Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for a radial SNARE super-complex mediating neurotransmitter release at the Drosophila neuromuscular junction

Summary The SNARE proteins VAMP/synaptobrevin, SNAP-25 and syntaxin are core components of the apparatus that mediates neurotransmitter release. They form a heterotrimeric complex, and an undetermined number of SNARE complexes assemble to form a super-complex. Here, we present a radial model of this nanomachine. Experiments performed with botulinum neurotoxins led to the identification of one arginine residue in SNAP-25 and one aspartate residue in syntaxin (R206 and D253 in Drosophila melanogaster). These residues are highly conserved and predicted to play a major role in the protein–protein interactions between SNARE complexes by forming an ionic couple. Accordingly, we generated transgenic Drosophila lines expressing SNAREs mutated in these residues and performed an electrophysiological analysis of their neuromuscular junctions. Our results indicate that SNAP-25-R206 and syntaxin-D253 play a major role in neuroexocytosis and support a radial assembly of several SNARE complexes interacting via the ionic couple formed by these two residues.
Distribution of adhesion molecules on HeLa cells, platelets and endothelium in an in vitro model mimicking the early phase of metastasis

The aim of the present study was to obtain information about the distribution of various adhesion molecules within and on the surface of HeLa cells, platelets and endothelial cells in an in vitro model mimicking the early phase of metastasis. Suspensions of HeLa cells and human platelets, added to a medium of cultured human umbilical‐vein endothelial cells, were stimulated by the addition of thrombin. Hirudin was added before thrombin in some experiments, and in other experiments the endothelium was pretreated with 0.5 mM acetylsalicylic acid (ASA). The distribution of platelet‐endothelial cell adhesion molecule (PECAM), P‐selectin, von Willebrand factor (vWf), fibrinogen (FG) and thrombospondin (TSP) was investigated on fixed material from the three experimental settings by using an immunogold electron‐microscopic technique on frozen thin sections. Cells that had not been exposed to thrombin or any other type of stimulation were used as controls. PECAM was the only adhesion molecule detected on HeLa cells. It outlined the membrane on tumour cells that were not adherent to platelets in both basic and hirudin experiments. However, tumour cells in close proximity to activated platelets were unlabelled. In contrast, PECAM was detected on both platelets and endothelium in all experimental settings and in controls. P‐selectin was only demonstrable on platelets in basic experiments. vWf was found both in endothelium and in platelets in controls and in all experimental settings. FG and TSP were found on platelets only, in a manner similar to that seen with vWf. Thus, among the adhesive factors examined in our experimental model, PECAM is the only one demonstrated on HeLa cells. This suggests that PECAM on tumour cells may play a role as adhesion molecule in the early stage of metastasis. P‐selectin, vWf, FG and TSP were also consistently expressed. Therefore, these factors may contribute to the adhesive reactions involved in early metastasis.
Bmc Musculoskeletal Disorders Effectiveness of Early Part-time Sick Leave in Musculoskeletal Disorders

Background: The importance of staying active instead of bed rest has been acknowledged in the management of musculoskeletal disorders (MSDs). This emphasizes the potential benefits of adjusting work to fit the employee's remaining work ability. Despite part-time sick leave being an official option in many countries, its effectiveness has not been studied yet. We have designed a randomized controlled study to assess the health effects of early part-time sick leave compared to conventional full-day sick leave. Our hypothesis is that if work time is temporarily reduced and work load adjusted at the early stages of disability, employees with MSDs will have less disability days and faster return to regular work duties than employees on a conventional sick leave.
Scope and impact of financial conflicts of interest in biomedical research: a systematic review.

CONTEXT Despite increasing awareness about the potential impact of financial conflicts of interest on biomedical research, no comprehensive synthesis of the body of evidence relating to financial conflicts of interest has been performed. OBJECTIVE To review original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research. DATA SOURCES Studies were identified by searching MEDLINE (January 1980-October 2002), the Web of Science citation database, references of articles, letters, commentaries, editorials, and books and by contacting experts. STUDY SELECTION All English-language studies containing original, quantitative data on financial relationships among industry, scientific investigators, and academic institutions were included. A total of 1664 citations were screened, 144 potentially eligible full articles were retrieved, and 37 studies met our inclusion criteria. DATA EXTRACTION One investigator (J.E.B.) extracted data from each of the 37 studies. The main outcomes were the prevalence of specific types of industry relationships, the relation between industry sponsorship and study outcome or investigator behavior, and the process for disclosure, review, and management of financial conflicts of interest. DATA SYNTHESIS Approximately one fourth of investigators have industry affiliations, and roughly two thirds of academic institutions hold equity in start-ups that sponsor research performed at the same institutions. Eight articles, which together evaluated 1140 original studies, assessed the relation between industry sponsorship and outcome in original research. Aggregating the results of these articles showed a statistically significant association between industry sponsorship and pro-industry conclusions (pooled Mantel-Haenszel odds ratio, 3.60; 95% confidence interval, 2.63-4.91). Industry sponsorship was also associated with restrictions on publication and data sharing. The approach to managing financial conflicts varied substantially across academic institutions and peer-reviewed journals. CONCLUSIONS Financial relationships among industry, scientific investigators, and academic institutions are widespread. Conflicts of interest arising from these ties can influence biomedical research in important ways.
Rapid detection of human group C rotaviruses by reverse passive hemagglutination and latex agglutination tests using monoclonal antibodies

Reverse passive hemagglutination (RPHA) tests and a latex agglutination test with monoclonal antibodies (MAbs) were developed for the rapid detection of noncultivatable human group C rotaviruses. For RPHA tests, two MAbs, MAb 5A12 recognizing the outer capsid and MAb 13A3 recognizing the inner capsid, were separately used for the coating of sheep erythrocytes (SRBCs). Forty-six fecal samples were examined to confirm the practicality of the tests. As a result, there was concordance between the RPHA test with SRBCs coated with MAb 5A12 and polyacrylamide gel electrophoresis of viral RNA (RNA-PAGE) in 44 (95.6%) of 46 samples, while the diagnoses by the RPHA test with SRBCs coated with MAb 13A3 were in complete agreement with those by RNA-PAGE. Furthermore, a latex agglutination test with MAb 13A3 was also developed, and this test was fast enough and sensitive enough to successfully detect the viruses from most fecal samples within 2 min. The present procedures would be useful for the diagnosis of human group C rotavirus infections in clinical laboratories which are not well equipped.
Biomaterials for the central nervous system

Biomaterials are widely used to help treat neurological disorders and/or improve functional recovery in the central nervous system (CNS). This article reviews the application of biomaterials in (i) shunting systems for hydrocephalus, (ii) cortical neural prosthetics, (iii) drug delivery in the CNS, (iv) hydrogel scaffolds for CNS repair, and (v) neural stem cell encapsulation for neurotrauma. The biological and material requirements for the biomaterials in these applications are discussed. The difficulties that the biomaterials might face in each application and the possible solutions are also reviewed in this article.
The Mysterious 14C Decline

Fundamental to the field of radiocarbon dating is not only the establishment of the temporal record of the calendar age-radiocarbon age offsets but also the development of an understanding of their cause. Although part of the decline in the magnitude of this offset over the past 40,000 can be explained by a drop in 14C production rate associated with a progressive increase in the strength of the Earth's magnetic shielding, it is clear that changes in the distribution of 14C among the Earth's active carbon reservoirs are also required. In particular, the steep 15% decline in the 14C to C ratio in atmospheric CO2 and surface ocean ΣCO2, which occurred in a 3 kyr-duration interval marking the onset of the last deglaciation, appears to require that a very large amount (at least 5000 gigatons) of 14C-deficient carbon was transferred to or within the ocean during this time interval. As no chemical or stable isotope anomaly associated with this injection appears in either the marine sediment or polar ice records, this injection must involve a transfer within the ocean (i.e. a mixing of 2 ocean reservoirs, one depleted in 14C and the other enriched in 14C). Although evidence for the existence of a salt-stabilized glacial-age abyssal ocean reservoir exists, a search based on benthic-planktic age differences and 13C measurements appears to place a limit on its size well below that required to account for the steep 14C decline.
Lactobacillus paracasei CBA L74 Metabolic Products and Fermented Milk for Infant Formula Have Anti-Inflammatory Activity on Dendritic Cells In Vitro and Protective Effects against Colitis and an Enteric Pathogen In Vivo

The rapid expansion of commercially available fermented food products raises important safety issues particularly when infant food is concerned. In many cases, the activity of the microorganisms used for fermentation as well as what will be the immunological outcome of fermented food intake is not known. In this manuscript we used complex in vitro, ex-vivo and in vivo systems to study the immunomodulatory properties of probiotic-fermented products (culture supernatant and fermented milk without live bacteria to be used in infant formula). We found in vitro and ex-vivo that fermented products of Lactobacillus paracasei CBA L74 act via the inhibition of proinflammatory cytokine release leaving anti-inflammatory cytokines either unaffected or even increased in response to Salmonella typhimurium. These activities are not dependent on the inactivated bacteria but to metabolic products released during the fermentation process. We also show that our in vitro systems are predictive of an in vivo efficacy by the fermented products. Indeed CBA L74 fermented products (both culture medium and fermented milk) could protect against colitis and against an enteric pathogen infection (Salmonella typhimurium). Hence we found that fermented products can act via the inhibition of immune cell inflammation and can protect the host from pathobionts and enteric pathogens. These results open new perspectives in infant nutrition and suggest that L. paracasei CBA L74 fermented formula can provide immune benefits to formula-fed infants, without carrying live bacteria that may be potentially dangerous to an immature infant immune system.
Adenosine A1 receptors modulate high voltage‐activated Ca2+ currents and motor pattern generation in the Xenopus embryo

1 Adenosine causes voltage‐ and non‐voltage‐dependent inhibition of high voltage‐activated (HVA) Ca2+ currents in Xenopus laevis embryo spinal neurons. 2 As this inhibition can be blocked by 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) and mimicked by N6‐cyclopentyladenosine (CPA) it appears to be mediated by A1 receptors. Agents active at A2 receptors either were without effect or could be blocked by DPCPX. AMP had no agonist action on these receptors. 3 By using ω‐conotoxin GVIA we found that adenosine inhibited an N‐type Ca2+ current as well as a further unidentified HVA current that was insensitive to dihydropyridines, ω‐agatoxin TK and ω‐conotoxin MVIIC. Both types of current were subject to voltage‐ and non‐voltage‐dependent inhibition. 4 We used CPA and DPCPX to test whether A1 receptors regulated spinal motor pattern generation in spinalized Xenopus embryos. DPCPX caused a near doubling of, while CPA greatly shortened, the length of swimming episodes. In addition, DPCPX slowed, while CPA greatly speeded up, the rate of run‐down of motor activity. 5 Our results demonstrate a novel action of A1 receptors in modulating spinal motor activity. Furthermore they confirm that adenosine is produced continually throughout swimming episodes and acts to cause the eventual termination of activity.
Phenotypic selection on morphology at independence in the Chinstrap penguin Pygoscelis antarctica

Every year, shortly after the emancipation of chicks at our study colony (Deception Island, South Shetlands), hundreds of carcasses of presumably starved Chinstrap penguin Pygoscelis antarctica chicks are washed on the shore. In 1997 we measured the flippers of fresh carcasses and compared their lengths with those of live chicks about to become independent. There was a highly significant difference of 6.5 mm between both distributions, which suggests strong directional phenotypic selection on skeletal size operating through its association with body reserves at independence. Given that heritabilities of flipper length and body weight measured on 36 families are 0.73(± 0.32) and 0.075(± 0.081), and that both characters show a genetic correlation of 0.44(± 0.14), we can expect an evolutionary response to this selection episode. Assuming that the target of selection is weight at emancipation (heavier chicks carry proportionally larger reserves), and that flipper length changes as a consequence of its genetic correlation with weight, we can predict a response of 1.32–2.87 mm or 0.23–0.51 standard deviation units for flipper length. This substantial evolutionary response may be countered by other selective pressures affecting other life stages of these birds. Selection on reserve storage capacity at independence may affect morphological traits also in other species.
On whitespace and stability in mixed-size placement and physical synthesis

In the context of physical synthesis, large-scale standard-cell placement algorithms must facilitate incremental changes to layout, both local and global. In particular, flexible gate sizing, net buffering and detail placement require a certain amount of unused space in every region of the die. The need for "local" whitespace is further emphasized by temperature and power-density limits. Another requirement, the stability of placement results from run to run, is important to the convergence of physical synthesis loops. Indeed, logic resynthesis targetting local congestion in a given placement or particular critical paths may be irrelevant for another placement produced by the same or a different layout tool. In this work we offer solutions to the above problems. We show how to tie the results of a placer to a previously existing placement, and yet leave room for optimization. In our experiments this technique produces placements with similar congestion maps. We also show how to trade-off wirelength for routability by manipulating whitespace. Empirically, our techniques improve circuit delay of sparse layouts in conjunction with physical synthesis. In the context of earlier proposed techniques for mixed-size placement, we tune a state-of-the-art recursive bisection placer to better handle regular netlists that offer a convenient way to represent memories, data paths and random-logic IP blocks. These modifications and better whitespace distribution improve results on recent mixed-size placement benchmarks.
Localization of sequences within the latency-related gene of bovine herpesvirus 1 that inhibit mammalian cell growth

The latency-related (LR) RNA of bovine herpes virus 1 (BHV-1) is abundantly expressed in sensory neurons of latently infected cattle. Wild-type expression of LR gene products is required for the latency-reactivation cycle. LR gene products inhibit apoptosis, bICP0 expression, and mammalian cell growth. The cell growth inhibitory function of the LR gene maps to a 463-bp XbaI-PstI fragment. Introduction of stop codons into the XbaI-PstI fragment had no effect on inhibiting growth. Expression of a LR strand-specific transcript correlates with growth inhibition in bovine fibroblasts and mouse neuroblastoma cells.
Mechanisms of pulmonary fibrosis.

Tissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the recruitment, activation, apoptosis, and eventual clearance of key effector cells. In this review, we propose the concept of pulmonary fibrosis as a dysregulated repair process that is perpetually "turned on" even though classical inflammatory pathways may be dampened or "switched off. " Significant regional heterogeneity, with varied histopathological patterns of inflammation and fibrosis, has been observed in individual patients with idiopathic pulmonary fibrosis. We discuss environmental factors and host response factors, such as genetic susceptibility and age, that may influence these varied manifestations. Better understanding of the mechanisms of lung repair, which include alveolar reepithelialization, myofibroblast differentiation/activation, and apoptosis, should offer more effective therapeutic options for progressive pulmonary fibrosis.
Reservoir evaluation tests on RRGE 1 and RRGE 2, Raft River Geothermal Project, Idaho

Results of the production and interference tests conducted on the geothermal wells RRGE 1 and RRGE 2 in Raft River Valley, Idaho during September--November, 1975 are presented. In all, three tests were conducted, two of them being short-duration production tests and one, a long duration interference test. In addition to providing estimates on the permeability and storage parameters of the geothermal reservoir, the tests also indicated the possible existence of barrier boundaries. The data collected during the tests also indicated that the reservoir pressure varies systematically in response to the changes in the Earth's gravitational field caused by the passage of the sun and the moon. Overall, the results of the tests indicate that the geothermal reservoir in southern Raft River valley is fairly extensive and significantly permeable and merits further exploration.
Enhanced acidification of global coral reefs driven by regional biogeochemical feedbacks

Physical uptake of anthropogenic CO2 is the dominant driver of ocean acidification (OA) in the open ocean. Due to expected decreases in calcification and increased dissolution of CaCO3 framework, coral reefs are thought to be highly susceptible to OA. However, biogeochemical processes can influence the pCO2 and pH of coastal ecosystems on diel and seasonal time scales, potentially modifying the long‐term effects of increasing atmospheric CO2. By compiling data from the literature and removing the effects of short‐term variability, we show that the average pCO2 of coral reefs throughout the globe has increased ~3.5‐fold faster than in the open ocean over the past 20 years. This rapid increase in pCO2 has the potential to enhance the acidification and predicted effects of OA on coral reef ecosystems. A simple model demonstrates that potential drivers of elevated pCO2 include additional anthropogenic disturbances beyond increasing global atmospheric CO2 such as enhanced nutrient and organic matter inputs.
THE EFFECT OF PHAGOCYTOSIS AND SPREADING ON MACROPHAGE SURFACE RECEPTORS FOR CONCANAVALIN A

Phagocytosis involves at tachement of a particle to the cell surface (12), followed by engulfment of the particle within a membrane-bounded vacuole (7, 20). It can be assumed that the plasma membrane is reduced by the amount interiorized. Much morphological evidence supports this assumption; however, there is little direct evidence on the fate of membrane surface markers during phagocytosis. Tsan and Berlin (19) provided intriguing evidence that several membrane transport carriers are not internalized during phagocytosis. They suggested that during membrane interiorization, transport and phagocytic sites go their separate ways, an idea consistent with Singer's fluid mosaic
Coping strategies and adherence to treatment in patients with type 2 diabetes mellitus.

INTRODUCTION Diverse psychosocial and cultural factors are related to adherence to treatment of type 2 Diabetes mellitus (DM2) such as social support, coping styles and the cost of medical attention. OBJECTIVE To study the influence of diverse psychosocial factors on adherence to treatment in patients with DM2. MATERIAL AND METHODS In a cross sectional design we studied adherence to diet and medication, and its relationship with CS for diabetes, belief in conventional medicine, social support, and the perception of the burden of treatment cost on family finances. RESULTS We included 210 patients a mean age of 56.3 years, 9.4 years since diagnosis. Male DM patients had better adherence to medication (p<0.016) and social support (p<0.004), and higher rates for supportant CS (31.8 vs. 29.0; p<0.009). Adherence to diet was associated with belief in conventional medicine (p<0.035) and marginally related to fatalistic CS (p<0.05). After testing social security coverage as dummy variable, a marginal association was found (p<0.15). Adherence to medication was associated with supportant CS (p<0.02) and marginally with avoidant CS (p<0.05). CONCLUSIONS Supportant CS was more frequent in men. Belief in conventional medicine, and supportant CS were associated with adherence to treatment. These factors should be considered for a more rational approach for the management of disease.
An Evaluation of Sorting as a Supercomputer Benchmark (preliminary Version)

We propose that sorting be considered an important benchmark for both scientific and commercial applications of supercomputers. The purpose of a supercomputer benchmark is to exercise various system components in an effort to measure important performance characteristics. In the past numerous benchmarks have been defined in an effort to measure the performance issues associated with numeric computing. These benchmarks stressed arithmetic operations (in particular, floating-point arithmetic). In recent years supercomputers manufactures have started to look closer at non-numeric processing tasks, such as databases and information retrieval. Tile ability to operate on large amounts of non-numeric data will be crucial in tile future. This paper discusses the appropriateness of sorting as a benchmark for non-numeric computing tasks. The paper describes previous work in this area and defines a set of architecture independent sorting benchmarks. 1School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213. This research was sponsored in part by the Avionics Laboratory, Wright Research and Development Center, Aeronautical Systems Division (AFSC), U.S. Air Force, Wright-Patterson AFB, Ohio 45433-6543 under Contract F3361590-C-1465, ARPA Order No. 7597 2NASA Ames Research Center, Moffett Field, CA 94035. The author is an employee of Computer Sciences Corp. Work funded by NASA Contract NAS 2-12961. 3Thinking Machines Corporation, 245 First Street, Cambridge, MA 02143. An Evaluation of Sorting as a Supercomputer Benchmark (preliminary version)