Miracle-dz/UniFAR-FTUs huggingface dataset:
Participation and performance trends in ultracycling

Background Participation and performance trends have been investigated in ultramarathons and ultratriathlons but not in ultracycling. The aim of the present study was to investigate (1) participation and performance trends in ultraendurance cyclists, (2) changes in cycling speed over the years, and (3) the age of the fastest male and female ultraendurance cyclists. Methods Participation and performance trends in the 5000 km Race Across America (RAAM) and in two RAAM-qualifier races – the 818 km Furnace Creek 508 in the United States and the 715 km Swiss Cycling Marathon in Europe – were investigated using linear regression analyses and analyses of variance. Results On average, ~41% of participants did not finish either the RAAM or the Furnace Creek 508, whereas ~26% did not finish the Swiss Cycling Marathon. Female finishers accounted for ~11% in both the RAAM and the Furnace Creek 508 but only ~3% in the Swiss Cycling Marathon. The mean cycling speed of all finishers remained unchanged during the studied periods. The winner’s average speed was faster for men than for women in the RAAM (22.6 ± 1.1 km · h−1 versus 18.4 ± 1.7 km · h−1, respectively; average speed difference between male and female winners, 25.0% ± 11.9%), the Swiss Cycling Marathon (30.8 ± 0.8 km · h−1 versus 24.4 ± 1.9 km · h−1, respectively; average speed difference between male and female winners, 27.8% ± 9.4%), and the Furnace Creek 508 (27.4 ± 1.6 km · h−1 versus 23.4 ± 3.0 km · h−1, respectively; average speed difference between male and female winners, 18.4% ± 13.9%). In both the Furnace Creek 508 and the Swiss Cycling Marathon, ~46% of the finishers were aged between 35 and 49 years. The mean age of winners, both male and female, across the years in the Furnace Creek 508 and in the Swiss Cycling Marathon was 37 ± 10 years. Conclusion These findings in ultracycling races showed that (1) ~26%–40% of starters were unable to finish, (2) the percentage of female finishers was ~3%–11%, (3) the gender difference in performance was ~18%–28%, and (4) ~46% of the successful finishers were master athletes. Future studies need to investigate the reasons for the low female participation and focus on the age-related performance decline in other ultraendurance events in order to confirm that master athletes are predisposed to ultraendurance performances.
Regulation of Msx genes by a Bmp gradient is essential for neural crest specification

There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest genetic cascade. In order to study the hierarchical relationship between msx1 and snail/slug we performed several rescue experiments using dominant negatives for these genes. The rescuing activity by snail and slug on neural crest development of the msx1 dominant negative, together with the inability of msx1 to rescue the dominant negatives of slug and snail strongly argue that msx1 is upstream of snail and slug in the genetic cascade that specifies the neural crest in the ectoderm. We propose a model where a gradient of Bmp activity specifies the expression of Msx genes in the neural folds, and that this expression is essential for the early specification of the neural crest.
Opposite Role of Tumor Necrosis Factor Receptors in Dextran Sulfate Sodium-Induced Colitis in Mice

Tumor necrosis factor-α (TNF-α) is a key factor for the pathogenesis of inflammatory bowel diseases (IBD), whose function is known to be mediated by TNF receptor 1 (TNFR1) or 2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, acute colitis was induced by dextran sulfate sodium (DSS) instillation in TNFR1 or 2−/− mice. TNFR1 ablation led to exacerbation of signs of colitis, including more weight loss, increased mortality, colon shortening and oedema, severe intestinal damage, and higher levels of myeloperoxidase compared to wild-type counterparts. While, TNFR2 deficiency had opposite effects. This discrepancy was reflected by alteration of proinflammatory cytokine and chemokine production in the colons. Importantly, TNFR1 ablation rendered enhanced apoptosis of colonic epithelial cells and TNFR2 deficiency conferred pro-apoptotic effects of lamina propria (LP)-immune cells, as shown by the decreased ratio of Bcl-2/Bax and enhanced nuclear factor (NF)-κB activity.
Vascular Endothelial Growth Factor Blockade Prevents the Beneficial Effects of &bgr;-Blocker Therapy on Cardiac Function, Angiogenesis, and Remodeling in Heart Failure

Background—Impaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, &bgr;-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart. Methods and Results—Eight weeks from surgically induced myocardial infarction, heart failure rats were randomized to receive bisoprolol (B) or vehicle. At the end of a 10-week treatment period, echocardiography revealed reduced cardiac diameters and improved cardiac function in B-treated compared with vehicle-treated rats. Moreover, B treatment was associated with increased cardiac angiogenesis and in vivo coronary perfusion and reduced cardiac fibrosis. Importantly, 2 weeks after B treatment was started, increased cardiac VEGF expression and Akt and endothelial NO synthase activation were observed by comparing B-treated with drug-untreated failing hearts. To test whether the proangiogenic effects of B act via activation of VEGF pathway, rats were intravenously injected with adenoviral vector encoding a decoy VEGF receptor (Ad-Flk) or a control adenovirus (Ad-C), at the start of the treatment with B. After 10 weeks, histological analysis revealed reduced capillary and coronary perfusion in B-treated plus Ad-Flk rats compared with B-treated plus Ad-C rats. Moreover, VEGF inhibition counteracted the positive effects of B on cardiac function and remodeling. Conclusions—&bgr;-Blockade promotes cardiac angiogenesis in heart failure via activation of VEGF signaling pathway. &bgr;-Blocker–induced enhancement of cardiac angiogenesis is essential for the favorable effects of this therapy on cardiac function and remodeling.
Molecular Characteristics and Interactions of the Intermediate Filament Protein Synemin

Synemin is a cytoskeletal protein originally identified as an intermediate filament (IF)-associated protein because of its colocalization and copurification with the IF proteins desmin and vimentin in muscle cells. Our sequencing studies have shown that synemin is an unusually large member (1,604 residues, 182,187 Da) of the IF protein superfamily, with the majority of the molecule consisting of a long C-terminal tail domain. Molecular interaction studies demonstrate that purified synemin interacts with desmin, the major IF protein in mature muscle cells, and with α-actinin, an integral myofibrillar Z-line protein. Furthermore, expressed synemin rod and tail domains interact, respectively, with desmin and α-actinin. Analysis of endogenous protein expression in SW13 clonal lines reveals that synemin is coexpressed and colocalized with vimentin IFs in SW13.C1 vim+ cells but is absent in SW13.C2 vim− cells. Transfection studies indicate that synemin requires the presence of another IF protein, such as vimentin, in order to assemble into IFs. Taken in toto, our results suggest synemin functions as a component of heteropolymeric IFs and plays an important cytoskeletal cross-linking role by linking these IFs to other components of the cytoskeleton. Synemin in striated muscle cells may enable these heterofilaments to help link Z-lines of adjacent myofibrils and, thereby, play an important role in cytoskeletal integrity.
What Do Magnetic Resonance–Based Measurements of Pi→ATP Flux Tell Us About Skeletal Muscle Metabolism?

Magnetic resonance spectroscopy (MRS) methods offer a potentially valuable window into cellular metabolism. Measurement of flux between inorganic phosphate (Pi) and ATP using 31P MRS magnetization transfer has been used in resting muscle to assess what is claimed to be mitochondrial ATP synthesis and has been particularly popular in the study of insulin effects and insulin resistance. However, the measured Pi→ATP flux in resting skeletal muscle is far higher than the true rate of oxidative ATP synthesis, being dominated by a glycolytically mediated Pi↔ATP exchange reaction that is unrelated to mitochondrial function. Furthermore, even if measured accurately, the ATP production rate in resting muscle has no simple relationship to mitochondrial capacity as measured either ex vivo or in vivo. We summarize the published measurements of Pi→ATP flux, concentrating on work relevant to diabetes and insulin, relate it to current understanding of the physiology of mitochondrial ATP synthesis and glycolytic Pi↔ATP exchange, and discuss some possible implications of recently reported correlations between Pi→ATP flux and other physiological measures.
A Generalized Hidden Markov Model for the Recognition of Human Genes in DNA

We present a statistical model of genes in DNA. A Generalized Hidden Markov Model (GHMM) provides the framework for describing the grammar of a legal parse of a DNA sequence (Stormo & Haussler 1994). Probabilities are assigned to transitions between states in the GHMM and to the generation of each nucleotide base given a particular state. Machine learning techniques are applied to optimize these probabilities using a standardized training set. Given a new candidate sequence, the best parse is deduced from the model using a dynamic programming algorithm to identify the path through the model with maximum probability. The GHMM is flexible and modular, so new sensors and additional states can be inserted easily. In addition, it provides simple solutions for integrating cardinality constraints, reading frame constraints, "indels", and homology searching. The description and results of an implementation of such a gene-finding model, called Genie, is presented. The exon sensor is a codon frequency model conditioned on windowed nucleotide frequency and the preceding codon. Two neural networks are used, as in (Brunak, Engelbrecht, & Knudsen 1991), for splice site prediction. We show that this simple model performs quite well. For a cross-validated standard test set of 304 genes [ftp:@www-hgc.lbl. gov/pub/genesets] in human DNA, our gene-finding system identified up to 85% of protein-coding bases correctly with a specificity of 80%. 58% of exons were exactly identified with a specificity of 51%. Genie is shown to perform favorably compared with several other gene-finding systems.
Psychotherapy and the Brain: The Dimensional Systems Model and Clinical Biopsychology

The dimensional systems model explains cortical processing on the basis of cortical column interactions, leading to a clinical biopsychological model which involves brain-based psychotherapy integration. The current paper provides a detailed explanation of the interface between these models in relation to psychological treatment. A specific discussion of certain psychotherapy treatment approaches is provided with suggestions on what cortical areas are being impacted. In reference to negative emotional memories there are specific, theoretically based suggestions on how to most effectively neutralize the continuing impact on a client’s current psychological functioning. Loss-related depression is explained on the basis of opponent-process theory as related to the brain model. It is hoped that this paper can generate interest among neuroscientists and clinicians to fully evaluate the value of these theoretical models.
Sponsorship Matters: Assessing Business Participation in Government- and Industry-Sponsored Voluntary Environmental Programs

Stakeholders who seek to reward or punish businesses for their environmental programs often cannot observe these organizations’ internal policies and operations. To address these informational problems, and signal their beyond-compliance environmental commitments, some businesses are participating in voluntary environmental programs (VEPs). This article examines whether business managers associate the brand value of VEPs – due to their differing program sponsors – with the perceived preferences of their critical stakeholders. Drawing on a novel data set of nearly 300 organizations, we assess business’ participation in 19 government- and industry-sponsored VEPs. We find that managers who recognize the importance of stakeholder influences on their business’ environmental practices are more likely to participate in a VEP but that pressures from different stakeholders are associated with variations in organizations’ participation in either government- or industry-sponsored VEPs.
On Achieving the "Best of Both Worlds" in Secure Multiparty Computation

Two settings are traditionally considered for secure multiparty computation, depending on whether or not a majority of the parties are assumed to be honest. Existing protocols that assume an honest majority provide “full security” (and, in particular, guarantee output delivery and fairness) when this assumption holds, but are completely insecure if this assumption is violated. On the other hand, known protocols tolerating an arbitrary number of corruptions do not guarantee fairness or output delivery even if only a single party is dishonest. It is natural to wonder whether it is possible to achieve the “best of both worlds”: namely, a single protocol that simultaneously achieves the best possible security in both the above settings. Here, we rule out this possibility (at least for general functionalities) and show some positive results regarding what can be achieved.
CSL311, a novel, potent, therapeutic monoclonal antibody for the treatment of diseases mediated by the common β chain of the IL-3, GM-CSF and IL-5 receptors

ABSTRACT The β common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of haematopoietic cells via a receptor complex incorporating cytokine-specific α and shared β common (βc, CD131) receptor. Evidence from animal models and recent clinical trials demonstrate that these cytokines are critical mediators of the pathogenesis of inflammatory airway disease such as asthma. However, no therapeutic agents, other than steroids, that specifically and effectively target inflammation mediated by all 3 of these cytokines exist. We employed phage display technology to identify and optimize a novel, human monoclonal antibody (CSL311) that binds to a unique epitope that is specific to the cytokine-binding site of the human βc receptor. The binding epitope of CSL311 on the βc receptor was defined by X-ray crystallography and site-directed mutagenesis. CSL311 has picomolar binding affinity for the human βc receptor, and at therapeutic concentrations is a highly potent antagonist of the combined activities of IL-3, GM-CSF and IL-5 on primary eosinophil survival in vitro. Importantly, CSL311 inhibited the survival of inflammatory cells present in induced sputum from human allergic asthmatic subjects undergoing allergen bronchoprovocation. Due to its high potency and ability to simultaneously suppress the activity of all 3 β common cytokines, CSL311 may provide a new strategy for the treatment of chronic inflammatory diseases where the human βc receptor is central to pathogenesis. The coordinates for the βc/CSL311 Fab complex structure have been deposited with the RCSB Protein Data Bank (PDB 5DWU).
Pirfenidone inhibits transforming growth factor-β1-induced fibrogenesis by blocking nuclear translocation of Smads in human retinal pigment epithelial cell line ARPE-19

Purpose Transforming growth factor-β (TGF-β) plays a key role in transforming retinal pigment epithelial (RPE) cells into mesenchymal fibroblastic cells, which are implicated in proliferative vitreoretinopathy. Herein, we tested the effect of pirfenidone, a novel antifibrotic agent, on TGF-β1-mediated fibrogenesis in the human RPE cell line ARPE-19. Methods The effect of pirfenidone on the TGF-β1-induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. Fibronectin and collagen production was measured with enzyme-linked immunosorbent assay, and cell migration activity was investigated using a scratch assay. Immunoblot analyses of cofilin, sma and mad protein (smad) 2/3, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and extracellular signal-related kinase expression were conducted to elucidate the cell signaling networks that contribute to the antifibrotic effect of pirfenidone. Results Treatment with TGF-β1 induced typical phenotypic changes such as formation of stress fiber running parallel to the long axis of cells and enhanced migration and production of extracellular matrix components such as collagen type I and fibronectin. This fibroblast-like phenotype induced by TGF-β1 was significantly inhibited by pretreatment with pirfenidone in a dose-dependent manner. We also elucidated the TGF-β signaling pathways as the target of the inhibitory effect of pirfenidone. Pirfenidone inhibited TGF-β signaling by preventing nuclear accumulation of active Smad2/3 complexes rather than phosphorylation of Smad2/3. Conclusions These results collectively provide a rational background for future evaluation of pirfenidone as a potential antifibrotic agent for treating proliferative vitreoretinopathy and other fibrotic retinal disorders.
Dynamic control of motion estimation search parameters for low complex H.264 video coding

This paper presents a novel technique to reduce the motion estimation (ME) complexity in H.264/AVC video coding. A low complexity context-aware controller is added to a basic search engine; at coding time the controller extracts from the search engine partial results information on the input signal statistics, using them to dynamically configure the ME search parameters, such as number of reference frames, valid block modes and search area. Unnecessary computations and memory accesses can be avoided, decreasing ME complexity while keeping unaltered coding efficiency for a wide range of applications: bit-rates from tens of kbits/s to tens of Mbits/s and video formats from QCIF to CCIR. The context-aware control can be used with any ME search engine and in the paper is successfully applied to full search and fast ME, as EPZS and UMHS, in the JM10 software model of H264/AVC
Regulation of nerve growth factor receptor gene expression in sympathetic neurons during development

We used quantitative reverse transcription (RT)/PCR to study the regulation of p75 mRNA and trkA mRNA expression in the developing sympathetic neurons of the mouse superior cervical sympathetic ganglion (SCG) in vivo and in vitro. At E13, the SCG contains proliferating cells that express many features of differentiated neurons. These immature neurons survived in culture without NGF, and NGF did not induce c-fos expression. Low levels of p75 and trkA mRNAs were expressed at this stage in vivo. There was no significant increase in the level of either trkA mRNA or p75 mRNA in E13 control cultures up to 72 h in vitro, and neither NGF nor depolarizing levels of K+ ions (40 mM KC1) affected the expression of trkA mRNA. In E14 cultures, NGF induced c-fos expression in 10-15% of the neurons and enhanced the survival of a similar percentage of neurons. The proportion of neurons responding to NGF increased with age, reaching 90% in E18 cultures. The in vivo level of trkA mRNA increased markedly from E14 onward, but in contrast to sensory neurons (in which p75 and trkA mRNA levels increase in parallel), the level of trkA mRNA initially increased far more rapidly than that of p75 mRNA. After E17, the level of p75 mRNA increased rapidly and approached that of trkA mRNA postnatally, but at no stage did this exceed the level of trkA mRNA. In E14 cultures, the level of trkA mRNA increased in the absence of neurotrophins or 40 mM KC1. The level of p75 mRNA in E14 cultures was enhanced by NGF but was unaffected by 40 mM KC1. Our findings show that NGF receptor expression during the earliest stages of sympathetic neuron development is not affected by depolarization but indicate that by an early developmental stage (between E13 and E14 in vivo), sympathetic neurons become specified to upregulate trkA mRNA in culture independently of added factors. In addition, our findings reveal several distinctive features of p75 mRNA and trkA mRNA expression in sympathetic neurons compared with sensory neurons and provide a plausible explanation for previously observed differences in the effects of a p75 null mutation on the response of sensory and sympathetic neurons during embryonic and postnatal development.