Miracle-dz/UniFAR-FTUs huggingface dataset:
Liquefaction of Semen Generates and Later Degrades a Conserved Semenogelin Peptide That Enhances HIV Infection

ABSTRACT Semen enhances HIV infection in vitro, but how long it retains this activity has not been carefully examined. Immediately postejaculation, semen exists as a semisolid coagulum, which then converts to a more liquid form in a process termed liquefaction. We demonstrate that early during liquefaction, semen exhibits maximal HIV-enhancing activity that gradually declines upon further incubation. The decline in HIV-enhancing activity parallels the degradation of peptide fragments derived from the semenogelins (SEMs), the major components of the coagulum that are cleaved in a site-specific and progressive manner upon initiation of liquefaction. Because amyloid fibrils generated from SEM fragments were recently demonstrated to enhance HIV infection, we set out to determine whether any of the liquefaction-generated SEM fragments associate with the presence of HIV-enhancing activity. We identify SEM1 from amino acids 86 to 107 [SEM1(86-107)] to be a short, cationic, amyloidogenic SEM peptide that is generated early in the process of liquefaction but that, conversely, is lost during prolonged liquefaction due to the activity of serine proteases. Synthetic SEM1(86-107) amyloids directly bind HIV-1 virions and are sufficient to enhance HIV infection of permissive cells. Furthermore, endogenous seminal levels of SEM1(86-107) correlate with donor-dependent variations in viral enhancement activity, and antibodies generated against SEM1(86-107) recognize endogenous amyloids in human semen. The amyloidogenic potential of SEM1(86-107) and its virus-enhancing properties are conserved among great apes, suggesting an evolutionarily conserved function. These studies identify SEM1(86-107) to be a key, HIV-enhancing amyloid species in human semen and underscore the dynamic nature of semen's HIV-enhancing activity. IMPORTANCE Semen, the most common vehicle for HIV transmission, enhances HIV infection in vitro, but how long it retains this activity has not been investigated. Semen naturally undergoes physiological changes over time, whereby it converts from a gel-like consistency to a more liquid form. This process, termed liquefaction, is characterized at the molecular level by site-specific and progressive cleavage of SEMs, the major components of the coagulum, by seminal proteases. We demonstrate that the HIV-enhancing activity of semen gradually decreases over the course of extended liquefaction and identify a naturally occurring semenogelin-derived fragment, SEM1(86-107), whose levels correlate with virus-enhancing activity over the course of liquefaction. SEM1(86-107) amyloids are naturally present in semen, and synthetic SEM1(86-107) fibrils bind virions and are sufficient to enhance HIV infection. Therefore, by characterizing dynamic changes in the HIV-enhancing activity of semen during extended liquefaction, we identified SEM1(86-107) to be a key virus-enhancing component of human semen.
Biochemical evidence for superior correction of neuronal storage by chemically modified enzyme in murine mucopolysaccharidosis VII

Enzyme replacement therapy has been used successfully in many lysosomal storage diseases. However, correction of brain storage has been limited by the inability of infused enzyme to cross the blood–brain barrier (BBB). We recently reported that PerT-GUS, a form of β-glucuronidase (GUS) chemically modified to eliminate its uptake and clearance by carbohydrate-dependent receptors, crossed the BBB and cleared neuronal storage in an immunotolerant model of murine mucopolysaccharidosis (MPS) type VII. In this respect, the chemically modified enzyme was superior to native β-glucuronidase. Chemically modified enzyme was also delivered more effectively to heart, kidney, and muscle. However, liver and spleen, which express high levels of carbohydrate receptors, received nearly fourfold lower levels of PerT-GUS compared with native GUS. A recent report on PerT-treated sulfamidase in murine MPS IIIA confirmed enhanced delivery to other tissues but failed to observe clearance of storage in neurons. To confirm and extend our original observations, we compared the efficacy of 12 weekly i.v. infusions of PerT-GUS versus native GUS on (i) delivery of enzyme to brain; (ii) improvement in histopathology; and (iii) correction of secondary elevations of other lysosomal enzymes. Such correction is a recognized biomarker for correction of neuronal storage. PerT-GUS was superior to native GUS in all three categories. These results provide additional evidence that long-circulating enzyme, chemically modified to escape carbohydrate-mediated clearance, may offer advantages in treating MPS VII. The relevance of this approach to treat other lysosomal storage diseases that affect brain awaits confirmation.
miR33 Inhibition Overcomes Deleterious Effects of Diabetes Mellitus on Atherosclerosis Plaque Regression in Mice

Rationale: Diabetes mellitus increases cardiovascular disease risk in humans and remains elevated despite cholesterol-lowering therapy with statins. Consistent with this, in mouse models, diabetes mellitus impairs atherosclerosis plaque regression after aggressive cholesterol lowering. MicroRNA 33 (miR33) is a key negative regulator of the reverse cholesterol transport factors, ATP-binding cassette transporter A1 and high-density lipoprotein, which suggested that its inhibition may overcome this impairment. Objective: To assess the effects of miR33 inhibition on atherosclerosis regression in diabetic mice. Methods and Results: Reversa mice, which are deficient in the low-density lipoprotein receptor and in which hypercholesterolemia is reversed by conditional inactivation of the microsomal triglyceride transfer protein gene, were placed on an atherogenic diet for 16 weeks, then either made diabetic by streptozotocin injection or kept normoglycemic. Lipid-lowering was induced by microsomal triglyceride transfer protein gene inactivation, and mice were treated with anti-miR33 or control oligonucleotides. Although regression was impaired in diabetic mice treated with control oligonucleotides, anti-miR33 treatment decreased plaque macrophage content and inflammatory gene expression in these mice. The decreased macrophage content in anti–miR33 treated diabetic mice was associated with a blunting of hyperglycemia-induced monocytosis and reduced monocyte recruitment to the plaque, which was traced to an inhibition of the proliferation of bone marrow monocyte precursors associated with the upregulation of their Abca1. Conclusions: miR33 inhibition overcomes deleterious effects of diabetes mellitus in atherosclerosis regression in mice, which suggests a therapeutic strategy in diabetic patients, who remain at elevated cardiovascular disease risk, despite plasma cholesterol lowering.
Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore

Background Rapid response to outbreaks of emerging infectious diseases is impeded by uncertain diagnoses and delayed communication. Understanding the effect of inefficient response is a potentially important contribution of epidemic theory. To develop this understanding we studied societal learning during emerging outbreaks wherein patient removal accelerates as information is gathered and disseminated. Methods and Findings We developed an extension of a standard outbreak model, the simple stochastic epidemic, which accounts for societal learning. We obtained expressions for the expected outbreak size and the distribution of epidemic duration. We found that rapid learning noticeably affects the final outbreak size even when learning exhibits diminishing returns (relaxation). As an example, we estimated the learning rate for the 2003 outbreak of severe acute respiratory syndrome (SARS) in Singapore. Evidence for relaxation during the first eight weeks of the outbreak was inconclusive. We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. By contrast, the expected outbreak size for societal learning twice as effective was 116 cases. Conclusion These results show that the rate of societal learning can greatly affect the final size of disease outbreaks, justifying investment in early warning systems and attentiveness to disease outbreak by both government authorities and the public. We submit that the burden of emerging infections, including the risk of a global pandemic, could be efficiently reduced by improving procedures for rapid detection of outbreaks, alerting public health officials, and aggressively educating the public at the start of an outbreak.
Evaluation of colestilan in chronic kidney disease dialysis patients with hyperphosphataemia and dyslipidaemia: a randomized, placebo-controlled, multiple fixed-dose trial.

BACKGROUND Colestilan is a non-absorbed, non-calcium-based, phosphate binder. It also binds bile acids and reduces serum levels of low-density lipoprotein cholesterol (LDL-C). This study evaluated the efficacy of a range of fixed doses of colestilan compared with placebo for the control of serum phosphorus and LDL-C levels in patients with CKD stage 5 on dialysis. METHODS This was a multicentre, randomized, double-blind, placebo-controlled, multiple fixed-dose trial in which 642 patients with CKD stage 5 on dialysis who had both hyperphosphataemia and dyslipidaemia, were randomized to treatment with colestilan 3, 6, 9, 12 or 15 g/day or placebo for 12 weeks. The co-primary endpoints were the mean changes in serum phosphorus and the mean per cent change in LDL-C from baseline to Week 12. RESULTS A significantly greater mean reduction in serum phosphorus level from baseline to Week 12 than seen with placebo was seen with 9 g (-0.28 mmol/L) and pooled colestilan 12/15 g (-0.34 mmol/L). The per cent reduction in LDL-C level was significantly greater with colestilan 3, 6 and 9 g and pooled colestilan 12/15 g than with placebo (reduction ranged from 15.9 to 27.6% dependent on dose). Colestilan also reduced total cholesterol, oxidized LDL-C, HbA1c and uric acid levels, and did not increase serum calcium levels. Colestilan was generally well tolerated; the most common adverse events affected the gastrointestinal system. CONCLUSIONS Colestilan is an effective treatment for hyperphosphataemia, and provides beneficial effects on other metabolic parameters associated with cardiovascular risk, notably LDL-C.
Identification of evolving fuzzy rule-based models

An approach to identification of evolving fuzzy rule-based (eR) models is proposed. eR models implement a method for the noniterative update of both the rule-base structure and parameters by incremental unsupervised learning. The rule-base evolves by adding more informative rules than those that previously formed the model. In addition, existing rules can be replaced with new rules based on ranking using the informative potential of the data. In this way, the rule-base structure is inherited and updated when new informative data become available, rather than being completely retrained. The adaptive nature of these evolving rule-based models, in combination with the highly transparent and compact form of fuzzy rules, makes them a promising candidate for modeling and control of complex processes, competitive to neural networks. The approach has been tested on a benchmark problem and on an air-conditioning component modeling application using data from an installation serving a real building. The results illustrate the viability and efficiency of the approach.
PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes

Background:Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. Methods:The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. Results:Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1–7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). Conclusions:Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.
The Berkeley Parser at the EVALITA 2009 Constituency Parsing Task

In this paper we describe our participation at the EVALITA 2009 Con- stituency Parsing Task. We used the Berkeley Parser, obtaining the best F1, that is 78:73. This result corresponds to an increment of 15.85% with respect to the best result obtained at EVALITA 2007 by the Bikel's parser (F1 = 67:96). A further important advantage of the Berkeley parser is that it does not require any language adaptation in addition to the need of retraining it on the new treebank. For comparison, we also report the results obtained by the Bikel's parser on the 2009 treebank.
The Business Cycle and Industry Comovement

The U.S. economy, as of the writing of this article, is in its longest postwar expansion. This expansion has prompted various proponents to declare a “new” economy and the death of the business cycle. These pronouncements may well turn out to be premature, as similar announcements have proved in the past. In this case we can already say that the current expansion shares one feature with all previous business cycles, namely that all parts of the economy take part in the expansion, although possibly to different degrees. In particular, although the symbol of the “new” economy appears to be the Internet, a general expansion of all industries in the manufacturing and the service sector accounts for the growth in GDP. Indeed, it is the general up and down movement of all parts of the economy that defines the business cycle in Burns and Mitchell’s (1946) early work. In contrast to this earlier work, modern business cycle research has focused for the most part on the comovement of aggregate variables, like output, employment, consumption, investment, the price level, interest rates, etc. In part, the focus on the aggregate economy has been justified by the observed comovement, which is supposed to indicate the presence of common aggregate disturbances to which all parts of the economy respond in a similar way. The argument for aggregate shocks as the source of business cycles proceeds as follows (Lucas 1977). Suppose the economy is subject to a large number of industry-specific disturbances which are unrelated to each other. Then we would expect that these disturbances change the relative productivities of various inputs such as labor. This change in relative productivities, in turn, should lead to a reallocation of inputs. That is, input use should decline in industries with falling relative productivities and should increase in industries with
Behavior of low-burnup metallic fuels for the integral fast reactor at elevated temperatures in ex-reactor tests

A series of ex-reactor heating tests on low burnup U-26wt. %Pu-10wt. %Zr metallic fuel for the PRISM reactor was conducted to evaluate fuel/cladding metallurgical interaction and its effect on cladding integrity at elevated temperatures. The reaction between the fuel and cladding caused liquid-phase formation and dissolution of the inner surface of the cladding. The rate of cladding penetration was below the existing design correlation, which provides a conservative margin to cladding failure. In a test which enveloped a wide range of postulated reactor transient events, a substantial temporal cladding integrity margin was demonstrated for an intact, whole fuel pin. The cause of the eventual pin breach was reaction-induced cladding thinning combined with fission-gas pressure loading. The behavior of the breached pin was benign. 7 refs., 7 figs., 1 tab.
Ganzfeld Stimulation or Sleep Enhance Long Term Motor Memory Consolidation Compared to Normal Viewing in Saccadic Adaptation Paradigm

Adaptation of saccade amplitude in response to intra-saccadic target displacement is a type of implicit motor learning which is required to compensate for physiological changes in saccade performance. Once established trials without intra-saccadic target displacement lead to de-adaptation or extinction, which has been attributed either to extra-retinal mechanisms of spatial constancy or to the influence of the stable visual surroundings. Therefore we investigated whether visual deprivation (“Ganzfeld”-stimulation or sleep) can partially maintain this motor learning compared to free viewing of the natural surroundings. Thirty-five healthy volunteers performed two adaptation blocks of 100 inward adaptation trials – interspersed by an extinction block – which were followed by a two-hour break with or without visual deprivation (VD). Using additional adaptation and extinction blocks short and long (4 weeks) term memory of this implicit motor learning were tested. In the short term, motor memory tested immediately after free viewing was superior to adaptation performance after VD. In the long run, however, effects were opposite: motor memory and relearning of adaptation was superior in the VD conditions. This could imply independent mechanisms that underlie the short-term ability of retrieving learned saccadic gain and its long term consolidation. We suggest that subjects mainly rely on visual cues (i.e., retinal error) in the free viewing condition which makes them prone to changes of the visual stimulus in the extinction block. This indicates the role of a stable visual array for resetting adapted saccade amplitudes. In contrast, visual deprivation (GS and sleep), might train subjects to rely on extra-retinal cues, e.g., efference copy or prediction to remap their internal representations of saccade targets, thus leading to better consolidation of saccadic adaptation.
Results of a Multicentre, Randomised Controlled Trial of Intra-Arterial Urokinase in the Treatment of Acute Posterior Circulation Ischaemic Stroke

Background: Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy. Methods: Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion. Results: Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group. Conclusions: These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.
Enabling efficient and accurate large-scale simulations of VANETs for vehicular traffic management

To study the impact of inter-vehicle communications on (vehicular) transport efficiency, e.g., for traffic management purposes, there is a need for efficient and accurate large-scale simulations that jointly consider both, the vehicular traffic and the communication system. To overcome the scalability limitations of current discrete event-based network simulators like NS-2, we propose a hybrid simulation approach that can significantly reduce the number of scheduled events by making use of statistical models. Basically, we treat some data traffic, which is not the primary concern of the simulation study, as 'noise' (e.g., beaconing of nodes). While accurately modeling this background traffic we only need to simulate via discrete event-based simulation the actual application we are interested in (e.g., a data dissemination protocol). We outline how the characterization of the background traffic is gained, statistically validated and used. The achievable speed-up is demonstrated in a first application study where a speed funnel is built using inter-vehicle communications. In this scenario, the conservatively estimated speed-up factor is about 500 compared to a pure discrete event-based simulation.
Temporal Modeling of Neural Net Input/Output Behaviors: The Case of XOR

In the context of the modeling and simulation of neural nets, we formulate definitions for the behavioral realization of memoryless functions. The definitions of realization are substantively different for deterministic and stochastic systems constructed of neuron-inspired components. In contrast to earlier generations of neural net models, third generation spiking neural nets exhibit important temporal and dynamic properties, and random neural nets provide alternative probabilistic approaches. Our definitions of realization are based on the Discrete Event System Specification (DEVS) formalism that fundamentally include temporal and probabilistic characteristics of neuron system inputs, state, and outputs. The realizations that we construct—in particular for the Exclusive Or (XOR) logic gate—provide insight into the temporal and probabilistic characteristics that real neural systems might display. Our results provide a solid system-theoretical foundation and simulation modeling framework for the high-performance computational support of such applications.
Repeatability and relative validity of two physical activity questionnaires in elderly women.

In a population of 33 women aged 51-71 yr, two physical activity questionnaires (a modified Baecke questionnaire and the pre-EPIC questionnaire) were tested for repeatability (5 and 11 months). For assessment of relative validity, the questionnaires were compared with a physical activity diary (12 d) as the main reference method, a single 24-h Caltrac accelerometer score, and energy intake estimated from a 24-h dietary recall repeated 12 times. Repeatability of the questionnaires at 5 months was 0.82 (Baecke) and 0.42 (pre-EPIC), at 11 months 0.73 and 0.60, respectively. Correlation with the activity diary was 0.51 for the Baecke and 0.64 for the pre-EPIC questionnaire. Correlation with the Caltrac was 0.22 for both questionnaires, and with energy intake -0.21 and 0.43, respectively. Factor analysis suggested that the questionnaires and the diary measured a common aspect of activity, which could be interpreted as "reported normal physical activity. " Women who reported sweating or breathlessness during the past week scored significantly higher only on the Baecke questionnaire. It was concluded that the two questionnaires seemed to be able to rank older women according to physical activity in epidemiological studies.