bluuebunny/crossref_metadata_2025 huggingface dataset:
Water quality: A hidden danger in anthropogenic desert catchments
Authors: Griffis‐Kyle Kerry L. , Kovatch Jeffery J. , Bradatan Cristina
Published: October 2013

Natural rock pools, tinajas, and constructed catchments in the Sonoran Desert provide water for a wide variety of organisms. In 2012, we monitored water quality and amphibian and dragonfly use of wildlife waters in southwestern Arizona, USA. We measured ammonia concentrations that exceeded the U.S. Environmental Protection Agency's guidelines for aquatic life and were well above concentrations that cause mortality in amphibians and other aquatic organisms. Both amphibians and dragonflies had lower species richness in catchments than in the tinajas, and amphibian species richness was negatively associated with ammonia concentration. These concentrations of ammonia alone cause concern for the management of biodiversity, specifically for wetland‐dependent organisms. Furthermore, ammonia concentrations may be high enough to impact terrestrial organisms of economic and conservation importance including humans. © 2013 The Wildlife Society.
Randomised controlled trials in plastic surgery: a systematic review of reporting quality
Authors: Agha Riaz Ahmed , Camm Christian F. , Doganay Emre , Edison Eric , Siddiqui Muhammed R. S. , Orgill Dennis P.
Published: October 2013

Background

We recently conducted a systematic review of the methodological quality of randomised controlled trials (RCTs) in plastic surgery. In accordance with convention, we are here separately reporting a systematic review of the reporting quality of the same RCTs.

Methods

MEDLINE® and the Cochrane Database of Systematic Reviews were searched by an information specialist from 1 January 2009 to 30 June 2011 for the MESH heading ‘Surgery, Plastic’. Limitations were entered for English language, human studies and randomised controlled trials. Manual searching for RCTs involving surgical techniques was performed within the results. Scoring of the eligible papers was performed against the 23-item CONSORT Statement checklist. Independent secondary scoring was then performed and discrepancies resolved through consensus.

Results

Fifty-seven papers met the inclusion criteria. The median CONSORT score was 11.5 out of 23 items (range 5.3–21.0). Items where compliance was poorest included intervention/comparator details (7 %), randomisation implementation (11 %) and blinding (26 %). Journal 2010 impact factor or number of authors did not significantly correlate with CONSORT score (Spearman rho = 0.25 and 0.12, respectively). Only 61 % declared conflicts of interest, 75 % permission from an ethics review committee, 47 % declared sources of funding and 16 % stated a trial registry number. There was no correlation between the volume of RCTs performed in a particular country and reporting quality.

Conclusions

The reporting quality of RCTs in plastic surgery needs improvement. Better education, awareness amongst all stakeholders and hard-wiring compliance through electronic journal submission systems could be the way forward. We call for the international plastic surgical community to work together on these long-standing problems.
Pressurized Pulse Irrigation with Saline Reduces Surgical‐site Infections following Major Hepatobiliary and Pancreatic Surgery: Randomized Controlled Trial
Authors: Nikfarjam Mehrdad , Weinberg Laurence , Fink Michael A. , Muralidharan Vijayaragavan , Starkey Graham , Jones Robert , Staveley‐O’Carroll Kevin , Christophi Christopher
Published: October 2013

Background

Surgical site infections (SSI) are a significant cause of postoperative morbidity. Pressurized pulse irrigation of subcutaneous tissues may lower infection rates by aiding in the debridement of necrotic tissue and reducing bacterial counts compared to simply pouring saline into the wound.

Methods

A total of 128 patients undergoing laparotomy extending beyond 2 h were randomized to treatment of wounds by pressurized pulse lavage irrigation (<15 psi) with 2 L normal saline (pulse irrigation group), or to standard irrigation with 2 L normal saline poured into the wound, immediately prior to skin closure (standard group). Only elective cases were included, and all cases were performed within a specialized hepatobiliary and pancreatic surgery unit.

Results

There were 62 patients managed by standard irrigation and 68 were managed by pulse irrigation. The groups were comparable in most aspects. Overall there were 16 (13 %) SSI. Significantly fewer SSI occurred in the pulse irrigation group [4 (6 %) vs. 12 (19 %); p = 0.032]. On multivariate analysis, the use of pulse irrigation was the only factor associated with a reduction in SSI with an odds ratio (OR) of 0.3 [95 % confidence interval (95 % CI) 0.1–0.8; p = 0.031]. In contrast, hospital length of stay of greater than 14 days was associated with increased infections with an OR of 7.6 (95 % CI 2.4–24.9; p = 0.001).

Conclusions

Pulse irrigation of laparotomy wounds in operations exceeding 2 h duration reduced SSI after major hepatobiliary pancreatic surgery. (Australian New Zealand Clinical Trials Registry, ACTRN12612000170820).
Educational internationalism, universal human rights, and international organisation: International Relations in the thought and practice of Robert Owen
Authors: DAVIES THOMAS RICHARD
Published: October 2013

Robert Owen, the early nineteenth-century social reformer, made a greatly more significant contribution to the theory and practice of International Relations than has hitherto been assumed. This article shows how Owen helped to develop an understudied but distinctive form of internationalist thought focusing on the role of education in the pursuit of peace. Owen's previously neglected contributions to human rights norms and to international organisation are also explored, including his promotion of universal rather than nationally-oriented human rights standards, his role in the nascent movement towards the formation of international non-governmental organisations, and his contribution to international federalist ideas. Following an introduction to Owen's place in the literature, this article discusses each of these contributions of Owen to the theory and practice of International Relations in turn. The analysis reveals that Owen's contributions in each of these aspects are as significant for their limitations as for their insights.
The Red Crag Shell Portrait
Authors: Stopes Marie C.
Published: October 2013

Owing to the continued expression of interest in the Red Crag Shell, which bears a crude carving of a human face upon it, and which my father first described so many years ago, the time seems ripe to collect the evidence regarding it. I wrote a letter to the “Geological Magazine” summarising the facts of the case, and giving the literature of the subject, and this was followed by a later note.

Many geologists and others have expressed themselves as desirous of seeing the shell, round which discussion and more or less heated opinion has revolved for thirty-two years. It was shown at the London meeting of the Prehistoric Society of East Anglia, when the President, Dr. Sturge, proposed that a committee should be formed critically to examine and report on it. In the present paper, therefore, I shall confine myself to stating its history, and bringing together what little contemporary evidence there is regarding its discovery.
Report of Special Committee
Authors: Sturge W. Allen , Moir T. Reid , Burrell W. H. , Clarke W. G.
Published: October 2013

At the suggestion of the President it was agreed to appoint a Special Committee to examine the shell forming the subject of Dr. Stopes' paper, and to report upon it. A Committee was accordingly formed consisting of the President of the Society (Dr. Allen Sturge), the Vice-President (Mr. J. Reid Moir, F.G.S.), the Secretary (Mr. W. G. Clarke), and Mr. W. H. Burrell, F.L.S.; the President to act as Chairman.

By invitation of the President, the Committee met at Icklingham Hall from May 17th to 19th. Dr. Marie Stopes was also present, to be responsible for the safety of the specimen and to give such further information as the Committee might desire.
A Discovery of Pleistocene Bones and Flint Implements in a Gravel Pit at Dovercourt, Essex
Authors: Underwood W.
Published: October 2013

The discovery with which this paper deals was made by me in August, 1908. In the early part of that month, while walking in Upper Dovercourt, I noticed a gravel pit being excavated in a field overlooking the Stour Valley, and thinking it was a likely spot to find river drift implements, I interviewed the workmen, and found that though they knew nothing of humanly-flaked flints, they had noticed and preserved a number of bones, which, however, had unfortunately been sold to a local rag and bone merchant. The occurrence of these bones made me feel confident that flint implements must be associated with them; so I took a representative series of Palæolithic implements for the men to see, and explained to them that it was such things I wanted them to look for. I also took the opportunity of examining the stone heaps in the pit, and was fortunate enough to discover two Moustier-like implements, which, though of no great importance, confirmed me in my opinion as to the implementiferous nature of the gravel bed.
Flint Implements from the Ploughlands of South-West Leicestershire
Authors: Pickering A. J.
Published: October 2013

In the autumn of 1913, Mr. T. C. Cantrill, F.G.S., of the Geological Survey, drew the writer's attention to the possibility of finding flint artefacts in the surface soils of Hinckley and neigh-bourhood wherever the chalky boulder clays and gravels were in evidence. During his survey of the drift in this district in that and the following year, he himself found a lozenge-shaped scraper (No. 163, Plate LXVIII) in a field at Sapcote, and also five spalls of unmistakable human origin in other neighbouring localities.

In the winter of that year, Mr. F. C. Grimes and I began a systematic search which by the following spring had resulted in sufficient material to encourage us to further efforts, and the following notes are the result of a by no means exhaustive survey during that and the two following winters.
The Mundford Pebble Industry
Authors: Layard Nina F.
Published: October 2013

The flint implements which are the subject of this paper were found near Mundford in Norfolk in 1918-19, and the work is still being continued on this area.

Although when thrown out by the plough the tools may be described as surface finds, strictly speaking, they belong to the red gravelly sands which immediately over-lie the chalk in this district, and which are covered by one to two feet of brown sandy loam.

The large number of true implements found in a comparatively limited space, warrants the belief that this must have been a settlement, where work had been carried on for a considerable time.

Having hitherto escaped the eye of the wandering collector, an unusually complete series has been secured.
Flint-Crust Engravings, and Associated Implements, from Grime's Graves, Norfolk
Authors: Armstrong A. Leslie
Published: October 2013

Excavations at Grime's Graves during September, 1920, resulted in several interesting discoveries, notably the location of a new chipping and occupation zone, situated near the S.E. margin of the mining area immediately west of the Tumulus Pit, a locality which previous excavations had proved to be rich in occupation sites. Here, upon a living level immediately overlying glacial sand, two pieces of engraved flint crust were discovered associated with a series of flint implements of Mousterian type, bone tools and pottery.

Engraving upon flint crust was first noticed at Grime's Graves in 1915, upon Floor 16, a piece bearing incised lines of indeterminate character being found (Fig. A, 10) which was described and figured in the Proceedings, Vol. II., Part III., by Dr. Peake. Since then numerous similar examples have been discovered upon other floors, which, together with the occurrence of gravers, the discovery of chalk carving in the round, and of chalk balls by Mr. D. Richardson, and by the President, pointed to the hope of definite engravings being ultimately forthcoming if systematically searched for. This hope was further stimulated by Dr. Peake finding a few days prior to our visit a piece of crust bearing an engraved outline suggesting portions of the human figure (Fig. A, 11) and resulted in the careful scrutiny of every fragment of crust turned up during the subsequent excavations, which was finally rewarded by the discovery of two fine engravings (Fig. E).
Some Notes on the Prehistory of the Eastern Part of Central Europe
Authors: Burkitt M. C.
Published: October 2013

Having lately returned from Czecho-Slovakia, where I was attending an Anthropological Congress and studying museum collections, I thought perhaps it might interest members of the P.S.E.A. to have a note on what appears to be the succession of prehistoric cultures in that country.

There seems to be nothing so far found corresponding to our Lower Palæolithic or earlier industries. It is true that there is one solitary lump of flint, roughly chipped, with large flake-scars and an ochreous patina that has been claimed as Lower Palæolithic in date, but it is really very little to go on. A poor kind of Mousterian, mostly not made of good flint, seems fairly common in Moravia although it has not been found near Prague. On the other hand, many of the tools in an undoubted Upper Palæolithic series recall by their technique and shape the industry of La Quina.
The Gravels at Reculver, Kent
Authors: Burchell J. P. T.
Published: October 2013

In January, 1912, Mr. Reginald Smith read a paper before the Society of Antiquaries entitled “Flint Implements of Special Interest,” in which figured an implement of the Thames pick type— the author relegating it to the palæolithic period. I will read an extract from this paper describing the “pick.”

“The implement in question was found during the War by the late Captain Harvey Webb while searching the coastal gravel near Netley Hospital. It is a flint rod of roughly triangular section, with one face chipped flat; one end is nosed with bold fluting, the other is crusted and therefore, not functional. The whole is patinated an ochreus colour and the ridges are much battered by rolling.

Length 6 inches—the flat face 2 inches across. It was submitted to the British Museum in November, 1916, with other (obviously palæolithic) specimens from the same deposits: a large pear-shaped hand-axe with brown patina; a white St. Acheul ovate much rolled; a cordate brown St. Acheul implement; unrolled; a pointed triangular hand-axe; and a brown chert ovate, this last being from the top of the loam beneath the gravel.”
Palæolithic Industries from the Great Ouse Gravels at and Near St. Neots
Authors: Tebbutt C. F. , Marr J. E. , Burkitt M. C.
Published: October 2013

The market town of St. Neots is situated a mile or so off the Great North Road, and on the right bank of the Great Ouse just where it forms the boundary between Huntingdonshire and Bedfordshire. It lies at an average height of 55 feet above O.D.

For some years I have visited the pits which are worked in the low level gravels in and near this town and have been successful in obtaining from them a number of Palæolithic implements and flakes, as well as mammalian remains. Nearly all the implements and flakes were found by myself on heaps of gravel recently raised from the pits, but a few, together with all the bones, were found by the workmen, who in some cases were able to give me the level of derivation.

The first pit to be considered is in the town of St. Neots, and is situated in the grounds of Hall Place, Cambridge Street, about 150 yards east of the Vicarage. It is not very extensively worked and gravel is dug to a depth of 9 feet. The surface, which is approximately 50 feet above O.D., is less than ten feet above the level of the river. I have only one definite implement from this site (Plate II., fig. c), which I found on a heap of gravel on the edge of the pit. Flakes, however, number ten. They are mostly rather thick and coarse, and five show some crust. Most of them have little patination except a faint bluish stain near the crust. One is of a dark honey colour, and another has an ochreous patination. Several of these might have been used as scrapers, and four seem to have been struck from a prepared platform. Red Deer, Rhinocerus tichorhinus and Bos or Bison have been discovered in this pit.
Pin Hole Cave Excavations, Creswell Crags, Derbyshire. Discovery of an Engraved Drawing of a Masked Human Figure
Authors: Armstrong A. Leslie
Published: October 2013

Excavations on behalf of the Research Committee for the Archæological Excavation of Derbyshire Caves (British Association and Royal Anthropological Institute) were commenced by the writer in the Pin Hole Cave, Creswell Crags, in September, 1924, at a point 23 feet from the entrance, where the superficial examination of the upper beds by the Rev. Magins Mello had terminated in 1873. The work has steadily progressed, and has now reached 80 feet beyond the datum point, and is proceeding in the large inner chamber which has been revealed by the removal of the deposits which, over half its area, had accumulated to the level of the roof. The section embraces an upper cave-earth from 6 to 7 feet in thickness, mostly sealed beneath stalagmite, or breccia, and containing artifacts ranging in time from Upper Mousterian at its base to Magdalenian at the top. The lower cave-earth, 10 to 11 feet in thickness, contains three lower Palæolithic cultural zones, the lowest of which is 13 feet beneath the floor of the cave.
Implements from High-Level Gravel near Canterbury
Authors: Smith Reginald A.
Published: October 2013

Though the terrace gravels and palaeoliths of north-west Kent are well-known, there is little published on the stratigraphy of implements elsewhere in the county, except the Sturry deposits, two miles north-east of Canterbury (Archaeologia, LXXIV, 117). The geological Drift map is old (the latest edition issued in 1875), and there is no memoir to elucidate any but the Dartford area; but in 1925 the geology of the Canterbury district was described by Messrs. Dewey, Wooldridge, Cornes and Brown in the Proceedings of the Geologists' Association, vol. XXXVI, pp. 257–290, and Messrs. Wooldridge & Kirkaldy read a paper to that Association this April on the physiographic evolution of north-east Kent, which throws much light on the problem presented by the Fordwich flints.

Formerly the port of Canterbury, Fordwich lies on the right or southern bank of the Great Stour opposite Sturry, and at the foot of a steep hill, which rises to 150 ft. and leads to an elevated plain between the valleys of the Great and Little Stour. In the angle between the road leading due southfrom Fordwich and that from Stodmarsh to Canterbury, west of Moat Cottages (6 in. O.S. map, Kent, XLVI, N.E.), gravel has been worked over a considerable area, the depth being about 7 feet on the east and over 20 feet at the west end. The nearest bench-mark is 151·4 feet and the base of the gravel on the west is therefore about 130 feet O.D., rising to the east. The tongue of high ground between the rivers is covered in patches with gravel and brick-earth resting on Thanet Sand, and forms a plateau about 5 miles long at about the 100 ft. level.
A Giant Hand-axe from Sheringham, Norfolk
Authors: Moir J. Reid
Published: October 2013

The remarkable series of deposits, known as “The Cromer Forest Bed,” is of never-failing interest to a great number of people. So far as we know no other part of England, and possibly no other part of the world, can boast of an accumulation precisely comparable to the Forest Bed. It was laid down when the present river Rhine flowed northwards through what is now the North Sea, and at a time separated from to-day by several hundreds of thousands of years. East Anglia, and no doubt other parts of the northern hemisphere, was then enjoying a warm climate, and was inhabited by herds of great game animals, and hunting people who left behind them a vast number of flint implements which delight, and in some cases, puzzle modern archaeologists. But there are other things than flint implements which puzzle archaeologists. In these days the mere finding of a humanly-flaked flint in a geological deposit is not the alpha and omega of the archæologist's task.
Excavations in a Dry Valley in Beer, S.E. Devon
Authors: Gertrude  , Woods Roland MacAlpine
Published: October 2013

The object of this paper is to make known the existence of a wide-spread implementiferous deposit hitherto unknown in Devonshire, although comparable discoveries have been made in East Anglia by Mr. Reid Moir and in the Thames Valley by Mr. J. P. T. Burchell.

A brief preliminary statement appeared in Vol. VII, part 2, in “Notes on Excavations,” which reported our finding a number of flint implements which lay to a depth of 12 ft. below the surface of a dry valley in Bovey Lane, Beer.

These specimens were revealed in an artificial cutting made in search of water, when only the faces of the sections could be examined, but by aid of a grant from the Percy Sladen Memorial Fund, we were later enabled to carry out two seasons of excavation.
Promoters maintain their relative activity levels under different growth conditions
Authors: Keren Leeat , Zackay Ora , Lotan‐Pompan Maya , Barenholz Uri , Dekel Erez , Sasson Vered , Aidelberg Guy , Bren Anat , Zeevi Danny , Weinberger Adina , Alon Uri , Milo Ron , Segal Eran
Published: October 2013

Most genes change expression levels across conditions, but it is unclear which of these changes represents specific regulation and what determines their quantitative degree. Here, we accurately measured activities of ∼900 S. cerevisiae and ∼1800 E. coli promoters using fluorescent reporters. We show that in both organisms 60–90% of promoters change their expression between conditions by a constant global scaling factor that depends only on the conditions and not on the promoter's identity. Quantifying such global effects allows precise characterization of specific regulation—promoters deviating from the global scale line. These are organized into few functionally related groups that also adhere to scale lines and preserve their relative activities across conditions. Thus, only several scaling factors suffice to accurately describe genome‐wide expression profiles across conditions. We present a parameter‐free passive resource allocation model that quantitatively accounts for the global scaling factors. It suggests that many changes in expression across conditions result from global effects and not specific regulation, and provides means for quantitative interpretation of expression profiles.
Effects of phosphorus doping on the bending strength of a single crystal silicon microbeam
Authors: Liu Bin , Tao Jun Yong , Zhang Yun An , Chen Xun , Wang Xiao Jing
Published: October 2013

The effects of phosphorus doping on the bending strength of a single crystal silicon (SCS) microbeam are reported. First, a specially designed bending microstructure test and a simple bending test device are presented. Secondly, the results of bending strength tests for six groups of specimens with different phosphorus doping concentrations are presented. The test results are comparatively analysed using a Weibull distribution, revealing that the bending strength has a monotonically increasing relationship with the phosphorus concentration. The effect of surface roughness on the bending strength is also investigated. Finally, the mechanism underlying this phenomenon is demonstrated. The results indicate that the bond strength of a phosphorus–silicon pair is larger than that of a silicon–silicon pair, and the phosphorus atoms increase the energy necessary to create new surfaces. Therefore more energy is required to fracture the microbeam, and the fracture strength increases. Research on this topic therefore shows some practical significance for improving the bending strength of a SCS microstructure.
Effects of natural weathering conditions on faecal cortisol metabolite measurements in the greater bilby (Macrotis lagotis)
Authors: Evans Nicole , Narayan Edward J. , Hero Jean-Marc
Published: October 2013

Natural weathering conditions can influence faecal cortisol metabolite (FCM) measurements in wildlife if fresh faeces cannot be collected immediately following defaecation. In this study, we evaluated this issue in a threatened Australian marsupial, the greater bilby (Macrotis lagotis). Fresh (<12 h since defaecation) faecal samples (n = 19 pellets per bilby) were collected one morning from seven adult bilbies kept in captivity. One control faecal sample (Day 1) from each bilby was immediately frozen. The remaining faecal pellets were randomly positioned outdoors. Subsequently, we froze one faecal pellet every 24 h for 19 days. FCM levels in bilby faeces were quantified using an enzyme-immunoassay. Mean FCM levels showed variation (daily mean coefficients of variation [CV %]) of 56.83–171.65% over 19 days. Overall, FCM levels were affected by exposure time; however, multiple comparisons showed that no significant change in FCM occurred after environmental exposure (no significant difference in mean FCM between control (Day 1) with any of the exposure days (Days 2–19). Individuals and sex also affected FCM levels. We found no correlation between mean daily CVs with daily minimum–maximum temperatures or rainfall. Our results indicate that FCM in bilby faeces is fairly stable to long-term environmental exposure (19 days). In future, freshly excreted bilby faeces (where the sample maintains a distinct odour for 9–13 days) should be used to study FCM levels in wild bilbies.
Developmental origins of the world’s largest flowers, Rafflesiaceae
Authors: Nikolov Lachezar A. , Endress Peter K. , Sugumaran M. , Sasirat Sawitree , Vessabutr Suyanee , Kramer Elena M. , Davis Charles C.
Published: October 2013

Significance

Rafflesiaceae produce the world’s largest flowers, but the developmental nature of their floral organs has remained a mystery. Most members of the family have a large floral chamber, which encloses their reproductive organs. We used comparative studies of development and gene-expression patterns to investigate the homology of their floral organs. Our results demonstrate that the similar floral chambers in two Rafflesiaceae subclades are constructed very differently. Thus, the characteristic features that define the floral chamber in these closely related clades are not homologous. Instead, these data indicate that similar floral chambers represent two distinct derivations of this morphology, which may have contributed to the explosive growth in floral diameter that arose secondarily within one subclade,
Rafflesia
.
Keratins significantly contribute to cell stiffness and impact invasive behavior
Authors: Seltmann Kristin , Fritsch Anatol W. , Käs Josef A. , Magin Thomas M.
Published: October 2013

Significance

In many processes such as wound healing, inflammation, and cancer progression, the cytoskeleton is influencing cell motility and cell shape. Thus far, in contrast to the actin and microtubule cytoskeleton, intermediate filament proteins are not well investigated in this context. Here, we show that keratin-free cells from mice skin lacking all keratins on genome engineering have about 60% higher cell deformability even for small deformations in contrast to a smaller effect generated by actin depolymerization. Keratin-free cells are more invasive and show an increased growth in a 3D assay. Our study highlights keratins’ role in cell stiffness and its influence in invasion, supporting the view that down-regulation of keratins observed during epithelial–mesenchymal transition directly contributes to the migratory and invasive behavior of tumor cells.
Cell responses only partially shape cell-to-cell variations in protein abundances in
Escherichia coli
chemotaxis
Authors: Mukherjee Sayak , Seok Sang-Cheol , Vieland Veronica J. , Das Jayajit
Published: October 2013

Significance

The relationship between form and function is ubiquitous in biology. Using a method (maximum entropy) from statistical physics, we investigated how function regulates form in the context of
Escherichia coli
chemotaxis. We found that the nearly perfect and robust chemotaxis behavior (function) does not fully determine the cell-to-cell variations of chemotaxis protein abundances (form) in
E. coli
. We show that additional constraints imposed by the protein synthesis machinery and nonchemotactic cell functions in conjunction with the constraints imposed by the chemotaxis program are required to determine the observed variations of protein abundances. This demonstrates that properties of a modular component (e.g., the chemotaxis signaling module) in a biological network also depend on the system of which the module is a part.
Cyclic diguanosine monophosphate represses bacterial flagella synthesis by interacting with the Walker A motif of the enhancer-binding protein FleQ
Authors: Baraquet Claudine , Harwood Caroline S.
Published: October 2013

Significance

Many bacteria respond to environmental cues by producing cyclic diguanosine monophosphate (c-di-GMP), which binds to proteins to modulate transitions between sessile and motile lifestyles important for chronic and acute infections, respectively. The breadth of protein targets and mechanisms of action of c-di-GMP remain unknown. In the opportunistic pathogenPseudomonas aeruginosa, c-di-GMP binds to FleQ, a transcription factor that is the master regulator of flagella synthesis and a member of the large family of AAA+ ATPase proteins. We found that c-di-GMP competitively inhibits FleQ ATPase activity and interacts with the ATP-binding site on FleQ. We suggest that AAA+ ATPases from other bacteria may respond to c-di-GMP, and that interference with ATPase activity is one mechanism of c-di-GMP action.
On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells
Authors: Avraham-Davidi Inbal , Yona Simon , Grunewald Myriam , Landsman Limor , Cochain Clement , Silvestre Jean Sebastien , Mizrahi Haim , Faroja Mohammad , Strauss-Ayali Dalit , Mack Matthias , Jung Steffen , Keshet Eli
Published: October 2013

Adult neovascularization relies on the recruitment of monocytes to the target organ or tumor and functioning therein as a paracrine accessory. The exact origins of the recruited monocytes and the mechanisms underlying their plasticity remain unclear. Using a VEGF-based transgenic system in which genetically tagged monocytes are conditionally summoned to the liver as part of a VEGF-initiated angiogenic program, we show that these recruited cells are derived from the abundant pool of circulating Ly6Chi monocytes. Remarkably, however, upon arrival at the VEGF-induced organ, but not the naive organ, monocytes undergo multiple phenotypic and functional changes, endowing them with enhanced proangiogenic capabilities and, importantly, with a markedly increased capacity to remodel existing small vessels into larger conduits. Notably, monocytes do not differentiate into long-lived macrophages, but rather appear as transient accessory cells. Results from transfers of presorted subpopulations and a novel tandem transfer strategy ruled out selective recruitment of a dedicated preexisting subpopulation or onsite selection, thereby reinforcing active reprogramming as the underlying mechanism for improved performance. Collectively, this study uncovered a novel function of VEGF, namely, on-site education of recruited “standard” monocytes to become angiogenic and arteriogenic professional cells, a finding that may also lend itself for a better design of angiogenic therapies.
AllergenFP: allergenicity prediction by descriptor fingerprints
Authors: Dimitrov Ivan , Naneva Lyudmila , Doytchinova Irini , Bangov Ivan
Published: October 2013

Motivation: Allergenicity, like antigenicity and immunogenicity, is a property encoded linearly and non-linearly, and therefore the alignment-based approaches are not able to identify this property unambiguously. A novel alignment-free descriptor-based fingerprint approach is presented here and applied to identify allergens and non-allergens. The approach was implemented into a four step algorithm. Initially, the protein sequences are described by amino acid principal properties as hydrophobicity, size, relative abundance, helix and β-strand forming propensities. Then, the generated strings of different length are converted into vectors with equal length by auto- and cross-covariance (ACC). The vectors were transformed into binary fingerprints and compared in terms of Tanimoto coefficient.

Results: The approach was applied to a set of 2427 known allergens and 2427 non-allergens and identified correctly 88% of them with Matthews correlation coefficient of 0.759. The descriptor fingerprint approach presented here is universal. It could be applied for any classification problem in computational biology. The set of E-descriptors is able to capture the main structural and physicochemical properties of amino acids building the proteins. The ACC transformation overcomes the main problem in the alignment-based comparative studies arising from the different length of the aligned protein sequences. The conversion of protein ACC values into binary descriptor fingerprints allows similarity search and classification.

Availability and implementation: The algorithm described in the present study was implemented in a specially designed Web site, named AllergenFP (FP stands for FingerPrint). AllergenFP is written in Python, with GIU in HTML. It is freely accessible at http://ddg-pharmfac.net/Allergen FP.

Contact:  idoytchinova@pharmfac.net or ivanbangov@shu-bg.net
Activity‐Guided Fractionation to Identify Blue Wheat (UC66049 Triticum aestivum L.) Constituents Capable of Inhibiting In Vitro Starch Digestion
Authors: Tyl Catrin E. , Bunzel Mirko
Published: October 2013

The inhibition or delay of starch digestion by dietary compounds could help manage postprandial blood glucose levels. The objective of this study was to identify constituents from whole grain blue wheat capable of decreasing α‐amylase‐catalyzed starch digestion. An activity‐guided fractionation approach based on liquid chromatography was used to identify solvent‐ and alkaline‐extractable blue wheat constituents reducing α‐amylase‐mediated starch digestion in vitro. Fatty acids, potentially released from cell wall polymers by alkaline hydrolysis, inhibited the digestion of amylose, probably through the formation of amylose‐lipid complexes. However, the degradation of amylopectin was not affected by fatty acids. In addition, 1‐(3,5‐dihydroxyphenyl)heneicosan‐2‐one, a 5‐(2′‐oxoalkyl)resorcinol, was found to reduce starch digestion. However, because the digestion of both amylopectin and amylose was reduced, the inhibition mechanism was different from that of fatty acids. Further research is needed to evaluate whether this component also reduces starch digestion in vivo. Other phenolic compounds of blue wheat such as anthocyanins or hydroxycinnamates were not identified as major starch digestion inhibitors by using the activity‐guided fractionation approach.
Genetic Diversity ofGrapevine virus Ain Washington and California Vineyards
Authors: Alabi Olufemi J. , Rwahnih Maher Al , Mekuria Tefera A. , Naidu Rayapati A.
Published: October 2013

Grapevine virus A (GVA; genus Vitivirus, family Betaflexiviridae) has been implicated with the Kober stem grooving disorder of the rugose wood disease complex. In this study, 26 isolates of GVA recovered from wine grape (Vitis vinifera) cultivars from California and Washington were analyzed for their genetic diversity. An analysis of a portion of the RNA-dependent RNA polymerase (RdRp) and complete coat protein (CP) sequences revealed intra- and inter-isolate sequence diversity. Our results indicated that both RdRp and CP are under strong negative selection based on the normalized values for the ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site. A global phylogenetic analysis of CP sequences revealed segregation of virus isolates into four major clades with no geographic clustering. In contrast, the RdRp-based phylogenetic tree indicated segregation of GVA isolates from California and Washington into six clades, independent of geographic origin or cultivar. Phylogenetic network coupled with recombination analyses showed putative recombination events in both RdRp and CP sequence data sets, with more of these events located in the CP sequence. The preponderance of divergent variants of GVA co-replicating within individual grapevines could increase viral genotypic complexity with implications for phylogenetic analysis and evolutionary history of the virus. The knowledge of genetic diversity of GVA generated in this study will provide a foundation for elucidating the epidemiological characteristics of virus populations at different scales and implementing appropriate management strategies for minimizing the spread of genetic variants of the virus by vectors and via planting materials supplied to nurseries and grape growers.
Comparative genomics of the marine bacterial genus Glaciecola reveals the high degree of genomic diversity and genomic characteristic for cold adaptation
Authors: Qin Qi‐Long , Xie Bin‐Bin , Yu Yong , Shu Yan‐Li , Rong Jin‐Cheng , Zhang Yan‐Jiao , Zhao Dian‐Li , Chen Xiu‐Lan , Zhang Xi‐Ying , Chen Bo , Zhou Bai‐Cheng , Zhang Yu‐Zhong
Published: October 2013

To what extent the genomes of different species belonging to one genus can be diverse and the relationship between genomic differentiation and environmental factor remain unclear for oceanic bacteria. With many new bacterial genera and species being isolated from marine environments, this question warrants attention. In this study, we sequenced all the type strains of the published species of Glaciecola, a recently defined cold‐adapted genus with species from diverse marine locations, to study the genomic diversity and cold‐adaptation strategy in this genus. The genome size diverged widely from 3.08 to 5.96 Mb, which can be explained by massive gene gain and loss events. Horizontal gene transfer and new gene emergence contributed substantially to the genome size expansion. The genus Glaciecola had an open pan‐genome. Comparative genomic research indicated that species of the genus Glaciecola had high diversity in genome size, gene content and genetic relatedness. This may be prevalent in marine bacterial genera considering the dynamic and complex environments of the ocean. Species of Glaciecola had some common genomic features related to cold adaptation, which enable them to thrive and play a role in biogeochemical cycle in the cold marine environments.
Management of placenta percreta: a review of published cases
Authors: Clausen Caroline , Lönn Lars , Langhoff‐Roos Jens
Published: October 2013

Publications on abnormally invasive placenta in general report what can be considered a mixture of the conditions true accreta, increta and percreta varieties. The aim of this review was to identify all published cases of the most severe condition, placenta percreta in order to describe complications associated with the three commonly used surgical strategies: local resection, hysterectomy or leaving the placenta in situ, and to describe the outcome, with respect to blood loss and transfusion requirements, with the different endovascular interventions that may be used as adjuncts in the management of the conditions. A PubMed search was performed in April 2013 and the final review included 119 published placenta percreta cases. Conservative management, where the placenta is left in situ for resorption, seems to be associated with severe long‐term complications of hemorrhage and infections, including a 58% risk that a hysterectomy will eventually be needed up till nine months after the delivery. Local resection seems to be associated with fewer complications within 24 h postoperatively compared with hysterectomy or leaving the placenta in situ. A selection bias in the direction of less severe cases for the local resection technique might in part explain the lower complication rates with that approach. Future prospective data collection activities should include intended as well as actual management, and long‐term follow‐up of all cases is of vital importance.
Temporal Leukocyte Numbers and Granulocyte Activation in Pulsatile and Rotary Ventricular Assist Device Patients
Authors: Woolley Joshua R. , Teuteberg Jeffrey J. , Bermudez Christian A. , Bhama Jay K. , Lockard Kathleen L. , Kormos Robert L. , Wagner William R.
Published: October 2013

Individual ventricular assist device (VAD) design may affect leukocytes and impact immunity. Few studies have presented leukocyte and infection profiles in VAD patients over the course of the implant period. CD11b (MAC‐1) expression on granulocytes is an indicator of activation during inflammation, mediating extravasation and the release of reactive oxygen species in tissue. No reported studies have presented MAC‐1 expression on circulating granulocytes in VAD patients. Fifty‐six patients implanted at a single center with a HeartMate II (HMII; n = 32), HeartWare (HW; n = 12), or Thoratec pneumatic VAD (PVAD; n = 12) between 1999 and 2011 were followed for 120 days of support. The leukocyte profiles and infectious events of all patients were evaluated; additionally, a subset had MAC‐1 expression on circulating granulocytes was measured (HMII n = 9; HW n = 7; PVAD n = 4). All groups exhibited a significant peak in leukocyte numbers at postoperative day (POD) 14 while simultaneously experiencing a significant decrease in hematocrit. HMII patients exhibited a 3.2‐fold increase in granulocyte MAC‐1 expression at POD 14, and the temporal trend over the implant period differed from that experienced by HW patients. Further, HW patients experienced significantly fewer infection events. Alterations in leukocyte profiles and granulocyte activation experienced by VAD patients appear to be device‐specific. Elevations in leukocyte activation may be related to an increased risk for infection, although the specific relationship between these phenomena in this patient group is not known.
Understanding genetic variation – the value of systems biology
Authors: Hütt Marc‐Thorsten
Published: October 2013

Pharmacology is currently transformed by the vast amounts of genome‐associated information available for system‐level interpretation. Here I review the potential of systems biology to facilitate this interpretation, thus paving the way for the emerging field of systems pharmacology. In particular, I will show how gene regulatory and metabolic networks can serve as a framework for interpreting high throughput data and as an interface to detailed dynamical models. In addition to the established connectivity analyses of effective networks, I suggest here to also analyze higher order architectural properties of effective networks.
Association of pretreatment neutrophil‐to‐lymphocyte ratio (NLR) and overall survival (OS) in patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with first‐line docetaxel
Authors: Nuhn Philipp , Vaghasia Ajay M. , Goyal Jatinder , Zhou Xian C. , Carducci Michael A. , Eisenberger Mario A. , Antonarakis Emmanuel S.
Published: October 2013

Objective

To determine whether the pretreatment neutrophil‐to‐lymphocyte ratio (NLR), a measure of systemic inflammatory response, is associated with overall survival (OS) in men receiving chemotherapy with docetaxel for metastatic castration‐resistant prostate cancer (mCRPC).

Patients and Methods

Records from 238 consecutive patients who were treated with first‐line docetaxel‐containing chemotherapy for mCRPC at a single high‐volume centre from 1998 to 2010 (and who had adequate information to enable calculation of NLR) were reviewed.

Univariable and multivariable Cox regression models were used to predict OS after chemotherapy initiation.

Results

In univariable analyses, the NLR as a discrete variable (optimal threshold 3.0) was significantly associated with OS (P = 0.001).

In multivariable analyses, a lower NLR (≤3.0) was associated with lower risk of all‐cause mortality (P = 0.002).

In Kaplan–Meier analysis, the median OS was higher (18.3 vs 14.4 months) in patients that did not have an elevated NLR than in those with an elevated NLR (log‐rank; P < 0.001).

Conclusions

Men who were treated with first‐line docetaxel for mCRPC who had a low pretreatment NLR (≤3.0) had significantly longer OS.

NLR may be a potentially useful clinical marker of systemic inflammatory response in predicting OS in men with mCRPC who receive docetaxel and may be helpful to stratify patients for clinical trials.

These findings derived from a retrospective analysis need to be validated in larger populations in prospective studies, and in the context of different therapies.
A GENERIC TRUST FRAMEWORK FOR LARGE‐SCALE OPEN SYSTEMS USING MACHINE LEARNING
Authors: Liu Xin , Tredan Gilles , Datta Anwitaman
Published: October 2013

In many large‐scale distributed systems and on the Web, agents need to interact with other unknown agents to carry out some tasks or transactions. The ability to reason about and assess the potential risks in carrying out such transactions is essential for providing a safe and reliable interaction environment. A traditional approach to reason about the risk of a transaction is to determine if the involved agent is trustworthy on the basis of its behavior history. As a departure from such traditional trust models, we propose a generic, trust framework based on machine learning where an agent uses its own previous transactions (with other agents) to build a personal knowledge base. This is used to assess the trustworthiness of a transaction on the basis of the associated features, particularly using the features that help discern successful transactions from unsuccessful ones. These features are handled by applying appropriate machine learning algorithms to extract the relationships between the potential transaction and the previous ones. Experiments based on real data sets show that our approach is more accurate than other trust mechanisms, especially when the information about past behavior of the specific agent is rare, incomplete, or inaccurate.
Nuclear expression of CDK4 correlates with disease progression and poor prognosis in human nasopharyngeal carcinoma
Authors: Jiang Qingping , Mai Chunping , Yang Huiling , Wu Qiangyun , Hua Shengni , Yan Chen , Long Yufei , Zhang Yajie , Long Xiaobin , Fang Weiyi , Liu Zhen
Published: October 2013

Aims

The purpose of this study was to examine the correlation between nuclear expression of cyclin‐dependent kinase 4 (CDK4) and clinicopathological data in nasopharyngeal carcinoma (NPC), including patient survival.

Methods and results

Using real‐time PCR and immunohistochemistry, the expression of CDK4 was examined in NPC and nasopharyngeal (NP) tissues. We observed that mRNA expression of CDK4 was elevated significantly in NPC tissues compared to NP tissues. Further, we found that CDK4 protein was expressed in both the nucleus and cytoplasm. Nuclear expression of CDK4 was correlated positively with clinical stage (P = 0.048), but not associated with other clinical features. Patients with tumours showing nuclear expression of CDK4 had poorer overall survival rates than those without nuclear tumour expression of CDK4. Nuclear expression of CDK4 was associated inversely with survival time for NPC patients in stages T1–2, stages N2–3 and clinical stages III–IV, and after treatment with radiotherapy or chemotherapy. Nuclear expression of CDK4 was an independent and unfavourable prognostic factor for patients with NPC.

Conclusions

Our findings suggest that nuclear expression of CDK4 is a potential marker for the progression and poor prognosis of NPC.