bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative zinc‐binding sites explain the redox sensitivity of zinc‐containing anti‐sigma factors
Authors: Heo Lim , Cho Yoo‐Bok , Lee Myeong Sup , Roe Jung‐Hye , Seok Chaok 
Published: May 2013

ABSTRACTCertain bacterial zinc‐containing anti‐sigma (ZAS) factors respond sensitively to thiol‐induced oxidative stress by undergoing conformational changes, which in turn reduce binding affinities for their cognate sigma factors. This redox sensitivity provides a mechanism for coping with oxidative stress by activating the transcription of antioxidant genes. Not all ZAS proteins are redox‐sensitive, but the mechanism of redox sensitivity is not fully understood. Here we propose that alternative zinc‐binding sites determine redox sensitivity. To support this proposal, we performed protein modeling and zinc docking on redox‐sensitive and redox‐insensitive ZAS proteins complexed with their cognate sigma factors. At least one strong alternative zinc‐binding pocket was detected for all known redox‐sensitive ZAS factors in actinomycetes, while no strong alternative zinc‐binding pocket was identified in redox‐insensitive ZAS factors, except for one controversial case. This hypothesis of alternative zinc‐binding sites can also explain residue‐specific contributions to the redox sensitivity of RsrA, a redox‐sensing ZAS protein from Streptomyces coelicolor, for which alanine mutagenesis experiments are available. Our results suggest a mechanistic model for redox sensitivity as follows: zinc ion can probabilistically occupy multiple sites in redox‐sensitive ZAS proteins, increasing the susceptibility of zinc‐coordinating cysteine residues to oxidation. This picture of probabilistic zinc occupation agrees with a previous structure and energy analysis on zinc finger proteins, and thus it may be more widely applicable to other classes of reactive zinc‐binding proteins. © 2013 Wiley Periodicals, Inc.
Transmission mode direct analysis in real time mass spectrometry for fast untargeted metabolic fingerprinting
Authors: Jones Christina M. , Fernández Facundo M. 
Published: May 2013

RATIONALEUntargeted metabolic fingerprinting is a discovery tool to better understand biochemical processes involved in detecting and characterizing disease states and responses to environmental stressors. Although current mass spectrometric (MS) methods are very powerful, there is a clear need for more rapid, high‐throughput MS approaches for metabolomics studies.METHODSA rapid metabolic fingerprinting method for human blood sera that utilizes a new transmission mode direct analysis in real time (TM‐DART) sampling technique coupled with quadrupole time of flight mass spectrometry (QTOFMS) is presented. In this approach, the sample is deposited directly on a stainless steel mesh that is held in the ionization region by a custom‐built module. As a result, the DART plasma gas stream interacts with the sample in a flow‐through fashion, which maximizes the interaction between the sample and ionizing species and minimizes variance in sample positioning.RESULTSThe optimization of TM‐DART parameters directly affecting metabolite desorption and ionization, such as sample position and ionizing gas desorption temperature, was critical in achieving high sensitivity and detecting a broad mass range of metabolites. Ramping the ionizing gas desorption temperature further enhanced analysis by adding a simple separation dimension to this ambient approach. In terms of reproducibility, TM‐DART compared favorably with traditional probe mode (PM‐) DART analysis, with coefficients of variation as low as 16%. The longer‐lasting TM‐DART signals enabled the acquisition of metabolite full scan and product ion accurate mass spectra in a single experiment, resulting in greater confidence in metabolite identification.CONCLUSIONSTM‐DART MS proved to be a powerful analytical technique for rapid metabolome analysis of human blood sera. Copyright © 2013 John Wiley & Sons, Ltd.
Rapidly formed quinalphos complexes with transition metal ions characterized by electrospray ionization mass spectrometry
Authors: Keller Bernd O. , Esbata Abdelhamid A. , Buncel Erwin , van Loon Gary W. 
Published: May 2013

RATIONALEElectrospray ionization tandem mass spectrometry (ESI‐MS/MS) offers the unique opportunity to characterize complexes of the organophosphorus pesticide (OP) quinalphos (PA‐Q) with transition metal ions immediately formed after contact. This study complements research looking at longer term kinetics of quinalphos hydrolysis in the presence of transition metal ions and gives insights into the structural features of the initial complex formation in solution. (Hydrolysis reaction: PA‐Q + H2O → PA‐OH + HQ, where PA‐OH is the diethyl phosphate product and HQ is hydroxyquinoxaline.)METHODSLow micromolar PA‐Q solutions with an approximately 3‐fold molar excess of transition metal ions were immediately analyzed after mixing. Fragmentation of the transition metal ion complexes with PA‐Q was accomplished in two different ways: first, in‐source fragmentation by elevating the declustering potential and second, low‐energy collision‐induced dissociation (CID).RESULTSFor Ag+, the [PA‐Q – Ag+] and respective Ag+‐containing degradation product ions are readily observed. For Cu2+, we observed the [PA‐Q + Cu2+ + NO3–] complex ion with weak intensity and strong signals from both the [2PA‐Q + Cu+] and the [PA‐Q + Cu+] ions, the latter two attributable to charge‐state reduction in the gas phase from Cu(II) to Cu(I), indicating that PA‐Q fulfills specific structural requirements of the formed complex for charge‐state reduction during transition from solution to the gas phase. For Hg2+, the [PA‐Q + Hg2+ + (PA‐OH – H)–] ion was the largest observed species containing one Hg2+ ion. No 1:1 species ([PA‐Q] or other degradation products:Hg2+) was observable.CONCLUSIONSESI‐MS/MS of complexes formed from PA‐Q and transition metal ions is a formidable technique to probe initial formation of these complexes in solution. Previous work from other groups established structural requirements that enable charge‐state reduction from Cu(II) to Cu(I) in ligand complexes during transition into the gas phase, and these rules allow us to propose structural features of PA‐Q complexes with copper ions in solution. Copyright © 2013 John Wiley & Sons, Ltd.
Structural elucidation of a new sildenafil analogue using high‐resolution Orbitrap mass spectrometry
Authors: Kee Chee‐Leong , Ge Xiaowei , Low Min‐Yong , Koh Hwee‐Ling 
Published: May 2013

RATIONALEOne new phosphodiesterase type 5 (PDE‐V) inhibitor, propoxyphenyl homohydroxysildenafil (PP‐HHS), has been isolated from one health supplement, and analyzed using high‐resolution Orbitrap mass spectrometry. High‐resolution mass spectrometry (HRMS) is useful to elucidate unknown substances at low concentrations.METHODSTwo isolated compounds, propoxyphenyl thiohomohydroxysildenafil (PP‐THHS) and propoxyphenyl homohydroxysildenafil (PP‐HHS), were infused into the Thermo Fischer Scientific LTQ Orbitrap XL™ hybrid FTMS system at a flow rate of 3 μL per min. The high‐resolution MS2 spectra were acquired using different high‐energy collision dissolution (HCD) mode; 40 V for PPT‐HHS and 45 V for PP‐HHS. The accurate mass measurement was assisted with the aid of Mass Frontier software, version 5.0.RESULTSThe fragmentation pattern of PP‐HHS in the MS2 spectrum is very similar to that of PP‐THHS except the product ions at m/z 519, 501, 325, 299 and 283 are less than PP‐THHS by 16 m/z units. This is a result of the replacement of sulfur atom by oxygen at the thiolactam moiety. All the mass errors are below 5.0 ppm.CONCLUSIONSHigh‐resolution Orbitrap mass spectrometry is an alternative method to determine unknown compounds like PDE‐V inhibitor analogues unambiguously by analyzing the product ions at high mass accuracy. PP‐HHS is an unapproved drug and no pharmacological study has been reported. Hence, it could be harmful to unknowing consumers with undesirable side effects. Copyright © 2013 John Wiley & Sons, Ltd.
Buckling analysis of thin‐walled steel structures using generalized beam theory (GBT): state‐of‐the‐art report
Authors: Camotim Dinar , Basaglia Cilmar 
Published: May 2013

AbstractThis paper addresses the use of generalized beam theory (GBT) to analyse the local and global buckling behaviour of thin‐walled steel members and structural systems. After a brief historical perspective of GBT developments, the main concepts and procedures involved in performing buckling analyses are summarized in a systematic fashion. That is followed by a state‐of‐the‐art report concerning the most recent GBT formulations and applications that have been developed to assess the buckling behaviour of members, frames and trusses with various loading and support conditions. In order to illustrate the unique modal features and show the potential of the GBT approach to buckling analysis, numerical results and a few practical applications are presented and discussed; for validation purposes, most of these results are compared with values yielded by shell finite element analyses, performed in the ABAQUS and ANSYS programs. The paper closes with a few words on the future perspectives of GBT‐based buckling analysis.
Axial capacity of perforated steel columns
Authors: Leach Philip , Weekes Laurence 
Published: May 2013

AbstractA research group has recently been formed at the University of Salford with the general aim of investigating lightweight structures. The first task of the group is to look at the behaviour of perforated steel columns used for storage racking.The steel columns used in storage racking are made from perforated light gauge steel, with the perforations facilitating the connection of the storage racking beams. Recent work by Casafont et al. [1] has investigated the axial capacity of such members by a combination of testing and calculation, whereas another approach has been reported by Dinis et al. [2].This paper describes the initial work of the group, investigating the possibility of assessing such capacity by using Eurocode 3 [3] equations to calculate the failure load of the column, using a critical buckling load that allows for the perforations in the column [4]. Critical buckling loads are calculated using both generalized beam theory and finite element analysis.The use of generalized beam theory is illustrated for problems of varying complexity, from a very simple uncoupled solution with one equation up to the final coupled finite difference eigenvalue solution.The paper concludes that it is currently possible to predict the capacity within a 15 % margin, and that further work could indeed improve this.
Sound and mechanised compositional verification of input‐output conformance
Authors: Sampaio Augusto , Nogueira Sidney , Mota Alexandre , Isobe Yoshinao 
Published: May 2013

SUMMARYThis paper mechanises conformance verification in the setting of the CSP process algebra. The verification strategy is captured by a theorem stated as a process refinement expression, which can be verified by a model checker such as FDR. The conformance relation,cspio, distinguishes input and output events. The process algebraic framework of CSP is used to address compositional conformance verification by establishing compositionality properties forcspiowith respect to the CSP operators. Althoughcspiohas been defined in the standard CSP traces model, one can address quiescence situations using a special output event, in which case it is formally established thatcspiois equivalent to Tretmansioco. All the results have been mechanically proved using the CSP‐Prover. The proposed testing theory has been adopted in an industrial context involving collaboration with Motorola, on testing mobile applications. Several examples and a case study are presented to illustrate the overall approach. Copyright © 2013 John Wiley & Sons, Ltd.
Prospective Study Examining Clinical Outcomes Associated with a Negative Pressure Wound Therapy System and Barker’s Vacuum Packing Technique
Authors: Cheatham Michael L. , Demetriades Demetrios , Fabian Timothy C. , Kaplan Mark J. , Miles William S. , Schreiber Martin A. , Holcomb John B. , Bochicchio Grant , Sarani Babak , Rotondo Michael F. 
Published: May 2013

AbstractBackgroundThe open abdomen has become a common procedure in the management of complex abdominal problems and has improved patient survival. The method of temporary abdominal closure (TAC) may play a role in patient outcome.MethodsA prospective, observational, open‐label study was performed to evaluate two TAC techniques in surgical and trauma patients requiring open abdomen management: Barker’s vacuum‐packing technique (BVPT) and the ABTheraTM open abdomen negative pressure therapy system (NPWT). Study endpoints were days to and rate of 30‐day primary fascial closure (PFC) and 30‐day all‐cause mortality.ResultsAltogether, 280 patients were enrolled from 20 study sites. Among them, 168 patients underwent at least 48 hours of consistent TAC therapy (111 NPWT, 57 BVPT). The two study groups were well matched demographically. Median days to PFC were 9 days for NPWT versus 12 days for BVPT (p = 0.12). The 30‐day PFC rate was 69 % for NPWT and 51 % for BVPT (p = 0.03). The 30‐day all‐cause mortality was 14 % for NPWT and 30 % for BVPT (p = 0.01). Multivariate logistic regression analysis identified that patients treated with NPWT were significantly more likely to survive than the BVPT patients [odds ratio 3.17 (95 % confidence interval 1.22–8.26); p = 0.02] after controlling for age, severity of illness, and cumulative fluid administration.ConclusionsActive NPWT is associated with significantly higher 30‐day PFC rates and lower 30‐day all‐cause mortality among patients who require an open abdomen for at least 48 h during treatment for critical illness.
Gastrointestinal and hepatic manifestations of mitochondrial disorders
Authors: Rahman Shamima 
Published: May 2013

AbstractInherited defects of oxidative phosphorylation lead to heterogeneous, often multisystem, mitochondrial diseases. This review highlights those mitochondrial syndromes with prominent gastrointestinal and hepatic symptoms, categorised according to underlying disease mechanism. Mitochondrial encephalopathies with major gastrointestinal involvement include mitochondrial neurogastrointestinal encephalopathy and ethylmalonic encephalopathy, which are each associated with highly specific clinical and metabolic profiles. Mitochondrial hepatopathies are most frequently caused by defects of mitochondrial DNA maintenance and expression. Although mitochondrial disorders are notorious for extreme clinical, biochemical and genetic heterogeneity, there are some pathognomonic clinical and metabolic clues that suggest a specific diagnosis, and these are highlighted. An approach to diagnosis of these complex disorders is presented, together with a genetic classification, including mitochondrial DNA disorders and nuclear‐encoded defects of mitochondrial DNA maintenance and translation, OXPHOS complex assembly and mitochondrial membrane lipids. Finally, supportive and experimental therapeutic options for these currently incurable diseases are reviewed, including liver transplantation, allogeneic haematopoietic stem cell transplantation and gene therapy.
Current Lynch Syndrome Tumor Screening Practices: A Survey of Genetic Counselors
Authors: Cohen Stephanie A. 
Published: May 2013

AbstractAn electronic survey of the National Society of Genetic Counselors Cancer Special Interest Group was conducted in July 2011 to assess Lynch syndrome tumor screening programs and identify barriers to implementation. Over half of respondents (52.8 %) reported having a routine Lynch syndrome tumor screening protocol for newly diagnosed colon and/or endometrial cancers, and approximately half of these used a universal approach. There was an increase in the number of those screening over time, especially in the past 3 years. Tumor screening methods varied; 34/53 (64.2 %) started with immunohistochemistry, 11/53 (20.8 %) started with microsatellite instability testing and 8/53 (15.1 %) performed both on newly diagnosed colorectal tumors. Just 21.7 % (23/106) of respondents indicated they have a tumor screening program in place for newly diagnosed endometrial cancers. Written consent is rarely obtained (7.1 %) and the method of how results were returned to the patient was variable among respondents. Prevalent barriers to implementation were concern about cost, bringing key players together and convincing medical staff of the necessity. Use of Lynch syndrome tumor screening is in clinical practice, but protocols vary widely. This survey provides a glimpse of current practices and common barriers, and identifies the need for tumor screening algorithms with outcomes data.
Oxidized Lipoprotein(a) Increases Endothelial Cell Monolayer Permeability via ROS Generation
Authors: Wei Deng‐heng , Zhang Xiao‐lei , Wang Ren , Zeng Jun‐fa , Zhang Kai , Yang Jian , Li Shuang , Lin Xiao‐long , Jiang Zhi‐sheng , Wang Gui‐xue , Wang Zuo 
Published: May 2013

AbstractOxidized lipoprotein(a) (oxLp(a)) is a more potent marker of atherogenesis than native Lp(a). However, the molecular mechanisms of oxLp(a) activity are not clear. Reactive oxygen species (ROS) have recently been suggested as acting as intracellular second messengers. In this study, the effects of oxLp(a) on endothelial cell monolayer permeability and the role of reactive oxygen species (ROS) generation in these effects were investigated. Our results showed that oxLp(a) inhibited desmoglein‐1 (DSG1) and desmocollin‐2 (DSC2) expression at both mRNA and protein levels in a dose‐ and time‐dependent manner, and increased the generation of cellular ROS. Down‐regulation of DSG1 and DSC2 was strengthened by pretreatment with H2O2 and attenuated by superoxide dismutase (SOD) treatment. Furthermore, oxLp(a) increased endothelial cell monolayer permeability, and this effect was enhanced by H2O2 and blunted by SOD. Taken together, these results demonstrate that oxLp(a) increases endothelial cell monolayer permeability, which is mediated at least in part via ROS generation.
Expression and roles of CCN2 in dental mesenchymal cells in primary culture—With findings in a case of odontogenic myxofibroma
Authors: Shimo Tsuyoshi , Koyama Eiki , Horikiri Yuu , Okui Tatsuo , Kurio Naito , Katase Naoki , Yoshida Shoko , Takebe Yuichiro , Kishimoto Koji , Yoshioka Norie , Nagatsuka Hitoshi , Sasaki Akira 
Published: May 2013

AbstractPurpose of the research: Tooth germ development involves multiple events, including cell proliferation and cell differentiation. Connective tissue growth factor (CTGF/CCN2) is a signaling protein involved in tooth germ development, and we investigated how it is expressed and what roles it may have in primary cultures of mesenchymal cells derived from the developing tooth germ. We also examined the expression of CCN2 in a human odontogenic myxofibroma, a benign tumor of odontogenic mesenchymal origin, and considered the possible roles of CCN2 in the development of myxofibromas.Materials and methods: Mesenchymal cells of early bell‐stage tooth germs were isolated from Day‐90 bovine embryos and placed in primary culture. A resected specimen from a patient with odontogenic myxofibroma was prepared for immunohistochemical studies.Principal results: The CCN2 expression level in proliferating odontogenic mesenchymal cells freshly isolated from the early bell stage of developing bovine tooth germs and placed in primary culture was 3 times higher than that in the confluent non‐proliferating cells. Recombinant CCN2 significantly increased the proliferation and type I collagen expression in odontogenic mesenchymal cells in primary culture. Immunohistochemical analysis on myxofibroma case revealed that CCN2 was detectable in MIB‐1, a cellular marker of proliferation‐positive odontogenic mesenchymal cells adjacent to capillary blood vessels and in the endothelial cells of the vessels in the tumor.Major conclusion: CCN2 signaling would influence the proliferation of and extracellular matrix production by dental mesenchymal cells. Our results suggest that the same mechanisms of CCN2 action toward dental mesenchymal cells would also be operative in the odontogenic myxofibroma microenvironment.
Sensitivity of stratified turbulence to the buoyancy Reynolds number
Authors: Bartello P. , Tobias S. M. 
Published: May 2013

AbstractIn this article we present direct numerical simulations of stratified flow at resolutions of up to $204{8}^{2} \times 513$, to explore scalings for the dynamics of stably stratified turbulence. Recent work suggests that for strong enough stratification, the vertical integral scale of the turbulence adjusts to yield a vertical Froude number, ${F}_{v} $, of order unity at high enough Reynolds number, whilst the horizontal Froude number, ${F}_{h} $, decreases as stratification is increased. Our numerical simulations are consistent with predictions by Lindborg (J. Fluid Mech., vol. 550, 2006, pp, 207–242), and with numerical simulations at lower resolution, in that the horizontal kinetic energy spectrum follows a Kolmogorov spectrum (after replacing the wavenumber with the horizontal wavenumber) and that the horizontal potential energy spectrum similarly follows the Corrsin–Obukhov spectrum for a passive scalar. Most importantly, we build upon these previous results by thoroughly exploring the dependence of the horizontal spectrum of horizontal kinetic energy on both the stratification and the relative size of the vertical dissipation terms, as quantified by the buoyancy Reynolds number. Our most important result is that variations in the power-law exponent scale entirely with the buoyancy Reynolds number and not with the stratification itself, lending considerable support to the Lindborg (2006) hypothesis that horizontal spectra are independent of stratification at large Reynolds numbers. We further demonstrate that even at the large numerical resolution of this study, the spectrum and hence the dynamics are affected by the buoyancy Reynolds number unless it is larger than $O(10)$, indicating that extreme care must be taken when assessing claims made from previous numerical simulations of stratified flow at low or moderate resolution and extrapolating the results to geophysical or astrophysical Reynolds numbers.
Inviscid Faraday waves in a brimful circular cylinder
Authors: Kidambi R. 
Published: May 2013

AbstractWe study inviscid Faraday waves in a brimful circular cylinder with pinned contact line. The pinning leads to a coupling of the Bessel modes and leads to an infinite system of coupled Mathieu equations. For large Bond numbers, even though the stability diagrams and the subharmonic and harmonic resonances for the free and pinned contact lines are similar, the free surface shapes can be quite different. With decreasing Bond number, not only are the harmonic and subharmonic resonances very different from the free contact line case but also interesting changes in the stability diagram occur with the appearance of combination resonance tongues. Points on these tongue boundaries correspond to almost-periodic states. These do not seem to have been reported in the literature.