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tomekkorbak

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[ "More than 800 miles added to U.S. Bicycle Route System\n\nA network of signed bicycle routes designed to criss-cross the US has grown to 6,790 miles with the certification of new routes in Washington state, Massachusetts, Ohio, Illinois and the District of Columbia.", "\n\nAdventure Cycling Association is coordinating efforts in the 40 states willing to participate in the plan to create a nationwide bicycle route system. ", "In a joint announcement, AASHTO’s executive director Bud Wright said his organization seeks to provide “safe and reliable transportation system no matter how many wheels their vehicles use.”", "\n\nWashington — USBR 10\n\nWashington state’s certification was reported here earlier this month: “US Bike Route 10 is approved for Washington state.” ", "It describes how the scenic corridor across the North Cascades National Park uses the Northern Tier Bicycle Route between Anacortes and Newport on the Idaho border.", "\n\nAt 407 miles, it was the longest among those approved in the latest certification. ", "Adventure Cycling points out that it ends at an international ferry terminal in Anacortes.", "\n\nMassachusetts — USBR 1\n\nThe approval for USBR 1 in Massachusetts includes many historical sites along the coast route. ", "It uses the Paul Dudley White Bicycle Path along the Charles River through Boston, Cambridge, Watertown, and Newton, along with the Northern Strand Community Trail to the north of Boston. ", "It is 20 miles long.", "\n\nParts of USBR 50 are in Maryland and Washington DC, following the Chesapeake and Ohio Canal Towpath. ", "Long range plans call for a corridor stretching all the way to San Francisco.", "\n\nWashington DC — USBR 50\n\nThe 3.6 miles of USBR 50 certified for the District of Columbia connects the C&O Canal Towpath to Georgetown.", "\n\nIllinois — USBR 36 and 37\n\nThe two routes combine for 76 miles along the Lake Michigan coastline and connect the Wisconsin border in the west and the Indiana border in the east. ", "USBR 36 and 37 also pass through Chicago, Highland Park and Lake County on roads and trails." ]

{ "pile_set_name": "Pile-CC" }

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[ "# Contributor Covenant Code of Conduct\n\n## Our Pledge\n\nIn the interest of fostering an open and welcoming environment, we as\ncontributors and maintainers pledge to making participation in our project and\nour community a harassment-free experience for everyone, regardless of age, body\nsize, disability, ethnicity, gender identity and expression, level of experience,\nnationality, personal appearance, race, religion, or sexual identity and\norientation.", "\n\n## Our Standards\n\nExamples of behavior that contributes to creating a positive environment\ninclude:\n\n* Using welcoming and inclusive language\n* Being respectful of differing viewpoints and experiences\n* Gracefully accepting constructive criticism\n* Focusing on what is best for the community\n* Showing empathy towards other community members\n\nExamples of unacceptable behavior by participants include:\n\n* The use of sexualized language or imagery and unwelcome sexual attention or\nadvances\n* Trolling, insulting/derogatory comments, and personal or political attacks\n* Public or private harassment\n* Publishing others' private information, such as a physical or electronic\n address, without explicit permission\n* Other conduct which could reasonably be considered inappropriate in a\n professional setting\n\n## Our Responsibilities\n\nProject maintainers are responsible for clarifying the standards of acceptable\nbehavior and are expected to take appropriate and fair corrective action in\nresponse to any instances of unacceptable behavior.", "\n\nProject maintainers have the right and responsibility to remove, edit, or\nreject comments, commits, code, wiki edits, issues, and other contributions\nthat are not aligned to this Code of Conduct, or to ban temporarily or\npermanently any contributor for other behaviors that they deem inappropriate,\nthreatening, offensive, or harmful.", "\n\n## Scope\n\nThis Code of Conduct applies both within project spaces and in public spaces\nwhen an individual is representing the project or its community. ", "Examples of\nrepresenting a project or community include using an official project e-mail\naddress, posting via an official social media account, or acting as an appointed\nrepresentative at an online or offline event. ", "Representation of a project may be\nfurther defined and clarified by project maintainers.", "\n\n## Enforcement\n\nInstances of abusive, harassing, or otherwise unacceptable behavior may be\nreported by contacting the project team at [mvvmcross@gmail.com](mailto:mvvmcross@gmail). ", "All\ncomplaints will be reviewed and investigated and will result in a response that\nis deemed necessary and appropriate to the circumstances. ", "The project team is\nobligated to maintain confidentiality with regard to the reporter of an incident.", "\nFurther details of specific enforcement policies may be posted separately.", "\n\nProject maintainers who do not follow or enforce the Code of Conduct in good\nfaith may face temporary or permanent repercussions as determined by other\nmembers of the project's leadership.", "\n\n## Attribution\n\nThis Code of Conduct is adapted from the [Contributor Covenant][homepage], version 1.4,\navailable at [http://contributor-covenant.org/version/1/4][version]\n\n[homepage]: http://contributor-covenant.org\n[version]: http://contributor-covenant.org/version/1/4/\n" ]

{ "pile_set_name": "Github" }

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[ "Long-term outcome of simultaneous transurethral resection of bladder tumor and prostate in patients with nonmuscle invasive bladder tumor and bladder outlet obstruction.", "\nWe evaluated the long-term outcome of simultaneous transurethral bladder tumor and prostate resection in patients with nonmuscle invasive bladder tumor and bladder outlet obstruction. ", "Between April 1997 and April 2006, 213 patients with nonmuscle invasive bladder tumor who had a minimum followup of 24 months were included in the study, including group 1-107 with transurethral resection of bladder tumor only and group 2-106 with transurethral bladder tumor and prostate resection. ", "Simultaneous transurethral bladder tumor and prostate resection was performed at surgeon discretion. ", "The records were retrospectively analyzed for clinicopathological parameters, recurrence and progression rates, time to recurrence and postoperative uroflowmetry results in the 2 groups. ", "There were no significant differences in clinicopathological parameters between the 2 groups. ", "At a mean followup of 54.3 and 50.1 months in groups 1 and 2, respectively, group 2 patients with a tumor less than 3 cm or a single tumor had a significantly lower recurrence rate than group 1 patients. ", "None of the 31 patients with recurrence in group 2 had recurrence in the bladder neck or prostatic urethra where transurethral prostate resection had been done. ", "There was no significant difference in the progression rate between the 2 groups. ", "The 60-month recurrence-free probability in groups 1 and 2 was 43.4% and 52.0%, respectively. ", "Three months after surgery the postvoid residual urine volume had significantly decreased in group 2. ", "Simultaneous transurethral bladder tumor and prostate resection may help decrease bladder cancer recurrence and delay time to recurrence without the risk of cancer implantation when transurethral prostate resection is done, especially in patients with a papillary, solitary-appearing bladder lesion less than 3 cm." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Carcinoma embolization in coronary artery causing myocardial infarction: diagnosis from coronary thromboaspirate.", "\nA unique case of myocardial infarction due to coronary artery tumor embolism from colonic adenocarcinoma is described. ", "A 79-year-old man with a history of rectal carcinoma with lung metastases 15 years and 9 years before, respectively, was subjected to primary percutaneous coronary intervention for myocardial infarction with aspiration of a thrombus from the occluded artery. ", "The retrieved material contained fragments of adenocarcinoma tissue. ", "To the best of our knowledge, this is the first reported case of adenocarcinoma coronary embolism diagnosed during life from coronary artery aspirate." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "# coding=utf-8\n# --------------------------------------------------------------------------\n# Copyright (c) Microsoft Corporation. ", "All rights reserved.", "\n# Licensed under the MIT License. ", "See License.txt in the project root for\n# license information.", "\n#\n# Code generated by Microsoft (R) AutoRest Code Generator.", "\n# Changes may cause incorrect behavior and will be lost if the code is\n# regenerated.", "\n# --------------------------------------------------------------------------\n\nfrom msrest.serialization import Model\n\n\nclass ApplicationGatewayBackendHealth(Model):\n \"\"\"List of ApplicationGatewayBackendHealthPool resources.", "\n\n :param backend_address_pools:\n :type backend_address_pools:\n list[~azure.mgmt.network.v2018_08_01.models.", "ApplicationGatewayBackendHealthPool]\n \"\"\"\n\n _attribute_map = {\n 'backend_address_pools': {'key': 'backendAddressPools', 'type': '[ApplicationGatewayBackendHealthPool]'},\n }\n\n def __init__(self, *, backend_address_pools=None, **kwargs) -> None:\n super(ApplicationGatewayBackendHealth, self).__init__(**kwargs)\n self.backend_address_pools = backend_address_pools\n" ]

{ "pile_set_name": "Github" }

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[ "package com.github.dhaval2404.imagepicker.sample\n\nimport android.widget.", "ImageView\nimport androidx.annotation.", "DrawableRes\nimport com.bumptech.glide.", "Glide\nimport com.bumptech.glide.request.", "RequestOptions\nimport java.io.", "File\n\nfun ImageView.setDrawableImage(@DrawableRes resource: Int, applyCircle: Boolean = false) {\n val glide = Glide.with(this).load(resource)\n if (applyCircle) {\n glide.apply(RequestOptions.circleCropTransform()).into(this)\n } else {\n glide.into(this)\n }\n}\n\nfun ImageView.setLocalImage(file: File, applyCircle: Boolean = false) {\n val glide = Glide.with(this).load(file)\n if (applyCircle) {\n glide.apply(RequestOptions.circleCropTransform()).into(this)\n } else {\n glide.into(this)\n }\n}\n" ]

{ "pile_set_name": "Github" }

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[ "INTRODUCTION {#s1}\n============\n\nMaraviroc (MVC) is a first-in-class selective chemokine coreceptor type-5 (CCR5) antagonist indicated for the treatment of CCR5-tropic (R5) HIV-1 infection in both treatment-naive and treatment-experienced patients in the United States,[@R1] and in treatment-experienced patients in the European Union.[@R2] MVC is primarily metabolized by hepatic cytochrome P450 (CYP) 3A enzymes, with negligible metabolic activity for other CYP enzymes and is also a substrate for the efflux transport P-glycoprotein (P-gp).[@R3] MVC exposures have been shown to increase significantly when coadministered with potent CYP3A/P-gp inhibitors.[@R3] As such, the recommended MVC dose in the presence of potent CYP3A/P-gp inhibitors is 150 mg twice daily (BID).[@R1]\n\nPatients with HIV-1 infection are disproportionately affected by viral hepatitis, specifically hepatitis C virus (HCV), which can lead to life-threatening complications.[@R4] Approximately 25% of HIV-infected patients in the United States and Europe are coinfected with HCV, accounting for \\>75% of liver-related deaths in HIV-infected patients.[@R5] Boceprevir (BOC) and telaprevir (TVR) are newly approved HCV protease inhibitors indicated (in combination with pegylated interferon alpha and ribavirin) for the treatment of genotype 1 chronic HCV in adult patients with compensated liver disease.[@R6] BOC is a potent inhibitor of CYP3A, and TVR is also a potent inhibitor of CYP3A and an inhibitor of P-gp[@R6]; however, some unexpected drug interactions with HIV protease inhibitors have led to recommendations against the coadministration of BOC with darunavir/ritonavir, atazanavir/ritonavir, lopinavir/ritonavir, and fosamprenavir/ritonavir, and against the coadministration of TVR with darunavir/ritonavir, lopinavir/ritonavir, and fosamprenavir/ritonavir.[@R6]\n\nGiven the limited treatment options for HIV-1 and HCV coinfected patients, it is therefore important to investigate potential drug interactions of BOC and TVR with MVC. ", "This study was conducted to estimate the effect of BOC 800 mg 3 times daily (TID) and TVR 750 mg TID on the pharmacokinetics (PK) of MVC, and to describe the PK of BOC and TVR when dosed in combination with MVC 150 mg BID. ", "The safety and tolerability of MVC in combination with BOC and TVR was also assessed.", "\n\nMETHODS {#s2}\n=======\n\nStudy Population {#s2-1}\n----------------\n\nEligible volunteers were healthy adults (aged 18--55 years) who had a body mass index of 17.5--30.5 kg/m^2^, and a body weight of more than 50 kg. ", "Volunteers who had used prescription or nonprescription drugs or dietary supplements within 7 days or 5 half-lives (whichever was longer) before the start of study treatment were not permitted to take part in the study. ", "Volunteers who had used herbal supplements or hormonal methods of contraception within 28 days (6 months for Depo-Provera) were also not permitted to take part in the study. ", "Volunteers with positive results for HIV-1, HIV-2, hepatitis B serology (hepatitis B surface antigen, hepatitis B core antibody), or anti-HCV serology (as determined by multi-antigen enzyme immunoassay), or who had a history of hypersensitivity to the study drugs, were excluded.", "\n\nStudy Design and Treatment {#s2-2}\n--------------------------\n\nThis was an open-label, fixed-sequence, phase I study (NCT01597895) conducted at a single site (Pfizer Clinical Research Unit, Brussels, Belgium). ", "After a screening visit within 28 days before the start of treatment, volunteers received MVC 150 mg BID (every 12 hours) for 5 days (treatment period 1), followed by MVC 150 mg BID plus BOC 800 mg TID (every 8 hours) for 10 days (treatment period 2), then MVC 150 mg BID plus TVR 750 mg TID (every 8 hours) for 10 days (treatment period 3), with a ≥10-day wash-out between periods 2 and 3 ([Fig. ", "1](#F1){ref-type=\"fig\"}).", "\n\n{#F1}\n\nStudy treatment was administered with 240 mL water at ambient temperature 30 minutes after a standard fat meal/snack (approximately 20 g fat and ≥500 calories). ", "On PK assessment days (day 5 of treatment period 1 and day 10 of treatment periods 2 and 3), volunteers ate a standardized breakfast containing approximately 20 g fat and 800--1000 calories and received only a single (morning) dose of MVC, as well as only the morning and afternoon doses of BOC and TVR. ", "Study personnel conducted mouth checks to ensure treatment compliance. ", "To standardize conditions on PK sampling days, all volunteers were required to refrain from lying down \\[except when required for vital signs and electrocardiogram (ECG) assessments\\] and eating and drinking beverages other than water during the first 4 hours after dosing.", "\n\nVolunteers could be discontinued from the study at any time at their own request, or on the grounds of safety concerns, behavioral reasons, or inability to comply with the study activity or procedures, at the investigators\\' discretion.", "\n\nThis study was conducted in compliance with the Declaration of Helsinki and Good Clinical Practice Guidelines established by the International Conference on Harmonization. ", "The final protocol, amendments, and informed consent documentation were reviewed and approved by the study center institutional review board. ", "All volunteers provided written, informed consent before participating in any study procedures.", "\n\nPharmacokinetic Assessment {#s2-3}\n--------------------------\n\nBlood samples for MVC PK analysis were collected predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on day 5 of treatment period 1 (MVC) and on day 10 of treatment periods 2 (MVC and BOC) and 3 (MVC and TVR). ", "Blood samples for BOC and TVR PK analysis were collected predose and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose on day 10 of treatment periods 2 and 3, respectively. ", "Samples of 4 mL were taken to provide a minimum volume of 1.5 mL plasma for PK analysis and were transferred into appropriately labeled tubes containing sodium heparin (MVC), dipotassium ethylenediaminetetra-acetic acid (K~2~EDTA) (BOC), or tripotassium ethylenediaminetetra-acetic acid (K~3~EDTA) (TVR). ", "All samples were centrifuged at approximately 1700 g for approximately 10 minutes at 4°C. ", "For MVC and BOC, plasma was extracted and stored in appropriately labeled screw-capped polypropylene tubes at approximately −20°C (MVC) or −70°C (BOC) within 1 hour of collection. ", "Plasma extraction for TVR followed the same process, although after centrifugation approximately 1 mL plasma was transferred to an appropriately labeled screw-capped polypropylene tube containing 0.05 mL of 10% formic acid, before mixing thoroughly and being stored at approximately −70°C. ", "Formic acid solution was added to plasma to allow for accurate quantification of TVR by preventing TVR epimerization.", "\n\nPlasma samples were analyzed for MVC (Tandem Labs, West Trenton, NJ),[@R10] and for BOC and TVR (Covance Bioanalytical Services, Shanghai, China), using a solid-phase extraction and a validated high-performance liquid chromatography/dual mass spectrometry assay.", "\n\nNoncompartmental analyses were performed using standard methods with eNCA version 2.2 (Pfizer, Inc, New York, NY). ", "Area under the plasma concentration--time curve (AUC) from predose (0 hours) to 12 hours (AUC~12~; MVC) or 8 hours postdose (AUC~8~; BOC and TVR) was determined by the linear/log trapezoidal method, whereas plasma concentration at 12 hours (C~12~; MVC) or 8 hours postdose (C~8~; BOC and TVR), maximum plasma concentration (C~max~), and time to C~max~ (T~max~) were determined by direct observation.", "\n\nSafety and Tolerability {#s2-4}\n-----------------------\n\nAll observed and volunteered adverse events (AEs) were recorded and assessed by the investigator for severity and relationship to study treatment. ", "Additional safety assessments included standard hematology, urinalysis, and chemistry laboratory assessments, physical examinations, vital signs (blood pressure and pulse) measurements, and ECGs. ", "Orthostatic hypotension, a concentration-dependent AE observed with MVC,[@R11] was defined as a decrease of ≥20 mm Hg for systolic blood pressure or ≥10 mm Hg for diastolic blood pressure 2 minutes after standing from a supine position, and may have been symptomatic or asymptomatic.", "\n\nSample Size {#s2-5}\n-----------\n\nA minimum sample size of 12 volunteers was required to provide 90% confidence intervals (CIs) for the difference between treatments on the natural logarithmic scale of ±0.1536 for MVC AUC~12~, ±0.2745 for MVC C~max~, and ±0.1493 for MVC C~12~, with 80% coverage probability. ", "To allow for any volunteers who might not complete the study, 14 volunteers were enrolled.", "\n\nConstruction of 90% CIs was chosen based on FDA Guidance \"Statistical Approaches to Establishing Bioequivalence.", "\"[@R12] Because of the nature of normal-theory construction of 90% CIs, this corresponds to performing 2 one-sided tests hypothesis at the 5% level of significance.", "\n\nStatistical Analysis {#s2-6}\n--------------------\n\nNatural log-transformed AUC~12~, C~max~, and C~12~ for MVC were analyzed using a mixed effect model with treatment as fixed effect and subject as a random effect. ", "MVC alone was the reference treatment, and MVC plus BOC and MVC plus TVR were the test treatments. ", "Estimates of the adjusted mean differences (Test--Reference) and corresponding 90% CIs were obtained from the model. ", "The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.", "\n\nBOC and TVR PK data were summarized descriptively and compared with mean historical minimum plasma concentrations (C~min~) data (102 ng/mL and 1802 ng/mL, respectively).[@R1] BOC and TVR data were determined to be comparable with the historical data if the mean C~8~ for both agents fell within the 50% range of their historical C~min~ values: 51--204 ng/mL for BOC and 901--3604 ng/mL for TVR, based on simulations. ", "Safety data were summarized descriptively.", "\n\nRESULTS {#s3}\n=======\n\nStudy Population {#s3-1}\n----------------\n\nA total of 14 volunteers were enrolled and treated. ", "All 14 completed treatment periods 1 and 2, but 1 volunteer withdrew during the wash-out period (between periods 2 and 3) because of an AE (severe asthmatic crisis) that was not considered to be related to treatment, and thus did not participate in treatment period 3.", "\n\nAll volunteers were men with a mean age (SD) of 33.3 years. ", "The majority (n = 12/14, 85.7%) were white with the remaining 2 volunteers (14.3%) being of other races (one of Hispanic ethnicity and one of Asian ancestry). ", "Volunteers had a mean (SD) weight of 79.3 (11.4) kg and body mass index of 24.4 (2.8) kg/m^2^.\n\nBioanalytical Summary {#s3-2}\n---------------------\n\nCalibration standard responses were linear over the range of 0.5--500 ng/mL for MVC, 25--2500 ng/mL for BOC, and 50--5000 ng/mL for TVR. ", "The between-day assay accuracy, expressed as percent relative error for quality-control concentrations in the low, medium, and high-diluted quality control samples ranged from 4.6%--7.3% for MVC, −5.2%--3.7% for BOC, and −0.6%--0.8% for TVR. ", "Assay precision, expressed as the between-day percent coefficient of variation (%CV) of the mean estimated concentrations of quality-control samples, was ≤7.4% for the low (1.5 ng/mL), medium (50 and 150 ng/mL), high (375 ng/mL), and diluted (375 ng/mL) concentrations of MVC. ", "Assay precision (%CV) for BOC was ≤5.6% for the low (75 ng/mL), medium (250 ng/mL), high (1800 ng/mL), and diluted (12,500 ng/mL) concentrations, and for TVR was ≤3.8% for the low (150 ng/mL), medium (500 ng/mL), high (3600 ng/mL), and diluted (25,000 ng/mL) concentrations.", "\n\nPlasma MVC PK {#s3-3}\n-------------\n\nMVC plasma exposure (based on AUC~12~ and C~max~) was increased by approximately 3-fold in the presence of BOC, and by approximately 8- to 9-fold in the presence of TVR ([Table 1](#T1){ref-type=\"table\"}; [Fig. ", "2](#F2){ref-type=\"fig\"}). ", "MVC C~12~ values were approximately 3-fold higher for MVC plus BOC (66.1 ng/mL), and approximately 10-fold higher for MVC plus TVR (235.5 ng/mL), when compared with MVC alone (23.8 ng/mL).", "\n\n###### \n\nGeometric Means and Adjusted Geometric Mean Ratios for MVC PK Parameters Alone and in the Presence of BOC and TVR\n\n![](", "qai-65-564-g002)\n\n{#F2}\n\nIntersubject variability for MVC, as measured by the geometric %CV for AUC~12~, C~max~, and C~12~ was 24%--36% when MVC was coadministered with either BOC or TVR ([Table 1](#T1){ref-type=\"table\"}).", "\n\nC~max~ was achieved within a median T~max~ of 2.0 (range, 1.0--6.0) hours when MVC was administered alone, 2.0 (range, 0.5--3.0) hours when MVC was administered with BOC, and 3.0 (range, 2.0--4.0) hours when MVC was given with TVR.", "\n\nPlasma BOC and TVR PK {#s3-4}\n---------------------\n\nWhen coadministered with MVC, BOC and TVR exposures were consistent with historical data ([Table 2](#T2){ref-type=\"table\"}), indicating that MVC had no notable impact on the PK profile of BOC and TVR.", "\n\n###### \n\nSummary of Plasma BOC and TVR Pharmacokinetic Parameters in the Presence and Absence (Historical Studies) of MVC\n\n![](", "qai-65-564-g004)\n\nSafety and Tolerability {#s3-5}\n-----------------------\n\nAE incidence was higher during treatment with MVC plus BOC (100%) and MVC plus TVR (92%) compared with MVC alone (43%), and the majority of AEs were considered to be treatment-related ([Table 3](#T3){ref-type=\"table\"}). ", "The most common treatment-related AEs occurring during treatment with MVC alone, MVC plus BOC, and MVC plus TVR, respectively, were headache, dysgeusia, and fatigue, as summarized in [Table 3](#T3){ref-type=\"table\"}. ", "No events of postural hypotension or dizziness were reported in this study.", "\n\n###### \n\nSummary of Safety\n\n![](", "qai-65-564-g005)\n\nAll AEs were mild to moderate in severity, with the exception of a severe event of asthmatic crisis following the completion of treatment period 2 (MVC plus BOC), which led to the discontinuation of 1 volunteer. ", "This AE was not considered to be related to treatment but related to a pre-existing and undisclosed history of asthma. ", "The event lasted 8 hours and resolved with treatment given.", "\n\nThere were no deaths, serious AEs, temporary discontinuations, or dose reductions because of AEs in this study. ", "No clinically significant changes in laboratory parameters, vital signs, or ECGs were reported.", "\n\nDISCUSSION {#s4}\n==========\n\nA significant proportion of HIV-infected individuals are coinfected with HCV and consequently are at increased risk for severe liver disease.[@R5] As liver fibrogenesis may be caused by stimulation of CCR5 receptors, MVC, a CCR5 antagonist, may have a beneficial effect on liver fibrosis. ", "There is, therefore, increasing interest in using MVC as part of treatment regimens for HIV/HCV coinfected patients. ", "Preliminary data from investigators from the University of Brescia (Italy) demonstrated a significant improvement in liver stiffness in 54 patients over 24 weeks when MVC 150 mg BID was added to antiretroviral regimens compared with existing regimens alone (*P* = 0.03).[@R17] Furthermore, an ongoing study (NCT01327547) is primarily evaluating the safety of MVC in 120 HIV/HCV coinfected patients, as well as assessing the potential antifibrotic activity of MVC as a secondary objective.", "\n\nBOC and TVR are newly approved HCV protease inhibitors that have been shown to cause significant drug interactions. ", "As such, many HIV protease inhibitors are not recommended to be coadministered with either BOC or TVR, thus limiting treatment options in HIV/HCV coinfected patients.[@R6] The study reported in this article was designed to investigate the effect of coadministration of BOC 800 mg BID and TVR 750 mg TID on the PK of MVC 150 mg BID, and to describe the PK of BOC and TVR when dosed in combination with MVC. ", "Our results confirm that, when coadministered with either BOC or TVR, overall MVC exposure is increased significantly.", "\n\nTVR seemed to have a greater impact on MVC plasma exposure than BOC, as indicated by an 8- to 9-fold increase in both mean MVC AUC~12~ and C~max~ values after coadministration compared with a 3-fold increase with BOC. ", "The greater increase in MVC exposures observed with TVR was expected, as TVR has been shown to increase the AUC of midazolam (a probe substrate for CYP3A) by 796% as compared with 430% with BOC after oral coadministration of midazolam and an increase in the AUC of digoxin (a probe for P-gp) by 85% as compared with 19% with BOC.[@R6] Furthermore, a potential mechanism for the magnitude of this interaction observed with TVR may be interplay between inhibition of CYP3A/P-gp and organic ion transporter 1B1 (OATP1B1) by TVR,[@R8] as MVC has been shown to be a substrate for OATP1B1.[@R18] In vitro data suggest that TVR is a more potent inhibitor of OATP1B1 with an IC~50~ of 2.2 μM compared with an IC~50~ of 18 μM for BOC.[@R20] Additionally, inhibition of OATP1B1 is more likely to occur in vivo with TVR given that the unbound C~max~/OATP1B1 IC~50~ ratio for TVR is 0.95, whereas the ratio for BOC is only 0.04.[@R20] The combination of CYP3A/OATP1B1 inhibition by TVR was most likely also observed in a study where TVR was coadministered with atorvastatin, a substrate for both CYP3A and OATP1B1.[@R8] In this study, TVR increased the AUC of atorvastatin 7.88-fold whereas in a similar study, BOC only increased the exposure of atorvastatin 2.30-fold.[@R6]\n\nThe magnitude of the MVC interaction with TVR is also consistent with that observed in a previous drug interaction study where MVC was dosed in combination with saquinavir/ritonavir (SQV/r), where MVC exposures were increased 9.77-fold.[@R1] To date, TVR and SQV/r are the only 2 agents shown to increase the geometric mean MVC AUC greater than 5-fold. ", "Similarly to TVR, SQV/r is a potent inhibitor of CYP3A (increases midazolam AUC 11.4-fold), an inhibitor of P-gp (increases digoxin AUC by 49%) and an inhibitor of OATP1B1 (IC~50~ = 2.1 μM).[@R22]\n\nIn the present study, MVC average concentrations (C~avg~), when dosed at 150 mg BID in the presence of TVR and BOC, were 474 ng/mL and 151 ng/mL, respectively. ", "The exposures seen in this study are within the exposure range observed in phase III clinical studies evaluating the efficacy and safety of MVC in patients with CCR5-topic HIV-1[@R24] and are at or above the C~avg~ exposure at which near maximal virologic efficacy is achieved with MVC (≥75--100 ng/mL).[@R25] These findings suggest that MVC should be dosed at 150 mg BID when coadministered with either BOC or TVR, consistent with current dose recommendations for MVC when dosed in combination with other potent CYP3A inhibitors.[@R1] However, as regulatory discussions are pending, we would suggest that prescribers should refer to your local prescribing information for MVC dosing recommendations with BOC and TVR in their region.", "\n\nAs with most drug--drug interaction studies, healthy volunteers, rather than patients, were enrolled in this study. ", "MVC is primarily metabolized by the liver and therefore exposures have the potential to be higher in HIV/HCV coinfected patients with hepatic impairment, as hepatic damage and disease may affect CYP enzyme activity.[@R27] A study conducted in HIV-negative subjects with hepatic impairment demonstrated that MVC exposures in subjects with mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic impairment had a geometric mean 25% (mild) and 46% (moderate) greater AUC~last~ and a 11% (mild) and 32% (moderate) greater C~max~ relative to subjects with normal hepatic function[@R33] after a single dose of MVC 300 mg. ", "As such, patients with moderate hepatic impairment receiving MVC with potent CYP3A inhibitors, such as BOC, should be monitored closely.[@R1] Currently, TVR is not recommended to be dosed in patients with moderate and severe hepatic impairment.[@R8] No exposure data are available for MVC in severe hepatic impairment, thus no recommendation in this population can be given at this time.", "\n\nIn this study, MVC did not seem to cause clinically significant changes in concentrations of either BOC or TVR as the mean PK exposures of BOC (AUC~8~ 5404 ng·h/mL; C~8~ 80.7 ng/mL) and TVR (AUC~8~ 21980 ng·h/mL; C~8~ 1943 ng/mL) after MVC coadministration were consistent with those previously reported when BOC (AUC~8~ 4601--7070 ng·h/mL; C~8~ 88.5--111 ng/mL) and TVR (AUC~8~ 18157--22300 ng·h/mL; C~8~ 1505--2030 ng/mL) were dosed alone.[@R1] These findings suggest that no dose adjustment for BOC or TVR is warranted when coadministered with MVC.", "\n\nFinally, MVC coadministered with BOC or TVR was generally well tolerated among the small population of healthy volunteers in this study. ", "Although AE incidence was higher during combination treatment, the majority of AEs were mild or moderate in severity, and there were no serious AEs, discontinuations because of treatment-related AEs, or deaths during the study. ", "The most frequently experienced AEs were dysgeusia and pruritus for the MVC plus BOC combination, and headache and fatigue for the MVC plus TVR combination. ", "Fatigue, dysgeusia, and pruritus seemed to be unique to the coadministration of MVC plus BOC or MVC plus TPV and were consistent with previous findings for BOC or TPV alone.[@R6] No postural hypotension or dizziness was reported in this study despite the significant increases in MVC exposures when coadministered with BOC or TVR.", "\n\nCONCLUSIONS {#s5}\n===========\n\nIn summary, MVC exposure was increased in the presence of BOC or TVR. ", "These findings are consistent with evidence that both BOC and TVR are potent inhibitors of CYP3A, and support dosing of MVC at 150 mg BID when coadministered with either BOC or TVR. ", "When coadministered with MVC, BOC and TVR exposures were consistent with historical BOC and TVR monotherapy data; therefore, no dose adjustment for BOC or TVR is warranted with MVC. ", "MVC coadministered with BOC or TVR was generally well tolerated with no unexpected safety findings.", "\n\nEditorial support was provided by Lynsey Stevenson of Complete Medical Communications.", "\n\nSupported by ViiV Healthcare and managed by Pfizer Inc.\n\nPresented at the 14th International Workshop on Clinical Pharmacology of HIV, April 23, 2013, Amsterdam, the Netherlands.", "\n\nM.V., A.P., C.K., A.F., and J.H. are employees of Pfizer, Inc and hold stock/stock options in Pfizer, Inc.\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy.", "\nRecent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). ", "To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. ", "All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). ", "Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. ", "Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. ", "Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. ", "Infants in the treated group had transient hyperglycemia and hypertension. ", "There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. ", "We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. ", "To substantiate our result, large randomized controlled trials are needed and warranted." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "/* crypto/engine/eng_openssl.c */\n/*\n * Written by Geoff Thorpe (geoff@geoffthorpe.net) for the OpenSSL project\n * 2000.", "\n */\n/* ====================================================================\n * Copyright (c) 1999-2001 The OpenSSL Project. ", " 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\n * are met:\n *\n * 1. ", "Redistributions of source code must retain the above copyright\n * notice, this list of conditions and the following disclaimer.", "\n *\n * 2. ", "Redistributions in binary form must reproduce the above copyright\n * notice, this list of conditions and the following disclaimer in\n * the documentation and/or other materials provided with the\n * distribution.", "\n *\n * 3. ", "All advertising materials mentioning features or use of this\n * software must display the following acknowledgment:\n * \"This product includes software developed by the OpenSSL Project\n * for use in the OpenSSL Toolkit. (", "http://www.OpenSSL.org/)\"\n *\n * 4. ", "The names \"OpenSSL Toolkit\" and \"OpenSSL Project\" must not be used to\n * endorse or promote products derived from this software without\n * prior written permission. ", "For written permission, please contact\n * licensing@OpenSSL.org.", "\n *\n * 5. ", "Products derived from this software may not be called \"OpenSSL\"\n * nor may \"OpenSSL\" appear in their names without prior written\n * permission of the OpenSSL Project.", "\n *\n * 6. ", "Redistributions of any form whatsoever must retain the following\n * acknowledgment:\n * \"This product includes software developed by the OpenSSL Project\n * for use in the OpenSSL Toolkit (http://www.OpenSSL.org/)\"\n *\n * THIS SOFTWARE IS PROVIDED BY THE OpenSSL PROJECT ``AS IS'' AND ANY\n * EXPRESSED OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE\n * IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR\n * PURPOSE ARE DISCLAIMED. ", " IN NO EVENT SHALL THE OpenSSL PROJECT OR\n * ITS CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,\n * SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT\n * NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES;\n * LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION)\n * HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT,\n * STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE)\n * ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED\n * OF THE POSSIBILITY OF SUCH DAMAGE.", "\n * ====================================================================\n *\n * This product includes cryptographic software written by Eric Young\n * (eay@cryptsoft.com). ", " This product includes software written by Tim\n * Hudson (tjh@cryptsoft.com).", "\n *\n */\n/* ====================================================================\n * Copyright 2002 Sun Microsystems, Inc. ALL RIGHTS RESERVED.", "\n * ECDH support in OpenSSL originally developed by\n * SUN MICROSYSTEMS, INC., ", "and contributed to the OpenSSL project.", "\n */\n\n#include <stdio.h>\n#include <openssl/crypto.h>\n#include \"cryptlib.h\"\n#include <openssl/engine.h>\n#include <openssl/dso.h>\n#include <openssl/pem.h>\n#include <openssl/evp.h>\n#include <openssl/rand.h>\n#ifndef OPENSSL_NO_RSA\n# include <openssl/rsa.h>\n#endif\n#ifndef OPENSSL_NO_DSA\n# include <openssl/dsa.h>\n#endif\n#ifndef OPENSSL_NO_DH\n# include <openssl/dh.h>\n#endif\n\n/*\n * This testing gunk is implemented (and explained) lower down. ", "It also\n * assumes the application explicitly calls \"ENGINE_load_openssl()\" because\n * this is no longer automatic in ENGINE_load_builtin_engines().", "\n */\n#define TEST_ENG_OPENSSL_RC4\n#define TEST_ENG_OPENSSL_PKEY\n/* #define TEST_ENG_OPENSSL_RC4_OTHERS */\n#define TEST_ENG_OPENSSL_RC4_P_INIT\n/* #define TEST_ENG_OPENSSL_RC4_P_CIPHER */\n#define TEST_ENG_OPENSSL_SHA\n/* #define TEST_ENG_OPENSSL_SHA_OTHERS */\n/* #define TEST_ENG_OPENSSL_SHA_P_INIT */\n/* #define TEST_ENG_OPENSSL_SHA_P_UPDATE */\n/* #define TEST_ENG_OPENSSL_SHA_P_FINAL */\n\n/* Now check what of those algorithms are actually enabled */\n#ifdef OPENSSL_NO_RC4\n# undef TEST_ENG_OPENSSL_RC4\n# undef TEST_ENG_OPENSSL_RC4_OTHERS\n# undef TEST_ENG_OPENSSL_RC4_P_INIT\n# undef TEST_ENG_OPENSSL_RC4_P_CIPHER\n#endif\n#if defined(OPENSSL_NO_SHA) || defined(OPENSSL_NO_SHA0) || defined(OPENSSL_NO_SHA1)\n# undef TEST_ENG_OPENSSL_SHA\n# undef TEST_ENG_OPENSSL_SHA_OTHERS\n# undef TEST_ENG_OPENSSL_SHA_P_INIT\n# undef TEST_ENG_OPENSSL_SHA_P_UPDATE\n# undef TEST_ENG_OPENSSL_SHA_P_FINAL\n#endif\n\n#ifdef TEST_ENG_OPENSSL_RC4\nstatic int openssl_ciphers(ENGINE *e, const EVP_CIPHER **cipher,\n const int **nids, int nid);\n#endif\n#ifdef TEST_ENG_OPENSSL_SHA\nstatic int openssl_digests(ENGINE *e, const EVP_MD **digest,\n const int **nids, int nid);\n#endif\n\n#ifdef TEST_ENG_OPENSSL_PKEY\nstatic EVP_PKEY *openssl_load_privkey(ENGINE *eng, const char *key_id,\n UI_METHOD *ui_method,\n void *callback_data);\n#endif\n\n/* The constants used when creating the ENGINE */\nstatic const char *engine_openssl_id = \"openssl\";\nstatic const char *engine_openssl_name = \"Software engine support\";\n\n/*\n * This internal function is used by ENGINE_openssl() and possibly by the\n * \"dynamic\" ENGINE support too\n */\nstatic int bind_helper(ENGINE *e)\n{\n if (!", "ENGINE_set_id(e, engine_openssl_id)\n || !", "ENGINE_set_name(e, engine_openssl_name)\n#ifndef TEST_ENG_OPENSSL_NO_ALGORITHMS\n# ifndef OPENSSL_NO_RSA\n || !", "ENGINE_set_RSA(e, RSA_get_default_method())\n# endif\n# ifndef OPENSSL_NO_DSA\n || !", "ENGINE_set_DSA(e, DSA_get_default_method())\n# endif\n# ifndef OPENSSL_NO_ECDH\n || !", "ENGINE_set_ECDH(e, ECDH_OpenSSL())\n# endif\n# ifndef OPENSSL_NO_ECDSA\n || !", "ENGINE_set_ECDSA(e, ECDSA_OpenSSL())\n# endif\n# ifndef OPENSSL_NO_DH\n || !", "ENGINE_set_DH(e, DH_get_default_method())\n# endif\n || !", "ENGINE_set_RAND(e, RAND_SSLeay())\n# ifdef TEST_ENG_OPENSSL_RC4\n || !", "ENGINE_set_ciphers(e, openssl_ciphers)\n# endif\n# ifdef TEST_ENG_OPENSSL_SHA\n || !", "ENGINE_set_digests(e, openssl_digests)\n# endif\n#endif\n#ifdef TEST_ENG_OPENSSL_PKEY\n || !", "ENGINE_set_load_privkey_function(e, openssl_load_privkey)\n#endif\n )\n return 0;\n /*\n * If we add errors to this ENGINE, ensure the error handling is setup\n * here\n */\n /* openssl_load_error_strings(); */\n return 1;\n}\n\nstatic ENGINE *engine_openssl(void)\n{\n ENGINE *ret = ENGINE_new();\n if (!", "ret)\n return NULL;\n if (!", "bind_helper(ret)) {\n ENGINE_free(ret);\n return NULL;\n }\n return ret;\n}\n\nvoid ENGINE_load_openssl(void)\n{\n ENGINE *toadd = engine_openssl();\n if (!", "toadd)\n return;\n ENGINE_add(toadd);\n /*\n * If the \"add\" worked, it gets a structural reference. ", "So either way, we\n * release our just-created reference.", "\n */\n ENGINE_free(toadd);\n ERR_clear_error();\n}\n\n/*\n * This stuff is needed if this ENGINE is being compiled into a\n * self-contained shared-library.", "\n */\n#ifdef ENGINE_DYNAMIC_SUPPORT\nstatic int bind_fn(ENGINE *e, const char *id)\n{\n if (id && (strcmp(id, engine_openssl_id) !", "= 0))\n return 0;\n if (!", "bind_helper(e))\n return 0;\n return 1;\n}\n\nIMPLEMENT_DYNAMIC_CHECK_FN()\n IMPLEMENT_DYNAMIC_BIND_FN(bind_fn)\n#endif /* ENGINE_DYNAMIC_SUPPORT */\n#ifdef TEST_ENG_OPENSSL_RC4\n/*-\n * This section of code compiles an \"alternative implementation\" of two modes of\n * RC4 into this ENGINE. ", "The result is that EVP_CIPHER operation for \"rc4\"\n * should under normal circumstances go via this support rather than the default\n * EVP support. ", "There are other symbols to tweak the testing;\n * TEST_ENC_OPENSSL_RC4_OTHERS - print a one line message to stderr each time\n * we're asked for a cipher we don't support (should not happen).", "\n * TEST_ENG_OPENSSL_RC4_P_INIT - print a one line message to stderr each time\n * the \"init_key\" handler is called.", "\n * TEST_ENG_OPENSSL_RC4_P_CIPHER - ditto for the \"cipher\" handler.", "\n */\n# include <openssl/rc4.h>\n# define TEST_RC4_KEY_SIZE 16\nstatic int test_cipher_nids[] = { NID_rc4, NID_rc4_40 };\n\nstatic int test_cipher_nids_number = 2;\ntypedef struct {\n unsigned char key[TEST_RC4_KEY_SIZE];\n RC4_KEY ks;\n} TEST_RC4_KEY;\n# define test(ctx) ((TEST_RC4_KEY *)(ctx)->cipher_data)\nstatic int test_rc4_init_key(EVP_CIPHER_CTX *ctx, const unsigned char *key,\n const unsigned char *iv, int enc)\n{\n# ifdef TEST_ENG_OPENSSL_RC4_P_INIT\n fprintf(stderr, \"(TEST_ENG_OPENSSL_RC4) test_init_key() called\\n\");\n# endif\n memcpy(&test(ctx)->key[0], key, EVP_CIPHER_CTX_key_length(ctx));\n RC4_set_key(&test(ctx)->ks, EVP_CIPHER_CTX_key_length(ctx),\n test(ctx)->key);\n return 1;\n}\n\nstatic int test_rc4_cipher(EVP_CIPHER_CTX *ctx, unsigned char *out,\n const unsigned char *in, size_t inl)\n{\n# ifdef TEST_ENG_OPENSSL_RC4_P_CIPHER\n fprintf(stderr, \"(TEST_ENG_OPENSSL_RC4) test_cipher() called\\n\");\n# endif\n RC4(&test(ctx)->ks, inl, in, out);\n return 1;\n}\n\nstatic const EVP_CIPHER test_r4_cipher = {\n NID_rc4,\n 1, TEST_RC4_KEY_SIZE, 0,\n EVP_CIPH_VARIABLE_LENGTH,\n test_rc4_init_key,\n test_rc4_cipher,\n NULL,\n sizeof(TEST_RC4_KEY),\n NULL,\n NULL,\n NULL,\n NULL\n};\n\nstatic const EVP_CIPHER test_r4_40_cipher = {\n NID_rc4_40,\n 1, 5 /* 40 bit */ , 0,\n EVP_CIPH_VARIABLE_LENGTH,\n test_rc4_init_key,\n test_rc4_cipher,\n NULL,\n sizeof(TEST_RC4_KEY),\n NULL,\n NULL,\n NULL,\n NULL\n};\n\nstatic int openssl_ciphers(ENGINE *e, const EVP_CIPHER **cipher,\n const int **nids, int nid)\n{\n if (!", "cipher) {\n /* We are returning a list of supported nids */\n *nids = test_cipher_nids;\n return test_cipher_nids_number;\n }\n /* We are being asked for a specific cipher */\n if (nid == NID_rc4)\n *cipher = &test_r4_cipher;\n else if (nid == NID_rc4_40)\n *cipher = &test_r4_40_cipher;\n else {\n# ifdef TEST_ENG_OPENSSL_RC4_OTHERS\n fprintf(stderr, \"(TEST_ENG_OPENSSL_RC4) returning NULL for \"\n \"nid %d\\n\", nid);\n# endif\n *cipher = NULL;\n return 0;\n }\n return 1;\n}\n#endif\n\n#ifdef TEST_ENG_OPENSSL_SHA\n/* Much the same sort of comment as for TEST_ENG_OPENSSL_RC4 */\n# include <openssl/sha.h>\nstatic int test_digest_nids[] = { NID_sha1 };\n\nstatic int test_digest_nids_number = 1;\nstatic int test_sha1_init(EVP_MD_CTX *ctx)\n{\n# ifdef TEST_ENG_OPENSSL_SHA_P_INIT\n fprintf(stderr, \"(TEST_ENG_OPENSSL_SHA) test_sha1_init() called\\n\");\n# endif\n return SHA1_Init(ctx->md_data);\n}\n\nstatic int test_sha1_update(EVP_MD_CTX *ctx, const void *data, size_t count)\n{\n# ifdef TEST_ENG_OPENSSL_SHA_P_UPDATE\n fprintf(stderr, \"(TEST_ENG_OPENSSL_SHA) test_sha1_update() called\\n\");\n# endif\n return SHA1_Update(ctx->md_data, data, count);\n}\n\nstatic int test_sha1_final(EVP_MD_CTX *ctx, unsigned char *md)\n{\n# ifdef TEST_ENG_OPENSSL_SHA_P_FINAL\n fprintf(stderr, \"(TEST_ENG_OPENSSL_SHA) test_sha1_final() called\\n\");\n# endif\n return SHA1_Final(md, ctx->md_data);\n}\n\nstatic const EVP_MD test_sha_md = {\n NID_sha1,\n NID_sha1WithRSAEncryption,\n SHA_DIGEST_LENGTH,\n 0,\n test_sha1_init,\n test_sha1_update,\n test_sha1_final,\n NULL,\n NULL,\n EVP_PKEY_RSA_method,\n SHA_CBLOCK,\n sizeof(EVP_MD *) + sizeof(SHA_CTX),\n};\n\nstatic int openssl_digests(ENGINE *e, const EVP_MD **digest,\n const int **nids, int nid)\n{\n if (!", "digest) {\n /* We are returning a list of supported nids */\n *nids = test_digest_nids;\n return test_digest_nids_number;\n }\n /* We are being asked for a specific digest */\n if (nid == NID_sha1)\n *digest = &test_sha_md;\n else {\n# ifdef TEST_ENG_OPENSSL_SHA_OTHERS\n fprintf(stderr, \"(TEST_ENG_OPENSSL_SHA) returning NULL for \"\n \"nid %d\\n\", nid);\n# endif\n *digest = NULL;\n return 0;\n }\n return 1;\n}\n#endif\n\n#ifdef TEST_ENG_OPENSSL_PKEY\nstatic EVP_PKEY *openssl_load_privkey(ENGINE *eng, const char *key_id,\n UI_METHOD *ui_method,\n void *callback_data)\n{\n BIO *in;\n EVP_PKEY *key;\n fprintf(stderr, \"(TEST_ENG_OPENSSL_PKEY)Loading Private key %s\\n\",\n key_id);\n in = BIO_new_file(key_id, \"r\");\n if (!", "in)\n return NULL;\n key = PEM_read_bio_PrivateKey(in, NULL, 0, NULL);\n BIO_free(in);\n return key;\n}\n#endif\n" ]

{ "pile_set_name": "Github" }

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[ "Yan Vichnyi\n\nYan Vichnyi (; born 27 February 1997 in Zaporizhya, Ukraine) is a professional Ukrainian football goalkeeper.", "\n\nCareer\nVichnyi is a product of FC Metalurh Zaporizhia and UFK Kharkiv youth sportive systems.", "\n\nHe spent his career in the Ukrainian Premier League Reserves club FC Vorskla Poltava. ", "And in summer 2015 Vichnyi was promoted to the main-squad team of the FC Vorskla in the Ukrainian Premier League. ", "He made his debut for Vorskla Poltava in the Ukrainian Premier League in a match against FC Dynamo Kyiv on 4 October 2015.", "\n\nReferences\n\nExternal links \n Profile on FFU site \n \n\nCategory:1997 births\nCategory:Living people\nCategory:People from Zaporizhia\nCategory:Ukrainian footballers\nCategory:Association football goalkeepers\nCategory:Ukrainian Premier League players\nCategory:FC Vorskla Poltava players" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "Dicerca tuberculata\n\nDicerca tuberculata is a species of metallic wood-boring beetle in the family Buprestidae. ", "It is found in North America.", "\n\nReferences\n\nFurther reading\n\n \n \n \n\nCategory:Buprestidae\nCategory:Articles created by Qbugbot\nCategory:Beetles described in 1837" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "Wadō-Kuroya Station\n\nis a railway station on the Chichibu Main Line in Chichibu, Saitama, Japan, operated by the private railway operator Chichibu Railway.", "\n\nLines\nWadō-Kuroya Station is served by the Chichibu Main Line from to , and is located from Hanyū.", "\n\nStation layout\nThe station is staffed and consists of a single island platform serving two tracks. ", "An additional bidirectional loop runs alongside track 2 for use by freight services.", "\n\nPlatforms\n\nAdjacent stations\n\nHistory\n\nThe station opened as Kuroya Station on October 27, 1914. ", "The station name was changed to Wadō-Kuroya Station from April 1, 2008.", "\n\nPassenger statistics\nIn fiscal 2000, the station was used by an average of 462 passengers daily.", "\n\nSurrounding area\n Arakawa River\n National Route 140\n Hijiri Shrine\n\nSee also\n List of railway stations in Japan\n\nReferences\n\nExternal links\n\n Wado-Kuroya Station information (Saitama Prefectural Government) \n Wado-Kuroya Station information \n\nCategory:Railway stations in Saitama Prefecture\nCategory:Railway stations opened in 1914\nCategory:1914 establishments in Japan" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "by Daniel Loxton\n\nSkull Island, Canadaa still from the film King Kong.", "A sketch made from Kemp’s description many months after his sighting. ", "© 1933 RKO Pictures Inc., © 2005 Warner Bros. Entertainment Inc.The 1933 and 2005 versions of King Kong share many rich details, and a moral. ", "There are those who suggest that moral must be something about the power of love, but I suggest the moral is this:“Never, ever go to Skull Island.", "”Skull Island, the setting for the second act of King Kong, is an utterly nightmarish place. ", "A steaming jungle packed with prehistoric beasts and crawling with unlikely monsters, it is a place where even the insects can drag you away for dinner.", "It’s not surprising that this exotic, terrifying place awed Depression-era movie audiences. ", "When Kong opened in 1933, no one had ever seen anything like it. ", "The revolutionary special effects, the scope of imagination, the depth of immersion in another world — all these created a blockbuster experience that still echoes in the popular imagination today.", "My story begins on another, sleepier island: Vancouver Island, off the western coast of British Columbia, Canada.", "At the southern tip lies the provincial capital city of Victoria, a bustling tourist destination with a busy cruise ship port. ", "Today it bills itself as “the City of Gardens,” but in 1933 it enjoyed worldwide fame for something altogether more mysterious — nothing less than an 80-foot sea monster, called Cadborosaurus.", "According to legend, an awesome, primeval monster — a huge serpent with flippers, a mane, and a head something like that of a camel or horse — slides undetected through the frigid waters off British Columbia and Washington State. ", "Could a living dinosaur, a monster out of time, lurk here beneath the waves?That question hinges on a moment in history.", "Imagine yourself in 1933 for a moment. ", "The Great Depression was causing tremendous hardship at home, while daily newspaper headlines carried ever more bad news about Adolph Hitler. ", "As tensions continued to mount between the new Nazi government of Germany and the rest of Europe, war seemed increasingly likely.", "The news featured one bummer story after another, and people needed a pick-me-up. ", "In Victoria, that came in the form of headlines proclaiming, “Yachtsmen Tell Of Huge Serpent Seen Off Victoria.", "”Two civil servants, named Langley and Kemp, told the Victoria Daily Times that they’d each independently seen huge sea monsters. ", "According to Langley, he and his wife were out sailing when they heard “a grunt and a snort accompanied by a huge hiss,” and then “saw a huge object about 90 to 100 feet off,” of which “[t]he only part of it that we saw was a huge dome of what was apparently a portion of its back.” ", "It was, he said, only visible for a few seconds before diving.", "What strikes me about Langley’s monster — and contemporary critics were quick to point this out — is that it swam like a whale, it sounded like a whale, and it looked a whale. ", "Now, whales definitely live in the area: Humpbacks, grey whales, sperm whales, and others. ", "Even today, boatloads of whale-watching tourists leave Victoria’s downtown Inner Harbour every few minutes. ", "Given that we have no data here except a momentary, unsubstantiated, undeniably whale-like anecdote, the Langley sighting seems to me to be a completely trivial case.", "But the Kemp case was more interesting. ", "It was his sustained daylight sighting that fueled a Cadborosaurus media frenzy in Victoria and across the continent, inspiring a rash of copycat sightings — and launching an enduring legend.", "According to Kemp’s 1933 story, he and his family were picnicking one afternoon in the previous year, on a group of tiny islands just off Victoria, when they saw something extraordinary. ", "A huge creature swam up the channel between Chatham and Strongtide Islands leaving an impressive wake. ", "Kemp recalled, “The channel at this point is about 500 yards wide. ", "Swimming to the steep rocks of the island opposite, the creature shot its head out of the water on to the rock, and moving its head from side to side, appeared to be taking its bearings. ", "Then fold after fold of its body came to the surface. ", "Towards the tale it appeared serrated, like the cutting edge of a saw, with something moving flail-like at the extreme end. ", "The movements were like those of a crocodile. ", "Around the head appeared a sort of mane, which drifted round the body like kelp.", "”Kemp estimated the animal was over 60 feet long. ", "Although it was indistinct with distance — it was at least 1200 feet away, maybe 1500 — this was no fleeting sighting. ", "According to Kemp, they watched the monster for several minutes before it slid off the rocks swam away.", "What was it? ", "It sounds to me like a group of sea lions among the distant kelp, viewed at too great a distance and remembered with too great a dollop of imagination. ", "But the interesting question is, “Whose imagination?”Kemp’s description gives a clue. ", "Despite copycat sightings describing literal “sea serpents,” and despite the serpentine image of Cadborosaurus now popular among cryptozoologists, it’s striking that neither of the original eyewitness reports described serpents at all!Langley described something like a whale; Kemp described something like a dinosaur. ", "His monster, he said, “gave the impression that it was much more like a reptile than a serpent….”Responding to the Kemp sighting, one letter to the editor offered an opinion that Caddy might be a sauropod dinosaur called diplodocus. ", "This writer noted Caddy’s long neck and long tail, and called it “probable that it has legs with webbed feet with which it propels itself.", "”Kemp seized on this dinosaur idea with enthusiasm, and produced an eyewitness sketch consistent with a sauropod. ", "He agreed, “Diplodocus describes better what we saw than anything else. ", "My first feelings on viewing the creature were of being transferred to a prehistoric period when all sorts of hideous creatures abounded.” ", "He said the creature’s movements “were not fishlike, but rather more like the movement of a huge lizard.", "”This combination of elements — a swimming sauropod dinosaur, and the notion of being transported to a prehistoric world full of terrible monsters — sounded very familiar to me. ", "I was reminded of another sauropod, filmed swimming in a primal environment teaming with hideous creatures: Skull Island, as depicted in the blockbuster film King Kong! ", "Comparing Kemp’s description and sketch with stills from the film, the parallels are striking.", "The most famous Loch Ness monster hoax photo () compared with a still from the film King Kong. ", "Both images feature small models. ", "© 1933 RKO Pictures Inc., © 2005 Warner Bros. Entertainment Inc.Could the film have inspired Kemp’s story? ", "The timeline certainly works: Kong, it happens, opened in Victoria just six months before Kemp and Langley created the legend of Cadborosaurus. ", "It blew movie-goers away, scared the socks off of people, and stuck in the memories of all who saw it. (", "Not coincidentally, the legend of the Loch Ness Monster was likewise created immediately after the release of King Kong, and the several key Nessie sightings seem almost lifted from the film. ", "It’s especially notable that the infamous fake “Surgeon’s Photo” looks virtually identical to a shot from the movie.)Is this similarity between Cadborosaurus and Kong suspicious? ", "You bet.", "Kemp’s original sighting was extremely uncertain, as he admitted, because of the tremendous distance involved (well over a thousand feet). ", "He couldn’t make out the key details. ", "For example, the creature’s head was just a blob. ", "It’s likely he saw a distant group of marine mammals swimming and climbing the rocks (as is entirely typical in the area), but was unable to make out what they were at that distance. ", "Perhaps he puzzled about it for a few months before King Kong planted a seed….When he finally met Langley, heard his sea monster story, and compared notes, Kemp’s memories were a year old, and very probably contaminated by Hollywood.", "That’s a recipe for a legend — but as scientific data, it’s a disaster.", "Where does this leave Cadborosaurus? ", "As so often in the paranormal world, it seems that the entire legendary edifice, all the sightings that followed, the books and TV programs and place in pop culture, all rests on a foundation of smoke.", "Smoke, and the flickering screen of a cinema._______________________________________________________________________________________________I found this interesting little article while poking around the web for Kong material... It's mostly about the Cadbororsaurus/Canadian sightings, of course, but it did mention that the Loch Ness Monster burst into public consciousness only after 1934, which was only a year after Kong's release. ", "Nessie has been sighted now and then for centuries before, but only after that photo popped up did it capture the world's attention... was it because of the ever-growing access to cameras, and thus more tangible proof, or were people's imaginations influenced by a Skull Island beast?Found here: http://www.skeptic.com/reading_room/sku ... nd-canada/" ]

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[ "Liquid Rhythms\n\nSaturdays from 1 am - 4 am\n\nLiquid Rhythms mixshow started on KRCL 90.9 FM back in Feb. 1997, and is now widely listened too one of the longest running mixshows of its kind, nationally and internationally. ", "DJ Kenn Burrola brings you a variety of Dance Music every week live in the mix. ", "From House Music, Electro House, Progressive House, EDM, etc. – ", "and also includes a RewindMix and an Old School mix." ]

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[ "Introduction: origin of chloroplasts {#Sec1}\n====================================\n\nOrganelles known as chloroplasts are characteristic for plant cells and eukaryotic algae (Leister [@CR49]). ", "Their main purpose is housing numerous metabolic reactions necessary for the life of the cell, such as photosynthesis---production of nutrients from water and carbon dioxide with use of absorbed sunlight. ", "They are believed to have originated from cyanobacteria, which have either invaded or been engulfed by a heterotrophic host cell approximately 1.5 billion years ago (Chan et al. [", "@CR10]). ", "In the process of primary endosymbiogenesis, the vast majority of cyanobacterial genes has either been lost or transferred to nucleus of host cell. ", "In parallel to these changes, some host genes acquired leading sequences, which made the transport of their products into the organelle possible (Green [@CR34]). ", "These changes eventually led to establishment of organelle known as primary plastid (Fig.", " [1](#Fig1){ref-type=\"fig\"}). ", "However, endosymbiosis has not ended there. ", "Majority of species belonging to Plantae has acquired secondary chloroplasts by establishing an endosymbiotic connection with chloroplast-containing algae. ", "The process begins with engulfment (or invasion by) a plastid-containing algal cell, which eventually either loses its nuclear genes or transfers them to the nucleus of a host cell (Fig.", " [1](#Fig1){ref-type=\"fig\"}) (Green [@CR34]; Turmel et al. [", "@CR83]). ", "It is worth noting that organelle-to-host nucleus gene transfer continues to this day (Kleine et al. [", "@CR45]). ", "This review will focus on analysis of the current knowledge about structure of chloroplast genomes and potential practical applications of plastome sequencing and engineering. ", "The terms 'plastid' and 'chloroplast' will be used throughout the text interchangeably. ", "The former term regards plastids that are not capable of photosynthesis due to the lack of chlorophyll.", "Fig.", " 1Structure of a typical chloroplast genome on example of *Arabidopsis thaliana*. *", "SSCR* small single copy region, *LSCR* large single copy region, and *IR-A and IR-B* inverted repeats. ", "Length of plastome and its parts in kbp\n\nStructure of chloroplast genome {#Sec2}\n===============================\n\nEach plastid has its own independent genome. ", "The vast majority of analyzed plastid DNA molecules (cpDNA) is inherited maternally and was found to be double-stranded and have a circular structure. ", "However, it is worth noting that branched and linear cpDNA molecules may also exist in some plants, such as maize seedlings and *Medicago truncatula* (Shaver et al. [", "@CR70], Oldenburg and Bendich [@CR64]). ", "cpDNA molecules are a part of protein-DNA complex known as nucleoid. ", "A single nucleoid contains 10--20 cpDNA copies and may be (1) surrounded by thylakoids in the center of chloroplast (red algae), (2) found in circular form in girdle lamellae (brown algae), or (3) found in matrix, between thylakoids (Kuroiwa [@CR48], Kobayashi et al. [", "@CR46]). ", "cpDNA usually exists in form of a monomer, but it is also capable of creating multimers (dimers, trimers, and the least common tetramers) (Lu et al. [", "@CR54]). ", "Unlike nuclear genome, plastome does not create complexes with histones. ", "However, the presence of plastome-encoded, histone-like HC protein has been confirmed in red algae (Kobayashi et al. [", "@CR46]).", "\n\n200--300 identical DNA molecules exist in the chloroplast. ", "Plastome size usually varies from 100 to 200 kbp. ", "The biggest size variation can be observed in green algae chloroplast genomes. ", "The smallest ones have been identified in *Helicosporidium* sp. *", "Simulium jonesie*---37.4 kbp and *Ostreococcus tauri* (71.6 kbp), while the largest ones were found in *Nephroselmis olivacea* (200.8 kbp) and *Dunaliella salina* (269 kbp) (Smith et al. [", "@CR76]). ", "Such differences have not been observed among land plants---their plastome size usually is within 120--160 kbp. (", "Table [1](#Tab1){ref-type=\"table\"}).Table 1Examples of selected parameters of the plastomes in different speciesSpeciesSequence length (kbp)Number of genesNumber of intronsTotal plastomeIR (A and B)SSCLSCProteinRNA*Arabidopsis thaliana*154.526.317.884.2854472*Nicotiana tabacum*155.825.318.486.7984575*Vitis vinifera*160.926.619.189.1845316*Phaseolus vulgaris*150.326.417.679.8834410*Triticum aestivum*134.520.712.880.3835063*Pinus thunbergii*119.70.653.065.712339nd*Zea mays*140.422.712.582.311146nd*Chlamydomonas reinhardtii*203.422.278.180.96940nd*Dunaliella salina*269.014.4112.9127.38236nd*Ostreococcus tauri*71.76.822.335.96133nd*Helicosporidium* sp. *", "ex Simulium*37.5ababab2628nd*Euglena gracilis*143.2ababab6748399*Nephroselmis olivacea*200.846.116.492.115545ab*Gracilaria tenuistipitata*183.8ababab20333ndAll data comes from NCBI and the Chloroplast Genome Database*IR* inverted repeats, *SSC* small single copy, *LSC* large single copy, *ab* absence, *nd* no data\n\nTypical plastomes have a pair of identical inverted repeats (IRs), 5--76 kbp each (although in *Pinus thunbergii* they are just 600 bp long), separated by small and large single copy regions (SSC and LSC, respectively) (Fig.", " [1](#Fig1){ref-type=\"fig\"}). ", "IRs usually contain three highly conservative regions coding rRNAs and some tRNAs and are very similar to each other. ", "Exceptions from this rule were discovered in *Pisum sativum*, *Vicia faba*, *Medicago sativa* (which contains a single IR-like sequence), and *Euglena gracilis* (3 direct repeats). ", "Some plastomes do not have inverted repeats (e.g., *Helicosporidium* sp. *", "ex Simulium*, *Euglena gracilis*, *Gracilaria tenuistipitata*).", "\n\nSequences separating IRs, short and long single copy regions, are unique. ", "Size of the latter has major influence on size of the entire plastome (Shaw et al. [", "@CR71]). ", "One of the largest LSCs (127.3 kbp) has been found in *Dunaliella salina* (Table [1](#Tab1){ref-type=\"table\"}).", "\n\nPlastome usually contains 100--120 functional genes, and their size does not directly correlate with plastome size. ", "All chloroplast genomes contain genes encoding proteins, tRNA and rRNA (De Las Rivas et al. [", "@CR22]; Cui et al. [", "@CR13]; Wicke et al. [", "@CR93]). ", "Among species with more genes, some genes (mostly protein-encoding ones) still need to be analyzed. ", "For example, *Chlorella vulgaris* is estimated to have 174 genes (including 63 of hypothetical or uncharacterized proteins) (Cui et al. [", "@CR13]). ", "Vast majority of telomic plants has 80--100 defined protein coding genes (and only a few undefined, whose products participate in: translation, transcription, photosynthesis, energy metabolism, fatty acid metabolism, transport, and cofactor biosynthesis (Barkan [@CR2]; Green [@CR34]). ", "RNA genes are defined more accurately---6--8 rRNA genes are present in IRs, and 36--40 tRNA genes are spread across the entire plastome (Wicke et al. [", "@CR93]).", "\n\nAside from aforementioned genes, many conserved hypothetical ORFs (ycfs) were discovered, but their functions remained unknown until recent years. ", "For a long time, *ycf1* gene remained the biggest mystery---while its presence was necessary for survival of researched organisms (*Nicotiana tabaccum* and *Chlamydomonas reinhardtii*), its function was unknown, and its absence in plastomes of *Poaceae* posed more questions (Boudreau et al. [", "@CR7]; Drescher et al. [", "@CR28]; Guisinger et al. [", "@CR36]; de Vries et al. [", "@CR23]). ", "However, in 2013, it has been discovered that in *Arabidopsis thaliana,* this gene encodes Tic214, which is a part of general TIC translocon, necessary for transfer of nuclear proteins into the chloroplast (Kikuchi et al. [", "@CR44]). ", "Currently, *ycf2* remains as the only hypothetical ORF whose protein has an unknown function.", "\n\nAn interesting parameter of plastomes is their number of introns. ", "In land plant plastomes, group I and II introns have been identified (with the latter representing over 90 % of intron pool) (Eckard [@CR30]). ", "However, plastomes of genus *Euglena* also contain 73--119 nt long group III introns, derived from group II introns, but lacking their D2--D5 domains (Sheveleva and Hallick [@CR73]). ", "Introns are present both in protein-coding and RNA genes.", "\n\nAmong selected species representing the monocots, the intron number is as follows: *Oryza sativa*---60; *Hordeum vulgare*---14; *Triticum aestivum*---63; among dicots: *Vitis vinifera*---16; *Solanum tuberosum*---22; *Nicotiana tabacum*---75; *Populus trichocarpa*---26; *Pinus koraiensis*---36; and *Arabidopsis thaliana*---72 (Cui et al. [", "@CR13]). *", "Euglena gracilis* has a distinctively high number of introns (399---over 40 % of total ctDNA). ", "Its special trait is the presence of 15 twintrons---group II and III introns present within other introns from these groups. ", "Simple and complex twintrons can be distinguished---in the former, a single intron is inserted into another, while the representatives of the latter group consist of at least two introns inserted into another intron (Hallick et al. [", "@CR38]).", "\n\nHowever, in most of species, the number of introns varies between one and few dozen, with no regularity among species from the same taxon---Solanaceae (*Solanum tuberosum*---22, *Nicotiana tabacum*---75, and *Lycopersicon esculentum cultivar LA3023*---17) and Fabaceae (*Lotus corniculatus*---69, *Glycine max*---25, and *Phaseolus vulgaris*---10) are a prime example. ", "On the other hand, some species have no introns whatsoever (*Cyanidioschyzon merolae*, *Cyanidium caldarium*, *Gracilaria tenuistipitata*, *Nephroselmis olivacea*, and *Porphyra purpurea*) (Cui et al. [", "@CR13]).", "\n\nA different content of GC pairs is a trait strongly distinguishing plastomes from nuclear genomes. ", "In former, GC pairs represent just \\~30 % of total base pairs---it is caused by multiple traits of chloroplast, such as specific properties of chloroplast DNA polymerase and repair systems (Nielsen et al. [", "@CR62]).", "\n\nChloroplast gene expression {#Sec3}\n===========================\n\nTranscription: PEP and NEP polymerases {#Sec4}\n--------------------------------------\n\nDespite heavily depending on nucleus-derived proteins, chloroplasts possess their own system responsible for expression of genes, which originate from ancestral cyanobacteria (Yagi and Shiina [@CR94]). ", "RNA polymerases, responsible for transcription, are a crucial part of this machinery. ", "Two types of them can be found in a chloroplast---bacterial-type plastid-encoded RNA polymerase known as PEP and nuclear-encoded RNA polymerase (NEP), characteristic for angiosperms and *Physcomitrella* moss (Barkan [@CR2], Yagi and Shiina [@CR94], Liere et al. [", "@CR51]). ", "PEP consists of four subunits, α-, β-, β′-, and β″, which are encoded by *rpoA*, *rpoB*, *rpoC1*, and *rpoC2* plastid genes, respectively (Serino and Maliga [@CR69]). ", "It shares multiple traits, such as need for sigma factors in promoter recognition, with eubacterial RNA polymerases (however, it is worth noting that plant sigma factors are encoded in nucleus) (Tiller and Bock [@CR81]). ", "There are multiple types of sigma factors, which grant promoter specificity and take part in transcription of different groups of genes (Lerbs-Mache [@CR50]; Yagi and Shiina [@CR94]). ", "Meanwhile, NEP is a single-subunit polymerase, which shares many similarities with its counterparts in mitochondria and T3/7-type bacteriophage (Liere et al. [", "@CR51]). ", "Chloroplasts of higher plants contain two types of NEP (RPOTp and RPOTmp), which are capable of aiding PEP with transcription of plastome genes (Swiatecka-Hagenbruch et al. [", "@CR80]).", "\n\nPEP and NEP also recognize different promoters. ", "PEP promoters usually contain consensus sequences, −35 (TTGaca) and −10 (TAtaaT), and resemble bacterial σ70 promoters (Gruissem and Zurawski [@CR35]; Yagi and Shiina [@CR94]). ", "On the other hand, NEP has two main types of promoters---type I has an YRTA motif, which bears many similarities to mitochondrial promoters, and sequences crucial for type II promoters are placed downstream of the transcription initiation site (Sriraman et al. [", "@CR77]; Swiatecka-Hagenbruch et al. [", "@CR80]).", "\n\nPost-transcriptional processing and translation {#Sec5}\n-----------------------------------------------\n\nAfter transcription, initial transcripts undergo a multi-step processing, which includes splicing, transforming primary RNA molecules into mono- or oligocistronic mRNAs, formation and maturation of 5′ and 3′ ends, and finally RNA editing (Stern et al. [", "@CR78]; Tiller and Bock [@CR81]). ", "Most of components of translation in plastids (including 70S ribosomes) have cyanobacterial homologues (Tiller and Bock [@CR81]). ", "However, plastid translation also involves plenty of protein translation factors and positive regulatory mRNA elements, which do not have bacterial counterparts and increase the overall complexity of the process (Manuell et al. [", "@CR56]).", "\n\nThe process usually is initiated by small subunit (30S) of the ribosome and transfer RNA (tRNA), which selects the initiation site on the 5′ end of mRNA (usually starting from AUG triplet, although in some cases, GUG and UUG can also serve that role) (Sugiura et al. [", "@CR79]). ", "Once the site is selected, 50S subunit is attached to the complex, resulting in activation of initiation complex and start of elongation phase (Manuell et al. [", "@CR56]). ", "During this stage, ribosome progresses toward 3′ end of mRNA and adds amino acids carried by tRNA to the growing polypeptide. ", "This process is supported by translation elongation factors: eEF1A, eEF1B, eEF2, and eEF5 (Doerfel et al. [", "@CR27]; Gutierrez et al. [", "@CR37]; Browning and Bailey-Serres [@CR9]). ", "Each of these factors has a different purpose: eEF1A is responsible for delivering tRNA to the peptidyl transferase center, eEF1B serves as exchange factor for eEF1A in recycling GDP for GTP, eEF2 plays a role in moving tRNA that already dropped its amino acid off from P-site to E-site and eEF5 increases the efficacy of proline and glycine-rich protein elongation (Browning and Bailey-Serres [@CR9]).", "\n\nTermination of translation is caused by the ribosome reaching one of STOP codons (UAA, UAG, UGA). ", "Once it happens, two release factors (eRF1 and eRF3) bind the STOP codon and cut the newly created peptide off, paving the way for recycling of the ribosome (Dever and Green [@CR25]).", "\n\nPlastid genome sequencing {#Sec6}\n=========================\n\nThe research focused on learning the primary structure of plastomes has begun significantly earlier than similar studies regarding nuclear genomes. ", "First, complete chloroplast genome sequences were published in second half of 1980s (Shinozaki et al. [", "@CR74]), while the analogous data about eukaryotic nuclear genomes and prokaryotic genomes emerged over a decade later. ", "It was caused by a major difference in genome size and the level of advancement of sequencing techniques. ", "These two factors are the main reason for current abundance of knowledge about structure and functioning of plastomes. ", "At first, it had a purely cognitive character, but with time, it also gained a major applicational importance. ", "Referential databases (such as NCBI) currently contain information about chloroplast DNA of over 1000 plant species. ", "Most of them represent *Viridiplantae*---a clade of green plants, containing Chlorophyta and telome plants (Cocquyt et al. [", "@CR12]). ", "However, representatives of other taxons can also be found there, providing multiple opportunities of performing multi-directional comparative analyses. ", "Knowledge regarding organization and mechanisms of functioning of these genomes has drawn increasing attention of scientists. ", "This interest is expressed in form of constantly growing number of analyzed species. ", "Plastomes became an attractive target of intentional modifications, whose purpose is utilizing their capabilities in many fields of modern biotechnology---this trend is reflected by the amount of realized sequencing projects. ", "Genome engineering includes transfer of new genes (or other specific elements, such as promoters) and changes aimed at controlling expression of endogenous genes. ", "Creation of new construct and precise control of results is easier in plastomes than in nuclear genome. ", "The following chapters describe selected aspects of plastome modification.", "\n\nPlastid genome engineering {#Sec7}\n==========================\n\nIn recent years, plastid transformation has emerged as an attractive alternative for nuclear gene transformation. ", "However, the specific nature of chloroplasts posed multiple challenges in designing techniques that could be utilized in this process.", "\n\nDesigning plastid transformation {#Sec8}\n--------------------------------\n\nThe first and biggest obstacle was selecting DNA vectors. ", "Contrary to a random, *Agrobacterium*-mediated T-DNA integration in nuclear transgenes, chloroplast transgene integration is targeted due to homologous recombination of vector's flanking sequences and target DNA (Verma and Daniell [@CR86]; Meyers et al. [", "@CR59]). ", "Because of that, transgene must be flanked by two targeting sequences, each around 1--2 kb in size (Meyers et al. [", "@CR59]). ", "Currently, *Escherichia coli* plasmids incapable of replication in plastids are the most popular vectors. ", "However, maintaining efficiency of transplastomic plant generation requires reconstructing the vectors when a different plant species is chosen (Verma and Daniell [@CR86]). ", "Depending on the state of a target, DNA is introduced either via polyethylene glycol treatment (when protoplasts are targeted) or gene gun (when plastids are in an undamaged tissue) (Dix and Kavanagh [@CR26]; Maliga and Bock [@CR55]). ", "Selection of transformed plants is usually done by utilizing marker genes encoding resistance to antibiotics. ", "Currently, the most popular choice is *aadA*, a gene from *E. coli* responsible for encoding aminoglycoside 3″-adenylyl transferase, which grants resistance to spectinomycin (Bock [@CR4]).", "\n\nIt must be remembered that usually no more than a few plastomes undergo transformation. ", "To prevent the subsequent loss of transplastomes, propagation of transplastomic cell lines under selection pressure has to be maintained until all the wild-type genomes perish (Bock [@CR5]).", "\n\nPlastid engineering: pros and cons {#Sec9}\n----------------------------------\n\nPlastid engineering holds some important advantages over its nuclear counterpart. ", "First, vast majority of angiosperms inherits chloroplasts maternally, thus significantly reducing the risk of transgenic plants outcrossing with weeds via pollen---in turn, reduction of that risk means that transgene silencing, utilized in commercially used transgenic plants to prevent outcrossing, is no longer necessary (Wani et al. [", "@CR90]). ", "Transformed plastids are also capable of producing a significantly higher amount of target protein, reaching from 4 to 46.1 % (or, in most extreme cases, over 70 %) of total soluble protein (TSP), compared with 1--2 % in plants where nuclear genome underwent transformation (De Cosa et al. [", "@CR21]; Daniell [@CR14]; Oey et al. [", "@CR63]; Meyers et al. [", "@CR59]). ", "Usefulness of plastome transformation is further boosted by lack of silencing mechanisms which can interfere with the process and the ability to transfer full metabolic pathways into the plastome while maintaining their efficiency (Meyers et al. [", "@CR59]).", "\n\nWhile plastome engineering seems promising, it is important to remember that this technique is not free of limitations. ", "Most importantly, multiple economically important plants lack feasible protocols for plastid transformation; the alternative is to transfer transgenic plastid from transformable plants to the species of choice (Sigeno et al. [", "@CR75]; Ovcharenko et al. [", "@CR65]). ", "Unfortunately, this method is costly and time-consuming, which significantly limits its application in comparison to nuclear transformation. ", "However, it has been discovered that movement of cpDNA between cells of grafted plants is possible and can potentially improve efficiency of the whole process (however, it happens at a cost of increased likelihood of mutations and is limited to closely related species) (Bock [@CR4]). ", "It is also worth noting that proteins do not undergo glycosylation in transformed chloroplasts, although the impact of lack of this process depends on the protein of interest (McCabe et al. [", "@CR58]).", "\n\nPotential use of plastome analysis and modification {#Sec10}\n===================================================\n\nThanks to significant progress in plastome research, a potential range of ways to utilize plastome analysis and modification has greatly increased. ", "Here, we present the most promising types of current plastome research.", "\n\nProduction of antigens, vaccines, and therapeutic proteins {#Sec11}\n----------------------------------------------------------\n\nOne of the most promising potential uses of plastome engineering is the production of recombinant proteins. ", "High yield of target protein in transformed plastids and, among many positive traits, ability to apply post-translational modifications combined with lack of silencing, makes using chloroplast modification for production of antigens, enzymes, therapeutic proteins and vaccines, and intriguing prospect.", "\n\nOver the last 15 years, we have witnessed the emergence of multiple reports on production of bacterial and viral antigens that can be used in vaccines directed against the most dangerous human diseases. ", "However, most of them have only been tested on mice so far, which means that developing effective vaccines for humans will still take time (Daniell et al. [", "@CR18]). ", "Initially, most of vaccine antigens were expressed in tobacco leaves. ", "The first antigen expressed in tobacco was the cholera toxin B subunit (CTB), whose accumulation reached 4.1 % of total soluble leaf protein (TLP) (Daniell et al. [", "@CR16]). ", "Fusing CTB with merozoite surface protein-1 (MSP1) and apical membrane antigen-1 (AMA1) further increased TSP values (to 10.11 and 13.17 %, respectively) and isolated antigens provided inoculated mice with long-time protection against *Vibrio cholerae* (Davoodi-Semiromi et al. [", "@CR20]). ", "Other bacterial antigens successfully accumulated in tobacco include: heat-labile enterotoxin subunit B of *E. coli* responsible for diarrhea (Kang et al. [", "@CR42]), tetanus toxin fragment C (Tregoning et al. [", "@CR82]), and anthrax protective antigen (Watson et al. [", "@CR92]; Ruhlman et al. [", "@CR68]).", "\n\nTobacco has also proved to be a promising platform for production of viral antigens. ", "In 2004, rotavirus VP6 protein was successfully accumulated in seedlings and young leaves of tobacco, reaching 3 % TSP, but it lacked stability and was never tested on animals (Birch-Machin et al. [", "@CR3]). ", "Since then, most of research focused on antigens of three viruses---cervical cancer-causing human papillomavirus (HPV), human immunodeficiency virus (HIV), and hepatitis virus. ", "Eventually, antigens derived from all of these viruses were produced in tobacco. ", "As it turned out, the target proteins maintained their effectiveness---human papillomavirus antigens (L1 and E7) induced systemic immune response in mice (Fernández-San Millán et al. [", "@CR32]; Venuti et al. [", "@CR85]), and so did p24 and C4V3 polypeptides isolated from HIV, which successfully elicited antibody responses in mice (Gonzalez-Rabade et al. [", "@CR33]; Rubio-Infante et al. [", "@CR67]).", "\n\nWhile the yield and stability of target proteins were satisfactory, tobacco's usefulness was limited by its high alkaloid content, which made it unsuitable for oral delivery. ", "Because of that, scientists have searched for more suitable plants for antigen accumulation, and they have found them in form of lettuce and tomatoes. ", "Both of them turned out to be effective for production and oral administration of target proteins, although it is worth noting that ripening of tomatoes reduced their transgene expression (Zhou et al. [", "@CR97]; Davoodi-Semiromi et al. [", "@CR20]; Lössl and Waheed [@CR53]). ", "Research on lettuce already resulted in successful production of multiple important therapeutic proteins; the first successful attempt was accumulating proinsulin, where old leaves of plants with chloroplasts transformed with human proinsulin--CTB complex managed to accumulate proinsulin up to 53 % of TLF, compared with 47 % in old tobacco leaves and just 1 % of total seed protein in *Arabidopsis* (Boothe et al. [", "@CR6]; Boyhan and Daniell [@CR8]). ", "Some algae have also proved to be capable of producing vaccine antigens---in 2010 *Chlamydomonas reinhardtii* was successfully utilized to accumulate AMA1 and MSP1, two potential candidates for vaccine against malaria-causing protozoa from *Plasmodium* genus (Dauvillée et al. [", "@CR19]).", "\n\nEnzyme production: obtaining biomass and raw material {#Sec12}\n-----------------------------------------------------\n\nTransplastomes can also be used to synthesize enzymes, which can be utilized to obtain material for biofuel. ", "Currently, biofuel production is an expensive process, which results in wasting of large amounts of potentially useful biomaterial. ", "Big part of expenses comes from obtaining enzymes necessary for degradation of cell walls---cellulases, hemicellulases, and accessory enzymes (Agrawal et al. [", "@CR1]). ", "That is why in recent year's utilization of modified plants as a source of enzymes became a popular field of research. ", "So far, none of the enzymes derived from transgenic plants are produced on a mass scale, but current results show immense promise. ", "For example, endoglucanase (cellulase) and pectate lyases (hemicellulases) from one of experimental cultivars of transplastomic tobacco were significantly less expensive than commercial enzymes (production was 3100-fold and 1057/1480-fold cheaper, respectively) (Verma et al. [", "@CR87]).", "\n\nAnother enzyme expressed in transformed tobacco chloroplasts is β-mannanase, a hemicellulase of *Trichoderma reesei.* ", "Once again, the results gave reasons to be optimistic---mannase produced in chloroplasts had wider pH optima and thermostability than its counterpart obtained from *E. coli* and displayed notable activity even without purification, potentially opening a route for its easier and cheaper utilization in the future (Agrawal et al. [", "@CR1]). ", "Another examples of fungal enzymes successfully obtained from transplastomic tobacco are swollenin and cutinase; however, it is unlikely for them to find any practical use soon, as they caused severe damage to plant cells---it included damaged thylakoid membranes, disruption of pigment-protein complexes, loss of chloroplasts, and decreased galactolipids content (Verma et al. [", "@CR88]). ", "Tobacco chloroplasts are also capable of producing bacterial enzymes, such as thermostable cellulases (Cel6A and Cel6B) of thermophilic actinobacteria, *Thermobifida fusca* (Yu et al. [", "@CR96]).", "\n\nCrop improvement {#Sec13}\n----------------\n\nEvery plant is exposed to a variety of biotic and abiotic stressors, which are capable of negatively impacting plant's development, size, and quality of its yield. ", "Because of that, plastome modifications introducing improved resistance to common stress factors are a popular field of research, which has potential to improve the yield, reduce the amount of used pesticides and insecticides, and give a chance to grow the crop in areas where wild-type plants would struggle to survive.", "\n\n### Herbicide resistance {#Sec14}\n\nThe increasing use of herbicides has resulted in the need for plants capable of surviving exposure to non-selective chemicals used against the weeds. ", "However, providing it by nuclear transformation of crops is a risky approach, as herbicide immunity genes can be transferred with pollen, potentially resulting in outcrossing with weeds and subsequent creation of superweeds, immune to herbicides. ", "While it is possible to significantly reduce that threat by silencing transgenes, this process further increases the cost of the whole operation. ", "This is why chloroplast transformation, free of risk coming with outcrossing, is being looked into.", "\n\nFirst successes in providing herbicide resistance through genetic engineering of plastome came in 1998. ", "The research focused on finding a way to reduce or remove the negative influence of glyphosate. ", "This objective was achieved by transferring to tobacco's chloroplast the petunia gene engineered to overexpress glyphosate's target, 5-enol-pyruvyl shikimate-3-phosphate synthase (EPSPS), catalyst of one of the key steps of aromatic amino acid biosynthesis, (Daniell et al. [", "@CR15]). ", "In the following years, it has been shown that prokaryotic EPSPS can also be successfully used in this procedure, although its accumulation and glyphosate tolerance did not correlate (Ye et al. [", "@CR95]).", "\n\nAnother example of successful induction of herbicide resistance includes improving resistance to some of the triketone herbicides by introducing barley's 4-hydroxyphenylpyruvate dioxygenase-synthesizing *hppd* gene, which is a part of plastoquinone and vitamin E biosynthesis pathway, into tobacco plastomes (Falk et al. [", "@CR31]; Venkatesh and Park [@CR84]). ", "In 2007, *hpdd* from *Pseudomonas fluorescens* was introduced into soybean plastomes; this experiment is especially noteworthy, as it was the first case of obtaining herbicide immunity in an economically important crop without utilizing antibiotic resistance markers (Dufourmantel et al. [", "@CR29]).", "\n\n### Pest and disease resistance {#Sec15}\n\nPests and diseases are some of the biggest problems for modern agriculture. ", "Their influence is capable of severely reducing the crop yield and forces the use of chemicals, which represent an environmental hazard and increase the overall cost of crop growth. ", "While nuclear transformation has managed to reduce the impact of these factors, chloroplast transformation can still provide additional biosafety and play a role when higher gene expression is needed (Venkatesh and Park [@CR84]).", "\n\nThe first discoveries in this field were made in 1995, when crylA(c) coding sequence of *Bacillus thuringiensis* (Bt) was used to produce Bt toxins in tobacco in concentrations which made it harmful for attacking insects, such as *Helicoverpa zea*, *Heliothis virescens,* and *Spodoptera exigua* larvae (McBride et al. [", "@CR57]). ", "Since then, Bt toxins were introduced into other transplastomic plants, such as cabbage (*Brassica oleracea*), but they never entered commercial production, mainly due to plenty of available alternatives obtained by nuclear tranformation (Liu et al. [", "@CR52]; Jin and Daniell [@CR40]).", "\n\nDisease-resistant tobacco was first created in 2001 by inserting the sequence encoding an antimicrobial peptide MSI-99, analog of magianin 2, defensive peptide secreted from the skin of *Xenopus laevis* (African clawed frog) (DeGray et al. [", "@CR24]). ", "Transplastomic plants significantly inhibited growth of pre-germinated *Aspergillus flavus*, *Fusarium moniliforme*, and *Verticillium dahlia* fungi, and *Pseudomonas syringae* pv. ", "tabaci bacteria (DeGray et al. [", "@CR24]). ", "Recent research also shows that MSI-99 expressed by tobacco chloroplasts is capable of suppressing the effects of rice blast, one of the most dangerous fungal rice diseases (Wang et al. [", "@CR89]).", "\n\n### Simultaneous resistance to herbcides, pests, and diseases {#Sec16}\n\nIn recent years, a number of transplastomic plants capable of simultaneously improving resistance to insects and diseases have emerged. ", "While this kind of immunity would usually require multi-gene engineering, transforming tobacco chloroplasts with agglutinin gene from *Pinellia ternata,* a popular Chinese medicinal herb, is enough to singlehandedly reduce the survival rate of a wide array of pests (*Bemisia tabaci* whitefly, *Myzus persicae* aphid, *Spodoptera exigua* armyworm, *Helicoverpa zea*, *Heliothis virescens,* and *Lepidopteran* insects) by 90--100 %; also, agglutinin displayed significant anti-viral activity (Jin et al. [", "@CR41]). ", "Another example of transplastomic plant immune to insects and phytopathogens is *Nicotiana benthamiana* whose plastids included genes encoding chitinase from *Paecilomyces javanicus*, sporamin from sweet potato and cystatin from *Colocasia esculenta* (Chen et al. [", "@CR11]). ", "Bioassays have confirmed that the transformation reduced the symptoms of soft rot caused by *Pectobacterium carotovorum* subsp. *", "carotovorum* and leaf spot disease associated with *Alternaria alternata* and caused growth retardation and death of *Spodoptera exigua* and *S. litura* larvae that ingested the leaves (Chen et al. [", "@CR11]).", "\n\n### Abiotic stress resistance {#Sec17}\n\nGrowing demand for plants capable of growing and giving yield in unfavorable conditions, combined with human exploitation and extreme weather phenomena lead to an increased need for plants with increased immunity to drought, extreme temperatures and salinity.", "\n\nTo increase immunity to salt stress and drought, osmoprotectants are necessary due to their role in stabilizing membranes and proteins during osmotic stress. ", "As most of plants cannot metabolize sugar alcohols, introducing genes encoding a product capable of that is a viable way to improve osmoprotection (Khan et al. [", "@CR43]). ", "One of such genes is *ArDH*, which encodes arabitol dehydrogenase, responsible for reduction of [d]{.smallcaps}-ribulose to [d]{.smallcaps}-arabitol, which accumulates in chloroplasts and increases tolerance to high NaCl concentrations. ", "Its expression in tobacco chloroplasts allows plants to grow normally on soil with up to 350-mM NaCl concentration (Khan et al. [", "@CR43]). ", "Another example is a betaine dehydrogenase (BADH) gene transformed into *Daucus carota* (carrot), which resulted in transformed plants accumulating 50- to 54-fold more betalaine than their untransformed counterparts in medium with 100-mM NaCl concentration (Kumar et al., [", "@CR47]). ", "Transplastomic *N. benthamiana* with genes encoding chitinase, sporamin, and cystatin, mentioned before due to its increased immunity to insects and diseases, also shows increased immunity to osmotic stress (Chen et al. [", "@CR11]). ", "Meanwhile, temperature stress resistance can be achieved by enhancing antioxidant defense, increasing the unsaturation of fatty acids or by the use of *E. colipanD* gene encoding [l]{.smallcaps}-aspartate-α-decarboxylase---the enzyme decarboxylating [l]{.smallcaps}-aspartate to β-alanine and carbon dioxide (Wani et al. [", "@CR91]).", "\n\nConclusions {#Sec18}\n===========\n\nOnce the most important issues related to mass cultivation of tranplastomic plants are solved, they are likely to become a viable alternative for plants with nuclear transgenes, because of their higher production of protein of interest, lack of silencing mechanism, significantly higher biosafety, ability to engineer entire metabolic pathways, freedom of applying desired posttranslational modifications to the protein of interest, and potentially, no need for purification of protein target. ", "At the moment, it is unclear whether transplastomic plants can become more important for agriculture or biopharmaceutics, as we still failed to get anywhere close to uncovering their real potential. ", "However, it is worth remembering that there are some exciting subjects related to both worlds, such as edible vaccines. ", "For this reason, cooperation between scientists, agricultural and biotechnological companies will be necessary for steady development of transplastomics.", "\n\nCurrently, the biggest challenges ahead are related to the lack of protocols for transforming plastomes of other plants than tobacco. ", "While attempts to express foreign genes in some important agricultural plants, such as lettuce and tomato, have already succeeded, their number is still too low, the protocols contain many flaws, and the need to create a separate protocol for every cultivar makes the whole process more expensive. ", "On top of that, there are still no successful attempts of creating transplastomic staple food crops, such as cereal, and expressing foreign genes in non-green plastids remains a challenge due to our poor understanding of their genetic structure and expression (Wani et al. [", "@CR91]). ", "It is very unlikely for any transplastomic plants to be commercially used in the near future due to the reasons mentioned above combined with low plant regeneration efficiency and widespread use of antibiotic resistance genes as markers. ", "At this time, it appears that the problem of markers is the closest to the solution, as safer, although not widespread markers unrelated to antibiotic resistance already exist and some of them, such as *BADH*, are even capable of improving the target plant (Daniell et al. [", "@CR17]).", "\n\nInformation about plastome structure can also be very valuable in phylogenetic analyses and is an efficient molecular tool due to low mutation rate, easy amplification and conservative sequences of chloroplast genome (Hu et al. [", "@CR39]). ", "To this day, plastomes have been used in multiple analyses on different taxonomy levels---from species of the same genus to clades (Moore et al. [", "@CR60], [@CR61], Hu et al. [", "@CR39]). ", "Until now, the biggest issue was a low number of sequenced plastomes, which negatively affected the quality of phylogenetic analysis (Rogalski et al. [", "@CR66]). ", "However, recent major progress in realization of such projects means that the aforementioned analyses have a chance to become more reliable.", "\n\n*Author contribution statement* {#d30e1556}\n-------------------------------\n\nSO, EŁ, TK and TS wrote the manuscript. ", "EŁ provided the tables and figures. ", "SO did final revisions of the manuscript. ", "All authors read and approved this manuscript.", "\n" ]

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[ "I found chimney pipe that somebody removed a wood stove and wants to get rid of. ", "Will this work? ", "This is all the info I have.", "\n\nI have 2 sections of stainless steel insulted stove pipe. ", "30 inches long 8 inch INSIDE DIAMETER. ", "Also cap and cone that sits on the roof. ", "Took out wood stove and no longer need it. ", "Its in really good shape. ", "I can't find any markings on the pipe. ", "I purchased it from some place that deals with insulated pipe and stuff. ", "I don't remember the name, however, this was/is the best that you could buy. ", "I just want rid of it\n\n__________________I don't care what folks say behind my back........They are either braggin or.......lyinTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts..\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\n__________________I don't care what folks say behind my back........They are either braggin or.......lyinTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts..\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nI had talked to the building dept last fall, I haven't started my oven yet. ", "At that time the inspector told me it was just a general permit needed and there were no real requirements as I had lots of questions. ", "I have been looking on Craigslist and have sourced lots of materials for free or very cheap. ", "I have been looking for a god deal on the chimney as I like that style best and finally found this one. ", "I just wanted to check to make sure this would be acceptable as I know absolutely nothing about chimneys. ", "Thanks for the quick reply, since it looks like this will work I'm going to email him right now. ", "Thanks again!", "\n\nI think you will be all right. ", "As for as \"depending on the application\" is conserned as long as you are not building inside your home or something attached to it. ", "That is where building codes get real sticky, for a real good reason though .", "\n\n__________________I don't care what folks say behind my back........They are either braggin or.......lyinTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts..\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nI bought one section of 8\" double wall SS double wall and the cap for 60 bucks (from a local salvage store) and just thought that I got a great deal. ", "I haven't totally ruled out using it if I need to extend my chimney in the future, but it is on stand by if I need it. ", "I want try to give a value of the 2 sections and cap that you purchased but the only local source which I priced was 250 bucks per section of 3 wall. ", "I think that you are getting a good deal.", "\n\n__________________I don't care what folks say behind my back........They are either braggin or.......lyinTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts..\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nTo view links or images in signatures your post count must be 0 or greater. ", "You currently have 0 posts.", "\n\nNo part of this website or content thereof may be reproduced, distributed or transmitted in any form or by any means, nor may any part of this website be stored in a database or other electronic retrieval system, or any other website, without the prior written permission of Forno Bravo." ]

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[ "“Green Room” star Callum Turner is in talks to play Newt Scamander’s brother in the next installment of Warner Bros.’ “Fantastic Beasts and Where to Find Them.”", "\n\nEddie Redmayne will return to the sequel as Scamander. ", "Jude Law is on board to play young Dumbledore, and Johnny Depp is attached to play Grindelwald. ", "David Yates is returning to direct.", "\n\nRowling, who made her screenwriting debut on “Fantastic Beasts and Where to Find Them,” has also written the script for the second installment. ", "The film is set in an increasingly dark time for the Wizarding World where Newt Scamander and company have to decide on their allegiances.", "\n\nPlot details are unknown at this time other than the film being set in Paris.", "\n\nThe first movie in the planned five-part “Fantastic Beasts” series grossed more than $813 million at the box office.", "\n\nThe sequel, which begins production this summer, also reunites producers Rowling, David Heyman, Steve Kloves and Lionel Wigram. ", "Neil Blair, Rick Senat and Danny Cohen are serving as executive producers.", "\n\nAfter a breakout role in the A24 thriller “Green Room,” Turner followed up with a critically acclaimed performance in Adam Leon’s “Tramps,” which bowed at the Toronto Film Festival. ", "He has since landed the lead in Marc Webb’s “The Only Living Boy in New York” opposite Jeff Bridges, which opens in August.", "\n\nTurner is repped by WME and Curtis Brown Group. “", "Fantastic Beasts 2” hits theaters on Nov. 16, 2018." ]

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[ "Q:\n\nCheck if two items are equal after replacing\n\nLet's say that an item is either a natural number or a list of items. ", "Examples of items are:\n\n1\n[2]\n[4, [3, 1], 3, 4]\n\nA rule states that two items are equal. ", "For example:\n\n1 = 2\n3 = [3, 1]\n[4, 3] = [1, 5]\n\nWhen using these example rules, we can transform [4, [3, 2]] into [4, [3, 1]] into [4, 3] into [1, 5] and we can say that [4, [3, 2]] equals [1, 5].", "\nI want to find an algorithm that, given items $a$ and $b$ and a finite set of rules, determines if $a = b$.\nI already thought of an algorithm that works in some cases. ", "But I hope to find an efficient algorithm that works in all cases. ", "It would also be nice if the algorithm can detect $a \\not= b$ instead of infinitely searching for ways to let $a = b$. Is this a known problem? ", "Any help is appreciated.", "\nNote: We can simplify the problem by only allowing the number 1 instead of every natural number. ", "This is equivalent, because we can transform 1 into [1], 2 into [1, 1], 3 into [1, 1, 1], etcetera.", "\n\nA:\n\nI found a solution to my problem. ", "Let's look at the simpler but equivalent problem in which an item is recursively defined as an empty list or a list of items. ", "I'll summarize the algorithm.", "\nVariables:\n\nInt counter starting at 0\nHash map: list of integers $\\to$ integer.", "\nThe integers represent equivalence classes.", "\n\nFunction find(item) $\\to$ int:\nFinds the equivalence class of an item. ", "Recursively call find on all the children of item. ", "Now you have a list of ints. ", "If this list of ints is contained in the hash map, return the corresponding value. ", "If not, add the list to the hash map with the counter as value. ", "Increase the counter and return the value.", "\nFunction merge(int a, int b):\nMerges two equivalence classes a and b. In the hash map, replace all occurences (both in keys and in values) of a by b. Now it can happen that one key is mapped to multiple values. ", "If that happens, again merge those values. ", " Repeat this until every key maps to a unique value.", "\nAlgorithm:\nFor every rule c = d, call merge(find(c), find(d)). ", "Then to see if a = b, check if find(a) = find(b).", "\n\n" ]

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[ "Gov’t completes computerised land registry\n\nGovernment has completed the noble project of computerising Uganda’s land registry which will greatly minimise the so many land conflicts in the country.", "\n\nGovernment has completed the noble project of computerising Uganda’s land registry which will greatly minimise the so many land conflicts in the country.", "\n\nBy Moses Mulondo\n\nGovernment has completed the noble project of computerising Uganda’s land registry which will greatly minimise the so many land conflicts in the country.", "\n\nIn an exclusive interview with New Vision on Thursday, lands minister Daudi Migereko revealed that the ministry had started using the computerised registry.", "\n\n“A few days ago, we started using the computerised land registry. ", "People can now get their computerised land titles in the land offices and communicate to us if they face any problem,” Migereko said.", "\n\nThe minister also revealed that in the course of computerising the registry, they discovered so many forgeries of land titles and investigations aimed at prosecuting the culprits have already commenced.", "\n\nMigereko said the project has cost government US$23.5m which was a grant by World Bank.", "\n\nWorld Bank is also supporting similar projects of computeriSing land registry in Ghana and Tanzania.", "\n\n“The computerised national land information will solve problems of forging titles, missing files AND the red tape in searching land information. ", "Storage and retrieval of information will be easier and faster,” Migereko stated with a smile of relief.", "\n\nHe however clarified that the first phase has dealt with land information in the six zonal (sub-region) areas of Kampala, Mukono, Wakiso, Masaka, Mbarara and Jinja.", "\n\nThe minister explained that unlike in the past when issuance of land leases and land tiles has been at the ministry headquarters in Kampala, the services will be provided in the zonal offices.", "\n\nThe coordinator for land sector reform, Richard Oput, explained that the ministry chose to begin with the above mentioned six zonal offices because 60%-70% of land transactions take place in those areas.", "\n\nOput reported that the second phase of computeriSing the land registry will commence in July.", "\n\nThe other zonal offices where offices have been built and equipped with computers, surveying equipment and other requirements but whose land information is yet to be computeriSed include Mbale, Kibaale, Fort Portal, Masindi, Arua, Gulu and Lira.", "\n\nOput stated that in those sub-regional offices which have been completed, residents will only have to go with references like the block, plot number and where the land is located to quickly get any information they want regarding their land.", "\n\nHe revealed that the other land reforms the ministry is working on include drafting a Bill seeking to regulate the activities of real estate dealers, and another new land law of land information system to guide the operations of the computerised land registry.", "\n\nThe ministry has also embarked on reviewing Uganda’s old land laws to undertake their amendment reconcile them with the modern changes in the society.", "\n\nThe ministry has also just re-opened the school of surveying and land management and equipped it with a modern resource center involving a computer laboratory, library, and modern surveying equipment.", "\n\nThe completion of computerising land registry in the areas where most land transactions take place will greatly minimise land wrangles and simplify the judicial process of adjudicating land cases in courts of law.", "\n\nMigereko revealed that the number of land titles in the country is slightly above 500,000 most of which are in the central region, Ankole,\nTooro, Busoga and Mbale but which constitute only 18% of the entire land in Uganda.", "\n\nThe rest of the other parts of Uganda there are no land titles as land is owned in clans and communal arrangements" ]

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[ "When life reaches rock bottom, it has no where to go but up. ", "Gary Oak, Pokemon Master for fifteen minutes, grandson of a too famous researcher, eternal rival of Ash Ketchum, loser in everything that matters, is about to find out. ", "egoshipping edited\n\nDisclaimer: Pokemon and its respective characters do not belong to me.", "\n\nEditted Version.", "\n\nChapter Three - An Eye for an Eye, A Book for a ShirtI woke to the sound of muffled voices.", "\n\nSlowly, deliberately, the fine veil of sleep lifted. ", "In vain, I clung desperately on the fleeting threads of dream. ", "Yet, unconsciousness, like water, quickly slid out of my reach and reality coagulated around me. ", "I opened my eyes only to meet blinding sunlight. ", "How unusual, I thought, as I lifted a hand to cover my eyes. ", "I, a perpetual insomniac, seldom wake up later than seven-thirty. ", "By the intensity of the sun, it must be at least nine.", "\n\nThrough a crack between two fingers I glanced at my bedside clock. ", "I found none. ", "The absence propelled my heavy mind into complete panic. ", "My eyes shot opened but I calmed when a frantic survey informed me that in fact Iwas not in my room at all. ", "As the series of sleep-laced thoughts gave way to clearer, morecoherent stream of consciousness, I recognized the room as one of Blaine's guestrooms, to be precise, the room across the living room. ", "Memories of the night before hit me in full: I was depressed, I drank more than I ought, I got more depressed, I completely drank myself silly, and then… I sprang up but a massive headache forced me back into the bed.", "\n\nI groaned.", "\n\nAt that particular moment, the muffled voices caught my attention again. ", "Too soft to comprehend, too loud to ignore, really, the worst sort of muffled voices. ", "The noise must be from the living room, which is next to the dining room, which is next to the kitchen…\n\nThe kitchen… for a moment my mind dwelled fondly on the Tylenol in the kitchen cupboard. ", "The thought of such an incentive gave me the boost of energy I needed to overcome my headache and get out of bed. ", "My legs wobbled under me – think Tylenol - My head ache multiplied in strength each step I took – think Tylenol - My hand felt heavy as I lifted it to the door knob – You need the Tylenol – Oh the world is spinning – Tylenol.", "\n\nSuch was my pattern of thoughts as I made my way to the kitchen with Tylenol as the carrot at the end of the stick. ", "The thirty feet of mahogany flooring separating my room from the kitchen felt like the longest thirty feet in the world. ", "When I reached my destination, I could not help but feel most accomplished.", "\n\nI navigated expertly around Blaine's kitchen, gathering a cup from a cupboard, hot water from the electronic kettle and of course, my due reward: the pack of Tylenol from the medicine box. ", "Two pills and a nice long drink of hot water later, my god-awful headache felt somewhat better, completely psychological I am sure, but nevertheless better. ", "I settled myself on a stool at the kitchen counter and ate plain white bread, the only food lying at hand length from where I sat, not exactly my choice of breakfast but definitely filling enough.", "\n\nHalf way through the piece of bread, my brain began registering a conversation, also known as the muffled voices I heard earlier, that the miserable head-ache had successfully shut out for five whole minutes.", "\n\n\"—am flattered you phoned me for an interview. ", "I was quite surprised really,\" a voice, most probably Miss Waterflower's said.", "\n\n\"Should you be, Ms. Waterflower? ", "You are the most esteemed water pokémon gym leader in the world,\" came the shameless flattery from an alien feminine voice, disturbingly high pitched, \"Of course you must be part of my research.\"", "\n\nI glanced with disdain at the closed door behind the doorway I came in from earlier, I wondered about the identity of the stranger. ", "A journalist from a local newspaper or a magazine perhaps? ", "An overly enthusiastic water pokémon trainer? ", "An aspiring to-be gym leader? ", "An obsessive fan? ", "I took another dry bite at my bread and listened on.", "\n\n\"What degree are you studying for again, Cassy?\"", "\n\n\"Master in marine biology.\"", "\n\nAh, so a student researching for her thesis then. ", "I nodded thoughtfully, recalling the interviews I have conducted for my own thesis during my days in university. ", "I have fond memories of university, a playground for educated hypothesis and free thoughts. ", "A place where at least some people would recognize me for my own work and not what my grandfather did. ", "A pity I had to do most of my degree through correspondence because of my gym responsibilities and freelance researching.", "\n\n\"I suppose I should start with a general question. ", "What is your favorite water pokémon and why?\"", "\n\n\"I love all water pokémon, of course, but I have a certain weakness for Tentacruels. ", "Not only are they strong, but the jewels on their heads are just very pretty.\"", "\n\nI almost gagged out loud. ", "Tentacruel of all things? ", "Pretty? ", "I stuck my tongue out at the thought. ", "I have always considered beautiful Tentacruel as an oxymoron. ", "I can understand why so many girls squeal at the sight of an Azumarill, Marill, or Azurill. ", "I can even understand why May loves the juvenile forms of water pokémon like Horsea, Mudkip and Wooper. ", "Those creatures are bubbly and cute. ", "They are huggable. ", "But Tentacruel? ", "Nor can I say Tentacruels are all that strong. ", "They are not especially weak, of course, being a mature form of a duo typed pokemon, but I would rather have a Gyarado or Dewgong on my team any day and I am not even trying to name the strongest water pokémon here.", "\n\nCassy laughed, alas a slightly nervous laugh. ", "Even she did not know what to make of the answer. \"", "I suppose Tentacruels do have their own kind of beauty…\" she said slowly and quickly steered the conversation away from the said monster, \"From your vast experience with water pokémon, which is the most memorable, extraordinary, unique, so to speak?\"", "\n\n\"All 380 odd pokémons,\" 386 to be exact – I noted in my mind. \"…", "are unique in their own ways. ", "The 63 water pokémon,\" 64 – I corrected silently. \"...", "in the world are no different. ", "Even pokémon of the same species are never the same. ", "But I think by far the most memorable water pokémon I have encountered is Suicune.\" ", "Ah… Suicune, I have seen a Suicune once, a rather magnificent, beautiful creature…\n\nThe phone rang. ", "Once, twice, three times. ", "No one picked up. ", "Blaine must be out. ", "At the forth ring I grudgingly gave in and picked up the phone. \"", "Hello, Blaine's residence speaking.\"", "\n\n\" Gary!\" ", "the voice at the other end sounded like he just met God. ", "To my horror, I recognized the voice as that of my lab supervisor, Steven.", "\n\n\"Steven!\" ", "I mimicked his excitement, less than please. ", "Honestly! ", "One cannot have time off even during vacation these days.", "\n\nA strained laugher. ", "I blenched, Steven, usually a calm and stoic man, would never laugh so nervously unless something went dreadfully wrong to the atomic level. ", "I prayed to God I was wrong. \"", "Timothy,\" he laughed that nervous laugh again, \"you know, that new assistant I hired—\"\n\n\"The one I hired only because he was your nephew?\" ", "I interrupted pointedly.", "\n\n\"Er… Yeah him... He just blew up something big.\"", "\n\nI bit my lips. \"", "How big?\"", "\n\n\"A back up water-pump.\"", "\n\n\"WHAT?\" ", "I practically screamed. ", "Hearing fearful whimper at the other end, I froze and closed my eyes. ", "Calm down, Gary, nothing can be solved if you scream at the panicking Steven. ", "Don't shoot the messenger. ", "Breath in in in out. ", "Breath in in in out…\n\nA minute of silence later, I finally spoke with a respectable amount of composure. \"", "Which one, Steven, and can it be fixed?\"", "\n\n\"The one responsible for the north end and no, it is a total lost.\" ", "Steven squeaked out.", "\n\n\"Alright,\" I said slowly, trying to remember what the insurance on my lab covered. \"", "Steven how did this happen?\"", "\n\n\"Timothy smoked in the non-smoking area and –\" he broke off, anxiety laced his voice, \"Oh I am sorry Mr. Oak, please don't fire me, you know I need this job a lot, and you have absolutely no idea how much it means to me and my family and—\" He was completely babbling.", "\n\n\"Steven, calm down. ", "You are not going to be fired, but Timothy has to go.\" ", "That affectively quieted him down and gave me the silence I needed to think. ", "If I remember correctly, my insurance only covers flood, mechanical failures, and pokemon related accidents, meaning this man-made accident would most likely not be covered. ", "I rubbed my temple gingerly. ", "The circumstance was definitely against me. ", "A new water pump of that size would cost about a hundred fifty thousand. ", "My emergency funding can offset half of that. ", "This leaves about eighty thousand unaccounted for.", "\n\nMy mind churned for possible solutions but found none completely to my liking. ", "Finally I gave up and sighed. \"", "Set up a meeting with the Dean of Science at Burkely for me, Steven.\"", "\n\n\"But that would mean--\"\n\nI cut him off irritably, \"I know what that means, Steven, but desperate time calls for desperate measures. ", "Even if we empty our emergency account, we still won't have enough to cover the pump. ", "We would have to prospone phase four of the research by at least a year if we are to earn the funding ourselves. ", "I rather publish my research through Burkely than delay any of part of the research plans for that long.\" ", "I paused to let my words sink in.", "\n\nSteven took a deep breath. \"", "I am sorry,\" he repeated in a low voice.", "\n\nI ran my fingers through my hair. \"", "It's not your fault,\" I pointed out, knowing blmaing him would not help the situation. \"", "Besides, it's not that bad,\" I added, more to convince myself than the lab supervisor, \"Burkely is a respectable univeristy and I have heard they have one of the least intrusive policy regarding external researches.\"", "\n\nI repeated a list of procedures to take seven times before I hung up. ", "The phone call left me in a rotten mood and even more horrible headache, in an effort to clear my mind I decided to head to my room and ready myself for a walk. ", "My mind, as full and heavy as lead, only led me out of the kitchen before betraying me completely. ", "In a moment of thoughtlessness, I confused the door to the living room with the door to the guest room: a fatal mistake.", "\n\nThe door edged opens soundlessly, a perfect imitation of a swinging door at the climax of a movie. ", "The two occupants of the room instantly froze. ", "For a moment they stared at me and I at them.", "\n\nMiss Waterflower maintained her unreadable stare and said nothing. ", "The stranger Cassy, a brunette in somewhat immodest clothing, corrected with an impish grin, \"Good afternoon, mister, it is past twelve.\"", "\n\nI glanced at the wall clock above the fifty two inch television and found, my eyes wide in disbelieve, that it was almost one. ", "That would mean I woke up at almost twelve, and that would mean I slept almost thirteen hours as oppose to my usual five. ", "I must have really over drunk myself. \"", "Forgive me. ", "I am still half asleep.\"", "\n\n\"I am really sorry about last night,\" I apologized genuinely, recalling the less than pleasant circumstances in which we met yesterday night as I added, \"Tell me how much your shirt cost. ", "I will pay for it.\"", "\n\nMisty snorted, \"You can't buy everything, Gary Oak, that was a very special shirt and no amount of your dirty money can replace it.\"", "\n\nI flinched at the accusation. ", "I did not expect her to bring up such an uneasy topic in front of a guest. \"", "Miss Waterflower, let's discuss this later,\" I eyed Cassy the student to ensure she understood my concern, \"I don't want to keep this Miss waiting.\"", "\n\n\"Do you mind, Cassy?\" ", "The edge in Misty's voice left the woman no choice but to shake her head.", "\n\nMy eyes narrowed. ", "She had every right to be angry, but that did not give her the right to humiliate me in front of a stranger. \"", "I am very sorry about what happened last night, Miss Waterflower, but I couldn't stop the force of nature when I am drunk.\"", "\n\n\"You call throwing up all over me natural?\"", "\n\nI rolled my eyes in exasperation. \"", "You know that was not what I meant and I said sorry!\"", "\n\n\"Sorry just doesn't cut it.\" ", "She glared.", "\n\nI glared back. ", "She was not the one who had to worry about gathering over a hundred thousand to replace water pump that an idiot blew up admist a throbbing headache. ", "I felt my temper rising dangerously, but not wanting to say anything I may seriously regret later, I decided to ignore her and march out of the room.", "\n\nUnfortunately, I got no farther than a step out of the living room before Misty caught up and blocked my way. \"", "What do you want, Waterflower?\"", "\n\n\"Oh? ", "No more 'Miss Waterflower' and fake civility?\"", "\n\n\"Believe me, civility is far too much of a hassle to fake for anyone let alone for the undeserving.\" ", "I sneered privately at the sight of her flaming eyes.", "\n\nShocked at the sudden address, alas formal address, my mouth remained opened agape while Misty Waterflower looked at me like I grew a second head before suddenly bursting out in laughter. \"", "You must be mistaken, Gary Oak is no doctor.\"", "\n\n\"Yes I am,\" I corrected coolly, secretly offended and hurt, \"I have a doctoral degree in pokémon genetics.\" ", "Knowledge has always been one of my prides. ", "Her comment was a direct attack on my self-esteem and any sort of attack on my ego, even those unintentional, could not be forgiven without retaliation. \"", "This reminds me,\" I spoke, my mouth curling into a smirk, \"just so you know, there are 64 water pokémon discovered so far, not 63 as you said, Great Water Pokémon Expert Misty Waterflower.\"", "\n\n\"You!\" ", "Misty Waterflower's face made me think of ripe tomatoes and autumn fire. ", "She was angry. ", "No, she was furious. ", "I felt strangely accomplished.", "\n\n\"The truth hurts, doesn't it? ", "Everyone calls you the Great Water Pokémon Expert and yet 'stupid jerk' me actually has to correct you on the number of water pokémon discovered in the world. ", "Disappointing, don't you think?\" ", "Those were not the kindest of words, but one with injured pride cared little for the feelings of the injurer. ", "My thoughts traveled in a rather straight forward and immature line: she humiliated me and I want to humiliate her back – an eye for an eye, a foot for a foot.", "\n\n\"You are such a—\"\n\nI pointedly ignored Misty Waterflower and turned to Cassy with a wide smile and an extended hand. \"", "Hello, nice to meet you, I am Gary Oak.\"", "\n\n\"I am Cassy White,\" she introduced herself enthusiastically, her old interest in Misty Waterflower cruelly forgotten, \"My professor, Doctor Andrea Lawlor, calls you one of the most talented researchers in the world! ", "I am so honored to see you in person.\"", "\n\nThe name of one of my all time favorite mentors, Doctor Lawlor, lifted my mood. \"", "Doctor Lawlor tends to grossly exaggerate praises. ", "She still specializes in marine life form genetics I heard?\"", "\n\n\"Yeah she still does. ", "But I don't think she exaggerated anything. ", "She showed us your thesis on Kyogre the first week of class and it was absolutely brilliant.\"", "\n\nI grinned at her compliments. ", "They sounded especially nice after everything Misty Waterflower said. \"", "Kyogre, the 64th water pokémon,\" I added with a glance at the Cerulean gym leader, who, if possible, looked more infuriated than even before, \"is indeed one of nature's great wonders.\"", "\n\n\"It is indeed,\" chipped Cassy, completely oblivious to, or at least chose to completely ignore, the stifling tension in the air. ", "Entirely unaware of anything outside of direct interest is a common trait among scientists after all, I suppose, afore all other roles Cassy is a scholar in biology.", "\n\nFrom the far corner of my eyes I saw Misty Waterflower stomped away after giving me one last lethal glare. ", "I did not turn to watch her leave. ", "Next to me, I vaguely registered Cassy speaking. \"", "You are much younger than I ever imagined…\" she blundered before her voice faded into the background. ", "My senses were so well tuned to Misty Waterflower's every movement that I felt and heard, even though I could not see, her walked out of the room, down the hall way, through the reception room and out the door with an angry slam.", "\n\nSo much for our first real conversation, I lamented as I turned my attention back to Cassy, suddenly regretting everything I have said. ", "I could only imagine her opinion of me after this episode.", "\n\nMy heart quivered.", "\n\nHow odd, I thought, that a man could fear losing what he could not even identify.", "\n\nWhen Cassy left at around two thirty, Blaine has yet return home and the magnitude of my still throbbing headache overrode my lurking hunger. ", "After taking yet another Tylenol, I headed to Blaine's study with a cup of hot Earl Gray. ", "The study has always been my favorite room in Blaine's house for its excellent view and the library, my library, all the old books I inherited from my parents and the new books I added on my own. ", "When I first moved out of my grandfather's house I spent almost ten percent of my wages on storage space for my books, a rather heavy financial burden, and the dire price for being stubborn. ", "Some may think my break from my grandfather illogical, of course it was, but like I mentioned before angry people don't make the wisest decisions and once I moved out my pride kept me from moving back in.", "\n\nBlaine has never been much of a reader but he has a spacious house and upon mentioning my hefty storage fees one day, he generously offered free space for my books. ", "I gradually transferred most of the books away when I acquired the gym and later on an apartment, but still a fair number of them remained on the forged vintage bookshelves in his study for my own enjoyment when I visit. ", "Blaine did not mind at all, he never read any of them but he considers those books home decor, after all, bookshelves full of well preserved hard cover books look rather impressive in any studies.", "\n\nI pulled out a small notebook containing a directory of the books on the shelves from the bottom draw of the desk. ", "I ran my finger down the list until I reached a title without a check mark: The Strange Case of Dr. Jekkyll and Mr. Hyde. ", "I took my pen out of my shirt pocket and marked the title with a new check before putting the notebook away again. ", "Then, standing up, I walked up to the bookshelves and found the said book, one of my parents', under the \"S\" section. ", "A few years ago I have anally reorganized my books by alphabetical order.", "\n\nSo, at three o'clock sharp I settled down in the comfortable leather sofa facing the bookshelves and began to reread the book. \"", "Mr. Utterson, the lawyer, was a man of a rugged countenance, that was never lighted by a smile; cold, scanty and embarrassed in discourse…\"\n\nI was just about to read the last chapter of the book when Blaine called me down to dinner at six-thirty. ", "The first clause of our mutually beneficial deal: he cooks and I wash dishes when ever I visit him or he visits me. ", "Living alone for the last five years have taught me to cook decently but knowing how to cook does not equate to wanting to cook. ", "In truth, I am usually too lazy to cook any more than one meal a day – a rather unhealthy habit but one that I cannot break despite Blaine's constant nagging.", "\n\nI marked my page with a bookmark and I walked down stairs with the book in hand in case Blaine called me down early as he does whenever he wants company. ", "In such a case I would be sitting across the counter from him in silence because Blaine never talks when he cooks. ", "Or so I thought.", "\n\nI first heard their laughter when I reached the bottom of the stairs. ", "I have never heard Blaine laughed quite like that. ", "With me, he often gives throaty, deep laughs, genuine but somewhat restrained, always held back. ", "But there and then his laughter contained an unreserved lightness that I never knew he processed. ", "I sometimes wonder how many single serving friends thirty years of gym leading on a remote tourist island brought to Blaine. ", "I often thought how lonely it must be for Blaine to be one of the few constants in the midst of an ever flowing river of people. ", "How comforting it was to know he has a friend that can make him laugh like that! ", "Unwilling to break the moment, I stood next to the door out of sight, simply listening and being glad.", "\n\nWhen their bantering finally died down, I let myself into the kitchen. \"", "Dinner smells good,\" I complemented, letting my presence be known.", "\n\nBlaine, still chuckling from the last joke turned and in a mismatching I-told-you-so tone he lectured, \"Enjoying your hangover?\" ", "He placed a meaningful glance at the bottle of Tylenol I left on the counter, \"Didn't you say you know your limits?\"", "\n\n\"Shut up, Blaine,\" I tried my best to ignore the unnatural stiffness of Miss Waterflower's back up on my entrance. \"", "Of course I revel in hangovers.\"", "\n\nThe exchange died with Blaine's throaty chuckle. ", "I at once began to regret walking into the room, but knowing nothing could change past deeds, I sat down on one of the kitchen stools behind the counter and reopened my book. ", "I intended to finish reading the novel but I could barely take in a word before my eyes found their way to Miss Waterflower and Blaine, the former tossing a salad and the latter stirring a pot of soup. ", "Eventually I gave up, closed the book, and attempted to start a conversation, \"What's for dinner?\" ", "I mentally slapped myself for the lame question.", "\n\nMiss Waterflower continued with her silent treatment but Blaine responded quite willingly, \"Clam chowder for soup, lamb rib with garlic bread and greens for our main course, and chocolate mousse cake for dessert,\" here my stomach gave an appropriate grumble. ", "Blaine gave a knowing smile, \"You didn't eat lunch, did you?\"", "\n\n\"It was too much of a headache,\" I returned, pun intended.", "\n\n\"Or you are too lazy,\" he accused rather bluntly. ", "I shrugged, sheepish smile glazed over my face. \"", "Did you even eat breakfast?\"", "\n\n\"I had a piece of white bread at twelve something.\"", "\n\nBlaine slapped his forehead with his hand. \"", "Good lord, you really don't take care of yourself well enough. ", "Good thing I cooked a big meal today.\"", "\n\nMiss Waterflower snorted, turned to Blaine with a look of utter horror, and finally joined the chitchat. \"", "You just realized, Blaine? ", "Anyone who would drink himself as drunk as he did does not care for health.\"", "\n\nBlaine laughed in good humor before the atmosphere could grow heavy, \"You really did see the kid at his worst didn't you?\" ", "He lifted the pot off the stove and turned off the gas. ", "Then, he walked toward me with his hands on his waist in a most mediator-like manner, \"Did you apologize, Gary?\"", "\n\nI sulked indignantly, \"I did already.\"", "\n\n\"Good.\" ", "He turned back to Miss Waterflower in a melodramatic way that made Misty giggle, \"Don't be too harsh on that kid, Misty,\" he pleaded with a bow, \"That boy was just having a bad day, I promise he is usually a lot more agreeable and intelligent than last night.\" ", "Subsequently, he elbowed me on the stomach in a not-so-subtle fashion.", "\n\nI glared at Blaine as I nursing my stomach and my back with gentle fingers but decided to take the opportunity to make amends anyway, \"I am sorry, Miss Waterflower.\" ", "It was the more sophisticated way of dealing with the situation especially when I have to coexist comfortably with her in the same house for a few more days.", "\n\nMiss Waterflower half heartedly turned back to the salad, for a few moments clearly in deep contemplation. \"", "I am sorry too, Gary, I spoke unfairly this afternoon.\"", "\n\n\"Good! ", "Now that stupid tension is gone we can start dinner!\" ", "Blaine announced with a clap of his hand.", "\n\nWe all grinned and set the table together. ", "I took care of the utensils, Blaine went down to the basement for wine, and Miss Waterflower brought the food to the table. ", "Everything seemed well again, we let our guards down, perhaps we should not have. ", "Storms brew under sunny skies, but who would anticipate a storm in perfect weather? ", "Who would expect what happened after this calm before the storm?", "\n\nI was getting the cutleries when I suddenly remembered about the book I have left on the counter unattended, begging for an accident. ", "I instantly swirled around, intending to quickly bring the book back up to the study, but I turned too late. ", "The book was already in danger: Miss Waterflower's wet fingers hovered only one inch away. ", "I reacted badly. \"", "Don't touch that!\"", "\n\nAt once Miss Waterflower's reaching hand retreated, confusion clear in her eyes. \"", "I just want to look at it,\" she hastily explained before her stubborn fingers advanced for the book a second time.", "\n\nKnives and forks forgotten, I strode to her just in time to snatch her hand away before any lasting damage occur. \"", "Looking does not involve hands, Miss Waterflower,\" I reprimanded, my voice harsh, my eyes narrow, \"When I said don't touch the book, I meant don't touch the book.\"", "\n\n\"It's not like I would have ruined it!\" ", "she exclaimed, her temper flared and she twisted her wrist out of my grip.", "\n\n\"Yes you would have,\" I corrected in a dry voice, \"your fingers are wet.\"", "\n\n\"My fingers are not wet enough to ruin any book,\" she insisted after one look at her fingers. \"", "What's your problem? ", "That's not even your book. ", "I saw it in Blaine's study a few days ago.\" ", "I opened my mouth to explain but she rambled on, \"Just because I forgave you for yesterday doesn't mean you can just be an unreasonable ass, you know.\" ", "She grabbed the book with lightning speed and before I could stop myself I let out an unmanly pained gasp.", "\n\n\"Give it back!\" ", "I demanded, reaching for the book.", "\n\nShe held the book up high: a challenge. \"", "No.\"", "\n\n\"Give it back!\" ", "I tried to grab the book again just to find her move the book away. ", "For some time we fought for the book, somewhat childishly as I later reflected, until finally she hid the book behind her back.", "\n\n\"NO!\"", "\n\nI scowled but withstood my temptation to reach for the book in front of her lest she wanted an excuse to call me a pervert on top of unreasonable ass and egotistic jerk.", "\n\nClosing my eyes, and after breathing deeply, I tried a more diplomatic approach, \"Miss Waterflower, please.\"", "\n\n\"Again, your fake civility!\"", "\n\nI could not believe Misty Waterflower and her twisted logic. \"", "You only think I faked my civility because you have none yourself! ", "Now for the last time, please give me the book Miss Waterflower.\" ", "She dashed around me but I was faster and I grabbed her wrist before she could escape. \"", "Are you deaf?\"", "\n\nShe shot me a glare and tried to pull her arm free but I tightened my grip and reached for the book with my other hand. ", "I would have gotten it too if not for what she did next.", "\n\nShe threw the book: an unforgivable act.", "\n\nI screamed a soundless scream as the book soar into the air in one smooth arc right into the sink. ", "I ran over to where the book landed only to verify what I already knew: the book was ruined.", "\n\n\"You guys are in luck! ", "I found a 1970 bottle… Hey, what's wrong? ", "Gary?\" ", "I turned, slowly, deliberately, to face Blaine. ", "He instantly noticed the wet book in my shaky hand. \"", "Oh Lord…\"\n\nNext to me, Misty Waterflower made a frantic apology, undeniably shaken, \" Blaine, I am sorry!\"", "\n\n\"Misty, what did you do?\" ", "Blaine asked in a melancholic whisper.", "\n\n\"I was fighting with Gary over your book and… and I accidentally dropped the book into the sink, I am really sorry.\"", "\n\nBlaine shook his head once. \"", "You really should not be apologizing to me,\" he muttered, wiping his face with his hand, \"That book is not mine.\"", "\n\n\"I hope, with that in mind, I am not as 'unreasonable' as you said, Misty Waterflower?\" ", "I questioned, my voice soft and eerily calm. ", "Misty Waterflower covered her mouth and for once in her life stayed silent at the right moment. \"", "You know best whether or not that was an accident. ", "You wanted revenge for the shirt? ", "You've got it. ", "A book for a shirt. ", "You win. ", "Excuse me,\" I gave a short nod to Blaine and made my way to the door.", "\n\nWhen I was young, before I took my first research project or considered science as a career, before I gain and lost my place as the pokémon master, before I watched Lance battle on television or met Ash, before I moved in with my grandfather, before I learned to hold back my tears, before I had any reasons to cry, before that one accident, my mother and father took turns reading to me at my bed side.", "\n\nOn Monday, Wednesday, Friday, and every other Sunday father read me articles from the Times as well as chapters of his novel of the month that always revolved around politics and intrigues. ", "I did not truly understand what he read, those passages were not written for children, but I loved the sound of his voice, a strange mix of knowledge, authority and gentleness. ", "I used to interrupt him with questions every time he hit a long word or abstract concept and he used to patiently give answers. ", "At a young age I knew words like pacifism, dystopian, totalitarianism, and liberalist. ", "I used to throw these large words around at school. ", "When a teacher tried to force me into a game of cop and robber, a game I hated with a passion, I would say, \"Sorry, I can't play because that's against my beliefs as a pacifist.\" ", "When I saw the schools geeks getting cornered by the school bullies I would say, \"You autocrats should stop terrorizing him.\" ", "By the miraculous the power of popularity I got away with all those lines, people liked me back then.", "\n\nOn Tuesday, Thursday, Saturday, and every other Sunday mother told me ancient myths and read me chapters from her novel of the week that always revolved around gods, princes, and dragons. ", "I did not truly understand what she read, she liked reading the unabridged versions of books way beyond my comprehension level but I loved the sound of her voice, so melodic, smooth, and exquisite like the finest Persian silk. ", "She did not like being interrupted when she read so she made me write down the words I did not understand and wait till she was finished to check those words in the dictionary. ", "At a young age I heard about twenty chapters from Lord of the Rings, random chapters from Le Morte D'Arthur, a few from Odyssey, and many other chapters from a long list of classics. ", "From her I learned about characters like Zeus, Isis, Morgan le Fay, and the three Fates. ", "I used to allude to them with lines like, \"Tragic like Oedipus?\" ", "or \"He is plain stupid, if you are going to nasty then you should at least have a brain like Loki.\" ", "I liked demonstrating my knowledge, proving to the world that I knew more than other average elementary school students.", "\n\nThen one night I found my bed-side empty and my room in a perfect dreadful silence.", "\n\nThat night Doctor Faustus and the Cat's Cradle, the two books my parents were reading, lied motionless on the shelves filled with books. ", "That night I drifted into fitful sleep.", "\n\nThe next afternoon I found myself, a seven and a bit year old boy, at the front door of a foreign house, a solemn, unfamiliar man, my grandfather, awaiting behind the door.", "\n\nBlaine has a habit of talking to his fish when he thinks no one can hear. \"", "Come on, little one, swim up there for some, don't let fatty – that's the way! ", "There's one more---\"\n\nI interrupted him with a cough. ", "I find that habit extremely depressing because of my preconception that only lonely old men talk to gold fish. ", "I never thought it my place to comment on how sad I find his conversations with fish but I always stop him when I do see him at it.", "\n\n\"Ah Gary,\" He swirled around at my voice. \"", "You are leaving now?\"", "\n\nHe always knows without me speaking, I snorted in private amusement, \"Your sixth sense told you?\" ", "I meant that as a joke so I laughed.", "\n\nHe did not laugh with me. \"", "No, just your bags,\" he spoke, his lips tilted into a light smirk.", "\n\nI shook my head and looked away, the saying 'parting is such sweet sorrow' swam in my mind. ", "Then, I remembered Miss Waterflower will keep him company after I leave and the knowledge lent me comfort. \"", "I just need to get away for a bit, there's an emergency in the lab.\" ", "It was not a lie. ", "An exploded water pump is definately considered an emergency.", "\n\n\"I hope that goes well,\" he responded in a deceptively kind tone but his eyes gave away his true feelings: he did not believe me at all.", "\n\n\"Me too.\"", "\n\n\"Gary, Misty she…\" Blaine started but when words failed him he resorted to a simple earnest, apologetic gaze.", "\n\nI combed my hair with my hand, \"Miss Waterflower keeps seeing me at my worst and I at hers,\" I bowed my head and traced the tiles with my foot, \"Perhaps we are just not meant to be friends.\"", "\n\n\"Don't say that…\"\n\n\"I need to go,\" I interrupted, suddenly feeling desperate to end the conversation, \"The last ferry off the island leaves in forty five minutes.\"", "\n\n\"I won't keep you then,\" Blaine sighed in defeat as he turned back to his goldfish, \"I saved some dinner for you, take the lunch box on the counter with you.\"", "\n\nI thanked him, grabbed the box, and walked into the night. ", "As I walked, alone and quiet, I contemplated on void, loneliness, and the all consuming empty darkness.", "\n\nChapter Three Ends\n\nOri: Well that took a while. ", "I had tons of trouble writing the second half. ", "I sent my first draft to Maia Pen a very long time ago, all the way back in April, you can ask her. ", "In my first draft the chapter was half the current length, but I realized I must end Gary's visit to Blaine's in this chapter for the story to have the same pace as what I have in mind. ", "Thus, I had to write on despite frustration and the temptation to just give up.", "\n\nThis story will be a Gary/Misty story, turmoil and obstacles are food for love.", "\n\nNext chapter, there will be reconciliation, a better explanation to Misty's bias against Gary, May's second appearance, good food, shopping spree, old vendetta, and more!", "\n\nReview if you have time! ", "I would love you if you do!", "\n\nThe author would like to thank you for your continued support. ", "Your review has been posted." ]

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[ "Regulation of biofilm formation and cellular buoyancy through modulating intracellular cyclic di-GMP levels in engineered cyanobacteria.", "\nThe second messenger cyclic dimeric (3'→5') GMP (cyclic di-GMP or c-di-GMP) has been implicated in the transition between motile and sessile lifestyles in bacteria. ", "In this study, we demonstrate that biofilm formation, cellular aggregation or flocculation, and cellular buoyancy are under the control of c-di-GMP in Synechocystis sp. ", "PCC 6803 (Synechocystis) and Fremyella diplosiphon. ", "Synechocystis is a unicellular cyanobacterium and displays lower levels of c-di-GMP; F. diplosiphon is filamentous and displays higher intracellular c-di-GMP levels. ", "We transformed Synechocystis and F. diplosiphon with a plasmid for constitutive expression of genes encoding diguanylate cylase (DGC) and phosphodiesterase (PDE) proteins from Vibrio cholerae or Escherichia coli, respectively. ", "These engineered strains allowed us to modulate intracellular c-di-GMP levels. ", "Biofilm formation and cellular deposition were induced in the DGC-expressing Synechocystis strain which exhibited high intracellular levels of c-di-GMP; whereas strains expressing PDE in Synechocystis and F. diplosiphon to drive low intracellular levels of c-di-GMP exhibited enhanced cellular buoyancy. ", "In addition, the PDE-expressing F. diplosiphon strain showed elevated chlorophyll levels. ", "These results imply roles for coordinating c-di-GMP homeostasis in regulating native cyanobacterial phenotypes. ", "Engineering exogenous DGC or PDE proteins to regulate intracellular c-di-GMP levels represents an effective tool for uncovering cryptic phenotypes or modulating phenotypes in cyanobacteria for practical applications in biotechnology applicable in photobioreactors and in green biotechnologies, such as energy-efficient harvesting of cellular biomass or the treatment of metal-containing wastewaters." ]

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[ "Loyola students receive national scholarships to study abroad\n\nLoyola University New Orleans junior Juli Smith is intrigued by Taiwan’s language and culture and has a special interest in studying Taiwanese Sign Language. ", "Malaika Lucien, also a junior, wants to spend a year studying business and perfecting her French, which she has grown up speaking. ", "Junior Sarah Willey seeks to immerse herself in Rabat, Morocco studying in both French and Arabic. ", "Those hopes will now become reality thanks to three prestigious Benjamin A. Gilman International Scholarships awarded to the Loyola students.", "\n\n\"Many Loyola students are prime candidates to apply for this outstanding award from the U.S. Department of State,\" said Alisa Jackson, study abroad adviser in the Center for International Education at Loyola. \"", "I am thrilled that three of our students were selected for the prestigious honor this year.\"", "\n\nThe Gilman scholarship program offers awards for undergraduate study abroad to students who are receiving Federal Pell Grant funding at a two- or four-year college or university. ", "Since its inception in 2001, more than 16,000 students nationwide have used the Gilman scholarship to study in 142 countries. ", "The program encourages students to choose non-traditional study abroad destinations outside of Western Europe, Australia and New Zealand. ", "The Gilman scholarship program is funded through the International Academic Opportunity Act of 2000 and is sponsored by the Bureau of Educational and Cultural Affairs at the U.S. Department of State.", "\n\nThe three Loyola students were selected from among 860 applicants from 332 colleges and universities across the U.S., Jackson said.", "\n\nSmith, an international business major, was awarded $5,000 to study in Taiwan during the full 2015-16 academic year. ", "She will study at Providence University, through International Student Exchange Program (ISEP). ", "Additionally, she was one of only three students selected to receive the Fund for Education Abroad’s Academic Year Scholarship of $10,000. ", "The mission of the Fund for Education Abroad (FEA) is to increase opportunities for dedicated American students to participate in high-quality, rigorous education abroad programs by reducing financial restrictions through the provision of grants and scholarships.", "\n\nLucien, a finance and political science double major, was also awarded $5,000 to study at the ESCE, a prestigious business school in Paris for the full year. ", "She also hopes to intern at a French company in the spring semester.", "\n\nWilley, a contract major in international development, was awarded $5,000 to study in Morocco through the Council on International Educational Exchange .", "\n\nMore information on the Gilman and FEA Scholarship programs and study abroad is available online." ]

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[ "Flag Springs, Missouri\n\nFlag Springs is an unincorporated community in Andrew County, in the U.S. state of Missouri.", "\n\nHistory\nA post office called Flag Springs was established in 1870, and remained in operation until 1907. ", "The community took its name from a nearby spring noted for the flag irises along its course.", "\n\nReferences\n\nCategory:Unincorporated communities in Andrew County, Missouri\nCategory:Unincorporated communities in Missouri" ]

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[ "Australian-born forward Chris McQueen is the surprise name in England's 20-man squad for the mid-season international against Samoa.", "\n\nCoach Wayne Bennett has handed the 29-year-old Wests Tigers back-rower his first call-up ahead of the one-off Test in Sydney on Saturday May 6.", "\n\nFormer South Sydney and Gold Coast Titans star McQueen's selection is something of a controversial choice having represented Queensland six times in State of Origin but qualifies for England through his father.", "\n\nThe move has echoes of Ben Te'o's call-up to this summer's British and Irish Lions' tour of his native New Zealand.", "\n\nMcQueen was approached to play for England in the 2013 World Cup but rejected it in the hope of winning Origin honours and he went on to play in six consecutive matches for the Maroons from 2013-14 and make a second appearance for an Australian Prime Minister's XIII against Papua New Guinea.", "\n\nMcQueen was the surprise name in Wayne Bennett's 20-man squad (Getty)\n\nThere is also a recall for another Australia-born forward, Chris Heighington, who was last selected under Steve McNamara in 2011, while Wigan loose forward Sean O'Loughlin returns to the squad as captain after missing the 2016 Four Nations tournament through injury.", "\n\nFull squad:" ]

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[ "Q:\n\nJava 5: java.util.concurrent.", "FutureTask - Semantics of cancel() and done()\n\nI am currently hunting a nasty bug in a multi-threaded environment using FutureTasks and Executors. ", "The basic idea is this to have a fixed number of threads execute individual FutureTasks that compute a result that is to be displayed in a a table (never mind the GUI aspect here). ", "\nI have been looking at this for so long, I am beginning to doubt my sanity.", "\nConsider this piece of code:\npublic class MyTask extends FutureTask<Result> {\n private String cellId;\n ...\n protected void done() {\n if (isCancelled()) return;\n try {\n Result r = get(); // should not wait, because we are done\n ... // some processing with r\n sendMessage(cellId, r);\n } catch (ExecutionException e) { // thrown from get\n ... \n } catch (InterruptedException e) { // thrown from get\n ... \n }\n }\n ...\n}\n\nWhen done() is called by an Executor handling an instance of MyTask, I check if I got there, because the task was cancelled. ", "If so, I skip all remaining activities, especially I do not call sendMessage().", "\nThe documentation for FutureTask.done() says:\n\nProtected method invoked when this task transitions to state isDone (whether normally or via cancellation). ", "The default implementation does nothing. ", "Subclasses may override this method to invoke completion callbacks or perform bookkeeping. ", "Note that you can query status inside the implementation of this method to determine whether this task has been cancelled.", "\n (API Reference)\n\nBut what I do not get from the documentation of FutureTask are the semantics while done() is being executed. ", "What if I pass the isCancelled() check at the beginning, but right after that some other thread calls my cancel() method? ", "Will that cause my task to change its mind and reply isCancelled() == true from then on?", "\nIf so, how would I later know if the the message was sent? ", "Looking at isDone() would just tell me that execution of the task was finished, but as isCancelled() were true then as well, I could not know if it got to send the message out in time. ", "\nMaybe this is obvious, but I do not really see it right now.", "\n\nA:\n\nFutureTask#done() is called no more than once for any given instance, and it's only called for one reason -- run() completed either with or without error, or cancel() ran before either of the preceding events occurred. ", "The record of completion by any of these outcomes is latching. ", "The reason a FutureTask completed can't change, regardless of competing events seemingly happening \"at the same time.\"", "\nHence, within FutureTask#done() only one of isCancelled() or isDone() will return true then and forever more. ", "It's difficult to distinguish between isDone() reporting true by way of error or successful completion. ", "You can't override set() or setException(Throwable) decisively, as both delegate to the inner AQS to decide whether the attempt to record a successful yielding of a value or encountering an exception should stick. ", "Overriding either method only lets you know that it was called, but you can't observe the decision made by the base implementation. ", "If either event occurs \"too late\"—say, after cancellation—the attempt to record the value or the exception will be ignored.", "\nStudying the implementation, the only way I see to discern a non-canceled successful outcome from an error is to bite the bullet and call get().", "\n\nA:\n\nFrom the API (emphasis mine):\n\npublic boolean cancel(boolean mayInterruptIfRunning)\nDescription copied from interface: Future\nAttempts to cancel execution of this task. ", "This attempt will fail if the task has already completed, already been cancelled, or could not be cancelled for some other reason.", "\n\nSo FutureTask is working off the assumption that you cannot cancel a task when it has transitioned to the isDone stage.", "\n\nA:\n\nWhy not send the message \"outside\" of the task, based on the outcome of the Future<V> object returned by an ExecutorService? ", "I've used this pattern and it seems to work well: Submit a bunch of Callable<V> tasks through an ExecutorService. ", "Then, for each primary task, submit a secondary task that waits on the Future<V> of the primary task and does some follow-up action (like send a message) only if the Future<V> indicates that the primary task completed successfully. ", "There is no guesswork with this approach. ", "When the call to Future<V>.get() returns, you're guaranteed that the task has reached a terminal state, as long as you don't call the version of get that takes a timeout argument.", "\nIf you take this approach, you should use two separate ExecutorService instances: one for the primary tasks and one for the secondary ones. ", "This is to prevent deadlocks. ", "You don't want secondary tasks to start up and potentially block primary tasks from starting when the thread pool size is limited.", "\nThere's no need to extend FutureTask<V> at all. ", "Just implement your tasks as Callable<V> objects. ", "But if for some reason you want to detect if the task was canceled from within the Callable<V> code, just check the interrupt status of the thread with Thread.interrupted().", "\n\n" ]

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[ "First completed model of 2020 – a Phobos Lieutenant for my Raptors army. ", "This is another model from the Shadowspear box that I’m slowly (but happily!) ", "working my way through. ", "I did a very minor conversion to swap the head with the captain from the same box." ]

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[ "g*2/(-3) a composite number?", "\nTrue\nSuppose -4*b + i = -23, -2*i + 1 = 5*b - 18. ", "Let o(l) = l**3 + 2. ", "Is o(b) a prime number?", "\nTrue\nIs (-108)/(-10) - (-4)/(-5) a prime number?", "\nFalse\nIs 77/2*(-2)/(-1) composite?", "\nTrue\nLet k(d) = -2*d. ", "Let s be k(-5). ", "Suppose 3*h - s = -y + 2*h, -3*y + 2*h = -55. ", "Suppose 2*w - 3*w = -y. ", "Is w composite?", "\nTrue\nSuppose -230 - 505 = -b. ", "Suppose 5*t - 350 - b = 0. ", "Is t prime?", "\nFalse\nLet u = -12 + 14. ", "Let k(t) = 17*t + 1. ", "Is k(u) composite?", "\nTrue\nSuppose -554 = -2*b + 3*d, -5*d + 0*d + 812 = 3*b. ", "Is b prime?", "\nFalse\nLet b(y) = -126*y - 6. ", "Let w be b(-5). ", "Suppose w = 4*j - 1224. ", "Let u = j + -319. ", "Is u a prime number?", "\nFalse\nSuppose 4*y = -m + 307, 6*m - m = -2*y + 1553. ", "Is m a prime number?", "\nTrue\nIs ((-1388)/(-6))/((-40)/(-60)) prime?", "\nTrue\nLet w = -3097 - -4754. ", "Is w prime?", "\nTrue\nLet m = 96 + -137. ", "Let b = -16 - m. Let c = b + -15. ", "Is c composite?", "\nTrue\nLet p = 9 - -60. ", "Suppose -m + 4*i + p = 0, 4*m = i - 0*i + 261. ", "Is m prime?", "\nFalse\nIs (15/30)/((-1)/(-974)) a composite number?", "\nFalse\nSuppose -3 = -4*p + 5. ", "Suppose -293 = -o + 3*m, -p*o - 5*m + 753 = 167. ", "Is o a prime number?", "\nTrue\nIs (-11)/((1/2)/(610/(-20))) a prime number?", "\nFalse\nLet h(a) = a - 2. ", "Let i(l) = -l**2 - l. Let v(p) = -h(p) - i(p). ", "Let r be v(0). ", "Suppose -57 = r*d - 5*d. ", "Is d a prime number?", "\nTrue\nLet v(f) = 2148*f**3 - f**2 + 2*f. ", "Is v(1) prime?", "\nFalse\nLet p(k) = -2 - 3*k**3 + 4*k - 3*k**2 + 4 - 1 + 4*k**3. ", "Is p(6) a prime number?", "\nFalse\nSuppose 0 = z - 2*h - 561, 2*h = -z - 0*z + 553. ", "Is z prime?", "\nTrue\nLet o = -29 + 40. ", "Suppose -3*p = 3*b + 15, o + 6 = -5*b + 3*p. ", "Let n(f) = -9*f - 5. ", "Is n(b) a prime number?", "\nTrue\nLet i(l) = -l**3 + 16*l**2 + 12*l + 4. ", "Is i(9) a composite number?", "\nTrue\nLet q(v) = -v**2 + 5*v**3 - 1 + 6*v**3 + 4*v - 4*v. ", "Let b be ((-6)/(-4))/(6/8). ", "Is q(b) prime?", "\nTrue\nLet i be 0 - (-11)/((-3)/(-3)). ", "Let x = -20 + i. Let c = -2 - x. Is c prime?", "\nTrue\nLet k(f) be the third derivative of -f**4/24 + 13*f**3/6 - 2*f**2. ", "Is k(6) prime?", "\nTrue\nLet v = 20 - 15. ", "Suppose 5*k - v*n = 1045, -k = -6*k - 2*n + 1059. ", "Is k composite?", "\nFalse\nLet u be 10231/7 + (-8)/14. ", "Suppose -4*k + 3*m = k - u, -5*k - 5*m + 1445 = 0. ", "Is k a prime number?", "\nFalse\nLet h(v) = 317*v + 29. ", "Is h(6) a prime number?", "\nTrue\nIs (-2990)/(-3) + (6/(-9) - -1) a composite number?", "\nFalse\nLet l(z) = -z**3 + 4*z**2 - 4. ", "Let k = -7 + 11. ", "Let a be l(k). ", "Let f = a - -23. ", "Is f a composite number?", "\nFalse\nLet q(r) = -3 + 19*r + 4 - 7 + 2. ", "Let i be 2*(-3)/4*-2. ", "Is q(i) a composite number?", "\nFalse\nLet d = 532 - 375. ", "Is d a composite number?", "\nFalse\nLet u(a) = -7*a - 5. ", "Let b be (4 + 0/2)*-2. ", "Is u(b) composite?", "\nTrue\nSuppose r + 3*d = d - 10, 0 = -2*r + 5*d + 16. ", "Is (-3)/r*46/3 a composite number?", "\nFalse\nSuppose -3*o = -4*p - 805, -5*p - 426 = -4*o + 647. ", "Is o composite?", "\nTrue\nLet t be (3 + 0)*32/6. ", "Is (-4)/t + 3354/8 a composite number?", "\nFalse\nLet g(u) = 234*u**2 + 8*u + 3. ", "Is g(-4) a prime number?", "\nFalse\nSuppose 2*w - 3*w = -2, 2*s - 2*w + 28 = 0. ", "Let f = -21 - -34. ", "Let y = f - s. Is y prime?", "\nFalse\nSuppose 2*s + 3*s - 433 = p, -2*p = 5*s - 439. ", "Is (20/(-6))/((-2)/s) a prime number?", "\nFalse\nLet f(g) = 63*g + 14. ", "Let a(m) = 21*m + 5. ", "Let z(o) = 17*a(o) - 6*f(o). ", "Let j be 2/(-1) + 3 + -2. ", "Is z(j) composite?", "\nTrue\nSuppose 0*o + 3*o - 483 = 0. ", "Is o prime?", "\nFalse\nLet n(z) = 1 + 2*z**3 + 8*z + 5*z**2 + 0*z**2 - 15*z**2. ", "Let f(y) = -y**2 + 8*y. ", "Let o be f(7). ", "Is n(o) prime?", "\nFalse\nLet w be 4/(-6) + 143/3. ", "Let u = w - 16. ", "Is u a prime number?", "\nTrue\nLet y = 40 + 1155. ", "Is y prime?", "\nFalse\nLet u be (-24)/108 - (-1012)/18. ", "Suppose 5*m - 3*i = 271, 5*i + 7 = m - u. Is m composite?", "\nFalse\nLet m be ((-1)/4)/((-10)/7960). ", "Suppose -5*d - 281 = -3*u, 2*u = 2*d - 9 + m. Is u composite?", "\nFalse\nIs (1/4)/(2 - 5061/2532) prime?", "\nTrue\nLet s(n) = 4*n + 1. ", "Let m(l) = l**2 - 8*l - 2. ", "Let f be m(6). ", "Let i be (-1)/(2 + f/6). ", "Is s(i) composite?", "\nFalse\nLet k = 1090 - 683. ", "Is k prime?", "\nFalse\nLet p = 3 - 1. ", "Let a be (-5)/10 + (-39)/p. ", "Is (-17)/(-4) + 5/a a prime number?", "\nFalse\nSuppose -407 = -5*p + 308. ", "Is p a prime number?", "\nFalse\nSuppose -2*n - 5*l + 209 = 0, 155 + 320 = 5*n + 3*l. ", "Let x be 1 + (0 - -2) + 1. ", "Suppose -x*u + n = -32. ", "Is u prime?", "\nTrue\nLet c(f) = -93*f - 17. ", "Is c(-6) a prime number?", "\nTrue\nLet y(t) = -13*t**2 + 12. ", "Let l be y(4). ", "Let b = 195 - -128. ", "Let r = l + b. Is r prime?", "\nTrue\nSuppose -14 = -3*q - m, -m = q - 5*m + 17. ", "Suppose 181 = q*o - 59. ", "Suppose 3*i = 2*p + 187, o = -3*i + 5*p + 255. ", "Is i prime?", "\nFalse\nLet i be 8 + (-4 - -2) + -1. ", "Suppose v = -3*x + 25, 3*x - i*x + 3*v = -24. ", "Suppose 4*k + x = 5*k. ", "Is k a composite number?", "\nTrue\nIs (4388/(-16))/(2/(-8)) a composite number?", "\nFalse\nSuppose 0*t = 2*t - 186. ", "Suppose n + 3*r - t = 0, -3*n + 2*r + 2*r = -214. ", "Let j = n - 39. ", "Is j a prime number?", "\nFalse\nLet k(q) = -5*q + 3. ", "Let j = -3 - -1. ", "Let c(x) = 6*x - 2. ", "Let s(b) = j*c(b) - 3*k(b). ", "Is s(4) prime?", "\nTrue\nLet g(r) be the third derivative of 1/24*r**4 - r**2 + 0 + 0*r**3 + 1/12*r**5 + 0*r. ", "Is g(-1) a composite number?", "\nTrue\nLet w(c) = c - 6. ", "Let i be w(9). ", "Suppose i*n - 354 + 117 = 0. ", "Is n prime?", "\nTrue\nSuppose 0*v + 376 = -4*v + c, 0 = v - 5*c + 94. ", "Let j be v/((-1)/(1/2)). ", "Suppose -2*l - 4*x + 63 = -j, -5*l = -4*x - 219. ", "Is l prime?", "\nTrue\nLet n(z) = 3*z**2 - 1. ", "Is n(10) composite?", "\nTrue\nSuppose 0 = 6*o - 4*o - 382. ", "Is o a prime number?", "\nTrue\nIs (948/8)/((-4)/(-8)) composite?", "\nTrue\nLet x(a) = a**3 + 7*a**2 + 5*a + 1. ", "Let f = 11 - 17. ", "Is x(f) composite?", "\nFalse\nLet v be (2*(-1 - -2))/(-2). ", "Let k = 18 - v. Is k prime?", "\nTrue\nLet q(p) = -p**3 - p**2 - p - 2. ", "Is q(-3) prime?", "\nTrue\nLet j = -4 + -11. ", "Let g be j/(-2)*(0 + 2). ", "Suppose -10 = -u + g. Is u composite?", "\nTrue\nLet n(i) = i**3 + 6*i**2 - 24*i - 23. ", "Is n(12) composite?", "\nFalse\nLet c(x) = 3*x + 1. ", "Let n = -31 + 43. ", "Is c(n) prime?", "\nTrue\nLet i(a) be the first derivative of 10*a - 1 + 10/3*a**3 + 1/4*a**4 + 3*a**2. ", "Is i(-9) prime?", "\nTrue\nLet g be 1 + 0 + 0/(-2). ", "Suppose 107 = 3*y - g. Suppose 0 = 7*i - 3*i - y. Is i prime?", "\nFalse\nSuppose 2*r + 0*r + 10 = 0, -3 = 3*j + 3*r. ", "Suppose z = -j*z. ", "Suppose z = -3*h - 20 + 62. ", "Is h composite?", "\nTrue\nSuppose 0 = 2*u - 0*u - 238. ", "Is u prime?", "\nFalse\nLet l(r) = 59*r**2 - 3*r + 5. ", "Is l(-4) a prime number?", "\nFalse\nLet c be (8/20)/((-2)/(-10)). ", "Suppose c*y + 3 = 7. ", "Is y/3*(-159)/(-2) a prime number?", "\nTrue\nSuppose -127 = -4*n + d, 90 = -0*n + 3*n + d. Is n a prime number?", "\nTrue\nSuppose -s - 69 = -3*i + 2*s, -3*i + 4*s + 68 = 0. ", "Suppose 3*q + 0*q - i = -f, 4*f = 3*q - 9. ", "Is q prime?", "\nTrue\nSuppose -2*l = -1 + 3. ", "Is (-1168 - l)*(-2)/6 prime?", "\nTrue\nLet g = -6 - -8. ", "Suppose 1 + g = l. Suppose -2*n = l*n - 955. ", "Is n prime?", "\nTrue\nSuppose 2*g + 25 = 7*g + 2*l, -3*g - 3*l = -24. ", "Suppose -1 = -u - c, 4*u + 3*c - g = 1. ", "Is u*(3 + -5) + 97 composite?", "\nTrue\nSuppose 0 = -0*h - h + 2. ", "Suppose -3*b + 10 = 3*c - 2*c, h*b + c - 6 = 0. ", "Is (-49)/(-2)*(b - 2) a prime number?", "\nFalse\nIs 3 - (0 - 83/1) a composite number?", "\nTrue\nLet n(c) = -32*c - 3. ", "Let h be (4/1)/2 - 4. ", "Let l be n(h). ", "Suppose 4*j = l - 9. ", "Is j a prime number?", "\nTrue\nSuppose 0 = 2*i - 0*i - 6. ", "Suppose 5*f - i*f - 74 = 0. ", "Is f a prime number?", "\nTrue\nSuppose 0 = -4*a + 5*a - 269. ", "Is a a prime number?", "\nTrue\nSuppose 8*l - 12*l + 19088 = 0. ", "Suppose -5*r = -r - l. Is r a composite number?", "\nFalse\nSuppose -3*l + 2*c = -0*c - 18, 2*l + 4*c = 12. ", "Let d(s) = 7*s - 9. ", "Is d(l) a prime number?", "\nFalse\nSuppose -36 = 2*m + 2*h, 0 = -m - 0*m + 4*h - 28. ", "Let s = m + 33. ", "Is s a prime number?", "\nTrue\nLet s(x) = 2*x**2 + 15*x + 9. ", "Is s(-10) a prime number?", "\nTrue\nSuppose 0*x - x = -5*t - 46, 74 = 2*x - 4*t. ", "Is x a prime number?", "\nTrue\nLet d(n) = -n**3 + 12*n**2 - 5*n + 3. ", "Let q be (22/(-8))/((-3)/12). ", "Is d(q) a prime number?", "\nFalse\nLet u = -343 + 560. ", "Is u a prime number?", "\nFalse\nLet j(o) = -o**2 - 7*o + 1. ", "Let p = -16 + 10. ", "Let c be j(p). ", "Is (c - 0) + (-2)/2 prime?", "\nFalse\nLet w be 30*1 - (4 + -6). ", "Let k = -18 + w. Is k a prime number?", "\nFalse\nLet i(x) = 4 - 4*x**2 + 0*x + 3*x + 3*x**2. ", "Let y be i(3). ", "Suppose -4*n = -3*v + y*v - 17, -14 = 2*n - 4*v. ", "Is n a prime number?", "\nTrue\nSuppose 0 = 6*t - 2*t - 2392. ", "Suppose 0 = -5*l + 5*s + 1000, -3*l + 6*l - s - t = 0. ", "Is l a prime number?", "\nTrue\nSuppose i + 2*o + 8 = 0, 0 = 3*i - i + 5*o + 21. ", "Suppose i*r - 96 = 62. ", "Is r a prime number?", "\nTrue\nLet u(c) = 6*c**2 + 8*c - 14. ", "Let v(d) = -5*d**2 - 7*d + 13. ", "Let i(z) = -4*u(z) - 5*v(z). ", "Suppose -h - 5*g = 27, 7*g = -3*h + 5*g - 29." ]

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[ "Psychological conditions diagnosed among veterans seeking Department of Defense Care for Gulf War-related health concerns.", "\nThe Comprehensive Clinical Evaluation Program is a US military program that provides a voluntary, clinically oriented evaluation for Gulf War health concerns. ", "This article presents administrative data on psychological conditions (as coded using the International Classification of Diseases, 9th Revision) from the first year of the program. ", "The most commonly diagnosed psychological conditions were medically unexplained physical-symptom syndromes; depression and anxiety, including post-traumatic stress disorder; and alcohol abuse or dependence. ", "Psychological conditions were significantly related to a higher number of workdays lost, and the 19% of veterans with a primary diagnosis of a psychological condition reported 28% of the lost workdays among veteran who participated. ", "Stressful Gulf War experiences were weakly but significantly related to psychological conditions. ", "We conclude that among Gulf War veterans seeking evaluation for Gulf War-related health concerns, psychological conditions are common and are associated with important occupational morbidity." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Forty years after its debut, the whole designated hitter thing is no less odd than it was when Ron Blomberg drew a bases-loaded walk off Luis Tiant in the first plate appearance by a DH on April 6, 1973.", "\n\nOdd because David Ortiz, the last great designated hitter, will play first base when the World Series shifts to St. Louis after the first two games in Boston.", "\n\nOdd because Allen Craig, who missed St. Louis' first two rounds of the playoffs with a foot injury, will DH for the Cardinals despite being a DH just twice in his career.", "\n\nTo DH or not to DH has been debated for as long as owners thought about keeping pitchers out of batters' boxes, and every October the debate takes on a different angle because nobody quite knows what to do in the World Series.", "\n\nThe current World Series setup - DH in American League parks, not National League parks - began in 1986. ", "From 1976 to 1985, it was used in all World Series games in even-numbered years - talk about odd.", "\n\nHideki Matsui had the most relevant World Series for a DH, winning MVP honors in 2009 despite starting three of six games for the Yankees. ", "The most irrelevant? ", "A case can be made for the Giants' three DHs in 2002, if only because all batted ninth.", "\n\nIt's the time of year when NL managers must invent DHs from their bench players and AL managers must make sure their pitchers reintroduce themselves to the bat rack. ", "It's not the norm from the regular season, but everyone must live with it.", "\n\nUniformity is better, but neither league is ready to budge, especially the AL, if only because the players' union wouldn't let go of the DH. ", "The pressure is beginning to mount for NL teams to consider a change now that season-long interleague play is here, but nothing's in the works.", "\n\nFor now, Ortiz is taking grounders and Craig is taking hacks. ", "We'll have two quality DHs for Games 1, 2 and, if necessary, 6 and 7, but iffy propositions in other games with Ortiz fielding (six starts at first during the season) and Boston pitchers hitting (1-for-26).", "\n\nThe World Series is baseball's biggest stage, yet two sets of rules apply. ", "It's odd, but that's nothing new." ]

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[ "Franklin MLB PHILLIES Kids Team Baseball Set Uniform. ", "The Franklin Sports MLB Kid's Team set will make any aspiring athlete feel like a part of their favorite team! ", "Complete with a team jersey, team wristbands and team helmet, this set is perfect for dress-up or a day in the park!", "\n\nTestimonials:\n\nL. FOSTER (PA)\n\n\"Omg what can I said. ", "I love it. ", "I love the prompt and courtesy service.", "And the quality is outstanding. ", "You have got a happy new customer for life.\" (", "E60969)\n\nS. SCHNEIDER (NC)\n\n\"This is the first year our private school has a cheer and dance team. ", "We needed uniforms and since they have a boy (Me) on the team we wanted to find something that we could all wear and look the same.", "\nThese shorts are fantastic and wear really well. ", "They also a really really good with E16436, which is a cheerleader football T-shirt. ", "We got red and white shorts with white and red T-shirts and socks and it looks totally fab. ", "And being shorts, I really like it. ", "They seem to wash well, but you need to be careful the first time they are washed.", "\n\" (E18344)\n\nProduct Description\n\nFranklin MLB PHILLIES Kids Team Baseball Set Uniform\n\nFeatures:The Franklin Sports MLB Kid's Team set will make any aspiring athlete feel like a part of their favorite team! ", "Complete with a team jersey, team wristbands and team helmet, this set is perfect for dress-up or a day in the park!", "\n\nEach set includes a 100% polyester team jersey, team wristbands and team helmet. ", "Jersey and wristbands are both machine washable.", "\n\nSize: One Size Fits Most - Ages 5-9\n\nNOTE: Team designs and logos subject to changeWARNING: Helmet must not be used as protective equipment in baseball or any other contact sport." ]

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[ "Foodies Read + TBR Pile Challenge | Cooking for Geeks by Jeff Potter\n\nPlease note: This review is for the FIRST edition of this title. ", "There is now a 2nd edition, which incl. ", "an additional 150 pages of new content!", "\n\nThis book includes an interesting combination of super basic recipes (hard boiled eggs, no-knead bread) and complicated or time-intensive recipes (duck confit sugo, 48-hour brisket). ", "The focus in all the recipes, regardless of required skill/interest level, is how the cooking techniques work.", "\n\nFor example, Potter doesn't just tell you that the \"shock and awe\" method of hard boiling eggs produces better-tasting eggs with shells that are easier to peel off; he walks you through the thermal gradient of the egg and what the shock of hot/cold water will do to the insides as well as the shell.", "\n\nThat being said, I have to confess that I have not actually tried any of the recipes in this book yet (no, not even the supposedly super-scientific perfect eggs). ", "I hesitate to \"review\" a cookbook without having tried the recipes, but here's why I went ahead and did it anyway:\n\n1. ", "Cooking for Geeks isn't just a collection of recipes. ", "It includes interviews, lots of tips for beginners, kitchen organization + equipment advice, and all kinds of science-y info on topics like taste, heat conduction methods, and food safety.", "\n\nSince reason number 2 is boring, let's talk some more about reason number 1.", "\n\n- - -\n\nI especially liked the sections on tastes (like bitter, sweet, sour, etc.) ", "and the kitchen organization + equipment info. ", "These are not topics that most \"cookbooks\" delve into but they're still very important to successful cooking. ", "I would recommend this book to beginner cooks, despite some of the more complicated recipes, simply because these sections are so dang helpful.", "\n\nPotter encourages experimentation. ", "There's a lot of \"What happens if we... ?\" ", "and \"Try X, Y, or Z instead and see how it turns out!\" ", "going on here. ", "That's cool with me, but if you're looking for extremely precise or strict recipes (and some people do prefer that!) ", "you'll just want to be aware that this is more of an experiment-friendly book.", "\n\nThe recipes themselves aren't even written in the traditional cooking time | ingredients list | steps | notes kind of way, nor will you find a lot of big glossy photos of pretty dishes. ", "The focus is all on figuring out how stuff works and how you can make it work even better.", "\n\n(That said, I love cookbooks with pretty pictures and would have appreciated some more illustrations/photos. ", "Still, since I was reading this on my Nook + phone, I wouldn't have been able to fully appreciate them anyway!)", "\n\n- - -\n\nAlso, keep in mind that a lot of the \"geek\" references are geared more towards developer/hacker types. ", "Like, if you think of yourself as a geek or nerd or whatever because you read a lot of comics and play tabletop RPGs, cool, let's be friends, but also you might miss out on some of the references meant for the more computer-y species of geek.", "\n\nDespite those geek species-specific references, this book covers a lot of science and techniques that you don't have to know anything about coding to get. ", "I'm saying that with a background in the natural sciences so basic household chemistry doesn't scare me anyway, but I truly think that as long as you have an interest in the subject of kitchen science you'll be able to understand all or most of the topics in this book." ]

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[ "Some Spider-Man fans really want Tobey Maguire to come back\n\nJust to be clear, this is not happening. ", "Not in a million years.", "\n\nHope is a beautiful thing. ", "For Spider-Man fans, hope is what kept them going through the horrors of Spider-Man 3 and its dancing goth Peter Parker, the mediocrity of the Amazing Spider-Man reboot, and Sony‘s endless back-and-forth as they desperately tried to work out what to do with the franchise.", "\n\nThe good news is, all that hoping and waiting has finally paid off. ", "Sony and Marvel have worked out a crossover deal where Spider-Man will appear in the Marvel Cinematic Universe, most likely in Captain America: Civil War. ", "This news inspired a near-religious fervor among Marvel aficionados, many of whom are treating it more like the second coming than what it actually is: a corporate merger.", "\n\nMarvel never needed Sony, Marvel just wanted to give us what us fans have always dreamed of. ", "Because Marvel is love... Marvel is life.", "\n\nAnyway, now that we’ve got that first flush of excitement out of the way, it’s time to get down to the nitty-gritty of baseless casting speculation. ", "And what better place to start than everyone’s first choice of Spider-Man, Tobey Maguire?", "\n\nWhile we are not an oracle imbued with the power to predict Marvel’s decisions, it feels safe to say that they will not be bringing back Tobey Maguire. ", "That is not a thing that will happen in the real world. ", "Although there is one instance in which we could get behind this idea, and that’s a movie where Tobey Maguire plays a middle-aged mentor figure to Miles Morales.", "\n\nhttps://twitter.com/Parkour3012/status/565091738327728128\n\nHowever, that is also not going to happen. ", "The Marvel–Sony agreement makes it slightly more likely that Miles Morales will appear at some point, but unfortunately, we doubt that he’s going to be the lead character.", "\n\nMarvel’s announcement implied that a new actor would be cast, saying “the new Spider-Man will first appear in a Marvel film” before appearing in the next installment of Sony’s franchise. ", "Whether that Sony film will be a sequel or another reboot is unclear, but either way, it won’t star Tobey Maguire.", "\n\nGavia Baker-Whitelaw is a staff writer at the Daily Dot, covering geek culture and fandom. ", "Specializing in sci-fi movies and superheroes, she also appears as a film and TV critic on BBC radio. ", "Elsewhere, she co-hosts the pop culture podcast Overinvested. ", "Follow her on Twitter: @Hello_Tailor" ]

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