bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐peptide monoclonal antibody imaging of a common binding domain involved in muscle regulation
Authors: Van Eyk Jennifer E. , Caday‐Malcolm Rosalinda A. , Hodges Robert S. , Yu Lei , Irvin Randall T. 
Published: June 2010

AbstractMultiple‐component regulatory protein systems function through a generalized mechanism where a single regulatory protein or ligand binds to a variety of receptors to modulate specific functions in a physiologically sensitive context. Muscle contraction is regulated by the interaction of actin with troponin I (TnI) or myosin in a Ca2+‐sensitive manner. Actin utilizes a single binding domain (residues 1–28) to bind to residues 104–115 of TnI (Van Eyk JE, Sönnichsen FD, Sykes BD, Hodges RS, 1991, In: Rüegg JC, ed, Peptides as probes in muscle research, Heidelberg, Germany: Springer‐Verlag, pp 15–31) and to myosin subfragment 1 (S1, an enzymatic fragment of myosin containing both the actin and ATP binding sites) (Van Eyk JE, Hodges RS, 1991, Biochemistry 30:11676–11682) in a Ca2+‐sensitive manner. We have utilized an anti‐TnI peptide (104–115) monoclonal antibody, Mab B4, that binds specifically to TnI, to image the common binding domain of actin and thus mimic the activity of actin including activation of the S1 ATPase activity and TnI‐mediated regulation of the S1 ATPase. Mab B4 has also been utilized to identify a receptor binding domain on myosin (residues 633–644) that is recognized by actin. Interestingly, Mab B4 binds to the native protein receptors TnI and S1 with relative affinities of 100‐ and 25,000‐fold higher than the binding affinity to the 12‐residue peptide immunogen. Thus, anti‐peptide monoclonal antibodies prepared against a receptor binding domain can mimic the ligand binding domain and be utilized as a powerful tool for the detailed analysis of complex multiple‐component regulatory systems.
Circular permutation within the coenzyme binding domain of the tetrameric glyceraldehyde‐3‐phosphate dehydrogenase from Bacillus stearothermophilus
Authors: Vignais Marie‐Luce , Corbier Catherine , Mulliert Guillermo , Branlant Christiane , Branlant Guy 
Published: June 2010

AbstractA circularly permuted (cp) variant of the phosphorylating NAD‐dependent glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) from Bacillus stearothermophilus has been constructed with N‐ and C‐termini created within the coenzyme binding domain. The cp variant has a kcat value equal to 40% of the wild‐type value, whereas Km and KD values for NAD show a threefold decrease compared to wild type. These results indicate that the folding process and the conformational changes that accompany NAD binding during the catalytic event occur efficiently in the permuted variant and that NAD binding is tighter. Reversible denaturation experiments show that the stability of the variant is only reduced by 0.7 kcal/mol compared to the wild‐type enzyme. These experiments confirm and extend results obtained recently on other permuted proteins. For multimeric proteins, such as GAPDH, which harbor subunits with two structural domains, the natural location of the N‐ and C‐termini is not a prerequisite for optimal folding and biological activity.
Building proteins from Cα coordinates using the dihedral probability grid Monte Carlo method
Authors: Mathiowetz Alan M. , Goddard William A. 
Published: June 2010

AbstractDihedral probability grid Monte Carlo (DPG‐MC) is a general‐purpose method of conformational sampling that can be applied to many problems in peptide and protein modeling. Here we present the DPG‐MC method and apply it to predicting complete protein structures from Cα coordinates. This is useful in such endeavors as homology modeling, protein structure prediction from lattice simulations, or fitting protein structures to X‐ray crystallographic data. It also serves as an example of how DPG‐MC can be applied to systems with geometric constraints. The conformational propensities for individual residues are used to guide conformational searches as the protein is built from the amino‐terminus to the carboxyl‐terminus. Results for a number of proteins show that both the backbone and side chain can be accurately modeled using DPG‐MC. Backbone atoms are generally predicted with RMS errors of about 0.5 Å (compared to X‐ray crystal structure coordinates) and all atoms are predicted to an RMS error of 1.7 Å or better.
Similarity of different β‐strands flanked in loops by glycines and prolines from distinct (α/β)8‐barrel enzymes: Chance or a homology?
Authors: Janeček ŠTefan 
Published: June 2010

AbstractMany (α/β)8‐barrel enzymes contain their conserved sequence regions at or around the β‐strand segments that are often preceded and succeeded by glycines and prolines, respectively. α‐Amylase is one of these enzymes. Its sequences exhibit a very low degree of similarity, but strong conservation is seen around its β‐strands. These conserved regions were used in the search for similarities with β‐strands of other (α/β)8‐barrel enzymes. The analysis revealed an interesting similarity between the segment around the β2‐strand of α‐amylase and the one around the β4‐strand of glycolate oxidase that are flanked in loops by glycines and prolines. The similarity can be further extended on other members of the α‐amylase and glycolate oxidase subfamilies, i.e., cyclodextrin glycosyltransferase and oligo‐l,6‐glucosidase, and flavocytochrome b2, respectively. Moreover, the α‐subunit of tryptophan synthase, the (α/β)8‐barrel enzyme belonging to the other subfamily of (α/β)8‐barrels, has both investigated strands, β2 and β4, similar to β2 of α‐amylase and β4 of glycolate oxidase. The possibilities of whether this similarity exists only by chance or is a consequence of some processes during the evolution of (α/β)8‐barrel proteins are briefly discussed.
Binding site prediction and improved scoring during flexible protein–protein docking with ATTRACT
Authors: Fiorucci Sébastien , Zacharias Martin 
Published: June 2010

AbstractThe ATTRACT protein–protein docking program combined with a coarse‐grained protein model has been used to predict protein–protein complex structures in CAPRI rounds 13–19. For six targets acceptable or better quality solutions have been submitted (high quality predictions for targets 32, 40, 41, and 42). The improved performance compared to previous rounds can be attributed in part to the inclusion of conformational flexibility during systematic searches and an optimized scoring function. In addition, a recently developed method for the prediction of putative protein binding sites based on the electrostatic penalty to place neutral low dielectric probes on the protein surface was applied to the most recent targets. The approach resulted in useful predictions of putative binding sites that can help to limit the systematic docking searches. Possible improvements of the docking approach in particular at the scoring and refinement steps are discussed. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Variance scaling in shallow‐cumulus‐topped mixed layers
Authors: Neggers R. A. J. , Stevens B. , Neelin J. D. 
Published: July 2010

AbstractScaling of thermodynamic variance in shallow‐cumulus‐topped mixed layers is studied using large‐eddy simulation (LES). First, the performance of the top‐down scaling (the turbulent flux at mixed‐layer top divided by w*) is evaluated for transient shallow‐cumulus convection over land. The results indicate that this scaling fails to capture all the variance in the top half of the mixed layer when shallow cumulus clouds are present. A variance‐budget analysis is then performed, to derive a new scaling for the variance at mixed‐layer top, which differs from the standard top‐down scaling by a factor of one Richardson number. The essential new features of the proposed scaling are that the local vertical gradient is retained and that a balance is assumed between gradient production of variance and removal by transport and dissipation, using an adjustment time‐scale given by w*/h. Evaluation against LES for a range of different cases, including a dry convective boundary layer as well as steady‐state marine and transient continental shallow cumulus, reveals a data‐collapse of the newly‐scaled variance, for all hours and all cases in the top half of the mixed layer. The corresponding vertical structure is shown to resemble a power‐law function. The results suggest that the structure of variance in the dry convective boundary layer is similar to that in the sub‐cloud mixed layer. In transient situations, the scaling reproduces the time‐development of variance at sub‐cloud mixed‐layer top. The new cloud‐base variance scale is then further interpreted in the context of statistical cloud schemes, which depend on the variance as the second moment of the associated probability density function. The results suggest that the area fraction of the moist convective thermals uniquely depends on the ratio of cloud‐base transition‐layer depth to sub‐cloud mixed‐layer depth. This puts ‘valve’‐ or ventilation‐type closures for the cloud‐base mass flux in the context of the variance budget for the sub‐cloud layer. Copyright © 2007 Royal Meteorological Society
In situ measurements of liquid water content profiles in midlatitude stratiform clouds
Authors: Korolev A. V. , Isaac G. A. , Strapp J. W. , Cober S. G. , Barker H. W. 
Published: July 2010

AbstractStatistical characteristics of 584 liquid water content (LWC) profiles collected mainly in midlatitude supercooled stratiform frontal clouds during five field campaigns are presented. It has been found that the majority (55%) of liquid layers have thickness less than 500 m and the depth of these layers decreases with decreasing temperature. LWC profiles for thin cloud layers are usually close to quasi‐adiabatic, whereas for thick clouds they are approximately constant with an average LWC value close to 0.14 g m−3. Good agreement was observed between cumulative distributions for liquid water paths derived from in situ LWC profiles and those inferred in previous experiments from ground‐based 37 GHz radiometers. Copyright © 2007 Crown in the right of Canada. Published by John Wiley & Sons, Ltd
The value of observations. I: Data denial experiments for the Atlantic and the Pacific
Authors: Kelly Graeme , Thépaut Jean‐Noël , Buizza Roberto , Cardinali Carla 
Published: July 2010

AbstractAdding targeted observations to the array of observations routinely available to numerical weather prediction is generally found to give small impact, although studies have often focused on a very limited number of cases in field experiments. It is expected that observation targeting in sensitive areas may have more impact on forecasts ‘busts’. A forecast ‘bust’ in a given verification region is defined as a doubling of the mean monthly error for the day‐two forecast. This does not occur very often in the operational ECMWF system. The primary purpose of this study is to produce three reference data‐assimilation experiments: the first assimilation experiment uses all available observations (as they are used in the operational ECMWF analysis system). The second assimilation experiment systematically excludes all observations in the North Pacific oceanic region. The third assimilation experiment systematically excludes all observations in the North Atlantic oceanic region. These three experiments are then used to evaluate the potential of targeting strategies which are described in two separate papers (parts II and III of this study).Results, based on a summer and a winter season, indicate that on average:

Oceanic data are important to reduce day‐2 forecast errors over the downstream land areas, the downstream impact of observations over the Pacific Ocean being larger than the downstream impact of observations over the Atlantic Ocean.
The removal of observations taken over the Pacific Ocean has generally a small impact on medium‐range forecasts verified over Europe, but results strongly depend on the data‐assimilation system used to assimilate the observations.
Forecasts started from 3D‐Var analyses are worse than forecasts started from 4D‐Var analyses and, given the current observing system, the relative impact of ocean observations is higher if a 3D‐Var system is used instead of a 4D‐Var system. In other words, 4D‐Var is better capable of propagating information from data‐rich to data‐void areas, and is therefore less vulnerable to data gaps in a system which otherwise includes a large number of satellite observations. Copyright © 2007 Royal Meteorological Society
Reversed flow in the south‐Alpine Toce Valley during MAP‐IOP 8: Further analysis of latent cooling effects
Authors: Zängl G. 
Published: July 2010

AbstractNumerical simulations are presented to examine the physical mechanisms leading to downvalley flow in the south‐Alpine Toce Valley during MAP IOP 8 (20–21 October 1999), continuing a recent study by Asencio and Stein. The downvalley flow occurred during a phase of moderate precipitation, opposing the southerly (upslope) flow at higher levels that generated the precipitation. Based on sensitivity experiments with suppressed latent cooling by melting and evaporation, Asencio and Stein concluded that cooling by melting was important for maintaining a northerly low‐level flow in the exit region of the Toce Valley and the adjacent parts of the Po Valley. Here, the investigation is extended to the Toce Valley itself, using a finer model resolution that allows the valley topography to be properly resolved. The effects of cooling by melting and evaporation are tested separately. In addition, the evaporation of precipitating hydrometeors and cloud water is considered separately. The tests indicate that the effects of cooling by melting and evaporation of precipitating hydrometeors are quite small. A markedly larger impact is found for the evaporation of cloud water, which is advected into the valley area by the subsiding motion compensating for the low‐level downvalley flow. This appears to be related to the fact that cloud water is assumed to evaporate instantaneously in a subsaturated atmosphere via saturation adjustment, whereas larger hydrometeors have a fairly small evaporation rate in a nearly saturated atmosphere. Nevertheless, the sensitivity of the simulated flow field to completely suppressing latent cooling is not as large as found in the preceding study. Though latent cooling substantially intensifies the downvalley flow and prevents temporary changes to upvalley flow, it does not appear to be essential for the development of downvalley flow. An additional driving mechanism based on the evolution of the mesoscale pressure field is proposed. Copyright © 2007 Royal Meteorological Society
The contamination of ‘data impact’ in global models by rapidly growing mesoscale instabilities
Authors: Hodyss Daniel , Majumdar Sharanya J. 
Published: July 2010

AbstractThis paper illustrates a caveat in the ‘data impact’ method, in which the influence of assimilating a specific set of observations on a numerical weather forecast is evaluated. The ‘signal’ of data impact is defined as the difference between two forecasts, which are identical except that one forecast withholds the data in question from the assimilation. While it is anticipated that a coherent signal from observations in the midlatitude storm track is propagated dynamically by a forecast model from the vicinity of the observation locations, the reality is that the signal may become contaminated by initially small instabilities in dynamically unrelated locations. The initial signal may be non‐zero in these remote locations due to small differences between the two analyses arising from truncation errors in the data assimilation scheme and/or the model's truncated spectral basis. The notion that the dynamical signal is contaminated is corroborated by assessing the data impact in the Northern Hemisphere of one rawinsonde released over Antarctica. After just a few hours, an amplifying signal manifests itself in convective areas in the Tropics, and even in locations along the midlatitude storm track where moist instabilities exist. Rapid growth and upscale evolution from the mesoscale to synoptic scales is evident. We find that the evaluation of the efficacy of a given set of observations on weather forecasts of more than two days may be compromised by initially small instabilities, particularly for spectral models and data assimilation schemes. The effective time is expected to be shorter in the Tropics. Copyright © 2007 Royal Meteorological Society
Clinical Issues—July 2010
Authors: Denholm Bonnie , Burlingame Byron 
Published: July 2010

This MonthIntravasation and fluid deficit during hysteroscopy proceduresKey words: fluid management, fluid deficit, fluid overload, intravasation, hyponatremia, hysteroscopy.Fluid selection during minimally invasive surgeryKey words: minimally invasive surgery, fluid selection, electrolyte solutions, distention media, irrigation solutions, fluid risks.Comparing hysteroscopic insufflators and laparoscopic insufflatorsKey words: insufflators, hysteroscopy, laparoscopy, minimally invasive surgery, distention media.Using IV bags to position patientsKey words: patient positioning, positioning equipment, IV bags, burns.Storage of disinfected laryngoscope bladesKey words: laryngoscope blades, high‐level disinfection, packaging.
Phosphorylation of spinal N‐methyl‐d‐aspartate receptor NR1 subunits by extracellular signal‐regulated kinase in dorsal horn neurons and microglia contributes to diabetes‐induced painful neuropathy
Authors: Daulhacl Laurence , Maffrel Violette , Malletl Christophe , Etiennel Monique , Privatl Anne‐Marie , Kowalski‐Chauvell Aline , Seval Catherine , Fialipl Joseph , Eschalierl Alain 
Published: July 2010

AbstractThe N‐methyl‐d‐aspartate receptor (NMDAR) contributes to central sensitization in the spinal cord, a phenomenon which comprises various pathophysiological mechanisms responsible for neuropathic pain‐like signs in animal models. NMDAR function is modulated by post‐translational modifications including phosphorylation, and this is proposed to underlie its involvement in the production of pain hypersensitivity. As in diabetic patients, streptozotocin‐induced diabetic rats exhibit or not somatic mechanical hyperalgesia; these rats were named DH and DNH respectively. At three weeks of diabetes, we present evidence that somatic mechanical hyperalgesia was correlated with an enhanced phosphorylation of the NMDAR NR1 subunit (pNR1) in the rat spinal cord. This increase was not found in normal and DNH rats, suggesting that this regulation was specific to hyperalgesia. Double immunofluorescence studies revealed that the numbers of pNR1‐immunoreactive neurons and microglial cells were significantly increased in all laminae (I—II and III—VI) of the dorsal horn from DH animals. Western‐blots analysis showed no change in NR1 protein levels, whatever the behavioural and glycemic status of the animals. Chronic intrathecal treatment (5μg/rat/day for 7 days) by U0126 and MK801, which blocked MEK (an upstream kinase of extracellular signal‐regulated protein kinase: ERK) and the NMDAR respectively, simultaneously suppressed somatic mechanical hyperalgesia developed by diabetic rats and decreased pNR1. These results indicate for the first time that increased expression of pNR1 is regulated by ERK and the NMDAR via a feedforward mechanism in spinal neurons and microglia and represents one mechanism involved in central sensitization and somatic mechanical hyperalgesia after diabetes.
Enhancing Service Delivery Capacity through Knowledge Exchange: The Seniors Health Research Transfer Network
Authors: Conklin James , Stolee Paul , Luesby Deirdre , Sharratt Michael T. , Chambers Larry W. 
Published: July 2010

The Seniors Health Research Transfer Network (SHRTN) was launched in 2005 in Ontario to improve the quality of health care provided to seniors by facilitating knowledge exchange opportunities for formal and informal caregivers, researchers and policymakers. This article describes the conceptual basis and development of SHRTN, as well as achievements, challenges and lessons learned during its first year of operation, which ended in March 2006. We begin by discussing knowledge exchange networks and their conceptual basis. We then offer a brief history of SHRTN, tracing its origins to both a broad interprofessional interest in creating and sharing knowledge within and across organizations, and also to the efforts of a small group of early champions. After this, we describe the main events, achievements and surprises of SHRTN's first year. Experience with SHRTN has highlighted the importance of careful attention to governance issues in the organization of knowledge exchange networks, and the challenge of balancing management control with broad participation and flexibility. Collaboration can yield synergy and innovation, but requires commitment from participants. The SHRTN experience has demonstrated that planning and coordinating a provincial network that engages diverse stakeholders is a logistical challenge that requires dedicated infrastructure and funding support.
Introducing “Evidence” into Board Decision-Making
Authors: Menon Devidas , Gebran Joseph 
Published: July 2010

The purpose of this article is to report on the results of a workshop that introduced evidence-based decision-making techniques to Board members of regional health authorities in Alberta. Results and conclusions: The workshop demonstrated that it is possible to design a process for the incorporation of evidence in administrative decision-making. The participants demonstrated that they were able to apply scientific evidence in administrative decision making and that the decisions taken were reasonably consistent. Also, in the absence of evidence, values took precedence in the decision-making process and the decisions taken were less consistent.
Total Hip and Knee Replacement Surgeries in Alberta Utilization and Associated Outcomes
Authors: Alibhai Arif , Saunders Duncan , Johnston DWC , Bay Kyung 
Published: July 2010

Objective: Between 1994/95 and 1996/7, the healthcare system in Alberta underwent a radical transformation that saw the regionalization of service delivery and a reduction in overall healthcare funding. The aim of this study is to examine trends in utilization and associated post-operative complications and readmissions for two procedures, total hip arthroplasty (THA) and total knee arthroplasty (TKA) during this period of restructuring. Methods: This is a six-year retrospective analysis using hospital separation and healthcare insurance plan registry databases. During the study period, we looked at trends in inpatient procedure volumes, average lengths of stay, postoperative complications during the index hospital stay and readmissions within one year. Results: Over a six-year period, the age-sex standardized provincial rate of THAs increased by 18% while the rate of TKAs increased by 73%. Average lengths of stay decreased for both procedures by over 50%. The rate of procedures with at least one postoperative complication within the index episode of care decreased over the study period by 19% for THA and 21% for TKA. Readmissions due to complications of surgery increased overall by 32% for THA and 2% for TKA. Regional and sex differences were observed throughout the period. Conclusions: While the overall rate of hospitalizations has decreased in Alberta, the rates of THA and TKA procedures have increased. The lengths of stay following these procedures have, at the same time, reduced dramatically. Adverse outcomes as measured by complication rates associated with these procedures have decreased, though readmissions due to complications after surgery have increased.