bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the Limits of Substrate Specificity of the Adenylation Domain of TycA
Authors: Villiers Benoit R. M. , Hollfelder Florian 
Published: February 2009

AbstractThe limits and potential of substrate promiscuity of the adenylation domain of tyrocidine synthetase 1 were systematically explored. Substrate acceptance is governed by hydrophobic effects (as shown by the correlation of kcat/KM and side‐chain log P), shape complementarity and steric exclusion. The quantification of these factors provides ground rules for understanding and possibly evolving substrate specificity in this class of enzymes.magnified imageThe catalytic potential of tyrocidine synthetase 1 (TycA) was probed by the kinetic characterization of its adenylation activity. We observed reactions with 30 substrates, thus suggesting some substrate promiscuity. However, although the TycA adenylation (A) domain was able to accommodate alternative substrates, their kcat/KM values ranged over six orders of magnitude. A comparison of the activities allowed the systematic mapping of the substrate specificity determinants of the TycA A‐domain. Hydrophobicity plays a major role in the recognition of substrate analogues but can be combined with shape complementarity, conferring higher activity, and/or steric exclusion, leading to substantial discrimination against larger substrates. A comparison of the kcat/KM values of the TycA A‐domain and phenylalanyl‐tRNA synthetase showed that the level of discrimination was comparable in the two enzymes for the adenylation reaction and suggested that TycA was also subjected to high selective pressure. The specificity patterns observed and the quantification of alternative activities provide a basis for exploring possible paths for the future directed evolution of A‐domain specificity.
Fluorescent Polyurethane Nanocapsules Prepared via Inverse Miniemulsion: Surface Functionalization for Use as Biocarriers
Authors: Paiphansiri Umaporn , Dausend Julia , Musyanovych Anna , Mailänder Volker , Landfester Katharina 
Published: January 2009

AbstractThe functionalization of well‐defined PU nanocapsules with an aqueous core prepared by performing a polyaddition at the interface of inverse (water‐in‐oil) miniemulsion droplets is demonstrated. The miniemulsion technique involving the nanoreactor concept allows one to obtain an encapsulation efficiency as high as 90% within the nanocapsules. A pH independent fluorescent dye is used as a model system for the aqueous core. By varying the molar ratio of the diol to the diisocyanate at a fixed surfactant concentration, the shell thickness of the nanocapsules can be finely tuned. The carboxy‐ and amino‐functionalized surface of the nanocapsules can be tailored by an in‐situ carboxymethylation reaction and by physical adsorption of a cationic polyelectrolyte, i.e. PAEMA or PEI. The increased uptake of amino‐functionalized fluorescent nanocapsules by HeLa cells clearly demonstrates the potential of the functionalized nanocapsules to be successfully exploited as biocarriers.magnified image
Delta relaxation enhanced MR: Improving activation‐specificity of molecular probes through R1 dispersion imaging
Authors: Alford Jamu K. , Rutt Brian K. , Scholl Timothy J. , Handler William B. , Chronik Blaine A. 
Published: February 2009

AbstractMR molecular imaging enables high‐resolution, in vivo study of molecular processes frequently utilizing gadolinium‐based probes that specifically bind to a particular biological molecule or tissue. While some MR probes are inactive when unbound and produce enhancement only after binding, the majority are less specific and cause enhancement in either state. Accumulation processes are then required to increase probe concentration in regions of the target molecule/tissue. Herein, a method is described for creating specificity for traditionally nonspecific probes. This method utilizes MR field‐cycling methods to produce MRI contrast related to the dependence of R1 upon magnetic field. It is shown that the partial derivative of R1 with respect to magnetic field strength, R1′, can be used as an unambiguous measure of probe binding. T1‐weighted images and R1′ images were produced for samples of albumin and buffer both enhanced with the albumin‐binding agent Vasovist. For T1 images, samples with low concentrations of Vasovist in an albumin solution could not be differentiated from samples with higher concentrations of Vasovist in buffer. Conversely, the R1′ images showed high specificity to albumin. Albumin samples with a 10‐μM concentration of Vasovist were enhanced over buffer samples containing up to 16 times more Vasovist. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Sources of error and its control in studies on the diagnostic accuracy of “‐omics” technologies
Authors: Lumbreras Blanca , Porta Miquel , Marquez Soledad , Pollán Marina , Parker Lucy A. , Hernández‐Aguado Ildefonso 
Published: January 2009

AbstractAnalyses of errors in diagnostic studies have led to improvements in the methodological quality of traditional laboratory research. However, since features of genomics and proteomics research (“‐omics”) differ from those of traditional research, sources of error are also likely to be distinct. We examine the main sources of error that are particularly relevant to “‐omics”‐based diagnostic techniques through the analysis of primary research papers which address these potential errors, their solutions, and the resulting spurious effect on diagnostic accuracy prediction. The main sources of error described in “‐omics”‐based research are mainly associated with chance: overfitting and inadequate sample size; variation: preanalytical variation (specimen collection and management), analytical variation (test procedures and reproducibility) and biological variation. We conclude that “‐omics”‐based research is prone to several errors. We have characterized them and shown the range of available solutions. This is a key step in the application of genomic discoveries to clinical and public health practice.
Protein microarrays as an application for disease biomarkers
Authors: Caiazzo Robert J. , Maher Andrew J. , Drummond Michael P. , Lander Corey I. , Tassinari Oliver W. , Nelson Bryce P. , Liu Brian C.‐S. 
Published: January 2009

AbstractProtein microarrays are an increasingly powerful technology in the hunt for new and novel diagnostic and prognostic biomarkers. Lending credit to the highly established DNA microarray, protein microarrays are versatile tools that utilize a variety of formats to facilitate the discovery of new biomarkers and our understanding of disease pathways. The aims of this review are: to detail a variety of protein microarray technologies currently used, including forward‐phase technologies and reverse‐phase technologies useful in both the discovery and validation of candidate biomarkers; to explore the strengths and weaknesses of various proteomic microarray platforms; to explain how bioinformatics helps compare data between microarray data sets; and to discuss the downstream applications of such technologies as they relate to the development of a highly personalized approach to medicine.
Proteomics in gastric cancer research: Benefits and challenges
Authors: Li Jing‐Jing , Qi Robert Z. , Ng Gary Kar Ho , Xie Dong 
Published: January 2009

AbstractAmong various cancers, gastric cancer (GC) exhibits relatively high morbidity and mortality rate worldwide. The lack of effective methods in early detection and diagnosis, and immediate therapies makes treating such disease a challenge for both clinicians and oncologists. Proteomics has emerged as a promising technology platform for rationally identifying biomarkers and novel therapeutic targets for GC, as well as discovering underlying mechanisms of carcinogenesis. Its application has greatly benefited mechanistic studies of this disease. This review will demonstrate the applications of proteomic technology in GC research. The advantages and shortcomings of this technology, as reflected by current studies, will also be discussed to improve and expand its application in the field of cancer research.
Lectin microarray
Authors: Hu Shen , Wong David T. 
Published: January 2009

AbstractLectin microarray is a new technology that utilizes a panel of lectins immobilized on well‐defined substrate for high‐throughout analysis of glycans and glycoproteins. In this article, we have reviewed the fabrication and detection schemes in lectin microarray and discussed its novel applications in glycomics. We have also demonstrated a lectin array on PDMS with MALDI‐TOF‐MS for glycoprotein analysis. This method has been demonstrated for differential analysis of serum glycoproteins in oral cancer and healthy control subjects.
Prostate cancer proteomics: The urgent need for clinically validated biomarkers
Authors: Evans Caroline A. , Glen Adam , Eaton Colby L. , Larré Stéphane , Catto James W. F. , Hamdy Freddie C. , Wright Phillip C. , Rehman Ishtiaq 
Published: January 2009

AbstractProstate cancer (PCa) is the most common cancer diagnosis and the second most common cause of cancer‐related deaths in men. Currently, serum prostate‐specific antigen (PSA) is the only biomarker widely used in the diagnosis and management of patients with PCa. However, PSA lacks diagnostic sensitivity and specificity, leading to false‐negative and false‐positive test results. PSA cannot distinguish indolent from aggressive disease, leading to many patients being over‐treated with associated side‐effects. Furthermore, PSA is unable to identify which tumors are likely to become unresponsive to treatment at an early stage. Thus, there is an urgent need for clinically validated biomarkers which will improve the diagnosis and management of PCa. Given the heterogeneity of PCa it is likely that a panel of biomarkers will be required. In the quest for PCa biomarkers, a wide range of samples including urine, serum, tissues, and cell lines have been studied using proteomic approaches such as 2‐DE, SELDI‐TOF, SILAC, ICAT, iTRAQ, and MALDI‐IMS. The value of these technologies, and other emerging platforms such as selected reaction monitoring (SRM) and multiple reaction monitoring (MRM), are discussed in the context of biomarker discovery, validation and addressing the “bottle‐necks” that exist prior to clinical translation.
Modern strategies to identify new molecular targets for the treatment of liver diseases: The promising role of Proteomics and Redox Proteomics investigations
Authors: Scaloni Andrea , Codarin Erika , Di Maso Vittorio , Arena Simona , Renzone Giovanni , Tiribelli Claudio , Quadrifoglio Franco , Tell Gianluca 
Published: January 2009

AbstractOxidative stress, due to an imbalance between the generation of ROS and the antioxidant defense capacity of the cell, is a major pathogenetic event occurring in several liver diseases, ranging from metabolic to proliferative. Main sources of ROS are represented by mitochondria and cytochrome P450 enzymes in the hepatocytes, Küppfer cells, and neutrophils. Oxidative stress affects major cellular components including lipids, DNA, and proteins. Through modulation of protein structure/function, ROS can influence gene expression profile by affecting intracellular signal transduction pathways. While several enzymatic and nonenzymatic markers of chronic oxidative stress are well known in liver, early protein targets of oxidative injury are yet poorly defined. Identification of these biomarkers will enable early detection of liver diseases and will allow monitoring the degree of liver damage, the response to pharmacological therapies, and the development of new therapeutic approaches. In the era of molecular medicine, new proteomic methodologies promise to establish a relationship between pathological hallmarks of the disease and protein structural/functional modifications, thus allowing a better understanding and a more rational therapy on liver disorders. Purpose of this review is to critically analyze the application of proteomic and redox proteomic approaches to the study of oxidative stress‐linked liver diseases.
Proteomics in obesity research
Authors: Barceló‐Batllori Sílvia , Gomis Ramon 
Published: January 2009

AbstractObesity has emerged as one of the major global epidemics of the 21st century and is now reaching alarming proportions. Obese subjects have an increased morbidity and mortality, decreased quality of life and a major risk of developing pathologies such as diabetes mellitus, insulin resistance and cardiovascular disease. Obesity is a complex disease characterised by an increase in body fat mass resulting from an imbalance between energy intake and expenditure. Signal integration between adipose tissue, other peripheral organs and the CNS seems to regulate energy homeostasis. Proteomics may be useful in unravelling the pathogenesis of obesity, since a combination of genetic predisposition and environmental factors account for its development. Most of the proteomic studies performed to date have focused on protein profiling of adipose tissue in different models of experimental obesity and the study of the adipocyte differentiation process. Another issue that has recently attracted attention is the characterisation of the adipocyte secretome, which may be important in signalling to other organs and in regulating energy balance. Target identification of potential therapies has also been investigated by proteomics. This review focuses on the contributions of proteomics to understanding the molecular mechanisms of obesity and their potential therapies.
Field distribution in an electrospray ionization source determined by finite element method
Authors: Zhong Xuefei , Yi Rong , Holliday Alison E. , Chen David D. Y. 
Published: February 2009

AbstractThree‐dimensional computer models of electrospray ionization sources were constructed in COMSOL Multiphysics™ to solve the static electric fields using finite element methods. The magnitude of the electric field strength for onset of electrospray and optimum signal was calculated under various conditions. The modification of the electric field distribution in the ion source by an atmospheric pressure ion lens was also investigated by plotting the equipotential surfaces, electric field lines and trajectories of charged droplets. Both the calculated and the experimental results demonstrate that the changes in the ion signal detected by the mass spectrometer are attributable to the focusing effect of the ion lens when appropriate voltages are applied on the sprayer and ion lens. The optimum signal was found by setting the sprayer voltage from 3000 to 5000 V while scanning the ion lens voltage. The calculated strengths of the electric field at the sprayer tip for optimum signals are similar although the applied voltages at the sprayer and ion lens are significantly different. Copyright © 2009 John Wiley & Sons, Ltd.
Open Surgical is Superior to Percutaneous Access for Radiofrequency Ablation of Hepatic Metastases
Authors: Eisele Robert M. , Neumann Ulf , Neuhaus Peter , Schumacher Guido 
Published: January 2009

AbstractPurposeThis study was designed to determine the best approach to radiofrequency ablation (RFA) in the liver.MethodsFrom a total of 41 procedures, 37 patients with 47 tumors were treated with RFA for metastatic disease. Indications included colorectal cancer (n = 28, 68%), neuroendocrine tumors (n = 2, 5%), gynecological primaries (n = 4, 10%), pancreatic/duodenal cancer (n = 2, 5%), and miscellaneous entities (n = 5, 12%). Mean follow‐up period was 18 (median, 18) months. All ways of approach to RFA were applied: percutaneous was chosen in 17 (41.5%), laparoscopic and hand‐assisted laparoscopic in 5 (12.2%), and open surgical in 19 cases (46.3%), and in 10 cases, RFA was combined with hepatic resection. The average maximum tumor size was 2.3 (range, 0.8–6) cm, and the mean number of nodules treated per patient in a single session was 1.3 (range, 1–3).ResultsOverall survival was 59.5% at 2 years, recurrence‐free 2‐year survival was 12.6%, local tumor recurrence rate was 34%, and overall recurrence was 75.6%. Local tumor recurrence and disease‐free survival were significantly improved in the open surgically treated patients compared with the percutaneous treatment group (15.8% [n = 3] vs. 58.8% [n = 10] and 11.5 vs. 7.9 months, p < 0.01 [χ2 test] and p < 0.05 [log‐rank test], respectively).ConclusionsOpen surgical approach is superior to percutaneous access for RFA in metastatic hepatic disease.
Cirrhosis and Trauma Are a Lethal Combination
Authors: Georgiou Chrysanthos , Inaba Kenji , Teixeira Pedro G. R. , Hadjizacharia Pantelis , Chan Linda S. , Brown Carlos , Salim Ali , Rhee Peter , Demetriades Demetrios 
Published: January 2009

AbstractBackgroundThe objective of this study was to evaluate the risk of mortality and complications associated with cirrhosis in trauma patients.MethodsThis is an IRB‐approved retrospective trauma registry study of patients admitted to an academic level 1 trauma center from 1997 to 2006. The following parameters were abstracted for analysis: age, gender, mechanism of injury, Abbreviated Injury Score, Injury Severity Score, Glasgow Coma Scale, mortality, and complications (ARDS, acute renal failure, pneumonia, intra‐abdominal abscess, trauma‐associated coagulopathy). Multivariable analysis was utilized to compare the mortality and complication rates between cirrhotic and noncirrhotic trauma patients. The subgroup of patients who underwent laparotomy was also analyzed.ResultsDuring the 10‐year study period there were 36,038 trauma registry patients, of which 468 (1.3%) had a diagnosis of cirrhosis. The mortality in the cirrhotic group was 12% vs. 6% in the noncirrhotic group [adjusted odds ratio = 5.65 (95% CI = 3.72 − 8.41, p < 0.0001)]. ARDS, trauma‐associated coagulopathy, and septic complications were significantly more common in the cirrhotic group. The overall severe complication rate in the two groups was 10 and 4%, respectively [adjusted odds ratio = 2.05 (95% CI = 1.45 − 2.84, p < 0.0001)]. For the subgroup of patients who underwent emergent abdominal exploration, the mortality rate increased to 40% compared with that of noncirrhotics at 15% [adjusted odds ratio = 4.35 (95% CI = 2.00 − 9.18, p = 0.0002)].ConclusionCirrhosis is an independent risk factor for increased mortality and higher complication rate following trauma. Injured patients who undergo laparotomy are significantly more likely to die than noncirrhotic patients. Injured patients with cirrhosis warrant aggressive monitoring and treatment.
Early modes of transport in the United States: Lessons for modern energy policymakers
Authors: Sovacool Benjamin K 
Published: January 2009

Abstract
The belief that modern alternative vehicles and modes of transport continue to fail primarily for technical reasons glosses over the importance of the economic, political, social and cultural dimensions of gasoline powered automobiles. This article investigates the changes that caused manufacturers and customers to abandon bicycles, horses, electric vehicles, cable cars, trolleys, and trains and to overwhelmingly prefer gasoline-powered vehicles from 1890 to 1940 in the United States. It then focuses on the lessons that the historical transition to gasoline vehicles offers modern policymakers.
North Atlantic control on precipitation pattern in the eastern Mediterranean/Black Sea region during the last glacial
Authors: Kwiecien Olga , Arz Helge W. , Lamy Frank , Plessen Birgit , Bahr André , Haug Gerald H. 
Published: January 2009

AbstractBased on proxy records from western Black Sea cores, we provide a comprehensive study of climate change during the last glacial maximum and late-glacial period in the Black Sea region. For the first time we present a record of relative changes in precipitation for NW Anatolia based on variations in the terrigenous supply expressed as detrital carbonate concentration. The good correspondence between reconstructed rainfall intensity in NW Anatolia and past western Mediterranean sea surface temperatures (SSTs) implies that during the glacial period the precipitation variability was controlled, like today, by Mediterranean cyclonic disturbances. Periods of reduced precipitation correlate well with low SSTs in the Mediterranean related to Heinrich events H1 and H2. Stable oxygen isotopes and lithological and mineralogical data point to a significant modification in the dominant freshwater/sediment source concomitant to the meltwater inflow after 16.4 cal ka BP. This change implies intensification of the northern sediment source and with other records from the Mediterranean region, consistently suggests a reorganization of the atmospheric circulation pattern affecting the hydrology of the European continent. The early deglacial northward retreat of both atmospheric and oceanic polar fronts was responsible for the warming in the Mediterranean region, leading simultaneously to more humid conditions in central and northern Europe.
The influence of kinship on seventeenth-century immigration to Canada
Authors: Guillemette André , Légaré Jacques 
Published: January 2009

Im 17. Jahrhundert kamen etwa 15.000 französische Einwanderer nach Kanada, von denen ein Drittel für immer in der Kolonie blieb. Wie so häufig, handelte es sich in der Mehrzahl um unverheiratete junge Männer, zwischen denen jedoch gleichzeitig feste Verwandtschaftsbeziehungen bestanden, von einfachen Geschwistergruppenbis hin zu Gruppen, die mehrere Familien umfaßten. Fast 25 Prozent der Männer und 40 Prozent der Frauen waren mit wenigstens einem weiteren Einwanderer verwandt.Die Untersuchung zeigt, daß die Ankunft solcher verwandter Einwanderer von Fluktuationen bestimmt war, die offensichtlich auf den Einfluß der französischen Regierungspolitik zurückzuführen sind. Darüberhinaus scheinen aber auch die Familienbande selbst die Ankunft von Einwanderern begünstigt zu haben, insbesondere dann, wenn die Rekrutierung der Ankömmlinge auf private Initiative zurückging. Andererseits waren die bestehenden Verwandtschaftsbeziehungen für den Entschluß, sich in Neufrankreich niederzulassen, wohl weniger ausschlaggebend. Vielmehr scheinen dafür die neugeschaffenen Familienbande, die in der Kolonie selbst durch Heirat zwischen Einwanderern oder deren Kindern entstanden waren, wichtiger gewesen zu sein.
‘Teach her to live under obedience’: the making of women in the upper ranks of early modern England
Authors: Pollock Linda 
Published: January 2009

Cet article essaie, en étudiant l'education des filles, de résoudre le paradoxe de la contradiction entre le point de vue coutumier du rôle de la femme dans la société anglaise du 17e siècle et le comportement réel de celle-ci.Après l'étude de papiers de famille et de documents autobiographiques 1'auteur estime que pour comprendre le rôle de la femme dans la société il faut accepter deux prémisses notamment que chacun des deux sexes possède les caractéristiques de l'autre et que la femme est sensée de jouer le double rôle de la compétence et de la subordination. Le but de la socialisation de l'enfance n'était pas d'éliminer la capacité de la pensée individuelle et de l'action, mais bien d'assurer que les femmes ne disputent pas la suprématie, alors en vigueur, de leurs époux.