob, the highly connected tennis figure with a long history of alleged violence, is resigning from his post on the ATP board of directors. ", "Gimelstob felt he had become “too much of a distraction and a liability,” he told the New York Timesfrom Madrid, where he had flown to personally disclose his decision to his ally and ATP player council president, Novak Djokovic.", "\n\nIt has been an honor and a privilege to hold this position for the past 11 years. ", "My job was to best represent the players, the ATP, and be a custodian of the sport. ", "My choices and actions last Halloween night prohibit me from doing that at this time. ", "My role is designed to work on behalf of the players and the sport and it is clear that I have now become a significant burden and distraction to both. ", "That is not something that could or should continue. ", "I’m heartbroken to walk away from something I love so much, but given the current climate I do not deserve to be in this position of influence.", "\n\nFor the better part of my life, tennis has been much more than my occupation, it has been my passion. ", "I love the sport. ", "It has given me so much personally and professionally, for which I am very grateful. ", "Along the way I have had some successes and failures, and undoubtedly have made my share of mistakes. ", "I sincerely hope that I can and will be judged by my complete body of work throughout my career on and off the court; my passion, my energy, and my tireless work on behalf of my constituents and the game.", "\n\nGiving up or conceding is not in my DNA, but it has become clear that I need to take a step back - for the good of the players, the game and for myself. ", "Solely for that reason, I now more than ever appreciate that people in elected positions of influence must be held to the highest standard of conduct. ", "I breached that standard on a night last October. ", "I have always taken responsibility for my role in the events that evening and will continue to do so. ", "While I can, have, and will continue to dispute the way that evening has been depicted, the material matter is that my judgment that evening compromised the sport and the people that entrusted me with the authority to represent them. ", "I am deeply saddened and remorseful that my actions have caused the sport, players, my colleagues, friends and family such a distraction. ", "Actions have consequences and me stepping away from a role I cherished is one of them that I accept.", "\n\nAdvertisement\n\nAlthough Gimelstob’s violent history has seemingly been common knowledge in tennis circles for a while now, somehow public pressure for him to step down only began to ramp up in recent months, and intensified after he pleaded no contest to a felony battery charge on April 22. ", "Another prominent voice chimed in yesterday, when three-time major winner Stan Wawrinka made this statement:" ]
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[ "/*\n * Copyright (c) 2003, 2004, Oracle and/or its affiliates. ", "All rights reserved.", "\n * DO NOT ALTER OR REMOVE COPYRIGHT NOTICES OR THIS FILE HEADER.", "\n *\n * This code is free software; you can redistribute it and/or modify it\n * under the terms of the GNU General Public License version 2 only, as\n * published by the Free Software Foundation.", "\n *\n * This code is distributed in the hope that it will be useful, but WITHOUT\n * ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or\n * FITNESS FOR A PARTICULAR PURPOSE. ", " See the GNU General Public License\n * version 2 for more details (a copy is included in the LICENSE file that\n * accompanied this code).", "\n *\n * You should have received a copy of the GNU General Public License version\n * 2 along with this work; if not, write to the Free Software Foundation,\n * Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA.", "\n *\n * Please contact Oracle, 500 Oracle Parkway, Redwood Shores, CA 94065 USA\n * or visit www.oracle.com if you need additional information or have any\n * questions.", "\n *\n */\n\npackage sun.jvm.hotspot.utilities.soql;\n\npublic class SOQLException extends Exception {\n public SOQLException(String msg) {\n super(msg);\n }\n\n public SOQLException(String msg, Throwable cause) {\n super(msg, cause);\n }\n\n public SOQLException(Throwable cause) {\n super(cause);\n }\n}\n" ]
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[ "Q:\n\nChecking a checkbox by clicking its parent but not itself\n\nI've got checkboxes in li's. ", "I've made it so clicking the li will toggle the checkbox but the trouble I've run into is clicking the checkbox itself will launch both a toggle on and toggle off.", "\nCode:\n$('li').click(function(){\n $('input[type=\"checkbox\"]',this).each(function () { this.checked = !", "this.checked; });\n})\n\nhttp://jsfiddle.net/mattcoady/Vzqj3/\nI want the checkbox to still function as it normally would. ", "What can I do?", "\n\nA:\n\nStop the propagation of the event. ", "\nAdd the click event for the checkbox which would stop event bubbling.", "\n$('input[type=\"checkbox\"]').on('click', function(e) {\n e.stopPropagation();\n});\n\nCheck Fiddle\n\nA:\n\nNo need for JavaScript here. ", "Wrap the label around the entire contents of the list element, make it display: block (so it's full-width), and remove the JavaScript altogether.", "\nCSS:\nli label {\n display: block;\n}\n\nHTML:\n<ul>\n <li><label>\n <input type=\"checkbox\">\n The Checkbox\n </label></li>\n <li><label>\n <input type=\"checkbox\">\n The Checkbox\n </label></li>\n</ul>\n\nhttp://jsfiddle.net/mblase75/XFgt4/\n\n" ]
{ "pile_set_name": "StackExchange" }
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[ "Vitamin B6 in the treatment of the premenstrual syndrome--a review.", "\nA search of the literature yielded 12 controlled trials on vitamin B6 in the treatment of the premenstrual syndrome. ", "These are discussed with emphasis on methodological aspects. ", "A major drawback of the trials is the limited number of patients included. ", "The existing evidence of positive effects of vitamin B6 is weak, and some well-designed trials with positive results would be needed to change this view." ]
{ "pile_set_name": "PubMed Abstracts" }
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[ "Samuel Island\n\nSamuel Island is a small island in the southern Gulf Islands, located in the Strait of Georgia southeast of Mayne Island in British Columbia, Canada.", "\n\nSee also\nList of islands of British Columbia\n\nReferences\n\nCategory:Islands of the Gulf Islands" ]
{ "pile_set_name": "Wikipedia (en)" }
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[ "Anthropometry, strength and benchmarks for development: a basis for junior rowers' selection?", "\nThe aims of this study were to establish whether anthropometry, muscle strength and endurance accounted for differences between junior and senior elite rowing ergometer performance, and to determine annual development rates for juniors associated with training. ", "Twenty-six junior (8 females, age 18.0 ± 0.3 years and 18 males, age 17.9 ± 0.2 years) and 30 senior (12 females, 23.7 ± 3.0 years and 18 males, 24.0 ± 3.9 years) heavyweight rowers, were assessed anthropometrically, performed a 2000-m ergometer time-trial, and completed various muscular strength and endurance tests. ", "There were no anthropometrical differences between males; however after controlling for body-fat and standing-height, senior females were of greater body-mass (70.5 ± 4.6 kg and 77.2 ± 5.9 kg, P = 0.01) and sitting-height (89.8 ± 2.2 cm and 92.2 ± 6.1 cm, P = 0.04) than juniors. ", "Moderate to very large standardised differences in all strength and endurance tests were observed between juniors and seniors (effect size (ES) range 0.9-1.9). ", "Greater development rates (5.0% to 6.0%) and adjusted 2000-m performance was associated with upper-body strength (males) and endurance (females). ", "In conclusion, after identification of desirable anthropometry, the 2000-m ergometer potential of juniors may be accounted for by upper-body strength and endurance." ]
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[ "Many polypeptides that are naturally immunogenic lose this property when expressed recombinantly. ", "In some cases the native polypeptide has structural features which do not form during expression in a heterologous host e.g. post-translational modifications may be incorrect, intermolecular interactions which influence conformation may be lost, etc. ", "A further cause of lost immunogenicity is where a polypeptide (e.g. a surface-exposed polypeptide) is naturally oligomeric, and where this quaternary structure is required for immunogenicity (e.g. where the polypeptide has epitopes that are displayed only when a specific quaternary oligomeric structure is present). ", "Loss of oligomeric structure can mean that the monomeric protein is less immunogenic than its native oligomeric counterpart.", "\nIn other cases the native polypeptide may be a transmembrane polypeptide that is not amenable to expression in a recombinant host. ", "These problems are often seen when eukaryotic polypeptides (including those of eukaryotic viruses) are to be expressed in prokaryotes. ", "One way of improving expression of viral transmembrane polypeptides is to remove their transmembrane domains and express only the antigenic extracellular domains {1}. ", "However, this “soluble receptor” technology again suffers from loss of quaternary structure. ", "If a native receptor exists in an oligomeric form on the surface of a virus, and the oligomerisation arises from sequences in the transmembrane region, the soluble receptor will lose its ability to oligomerise, and this loss can have functional consequences e.g. loss of signalling or of avidity. ", "Loss of binding avidity, even though binding affinity may be retained, is a particular problem for antigens e.g. those used in vaccines.", "\nTechniques for oligomerising proteins have been disclosed in references 2 and 3.", "\nIt is an object of the invention to provide ways of improving the expression of polypeptides, and particularly of antigenic polypeptides e.g. to retain their oligomeric structure." ]
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[ "<?", "xml version=\"1.0\" encoding=\"utf-8\"?", ">\n<project name=\"train-times\" default=\"build\" basedir=\".\"", ">\n\t\n\t<!-- ", "build.local.properties and sdk.local.proprties are optional files that\n\t\tcan be used to override the default properties. --", ">\n\t<property file=\"./build.local.properties\"/>\n\t<property file=\"./sdk.local.properties\"/>\n\t<property file=\"./build.properties\"/>\n\t<!-- ", "inherit SDK properties from the root of the repository -->\n\t<property file=\"../../sdk.properties\"/>\n\t\n\t<fail unless=\"ios.provision.path\"/>\n\t<fail unless=\"ios.certificate.path\"/>\n\t<fail unless=\"ios.certificate.password\"/>\n\t\n\t<fail unless=\"android.certificate.path\"/>\n\t<fail unless=\"android.certificate.password\"/>\n\n\t<target name=\"build\" depends=\"build-web,build-android,build-ios\"/>\n\n\t<target name=\"prepare\">\n\t\t<delete dir=\"${output.path}\"/>\n\t</target>\n\n\t<target name=\"build-web\" depends=\"prepare\">\n\t\t<echo message=\"Building TrainTimesWeb.swf\"/>\n\t\t<java jar=\"${mxmlc}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"true\">\n\t\t\t<arg value=\"-load-config=${flashplayer.config}\"/>\n\t\t\t<arg value=\"-swf-version=${swf.version}\"/>\n\t\t\t<arg value=\"-frame=two,feathers.examples.trainTimes.", "Main\"/>\n\t\t\t<arg value=\"-source-path+=source\"/>\n\t\t\t<arg value=\"-source-path+=${starling.root}\"/>\n\t\t\t<arg value=\"-source-path+=${feathers.root}\"/>\n\t\t\t<arg value=\"source/TrainTimesWeb.as\"/>\n\t\t\t<arg value=\"-output=${output.path}/TrainTimesWeb.swf\"/>\n\t\t</java>\n\t</target>\n\n\t<target name=\"build-air-swf\" depends=\"prepare\">\n\t\t<echo message=\"Building TrainTimes.swf\"/>\n\t\t<java jar=\"${mxmlc}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"true\">\n\t\t\t<arg value=\"-load-config=${airmobile.config}\"/>\n\t\t\t<arg value=\"-swf-version=${swf.version}\"/>\n\t\t\t<arg value=\"-source-path+=source\"/>\n\t\t\t<arg value=\"-source-path+=${starling.root}\"/>\n\t\t\t<arg value=\"-source-path+=${feathers.root}\"/>\n\t\t\t<arg value=\"source/TrainTimes.as\"/>\n\t\t\t<arg value=\"-output=${output.path}/TrainTimes.swf\"/>\n\t\t</java>\n\t</target>\n\t<target name=\"build-ios\" depends=\"build-air-swf\">\n\t\t<echo message=\"Packaging TrainTimes.ipa\"/>\n\t\t<java jar=\"${adt}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"true\">\n\t\t\t<arg value=\"-package\"/>\n\t\t\t<arg value=\"-target\"/>\n\t\t\t<arg value=\"ipa-app-store\"/>\n\t\t\t<arg value=\"-provisioning-profile\"/>\n\t\t\t<arg value=\"${ios.provision.path}\"/>\n\t\t\t<arg value=\"-keystore\"/>\n\t\t\t<arg value=\"${ios.certificate.path}\"/>\n\t\t\t<arg value=\"-storetype\"/>\n\t\t\t<arg value=\"pkcs12\"/>\n\t\t\t<arg value=\"-storepass\"/>\n\t\t\t<arg value=\"${ios.certificate.password}\"/>\n\t\t\t<arg value=\"${output.path}/TrainTimes.ipa\"/>\n\t\t\t<arg value=\"source/TrainTimes-app.xml\"/>\n\t\t\t<arg value=\"-C\"/>\n\t\t\t<arg value=\"${icon.path}\"/>\n\t\t\t<arg line=\"icon29.png icon48.png icon50.png icon57.png icon58.png icon72.png icon87.png icon96.png icon100.png icon114.png icon128.png icon144.png icon180.png\"/>\n\t\t\t<arg value=\"-C\"/>\n\t\t\t<arg value=\"${launch.image.path}\"/>\n\t\t\t<arg value=\"Default~iphone.png\"/>\t\t\t\t\t\t\t<!-- ", "iphone 3gs -->\n\t\t\t<arg value=\"Default@2x~iphone.png\"/>\t\t\t\t\t\t<!-- ", "iphone 4/4s -->\n\t\t\t<arg value=\"Default-568h@2x~iphone.png\"/>\t\t\t\t\t<!-- ", "iphone 5/5c/5s -->\n\t\t\t<arg value=\"Default-375w-667h@2x~iphone.png\"/>\t\t\t\t<!-- ", "iphone 6/7/8 -->\n\t\t\t<arg value=\"Default-812h@3x~iphone.png\"/>\t\t\t\t\t<!-- ", "iphone x (portrait) -->\n\t\t\t<arg value=\"Default-Landscape-812h@3x~iphone.png\"/>\t\t\t<!-- ", "iphone x (landscape) -->\n\t\t\t<arg value=\"Default-414w-736h@3x~iphone.png\"/>\t\t\t\t<!-- ", "iphone 6/7/8 plus (portrait) -->\n\t\t\t<arg value=\"Default-Landscape-414w-736h@3x~iphone.png\"/>\t<!-- ", "iphone 6/7/8 plus (landscape) -->\n\t\t\t<arg value=\"Default-Portrait~ipad.png\"/>\t\t\t\t\t<!-- ", "ipad 1/2 (portrait) -->\n\t\t\t<arg value=\"Default-PortraitUpsideDown~ipad.png\"/>\t\t\t<!-- ", "ipad 1/2 (portrait upside down) -->\n\t\t\t<arg value=\"Default-Landscape~ipad.png\"/>\t\t\t\t\t<!-- ", "ipad 1/2 (landscape left) -->\n\t\t\t<arg value=\"Default-LandscapeRight~ipad.png\"/>\t\t\t\t<!-- ", "ipad 1/2 (landscape right) -->\n\t\t\t<arg value=\"Default-Portrait@2x~ipad.png\"/>\t\t\t\t\t<!-- ", "ipad 3/air (portrait) -->\n\t\t\t<arg value=\"Default-LandscapeLeft@2x~ipad.png\"/>\t\t\t<!-- ", "ipad 3/air (landscape left) -->\n\t\t\t<arg value=\"Default-LandscapeRight@2x~ipad.png\"/>\t\t\t<!-- ", "ipad 3/air (landscape right) -->\n\t\t\t<arg value=\"Default-Portrait@2x.png\"/>\t\t\t\t\t\t<!-- ", "ipad pro (portrait) -->\n\t\t\t<arg value=\"Default-Landscape@2x.png\"/>\t\t\t\t\t\t<!-- ", "ipad pro (landscape) -->\n\t\t\t<arg value=\"-C\"/>\n\t\t\t<arg value=\"${output.path}\"/>\n\t\t\t<arg value=\"TrainTimes.swf\"/>\n\t\t</java>\n\t</target>\n\t<target name=\"build-android\" depends=\"build-air-swf\">\n\t\t<echo message=\"Packaging TrainTimes.apk\"/>\n\t\t<java jar=\"${adt}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"true\">\n\t\t\t<arg value=\"-package\"/>\n\t\t\t<arg value=\"-target\"/>\n\t\t\t<arg value=\"apk-captive-runtime\"/>\n\t\t\t<arg value=\"-storetype\"/>\n\t\t\t<arg value=\"pkcs12\"/>\n\t\t\t<arg value=\"-keystore\"/>\n\t\t\t<arg value=\"${android.certificate.path}\"/>\n\t\t\t<arg value=\"-storepass\"/>\n\t\t\t<arg value=\"${android.certificate.password}\"/>\n\t\t\t<arg value=\"${output.path}/TrainTimes.apk\"/>\n\t\t\t<arg value=\"source/TrainTimes-app.xml\"/>\n\t\t\t<arg value=\"-C\"/>\n\t\t\t<arg value=\"${icon.path}\"/>\n\t\t\t<arg line=\"icon29.png icon48.png icon50.png icon57.png icon58.png icon72.png icon87.png icon96.png icon100.png icon114.png icon128.png icon144.png icon180.png\"/>\n\t\t\t<arg value=\"-C\"/>\n\t\t\t<arg value=\"${output.path}\"/>\n\t\t\t<arg value=\"TrainTimes.swf\"/>\n\t\t</java>\n\t</target>\n\t<target name=\"install-android\">\n\t\t<echo message=\"Installing TrainTimes.apk\"/>\n\t\t<java jar=\"${adt}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"false\">\n\t\t\t<arg value=\"-uninstallApp\"/>\n\t\t\t<arg value=\"-platform\"/>\n\t\t\t<arg value=\"android\"/>\n\t\t\t<arg value=\"-appid\"/>\n\t\t\t<arg value=\"com.feathersui.examples.", "TrainTimes\"/>\n\t\t</java>\n\t\t<java jar=\"${adt}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"true\">\n\t\t\t<arg value=\"-installApp\"/>\n\t\t\t<arg value=\"-platform\"/>\n\t\t\t<arg value=\"android\"/>\n\t\t\t<arg value=\"-package\"/>\n\t\t\t<arg value=\"${output.path}/TrainTimes.apk\"/>\n\t\t</java>\n\t</target>\n\t<target name=\"install-ios\">\n\t\t<echo message=\"Installing TrainTimes.ipa\"/>\n\t\t<java jar=\"${adt}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"false\">\n\t\t\t<arg value=\"-uninstallApp\"/>\n\t\t\t<arg value=\"-platform\"/>\n\t\t\t<arg value=\"iOS\"/>\n\t\t\t<arg value=\"-appid\"/>\n\t\t\t<arg value=\"com.feathersui.examples.", "TrainTimes\"/>\n\t\t</java>\n\t\t<java jar=\"${adt}\" dir=\"${basedir}\" fork=\"true\" failonerror=\"true\">\n\t\t\t<arg value=\"-installApp\"/>\n\t\t\t<arg value=\"-platform\"/>\n\t\t\t<arg value=\"iOS\"/>\n\t\t\t<arg value=\"-package\"/>\n\t\t\t<arg value=\"${output.path}/TrainTimes.ipa\"/>\n\t\t</java>\n\t</target>\n</project>" ]
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[ "Market Research Store\n\nMarket Research Store: has added latest report on \"Global Flooring Market Outlook (2014-2022)\" in their database.", "\n\nDeerfield Beach, FL -- (SBWIRE) -- 10/29/2015 -- The Global Flooring market accounted for $246 billion in 2014 and it is projected to reach $367.82 Billion by 2022, growing at a CAGR of 5.16% from 2014 to 2022. ", "Rapid focus on break-through flooring that is long-lasting in nature is expected to drive market growth. ", "Augmented insulation demand is also expected to give thrust to the market. ", "Changing customer lifestyles, growing demand for insulation and surging demand in the construction industry are the major drivers. ", "New trends, innovations and availability of several designs have considerably driven flooring market growth. ", "Presently, consumers are resorting to more cost-effective and eco-friendly materials, which is also expected to positively impact flooring market growth. ", "Accessibility of durable construction solutions that require low maintenance is to spur the demand for flooring solutions. ", "Customer knowledge and their readiness to use the product are likely to fuel the market growth.", "\n\nThe Flooring market is segmented into Material, Flooring Systems, Applications and Regions. ", "Depending on the type of materials the market is further classified into Carpet, Ceramic Tile, Hardwood, Laminates, Stone, Vinyl, and other Resilient. ", "On the basis of Flooring systems market is classified into Hard Flooring Systems and Raised Flooring Systems. ", "Depending on applications it is segregated into Residential, Commercial and Industrial. ", "Residential segment was the largest application area in 2014, accounting for over half of the market volume. ", "Owing to the increasing demand from the construction industry, increased home improvement and renovation projects, the market for flooring products in residential applications is expected to witness high growth during the forecast period.", "\n\nGeographically flooring market is segmented into North America, Europe, Asia Pacific and Rest of the World (ROW). ", "The increased affordability, rising urbanized population, and increase in industrialization in recent years are the favorable factors for the market growth in Asia Pacific region." ]
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[ "Q:\n\nCan I use a rental airplane to conduct air tours?", "\n\nCan a commercial pilot perform non-stop air tour operations under part 91 within 25SM of the airport using a rental airplane from the FBO? ", "\nI noticed that in the LOA application, the operation needs to provide:\n\nType of aircraft, registration number(s), and make/model/series;\n\nI wonder if this has to be the operator's own aircraft?", "\n\nA:\n\nBeyond the aviation angle of this question there are legal liability and insurance concerns common to any business that ought to be addressed. ", " Any person renting equipment ostensibly for personal use, but in reality is using it to run a business on the side, ought to have a commercial lease agreement in place with the owner of the equipment. ", " Have you spoken with the FBO about your plans?", "\nRegarding aviation specifics, these sort of questions have come up before and the CFRs don't offer much in the way of ownership requirements for aircraft involved in commercial operations. ", " Own vs lease just doesn't seem too critical from an operational standpoint as far as the Feds are concerned. ", " I won't start another \"holding out\" discussion here, but you should definitely talk to the FBO about your plans before moving forward with this idea.", "\n\n" ]
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[ "Im considering purchasing the above mentioned wheelset for a new build. ", "I'm having trouble finding information on them online. ", "At 1080gr for the set its surprising there is little to no mention of them on this board.", "\n\nThey're used by Astana so they are no secret in the peleton. ", "If anyone has any feedback on them please pitch in.", "\n\nEDIT: By the way I have received a direct quote from Corima of 2900euros. ", "A few english online retailers are selling them for 2200£ a set.", "\n\nthese are some of the best wheels I have owned. ", "They are incredibly stiff, roll very fast, and have very little to no effect in crosswinds. ", "For the weight they seems to roll forever which I like. ", "Seems as other lightweight wheels feel as if you have to work really hard to keep the speed up. ", "Oh and they are drop dead sexy!!!", "\n\nI'm riding the new 47mm MCC S+'s and braking with the Corima pads is on par with my Zipp FC's. ", "I don't ride in the wet [yes I know i'm soft but I ride for pleasure and not for pay] so I can't give feedback on that scenario\n\nHow do they do in wet braking? ", "They don't seem to have a textured braking surface so quite curious if they're reliable in the rain.", "\n\nIf you buy them, do not play around with different brake pads!!Only pad allowed is the standard Corima pad.", "I was told by Corima, SwissStop pads may cause burns in the rims surface layer (then those rims are smoked).", "\n\nWho is online\n\nUsers browsing this forum: No registered users and 6 guests\n\nYou cannot post new topics in this forumYou cannot reply to topics in this forumYou cannot edit your posts in this forumYou cannot delete your posts in this forumYou cannot post attachments in this forum" ]
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[ "The campaign of Sen. Bernie Sanders (I-Vt.) ", "was optimistic after winning a handful of Super Tuesday states, stressing that Hillary Clinton probably saw her best primary day with a schedule ahead that should work in Bernie’s favor as delegates continue to be divided.", "\n\nCampaign manager Jeff Weaver told reporters this morning that they shot for five states and “got 4.9,” demonstrating they “still have the momentum.”", "\n\nWeaver also highlighted Sanders’ success with the “critical bedrock of this campaign” — fundraising from small donors in the absence of a super PAC. ", "Sanders raised more than $42 million in February, the most raised in a month by any candidate in this election cycle. ", "That haul broke down to more than 1.4 million contributions averaging $30.", "\n\nThe Sanders’ camp was especially grateful that donations continued to pour in after Clinton stomped Bernie in South Carolina.", "\n\n“In terms of fundraising, Clinton cannot win a fair fight,” Weaver said.", "\n\nSanders won most of his target states: 58.9 percent to Hillary’s 40.4 percent in Colorado, 61.7 percent to Hillary’s 38.3 percent in Minnesota, 51.9 percent to Hillary’s 41.5 percent in Oklahoma, and a whopping 86.1 percent to 13.6 percent in Bernie’s home state, Vermont.", "\n\nTheir fifth target state, Massachusetts, seemed to be in play much of the night, but Clinton pulled out a 50.1 percent to 48.7 percent victory, effectively splitting delegates there.", "\n\nSanders’ senior advisor Tad Devine noted that Clinton defeated Barack Obama by “substantial double-digit margins” in Massachusetts eight years ago.", "\n\n“We did not target 11 states yesterday,” Devine stressed. “", "We understand that we have a long road ahead of us we have to take if we want to win the nomination” — therefore, “allocation of resources” is key.", "\n\nDevine added that Clinton’s best electoral days could be behind her. “", "Super Tuesday was the single best day on the calendar for Hillary Clinton,” he said, emphasizing “you will not win a nomination in the Democratic Party unless you consistently win throughout the calendar.”", "\n\n“A lot of thing will happen in the weeks and months ahead,” Devine predicted, stressing the “dynamic nature of this process” and how “questions will be raised” about Clinton’s general election viability if she doesn’t have consistent wins from here on out.", "\n\nBecause of superdelegates who changed their allegiance from Hillary to Obama the last time out — more than 120 “changed allegiance” before the convention — and pledged delegates who no longer will be bound, “we believe Bernie Sanders will have more delegates than Hillary Clinton.”", "\n\nDevine also stressed that Sanders is a “much stronger candidate” in general election polls, “beating Donald Trump by a more decisive margin” than Hillary. “…", "If they want to beat Trump, we’re going to need Bernie to be the nominee.”", "\n\nOn the schedule moving forward, Devine predicted the Maine caucus on Sunday “should be good for us,” while Michigan next Tuesday is a “critical showdown” where Sanders is stressing that he’s the “consistent opponent of job-gutting trade deals.”", "\n\nOn Sanders’ task of trying to court minority voters, Devine said it’s “pretty clear that that the African-American community is not monolithic” and the senator can still make inroads with his “incredible personal story” of participation in the Civil Rights Movement and telling voters “his agenda for the future is simply better.”", "\n\n“We think we’re already doing better with Latino voters,” he said, highlighting that even though they don’t have exit polling data from Colorado “I don’t know how you win Colorado without very strong support from Latino voters in that state.” ", "The campaign later sent out a breakdown stressing that Sanders “convincingly carried 10 of the top 15 Latino counties in Colorado, many by wide margins.”", "\n\nTurnout in Colorado was so huge people they got reports of people caucusing in parking lots because fire officials deemed buildings to be overflowing with voters.", "\n\nDevine acknowledged Trump “is going to run a vicious campaign — I think we all recognize his tactics.” ", "He underscored Sanders’ strong polling on “critical attributes” to voters, including integrity and caring about people. ", "He also said Bernie is stronger than Hillary on bringing in independent voters, which would be particularly important if Clinton went up against Sens. ", "Marco Rubio (R-Fla.) or Ted Cruz (R-Texas), whom she trails in the polls while leading Trump.", "\n\nSanders is also “bringing in millions of young people,” which is “a huge contribution Bernie Sanders can make not just to Hillary Clinton but to every Democrat.”", "\n\n“She has a substantial advantage — we believe we can make that up between now and June… we still think we have a winning hand in this game and we’re going to play it for a while.”", "\n\nSanders declared in a statement early this morning that his campaign is “just getting started” as they move on to Maine and Michigan with their war chest. “", "We’re going all the way to the Democratic National Convention in Philadelphia and beyond,” the senator said.", "\n\n“Tomorrow, I look forward to a contest this fall between democracy and demagoguery, between ordinary Americans and the oligarchs,” Sanders added. “", "I look forward to the chance for our people-powered campaign to show Donald Trump that the United States of America belongs to all of us and not just billionaire bullies.”" ]
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[ "Political Will Disappearing, New Jersey’s ARC Project Could be On the Way Out\n\nJust to be clear from the start, there are a lot of things to dislike about New Jersey’s Access to the Region’s Core (ARC) project. ", "Despite an expected construction cost of $8.7 billion, it won’t provide New Jerseyans a direct ride to Manhattan’s east side but instead duplicate the existing path to Penn Station. ", "Instead of taking advantage of excess capacity at that west side terminal, the project will force customers into a massive (and very expensive) new terminal deep underground.", "\n\nEven so, the expansion of direct commuter rail services from New Jersey into Manhattan will represent a significant mobility benefit for a large percentage of the suburban workforce, now required to make time-consuming transfers to get into New York’s central business district. ", "Nine miles of new tunnels under the Palisades and Hudson River would double train capacity and allow NJ Transit to shuttle in by commuter rail almost 100,000 additional commuters daily by 2018. ", "And there is evidence that many of the flaws of the program’s design are either unchangeable or could be improved upon in coming years.", "\n\nThose big expansions in service promised by the project make this week’s 30-day shutdown of the project by New Jersey Governor Chris Christie (R) quite disappointing. ", "Citing fears that the state cannot afford the project and that construction costs will continue to mount, Mr. Christie called a moratorium on the awarding of new contracts.", "\n\nARC entered the construction phase last year, with a commitment of $3 billion from the federal government, $3 billion from the Port Authority of New York and New Jersey, and $2.7 billion from the State of New Jersey. ", "Governor Christie was in favor of the project in April of this year, at least on paper. ", "Washington has never before agreed to spend so much money on any individual transit project anywhere in the nation.", "\n\nThough the federal government has not highlighted any specific concerns about cost overruns on the ARC program, it has warned New Jersey that financing difficulties with projects in New York City — the Second Avenue Subway, Fulton Street Transit Center, and East Side Access — could be repeated across the river. ", "Mr. Christie is expected to meet with federal officials later this month to discuss problems with the program. ", "Though this delay is worrisome, it does not necessarily mean that the ARC tunnel has been canceled. ", "Indeed, it is worth noting that it is possible that the project could resume with no changes in a month.", "\n\nGovernor Christie, who has never been particularly realistic about the condition of his state’s transportation financing mechanisms, has posited in recent days the argument that car drivers are already being asked to increase their financial contributions to an unreasonable extent compared to transit users. ", "In addition, the state’s Transportation Trust Fund, which provides the majority of contributions to both highway and transit capital projects, faces bankruptcy. ", "Some have suggested that Mr. Christie’s main motivation in delaying the ARC project, and potentially eventually canceling it, is to resuscitate the Fund.", "\n\nHowever, the governor’s assessment is incorrect; transit users in New Jersey have in fact seen a larger increase in fares than drivers have seen in tolling. ", "In addition, NJ Transit has been forced to reduce operations on some services recently because of inadequate state funding.", "\n\nThe elimination of the project would mean the forfeit of $3 billion in federal dollars, which would likely be transferred to other parts of the country looking for a major investment in new transportation programs. ", "The use of the Port Authority’s $3 billion commitment, if not used for the ARC tunnel, has not been established or even discussed openly.", "\n\nMr. Christie, a conservative Republican, has never been one to take up the mantel of increased government investment, so it shouldn’t be much of a surprise that in the face of a difficult funding environment he has chosen to put ARC on hold. ", "If he were truly committed to the program, he arguably could have begun a reevaluation of the project’s fundamentals even as construction moved forward. ", "But the delay indicates much less political support for the scheme than was previously assumed to be the case. ", "And the governor’s attempt to approach the decision in a car-versus-transit users frame suggests that he has no real love for public transportation.", "\n\nFor the state’s commuters, this lack of will to find the means to fund the proposal will result in years more of long travel times and little relief for the overbooked North River Tunnel, whose two tracks simply aren’t enough to carry all the NJ Transit commuter and Amtrak intercity trains the New York area needs to remain economically competitive.", "\n\nFor those who suggest that a delay in the project could mean a rethink significant enough to mend the flaws in the current proposal, I suggest a consideration of what has occurred to other New York-area transit projects when they were put on hold because of a lack of adequate funds. ", "The Second Avenue Subway, under construction in the early 1970s, has seen its plans reduced from an eight-mile, sometimes four-track line to a two-mile, two-track spur. ", "The prolongation of the Hudson-Bergen light rail system into Bergen County has morphed into a possible future diesel light rail line.", "\n\nWould a helpful reevaluation of the ARC project at this point — when construction has already begun and when plans are already drawn up — actually be beneficial in the long-term?", "\n\nThere are pros to this:\nThis might lead to an opportunity to connect Penn Station\nReduce spending on a giant underground labrynth\nThere are cons though:\nExpanding capacity into New York City will most likely be delayed.", "\nThere are federal dollars on the line\n\nMy understanding on the connection to the current Penn Station is that the # 7 line extension to the Javits Center on the far west side of Manhattan made it difficult (a higher than acceptable grade if I remember correctly) to connect to. ", "I don’t see how that could be changed but maybe the station under 34th St can be built in a way to allow for expansion to the East Side once the new Water Tunnel opens up.", "\n\nThat said, as a person from New Jersey, I personally don’t think this is a good move. ", "For all the reasons Yonah mentioned and the fact that costs will escalate as happens everywhere in the country.", "\n\nIt seems clear to me that ARC is dead. ", "I understand the RPA trying to avoid it being killed, but they shouldn’t tell porkies, even in a good cause.", "\n\n“Dozens of buildings would” NOT “have to be razed. ", "The obvious alignment for cut and cover is W 31st St. A tunnel under the Hudson could continue bored at least to the Highline, probably to 11th Ave. ", "Cut and cover from 11th Ave. ", "along W. 31st St to some point east of Dyer Ave. (", "where the new tracks could be brought in to meet the existing tracks in the open cut between the Farley Building and the Ziggurat) wouldn’t be not massively disruptive.", "\n\nIt is NOT “inconceivable that the existing Penn Station could handle the additional people coming in via ARC.” ", "Penn Station’s trackage is severely underused. ", "Phase 1 of the Moynihan Station project will create new paths for passenger flow to and from the platforms. ", "The LIRR will be bringing many fewer trains into Penn Station once East Side Access is functional. ", "Fewer trains mean fewer passengers. ", "Penn Station’s current capacity issues are essentially passenger flow issues and those issues are being addressed. ", "The notion that a new station will handle 24-25 trains an hour using six stub tracks, while the existing station can’t handle that addition with its 21 existing tracks (only four of which are stub) and two more accessible from the Farley Building is fantasy.", "\n\nAgain, as I said somewhere, we could wish that the Hudson Tunnels would be built and connected to Penn Station (the designs and preliminary engineering diagrams for the connections *already exist* and have *passed EIS review*), and that the 34th St. Cavern was deferred.", "\n\nThat may be too much to hope for, but it’s worth pushing for because it *makes sense*.", "\n\nIt’s strange how so much money is spent on this project rather than creating an integrated plan for all the commuter rail systems going into New York; especially including through-routing. ", "Like Alon Levy detailed in some post on this blog a while back.", "\n\nWhile this project was far from perfect, anyone who thinks that any additional rail capacity across the Hudson will be built in the next 15 years is deluding themselves. ", "If this gets cancelled no new rail capacity will get built in the near future period. ", "This will not be good news for any large transit project. ", "If anything this is a glimpse of what is to come once the tea party anti government inspired GOP takes over part of congress and lots of states. ", "I’m going to bet transit and high speed rail projects will be up on the chopping block. ", "Sorry about the rant but this is becoming a new rallying cry just look at Wisconsin. ", "The Hudson crossing so desperately needs more rail capacity as it is a major transit chokepoint. ", "Id rather stand behind this than get nothing for twenty years.", "\n\nFrom what I understand, this is a very complicated project, not just because of the many stakeholders that have an interest in improved transit access between NJ and NYC (Amtrak, NJT, Port Authority, MTA, the states of NJ & NY and NYC, the feds), but also because of the dense infrastructure that has been built since the original Hudson river tunnels were built a 100 years ago.", "\n\nThe key problem, as I see it, is that the 2 existing Hudson river tunnels are at 100% capacity routinely during peak morning and afternoon periods and are absolutely critical to the main intercity rail corridor of the US, the NEC, and for many thousands of daily commuters from northern NJ to/from NYC. ", "If one of those 100 year old tunnels is found to have a serious problem that require it to be taken out of service for an extended period for repair, the damage to NEC and NJT operations would be epic. ", "The four East River tunnels provide more reserve capacity, because shutting down 1 of 4 tunnels is a much less worse situation than shutting down 1 of 2.", "\n\nAfter this many years of NJT controlled studies, changing the project at this late stage would result in years of delay. ", "But, still, maybe this should have been defined as a two stage national infrastructure project. ", "First, build 2 new tunnels that connect to the existing Penn station tracks along with a major upgrade to the station capacity under the umbrella of the Moniyhan station project. ", "This might not allow NJT to add the ~24 trains per hour additional capacity, but should allow both NJT and Amtrak to run more trains to NJ. ", "Fix the most critical weak link first.", "\n\nThen as stage 2, in 10+ years if the need is still there, build 2 more tunnels under the Hudson to a new underground station. ", "I would expect that a major chunk of the $8.7 billion cost is for building the Penn Station Extension because clearing out a huge cavern space deep under NYC with access shafts and passageways, air & service shafts, with platforms & tracks is a huge project. ", "But maybe the new underground station should not be next to Penn station; maybe instead build the new station further north near Grand Central or, if it is physically possible, next to the new LIRR complex under Grand Central.", "\n\nProblem is that this would be a national infrastructure project which would need considerable federal and state leadership. ", "Gov. Cristie of NJ does not come across as overly supportive of mass transit. ", "Which is odd in some ways, because the New Jersey economy, speaking at a state wide level, is probably the most transit dependent state in the US.", "\n\nAlan, if they build two new tunnels to the existing Penn Station, then they will never have a reason to build two deep level tunnels to a new station. ", "The cost of squeezing 24 tph out of a new tunnel pair is next to nothing. ", "Given current infrastructure, it requires either through-running, or slightly shorter turnaround times. ", "But given ESA, it would require nothing at all, as NJT would be able to use tracks vacated by the LIRR. ", "As an extra bonus, the LIRR platforms have more staircases than the NJT platforms, inherently allowing shorter dwell times.", "\n\nWhat’s the interlocking going to look like and operate? ( ", "Very difficult to have two trains occupy the same track at the same time, at least in our universe – in universes with more than three dimensions it may not be much of a problem ) Where are all the new passengers going to go?", "\n\nI took Adirondacker’s question as whether the new tunnels could connect through the interlocking with the platforms that LIRR currently uses (tracks 17-21). ", "If they come in from the south, adding crossovers in the dumb, obvious way connects the new tunnels just to tracks 1-13.", "\n\nThe new tunnels, the ones that will be built soon, won’t go anywhere near the current rat’s nest of switches in Penn Station. ", "They will be aiming trains at the current Penn Station or the annex west of Secaucus. ", "Many of the trains leaving the annex will never be on the Northeast Corridor.", "\n\nJim, there’s no need for NJT trains to use tracks 17-21. ", "The multi-staircase platforms go further to the south and include the middle Amtrak platform. ", "I forget how many of the middle platforms have 4-5 staircases – I’ll check my station map later tonight.", "\n\nAt any rate, it’s not mission-critical to connect the new tunnels to the northern tracks. ", "The old tunnels can already connect to them. ", "The advantage of having a single four-track crossing, with all trains heading into the same station, is that it’s easy to route trains partly on the old tunnel pair and partly on the new tunnel pair.", "\n\nIf New Jersey’s governor gets this project cancelled, he is shooting his state’s economy in the foot for the forseeable future while wasting many years of professional studies and professional services, all done by people that truly care about transportation. ", "It’s amazing how much damage one person without vision can do.", "\n\nIt strikes me that Christie may know more than we do, indeed more than NJT does, about the future volume of New Jersey Transit trains: how many trains NJT is going to be able to afford to run after all the budget cuts have been made.", "\n\nDoes anyone know if there’s been any sort of study of building just a single tunnel into the existing Penn Station, 2.7% grade and all, to be operated on a “morning in, evening out” basis? ", "Presumably NJT would have to work around that some of its equipment would have to exclusively use the North River tunnels and might have to procure additional relatively lightweight equipment to use through the new tube. ", "And obviously at least half the NJT trains coming in during AM peak would have to be stored east of the Hudson, in Sunnyside Yard or (since there’ll be a lot less LIRR trains after ESA) in Hudson Yards. ", "But it doesn’t seem impracticable on its face, and should be cheaper (boring one tube is not much more than half the cost of boring two and avoiding excavating a two avenue block long cavern saves a lot of money), even after allowing for the cost to NJT of procuring additional lightweight equipment for its electrified lines.", "\n\nAny new tunnel should function as a relief for the existing tunnels, for maintenance and repair. ", "It was a major drawback that ARC didn’t do that.", "\n\nIf they had completed ESA in the 70s or 80s perhaps. ", "The MTA is predicting that traffic will barely change in Penn Station. ( ", "I think that includes Metro North service. )", "\n\nAny new tunnel should function as a relief for the existing tunnels, for maintenance and repair.", "\n\nThere’s no reason why Amtrak trains can’t go to the new tracks. ", "If Amtrak decides they need to shut down both of the old tunnels they can do it, the trains will just have to arrive and depart on tracks 22-27.", "\n\nI’m not going to spend an afternoon dissecting Amtrak schedules. ", "I put Philadelphia to New Haven into their trip planner for next Tuesday. ", "There’s 21 trains. ", "Philadelphia to NY there are 46 trains and since the long distance trains won’t carry “local” traffic they don’t appear in the options.", "\n\nI wounder would there be any subway tunnels for the New York City subway tracks that run under the river from New Jersery into New York City. ", "What they could do is build a rail line to link the NEC into one of them and if the trains fit into the subway tunnels under the river they could have the trains run though a section of the subway system and then exit out of the subway system into the Hell Gate Bridge main line across the Hell Gate Bridge.", "\n\nI always wondered why, beyond cost and difficulty, the NYC subway system never served NJ more directly – if it were extended, NJT passengers could transfer directly to the subway in NJ and take that in to Manhattan. ", "Is there some other reason, such as legislative, etc, that precludes the subway from leaving NYC city limits? ", "The el, in Chicago, for instance, serves six suburbs directly.", "\n\nNJT and/or LIRR trains will not fit into NYC subway tunnels as they are too high and long.", "There would also be serious power issue with the NJT trains. ", "The NY subway tunnels were not designed to fit overhead catenary. ", "In addition there are the numerous FRA and union work rule issues that would render the sharing of the same tracks by mainline railroad and rapid transit trains virtually impossible.", "\nNYC subway lines could be readily extended into NJ. ", "There are no legislative prohibitions to my knowledge. ", "Both the “L” line on 14th St and the #7 would be prime candidates. ", "Also, the GWB was designed to carry trains on the lower level. ", "As a result the tail tracks of the 8th Ave local (north of 168th St) were built with provision for a possible GWB extension.", "\n\nPATH runs on the same loading gauge as the IRT. ", "However, there’s no political or institutional interest in merging the systems. ", "The local perception is that the subway is for New Yorkers, and the inner parts of Jersey should be served with PATH.", "\n\nThe NJT/PATH connection is actually pretty good. ", "At Newark, it’s cross-platform in one direction, though there are faregates in between. ", "It’s the easiest way to get between NJT’s Newark Division and Lower Manhattan. ", "However, the NJT/PATH/subway connection is really bad, because WTC/Fulton is a maze.", "\n\nThe westbound connection from PATH to NJTransit isn’t bad, one flight down the stairs or ramps to the track you want.", "\nNot terrible at Herald Square either.", "\n\nPATH is at capacity at rush hour now. ", "Direct access for NJTransit to the Fulton Transit center – a shuttle that runs between Jamaica and Newark or Newark Airport. ", "Or run the suburban NJ trains all the way to Jamaica. ", "Assuming 25kV catenary, Amtrak could serve Fulton, Brooklyn and Jamaica.", "\n\nIt seems more connections might ease some congestion and provide cross region commuting (wasn’t there a proposal here about a regional system?). ", "NYCTA maps always seem to ignore NJ overall. ", "And it would be a great make work project to do all this, dreaming sure is fun….", "\n\nThe Amtrak service yard for Penn Station (NYP) is Sunnyside in Queens. ", "The trains starting at NYP that head south go from Sunnyside to NYP. ", "If Amtrak were to use Penn Station Extension, the trains from Sunnyside would have to go through NYP, through the North River tunnels, switch in northern NJ, and do a reverse move through the new tunnels to the new underground station. ", "This would be TWO non-revenue moves through the busy tunnels under the Hudson river. ", "Not very practical. ", "Ok, maybe Amtrak could store the trains in Philly or use NJ Transit facilities in NJ, but Sunnyside is Amtrak’s major service and storage yard.", "\n\nThe Port Authority isn’t really an independent entity. ", "It’s controlled equally by the states of New Jersey and New York, which means, in effect, it’s controlled by the two governors. ", "So we won’t see an end run around Christie on this one.", "\n\nWe might see the Port Authority’s Hudson tunnels contribution diverted half and half to other projects in the two states. ", "It might be enough to cover the latest round of cost-overruns on the Second Avenue Subway. ", "And I’m sure similar spending opportunities can be found in Jersey.", "\n\nI don’t think Christie cares one way or another about the tunnel. ", "He cares about the money. ", "As long as no State money goes to it, it can be built. ", "If New York wants it, then the PA might want to continue (then again, they might not). ", "If the PA money doesn’t go to this, the Goethals Bridge replacement is probably high on the list of things the PA could fund instead.", "\n\nI don’t know — don’t underestimate the ability of certain people to be rabidly hostile to any public transportation project whatsoever, regardless of the cost/benefit ratio, regardless of the money. ", "I don’t know if Christie is one of those, but he might be.", "\n\nYonah tweeted (on the sidebar) that NJT sources are saying that Christie wants to defund ARC to divert the $2.7B NJ money to other transportation needs.", "\n\nSo he might see the PA continuing a scaled back tunnel as a win-win. ", "He gets his $2.7B back to spend on the things he wants to spend it on and a tunnel gets built anyway. ", "A victory for hard-headed conservatism!", "\n\nThe $2.7B Jersey share can be transferred. ", "The $3B Port Authority share can’t be redirected at the NJ Governor’s whim, but will have to be spent on something related to New York/New Jersey, and the $3B FTA share is Federal money and will be redirected to other transit projects (not necessarily in New Jersey, nor even in the Northeast).", "\n\nThis decision by the governor reinforces the ideology that the market can solve all problems and public government is not the answer, but it ignores the fact that private corporate solutions result in a de facto government by only providing a product that will sell, not necessarily one that is needed.", "Christie’s answer is more private solutions to public problems: more private transportation, less public transportation,which ignores the long term cost by not adequately funding transit infrastructure, hence more consumer spending over time.", "\n\nThe Pennsyvinia Railroad really got a lot of bang for their buck with those two 1910’s built railroad tunnels. ", "They outlasted four to five railroads and are right now the only way by rail for main line over head wired powered trains.", "\n\nI some how think this is going to be a poltical fescio in that they most likely are going to eather have a 12 billon dollar project by the end of it or they are going to stop work on it right in the middle of working on it and the river is going to find away to get into it and turn it into a two billon dollar fish tank ortament.", "\n\nFor the $6 or $7 billion that will ultimately be spent on the LIRR/Grand Central connection and the $8.7 billion proposed here wouldn’t it have been far cheaper to build additional track under 34th St. (or 33rd or 35th) and a new station on the east side along the route that NJTransit and LIRR trains already use between Sunnyside and Penn Station?", "\n\nFor $15 billion it seems to me like you could’ve had all that plus you could’ve brought Metro North trains down to 34th St. and had a true regional rail system.", "\n\nAnother tunnel under the Hudson is still needed but it seems incredibly shortsighted to me to have NJTransit and LIRR/MTA look at and fund these as separate projects and try to jam 100,000+ more people (each) into already crowded stations when most riders are probably looking for subway/surface connections anyway.", "\n\nI was thinking the same thing. ", "If there are track capacity problems due to all the trains terminating at Penn Station, then route them through downtown. ", "If then there are passenger capacity problems at Penn Station – both because the labyrinth doesn’t support that many people, and because everybody exiting the trains there causes long dwell times which requires longer headway between trains – then add another station at the East Side. ", "This way not everybody has to go through Penn Station, which would reduce congestion on the one hand and might mean better connections (=fewer transfers) for many passengers on the other.", "\n\nI agree with Christie – why not use the funds to increase transportation in New Jersey – why make it easier for people to get to New York City? ", "Why not put the money into improving transit in Newark and other of New Jersey’s large urban areas, and seek to have business relocate over here? ", "Why should New Jersey be relegated to a bedroom community for New York City – let’s change things here to make the state attractive to business. ", "Like, maybe, lowering taxes, getting rid of anti-business policies and regulations.", "\n\nNo Republican *ever* gets rid of anti-business policies and regulations.", "\n\nThis is one of the dirty little secrets of Republican politicians for the last few decades. ", "They love to get rid of regulations which actually help people’s health, but when it comes to onerous paperwork which puts small businesses at a disadvantage to big business — well, they love that paperwork too. ", "They use small businesses as a stalking horse, but they implement policies designed to make it hard for small businesses to compete with big businesses.", "\n\nIt’s very consistent. ", "It’s unfortunate that there isn’t an actual party which backs small business (Democratic politicans generally don’t think about the impact on small business, while Republican politicians actively attempt to destroy small business.)", "\n\nRepublicans are also well-known for cutting taxes on the richest and the largest corporations, while *raising* taxes and fees on the poor, the middle class, and small businesses. ", "It’s standard operating practice. ", "Therefore, Republican promises to “cut taxes” are generally a big fat scam, unless you’re Exxon Mobil.", "\n\nIt’s an impressive set of scams. ", "A party which did what the Republicans *claim* to support for small business would be useful. ", "But in practice, the Republican Party does the exact opposite, being filled with politicans who do whatever they can to destroy small business." ]
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[ "1. ", "Field of the Invention\nThe present invention relates to in vivo cell growth inhibitors, and more particularly to an in vivo cancer cell growth inhibitor formulated to inhibit colon cancer cell growth in mammals. ", "Specifically, the present invention relates to an in vivo colon cancer cell growth inhibitor or naturaceutical composition formulated with Morinda Citrifolia from the Indian Mulberry plant.", "\n2. ", "Background of the Invention and Related Art\nCancer of the colon is a deadly form of cancer affecting millions of people. ", "Research is ongoing in the fight against cancer, with hopes of one day finding a complete cure for this ugly disease. ", "Until a complete cure is found, researchers, medical professionals, and several interested groups are furthering efforts to treat those currently suffering from the disease. ", "As such, information and treatment possibilities are continuously being updated. ", "The following represents the most current and up-to-date information pertaining to cancer of the colon.", "\nCancer of the colon is a disease in which malignant cells proliferate in the tissues of the colon, a vital organ of the digestive system of the body. ", "As the purpose of the digestive system is to remove nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) from the foods eaten and to store the waste until it passes out of the body, the colon plays a critical role in the overall function of our body. ", "The digestive system is made up of the esophagus, stomach, and the small and large intestines. ", "The first 6 feet of intestine is called the large intestine or colon.", "\nSeveral tests may be conducted to determine whether any abnormal genes or growths are present within the tissues of the colon. ", "If tissue that is not normal is found, a small portion of the tissue may be removed to determine whether there are any cancerous cells present in the tissue.", "\nIf cancerous cells are discovered, the prognosis, or chance of recovery and choice of treatment depend on several factors, namely, the stage of the cancer (e.g. whether it is just in the inner lining of the colon or if it has spread to other places), and the patient's general state of health. ", "After treatment, a blood test (to measure amounts of carcinoembryonic antigen or CEA in the blood) and x-rays may be done to see if the cancer is in remission.", "\nThe various stages of cancer serve to categorize the degree of growth of cancerous cells, as well as to determine whether the cancer has spread to other parts of the body. ", "Knowing the stage of the disease will assist a physician in effectively planning further treatment.", "\nThere are currently three primary treatments available for patients with cancer of the colon. ", "These treatments depend upon the stage of the cancer and the health of the individual seeking the treatment. ", "Each one is briefly discussed.", "\nFirst, cancerous cells may be surgically removed. ", "This involves an expensive and dangerous process where the cancer is physically cut out and removed from the body. ", "Surgery is the most common treatment of all stages of cancer of the colon. ", "A doctor may surgically remove cancer from the colon using one of the following: if the cancer is found at a very early stage, the physician may laparoscopically excise the cancer. ", "If the cancer is larger, the physician may excise the affected tissue and a small amount of healthy tissue around it (bowel or colon resection). ", "The healthy parts of the colon are then sewn together (anastomosis). ", "The physician will also take out lymph nodes near the intestine and look at them under the microscope to see if they contain cancer. ", "If the physician is not able to sew the colon back together, he or she will make an opening (stoma) on the outside of the body for waste to pass out of the body. ", "This is called a colostomy. ", "Sometimes, the colostomy is only needed until the colon has healed, and then it can be reversed. ", "However, the doctor may have to take out the entire lower colon and the colostomy is permanent. ", "If a patient has a colostomy, a special bag will need to be worn to collect body wastes. ", "This special bag, which sticks to the skin around the stoma with a special glue, can be thrown away after it is used. ", "This bag does not show under clothing, and most people take care of these bags themselves.", "\nThe next form of treatment is radiation therapy. ", "Radiation therapy involves using high-dose x-rays or other high energy radiation to kill the cancer cells. ", "Radiation therapy is the use of x-rays or other high-energy rays to kill cancer cells and shrink tumors. ", "Radiation may come from a machine outside the body (external radiation therapy) or from putting materials that contain radiation through thin plastic tubes (internal radiation therapy) in the intestine area. ", "Radiation can be used alone or in addition to surgery and/or chemotherapy.", "\nChemotherapy is another possible treatment. ", "This procedure uses drugs to kill cancerous cells. ", "Chemotherapy may be administered through capsules, or intravenously. ", "A patient may be given chemotherapy through a catheter while a small pump gives the patient constant treatment over a period of weeks. ", "Chemotherapy is a systemic treatment because the drug enters the bloodstream, travels through the body, and can kill cancer cells outside the colon. ", "If the cancer has spread to the liver, the patient may be given chemotherapy directly into the artery going to the liver. ", "If the doctor removes all of the cancer that can be seen at the time of the operation, the patient may be given chemotherapy after surgery to kill any cancer cells that are left. ", "Chemotherapy given after an operation to a person who has no cancer cells that can be seen is called adjuvant chemotherapy.", "\nThe following five stages are used to determine the progression of cancer of the colon.", "\nStage 0 cancer of the colon, or carcinoma in situ, is very early cancer. ", "The cancer is found only in the innermost lining of the colon. ", "Treating stage 0 colon cancer may involve local excision or simple polypectomy to remove all the cancer, or surgery (bowel resection).", "\nStage I cancer of the colon, or Dukes A colon cancer, is more progressive in that the cancer has spread beyond the innermost lining of the colon to the second and third layers and involves the inside wall of the colon, but has not spread to the outer wall of the colon or outside the colon. ", "Treating stage I colon cancer usually involves surgery (bowel resection) to remove the cancer and join the cut ends of the bowel.", "\nStage II cancer of the colon, or Dukes B colon cancer, is cancer that has spread outside the colon to nearby tissue, but has not yet gone into the lymph nodes—small, bean-shaped structures found throughout the body that produce and store cells that fight infection. ", "Treating stage II colon cancer may involve surgery (bowel resection) to remove the cancer, clinical trials of chemotherapy, radiation therapy, or biological therapy following surgery, or if the tumor has spread to nearby tissue, a patient may also receive chemotherapy and/or radiation therapy following surgery.", "\nStage III cancer of the colon, or Dukes C colon cancer, is cancer that has spread to nearby lymph nodes, but not yet to other parts of the body. ", "Treating stage II colon cancer usually involves surgery (bowel resection) to remove the cancer, followed by chemotherapy. ", "In addition, clinical trials of chemotherapy, radiation therapy, and/or biological therapy following surgery may also be employed.", "\nStage IV cancer of the colon, or Dukes D colon cancer, is cancer that has spread to other parts of the body. ", "This is the most severe of the stages. ", "Treating stage IV colon cancer may involve surgery to remove the cancer or to make the colon go around the cancer so that it can still work; surgery to remove parts of other organs such as the liver, lungs, and ovaries, where the cancer may have spread; chemotherapy to relieve symptoms; clinical trials of chemotherapy or biological therapy; and radiation therapy to relieve symptoms.", "\nWhile these efforts alleviate, and in some instances remove, the threat of colon cancer in an individual, these treatments can be extremely costly and unpredictable. ", "Moreover, these treatments can be dangerous, not to mention putting incredible amounts of physical strain upon the individual." ]
{ "pile_set_name": "USPTO Backgrounds" }
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[ "A comparison of hepatoprotective activities of aminoguanidine and N-acetylcysteine in rat against the toxic damage induced by azathioprine.", "\nAzathioprine (AZA) is an important drug used in the therapy of autoimmune system disorders. ", "It induces hepatotoxicity that restricts its use. ", "The rationale behind this study was the proven efficacy of N-acetylcysteine (NAC; a replenisher of sulfhydryls) and reports on the antioxidant potential of aminoguanidine (AG; an iNOS inhibitor), that might be useful to protect against the toxic implications of AZA. ", "AG (100 mg/kg; i.p.) ", "or NAC (100 mg/kg; i.p.) ", "were administered to the Wistar male rats for 7 days and after that AZA (15 mg/kg, i.p.) ", "was given as a single dose. ", "This caused an increase in the activity of hepatic aminotransferases (AST and ALT) in the serum 24 h after AZA treatment. ", "AZA (7.5 or 15 mg/kg, i.p.) ", "also caused an increase in rat liver lipid peroxides and a lowering of reduced glutathione (GSH) contents. ", "In the other part of experiment, protective effects of AG and NAC were observed on AZA induced hepatotoxicity. ", "NAC significantly protected against the toxic effects produced by AZA. ", "Pretreatment with NAC prevented any change in the activities of both the aminotransferases after AZA. ", "This pretreatment also resulted in a significant decline in the contents of lipid peroxides and a significant elevation in GSH level was evident after AZA treatment. ", "In the group with AG pretreatment the activities of AST and ALT did not increase significantly after AZA when compared to control. ", "However, the lipid peroxides and GSH levels did not have any significant difference when compared to AZA group. ", "These observations also indicate that the improvement in the GSH levels by NAC is the most significant protective mechanism rather than any other mechanistic profile. ", "The protective effect of AG against the enzyme leakage seems to be through the liver cell membrane permeability restoration and is independent of any effects on liver GSH contents." ]
{ "pile_set_name": "PubMed Abstracts" }
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[ "//----------------------------------------------------------------------------\n//\n// TSDuck - The MPEG Transport Stream Toolkit\n// Copyright (c) 2005-2020, Thierry Lelegard\n// All rights reserved.", "\n//\n// Redistribution and use in source and binary forms, with or without\n// modification, are permitted provided that the following conditions are met:\n//\n// 1. ", "Redistributions of source code must retain the above copyright notice,\n// this list of conditions and the following disclaimer.", "\n// 2. ", "Redistributions in binary form must reproduce the above copyright\n// notice, this list of conditions and the following disclaimer in the\n// documentation and/or other materials provided with the distribution.", "\n//\n// THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS \"AS IS\"\n// AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE\n// IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE\n// ARE DISCLAIMED. ", "IN NO EVENT SHALL THE COPYRIGHT OWNER OR CONTRIBUTORS BE\n// LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR\n// CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF\n// SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS\n// INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN\n// CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE)\n// ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF\n// THE POSSIBILITY OF SUCH DAMAGE.", "\n//\n//----------------------------------------------------------------------------\n\n#include \"tsBAT.h\"\n#include \"tsBinaryTable.h\"\n#include \"tsTablesDisplay.h\"\n#include \"tsPSIRepository.h\"\n#include \"tsPSIBuffer.h\"\n#include \"tsDuckContext.h\"\n#include \"tsxmlElement.h\"\nTSDUCK_SOURCE;\n\n#define MY_XML_NAME u\"BAT\"\n#define MY_CLASS ts::BAT\n#define MY_TID ts::TID_BAT\n#define MY_PID ts::PID_BAT\n#define MY_STD ts::Standards::DVB\n\nTS_REGISTER_TABLE(MY_CLASS, {MY_TID}, MY_STD, MY_XML_NAME, MY_CLASS::DisplaySection, nullptr, {MY_PID});\n\n\n//----------------------------------------------------------------------------\n// Constructors and assignment.", "\n//----------------------------------------------------------------------------\n\nts::BAT::BAT(uint8_t vers, bool cur, uint16_t id) :\n AbstractTransportListTable(MY_TID, MY_XML_NAME, MY_STD, id, vers, cur),\n bouquet_id(_tid_ext)\n{\n}\n\nts::BAT::BAT(DuckContext& duck, const BinaryTable& table) :\n AbstractTransportListTable(duck, MY_TID, MY_XML_NAME, MY_STD, table),\n bouquet_id(_tid_ext)\n{\n}\n\nts::BAT::BAT(const BAT& other) :\n AbstractTransportListTable(other),\n bouquet_id(_tid_ext)\n{\n}\n\nts::BAT& ts::BAT::operator=(const BAT& other)\n{\n if (&other !", "= this) {\n // Assign super class but leave uint16_t& bouquet_id unchanged.", "\n AbstractTransportListTable::operator=(other);\n }\n return *this;\n}\n\n\n//----------------------------------------------------------------------------\n// A static method to display a BAT section.", "\n//----------------------------------------------------------------------------\n\nvoid ts::BAT::DisplaySection(TablesDisplay& disp, const ts::Section& section, PSIBuffer& buf, const UString& margin)\n{\n // Display bouquet information\n disp << margin << UString::Format(u\"Bouquet Id: %d (0x%<X)\", {section.tableIdExtension()}) << std::endl;\n disp.displayDescriptorListWithLength(section, buf, margin, u\"Bouquet information:\");\n\n // Transport stream loop\n buf.skipBits(4);\n buf.pushReadSizeFromLength(12); // transport_stream_loop_length\n while (buf.canReadBytes(6)) {\n const uint16_t tsid = buf.getUInt16();\n const uint16_t nwid = buf.getUInt16();\n disp << margin << UString::Format(u\"Transport Stream Id: %d (0x%<X), Original Network Id: %d (0x%<X)\", {tsid, nwid}) << std::endl;\n disp.displayDescriptorListWithLength(section, buf, margin);\n }\n buf.popState(); // transport_stream_loop_length\n}\n\n\n//----------------------------------------------------------------------------\n// XML serialization\n//----------------------------------------------------------------------------\n\nvoid ts::BAT::buildXML(DuckContext& duck, xml::Element* root) const\n{\n root->setIntAttribute(u\"version\", version);\n root->setBoolAttribute(u\"current\", is_current);\n root->setIntAttribute(u\"bouquet_id\", bouquet_id, true);\n descs.toXML(duck, root);\n\n for (TransportMap::const_iterator it = transports.begin(); it !", "= transports.end(); ++it) {\n xml::Element* e = root->addElement(u\"transport_stream\");\n e->setIntAttribute(u\"transport_stream_id\", it->first.transport_stream_id, true);\n e->setIntAttribute(u\"original_network_id\", it->first.original_network_id, true);\n if (it->second.preferred_section >= 0) {\n e->setIntAttribute(u\"preferred_section\", it->second.preferred_section, false);\n }\n it->second.descs.toXML(duck, e);\n }\n}\n\n\n//----------------------------------------------------------------------------\n// XML deserialization\n//----------------------------------------------------------------------------\n\nbool ts::BAT::analyzeXML(DuckContext& duck, const xml::Element* element)\n{\n xml::ElementVector children;\n bool ok =\n element->getIntAttribute(version, u\"version\", false, 0, 0, 31) &&\n element->getBoolAttribute(is_current, u\"current\", false, true) &&\n element->getIntAttribute(bouquet_id, u\"bouquet_id\", true, 0, 0x0000, 0xFFFF) &&\n descs.fromXML(duck, children, element, u\"transport_stream\");\n\n for (size_t index = 0; ok && index < children.size(); ++index) {\n TransportStreamId ts;\n ok = children[index]->getIntAttribute(ts.transport_stream_id, u\"transport_stream_id\", true, 0, 0x0000, 0xFFFF) &&\n children[index]->getIntAttribute(ts.original_network_id, u\"original_network_id\", true, 0, 0x0000, 0xFFFF) &&\n transports[ts].descs.fromXML(duck, children[index]);\n if (ok && children[index]->hasAttribute(u\"preferred_section\")) {\n ok = children[index]->getIntAttribute(transports[ts].preferred_section, u\"preferred_section\", true, 0, 0, 255);\n }\n else {\n transports[ts].preferred_section = -1;\n }\n }\n return ok;\n}\n" ]
{ "pile_set_name": "Github" }
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[ "Q:\n\nWhat happens if a petitioner is brought back to the Material Plane?", "\n\nA petitioner is, essentially, the soul of a deceased character that has found its way to the plane to which it belongs. ", "However, as far as I am aware, it does retain its level and abilities - at least to a degree.", "\nWhat would happen if a petitioner is subjected to the Plane Shift or similar spell - either by its own casting or otherwise - and, through that manner, brought back to the Material Plane? ", "What would its type and/or statistics be? ", "Would this at all be possible?", "\nAnd would there be any consequences beyond pure mechanics to the petitioner in question? ", "Consequences for the plane of origin and the arrival plane, for example?", "\n\nA:\n\nPetitioners can't leave their plane.", "\nAccording to Manual of the Planes, p. 55, petitioners are bound to their plane and cannot be made to leave:\n\nPlanar Commitment: Petitioners cannot leave the plane they inhabit. ", "They are teleported one hundred miles in a random direction if an attempt is made to force them to leave.", "\n\nA:\n\nIn the novel Annihilation from the War of the Spider Queen series of novels, a halfling petitioner named Dietr manages to come back to the Prime Material Plane via a portal, but he becomes a huecuva as a consequence/punishment.", "\n\n" ]
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[ "Mutation His322Asn in human acetylcholinesterase does not alter electrophoretic and catalytic properties of the erythrocyte enzyme.", "\nThe YT blood group antigen is located on human red blood cell (RBC) acetylcholinesterase. ", "Wild-type acetylcholinesterase, YT1, has histidine at codon 322, whereas the genetic variant of acetylcholinesterase, YT2, has asparagine. ", "This mutation is located within exon 2 of the ACHE gene, an exon that is present in all alternatively spliced forms of acetylcholinesterase. ", "Therefore, acetylcholinesterase in brain and muscle has the same mutation as RBC acetylcholinesterase. ", "We compared the electrophoretic and kinetic properties of RBC acetylcholinesterases having His 322 or Asn 322. ", "We found no differences in the isoelectric point, mobility on non-denaturing gel electrophoresis, affinity for acetylthiocholine, activity per milligram of RBC ghost protein, substrate inhibition constants, binding to the peripheral site ligand (propidium), and binding to active site ligands (tetrahydroaminoacridine and edrophonium). ", "Thus, although the point mutation elicits antibody production in nonmatching blood transfusion recipients, it has no effect on the enzymatic properties of acetylcholinesterase." ]
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[ "Pennsylvania’s commitment to the preservation of its prized natural resources is exhibited by its many environmentally-friendly facilities and opportunities for visitors to connect with nature.", "\n\nFeatured Trip Ideas\n\n1\n\nThe Nature Inn at Bald Eagle State Park\n\nA 2,800-gallon rainwater harvesting system is just one of the environmentally friendly features at The Nature Inn at Bald Eagle State Park in Howard.", "\n\nGet inspired at these earth-friendly attractions, including many buildings with the U.S. Green Building Council’s LEED® certification (Leadership in Energy and Environmental Design) – a coveted benchmark in green building.", "\n\nIn-room energy monitors, a 2,800-gallon rainwater harvesting system, and solar-thermal hot water system make this bed and breakfast a model of environmental stewardship. ", "The inn is also an acclaimed interpretive center for birding and offers many resources to help guests spot the park’s winged beauties, including field guides, a bird-tracker kiosk, and Children’s Discovery Area.", "\n\nTaste super-smooth vodka, gin, rum, whiskey, and bourbon at Big Spring Spirits’ tasting room in Bellefonte, the first LEED®-certified distillery in the country. ", "The spirits maker uses water from the local Big Spring and follows a grain-to-grass philosophy by only using ingredients grown by local farmers.", "\n\nCheer on the Pittsburgh Penguins at the first NHL arena to receive a LEED® Gold certification. ", "Constructed primarily from locally sourced and recycled materials, the center has a large glass atrium for natural light and high-efficiency heating and cooling systems.", "\n\nThree solar greenhouses at this sustainable farm facilitate the growth of vegetables throughout the winter – so fresh produce is available year-round. ", "Located in northeast Pennsylvania’s Endless Mountains, the farm also uses crop rotation and follows organic practices to support healthy soil.", "\n\nThe location and layout of this LEED® Gold-certified wildlife center were chosen to minimize impact on the surrounding ecosystem, the roaming grounds of the largest wild elk herd in the northeastern U.S. Other green features of the center include solar-oriented windows for natural warmth and lighting and a renewable geothermal heating and cooling system.", "\n\nWater conservation initiatives, sensors to monitor and control energy use, and recycled plastic seats are just a few environmentally friendly features of Medlar Field, home to the Nittany Lions Baseball and Softball and State College Spikes. ", "The field became the first baseball stadium in the U.S. to achieve LEED® certification in 2007.", "\n\nOther Places to Connect with Pennsylvania’s Natural Landscape\n\nFind out how Pennsylvania farmers are using sustainable practices to produce organic fruits and veggies, meats, and dairy products at more than 30 farms in Butler County.", "\n\nLearn the natural process behind honey production by watching the bees at Draper’s Super Bee Apiaries in Millerton, where free tours uncover how bees impact ecological balance and how honey is collected." ]
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[ "Recreation Management: What We Should Keep and Add\n\nThe 2018 RMS Survey Proposals drop important Actions from the Current Recreation Management Strategy 2010-2030. ", "We discuss what we’d want kept, and propose other useful key projects.", "\n\nActions to Retain from Current RMS 2010-2030\n\nAll the partner organizations were part of the extensive consultation that produced the existing strategy, which they would have had substantial say in and adoption. ", "The objectives of the existing Strategy are “owned” by definition by the National Park which includes that Strategy as one of its core documents. ", "Whilst it’s true that the Park Authority has limited direct responsibilities and powers, it’s incumbent on them to use their influence on those organizations that do, and there is a legal obligation for those bodies to listen and act accordingly.", "\n\nOne of the reasons that we find that the new proposals are not a substantial improvement over the existing RMS is that it leaves out specified actions which we continue to support. ", "In some instances there are references to these in the survey, but passing or implied inclusion of these actions is insufficient as they should be explicitly included. ", "Here is a non-exhaustive list of actions which should be considered for stated inclusion, with some suggestion for amendment or extension into new projects.", "\n\nDevelop a National Park Ranger Service\n\n5.3 Raising awareness and understanding\n5.3.3 Work with the recreation user groups and land managers, to promote responsible behaviour amongst all users that respects the special qualities of the National Park and the needs of others through a range of mechanisms, and especially by:\nA.. Face to face contact with co-ordinated ranger services, providing a friendly and knowledgeable presence able to convey consistent messages\n5.3.5 Develop a National Park Ranger Service which is responsive to the needs of the Forest as they emerge, and facilitate the co-ordination of existing ranger services within the National Park. ", "Consider establishing a Young Friends of the New Forest Group to involve and engage young people more in the area.", "\n\nCredible enforcement of any rules developed, or even the existing byelaws, would require an investment in personnel. ", "We would want to see this ambassadorial role extended to include some elements of enforcement.", "\n\nWe cannot necessarily expect either FC Keepers or Rangers, or NPA Rangers to fulfil the role of enforcement. ", "It may be that a new role modelled after the Foreign style “Park Ranger”, that is with some police training and enforcement powers should be considered. ", "There needs to be enough of a perceived enforcement presence, whether directly from beats of such rangers, or the extended eyes and ears of the combined other Rangers/Keepers/Agisters network for Park users to sense that they could be seen or challenged for inappropriate or illegal behaviour. ", "We recognize that this would require funding, but providing this service would shore up any funding plans that require charging which itself would need enforcement to be effective.", "\n\nInfluencing beyond the boundaries of the National Park\n\n5.9 Influencing recreational provision beyond the boundaries of the National Park\n5.9.1 Outside the National Park, work in partnership with other Authorities to improve recreational provision that provides for their community needs (thereby helping to relieve pressure on the New Forest Special Area of Conservation). ", "Ensure that recreation provision is at the forefront of planning for major urban expansion within a 20km radius beyond the boundary of the New Forest.", "\n5.9.2 In partnership with neighbouring authorities, actively support their search to identify and implement opportunities for new Country Parks or similar and advocate the inclusion of these aspirations in the local development frameworks and core strategies of neighbouring authorities.", "\n\n5.9.1 is not indicated in any way by the new proposals. ", "In light of NFDC’s current draft local plan targeting 10,500 houses over 10 years, the commensurate surge in local population using the Forest, and NFDC’s low quality standards for Suitable Alternate Natural Greenspace (proposal to use degraded arable rather than setting a standard to offer land restored to a quality commensurate with the protected habitats for which it is meant to mitigate), this is clearly an important action.", "\n\n5.9.2 could be construed to have a passing mention as an ambition Objective 4’s statement and glancing mention in Objective 5 Funding, but it is not featured amongst the Actions. ", "Given that infrastructure needs may demand the wholesale destruction of the nearby habitat of Dibden Bay along with greater stress on local transport infrastructure, perhaps it would be reasonable to suggest that the National interest would demand a substantial mitigation which perhaps could include compulsory purchase of sufficient well placed land to fulfil the ambitions for Country Parks that would offset damage and act as preferred recreation sites.", "\n\nBelow we have proposed new projects to extend influence to neighbouring authorities: “Habitat Mitigation Framework for the Forest that is Fit for Purpose” and a “Strategic Regional Development Forum.”", "\n\nCamping and Parking Infrastructure\n\n5.6 Providing sustainable services and facilities\n5.6.1 Undertake a review of recreational and visitor facilities in the National Park.", "\n5.6.3 Manage car parking in the National Park as a means of providing access for people to the New Forest and managing impacts on the most sensitive areas. ", "Overall car parking capacity across the National Park is not anticipated to increase or decrease significantly from existing levels:\nA.. Audit car parking provision within the National Park6.4 Camping and caravanning\n6.4.1 Audit the provision of camping in the National Park and maintain the unique experience the New Forest offers; sustain the significant contribution it makes to the local economy whilst ensuring that campsite management does not adversely damage the Park’s special qualities.", "\n6.4.2 Work with partners to identify potential alternative sites to which the phased relocation of the more damaging campsites (e.g. Hollands Wood, Longbeech and Denny Wood) might be achieved whilst providing a similar quality of camping experience. ", "It must be recognised the difficulties in finding alternative sites; many issues will have to be taken into consideration, including the local economy, transport links, access to facilities (e.g. villages, shops) and the camping experience.", "\n6.4.3 Work with campsite operators to reduce the environmental footprint and impact of camping and caravanning on sensitive areas to enhance landscape and visitor satisfaction by:\n.. preventing the extension of existing and development of new camping and caravan sites\n.. restricting the spread of new supporting built facilities\n.. ensuring that any built facilities that are provided reflect their surroundings\n.. securing more sympathetic conservation management of existing camp sites\n.. monitoring the condition and operation of the sites on designated areas.6.4.4 Explore opportunities to develop campsites as substitutes to those displaced from the commonable lands as a valuable form of farm and business diversification in robust locations.", "\n6.4.5 Provide further guidance on the future management of campsites to reduce the dependency on car use, for example, by encouraging campers to leave their cars on site whilst visiting the National Park and continuing to promote alternatives to the private car for travel around the Forest.", "\n\n5.6.1, 5.6.3 and 6.4.1 Audit of parking and camping provisions and facilities – a very straightforward achievable bit of work, unfortunately not yet done eight years later.", "\n\nBelow we have proposed new projects to address campsite issues: “Bring temporary campsites under a regimen of consistent standards and controls” and “Close Hollands Wood, Denny Wood and Longbeech Campsites”. ", "Both of these would augment the goal in Policy DP18 “enable the removal of pitches from sensitive areas by the relocation of part of a site to a less sensitive area”.", "\n\nNew Forest National Park Core Strategy Policy DP18: Extensions to Holiday Parks and Camp Sites\nExtensions to existing holiday parks, touring caravan or camping sites will only be permitted to enable the removal of pitches from sensitive areas by the relocation of part of a site to a less sensitive area adjoining an existing site, providing:\n\na) there would be overall environmental benefits\n\nb) there would be no increase in the overall site area or site capacity\n\nc) the area where pitches or other facilities are removed from would be fully restored to an appropriate New Forest landscape, and any existing use rights are relinquished.", "\n\nTo be supplanted by almost identical Submission Draft Local Plan 2016-2036 Policy DP47: Holiday Parks and Camp Sites removes the restrictive stipulation “adjoining an existing site”\n\nPossible RMS Projects\n\nThis is a non-exhaustive list of possible projects that would be welcome ways of delivering the aspirations which should have been more explicitly spelled out in the survey document.", "\n\nResearch Station for the Forest\n\nThis would pool resources to staff and deliver a focus for New Forest research. ", "It would maintain a catalogue/concordance of extant research, coordinate research efforts from academic institutions, quality check citizen science, and encourage research to provide evidentiary base for spatial strategy, recreation and livestock impacts on habitat, climate change or any other key criteria for future decision making.", "\n\nHabitat Mitigation Framework for the Forest that is Fit for Purpose\n\nMitigation regimes use formula developed by Natural England for Thames Basin Heaths, which does not scale appropriately to the Forest because a) the Forest is much richer in features and biodiversity at threat and should cost developers more b) the morphology of the Forest is different: Thames Basin Heaths spatially has greater opportunity for alternative spaces, where the Forest, surrounded, creates more of a siege situation (with only one defence to the West at Moors Valley, and plans to the East eternally pipe dreamed).", "\n\nStrategic regional development Forum\n\nIn the past some planning regimes managed on a more regional basis was able to reduce pressure in and around the Forest. ", "Both the promises of the government’s 25 Year Environment Plan and its subsequent upcoming review of National Parks should be an opportunity to put the case again. ", "Recreation pressure on the Forest is directly affected by population proximity, housing targets within and on the borders of the Park. ", "If the park and its borders cannot be afforded a sufficient buffer zone that retains its own green belt with sufficient alternative natural greenspace, then the government’s promise of increased protection to our parks and habitats is hollow. ", "The Draft Action proposals have relegated engagement with other authorities to mitigation (which as already noted is undercooked), housing targets with direct impact on Forest recreation are relevant under Section 62 Duties.", "\n\nBring temporary campsites under a regimen of consistent standards and controls\n\nBoth these camping projects (see below) could help address the obligation under the 2001 SAC Management plan to relocate three FC Campsites (Five year priority 6.4.2 of RMS 2010). ", "Temporary campsite provision in and around the Forest should provide a consistent minimal standard and be subject to appropriate licensing. ", "This could lead to a Charter, or even a scheme similar to “New Forest Marque” for campsites to assure visitors of a Park led standard of quality, and perhaps, oversight. ", "It may also be appropriate to encourage some small pop-up sites as alternative temporary use of backup land during the peak tourist summer season, which could serve as an additional income for commoning.", "\n\nClose Hollands Wood, Denny Wood and Longbeech Campsites.", "\n\nThe Natural England’s SAC Management Plan for the New Forest 2001 (page 30, Part 3: General Prescriptions) gave “Unfavourable Declining” condition assessments to Hollands Wood, Denny Wood and Longbeech due to the presence and management of the campsites. ", "The Campsite Survey (New Forest Camp site Baseline Survey: Final Report (Cox, Jonathan: July 2010: Lyndhurst: New Forest Association)) showed these have less than half the canopy they ought. ", "This Authority’s Landscape Action Plan doesn’t even have the word campsite in it, let alone a consideration of their impact. ", "The NPA need to address this remiss approach.", "\n\nContact Us\n\nTwitter\n\nFacebook\n\nBeautifully observed phenomenon from our friends across the pond...Have you seen the same?Crown shyness is a naturally occurring phenomenon in some tree species where the uppermost branches in a forest canopy avoid touching one another. ", "The visual effect is striking as it creates clearly defined borders akin to cracks or rivers in the sky when viewed from below.", "\n\nAlthough the phenomenon was first observed in the 1920s, scientists have yet to reach a consensus on what causes it.", "\n\nAccording to Wikipedia, it might simply be caused by the trees rubbing against one another, although signs also point to more active causes such as a preventative measure against shading (optimizing light exposure for photosynthesis) or even as a deterrent for the spread of harmful insects.", "\n\nFor you die hard consultation fans: our deeply detailed evaluation of all the objectives and actions in this year's Recreation Management Survey, expressed in the way you were not allowed to in the on-line survey.", "Enjoy! ... ", "See MoreSee Less" ]
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[ "Tam Tams\n\nREDIRECT Tam-Tams" ]
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[ "1. ", "Technical Field\nThe present invention relates to a pharmaceutical preparation which is stable to light (especially ultraviolet rays) or heat, and which has excellent storage-stability; and a coating agent which is a raw material of such a pharmaceutical preparation.", "\n2. ", "Background Art\nIt has been found that O.sup.6 -benzylguanine is decomposed in an aqueous solution of polyethylene glycol 400 at room temperature by the reaction of formaldehyde (present as an impurity of polyethylene glycol 400 and probably produced by air oxidation of polyethylene glycol 400) with O.sup.6 -benzylguanine [Pharmaceutical Research, 11 (7), 1060-1064 pp. (", "1994)].", "\nJP-A-63-301816 (EP-A1-0277741) mentions an enteric coating using an enteric film-liquid including titanium oxide and polyethylene glycol 6000.", "\nChemical Abstracts 122:388853 mentions tablets containing vitamin C, Yinqiao extracts, acetaminophen, chlorphenramine, calcium carbonate, starch, dextran, peppermint oil and Yinqiao and jingfang volatile oils coated with a composition containing hydroxypropylmethyl cellulose, no.2 enteric vinyl resin, PEG 6000, sesame oil, Tween 80, titanium oxide, talc, Mg stearate, food color, 95% ethanol, and distilled water.", "\nJP-A-63-166824 mentions soft capsules comprising oily solution containing pharmaceutically active ingredient unstable in light, coated with a coating agent containing fine particles of titanium oxide of at least 85% with particle size of 0.1 .mu.m or less.", "\nWhen a pharmaceutical preparation which is unstable to light is provided to consumers, the pharmaceutical preparation has to be wrapped or coated for protection from light. ", "However, when storage conditions of a pharmaceutical preparation at a pharmacy in a hospital or at patients are considered, it is difficult to say that sufficient quality of the pharmaceutical preparation is guaranteed by wrapping for protection from light. ", "Therefore, when a pharmaceutical preparation which is unstable to light is manufactured, coating for protection from light is desired.", "\nHowever, in case of manufacturing a pharmaceutical preparation comprising a drug which is unstable to light, when a tablet comprising the drug was coated with a coating agent which comprises an agent for protection from light such as titanium oxide and a plasticizer such as polyethylene glycol, there was a problem that the obtained film-coated tablet was less stable to light than before coating." ]
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[ "Q:\n\nHow to customize a workflow details page in Alfresco Share?", "\n\nI want to modify the Share workflow details page (/share/page/workflow-details?workflowId=activiti$XXXXX). ", "Specifically, I want to replace the column Type in the history tables with another one that will show the task title (adding it as a new column is a good solution too). ", "I'm working with Alfresco Community 4.0e.", "\nI read this wiki article Custom Share Workflow UI (section \"Workflow Details Form\"), but that is not the part of the page I need to change. ", "\nAny ideas, please?", "\nYou can see the columns I want to modify in this picture (see red squares):\n\nFor example, where it shows these values (task type):\nReview\n\nWorkflow Task\n\n...I want to print this (task name/title):\nQuality Documents Review\n\nQuality Documents Edition\n\nA:\n\nTo add new column or modify shown data, you should modify\ncurrentTasksColumnDefinitions and historyColumnDefinitions in\nworkflow-form.js i.e, apache-tomcat\\webapps\\share\\components\\workflow\\workflow-form.js.", "\nTo modify existing task title, you need to modify only in property\nfile namely workflow-messages.properties in apache-tomcat\\webapps\\alfresco\\WEB-INF\\classes\\alfresco\\workflow\\workflow-messages.properties\n\n" ]
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[ "All relevant data are within the paper.", "\n\nIntroduction {#sec001}\n============\n\nBurn-related neuropathic pain has been reported in 52% to 67.3% of burn injury patients \\[[@pone.0137563.ref001], [@pone.0137563.ref002]\\]. ", "Neuropathic pain is a localized sensation of discomfort, such as allodynia and hyperalgesia, and it is difficult to treat with even the most potent analgesic compound \\[[@pone.0137563.ref003]\\]. ", "Autologous fat grafting has reportedly improved traumatic neuropathic pain in patients with burn induced neuropathic pain, postmastectomy pain syndrome, and traumatic scar pain \\[[@pone.0137563.ref004]--[@pone.0137563.ref006]\\]. ", "The mechanism of fat graft pain relief is unclear. ", "Many hypotheses have been proposed regarding the mechanism of fat grafting such as scar softness, improved scar tissue differentiation, nerve entrapment relief \\[[@pone.0137563.ref007]\\], and improved nerve liberation \\[[@pone.0137563.ref008]\\]. ", "Klinger et al and Valenti et al also reported that fat grafting reduces scar adherents and similar cushions on the nerve stump \\[[@pone.0137563.ref008]--[@pone.0137563.ref010]\\]. ", "Rigotti et al indicated that the fat grafting effect of neuropathic pain may be related to adipose-derived stem cells in fat grafts \\[[@pone.0137563.ref011]\\]. ", "Fat grafts and their mesenchymal stem cells have been reported to alleviate inflammation in colitis, stroke, and inflammatory models \\[[@pone.0137563.ref012], [@pone.0137563.ref013]\\], further prevent second necrosis and apoptosis \\[[@pone.0137563.ref014]\\]. ", "A rat model of fat graft alleviated burn-induced neuropathic pain has been established \\[[@pone.0137563.ref004]\\]. ", "We used this model to explore the mechanism of fat grafts in improving neuropathic pain.", "\n\nPain is processed in a neural network, and the interaction between neurons, microglia, and astrocytes is critical for the initiation and maintenance of chronic pain. ", "Activation of glia cells (eg, microglia and astrocytes) contributes to the pathogenesis of chronic pain through neuron-glial interaction \\[[@pone.0137563.ref015], [@pone.0137563.ref016]\\]. ", "Evidence increasingly suggests that astrocytes are crucial for promoting and maintaining chronic neuropathic pain and pain sensitization \\[[@pone.0137563.ref017]\\]. ", "The activation of astrocytes results in the activation of the nuclear factor κB (NFκB), extracellular regulated kinase (ERK), and Jun N-terminal kinase (JNK) signal pathways\\[[@pone.0137563.ref018]\\] and the production of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), nitric oxide (NO), prostaglandin, and neurotrophins \\[[@pone.0137563.ref017]\\]. ", "Inflammation also induces cyclooxygenase-2 (COX-2), causing the sensitization of peripheral nociceptors and generation of pain hypersensitivity, which leads to central sensitization and accompanying chronic pain \\[[@pone.0137563.ref015],[@pone.0137563.ref018],[@pone.0137563.ref019]\\]. ", "This persistent pain caused by neuroinflammation also triggers neuronal apoptosis \\[[@pone.0137563.ref020], [@pone.0137563.ref021]\\].", "\n\nNO, which is synthesized by NO synthase (NOS), is involved in processes related to the regeneration of neuropathic pain \\[[@pone.0137563.ref022]\\]. ", "Inhibitors of NOS may have analgesic effects and can be used to treat inflammatory and neuropathic pain \\[[@pone.0137563.ref023]\\]. ", "NOS, a key enzyme for neuronal NOS (nNOS) or inducible NOS (iNOS), mediates numerous neuropathic pain symptoms \\[[@pone.0137563.ref024]\\]. ", "In the neuropathic pain model, inhibition of NOS diminishes the upregulation of iNOS and nNOS in the in spinal cord and skin. ", "This indicates the efficiency of neuropathic pain alleviation. ", "In this study, we focused on whether fat grafts can regulate cytokines and the downstream target of NO in inflammatory pain and isoforms of NOS, which involved in pain modulation \\[[@pone.0137563.ref025]\\].", "\n\nWe hypothesized that autologous fat grafts alleviate burn-induced neuropathic pain through the alleviation of skin inflammation and that neuroinflammation in the spinal cord further diminishes neuron cell apoptosis. ", "The aim of this study was to determine the effect of fat grafts on allodynia and hyperalgesia in burn-induced neuropathic pain. ", "Moreover, we examined hind paw skin inflammatory cytokine expression and NOS. ", "Furthermore; we observed the astrocytic response, iNOS, nNOS, COX-2, B cell lymphoma/lewkmia-2 (Bcl-2) family protein, and apoptosis protein expressions in the spinal cord dorsal horn after fat grafting.", "\n\nMaterials and Methods {#sec002}\n=====================\n\nAnimals and experimental design {#sec003}\n-------------------------------\n\nAll experiments were performed on adult male Sprague-Dawley rats weighing 180--200 g that were randomly obtained from BioLASCO Taiwan Co., Ltd. All animals were housed in an animal facility at 22°C with a relative humidity of 55% in a 12-hour light--dark cycle with food and sterile tap water available ad libitum. ", "All procedures were approved by the Institutional Animal Care and Use Committee at Kaohsiung Medical University (approval no. ", "10048). ", "The rats were divided into four groups (n = 6 in each group) as follows: Group A, received saline injections 4 weeks after sham burns (Sham-burn + Saline); Group B, received fat grafts 4 weeks after sham burns (Sham-burn + Fat graft); Group C, received saline injections 4 weeks after burn injuries (Burn + Saline); and Group D, received fat grafts 4 weeks after burn injuries (Burn + Fat graft). ", "The experimental flow chat was presented in [Fig 1A](#pone.0137563.g001){ref-type=\"fig\"}.", "\n\n![", "The flowchart of this study and the behavior tests from various groups.\\\n(**A**) A flowchart of the study D (day) and W (week). (**", "B**) The response thresholds to the mechanical stimuli decreased strongly on the burn injury side hind paws in Group C and Group D, 1--4 weeks post burn injury. ", "After the fat grafting, Group D thresholds significantly increased in the following weeks versus Group C. (**C**) The response thresholds to the radiant heat stimuli did not show significant differences between the groups. ", "The sample size was n = 6 for each group. (", "Data are plotted as mean ± SEM; \\*\\*\\**P* \\< 0.001; \\*\\**P* \\< 0.01; \\**P* \\< 0.05).](pone.0137563.g001){#pone.0137563.g001}\n\nFull-thickness burn injury and behavior test {#sec004}\n--------------------------------------------\n\nAs described in our previous study \\[[@pone.0137563.ref004]\\], the third-degree burn was caused by placing the right hind paw on the 75 ± 0.5°C heated metal block in a water bath with a 100 g weight on the hind paw for 10 seconds under anesthesia with Zoletil^®^ 50 (50 mg/kg body weight) (Virbac Laboratories, Carros, France). ", "Silver sulfadiazine cream was applied to the wound for approximately 3 weeks until it healed. ", "Paw withdrawal latency tests (PWLs) and paw withdrawal threshold tests (PWTs) were measured using the same method as our previous study 1 day before the burn injury, 4 weeks after the burn injury and at 1 week intervals for an additional 4 weeks.", "\n\nThese behavioral reactions were measured in the burned hind paw and on the contralateral side. ", "The PWL was used to estimate thermal hyperalgesia. ", "The PWL was recorded using a Plantar Test (Hargreaves Apparatus, Ugo Basile, Varese, Italy). ", "In brief, an infrared radiant heat source was positioned beneath the plantar surface of the hind paw. ", "The time from application of the heat source to withdrawal of the hind paw was defined as the PWL (measured in seconds).", "\n\nThe PWT was recorded using a Dynamic Plantar Aesthesiometer (Ugo Basile, Varese, Italy). ", "The rats were placed on a metal mesh, and a mechanical stimulus was applied using the automated tester with a metal rod (2 mm in diameter) to stimulate the plantar surface of the hind paw. ", "The pressure applied to the rod was increased at a rate of 2.5 g/second until the animal withdrew the paw, which was recorded as the lowest force (g). ", "Each measurement was repeated six times at intervals of 10 minutes with 30 minutes of rest between hind paw applications.", "\n\nAutologous fat graft {#sec005}\n--------------------\n\nFour weeks after burn injuries, the left inguinal fat was harvested under Zoletil 50 anesthesia. ", "The adipose tissue was cut into pieces with scissors and aspirated into a 1-mL syringe until 0.4 mL of volume was reached. ", "The fat graft was injected into the subcutaneous area of the burn-injured hind paw skin with a 19-gauge needle. ", "The donor site was closed with nylon 4--0. ", "The control group was injected with 0.4 mL of normal saline in the burn-injured hind paw skin subcutaneously.", "\n\nWestern blot analysis {#sec006}\n---------------------\n\nRats were sacrificed 4 weeks after burn injuries by an overdose of Zoletil 50. ", "Lumbar 3,4,5 (L345) spinal cords were collected, and the dorsal horn area and skin were separated, frozen in liquid nitrogen, and stored at -80°C. ", "L345 dorsal horn specimens and skin were homogenized in an ice-cold lysis buffer, T-PER Tissue Protein Extraction Reagent (Thermo Scientific) with one tablet of Complete Protease Inhibitor Cocktail (Roche) per 25 mL and then centrifuged (15,000 g) for 30 minutes at 4°C. ", "Each protein concentration in the supernatant was measured using bovine serum albumin as the standard. ", "The procedures and analyses of Western blots were performed through the same method as our previous report \\[[@pone.0137563.ref026]\\]. ", "The primary antibodies of COX-2 (1:1000, Cell Signaling, Danvers, MA), iNOS (1:1000, Abcam, Cambridge, MA), and nNOS (1:1000, Abcam, Cambridge, MA), protein kinase B (AKT) (1:1000, Cell Signaling, Boston, MA), p-AKT (1:1000, Cell Signaling, Boston, MA), Bcl-2 Associated X protein (Bax) (1:1000, Proteintech Group, Chicago, IL), Bcl-2 (1:1000, Abcam, Cambridge, MA), and β**-**actin (1:20000 dilution, Sigma-Aldrich, Saint Louis, MO) were used in this study.", "\n\nImmunohistochemistry (IHC) detections of COX-2, iNOS, and nNOS {#sec007}\n--------------------------------------------------------------\n\nHind paw skin was formalin-fixed and embedded in paraffin, and skin of 10 μm thickness was cut and mounted on glass slides, deparaffinized, and rehydrated in graded alcohol solutions. ", "The skin sections were subjected to antigen retrieval by heating the sections to 121°C in 0.1 mol/L of citrate buffer (pH 6.0) in an autoclave for 10 minutes and slowly cooling the sections to room temperature. ", "Furthermore, the sections were incubated for 5 minutes with 3% of H~2~O~2~ to quench the endogenous peroxidase activity. ", "After the blocking of nonspecific sites with 5% goat serum in a phosphate buffered saline (PBS) for 30 minutes, the sections were incubated overnight at 4°C with a rabbit polyclonal antibody against COX-2 (1:200, Cell Signaling, Danvers, MA), iNOS (1:200, Abcam, Cambridge, MA) and nNOS (1:200, Abcam, Cambridge, MA). ", "The sections were then incubated with a secondary antibody conjugated with horseradish peroxidase for 30 minutes at room temperature. ", "Finally, the slides were incubated in 3,3-diaminobenzidine for 5 minutes before undergoing Mayer's hematoxylin counterstaining for 60 seconds and being mounted.", "\n\nMeasurement of IL-1β and TNF-α in the spinal cord dorsal horn {#sec008}\n-------------------------------------------------------------\n\nThe lumbar spinal cord segments were dissected. ", "Spinal cord dorsal horn tissues were homogenized in a lysis buffer. ", "The Bicinchoninic Acid Protein Assay (Pierce) is used to check protein concentrations. ", "And ELISA was performed as in previous studies \\[[@pone.0137563.ref026]\\]. ", "The standard curve was included in each experiment. ", "IL-1β and TNF-α levels were measured using enzyme-linked immunosorbent assay kits for the quantitative detection of IL-1β and TNF-α (eBioscience, USA). ", "The reference range for the enzyme-linked immunosorbent assay kit was from 0 to 1400 (IL-1β), and from 0 to 750 (TNF-α) pg/mL. All the measurements were recorded in triplicate.", "\n\nImmunofluorescence detection of p-IκB and p-NFκB {#sec009}\n------------------------------------------------\n\nThe lumbar spinal cord segments were harvested 4 weeks after the fat grafts or vehicle treatments. ", "The fresh-frozen sections were performed through the same method as the previously mentioned immunohistochemistry procedure \\[[@pone.0137563.ref004]\\]. ", "For double immunofluorescence staining, the spinal cord dorsal horn was incubated with a mix of polyclonal p-I*κ*B (1:100 dilution, Cell Signaling) and monoclonal NeuN (a neuron cell marker, 1:1000, Millipore, Temecula, CA); polyclonal p-NF*κ*B (1:100 dilution, Cell Signaling, Boston, MA); monoclonal GFAP (an astrocyte marker, 1:1000 dilution, BD Biosciences San Diego, CA); and p-JNK (1:100 dilution, Cell Signaling, Boston, MA) overnight at 4°C. ", "The appropriate secondary antibody conjugated with goat anti-rabbit Cy3 (red, Millipore, Temecula, CA) and goat anti-mouse Alexa Flour 488 (green, Invitrogen, Carlsbad, CA) was added. ", "Images were acquired using a fluorescence microscope (Leica DMI6000).", "\n\nMeasurement of apoptosis in the spinal cord {#sec010}\n-------------------------------------------\n\nThe L3 to L5 segments were removed and embedded in an optimal cutting temperature compound to prepare frozen sections cut into 16 mm thick slices. ", "The procedures were mentioned in previous report \\[[@pone.0137563.ref026]\\]. ", "Briefly, apoptotic cell death was detected using the TUNEL assay according to the manufacturer's suggestions (Millipore, ApopTag fluorescein in situ apoptosis detection kit S7110), following incubated with an NeuN primary antibody (1:1000, Merck Millipore, Bedford, MA) at 4°C. ", "The sections were then incubated with a Cy3-conjugated antimouse IgG secondary antibody (Merck Millipore, Bedford, MA) at room temperature for an additional hour, rinsed 3 times with PBS for 5 minutes each, and mounted with a mounting medium containing 4,6-diamidino-2-phenylindole (DAPI).", "\n\nStatistical analysis {#sec011}\n--------------------\n\nFor statistical analysis, SPSS software (Version 14.0, Chicago, IL) was used. ", "Each sample was measured in triplicated, and data were expressed as mean ± standard error of the mean (SEM) (rat, n = 6 for each group). ", "Tissue cytokine and Western blot measurements were tested using one-way analysis of variance and Tukey pairwise comparison with *P* \\< 0.05 representing statistical significance.", "\n\nResults {#sec012}\n=======\n\nFat grafts ameliorates burn-induced neuropathic pain {#sec013}\n----------------------------------------------------\n\nBurn-induced hindpaw skin inflammations caused mechanical allodynia, and the PWT (g) of rats significantly decreased. ", "The burns elicited mechanical allodynia. ", "No significant change occurred in the PWL(s) and PWT (g) observations in the sham group or in the sham burn with fat graft treatment group ([Fig 1B and 1C](#pone.0137563.g001){ref-type=\"fig\"}). ", "A marked decrease in the PWT following burn injuries was noted 1 week after the burn injuries. ", "After the fat graft injection to the hind paw skin, the PWT (g) of rat increased significantly in rats compared with the burn with saline injection group at 5, 6, 7, and 8 weeks. ", "In other words, the anti-nociceptive effects of the fat grafts were strikingly different from 5 to 8 weeks after the burn injuries compared with Group C. Taken together; the results demonstrated that fat grafts ameliorated burn-induced pain such as mechanical allodynia.", "\n\nFat grafts reduce COX-2, iNOS, and nNOS in immunohistochemical localization and attenuates protein expressions in the hind paw skin {#sec014}\n-----------------------------------------------------------------------------------------------------------------------------------\n\nIHC staining images ([Fig 2A](#pone.0137563.g002){ref-type=\"fig\"}) and protein expressions ([Fig 2B](#pone.0137563.g002){ref-type=\"fig\"}) further confirmed that COX-2, iNOS, and nNOS activations were involved in the hind paw skin after the burn injuries. ", "We found that the burns induced an increase of COX-2, iNOS, and nNOS protein levels in the hind paw skin 8 weeks after injury. ", "Fat grafts significantly attenuated burn-induced COX-2, iNOS, and nNOS protein levels 4 weeks after treatment.", "\n\n![", "IHC staining images and protein expressions of COX-2, iNOS, and nNOS in the hind paw skin.\\\n(**A**) The effect of fat grafts on the expression of the inflammatory proteins,COX-2, iNOS and nNOS in the hind paw skin induced by a third-degree burn. (**", "B**) Western blot analyses of COX-2, iNOS and nNOS in the hind paw skin at week-8 after the burn injury. (", "Above) Western blot images were illustrated, and β**-**actin was used as the internal control. (", "Bottom) Quantitative result analyses were demonstrated, and the sample size was n \\> 3 for each test. ", "The expressions of COX-2, iNOS and nNOS were decreased significantly in the burn with fat graft (Group D) compared with the burn with saline injection (Group C). ", "\\**P* \\< 0.05.](pone.0137563.g002){#pone.0137563.g002}\n\nThe inflammatory COX-2, iNOS, and nNOS proteins and pro-inflammatory cytokines in the spinal cord dorsal horns are significantly attenuated after fat graft injection {#sec015}\n---------------------------------------------------------------------------------------------------------------------------------------------------------------------\n\nBurns induced the expression of several inflammatory proteins in the spinal cord dorsal horns. ", "COX-2, iNOS, and nNOS were shown 8 weeks after the burn injuries compared with Group A, Group B and Group D. The fat grafting in the Group B showed no significant effects on these proteins compared with Group A. The fat grafts significantly attenuated inflammatory proteins in the spinal cord dorsal horns compared with Group D ([Fig 3A](#pone.0137563.g003){ref-type=\"fig\"}). ", "To explore the possible mechanism of the fat grafting effect on burn-induced neuropathic pain, we quantified the levels of IL-1β and TNF-α in the spinal cord dorsal horns ([Fig 3B](#pone.0137563.g003){ref-type=\"fig\"}). ", "We found significant neuropathic pain in paw withdrawal latency and inflammatory proteins in the spinal cords after burn injury. ", "Therefore, pro-inflammatory cytokines were assessed; IL-1β and TNF-α levels were markedly decreased in Group D compared with Group C. Fat grafting thus alleviated neuroinflammation in the burn-induced neuropathic pain.", "\n\n![", "Fat grafting inhibited the expressions of inflammatory proteins, COX-2, iNOS and nNOS, in the spinal cord dorsal horn, and reduced the secreted levels of pro-inflammatory cytokines, IL-1β and TNF-α.\\\n(**A**) Western blot analyses of COX-2, iNOS and nNOS in the spinal cord dorsal horn at 8 weeks after the burn injury. ", "β**-**actin was used as the internal control. ", "The presentation format is similar to [Fig 2](#pone.0137563.g002){ref-type=\"fig\"}. ", "Protein expressions of COX-2, iNOS and nNOS were decreased significantly in the burn with fat graft group compared with the burn with saline injection group (Group D vs. Group C). (**", "B**) Fat grafts appreciably reduced the secretions of the pro-inflammatory cytokines, IL-1β and TNF-α, in the spinal cord dorsal horn. ", "IL-1β and TNF-α assessment was conducted at least in triplicate, n \\> 3, \\**P* \\< 0.05.](pone.0137563.g003){#pone.0137563.g003}\n\nFat grafts increased p-IκB, reduced the p-NFκB expression and attenuated apoptosis in the spinal cord dorsal horns {#sec016}\n------------------------------------------------------------------------------------------------------------------\n\nTo reveal p-NFκB activation and neuron cell apoptosis in the spinal cords, we performed double immunofluorescent staining to measure p-IκB (blocking NFκB activation), p-NFκB (an inflammation marker) followed by p-JNK (an inflammation marker), and TUNEL (an apoptosis marker) ([Fig 4](#pone.0137563.g004){ref-type=\"fig\"}). ", "The total number of NeuN and p-IκB double positive cells in Group C decreased significantly compared with other groups. ", "Additionally, the number of p-NFκB-expressing astrocytes was significantly higher in Group C than in Group D. Double immunofluorescent staining for p-JNK and TUNEL was performed in the spinal dorsal horns 4 weeks after fat grafts or saline injections. ", "P-JNK and TUNEL double positive cells were significantly decreased in the spinal dorsal horn in Group D compared with Group C.\n\n![", "Fat grafts increased p-IκB, reduced the p-NFκB protein, and through the inhibition of p-JNK, attenuated apoptosis in the spinal cord dorsal horn.\\\n(**A**) Double immunofluorescent staining was performed to measure p-IκB and p-NFκB. Few p-IκB proteins were expressed in Group C, but p-IκB were increased in Group D. The expression of p-NFκB was abolished and reduced by fat grafts in Group D versus Group C. (**B**) Double immunofluorescence images in p-JNK and TUNEL expression were elevated following an increase in the TUNEL-positive cells. ", "In Group D, we found that the inhibition from fat graft of p-JNK attenuated apoptosis in the spinal cord dorsal horn.](pone.0137563.g004){#pone.0137563.g004}\n\nFat grafts decreased the p-AKT/AKT and Bax/Bcl-2 ratios in the spinal cord dorsal horns {#sec017}\n---------------------------------------------------------------------------------------\n\nThe p-AKT/AKT and Bax/Bcl-2 expressions were assessed by Western blotting. ", "The expression of 42 kb β-actin was used as a loading control. ", "Group D significantly decreased both in p-AKT/AKT and Bax/Bcl-2 ratios compared with Group C. An increase in the Bax downstream processes of apoptosis in the spinal cord dorsal horn was also observed ([Fig 5](#pone.0137563.g005){ref-type=\"fig\"}).", "\n\n![", "Fat graft regulated p-AKT/AKT and Bax/Bcl-2 ratios in the spinal cord dorsal horn.\\\n(**A** and **B**) Both expression ratios of p-AKT/AKT and Bax/Bcl-2 increased significantly in Group C versus Group D. These results indicated that fat grafting reduced cell death of neuron in the spinal cord (Data were presented with mean ± SEM, \\*\\**P* \\< 0.01; \\**P* \\< 0.05).](pone.0137563.g005){#pone.0137563.g005}\n\nDiscussion {#sec018}\n==========\n\nFat grafts alleviate burn-induced neuropathic pain or traumatic painful scar had been reported, but the mechanism of fat graft in neuropathic pain is still not been elucidated \\[[@pone.0137563.ref004], [@pone.0137563.ref005]\\]. ", "In this study, we have demonstrated that fat grafting is a promising method for alleviated burn-induced neuropathic pain, fat grafts reduce skin inflammation and neuroinflammation in the spinal cord further diminishes neuron cell apoptosis. ", "Furthermore, fat graft also reduced inflammation protein expression such as effect iNOS, nNOS, COX-2 in burn-injured skin as well as in spinal cord dorsal horn.", "\n\nIpaktchi et al. ", "reported that burn would induce excessive local inflammation and producing inflammatory cytokines \\[[@pone.0137563.ref027]\\]. ", "Furthermore, burn wounds and their healing processes can cause inflammatory mediators and cells, such as T-helper cells and macrophages. ", "In the wound healing process, pro-inflammatory mediators, such as TNF-α, TGF-β, and the interleukin family are highly up-regulated \\[[@pone.0137563.ref028]\\]. ", "Therefore, inflammation is a physiologic phenomenon of wound healing that may occur for over 12 months until scars mature \\[[@pone.0137563.ref029]\\]. ", "Inflammation and nerve injuries induce transcriptional change and the induction of COX-2 in dorsal horn neurons \\[[@pone.0137563.ref030]\\]. ", "This causes burn scar neuropathic pain, and if inflammation persists, it also causes second necrosis and apoptosis in the spinal cord \\[[@pone.0137563.ref031]\\].", "\n\nIn addition to the inflammatory induction of COX-2, which leads to the release of prostanoids and localized pain hypersensitivity, this local inflammation also induced pain in uninjured area by increasing neuronal excitability in the central nerve system thus as spinal cord (also known as central sensitization). ", "Samad et al demonstrated that in the hind paw inflammation model evoked by complete Freund's adjuvant, the hind paw skin produced high increases in COX-2 mRNA and a similar increase in the lumbar spinal cord. ", "The inhibition of IL-1β signaling prevents transcriptional upregulation of the COX-2 gene, reduced mechanical hyperalgesia, and normalized pain sensitivity \\[[@pone.0137563.ref032]\\]. ", "The pro-inflammatory cytokines, IL-1β and TNF-α, were key cytokines during inflammation and reduced mechanical pain thresholds. ", "Moreover, pro-inflammatory cytokine antagonists were able to reduce hyperalgesia in the inflammation model, meaning that the activation of IL-1β and TNF-α was a crucial step in the generation of inflammatory pain \\[[@pone.0137563.ref025]\\]. ", "Our data showed that fat grafting decreased the expression of COX-2 in IHC staining and in western blot in skin and spinal cord dorsal horn. ", "Furthermore, fat grafting decreased the level of IL-1β and TNF-α in the spinal cord dorsal horn. ", "Therefore, we suggested that fat grafting alleviated burn-induced neuropathic pain by decreasing the level of IL-1β and further reduced the expression of COX-2 to alleviate the inflammation process.", "\n\nThe overexpression or inappropriate NO produced by iNOS and/or nNOS is associated with inflammatory and neuropathic pain. ", "Upregulated nNOS and iNOS expressions are noted in the spinal cord and skin after nerve or burn injuries in neuropathic pain animal models \\[[@pone.0137563.ref033], [@pone.0137563.ref034]\\]. ", "Payne et al demonstrated that iNOS/nNOS inhibitors were effective in the model of neuropathic pain \\[[@pone.0137563.ref035]\\]. ", "The inhibition of NOS in the neuropathic pain model diminishes the upregulation of iNOS and nNOS in the spinal cord and skin. ", "Therefore, iNOS and nNOS can indicate neuropathic pain. ", "Keihoff et al demonstrated the time-course of neuropathic pain in chronic constriction injury (CCI) model, in wild-type mice, the neuropathic pain was noted in day 10 after chronic constriction injury (CCI) and was normalized on day 52. ", "However, the pain threshold normalized on day 6 in the nNOS- knockout mice and day 17 in the iNOS mice. ", "This resulted from the required regulatory role of iNOS in the upregulation of nNOS \\[[@pone.0137563.ref022], [@pone.0137563.ref036]\\]. ", "In our results, fat grafts alleviated allodynia in the behavior test, decreased iNOS and nNOS expression in the IHC staining images and decreased protein expression. ", "Additionally, an increased protein expression was shown in the spinal cord dorsal horn. ", "These results indicated that fat grafting alleviated the skin and spinal cord neuroinflammatory reaction and improved the neuropathic pain.", "\n\nNFκB is a nuclear transcription factor that regulates inflammation and apoptosis. ", "Activation of the NFκB signal pathway depends on phosphorylation and degradation of IκB proteins \\[[@pone.0137563.ref037]\\]. ", "The MAPKs play essential regulatory roles in neuronal inflammatory response \\[[@pone.0137563.ref038],[@pone.0137563.ref039]\\]. ", "A recent study indicated that the JNK pathway mediated apoptosis involving an inflammatory response in the neuroblastoma cell line \\[[@pone.0137563.ref040]\\]. ", "This apoptosis reaction was also revealed in the expression of AKT and the increasing of the Bax/Bcl-2 ratio \\[[@pone.0137563.ref041], [@pone.0137563.ref042]\\]. ", "Activation of phosphatidylinositol 3 kinase/AKT has been linked to cytotoxic cell death, and AKT inhibitors also protect cultured neurons against photodynamic-induced necrosis \\[[@pone.0137563.ref043]\\]. ", "Bax and Bcl-2 play central roles in regulating apoptosis. ", "The decreasing expression of Bax and the increasing expression of Bcl-2 promote cell survival by inhibiting apoptosis \\[[@pone.0137563.ref042]\\]. ", "Our data revealed that fat grafting may increase p-IκB and decrease the NFκB transcription in anti-inflammation. ", "Through the inhibition of AKT and JNK phosphorylation in astrocytes, decreasing the expression of Bax and increasing the expression of Bcl-2 to alleviate apoptosis in the spinal cord dorsal horn thus alleviates apoptosis \\[[@pone.0137563.ref043],[@pone.0137563.ref044]\\]. ", "We speculated that fat grafting alleviated neuropathic pain through the anti-inflammatory effect and ameliorated the apoptosis in the spinal cord dorsal horn neuron cells.", "\n\nConclusions {#sec019}\n===========\n\nThe subcutaneous injection of fat grafts in burn-injured hind paw skin significantly attenuated burn-induced neuropathic pain. ", "In summary, our results revealed that fat grafting reduced p-NFκB activation in spinal astrocytes and attenuated inflammatory proteins including COX-2, iNOS, and nNOS in spinal cord and burn scar. ", "Our findings thus showed that fat grafting, because of its anti-inflammatory effect, can be used as an innovative therapeutic method for burn-induced neuropathic pain.", "\n\nWe also gratefully acknowledge Yen-Hsin Kuo and Shu-Chuan Lee for technical assistances and preparing figures within this article.", "\n\n[^1]: **Competing Interests:**The authors have declared that no competing interests exist.", "\n\n[^2]: Conceived and designed the experiments: S-HH H-MDW C-SL. ", "Performed the experiments: S-HH. ", "Analyzed the data: S-HH S-HW S-SL H-MDW C-SL. ", "Contributed reagents/materials/analysis tools: K-PC C-YC J-LY S-DL A-LK. ", "Wrote the paper: S-HH H-MDW C-SL.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "The Big Call (film)\n\nThe Big Call (; formerly known as Fraud Squad), is a 2017 Chinese crime drama film directed by Oxide Pang, starring Cheney Chen, Joseph Chang, Gwei Lun-mei and Jiang Mengjie.", "\n\nCast\n Cheney Chen as Ding Xiaotian\n Joseph Chang as Lin Yahai \t\n Gwei Lun-mei as Liu Lifang\n Jiang Mengjie as Xu Xiaotu\n Jiang Chao\n Cheung Siu-fai as Inspector Tan\n Tony Ho\n John Ching\n Ken Lok as Lu Chixiong\n Peng Xinchen as Lin Xiaoqin\n Zuo Kan as Qiqi\n\nReferences\n\nExternal links\n\nCategory:2010s crime drama films\nCategory:Chinese crime drama films\nCategory:Chinese films\nCategory:Films directed by Oxide Pang\nCategory:2017 films" ]
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[ "---\nabstract: 'We present a scheme to realize a deterministic solid state source of time-bin entangled photon pairs using cavity-assisted stimulated Raman adiabatic passage (STIRAP) in a single quantum dot. ", "The quantum dot is embedded inside a semiconductor cavity, and the interaction of a coherent superposition of two temporally separated input pulses and the cavity mode leads to a two-photon Raman transition, which produces a time-bin entangled photon pair through the biexciton-exciton cascade. ", "We show that the entanglement of the generated state can be measured using triple coincidence detection, and the degree of entanglement is quantified as the visibility of the interference. ", "We also discuss the effect of pure dephasing on entanglement of the generated photon pair. ", "Pronounced interference visibility values of greater than $1/\\sqrt{2}$ are demonstrated in triple coincidence measurement using experimentally achievable parameters, thus demonstrating that the generated photons are suitable for applications with Bell’s inequality violation and quantum cryptography.'", "\naddress: 'Department of Physics, Queen’s University, Kingston, ON K7L 3N6, Canada'\nauthor:\n- 'P. K. Pathak and S. Hughes'\ntitle: 'Generation of time-bin entangled photon pairs using a quantum-dot cavity system'\n---\n\nIntroduction\n============\n\nA source of entangled photon pairs is an essential building block for various quantum information processing protocols[@qinfo], such as quantum cryptography[@crypto] and quantum teleportation[@tele]. ", "Generally, the employed entangled state of photons in these experiments are entangled in both the energy and the polarization degrees of freedom[@kwait]. ", "However, because of unavoidable polarization dispersion in optical fibers, the polarization entangled photons are not suitable for distribution over large distances. ", "In related experiments[@tbin; @tbin2; @tbin3; @tbin4], entangled states of photons in energy and time degrees of freedom, using discrete time interval (time-bin) for photon emission, have been demonstrated and the entanglement between these photons has been successfully distributed over distance of 50km [@tbin4]. ", "In these experiments, the time-bin entangled photons were generated through the parametric down convertor (PDC) using the pump as a superposition of two time separated pulses. ", "A PDC is a heralded source of entangled photons where the number of generated photon pairs are probabilistic [@mandelwolf]. ", "At low pump intensity, when the probability of generating more than one photon pair remains small, the efficiency of the source remains very low (less than 20% [@tbin3]). ", "For quantum information processing applications, one requires a scalable source which generates precisely a single photon pair on demand[@scalable]. ", "In the last few years, there has been considerable progress for developing [*on demand*]{} single photon and entangled photon sources using single quantum dots (QDs)[@yamamoto; @akopian; @mfield; @efield], where the QDs provide the potential advantages of integrability and scalability in such experiments. ", "In semiconductor QDs, polarization entangled photons have been successfully generated in the biexciton-exciton cascade decay [@akopian; @mfield; @efield].", "\n\nIn 2005, Simon and Poizat [@simon] proposed an on-demand generation of time-bin entangled photons through the biexciton-exciton cascade in idealized QDs, where the bi-exciton state is created by pumping through two pulses interacting at two distinct times. ", "The state of the time-bin entangled photon pair is given by $\n|\\psi\\rangle=\\sqrt{p_1}|early\\rangle_1|early\\rangle_2+e^{i\\theta}\\sqrt{p_2(1-p_1)}|late\\rangle_1|late\\rangle_2,\n$ where [*early*]{} and [*late*]{} are two time bins and $p_1$ is the probability of generating a photon pair in the early time bin (from the first pulse) and $p_2$ is probability of generating a photon pair in the late time bin (from the second pulse); the total probability is then $p_1+p_2=1$. For generating maximally entangled state $|\\psi\\rangle$, one requires $p_1=p_2=1/2$. Therefore, a precisely regulated population transfer between the QD energy levels is essential. ", "Moreover, pure dephasing processes present in semiconductor produce detrimental effects on the entanglement of the generated state. ", "In quantum information protocols, such as entanglement swapping, it is essential that the photons should not have any other correlation except the time-bin entanglement. ", "However, in the biexciton-exciton cascade, emitted photons also have time correlations. ", "These undesirable temporal correlations can be minimized by manipulating emission rates of photons using resonant cavities[@simon].", "\n\nIn this work, we propose to generate an efficient time-bin entangled photon pair using stimulated Raman adiabatic passage (STIRAP). ", "The coherent excitation in the system of QDs embedded in a semiconductor cavity have been an active area of research [@coherent; @ates]. ", "We consider the intitial QD state is in a metastable state, and there have been several methods for achieving this using electrical control of QD-cavity mode resonce[@jelena; @electric]. ", "We demonstrate that the STIRAP process then provides an efficient regulated way for population transfer. ", "We also investigate how the cavity enhanced decay rates suppress the detrimental effects of pure dephasing.", "\n\nOur paper is organized as follows. ", "In Sec.", " II, we present a formal theory of generation of time-bin entangled photon pair from a single QD coupled to a semiconductor cavity. ", "In Se.", " III, we investigate the measure of photon entanglement by a triple coincidence detection and also study the effects of dephasing. ", "In section IV, we present our conclusions.", "\n\nGenerating time-bin entangled photon pairs using STIRAP {#Sec:Theory}\n=======================================================\n\nWe consider a QD embedded in a semiconductor microcavity, where the energy level diagram of the system is shown in Fig.", " \\[fig1\\]. ", "The dipole transitions from the biexciton state $|u\\rangle$ to the exciton state $|y\\rangle$, and from the exciton state $|y\\rangle$ to the ground state $|g\\rangle$, are coupled through a $y$-polarized single mode of the semiconductor cavity, with coupling constants $g_1$ and $g_2$, respectively. ", "Because of the large biexciton binding energy of semiconductor QDs, it is not possible to couple the biexciton and exciton transitions from the same cavity mode, and thus manipulation of the biexciton binding energy becomes essential in these systems[@ourprb; @reimer]. ", "Usually the binding energy of the charge-neutral biexciton has a negative value, however by changing the confinement size[@size] or by changing the strain[@strain], it has been found that the biexciton binding energy can be tuned to zero or a positive value. ", "Very recently, manipulation of the binding energy of the biexciton has also been reported by applying lateral electric fields[@reimer]. ", "Moreover, construction of an electrode for applying a lateral electric field in the vicinity of a QD within a photonic crystal cavity has also been reported[@jelena]. ", "Therefore, it is now possible to manipulate the binding energy of biexcitons inside semiconductor cavities. ", "The another advantage of lateral electric fields is that they can be used to create a voltage-tunable metastable exciton state $|m\\rangle$.\n\nIn III-V QDs, bright netral excitons are formed when an electron from the $s-$shell or the $p-$shell of the valance band is excited to the $s-$shell or $p-$shell of the conduction band, respectively; the transitions from $s-$shell to $p-$shell and vice versa are essentially [*symmetrically forbidden*]{}. ", "However, in the presence of an applied lateral voltage, the charge carrier symmetry can be suitably broken broken so that a bright exciton is formed, e.g., from the $s-$shell conduction band to $p-$shell conduction band[@reimer]. ", "Consequently, by applying a lateral voltage larger than the values required to break the symmetry, and then using a $\\pi$ pulse excitation to this state, a symmetrically forbidden exciton can be created which behaves as the metastable state $|m\\rangle$, after lowering the applied voltage again. ", "In what follows below, we will assume that this initial state can be created and focus on its evolution after applying STIRAP pulses.", "\n\n![(", "Color online) Schematic diagram for time-bin entangled photon generation. ", "The transitions from the biexciton state $|u\\rangle$ to the exciton states $|y\\rangle$ and $|y\\rangle$ to ground state $|g\\rangle$ are coupled by a $y$-polarized cavity mode. ", "The QD is pumped from the metastable state $|m\\rangle$ to biexciton state through the superposition of two input pulses.[]{data-label=\"fig1\"}](fig1){width=\"3in\" height=\"2.5in\"}\n\nInitially, the QD is prepared in the metastable state $|m\\rangle$ and the cavity mode in the vacuum state. ", "An $x$-polarized pump field with a Rabi frequency $\\Omega_p(t)$ is applied between the metastable state $|m\\rangle$ and the biexciton state $|u\\rangle$. The Hamiltonian of the system, in the rotating frame at the pump frequency (interaction picture), can be written as $$\\begin{aligned}\n&&H = \\hbar\\Delta_p|m\\rangle\\langle m|+\\hbar\\Delta_1|y\\rangle\\langle y|+\\hbar(\\Delta_1+\\Delta_2)|g\\rangle\\langle g|\\nonumber\\\\\n&&+ \\hbar\\left[\\Omega_p(t)|u\\rangle\\langle m|\n+g_1|u\\rangle\\langle y|a+g_2|y\\rangle\\langle g|a+H.c.\\right],\n\\label{ham}\\end{aligned}$$ where $\\Delta_p$, and $\\Delta_1$ ($\\Delta_2$) are the detunings of the pump field, and the cavity mode with the biexciton (exciton) transition frequencies, respectively; $H.c$ refers to Hermitian conjugate. ", "For simulating the dynamics of the system, we perform quantum master equation calculations in the density matrix representation. ", "The evolution of the QD-cavity system is given by $$\\begin{aligned}\n{\\dot\\rho}=-\\frac{i}{\\hbar}[H,\\rho]-\\frac{1}{2} \\sum_{\\mu} [L_{\\mu}^{\\dag}L_{\\mu}\\rho\n-2L_{\\mu}\\rho L_{\\mu}^{\\dag}+\\rho L_{\\mu}^{\\dag}L_{\\mu}] ,\n\\label{master}\\end{aligned}$$ where $L_{\\mu}$ are the Lindblad operators, with terms $\\sqrt{\\gamma_1}|m\\rangle\\langle u|$, $\\sqrt{\\gamma_1}|y\\rangle\\langle u|$, and $\\sqrt{\\gamma_2}|g\\rangle\\langle y|$ corresponding to the spontaneous decays, and $\\sqrt{2\\gamma_d}|u\\rangle\\langle u|$, $\\sqrt{\\gamma_d}|m\\rangle\\langle m|$, and $\\sqrt{\\gamma_d}|y\\rangle\\langle y|$, corresponding to pure dephasing of the biexciton and exciton states. ", "The emission of the photons from the cavity mode is given by the Lindblad operator $\\sqrt{\\kappa}a$, where $2\\kappa$ is the decay rate of the leaky cavity. ", "We safely neglect the spontaneous decay of the metastable state $|m\\rangle$ during the evolution, as the lifetime of the metastable state is, by definition, very large.", "\n\nWe numerically solve the optical Bloch equations using Eq.", " (\\[master\\]), for density matrix elements $\\rho_{ij}=\\langle i|\\rho|j\\rangle$. To simplify the nottaion, we use the definitions $|Y\\rangle=|y,1\\rangle$, $|G\\rangle=|g,1\\rangle$, and $|G'\\rangle=|g,2\\rangle$, where the alpha-numeric notation corresponds to the energy state of QD and the number corresponds to the cavity photon. ", "The complete dynamics of the system is expressed by the following equations of motion: $$\\begin{aligned}\n\\label{meq1}\n\\dot\\rho_{mm}&=&-i\\Omega^*_p(t)\\rho_{um}+i\\Omega_p(t)\\rho_{mu}+\\gamma_1\\rho_{uu},\\\\\n\\dot\\rho_{uu}&=&i\\Omega^*_p(t)\\rho_{um}-i\\Omega_p(t)\\rho_{mu}+ig_1\\rho_{uY}-ig_1\\rho_{Yu} \\\\ \\nonumber\n&& -2\\gamma_1\\rho_{uu},\\\\\n\\dot\\rho_{YY}&=&-ig_1\\rho_{uY}+ig_1\\rho_{Yu}-ig_2\\sqrt{2}\\rho_{G'Y}+ig_2\\sqrt{2}\\rho_{YG'}\\nonumber\\\\\n&&-(\\kappa+\\gamma_2)\\rho_{YY},\\\\\n\\dot\\rho_{G'G'}&=&ig_2\\sqrt{2}\\rho_{G'Y}-ig_2\\sqrt{2}\\rho_{YG'}-2\\kappa\\rho_{G'G'},\\\\\n\\dot\\rho_{GG}&=&\\!ig_2(\\rho_{Gy}\\!+\\!\\rho_{yG})+2\\kappa\\rho_{G'G'}+\\gamma_2\\rho_{YY}-\\kappa\\rho_{GG}, \\ \\\\\n\\dot\\rho_{yy}&=&-ig_2(\\rho_{Gy}\\!-\\!\\rho_{yG})+\\kappa\\rho_{YY}+\\gamma_1\\rho_{uu}-\\gamma_2\\rho_{yy}, \\ \\\\\n\\dot\\rho_{gg}&=&\\kappa\\rho_{GG}+\\gamma_2\\rho_{yy},\\\\\n\\dot\\rho_{um}&=&-i\\Delta_p\\rho_{um}-i\\Omega_p\\rho_{mm}-ig_1\\rho_{Ym}+i\\Omega_p\\rho_{uu}\\\\\n&&-(\\gamma_1+\\frac{3\\gamma_d}{2})\\rho_{um},\\\\\n\\dot\\rho_{uY}&=&-i\\Delta_1\\rho_{uY}-i\\Omega_p\\rho_{mY}-ig_1\\rho_{YY}+ig_1\\rho_{uu}\\nonumber\\\\\n&&+ig_2\\sqrt{2}\\rho_{uG'}-(\\gamma_1+\\frac{\\kappa+\\gamma_2+3\\gamma_d}{2})\\rho_{um},\\\\\n\\dot\\rho_{YG'}&=&-i\\Delta_2\\rho_{YG'}-ig_1\\rho_{uG'}-ig_2\\sqrt{2}\\rho_{G'G'}\\nonumber\\\\\n&&+ig_2\\sqrt{2}\\rho_{YY}-(\\frac{3\\kappa+\\gamma_2+\\gamma_d}{2})\\rho_{YG'},\\\\\n\\dot\\rho_{mY}&=&-i(\\Delta_1-\\Delta_p)\\rho_{mY}-i\\Omega^*_p(t)\\rho_{uY}+ig_1\\rho_{mu}\\nonumber\\\\\n&&+ig_2\\sqrt{2}\\rho_{mG'}-(\\gamma_d+\\frac{\\kappa+\\gamma_2}{2})\\rho_{mY},\\\\\n\\dot\\rho_{uG'}&=&-i(\\Delta_1+\\Delta_2)\\rho_{uG'}-i\\Omega_p(t)\\rho_{mG'}-ig_1\\rho_{YG'}\\nonumber\\\\\n&&+ig_2\\sqrt{2}\\rho_{uY}-(\\gamma_d+\\kappa+\\gamma_{2})\\rho_{uG'},\\\\\n\\dot\\rho_{mG'}&=&-i(\\Delta_1+\\Delta_2-\\Delta_p)\\rho_{mG'}-i\\Omega^*_p(t)\\rho_{uG'}\\nonumber\\\\\n&&+ig_2\\sqrt{2}\\rho_{mY}-(\\kappa+\\frac{\\gamma_d}{2})\\rho_{mG'},\\\\\n\\dot\\rho_{yG}&=&-i\\Delta_2\\rho_{yG}-ig_2\\rho_{GG}+ig_2\\rho_{yy}\\nonumber\\\\\n&& -\\frac{(\\kappa+\\gamma_2+\\gamma_d)}{2}\\rho_{yG},\n\\label{meq2}\\end{aligned}$$\n\n![(", "Color online)Populations in state $|m\\rangle$ (black solid line), in state $|g\\rangle$ (red dashed line) and in state $|u\\rangle$ (blue dotted line) during the evolution. ", "Two Gaussian pump pulses of different amplitude are employed such that $p_1=p_2=1/2$. Using the parameters $g_1=g_2=g$, $\\kappa=2.5g$, $\\gamma_2=\\gamma_1=10^{-3}g$, $\\gamma_d=10^{-2}g$, $\\Delta_1=-3g$, $\\Delta_2=2g$, $\\Delta_p=-1.5g$, $\\Omega_1(t)/g=0.74\\exp[-(t-2\\tau_p)^2/\\tau_p^2]$, $\\Omega_2(t)/g=3\\exp[-(t-9.5\\tau_p)^2/\\tau_p^2]$, and $g\\tau_p=2\\pi$.[]{data-label=\"fig2\"}](fig2){width=\"3in\" height=\"2.5in\"}\n\nWhen the pump field and the cavity mode satisfy the two-photon Raman resonance condition $\\Delta_p\\approx\\Delta_1+\\Delta_2$, the evolution of the population in the QD energy levels follows the cavity-assisted STIRAP. ", "Here, one must also remember that the Stark shifts of energy levels also play an important role in two-photon Raman resonance condition[@stirap]. ", "However, for constant cavity couplings, the Stark shifts in energy states remains constant and the two-photon Raman resonance condition can be satisfied easily by changing the detuning of the pump field ($\\Delta_p$) only.", "\n\nIn Fig.", " \\[fig2\\], we show the numerical simulations after solving Eqns.", " (\\[meq1\\])-(\\[meq2\\]). ", "The pump field is chosen to be a coherent superposition of two time-separated Gaussian pulses of the same width, but different amplitudes, which can be generated by passing a Gaussian pulse through an unbalanced two arm interferometer. ", "The Rabi frequency of the pump field is given by $\\Omega_p(t)=\\Omega_1(t)+\\Omega_2(t-T)$, where $\\Omega_{1,2}(t)$ is the Rabi frequency of each pulse and $T$ is the time gap between the pulses. ", "We select a typical value of $\\Omega_1(t)$ such that the population of the state $|m\\rangle$ is pumped to the state $|y,1\\rangle$ in STIRAP with probability $p_1=1/2$. Due to the nature of the leaky cavity mode, the photon is emitted from the final state $|y,1\\rangle$ and the system is evolved into the state $|y,0\\rangle$ state. ", "The population in state $|y,0\\rangle$ is transferred to the state $|g,1\\rangle$ through the cavity mode. ", "After emitting another photon from the state $|g,1\\rangle$, the system finally reaches the ground state $|g,0\\rangle$. Thus a photon pair in the early time bin is emitted during the interaction of the first pulse $\\Omega_1(t)$. The remaining population in state $|m\\rangle$ is similarly pumped by another pulse $\\Omega_2(t-T)$ and a photon pair is generated with probability $p_2=1-p_1$ in the late time bin. ", "The state of the generated photon pair is thus maximally time-bin entangled state. ", "For a QD embedded in a microcavity, the off-resonant exciton has a spontaneous decay rate of the order of $0.1-1\\,\\mu$eV ($10^{-3} g$ for $g =0.1\\,$meV), and the cavity decay condition $\\kappa>>g$ can be achieved easily. ", "We stress that all of these parameters correspond closely to those in present day experiments [@coherent; @ates].", "\n\nDuring the time interaction with the pump pulses, the population in the upper state $|u\\rangle$ remains always less that $0.1$ and the population in $|g,2\\rangle$ remains negligible. ", "The state of emitted photon pair from the cavity mode can therefore be written as $$|\\psi(t)\\rangle=\\left[a^{\\dag}_1(t)a^{\\dag}_2(t)+a^{\\dag}_1(t-T)a^{\\dag}_2(t-T)\\right]|\\{0\\}\\rangle,\n\\label{tstate}$$ where $|\\{0\\}\\rangle$ is vacuum field, $\\langle\na_1(t)\\rangle=\\langle\\sigma_{yY}(t)\\rangle$, and $\\langle a_2(t)\\rangle=\\langle\\sigma_{gG}(t)\\rangle$, for $\\sigma_{ij}=|i\\rangle\\langle j|$. In quantum information protocols, such as entanglement swapping, it is essential that the photons in the mode $a_1$ and $a_2$ should not have any other correlation except the time-bin entanglement. ", "However, in the biexciton-exciton cascade, the $a_1$ mode photon is always generated after the emission of the $a_2$ mode photon. ", "Thus the $a_1$ and $a_2$ modes remain time correlated. ", "This undesirable temporal correlation becomes negligible for $\\Gamma_1/\\Gamma_2>>1$ [@simon], where $\\Gamma_i$ is the emission rate of the photon in $a_i$ mode. ", "In our scheme above, the first photon in mode $a_1$ is generated in resonant Raman process, which is emitted with the cavity mode decay rate $\\kappa$, and the second photon is generated through cavity enhanced spontaneous emission. ", "The condition $\\Gamma_1/\\Gamma_2>>1$ can therefore be easily satisfied by choosing a suitably large value of the detuning $\\Delta_2$ such that $g_2^2\\kappa/(\\kappa^2+\\Delta_2^2)<<\\kappa$.\n\nTriple coincident detection of the photon entanglement, and the influence of pure dephasing\n===========================================================================================\n\nNext, we discuss how to measure the entanglement of the generated state of the photons. ", "The Concurrence of the state (\\[tstate\\]) is directly related to the coherence of the state [@akopian]. ", "For measuring the degree of entanglement, photons from each mode are passed through an unbalanced two path interferometer[@tbin]; the time difference between two arms is $T$, with phase difference $\\phi$, and $T$ is similar to the time difference between the two pulses in the pump fields. ", "After passing through the interferometers, the field operators at the output of the interferometers can be expressed as $$\\begin{aligned}\n\\label{a3} a_3(t) =a_1(t)+e^{i\\phi}a_1(t-T), \\ \\ \\\\\na_4(t)=a_2(t)+e^{i\\phi}a_2(t-T). \\ \\ ", "\\label{a4}\\end{aligned}$$ The post-selection, for detecting both photon simultaneously after passing through the interferometers, projects the state (\\[tstate\\]) into the state $$\\begin{aligned}\n|\\psi_c(t)\\rangle=\\left[a^{\\dag}_1(t)a^{\\dag}_2(t)+(1+e^{2i\\phi})a^{\\dag}_1(t-T)a^{\\dag}_2(t-T)\\right.\\nonumber\\\\\n\\left.+a^{\\dag}_1(t-2T)a^{\\dag}_2(t-2T)\\right]|\\{0\\}\\rangle. \\", "\n\\label{post}\\end{aligned}$$ Clearly, the state (\\[post\\]) has three terms which are distinguishable in time. ", "The middle term, appearing at $t=T$, provides the information about the entanglement of state (\\[tstate\\]). ", "For separating different terms in state (\\[post\\]), the time of detection of photons is measured with reference to the pump photons using a triple coincidence detection. ", "The probability of triple coincidence detection of one photon at the output of each interferometer, and one from the input pulse $\\Omega_1$, is given by $$\\begin{aligned}\n&&\\!\\!G^{(3)}(\\tau)=\\int_0^{\\infty} dt'\\int_{-T_{bin}}^{T_{bin}}d\\tau'\n|\\Omega_1(t')|^2 \\times \\nonumber\\\\\n&&\\!\\!\\langle\na^{\\dag}_3(t'+\\tau)a^{\\dag}_4(t'+\\tau+\\tau')a_4(t'+\\tau+\\tau')a_3(t'+\\tau)\\rangle,\n\\label{corr} \\ \\ \\ \\ \\\\end{aligned}$$ where $T_{bin}$ is the width of the time-bins; which is chosen larger than the biexciton-exciton cascade decay and smaller than $T$. We can simplify the above expression for $G^{(3)}(\\tau)$ using the property of field operators, $a_1(t)a_2(t-T)|\\{0\\}\\rangle=0$, as both photons are generated almost together in the cascade decay. ", "Subsequently, we can simplify the correlation function in (\\[corr\\]) as\n\n$$\\begin{aligned}\n\\langle a^{\\dag}_3(t'+\\tau)a^{\\dag}_4(t'+\\tau+\\tau')a_4(t'+\\tau+\\tau')a_3(t'+\\tau)\\rangle&&\n \\!\\!\\!\\!= \\langle a^{\\dag}_1(t'+\\tau)a^{\\dag}_2(t'+\\tau+\\tau')a_2(t'+\\tau+\\tau')a_1(t'+\\tau)\\rangle \\nonumber \\\\\n&\\hbox{} &\n\\!\\!\\!\\! ", "+ \\ \\langle a^{\\dag}_1(t'-T+\\tau)a^{\\dag}_2(t'-T+\\tau+\\tau')a_2(t'-T+\\tau+\\tau')a_1(t'-T+\\tau)\\rangle \\nonumber \\\\\n&\\hbox{} &\n\\!\\!\\!\\! ", "+ \\ 2\\cos2\\phi\\langle a^{\\dag}_1(t'+\\tau)a^{\\dag}_2(t'+\\tau+\\tau')a_2(t'-T+\\tau+\\tau')a_1(t'-T+\\tau)\\rangle, \\ \\ \\ \\ \\ \\\\end{aligned}$$\n\nwhich is evaluated for state (\\[tstate\\]) by applying quantum regression formula[@book]. ", "We relegate the details of the $G^{(3)}$ calculation to the Appendix.", "\n\nIn Fig.", " \\[fig3\\], we plot $G^{(3)}(\\tau)$ for the same parameters used in Fig.", " \\[fig2\\], where the time-dependent populations were shown. ", "The computed value of $G^{(3)}(\\tau)$ has three peaks centered at $\\tau=0$, $T$, and $2T$. The first peak at $\\tau=0$ correspond to the photons generated in the early time-bin that have passed through the short arms of the interferometers. ", "Similarly the peak centered at $\\tau=2T$ corresponds to the photon pair generated in the late time-bin that have passed through the long arms of the interferometers. ", "The central peak at $\\tau=T$ corresponds to the overlap of the photons generated in early time bin and passed through the longer arms in the interferometers and the photons generated in the late time-bin and passed through the short arms. ", "Thus only the central peak contains the information about the entanglement and can be easily selected by choosing a narrow time window around $\\tau=T$. We have also found that the required value of $T$ is slightly less than the actual time between the pump pulses, which shows that in STIRAP, the photons are actually generated before the pump pulse reaches its maximum. ", "For the parameters used in Fig.", " \\[fig2\\], the time between pump pulses is $15\\pi/g$, but the central peak in Fig.", " \\[fig3\\] is a maximum for $T=14\\pi/g$.\n\n![", "The triple coincidence correlation of detecting one photon at output of each interferometer and one from the input pulse $\\Omega_1$ for $T=14\\pi/g$. The other parameters are the same as in Fig.", " 2[]{data-label=\"fig3\"}](fig3){width=\"3in\" height=\"2.5in\"}\n\n![", "The integrated value of the triple coincidence correlation $G^{(3)}(\\tau)$ along the central peak at $\\tau=T$. The interference pattern appears on changing the phase $\\phi$ produced by the interferometers.[]{data-label=\"fig4\"}](fig4){width=\"2.5in\" height=\"5.0cm\"}\n\n![", "The dependence of the visibility, i.e. entanglement of the generated time-bin entangled state of the photon on dephasing rate $\\gamma_d$.[]{data-label=\"fig5\"}](fig5){width=\"2.5in\" height=\"5.0cm\"}\n\nThe coherence in the generated state (\\[tstate\\]) can be measured by varying the phase $\\phi$ between the overlapping amplitudes corresponding to the early and the late time bins along the central peak. ", "In Fig.\\[fig4\\], we plot the interference pattern produced in the measurement of $P_c=\\int_{T-T_{bin}}^{T+T_{bin}}G^{(3)}(\\tau)d\\tau$. The visibility of the interference pattern, defined as $V$=(maximum of $P_c$ - minimum of $P_c$)/ (maximum of $P_c$ + minimum of $P_c$), gives the concurrence and the purity of the generated state (\\[tstate\\]).", "\n\nIn Fig.", " \\[fig5\\], we show the dependence of the visibility on the dephasing rate. ", "In the presence of pure dephasing, the visibility, i.e. concurrence of the generated state (Eq.", " \\[tstate\\]), is strongly inhibited. ", "Further the dephasing in the state (Eq.", " \\[tstate\\]) only occurs during the interaction of the pump pulses. ", "The dephasing during the time gap between the pump pulses plays no role as the coherence in the state is produced by the coherence between the input pulses. ", "The inhibition of interference due to dephasing can be understood as due to pure dephasing (e.g., phonon) interactions the information about the photon generating in different time bin is partially imprinted in the phonon baths and thus as a result of quantum complementarity the interference is inhibited. ", "However, for small dephasing rate $\\gamma_d\\approx0.01g_{1}$, the value of visibility is larger than $1/\\sqrt{2}$, which is required for violation of Bell’s inequalities[@bell].", "\n\nConclusions {#Sec:Conclusions}\n===========\n\nWe have presented a cavity-QED STIRAP scheme for generating a scalable source of time-bin entangled photon pairs, and we also investigated the role of pure dephasing on entanglement. ", "The generated state of the photons can be detected by measuring the correlations between the pump and the generated photons. ", "We found that for small values of pure dephasings, it is possible to achieve larger values of entanglement using current working technologies.", "\n\nAcknowledgements\n================\n\nThis work was supported by the National Sciences and Engineering Research Council of Canada, and the Canadian Foundation for Innovation. ", "We acknowledge useful discussions with Robin Williams and Gregor Weihs.", "\n\nCalculation of multi-time correlations\n======================================\n\nHere we briefly discuss the method for calculating two-time correlation and four-time correlation used in Sec.", " III. ", "We follow the approach discussed by Gardiner and Zoller [@book] for evaluating multi-time correlations. ", "The required two time correlation can be expressed as $$\\begin{aligned}\n&&\\langle\na^{\\dag}_1(t)a^{\\dag}_2(t+\\tau)a_2(t+\\tau)a_1(t)\\rangle\\nonumber\\\\\n&&=Tr\\left\\{a_2(t+\\tau)a_1(t)\\rho(0) a^{\\dag}_1(t)a^{\\dag}_2(t+\\tau)\\right\\}\\\\\n&&=Tr\\left\\{a_2(t+\\tau)\\rho'(t)a^{\\dag}_2(t+\\tau)\\right\\},\\\\\n&&=Tr\\left\\{a_2\\rho'(t+\\tau)a^{\\dag}_2\\right\\}\n\\label{2time}\\end{aligned}$$ where $Tr$ stands for trace and operators $a_i$ appearing without time parenthesis are in Schrodinger picture, $\\rho'(t)=a_1(t)\\rho(0) a^{\\dag}_1(t)=a_1\\rho(t) a^{\\dag}_1$ is calculated after evolving the initial state $\\rho(0)=\\rho_{mm}|m\\rangle\\langle m|$ for time $t$ using Eqs.(\\[meq1\\])-(\\[meq2\\]) and then operating by $a_1$ and $a^{\\dag}_1$ from left and right, respectively. ", "Clearly, $\\rho'$ also follows the same equations of motions (\\[meq1\\])-(\\[meq2\\]). ", "Now, using initial value $\\rho'(t)=a_1\\rho(t) a^{\\dag}_1$ at time $t$, and evolving for time $\\tau$, $\\rho'(t+\\tau)$ is calculated. ", "The value of the required correlation is calculated using Eq. (", "\\[2time\\]). ", "A similar straightforward approach, considering the times appearing in the $a$ operators in ascending order, is applied in evaluating the four time correlations as follows: $$\\begin{aligned}\n&&\\langle\na^{\\dag}_1(t)a^{\\dag}_2(t+\\tau)a_2(t-T+\\tau)a_1(t-T)\\rangle, \\nonumber\\\\\n&&=Tr\\left\\{a_2(t-T+\\tau)a_1(t-T)\\rho(0) a^{\\dag}_1(t)a^{\\dag}_2(t+\\tau)\\right\\} \\nonumber \\\\\n&& \\\\\n&&=Tr\\left\\{a_2(t-T+\\tau)\\rho_1(t-T)a^{\\dag}_1(t)a^{\\dag}_2(t+\\tau)\\right\\},\\\\\n&&=Tr\\left\\{\\rho_2(t-T+\\tau)a^{\\dag}_1(t)a^{\\dag}_2(t+\\tau)\\right\\}, \\\\\n&&=Tr\\left\\{\\rho_3(t)a^{\\dag}_2(t+\\tau)\\right\\}, \\\\\n&&=Tr\\left\\{\\rho_3(t+\\tau)a^{\\dag}_2\\right\\},\n\\label{4times}\\end{aligned}$$ where $\\rho(0)=\\rho_{mm}|m\\rangle\\langle m|$, $\\rho_1(t-T)\\equiv a_1(t-T)\\rho(0)\\equiv a_1\\rho(t-T)$, $\\rho_2(t-T+\\tau)\\equiv a_2(t-T+\\tau)\\rho_1(t-T)\\equiv a_2\\rho_1(t-T+\\tau)$, and $\\rho_3(t)\\equiv\\rho_2(t-T+\\tau)a_1^{\\dag}(t)\\equiv\\rho_2(t)a_1^{\\dag}$. Thus the density matrices $\\rho$, $\\rho_1$, $\\rho_2$, and $\\rho_3$ are evolved for times, $0$ to $t-T$, $t-T$ to $t-T+\\tau$, $t-T+\\tau$ to $t$, and $t$ to $t+\\tau$ respectively. ", "The evolution of $\\rho(0)$ is given by Eqs. (", "\\[meq1\\])-(\\[meq2\\]), while the evolutions of density matrices $\\rho_i$ for i=1,2,3, follow the similar equations, written for $\\rho$, as $$\\begin{aligned}\n\\label{meqcorr1}\n\\dot\\rho_{Yy}&=&-ig_1\\rho_{uy}-ig_2\\sqrt{2}\\rho_{G'y}+ig_2\\rho_{YG}\\nonumber\\\\\n&&-(\\gamma_2+\\kappa/2+\\gamma_d)\\rho_{Yy},\\\\\n\\dot\\rho_{G'G}&=&-ig_2\\sqrt{2}\\rho_{YG}+ig_2\\rho_{G'y}-\\frac{3}{2}\\kappa\\rho_{G'G},\\\\\n\\dot\\rho_{Gg}&=&-ig_2\\rho_{yg}-\\frac{1}{2}\\kappa\\rho_{Gg},\\\\\n\\dot\\rho_{uy}&=&-i\\Delta_1\\rho_{uy}-i\\Omega_p(t)\\rho_{my}-ig_1\\rho_{Yy}+ig_2\\rho_{uG}\\nonumber\\\\\n&&-(\\gamma_1+\\gamma_2/2+3\\gamma_d/2)\\rho_{uy},\\\\\n\\dot\\rho_{G'y}&=&i\\Delta_2\\rho_{G'y}-ig_2\\sqrt{2}\\rho_{Yy}+ig_2\\rho_{G'G}\\nonumber\\\\\n&&-(\\kappa+\\gamma_2/2+\\gamma_d/2)\\rho_{G'y},\\\\\n\\dot\\rho_{YG}&=&-i\\Delta_2\\rho_{YG}-ig_1\\rho_{uG}-ig_2\\sqrt{2}\\rho_{G'G}+ig_2\\rho_{Yy}\\nonumber\\\\\n&&-(\\kappa+\\gamma_2/2+\\gamma_d/2)\\rho_{YG},\\\\\n\\dot\\rho_{yg}&=&-i\\Delta_2\\rho_{yg}-ig_2\\rho_{Gg}-\\frac{1}{2}(\\gamma_2+\\gamma_d)\\rho_{yg},\\\\\n\\dot\\rho_{my}&=&-i(\\Delta_1-\\Delta_p)\\rho_{my}-i\\Omega_p^*(t)\\rho_{uy}+ig_2\\rho_{mG}\\nonumber\\\\\n&&-(\\gamma_2/2+\\gamma_d)\\rho_{my},\\\\\n\\dot\\rho_{uG}&=&-i(\\Delta_1+\\Delta_2)\\rho_{uG}-i\\Omega_p\\rho_{mG}-ig_1\\rho_{YG}+ig_2\\rho_{uy}\\nonumber\\\\\n&&-(\\kappa/2+\\gamma_1+\\gamma_d)\\rho_{uG},\\\\\n\\dot\\rho_{mG}&=&-i(\\Delta_1+\\Delta_2-\\Delta_p)\\rho_{mG}-i\\Omega_p^*(t)\\rho_{uG}+ig_2\\rho_{my}\\nonumber\\\\\n&&-\\frac{1}{2}(\\kappa+\\gamma_d)\\rho_{mG},\\\\\n\\dot\\rho_{G'g}&=&-ig_2\\sqrt{2}\\rho_{Yg}-\\kappa\\rho_{G'g},\\\\\n\\dot\\rho_{Yg}&=&-i\\Delta_2\\rho_{Yg}-ig_2\\sqrt{2}\\rho_{G'g}-ig_1\\rho_{ug}\\nonumber\\\\\n&&-\\frac{1}{2}(\\kappa+\\gamma_2+\\gamma_d)\\rho_{Yg},\\\\\n\\dot\\rho_{ug}&=&-i(\\Delta_1+\\Delta_2)\\rho_{ug}-i\\Omega_p\\rho_{mg}-ig_1\\rho_{Yg}\\nonumber\\\\\n&&-(\\gamma_1+\\gamma_d)\\rho_{ug},\\\\\n\\dot\\rho_{mg}&=&-i(\\Delta_1+\\Delta_2-\\Delta_p)\\rho_{mg}-i\\Omega_p^*(t)\\rho_{ug} \\nonumber \\\\\n&& -\\frac{1}{2}\\gamma_d\\rho_{mg}.", "\n\\label{meqcorr2}\\end{aligned}$$ Finally, the value of four-times correlations used in Sec.", "III are found using Eq.", " (\\[4times\\]).", "\n\n[1]{} W. 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[ "Q:\n\nNode.js error: too many parameters Error while uploading bulk data\n\nI have a task to upload user data in bulk through csv file. ", "I am using nodejs and express framework. ", "When i submit csv file having 60 to 70 rows it works fine, but when it exceeds 70 rows it starts giving server error too many parameters. ", "After some research i concluded that it may be the problem of body parser size, so i tried This blog , but it didnt worked error is still same.", "\nhere is my code for body parser:\nvar cookieParser = require('cookie-parser');\nvar bodyParser = require('body-parser');\napp.use(cookieParser());\napp.use(bodyParser({limit: '50mb'}));\napp.use(bodyParser.json({limit: '50mb'}));\napp.use(bodyParser.urlencoded({ extended: false }));\n\nError message:\n2016-04-19T10:29:45.299Z - error: [req#d3a1fa1a-278e-496e-9cb1-b3a944e3d1c8/app] [App] Error: too many parameters Error: too many parameters\n at queryparse (d:\\Git\\gap-vm 13416\\node_modules\\body-parser\\lib\\types\\urlencoded.js:119:17)\n at parse (d:\\Git\\gap-vm 13416\\node_modules\\body-parser\\lib\\types\\urlencoded.js:64:9)\n at d:\\Git\\gap-vm 13416\\node_modules\\body-parser\\lib\\read.js:91:18\n at IncomingMessage.onEnd (d:\\Git\\gap-vm 13416\\node_modules\\raw-body\\index.js:136:7)\n at IncomingMessage.g (events.js:273:16)\n at emitNone (events.js:80:13)\n at IncomingMessage.emit (events.js:179:7)\n at endReadableNT (_stream_readable.js:906:12)\n at nextTickCallbackWith2Args (node.js:474:9)\n at process._tickCallback (node.js:388:17)\n\nSo , can anyone tell me where i am going wrong. ", "Any suggestion would be helpful. ", "Thanx in advance.", "\n\nA:\n\nAs others mention, you'll need to set the parameterLimit to deal with the \"too many parameters\" error. ", "You may also need to set the limit to a larger size to avoid a load size error. ", "In the case of CSV, the urlencoded limits will be applied, but others may also want to set the JSON limits too. ", "The following setting will work unless there are other places in the code that are overriding these settings:\nvar bodyParser = require('body-parser');\napp.use(bodyParser.json({limit: '50mb'}));\napp.use(bodyParser.urlencoded({limit: '50mb', extended: true, parameterLimit: 1000000}));\n\nA:\n\nIn your code it you are not using the parameterLimitat all, as pointed out as in the blog posted you linked.", "\nvar bodyParser = require('body-parser');\napp.use(bodyParser.urlencoded({ \n extended: false,\n parameterLimit: 1000000 // experiment with this parameter and tweak\n}));\n\nA:\n\nI'm not sure where you guys are testing your API but for me it was because I set the Content-Type header to application/x-www-form-urlencoded in Postman. ", "Once I removed the header and used form-data under the body section, it solved the issue. ", "Make sure to always use form-data when uploading files. ", "\nHope it helps...\n\n" ]
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[ "Q:\n\nGiven probability of event\n\nIf I'm given the probability that a certain event will occur, how can I find the probability of at least $x$ events occurring given $y$ opportunities?", "\nFor example, the probability of a single coin landing heads is 50%. ", "What are the chances of landing at least 2 heads out of 5 coins?", "\n\nA:\n\nModel event $E$ happening as a Binomial random variable, that is, if the probability of event $E$ happening is $p$, then the probability of it happening exactly $m$ times in $n$ trials is:\n$$\\mathbb{P}[X=m]=\\binom{n}{m}p^m (1-p)^{n-m}.$$\nSince the event consisting of $E$ happening exactly $m_1$ times means the event didn't happen $m_2$ times ($m_1\\neq m_2$), the events $X=m_1$ and $X=m_2$ are disjoint, and the probability of a certain set of events happening is the sum of the corresponding probablities.", "\n\n" ]
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