Many-particle Brownian and Langevin Dynamics Simulations with the Brownmove package

<p>Abstract</p> <p>Background</p> <p>Brownian Dynamics (BD) is a coarse-grained implicit-solvent simulation method that is routinely used to investigate binary protein association dynamics, but due to its efficiency in handling large simulation volumes and particle numbers it is well suited to also describe many-protein scenarios as they often occur in biological cells.</p> <p>Results</p> <p>Here we introduce our "brownmove" simulation package which was designed to handle many-particle problems with varying particle numbers and allows for a very flexible definition of rigid and flexible protein and polymer models. Both a Brownian and a Langevin dynamics (LD) propagation scheme can be used and hydrodynamic interactions are treated efficiently with our recently introduced TEA-HI ansatz [Geyer, Winter, JCP 130 (2009) 114905]. With simulations of constrained polymers and flexible models of spherical proteins we demonstrate that it is crucial to include hydrodynamics when multi-bead models are used in BD or LD simulations. Only then both the translational and the rotational diffusion coefficients and the timescales of the internal dynamics can be reproduced correctly. In the third example project we show how constant density boundary conditions [Geyer et al, JCP 120 (2004) 4573] can be used to set up a non-equilibrium simulation of diffusional transport across an array of fixed obstacles. Finally, we demonstrate how the agglomeration dynamics of multiple particles with attractive patches can be analysed conveniently with the help of a dynamic interaction network.</p> <p>Conclusions</p> <p>Combining BD and LD propagation, fast hydrodynamics, a flexible protein model, and interfaces for "open" simulation settings, our freely available "brownmove" simulation package constitutes a new platform for coarse-grained many-particle simulations of biologically relevant diffusion and transport processes.</p

Bovine liver slices combined with an androgen transcriptional activation assay: an in-vitro model to study the metabolism and bioactivity of steroids

Previously we described the properties of a rapid and robust yeast androgen bioassay for detection of androgenic anabolic compounds, validated it, and showed its added value for several practical applications. However, biotransformation of potent steroids into inactive metabolites, or vice versa, is not included in this screening assay. Within this context, animal-friendly in-vitro cellular systems resembling species-specific metabolism can be of value. We therefore investigated the metabolic capacity of precision-cut slices of bovine liver using 17β-testosterone (T) as a model compound, because this is an established standard compound for assessing the metabolic capacity of such cellular systems. However, this is the first time that slice metabolism has been combined with bioactivity measurements. Moreover, this study also involves bioactivation of inactive prohormones, for example dehydroepiandrosterone (DHEA) and esters of T, and although medium extracts are normally analyzed by HPLC, here the metabolites formed were identified with more certainty by ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC–TOFMS) with accurate mass measurement. Metabolism of T resulted mainly in the formation of the less potent phase I metabolites 4-androstene-3,17-dione (4-AD), the hydroxy-T metabolites 6α, 6β, 15β, and 16α-OH-T, and the phase II metabolite T-glucuronide. As a consequence the overall androgenic activity, as determined by the yeast androgen bioassay, decreased. In order to address the usefulness of bovine liver slices for activation of inactive steroids, liver slices were exposed to DHEA and two esters of T. This resulted in an increase of androgenic activity, because of the formation of 4-AD and T

Understanding interactions in face-to-face and remote undergraduate science laboratories

This paper reviews the ways in which interactions have been studied, and the findings of such studies, in science education in both face-to-face and remote laboratories. Guided by a systematic selection process, 27 directly relevant articles were analysed based on three categories: the instruments used for measuring interactions, the research findings on student interactions, and the theoretical frameworks used in the studies of student interactions. In face-to-face laboratories, instruments for measuring interactions and the characterisation of the nature of interactions were prominent. For remote laboratories, the analysis of direct interactions was found to be lacking. Instead, studies of remote laboratories were mainly concerned with their practical scope. In addition, it is found that only a limited number of theoretical frameworks have been developed and applied in the research design. Existent theories are summarised and possible theoretical frameworks that may be implemented in studies of interactions in undergraduate laboratories are proposed. Finally, future directions for research on the interrelationship between student interactions and laboratory learning are suggested

Diversity and quantity of ammonia-oxidizing Archaea and Bacteria in sediment of the Pearl River Estuary, China

The diversity and abundance of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in the sediment of the Pearl River Estuary were investigated by cloning and quantitative real-time polymerase chain reaction (qPCR). From one sediment sample S16, 36 AOA OTUs (3% cutoff) were obtained from three clone libraries constructed using three primer sets for amoA gene. Among the 36 OTUs, six were shared by all three clone libraries, two appeared in two clone libraries, and the other 28 were only recovered in one of the libraries. For AOB, only seven OTUs (based on 16S rRNA gene) and eight OTUs (based on amoA gene) were obtained, showing lower diversity than AOA. The qPCR results revealed that AOA amoA gene copy numbers ranged from 9.6 × 106 to 5.1 × 107 copies per gram of sediment and AOB amoA gene ranged from 9.5 × 104 to 6.2 × 105 copies per gram of sediment, indicating that the dominant ammonia-oxidizing microorganisms in the sediment of the Pearl River Estuary were AOA. The terminal restriction fragment length polymorphism results showed that the relative abundance of AOB species in the sediment samples of different salinity were significantly different, indicating that salinity might be a key factor shaping the AOB community composition

Intra-Accumbens Injection of a Dopamine Aptamer Abates MK-801-Induced Cognitive Dysfunction in a Model of Schizophrenia

Systemic administration of the noncompetitive NMDA-receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. The present work investigated the ability of a dopamine-binding DNA aptamer to regulate these MK-801-induced cognitive deficits when injected into the nucleus accumbens. Rats were trained to bar press for chocolate pellet rewards then randomly assigned to receive an intra-accumbens injection of a DNA aptamer (200 nM; n = 7), tris buffer (n = 6) or a randomized DNA oligonucleotide (n = 7). Animals were then treated systemically with MK-801 (0.1 mg/kg) and tested for their ability to extinguish their bar pressing response. Two control groups were also included that did not receive MK-801. Data revealed that injection of Tris buffer or the random oligonucleotide sequence into the nucleus accumbens prior to treatment with MK-801 did not reduce the MK-801-induced extinction deficit. Animals continued to press at a high rate over the entire course of the extinction session. Injection of the dopamine aptamer reversed this MK-801-induced elevation in lever pressing to levels as seen in rats not treated with MK-801. Tests for activity showed that the aptamer did not impair locomotor activity. Results demonstrate the in vivo utility of DNA aptamers as tools to investigate neurobiological processes in preclinical animal models of mental health disease

Contributions of myofascial pain in diagnosis and treatment of shoulder pain. A randomized control trial

<p>Abstract</p> <p>Background</p> <p>Rotator cuff tendinopathy and subacromial impingement syndrome present complex patomechanical situations, frequent difficulties in clinical diagnosis and lack of effectiveness in treatment. Based on clinical experience, we have therefore considered the existence of another pathological entity as the possible origin of pain and dysfunction. The hypothesis of this study is to relate subacromial impingement syndrome (SIS) with myofascial pain syndrome (MPS), since myofascial trigger points (MTrPs) cause pain, functional limitation, lack of coordination and alterations in quality of movement, even prior to a tendinopathy. MTrPs can coexist with any degenerative subacromial condition. If they are not taken into consideration, they could perpetuate and aggravate the problem, hindering diagnosis and making the applied treatments ineffective.</p> <p>The aims and methods of this study are related with providing evidence of the relationship that may exist between this condition and MPS in the diagnosis and treatment of rotator cuff tendonitis and/or SIS.</p> <p>Method/design</p> <p>A descriptive transversal study will be made to find the correlation between the diagnosis of SIS and rotator cuff tendonitis, positive provocation test responses, the existence of active MTrPs and the results obtained with ultrasonography (US) and Magnetic Renonance Imaging (MRI). A randomized double blinded clinical trial will be carried out in experimental conditions: A Protocolized treatment based on active and passive joint repositioning, stabilization exercises, stretching of the periarticular shoulder muscles and postural reeducation. B. The previously described protocolized treatment, with the addition of dry needling applied to active MTrPs with the purpose of isolating the efficacy of dry needling in treatment.</p> <p>Discussion</p> <p>This study aims to provide a new vision of shoulder pain, from the perspective of MPS. This syndrome can, by itself, account for shoulder pain and dysfunction, although it can coexist with real conditions involving the tendons.</p> <p>Trail Registration</p> <p>ISRCTN Number: 30907460</p

Dementia and Depression with Ischemic Heart Disease: A Population-Based Longitudinal Study Comparing Interventional Approaches to Medical Management

BACKGROUND: We compared the proportion of ischemic heart disease (IHD) patients newly diagnosed with dementia and depression across three treatment groups: percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical management alone (IHD-medical). METHODS AND FINDINGS: De-identified, individual-level administrative records of health service use for the population of Manitoba, Canada (approximately 1.1 million) were examined. From April 1, 1993 to March 31, 1998, patients were identified with a diagnosis of IHD (ICD-9-CM codes). Index events of CABG or PCI were identified from April 1, 1998 to March 31, 2003. Outcomes were depression or dementia after the index event. Patients were followed forward to March 31, 2006 or until censored. Proportional hazards regression analysis was undertaken. Independent variables examined were age, sex, diabetes, hypertension and income quintile, medical management alone for IHD, or intervention by PCI or CABG. Age, sex, diabetes, and presence of hypertension were all strongly associated with the diagnosis of depression and dementia. There was no association with income quintile. Dementia was less frequent with PCI compared to medical management; (HR = 0.65; p = 0.017). CABG did not provide the same protective effect compared to medical management (HR = 0.90; p = 0.372). New diagnosis depression was more frequent with interventional approaches: PCI (n = 626; hazard ratio = 1.25; p = 0.028) and CABG (n = 1124, HR = 1.32; p = 0.0001) than non-interventional patients (n = 34,508). Subsequent CABG was nearly 16-fold higher (p<0.0001) and subsequent PCI was 22-fold higher (p<0.0001) for PCI-managed than CABG-managed patients. CONCLUSIONS: Patients managed with PCI had the lowest likelihood of dementia-only 65% of the risk for medical management alone. Both interventional approaches were associated with a higher risk of new diagnosed depression compared to medical management. Long-term myocardial revascularization was superior with CABG. These findings suggest that PCI may confer a long-term protective effect from dementia. The mechanism(s) of dementia protection requires elucidation

Traditional knowledge and cultural importance of Borassus aethiopum Mart. in Benin: interacting effects of socio-demographic attributes and multi-scale abundance

ResearchBackground: Eliciting factors affecting distribution of traditional knowledge (TK) and cultural importance of plant resources is central in ethnobiology. Socio-demographic attributes and ecological apparency hypothesis (EAH) have been widely documented as drivers of TK distribution, but their synergistic effect is poorly documented. Here, we focused on Borassus aethiopum, a socio-economic important agroforestry palm in Africa, analyzing relationships between the number of use-reports and cultural importance on one hand, and informant socio-demographic attributes (age category and gender) on the other hand, considering the EAH at multi-scale contexts. Our hypothesis is that effects of socio-demographic attributes on use-reports and cultural importance are shaped by both local (village level) and regional (chorological region level) apparency of study species. We expected so because distribution of knowledge on a resource in a community correlates to the versatility in the resource utilization but also connections among communities within a region. Methods: Nine hundred ninety-two face-to-face individual semi-structured interviews were conducted in six villages of low versus high local abundance of B. aethiopum spanning three chorological regions (humid, sub-humid and semiarid) also underlying a gradient of increasing distribution and abundance of B. aethiopum. Number of use-reports and score of importance of uses of B. aethiopum were recorded in six use-categories including medicine, food, handcraft, construction, firewood, and ceremonies and rituals. Data were analyzed using Poisson and ordered logistic modelsinfo:eu-repo/semantics/publishedVersio

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic