bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and demographic characteristics of patients receiving different oral hypoglycemic agents
Authors: Gomes Tara , Juurlink David N. , Lipscombe Lorraine L. , Mamdani Muhammad M.
Published: April 2009

Objective

To characterize the demographic and clinical profiles of older persons with diabetes treated with a thiazolidinedione (TZD) in comparison to other groups of patients, including all patients with diabetes and those taking other oral hypoglycemic agents (OHAs).

Research Design and Methods

We studied Ontario residents aged 66 and older and alive on 31 March 2008. Five groups were created based on diabetes status and history of treatment with OHAs, including patients prescribed rosiglitazone, patients prescribed pioglitazone, and a sample of three other groups: patients prescribed any other OHA in the preceding year, all patients with diabetes, and elderly Ontarians regardless of diabetes status. We excluded patients receiving insulin or multiple TZDs from the three OHA groups. Study groups were compared based on demographic information, measures of comorbidity, history of cardiovascular diseases, and concomitant use of drugs for cardiovascular disease.

Results

People treated with pioglitazone (n = 16 206) were highly similar to those treated with rosiglitazone (n = 16 066). Individuals treated with either TZD tended to be younger, less likely to reside in a long‐term care facility, and had similar cardiovascular profiles to samples of patients with diabetes (n = 50 000) and those taking other OHAs (n = 50 000).

Conclusions

Older patients started on TZDs have cardiovascular risk profiles comparable to other individuals with diabetes, including those taking other OHAs, suggesting that observational studies of TZD safety are not likely confounded by selection bias. Copyright © 2009 John Wiley & Sons, Ltd.
Cluster randomized trials to study the comparative effectiveness of therapeutics: stakeholders' concerns and recommendations
Authors: Mazor Kathleen M. , Sabin James E. , Goff Sarah L. , Smith David H. , Rolnick Sharon , Roblin Douglas , Raebel Marsha A. , Herrinton Lisa J. , Gurwitz Jerry H. , Boudreau Denise , Meterko Vanessa , Dodd Katherine S. , Platt Richard
Published: April 2009

Purpose

To describe the concerns raised by health plan members, providers and purchasers related to studying the comparative effectiveness of therapeutics using cluster randomized trials (CRTs) within health plans. An additional goal was to develop recommendations for increasing acceptability.

Methods

Eighty‐four qualitative in‐depth telephone interviews were conducted; 50 with health plan members, 21 with providers, and 13 with purchasers. Interviews focused on stakeholders' concerns about and recommendations for conducting CRTs in health plans.

Results

Members expressed concerns that CRTs might compromise their healthcare. Providers and purchasers recognized the value of and the need for comparative effectiveness research. Providers expressed concerns that they would not have sufficient time to discuss a CRT with patients, and that participation in such a study could negatively impact their relationships with patients. Purchasers would want assurances that study participation would not result in members receiving lesser care, and that benefits would remain equitable for all members.

Conclusions

This study provides insight into how health plan members, providers and purchasers might react to a CRT being conducted in their health plan. The recommendations reported here provide guidance for researchers and policy makers considering this methodological approach and suggest that with sufficient preparation and planning CRTs can be an acceptable and efficient methodology for studying the comparative effectiveness of therapeutics in real world settings. Copyright © 2009 John Wiley & Sons, Ltd.
Effect of ester group bulkiness of polyacrylates on miscibility with poly(vinyl acetate)
Authors: Princi Elisabetta , Vicini Silvia , Pedemonte Enrico
Published: April 2009

BACKGROUND: The miscibility of poly(vinyl acetate) (PVAc) with a series of polyacrylates, namely poly(methyl acrylate) (PMA), poly(ethyl acrylate) (PEA) and poly(butyl acrylate) (PBA), with ester chains of varying bulkiness was studied from both qualitative and quantitative points of view.

RESULTS: The evidence from thermal (differential scanning calorimetry) and Fourier transform infrared analyses demonstrates that the miscibility of PVAc with the polyacrylates is rapidly reduced on increasing the bulkiness of their ester chains. Miscibility is quantitatively discussed in the framework of the corresponding states theory applying the approximate Patterson form. For this reason the characteristic values of volume, temperature and pressure were preliminarily evaluated both experimentally, through dilatometric measurements, and by calculations. At the same time, calorimetric measurements allowed the evaluation of the enthalpies of mixing of the components.

CONCLUSION: The conclusions reached with this approach are that polar interactions are active among the repeat units of the blend components, but the intensities of these forces are progressively reduced by the shielding of the apolar groups of the polyacrylates. The steric hindrance of the hydrocarbon groups shields the interactions of the polar groups of PVAc with the COOR moieties of the acrylates, so that the miscibility progressively decreases from PMA to PEA to PBA. Copyright © 2009 Society of Chemical Industry
Numerical simulations of buried emitter back‐junction solar cells
Authors: Harder Nils‐P. , Mertens Verena , Brendel Rolf
Published: April 2009

We recently introduced the buried emitter back‐junction solar cell, featuring large area fractions of overlap betweenn+‐type andp+‐type regions at the rear side of the device. In this paper we analyse the performance of the buried emitter solar cell (BESC) and its generalisations by one‐dimensional device simulations and analytical model calculations. A key finding is that the generalised versions of the BESC structure allows achieving very high efficiencies by passivating virtually the entire surface ofp‐type emitters by an oxidisedn‐type surface layer. A disadvantage of this type of full‐area emitter passivation in the generalised back‐junction BESC is the need for an insulating layer between the metallisation of the emitter and the contact to the base, which is technologically difficult to achieve. Copyright © 2009 John Wiley & Sons, Ltd.
The Zn(S,O,OH)/ZnMgO buffer in thin film Cu(In,Ga)(S,Se)2‐based solar cells part I: Fast chemical bath deposition of Zn(S,O,OH) buffer layers for industrial application on Co‐evaporated Cu(In,Ga)Se2 and electrodeposited CuIn(S,Se)2 solar cells
Authors: Hubert C. , Naghavi N. , Roussel O. , Etcheberry A. , Hariskos D. , Menner R. , Powalla M. , Kerrec O. , Lincot D.
Published: April 2009

This paper is focused on the basic study and optimization of short time (<10 min) Chemical Bath Deposition (CBD) of Zn(S,O,OH) buffer layers in co‐evaporated Cu(In,Ga)Se2 (CIGSe) and electrodeposited CuIn(S,Se)2 ((ED)‐CIS) solar cells for industrial applications. First, the influence of the deposition temperature is studied from theoretical solution chemistry considerations by constructing solubility diagrams of ZnS, ZnO, and Zn(OH)2 as a function of temperature. In order to reduce the deposition time under 10 min, experimental growth deposition studies are then carried out by the in situ quartz crystal microgravimetry (QCM) technique. An optimized process is performed and compared to the classical Zn(S,O,OH) deposition. The morphology and composition of Zn(S,O,OH) films are determined using SEM and XPS techniques. The optimized process is tested on electrodeposited‐CIS and co‐evaporated‐CIGSe absorbers and cells are completed with (Zn,Mg)O/ZnO:Al windows layers. Efficiencies similar or even better than CBD CdS/i‐ZnO reference buffer layers are obtained (15·7% for CIGSe and 8·1% for (ED)‐CIS). Copyright © 2009 John Wiley & Sons, Ltd.
PPI spider: A tool for the interpretation of proteomics data in the context of protein–protein interaction networks
Authors: Antonov Alexey V. , Dietmann Sabine , Rodchenkov Igor , Mewes Hans W.
Published: April 2009

Recent advances in experimental technologies allow for the detection of a complete cell proteome. Proteins that are expressed at a particular cell state or in a particular compartment as well as proteins with differential expression between various cells states are commonly delivered by many proteomics studies. Once a list of proteins is derived, a major challenge is to interpret the identified set of proteins in the biological context. Protein–protein interaction (PPI) data represents abundant information that can be employed for this purpose. However, these data have not yet been fully exploited due to the absence of a methodological framework that can integrate this type of information. Here, we propose to infer a network model from an experimentally identified protein list based on the available information about the topology of the global PPI network. We propose to use a Monte Carlo simulation procedure to compute the statistical significance of the inferred models. The method has been implemented as a freely available web‐based tool, PPI spider (http://mips.helmholtz‐muenchen.de/proj/ppispider). To support the practical significance of PPI spider, we collected several hundreds of recently published experimental proteomics studies that reported lists of proteins in various biological contexts. We reanalyzed them using PPI spider and demonstrated that in most cases PPI spider could provide statistically significant hypotheses that are helpful for understanding of the protein list.
Proteomic analysis of parthenogenetic and in vitro fertilized porcine embryos
Authors: Gupta Mukesh Kumar , Jang Jung Mi , Jung Jin Woo , Uhm Sang Jun , Kim Kwang Pyo , Lee Hoon Taek
Published: April 2009

Proteomic data from embryos are essential for the completion of whole proteome catalog due to embryo‐specific expression of certain proteins. In this study, using reverse phase LC‐MS/MS combined with 1‐D SDS‐PAGE, we identified 1625 mammalian and 735 Sus scrofa proteins from porcine zygotes that included both cytosolic and membranous proteins. We also found that the global protein profiles of parthenogenetically activated (PA) and in vitro fertilized (IVF) zygotes were similar but differences in expression of individual proteins were also evident. These differences were not due to culture conditions, polyspermy or non‐activation of oocytes, as the same culture method was used in both groups, the frequency of polyspermy was 24.3±3.0% and the rates of oocyte activation did not differ (p>0.05) between PA and IVF embryos. Consistent with proteomic data, fluorescent Hoechst 33 342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay also revealed that PA embryos were of poor quality as they contained less cells per blastocyst and were more predisposed to apoptosis (p<0.05), although their in vitro development rates were similar. To our knowledge, this is the first report on global peptide sequencing and quantification of protein in PA and IVF embryos by LC‐MS/MS that may be useful as a reference map for future studies.
First evidence of a membrane‐bound, tyramine and β‐phenylethylamine producing, tyrosine decarboxylase in Enterococcus faecalis: A two‐dimensional electrophoresis proteomic study
Authors: Pessione Enrica , Pessione Alessandro , Lamberti Cristina , Coïsson Daniel Jean , Riedel Kathrin , Mazzoli Roberto , Bonetta Silvia , Eberl Leo , Giunta Carlo
Published: April 2009

The soluble and membrane proteome of a tyramine producing Enterococcus faecalis, isolated from an Italian goat cheese, was investigated. A detailed analysis revealed that this strain also produces small amounts of β‐phenylethylamine. Kinetics of tyramine and β‐phenylethylamine accumulation, evaluated in tyrosine plus phenylalanine‐enriched cultures (stimulated condition), suggest that the same enzyme, the tyrosine decarboxylase (TDC), catalyzes both tyrosine and phenylalanine decarboxylation: tyrosine was recognized as the first substrate and completely converted into tyramine (100% yield) while phenylalanine was decarboxylated to β‐phenylethylamine (10% yield) only when tyrosine was completely depleted. The presence of an aspecific aromatic amino acid decarboxylase is a common feature in eukaryotes, but in bacteria only indirect evidences of a phenylalanine decarboxylating TDC have been presented so far. Comparative proteomic investigations, performed by 2‐DE and MALDI‐TOF/TOF MS, on bacteria grown in conditions stimulating tyramine and β‐phenylethylamine biosynthesis and in control conditions revealed 49 differentially expressed proteins. Except for aromatic amino acid biosynthetic enzymes, no significant down‐regulation of the central metabolic pathways was observed in stimulated conditions, suggesting that tyrosine decarboxylation does not compete with the other energy‐supplying routes. The most interesting finding is a membrane‐bound TDC highly over‐expressed during amine production. This is the first evidence of a true membrane‐bound TDC, longly suspected in bacteria on the basis of the gene sequence.
Proteome analysis of adipocyte lipid rafts reveals that gC1qR plays essential roles in adipogenesis and insulin signal transduction
Authors: Kim Ki‐Bum , Kim Bong‐Woo , Choo Hyo‐Jung , Kwon Young‐Chan , Ahn Byung‐Yoon , Choi Jong‐Soon , Lee Jae‐Seon , Ko Young‐Gyu
Published: April 2009

Since insulin receptors and their downstream signaling molecules are organized in lipid rafts, proteomic analysis of adipocyte lipid rafts may provide new insights into the function of lipid rafts in adipogenesis and insulin signaling. To search for proteins involved in adipocyte differentiation and insulin signaling, we analyzed detergent‐resistant lipid raft proteins from 3T3‐L1 preadipocytes and adipocytes by 2‐DE. Eleven raft proteins were identified from adipocytes. One of the adipocyte‐specific proteins was globular C1q receptor (gC1qR), an acidic 32 kDa protein known as the receptor for the globular domain of complement C1q. The targeting of gC1qR into lipid rafts was significantly increased during adipogenesis, as determined by immunoblotting and immunofluorescence. Since the silencing of gC1qR by small RNA interference abolished adipogenesis and blocked insulin‐induced activation of insulin receptor, insulin receptor substrate‐1 (IRS‐1), Akt, and Erk1/2, we can conclude that gC1qR is an essential molecule involved in adipogenesis and insulin signaling.
Robust Project Network Design
Authors: De Orue David A. Ortiz , Taylor John E. , Chanmeka Arpamart , Weerasooriya Runi
Published: April 2009

Traditional project planning tools and methodologies fail to address the dynamic uncertainties that can arise during project execution. In this article, we develop an approach to enable project managers to design project networks capable of performing predictably under uncertainty. We integrate a validated project organization design simulation tool (Virtual Design Team) with a robust design experimental method to enable robust project network design. We test the framework on a 13-month, U.S. $11.5M public renovation project. We find that: (1) it is possible to integrate the project organization design tool with the robust design experimental method for the test case project; (2) the integrated approach enables project managers to identify and simulate the combination of interventions that will lead to the most robust project performance; and (3) the integrated approach can extend the capabilities of project managers to design project networks in dynamically uncertain project environments. The findings highlight the need to explore new ways to achieve predictable project performance in dynamically uncertain project execution environments.
Mistic: Cellular localization, solution behavior, polymerization, and fibril formation
Authors: Dvir Hay , Lundberg Matthew E. , Maji Samir K. , Riek Roland , Choe Senyon
Published: April 2009

Mistic represents a family of unique membrane‐associating proteins originally found in Bacillus subtilis (M110). As a fusion partner, it has been shown to assist overexpression of foreign integral membrane proteins in E. coli. We have expressed shorter Mistic homologs from other Bacillus species and surprisingly, unlike M110, found them abundant in the cytoplasm. These Mistic homologs including the corresponding shorter sequence (amino acids 27 through 110 of M110) exist as multimeric assemblies in solution in the absence of detergent. Crystals of Mistic from B. leicheniformis (M2) diffracted to 3.2 Å resolution, indicating that it exists as a multimer in the crystalline state as well. Moreover, we show that although M2 is mostly α‐helical, it tends to polymerize and form fibrils. Such oligomerization could potentially mask the charged surface of the monomeric Mistic to assist membrane integration.
Charge neutralization and collapse of the C‐terminal tail of alpha‐synuclein at low pH
Authors: McClendon Sebastian , Rospigliosi Carla C. , Eliezer David
Published: April 2009

Alpha‐synuclein (αS) is the primary component of Lewy bodies, the pathological hallmark of Parkinson's Disease. Aggregation of αS is thought to proceed from a primarily disordered state with nascent secondary structure through intermediate conformations to oligomeric forms and finally to mature amyloid fibrils. Low pH conditions lead to conformational changes associated with increased αS fibril formation. Here we characterize these structural and dynamic changes using solution state NMR measurements of secondary chemical shifts, relaxation parameters, residual dipolar couplings, and paramagnetic relaxation enhancement. We find that the neutralization of negatively charged side‐chains eliminates electrostatic repulsion in the C‐terminal tail of αS and leads to a collapse of this region at low pH. Hydrophobic contacts between the compact C‐terminal tail and the NAC (non‐amyloid‐β component) region are maintained and may lead to the formation of a globular domain. Transient long‐range contacts between the C‐terminus of the protein and regions N‐terminal to the NAC region are also preserved. Thus, the release of long‐range contacts does not play a role in the increased aggregation of αS at low pH, which we instead attribute to the increased hydrophobicity of the protein.
Vector supersymmetry from OSp(3,2|2): Casimir operators
Authors: Casalbuoni R. , Elmetti F. , Gomis J. , Kamimura K. , Tamassia L. , Van Proeyen A.
Published: April 2009

In this paper we briefly review the main results obtained in [1], where some algebraic properties of the ‘vector supersymmetry’ (VSUSY) algebra have been studied. VSUSY is a graded extension of the Poincaré algebra in 4 dimensions with two central charges. We derive all independent Casimir operators of VSUSY and we find two distinct spin–related operators in the case of nonvanishing central charges. One is the analogue of superspin for VSUSY and the other is a new spin, called C–spin, whose value is fixed to 1/2. We also show that the VSUSY algebra and its Casimir operators can be derived by an Inönü‐Wigner contraction from OSp(3,2 |2). This paper is based on the talk given in Varna, Bulgaria, during the 4‐th EU RTN Workshop 2008.
Massive type IIA supergravity and E10
Authors: Henneaux M. , Jamsin E. , Kleinschmidt A. , Persson D.
Published: April 2009

In this talk we investigate the symmetry under E10 of Romans' massive type IIA supergravity. We show that the dynamics of a spinning particle in a non‐linear sigma model on the coset space E10/K(E10) reproduces the bosonic and fermionic dynamics of massive IIA supergravity, in the standard truncation. In particular, we identify Romans' mass with a generator of E10 that is beyond the realm of the generators of E10 considered in the eleven‐dimensional analysis, but using the same, underformed sigma model. As a consequence, this work provides a dynamical unification of the massless and massive versions of type IIA supergravitiy inside E10.
Spinning strings in AdS4 × CP3 and quantum corrections
Authors: Alday L.F. , Arutyunov G. , Bykov D.
Published: April 2009

We derive the one‐loop correction to the space‐time energy of a folded string in AdS4 × CP3 carrying spin S in AdS4 and angular momentum J in CP3 in the long string approximation. From this general result in the limit J log S we obtain the one‐loop correction to the cusp anomalous dimension which turns out to be –(5 log 2)/(2π). This value appears to be in conflict with the prediction from the recently conjectured all‐loop Bethe ansatz.
Targeting the conformational transitions of MDM2 and MDMX: Insights into key residues affecting p53 recognition
Authors: Carotti Andrea , Macchiarulo Antonio , Giacchè Nicola , Pellicciari Roberto
Published: April 2009

The oncogenic proteins MDM2 and MDMX have distinct and critical roles in the control of the activity of the p53 tumor suppressor protein. Recently, we have used spatial coarse graining simulations to analyze the conformational transitions manifest in the p53 recognition of MDM2 and MDMX. These conformational movements are different between MDM2 and MDMX and unveil the presence of conserved and nonconserved interactions in the p53 binding cleft that may be exploited in the design of selective and dual modulators of the oncogenic proteins. In this study, we investigate the conformational profiles of apo‐ and p53‐bound states of MDM2 and MDMX using molecular dynamic simulations along a time scale of 60 ns. The analysis of the trajectories is instrumental to discuss energetical and conformational aspects of p53 recognition and to point out specific key residues whose conformational shifts have crucial roles in affecting the apo‐ and p53‐bound states of MDM2 and MDMX. Among these, in particular, linear discriminant analyses identify diverse conformations of Y99/Y100 (MDMX/MDM2) as markers of the apo‐ and p53‐bound states of the oncogenic proteins. The results of this study shed further light on different p53 recognition in MDM2 and MDMX and may prove useful for the design and identification of new potent and selective synthetic modulators of p53‐MDM2/MDMX interactions. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Variability of the Northern Hemisphere polar stratospheric cloud potential: the role of North Pacific disturbances
Authors: Orsolini Yvan J. , Karpechko Alexey Yu. , Nikulin Grigory
Published: April 2009

The potential of the Arctic stratosphere to sustain the formation of Polar Stratospheric Clouds (PSCs) is a key factor in determining the amount of ozone destroyed each winter, and is often measured as a ‘PSC volume’. The latter quantity has been shown to closely follow a near‐linear compact relationship with winter‐averaged column ozone loss, and displays a high variability from monthly to decadal time‐scales. We examine the connection between meteorological conditions in the troposphere and the variability of lower polar stratospheric temperatures over the last four decades, and specifically, conditions leading to a high PSC volume. In addition to the well‐established connection between the North Atlantic Oscillation (NAO) and the polar vortex, we demonstrate the large influence of precursory disturbances over the North Pacific and the Far East, the region of maximum climatological upward wave activity flux. Namely, very high monthly PSC volume (in the top 12%) predominantly follows the development of positive tropospheric height anomalies over the Far East, which lead to a weakening of the background planetary wave trough, and lessened upward wave activity flux into the stratosphere. Precursory anomalies over the Far East are reminiscent of East Asian monsoon amplification episodes. Copyright © 2009 Royal Meteorological Society
Buoyancy reversal in cloud‐top mixing layers
Authors: Mellado Juan Pedro , Stevens Bjorn , Schmidt Heiko , Peters Norbert
Published: April 2009

A theoretical and numerical small‐scale study of the evaporative cooling phenomenon that might appear in the stratocumulus‐topped boundary layers is presented. An ideal configuration of a cloud‐top mixing layer is considered as defined by two non‐turbulent horizontal layers, stably stratified and with buoyancy reversal within a certain range of mixture fractions due to the evaporative cooling. Linear stability analysis of the shear‐free configuration is employed to provide a new interpretation of the buoyancy reversal parameter, namely in terms of a time‐scale ratio between the stable and the unstable modes of the system. An incompressible high‐order numerical algorithm to perform direct numerical simulation of the configuration is described and two‐dimensional simulations of single‐mode perturbations are presented. These simulations confirm the role of the different parameters identified in the linear stability analysis and show that convoluted flow patterns can be generated by the evaporative cooling even for the low levels of buoyancy reversal found in stratocumulus clouds. They also show that there is no enhancement of turbulent entrainment of upper‐layer fluid in the shear‐free configuration, and turbulent mixing enhancement by the evaporative cooling is restricted to the lower layer. Copyright © 2009 Royal Meteorological Society
Consensus QSAR Modeling of Phosphor‐Containing Chiral AChE Inhibitors
Authors: Kuz'min Victor E. , Muratov Eugene N. , Artemenko Anatoly G. , Varlamova Ekaterina V. , Gorb Leonid , Wang Jing , Leszczynski Jerzy
Published: April 2009

In this article the Hierarchical QSAR technology (HiT QSAR) has been used for consensus QSAR modeling of Acetylcholinesterase (AChE) inhibition by various organophosphate compounds. Simplex representation of molecular structure (SiRMS) and Lattice model (LM) QSAR approaches have been used for descriptors' generation. Statistical models have been obtained by partial least squares (PLS) method. Various chiral organophosphates represented by their (R)‐ and (S)‐isomers, racemic mixtures and achiral structures have been investigated. Successful consensus model (R2=0.978) based on fourteen best QSAR models obtained using different QSAR approaches and training sets for several levels and methods of molecular structure representation (2.5D, double 2.5D, and 3D) has been used for the prediction of AChE inhibition of new compounds. In order to avoid chance correlations 1000 rounds of Y‐scrambling were performed for each selected model. Leverage and ellipsoid Applicability domain (DA) approaches have been used for additional estimation of the quality of prognosis. Molecular fragments enhancing and interfering with inhibitory activity have been determined. It was revealed that atom's individuality and stereochemistry of chiral surroundings of the asymmetric atom of phosphorus play a vital role in AChE inhibition. Thus, (R)‐isomers are always less active than the (S) isomers and the racemate. HiT QSAR proves to be a powerful tool for investigation of activity of stereo selective interactions and can be used in such subsequent studies.
3D‐QSAR Study of Pyridine Derivates as IKK‐2 Inhibitors
Authors: Sala Esther , Guasch Laura , Vaqué Montserrat , Mateo‐Sanz Josep Maria , Blay Mayte , Bladé Cinta , Garcia‐Vallvé Santiago , Pujadas Gerard
Published: April 2009

IkB kinase β (IKK‐2) is a serine‐threonine protein kinase that is critically involved in activating the transcription factor NF‐κβ in response to various inflammatory stimuli (hence, the interest in synthesizing molecules that can inhibit IKK‐2). Some pyridine derivates have been shown to be among the most potent IKK‐2 inhibitors known at present. This study reports how pyridine derivates have been used to develop a 3D‐QSAR model for rationalizing results from previous structure‐activity relationship studies on IKK‐2 inhibition by these molecules; and predicting the IC50 of other pyridine‐derivate IKK‐2 inhibitors whose activity is unknown. Therefore, 3D‐QSAR models were built with PHASE and a training set of 21 molecules with IC50 values that span five orders of magnitude (ranging from 0.004 to more than 20 μM) and in which each order of magnitude had from two to seven molecules. The resulting models were validated with a test set made up of 16 molecules of known IC50. Only 3 out of 1245 3D‐QSAR models had statistical parameter values in the following ranges: a) R2, Q2 and r‐Pearson value≥0.8000; b) RMSE/SD in the [0.90–1.05] interval; c) Q2/R2≈1; and d) P<0.05 (statistical significance). Moreover, a second test set (consisting of 63 molecules whose activity has been reported in the form of the IC50 interval to which it belongs) was used for selecting which of the three remaining 3D‐QSAR models makes the best predictions. The best 3D‐QSAR model obtained is associated with a pharmacophore that contains all the characteristics that previous structural‐activity studies have reported to be essential if IKK‐2 is to be inhibited by these ligands. Therefore, it is concluded that this 3D‐QSAR model can be used to reliably predict how other pyridine derivates inhibit IKK‐2.
Pharmacophore Model of Cruzain Inhibitors
Authors: Malvezzi Alberto , de Rezende Leandro , Amaral Antonia T.‐do
Published: April 2009

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most serious amongst the so‐called neglected diseases in Latin America, specially in Brazil. So far there has been no effective treatment for the chronic phase of this disease. Cruzain is a major cysteine protease of T. cruzi and it is recognized as a valid target for Chagas disease chemotherapy. The mechanism of cruzain action is associated with the nucleophilic attack of an activated sulfur atom towards electrophilic groups. In this report, features of a putative pharmacophore model of the enzyme, developed as a virtual screening tool for the selection of potential cruzain inhibitors, are described. The final proposed model was applied to the ZINC v.7 database and afterwards experimentally validated by an enzymatic inhibition assay. One of the compounds selected by the model showed cruzain inhibition in the low micromolar range.
Score test for age at onset genetic linkage analysis in selected sibling pairs
Authors: Callegaro A. , van Houwelingen H. C. , Houwing‐Duistermaat J. J.
Published: April 2009

A new score statistic is derived, which uses information from registries (age‐specific incidences) and family studies (sib–sib marginal correlation) to weight affected sibling pairs according to their age at onset. Age at onset of sibling pairs is modelled by a gamma frailty model. From this model we derive a bivariate survival function, which depends on the marginal survival and on the marginal correlation. The score statistic for linkage is a classical nonparametric linkage (NPL) statistic where the identical by descent sharing is weighted by a particular function of the age at onset data. Since the statistic is based on survival models, it can also be applied to discordant and healthy sibling pairs. Simulation studies show that the proposed method is robust and more powerful than standard NPL methods. As illustration we apply the new score statistic to data from a breast cancer study. Copyright © 2009 John Wiley & Sons, Ltd.
Interobserver repeatability of three‐ and four‐dimensional transperineal ultrasound assessment of pelvic floor muscle anatomy and function
Authors: Majida M. , Brækken I. H. , Umek W. , Bø K. , Šaltytė Benth J. , Ellstrøm Engh M.
Published: April 2009

Objective

To evaluate the interobserver repeatability of measurement of the pubovisceral muscle and levator hiatus, and the position of related organs, during rest, muscle contraction and Valsalva maneuver using three‐ and four‐dimensional (3D and 4D) transperineal ultrasound.

Methods

Seventeen women were included in the study. The position and dimensions of the pubovisceral muscle and levator hiatus in patients at rest and during contraction and Valsalva were determined from stored 3D and 4D ultrasound volumes. Analyses were conducted offline by two observers blinded to the clinical data and to each others' measurements.

Results

Measurements of levator hiatal dimensions at rest demonstrated intraclass correlation coefficient (ICC) values of 0.92 to 0.96. The ICC values for pubovisceral muscle thickness at rest varied between good and very good (ICC, 0.61–0.93), regardless of plane. During contraction, the ICC values for all measured parameters were very good, varying between 0.61 and 0.92. Measurement of the transverse diameter of the levator hiatus during the Valsalva maneuver showed good reliability (ICC, 0.86), but assessment of the anterior and posterior borders of the levator hiatus was only possible in 29% of cases.

Conclusions

3D and 4D transperineal ultrasound measurement of the pubovisceral muscle and levator hiatus is reliable in women with no or minor symptoms of prolapse at rest and during contraction. The technique for recording during the Valsalva maneuver requires improvement if it is to be useful in the diagnosis of pelvic organ prolapse. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Analysis and comparison of scheduling techniques for a BWA OFDMA mobile system
Authors: Tarchi Daniele , Fantacci Romano , Bonciani Emanuele
Published: April 2009

In the last few years the wireless metropolitan area networks (WMANs) have increased their popularity and attracted the interest of important research groups all over the world; as a consequence, several standards have been proposed. Among them, the IEEE 802.16 (WiMAX) is one of the most promising standard to carry out a full‐service broadband wireless network in an urban and suburban area. This standard provides high data rate within a wide coverage area with low implementation costs, possibility of multi‐traffic communications, and different network topologies. This paper deals with the analysis and performance comparison of different scheduling techniques for WiMAX networks for allowing quality of service (QoS) differentiation when different types of applications have to be supported and achieving a fair distribution of resource among users. In particular, the focus here is on the resource allocation problem for the case of mobile stations (MSs) active in an urban environment. The proposed scheduling algorithms exploit the orthogonal frequency division multiple access (OFDMA) scheme with adaptive modulation techniques in order to achieve a better network behavior. The performance of the proposed approaches will be derived here by means of theoretical analysis and computer simulations. Copyright © 2009 John Wiley & Sons, Ltd.
Adenosine‐to‐inosine RNA editing
Authors: Zinshteyn Boris , Nishikura Kazuko
Published: April 2009

Ribonucleic acid (RNA) editing is a mechanism that generates RNA and protein diversity, which is not directly encoded in the genome. The most common type of RNA editing in vertebrates is the conversion of adenosine to inosine in double‐stranded RNA which occurs in the higher eukaryotes. This editing is carried out by the family of adenosine deaminase acting on RNA (ADAR) proteins. The most‐studied substrates of ADAR proteins undergo editing which is very consistent, highly conserved, and functionally important. However, editing causes changes in protein‐coding regions only at a small proportion of all editing sites. The vast majority of editing sites are in noncoding sequences. This includes microRNAs, as well as the introns and 3′ untranslated regions of messenger RNAs, which play important roles in the RNA‐mediated regulation of gene expression. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Biological Mechanisms > Regulatory Biology

Laboratory Methods and Technologies > RNA Methods
Chronic lung diseases
Authors: Wu Wei , Kaminski Naftali
Published: April 2009

Chronic lung diseases often have high morbidity and mortality rate and have posed a serious threat to human health. The incidence of many chronic lung diseases such as asthma has been on the rise in the past decade, which causes serious economic burden. Despite many efforts which employed traditional experimental approaches to elucidate the mechanisms of the diseases have been made, little is known about the pathogenesis of complex lung diseases. Systems biology approaches which aim to integrate and analyze information gathered from multiple sources offer a great opportunity to examine complex human diseases from a new angle. Many attempts have been made using high‐throughput technologies such as microarrays to study chronic lung diseases; although compared with the full‐fledged systems biology approach, research strategies employed in most of these investigations still have much room to improve, promising findings have already emerged from these efforts, which demonstrates the potential of implementing systems biology in pulmonary biomedical research. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Physiology > Mammalian Physiology in Health and Disease
Experimentally based sea urchin gene regulatory network and the causal explanation of developmental phenomenology
Authors: Ben‐Tabou de‐Leon Smadar , Davidson Eric H.
Published: April 2009

Gene regulatory networks (GRNs) for development underlie cell fate specification and differentiation. Network topology, logic, and dynamics can be obtained by thorough experimental analysis. Our understanding of the GRN controlling endomesoderm specification in the sea urchin embryo has attained an advanced level such that it explains developmental phenomenology. Here we review how the network explains the mechanisms utilized in development to control the formation of dynamic expression patterns of transcription factors and signaling molecules. The network represents the genomic program controlling timely activation of specification and differentiation genes in the correct embryonic lineages. It can also be used to study evolution of body plans. We demonstrate how comparing the sea urchin GRN to that of the sea star and to that of later developmental stages in the sea urchin, reveals mechanisms underlying the origin of evolutionary novelty. The experimentally based GRN for endomesoderm specification in the sea urchin embryo provides unique insights into the system level properties of cell fate specification and its evolution. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Physiology > Physiology of Model Organisms
Arabidopsis thaliana as a model organism in systems biology
Authors: Van Norman Jaimie M. , Benfey Philip N.
Published: April 2009

Significant progress has been made in the identification of genes and gene networks involved in key biological processes. Yet, how these genes and networks are coordinated over increasing levels of biological complexity, from cells to tissues to organs, remains unclear. To address complex biological questions, biologists are increasingly using high‐throughput tools and systems biology approaches to examine complex biological systems at a global scale. A system is a network of interacting and interdependent components that shape the system's unique properties. Systems biology studies the organization of system components and their interactions, with the idea that unique properties of that system can be observed only through study of the system as a whole. The application of systems biology approaches to questions in plant biology has been informative. In this review, we give examples of how systems biology is currently being used in Arabidopsis to investigate the transcriptional networks regulating root development, the metabolic response to stress, and the genetic regulation of metabolic variability. From these studies, we are beginning to obtain sufficient data to generate more accurate models for system function. Further investigation of plant systems will require data gathering from specific cells and tissues, continued improvement in metabolic technologies, and novel computational methods for data visualization and modeling. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Physiology > Physiology of Model Organisms
Synthesis and Description of a Novel Metal‐organic Framework Based on Trigonal Prismatic Building Blocks
Authors: Li Bing , Zheng Shou‐Tian , Yang Guo‐Yu
Published: April 2009

A novel metal‐organic framework based on trigonal prismatic building blocks has been hydrothermally prepared and structurally characterized. It crystallizes in the cubic space group Pa$\bar{3}$ with Z = 8. The oxo‐centered trinuclear complex units are bridged by 1,3‐benzenedicarboxylate (1,3‐BDC) ligands, forming a new 3D open‐framework [Fe3O(H2O)3(1,3‐BDC)3][Cl]·9H2O (1). Its magnetic behavior has been quantitively analyzed by the Bleaney–Bowers equation, indicating the presence of antiferromagnetic interactions within the trinuclear FeIII atoms.
Intra‐Abdominal Pressure and Abdominal Compartment Syndrome in Acute General Surgery
Authors: Sugrue Michael , Buhkari Yasir
Published: April 2009

Background

Intra‐abdominal pressure (IAP) is a harbinger of intra‐abdominal mischief, and its measurement is cheap, simple to perform, and reproducible. Intra‐abdominal hypertension (IAH), especially grades 3 and 4 (IAP > 18 mmHg), occurs in over a third of patients and is associated with an increase in intra‐abdominal sepsis, bleeding, renal failure, and death.

Patients and methods

Increased IAP reading may provide an objective bedside stimulus for surgeons to expedite diagnostic and therapeutic work‐up of critically ill patients. One of the greatest challenges surgeons and intensivists face worldwide is lack of recognition of the known association between IAH, ACS, and intra‐abdominal sepsis. This lack of awareness of IAH and its progression to ACS may delay timely intervention and contribute to excessive patient resuscitation.

Conclusions

All patients entering the intensive care unit (ICU) after emergency general surgery or massive fluid resuscitation should have an IAP measurement performed every 6 h. Each ICU should have guidelines relating to techniques of IAP measurement and an algorithm for management of IAH.
Dynamics of Parathyroid Hormone Secretion After Total Parathyroidectomy and Autotransplantation
Authors: Conti‐Freitas Luiz Carlos , Foss‐Freitas Maria Cristina , Lucca Leandro Junior , da Costa Jose Abrão Cardeal , Mamede Rui Celso Martins , Foss Milton Cesar
Published: April 2009

Background

Secondary hyperparathyroidism is a common complication in uremic patients. Total parathyroidectomy combined with partial autotransplantation into brachioradialis muscle has been the preference among the options for surgical treatment. This study was designed to evaluate the reserve and ability of suppression of autotransplanted parathyroid tissue using dynamics tests.

Methods

We studied, prospectively, 12 patients in recent (RP) and late (LP) postoperative of total parathyroidectomy with autotransplantation. For analysis of the secretory reserve capacity, we induced hypocalcemia by ethylenediaminetetraacetic acid (EDTA) infusion. Furthermore, for analysis of the ability for parathyroid hormone (PTH) suppression, the hypercalcemia test was used, by intravenous administration of calcium in LP.

Results

In RP, there was a decrease in the average serum levels of PTH, phosphorus, and alkaline phosphatase, which ranged from 13 to 231 (87 ± 65) pg/ml, 2.3 to 6.2 (3.3 ± 1.1) mg/dl, and 77 to 504 (250 ± 135) U/L, respectively, similar to that observed in LP. The analysis of the average curve of variations in PTH during testing of the stimulus with EDTA showed lack of secretion in RP and partial response in LP. Impaired suppression ability of the graft in LP was observed in the test with intravenous calcium.

Conclusions

Total parathyroidectomy followed by partial autotransplantation was effective in reducing PTH serum levels in patients with terminal kidney disease. The elevation of serum calcium during the suppression test was not able to inhibit the autograft gland secretion of PTH. The assessment of parathyroid graft function demonstrated an inability to respond to the stimulus of hypocalcemia induced by EDTA, although there was a partial recovery, in late postoperative period.
The Transforming Power of Democracy: Regime Type and the Distribution of Electricity
Authors: BROWN DAVID S. , MOBARAK AHMED MUSHFIQ
Published: April 2009

Theory on democracy and its consequences turns on how democracy influences behavior among politicians and the citizenry. Ultimately, the literature seeks to determine who benefits under democratic rules. This is our concern, posed in a context that allows us to address a classic question: does democracy favor large but diffuse segments of society over small but concentrated interests? We employ sectoral electricity consumption data for a panel of 733 country-years to examine democracy's impact on the distribution of electricity across three sectors that represent distinct political interests: industry, agriculture, and residential consumers. We find that in poorer countries democratization produces significant increases in the residential share of electricity relative to industry, suggesting sectors with less per capita financial clout, but a stronger voice in elections benefit under democracy. Unlike the large literatures on democracy's impact on theamountsof publicly provided goods, our results are among the first on thedistributionof those goods.
Partisan Webs: Information Exchange and Party Networks
Authors: Koger Gregory , Masket Seth , Noel Hans
Published: April 2009

What is a party? This article presents the argument that rmal party apparatus is only one part of an extended network of interest groups, media, other advocacy organizations and candidates. The authors have measured a portion of this network in the United States systematically by tracking lists of names transferred between political organizations. Two distinct and polarized networks are revealed, which correspond to a more liberal Democratic group and a more conservative Republican group. Formal party organizations, like the Democratic National Committee and the Republican National Committee, tend to receive information within their respective networks, which suggests that other groups serve to funnel information towards the formal party.
À la défense du déontologisme doxastique
Authors: Laurier Daniel
Published: April 2009

RÉSUMÉ : Je réfute l’argument standard selon lequel nous n’avons aucune obligation de croire (ou ne pas croire) quoi que ce soit, parce que nous n’avons pas, sur nos croyances, le genre de contrôle nécessaire pour avoir des obligations. Je propose ensuite une interprétation de la distinction entre raisons épistémiques et raisons pratiques de croire qui est généralisable à d’autres attitudes telles que l’intention et qui semble impliquer (i) que les actes mentaux tels que les jugements et les décisions ne sont jamais des actions intentionnelles et (ii) que ces deux sortes de raisons sont incommensurables.
An Early Age of Commerce in Southeast Asia, 900–1300 CE
Authors: Wade Geoff
Published: April 2009

One of the most influential ideas in Southeast Asian history in recent decades has been Anthony Reid'sAge of Commercethesis, which sees a commercial boom and the emergence of port cities as hubs of commerce over the fifteenth to seventeenth centuries, which in turn spurred political, social and economic changes throughout the region. But how new were the changes described in Reid'sAge of Commerce? This paper argues that the four centuries from circa 900 to 1300 CE can be seen as an ‘Early Age of Commerce’ in Southeast Asia. During this period, a number of commercial and financial changes in China, South Asia, the Middle East and within the Southeast Asian region, greatly promoted maritime trade, which induced the emergence of new ports and urban centres, the movement of administrative capitals toward the coast, population expansion, increased maritime links between societies, the expansion of Theravada Buddhism and Islam, increased monetisation, new industries, new forms of consumption and new mercantile organisations. It is thus proposed that the period from 900 to 1300 be considered the Early Age of Commerce in Southeast Asian history.