bluuebunny/crossref_metadata_2025_split huggingface dataset:
cables1 is required for embryonic neural development: molecular, cellular, and behavioral evidence from the zebrafish
Authors: Groeneweg Jolijn W. , White Yvonne A.R. , Kokel David , Peterson Randall T. , Zukerberg Lawrence R. , Berin Inna , Rueda Bo R. , Wood Antony W. 
Published: December 2010

AbstractIn vitro studies have suggested that the Cables1 gene regulates epithelial cell proliferation, whereas other studies suggest a role in promoting neural differentiation. In efforts to clarify the functions of Cables1 in vivo, we conducted gain‐ and loss‐of‐function studies targeting its ortholog (cables1) in the zebrafish embryo. Similar to rodents, zebrafish cables1 mRNA expression is detected most robustly in embryonic neural tissues. Antisense knockdown of cables1 leads to increased numbers of apoptotic cells, particularly in brain tissue, in addition to a distinct behavioral phenotype, characterized by hyperactivity in response to stimulation. Apoptosis and the behavioral abnormality could be rescued by co‐expression of a morpholino‐resistant cables1 construct. Suppression of p53 expression in cables1 morphants partially rescued both apoptosis and the behavioral phenotype, suggesting that the phenotype of cables1 morphants is due in part to p53‐dependent apoptosis. Alterations in the expression patterns of several neural transcription factors were observed in cables1 morphants during early neurulation, suggesting that cables1 is required for early neural differentiation. Ectopic overexpression of cables1 strongly disrupted embryonic morphogenesis, while overexpression of a cables1 mutant lacking the C‐terminal cyclin box had little effect, suggesting functional importance of the cyclin box. Lastly, marked reductions in p35, but not Cdk5, were observed in cables1 morphants. Collectively, these data suggest that cables1 is important for neural differentiation during embryogenesis, in a mechanism that likely involves interactions with the Cdk5/p35 kinase pathway. Mol. Reprod. Dev. 78:22–32, 2011. © 2010 Wiley‐Liss, Inc.
Beyond pressure stabilization: A low‐order local projection method for the Oseen equation
Authors: Barrenechea Gabriel R. , Valentin Frédéric 
Published: December 2010

AbstractThis work proposes a new local projection stabilized finite element method (LPS) for the Oseen problem. The method adds to the Galerkin formulation new fluctuation terms that are symmetric and easily computable at the element level. Proposed for the pair ℙ1/ℙl, l = 0, 1, when the pressure is continuously or discontinuously approximated, well‐posedness and error optimality are proved. In addition, we introduce a cheap strategy to recover an element‐wise mass conservative velocity field in the discontinuous pressure case, a property usually neglected in the stabilized finite element context. Numerics validate the theoretical results and show that the present method improves accuracy to represent boundary layers when compared with alternative approaches. Copyright © 2010 John Wiley & Sons, Ltd.
Acceleration of DEM algorithm for quasistatic processes
Authors: Padbidri Jagan M. , Mesarovic Sinisa Dj. 
Published: December 2010

AbstractThe discrete element method (particle dynamics) is an invaluable tool for studying the complex behavior of granular matter. Its main shortcoming is its computational intensity, arising from the vast difference between the integration time scale and the observation time scale (similar to molecular dynamics). This problem is particularly acute for macroscopically quasistatic deformation processes. We first provide the proper definition of macroscopically quasistatic processes, on the basis of dimensional analysis, which reveals that the quasistatic nature of a process is size‐dependent. This result sets bounds for application of commonly used method for computational acceleration, based on superficially increased mass of particles. Next, the dimensional analysis of the governing equations motivates the separation of time scales for the numerical integration of rotations and translations. We take advantage of the existence of fast and slow variables (rotations and translations) to develop a two‐timescales algorithm based on the concept of inertial manifolds suggested by Gear and Kevrekidis. The algorithm is tested on a 2D problem with axial strain imposed by rigid plates and pressure on lateral boundaries. The benchmarking against the accurate short‐time step results confirms the accuracy of the new algorithm for the optimal arrangement of short‐ and long‐time steps. The algorithm provides moderate computational acceleration. Copyright © 2010 John Wiley & Sons, Ltd.
Adaptive component mode synthesis in linear elasticity
Authors: Jakobsson Håkan , Bengzon Fredrik , Larson Mats G. 
Published: December 2010

AbstractComponent mode synthesis (CMS) is a classical method for the reduction of large‐scale finite element models in linear elasticity. In this paper we develop a methodology for adaptive refinement of CMS models. The methodology is based on a posteriori error estimates that determine to what degree each CMS subspace influence the error in the reduced solution. We consider a static model problem and prove a posteriori error estimates for the error in a linear goal quantity as well as in the energy and L2 norms. Automatic control of the error in the reduced solution is accomplished through an adaptive algorithm that determines suitable dimensions of each CMS subspace. The results are demonstrated in numerical examples. Copyright © 2010 John Wiley & Sons, Ltd.
Access to international volunteering
Authors: McBride Amanda Moore , Lough Benjamin J. 
Published: December 2010

AbstractUsing the 2005 U.S. Current Population Survey, we identify the demographic profile of international volunteers from the United States. According to logistic regression results, those most likely to volunteer internationally are young, white, male, highly educated, foreign‐born individuals without dependent children in the home and not employed full time. These findings are discussed through the lens of access and inclusion, examining the possible influences of individual choice and programmatic structure on this demographic profile. Implications are drawn for future research.
Five dimensions of effectiveness for nonprofit annual reports
Authors: Gordon Teresa P. , Khumawala Saleha B. , Kraut Marla , Neely Daniel G. 
Published: December 2010

AbstractAnnual reports are an important communication device through which nonprofit entities can satisfy their duty to be accountable to donors and the public at large. The primary objective of this article is to identify best practices for annual reports based on five dimensions: completeness, accessibility, transparency, full disclosure, and relevance. This article reports on both the financial and nonfinancial content in voluntarily provided annual reports. Based on our survey, we include recommendations and examples to help nonprofit leaders improve communication with stakeholders. While many of the recommendations can be adopted at little or no additional cost, achieving the most important criterion, relevance, will require nonprofit leaders to substantially improve their reporting of organizational goals and accomplishments.
Thalassaemia: Its diagnosis and interpretation in past skeletal populations
Authors: Lewis M. E. 
Published: December 2010

ABSTRACTThe diagnosis of thalassaemia in archaeological populations has long been hindered by a lack of pathogonomic features, and the non‐specific nature of cribra orbitalia and porotic hyperostosis. In fact, clinical research has highlighted more specific diagnostic criteria for thalassaemia major and intermedia based on changes to the thorax (‘rib‐within‐a‐rib’ and costal osteomas). A recent re‐examination of 364 child skeletons from Romano‐British Poundbury Camp, Dorset revealed children with general ‘wasting’ of the bones and three children who demonstrated a variety of severe lesions (e.g. zygomatic bone and rib hypertrophy, porotic hyperostosis, rib lesions, osteopenia and pitted diaphyseal shafts) that are inconsistent with dietary deficiency alone, and more consistent with a diagnosis of genetic anaemia. Two of these children displayed rib lesions typical of those seen in modern cases of thalassaemia. The children of Poundbury Camp represent the first cases of genetic anaemia identified in a British archaeological population. As thalassaemia is a condition strongly linked to Mediterranean communities, the presence of this condition in a child from England, found within a mausoleum, suggests that they were born to wealthy immigrant parents living in this small Roman settlement in Dorset. This paper explores the diagnostic criteria for genetic anaemia in the archaeological literature and what its presence in ancient populations can contribute to our knowledge of past human migration. Copyright © 2010 John Wiley & Sons, Ltd.
Characterisation of proteins extracted from the surface of Salmonella Typhimurium grown under SPI‐2‐inducing conditions by LC‐ESI/MS/MS sequencing
Authors: Sherry Aileen E. , Inglis Neil F. , Stevenson Andy , Fraser‐Pitt Douglas , Everest Paul , Smith David G. E. , Roberts Mark 
Published: December 2010

AbstractSalmonella enterica has two pathogenicity islands encoding separate type three secretion systems (T3SS). Proteins secreted through these systems facilitate invasion and survival. After entry, Salmonella reside within a membrane bound vacuole, the Salmonella containing vacuole (SCV), where translocation of a second set of effectors by the Salmonella pathogenicity island 2 (SPI‐2) T3SS is initiated. SPI‐2 secretion in vitro can be induced by conditions that mimic the Salmonella containing vacuole. Utilising high‐throughput mass spectrometry, we mapped the surface‐attached proteome of S. Typhimurium SL1344 grown in vitro under SPI‐2‐inducing conditions and identified 108 proteins; using secretion signal prediction software, 43% of proteins identified contained a signal sequence. Of these proteins, 13 were known secreted effector proteins including SPI‐2 effector proteins SseB, SseC, SseD, SseL, PipB2 and SteC, although surprisingly five were SPI‐1 proteins, SipA, SipB, SipC, SipD and SopD, while 2 proteins SteA and SlrP are secreted by both T3SSs. This is the first in vitro study to demonstrate dual secretion of SPI‐1 and SPI‐2 proteins by S. Typhimurium and demonstrates the potential of high‐throughput LC‐ESI/MS/MS sequencing for the identification of novel proteins, providing a platform for subsequent comparative proteomic analysis, which should greatly assist understanding of the pathogenesis and inherent variation between serovars of Salmonella and ultimately help towards development of novel control strategies.
Lights and shadows of proteomic technologies for the study of protein species including isoforms, splicing variants and protein post‐translational modifications
Authors: Casado‐Vela Juan , Cebrián Arancha , Gómez del Pulgar Maria Teresa , Sánchez‐López Elsa , Vilaseca Marta , Menchén Laura , Diema Claudia , Sellés‐Marchart Susana , Martínez‐Esteso María José , Yubero Noemí , Bru‐Martínez Roque , Lacal Juan Caelos 
Published: December 2010

AbstractRecent reviews pinpointed the enormous diversity of proteins found in living organisms, especially in higher eukaryotes. Protein diversity is driven through three main processes: first, at deoxyribonucleic acid (DNA) level (i.e. gene polymorphisms), second, at precursor messenger ribonucleic acid (pre‐mRNA) or messenger ribonucleic acid (mRNA) level (i.e. alternative splicing, also termed as differential splicing) and, finally, at the protein level (i.e. PTM). Current proteomic technologies allow the identification, characterization and quantitation of up to several thousands of proteins in a single experiment. Nevertheless, the identification and characterization of protein species using these technologies are still hampered. Here, we review the use of the terms “protein species” and “protein isoform.” We evidence that the appropriate selection of the database used for searches can impede or facilitate the identification of protein species. We also describe examples where protein identification search engines systematically fail in the attribution of protein species. We briefly review the characterization of protein species using proteomic technologies including gel‐based, gel‐free, bottom‐up and top‐down analysis and discuss their limitations. As an example, we discuss the theoretical characterization of the two human choline kinase species, α‐1 and α‐2, sharing the same catalytic activity but generated by alternative splicing on CHKA gene.
Recent advances in the use ofSus scrofa(pig) as a model system for proteomic studies
Authors: Verma Nisha , Rettenmeier Albert W. , Schmitz‐Spanke Simone 
Published: December 2010

AbstractOf the numerous animal models available for proteomic studies only a small number have been successfully used in understanding human biology. To date, rodents have been widely employed in proteomic and genomic studies but often these models do not truly mimic the relevant human conditions. On the other hand, the pig shows similarity in size, shape and physiology to human and has been used as a major mammalian model for many studies concerning xenotransplantation, cardiovascular diseases, blood dynamics, nutrition, general metabolic functions, digestive‐related disorders, respiratory diseases, diabetes, kidney and bladder diseases, organ‐specific toxicity, dermatology and neurological sequelae. With the substantially improved knowledge of the structure and function of the pig genome in the last two decades it has been found that this animal shares a high sequence and chromosomal structure homology with humans. Nevertheless, in comparison to other available model organisms, very little work has been devoted to pig proteomics until recently. Keeping this in mind, the present review will highlight some of the advantages and disadvantages of pig as a model system for proteomic studies.
Proteomics in pancreatic cancer research
Authors: Cecconi Daniela , Palmieri Marta , Donadelli Massimo 
Published: December 2010

AbstractIn this review, we give an overview of the actual role of proteomic technologies in the study of pancreatic cancers (PCs). We describe PC proteomics on the basis of sample origins, i.e. tissues, body fluids, and PC cell lines. As regards PC tissues, we report the identification of a number of candidate biomarkers of precursor lesions that may allow early diagnosis of this neoplasia. Moreover, we describe cytoskeletal and hypoxia‐regulated proteins that confirm the involvement of cytoskeleton modifications and metabolism adaptations in carcinogenesis. We also discuss the most important biomarkers identified by proteomic analysis involved in local invasion and distant metastasis, and in the cross‐talk between pancreatic tumor and the surrounding stroma. Furthermore, we report novel candidate biomarkers identified in serum, plasma, and pancreatic juice of cancer patients compared with cancer‐free controls. Proteomic alterations in PC cell line models as compared to normal controls and studies on cell lines treated with drugs or new agents to understand their mechanism of pharmacological action or the onset of drug resistance are also presented. Finally, we discuss the recent improvements obtained in classical 2‐DE and high‐throughput proteomic strategies able to allow the overcoming of relevant proteomic drawbacks.
Counting peptide‐water hydrogen bonds in unfolded proteins
Authors: Gong Haipeng , Porter Lauren L. , Rose George D. 
Published: December 2010

AbstractIt is often assumed that the peptide backbone forms a substantial number of additional hydrogen bonds when a protein unfolds. We challenge that assumption in this article. Early surveys of hydrogen bonding in proteins of known structure typically found that most, but not all, backbone polar groups are satisfied, either by intramolecular partners or by water. When the protein is folded, these groups form approximately two hydrogen bonds per peptide unit, one donor or acceptor for each carbonyl oxygen or amide hydrogen, respectively. But when unfolded, the backbone chain is often believed to form three hydrogen bonds per peptide unit, one partner for each oxygen lone pair or amide hydrogen. This assumption is based on the properties of small model compounds, like N‐methylacetamide, or simply accepted as self‐evident fact. If valid, a chain of N residues would have approximately 2N backbone hydrogen bonds when folded but 3N backbone hydrogen bonds when unfolded, a sufficient difference to overshadow any uncertainties involved in calculating these per‐residue averages. Here, we use exhaustive conformational sampling to monitor the number of H‐bonds in a statistically adequate population of blocked polyalanyl‐six‐mers as the solvent quality ranges from good to poor. Solvent quality is represented by a scalar parameter used to Boltzmann‐weight the population energy. Recent experimental studies show that a repeating (Gly‐Ser) polypeptide undergoes a denaturant‐induced expansion accompanied by breaking intramolecular peptide H‐bonds. Results from our simulations augment this experimental finding by showing that the number of H‐bonds is approximately conserved during such expansion⇋compaction transitions.
A new liquid chromatography/mass spectrometry method for 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL) in urine
Authors: Bhat Showket H. , Gelhaus Stacy L. , Mesaros Clementina , Vachani Anil , Blair Ian A. 
Published: December 2010

Abstract4‐(Methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) is a carcinogenic nitrosamine produced upon curing tobacco. It is present in tobacco smoke and undergoes metabolism to 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL) in the lungs. NNAL undergoes further uridine diphosphate glucuronosyltransferase (UGT)‐mediated metabolism to give N‐ and O‐glucuronide metabolites, which together with free (non‐conjugated) NNAL are then excreted in the urine. The ability to conduct validated analyses of free and conjugated NNAL in human urine is important in order to assess inter‐individual differences in lung cancer risk from exposure to cigarette smoke. The use of stable isotope dilution (SID) methodology in combination with liquid chromatography/multiple reaction monitoring/mass spectrometry (LC/MRM‐MS) provides the highest bioanalytical specificity possible for such analyses. We describe a novel derivatization procedure, which results in the formation of a pre‐ionizedN‐propyl‐NNAL derivative. The increased LC/MS sensitivity arising from this derivative then makes it possible to analyze free NNAL in only 0.25 mL urine. This substantial reduction in urine volume when compared with other methods that have been developed will help preserve the limited amounts of stored urine samples that are available from on‐going longitudinal biomarker studies. The new high sensitivity SID LC/MRM‐MS assay was employed to determine free and conjugated NNAL concentrations in urine samples from 60 individual disease‐free smokers. Effects of inter‐individual differences in urinary creatinine clearance on NNAL concentrations were then assessed and three metabolizer phenotypes were identified in the 60 subjects from the ratio of urinary NNAL glucuronides/free NNAL. Poor metabolizers (PMs, 14 subjects) with a ratio of NNAL glucuronides/free NNAL <2 (mean = 1.3), intermediate metabolizers (IMs, 36 subjects) with a ratio between 2 and 5 (mean = 3.4), and extensive metabolizers (EMs, 10 subjects) with a ratio >5 (mean = 11.1). Copyright © 2010 John Wiley & Sons, Ltd.
Surface‐assisted laser desorption/ionization mass spectrometry with a rotating ball interface
Authors: Alimpiev Sergey , Grechnikov Alexander , Sunner Jan , Karavanskii Vladimir , Simanovsky Yaroslav , Nikiforov Sergey 
Published: December 2010

AbstractA rotating ball interface for surface‐assisted laser desorption/ionization (SALDI) mass spectrometry was designed and tested. One side of the ball was exposed to atmospheric pressure and the other to the vacuum in a time‐of‐flight mass spectrometer. Analytes (arginine, atenolol, reserpine, tofisopam, and chloropyramine) were applied using electrospray to a silicon substrate on the atmospheric side, the ball was rotated 180°, and the analyte was desorbed on the vacuum side using a pulsed, 200 Hz, 355 nm laser. In order to increase the desorption area, the laser focus was scanned over the substrate in a raster pattern repeated once every second. The design allows for rapid sample throughout with a sample turn‐around time as short as 5 s. Newly produced porous silicon substrates initially yielded very low ion signals, and they required several hundred laser shots to attain maximum sensitivity. In contrast, amorphous silicon did not require such ‘activation’. Quantitative analysis showed a sample‐to‐sample reproducibility of about 10%. The sensitivities with model analytes were in the 1000 to 10 000 ions/fmole range and detection limits in the low fg range. Copyright © 2010 John Wiley & Sons, Ltd.
Fourier transform ion cyclotron resonance cell with dynamic harmonization of the electric field in the whole volume by shaping of the excitation and detection electrode assembly
Authors: Boldin Ivan A. , Nikolaev Eugene N. 
Published: December 2010

AbstractA new principle of formation of the effective electric field distribution in a Penning trap is presented. It is based on the concept of electric potential space averaging via charged particle cyclotron motion. The method of making hyperbolic‐type field distribution in the whole volume of a cylindrical Penning trap is developed on the basis of this new principal. The method is based on subdividing the cell cylindrical surface into segments with shapes producing quadratic dependence on axial coordinate of an averaged (along cyclotron motion orbit) electric potential at any radius of cyclotron motion. The cell performance is compared in digital experiments with the performance of a Gabrielse‐type cylindrical cell with four compensation electrodes and is shown to be more effective in ion motion harmonization at higher cyclotron radii and axial oscillation amplitude. Copyright © 2010 John Wiley & Sons, Ltd.
Vortex‐assisted tryptic digestion
Authors: Yang Hyo‐Jik , Shin Seongjae , Kim Jinhee , Hong Jangmi , Lee Sunyoung , Kim Jeongkwon 
Published: December 2010

AbstractThe effect of vortex‐induced vibration during tryptic digestion was investigated by applying different vibrational speeds (0, 600, 1200, or 2500 rpm) to digestion solutions for varying durations (10, 20, 30, 40, or 60 min) at two different incubation temperatures (25°C or 37°C). The most rapid digestion was observed with the highest vibrational speed and temperature. With the application of 2500 rpm at 37°C, the tryptic digestion of each of three standard proteins (cytochrome c, myoglobin, or bovine serum albumin) provided complete disappearance of the protein within 60 min, as determined by matrix‐assisted laser desorption/ionization mass spectrometry. Compared to conventional overnight digestion, 60‐min vortex‐assisted tryptic digestion generated longer peptides, due primarily to the limited digestion time and provided better sequence coverages (89% vs. 78% for cytochrome c, 100% vs. 87% for myoglobin, and 38% vs. 26% for BSA). The longer peptides should be advantageous to analytical methods such as the middle‐down approach that benefit from increased sequence coverage of proteins. Vortex‐assisted tryptic digestion is expected to be a useful method for rapid tryptic digestion of proteins. Copyright © 2010 John Wiley & Sons, Ltd.