Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric networks in thrombin distinguish procoagulant vs. anticoagulant activities

The serine protease α-thrombin is a dual-action protein that mediates the blood-clotting cascade. Thrombin alone is a procoagulant, cleaving fibrinogen to make the fibrin clot, but the thrombin–thrombomodulin (TM) complex initiates the anticoagulant pathway by cleaving protein C. A TM fragment consisting of only the fifth and sixth EGF-like domains (TM56) is sufficient to bind thrombin, but the presence of the fourth EGF-like domain (TM456) is critical to induce the anticoagulant activity of thrombin. Crystallography of the thrombin–TM456 complex revealed no significant structural changes in thrombin, suggesting that TM4 may only provide a scaffold for optimal alignment of protein C for its cleavage by thrombin. However, a variety of experimental data have suggested that the presence of TM4 may affect the dynamic properties of the active site loops. In the present work, we have used both conventional and accelerated molecular dynamics simulation to study the structural dynamic properties of thrombin, thrombin:TM56, and thrombin:TM456 across a broad range of time scales. Two distinct yet interrelated allosteric pathways are identified that mediate both the pro- and anticoagulant activities of thrombin. One allosteric pathway, which is present in both thrombin:TM56 and thrombin:TM456, directly links the TM5 domain to the thrombin active site. The other allosteric pathway, which is only present on slow time scales in the presence of the TM4 domain, involves an extended network of correlated motions linking the TM4 and TM5 domains and the active site loops of thrombin.
The Impact of Stimulus Properties on Low- and High-Frequency Median Nerve Somatosensory Evoked Potentials

Summary: Questioning whether stimulation properties in median nerve somatosensory evoked potentials show interactions multichannel recordings were performed in a three-factorial repeated measures design with the parameters (i) eyes opened versus eyes closed, (ii) stimulation intensity above motor threshold versus intensity sub motor threshold, (iii) stimulation rate 0.5 Hz versus 9 Hz resulting in somatosensory evoked potentials recorded during eight different conditions. Varying the stimulation intensity revealed an impact on the amplitude and the latency of the N20 source activity and on the amplitude, the duration and the number of peaks of the high frequency oscillatory (HFOs) sources. Modifying the stimulation rate lead to an effect on the amplitude and latency of the N20 and on the amplitude of the high-frequency oscillatory sources. The condition opened/closed eyes had an impact on the duration and number of high-frequency oscillatory. No relevant interactions between the stimulation properties were found. In consequence, varying one stimulus parameter already leads to a saturation of the low as well as high-frequency somatosensory evoked potentials components. Thus, the careful choice of stimulation parameters is a condition precedent for reasonable data interpretation.
PreservCyt Transport Medium Used for the ThinPrep Pap Test Is a Suitable Medium for Detection of Chlamydia trachomatis by the COBAS Amplicor CT/NG Test: Results of a Preliminary Study and Future Implications

ABSTRACT The commercial COBAS Amplicor CT/NG test (Roche Diagnostic Systems, Meylan, France) is a sensitive and specific method for detection of Chlamydia trachomatis infections. This test currently consists of using a nucleic acid amplification method to detect C. trachomatis in first-void urine specimens and in endocervical swabs collected in 2-sucrose-phosphate (2SP) transport medium. We conducted a prospective study to determine whether the automated COBAS Amplicor CT/NG test can detect C. trachomatis in cervical specimens collected in PreservCyt transport medium (ThinPrep Pap Test; Cytyc Corporation, Boxborough, Mass.). PreservCyt medium is used to preserve cervical samples before the preparation of ThinPrep slides. We collected 1,000 cervical specimens from young women (age range, 15 to 25 years) during routine Pap smear tests. Only specimens with normal cytology and in which the gynecologist found no clinical evidence of urogenital infections were selected. The samples were stored in PreservCyt transport medium at 15 to 20°C. C. trachomatis was detected in 22 of the 1,000 cervical specimens that had been stored in PreservCyt. To confirm the positive samples, the test was repeated on new endocervical swab specimens collected in 2SP transport medium. Only 9 of the 22 positive patients agreed to undergo this control, but all 9 retested positive. To evaluate the influence of storage conditions on the sensitivity of the C. trachomatis PCR test, all of the positive samples were stored at 15 to 20°C in PreservCyt transport medium and were retested every 2 weeks for 6 weeks. C. trachomatis was successfully amplified from all 22 specimens for the whole 6-week period. The prevalence of C. trachomatis infection was 2.2% in our study population. These results demonstrate that PreservCyt transport medium is a suitable transport medium for detection of C. trachomatis by the COBAS Amplicor CT/NG test. The ThinPrep Pap Test may enable gynecologists to monitor for both cervical lesions and C. trachomatis infections with a single endocervical specimen.
Interplay between Genetic and Clinical Variables Affecting Platelet Reactivity and Cardiac Adverse Events in Patients Undergoing Percutaneous Coronary Intervention

Several clinical and genetic variables are associated with influencing high on treatment platelet reactivity (HTPR). The aim of the study was to propose a path model explaining a concurrent impact among variables influencing HTPR and ischemic events. In this prospective cohort study polymorphisms of CYP2C19*2, CYP2C19*17, ABCB1, PON1 alleles and platelet function assessed by Multiple Electrode Aggregometry were assessed in 416 patients undergoing percutaneous coronary intervention treated with clopidogrel and aspirin. The rates of major adverse cardiac events (MACE) were recorded during a 12-month follow up. The path model was calculated by a structural equation modelling. Paths from two clinical characteristics (diabetes mellitus and acute coronary syndrome (ACS)) and two genetic variants (CYP2C19*2 and CYP2C19*17) independently predicted HTPR (path coefficients: 0.11 0.10, 0.17, and -0.10, respectively; p<0.05 for all). By use of those four variables a novel score for prediction of HTPR was built: in a factor-weighted model the risk for HTPR was calculated with an OR of 3.8 (95%CI: 3.1–6.8, p<0.001) for a score level of ≥1 compared with a score of <1. While MACE was independently predicted by HTPR and age in the multivariate model (path coefficient: 0.14 and 0.13, respectively; p<0.05), the coexistence of HTPR and age ≥75 years emerged as the strongest predictor of MACE. Our study suggests a pathway, which might explain indirect and direct impact of variables on clinical outcome: ACS, diabetes mellitus, CYP2C19*2 and CYP2C19*17 genetic variants independently predicted HTPR. In turn, age ≥75 years and HTPR were the strongest predictors of MACE.
Towards shallow grammar induction for an adaptive assistive vocal interface : a concept tagging approach

This paper describes research within the ALADIN project, which aims to develop an adaptive, assistive vocal interface for people with a physical impairment. One of the components in this interface is a self-learning grammar module, which maps a user’s utterance to its intended meaning. This paper describes a case study of the learnability of this task on the basis of a corpus of commands for the card game patience. The collection, transcription and annotation of this corpus is outlined in this paper, followed by results of preliminary experiments using a shallow concept-tagging approach. Encouraging results are observed during learning curve experiments, that gauge the minimal amount of training data needed to trigger accurate concept tagging of previously unseen utterances.
Numerical Simulation of Microwave Sintering of Zinc Oxide

Experiments at the University of Maryland Plasma Physics Laboratory have discovered an unusual temperature response in the form of a " thermal wave " which begins at the center and propagates towards the surface of a zinc oxide sample, when heated in a microwave cavity without the presence of oxygen. This effect is believed to be caused by the irregular temperature dependence of the dielectric properties of zinc oxide, particularly dielectric loss. Two thermocouple probes were used to measure the temperature response in a small cylindrical sample of zinc oxide packed in powder insulation, and heated in a microwave oven. In order to determine if the unusual response is caused by the dielectric properties, this work uses a finite-difference mathematical model to simulate the experiments, both for the case of zinc oxide heated in ordinary air, as well as for the case of zinc oxide heated in nitrogen. A revised version of the model is used to determine if the thermocouple probe has any effect on the temperature of the sample. The spatial and temporal temperature distribution results from the model indicate that the thermocouple probe has a negligible effect on the results and that the " thermal wave " can be attributed to the irregular temperature dependence of the dielectric loss of the material. iii Acknowledgments I would like to thank my advisor, Dr. J.R. Thomas, for his guidance through my graduate studies including this thesis. His knowledge, patience, and enthusiasm for research proved to be very valuable in assisting me in this endeavor. I would also like to thank Dr. for an excellent graduate education, as well as for providing me with the opportunity to earn the necessary funding through a teaching assistant position. Finally, I would like to thank my family for their limitless encouragement and support.
Localization of calcitonin receptor‐like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat

Calcitonin receptor‐like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene related peptide (CGRP) and intermedin. Although CGRP is widely expressed in the nervous system, less is known about the localization of CLR and RAMP1. To localize these proteins, we raised antibodies to CLR and RAMP1. Antibodies specifically interacted with CLR and RAMP1 in HEK cells coexpressing rat CLR and RAMP1, determined by Western blotting and immunofluorescence. Fluorescent CGRP specifically bound to the surface of these cells and CGRP, CLR, and RAMP1 internalized into the same endosomes. CLR was prominently localized in nerve fibers of the myenteric and submucosal plexuses, muscularis externa and lamina propria of the gastrointestinal tract, and in the dorsal horn of the spinal cord of rats. CLR was detected at low levels in the soma of enteric, dorsal root ganglia (DRG), and spinal neurons. RAMP1 was also localized to enteric and DRG neurons and the dorsal horn. CLR and RAMP1 were detected in perivascular nerves and arterial smooth muscle. Nerve fibers containing CGRP and intermedin were closely associated with CLR fibers in the gastrointestinal tract and dorsal horn, and CGRP and CLR colocalized in DRG neurons. Thus, CLR and RAMP1 may mediate the effects of CGRP and intermedin in the nervous system. However, mRNA encoding RAMP2 and RAMP3 was also detected in the gastrointestinal tract, DRG, and dorsal horn, suggesting that CLR may associate with other RAMPs in these tissues to form a receptor for additional peptides such as adrenomedullin. J. Comp. Neurol. 490:239–255, 2005. © 2005 Wiley‐Liss, Inc.
Revisiting the Appropriateness of Carotid Endarterectomy

Background and Purpose— In the 1980s, carotid endarterectomy was controversial because proof of efficacy was lacking, complication rates were high, and one third of cases were reported to be inappropriate. Since publication of several randomized controlled trials (RCTs), rates of carotid endarterectomy have doubled nationwide. This study assesses the appropriateness and use of carotid endarterectomy since publication of the RCTs. Methods— Using the literature, we developed a list of 1557 mutually exclusive indications for carotid endarterectomy and asked a panel of national experts to rate the appropriateness of each indication using the RAND methodology. We used these ratings to assess appropriateness in a sample of 2124 patients who underwent the procedure in 1997 to 1998 in 6 hospitals. We also analyzed the reasons for the procedure and rates of death, stroke, and myocardial infarction within 30 days of surgery. Results— Overall, 84.9% of operations were done for appropriate reasons, 4.5% for uncertain reasons, and 10.6% for inappropriate reasons. Among procedures considered inappropriate, the most common reasons were high comorbidity (46.6%) and minimal stenosis (27.1%). Overall, 72.5% were asymptomatic, 17.4% had a carotid transient ischemic attack, and 10.1% had a stroke. The 30-day rate of death or stroke was 5.47% for symptomatic patients and 2.26% for asymptomatic patients. Among patients having combined carotid and coronary artery bypass graft surgery, the rate was 10.32%. The complication rate in asymptomatic patients with high comorbidity was 5.56%. Conclusions— Since the RCTs, rates of overuse appear to have fallen considerably, although they are still significant. A major shift has occurred toward operating on asymptomatic patients. Although overall complication rates were low, rates among asymptomatic patients with high comorbidity exceeded recommended thresholds.
On the Betti numbers of sign conditions

Let R be a real closed field and let Q and P be finite subsets of R[X 1 ,. ,X k ] such that the set P has s elements, the algebraic set Z defined by Λ Q ∈ Q Q = 0 has dimension k' and the elements ofQ and P have degree at most d. For each 0 0 or P < 0 for P ∈ P, is bounded by Σ k' i=0 Σ k'-i j=0 (sj)6 j d(2d-1) k-1 . making the bound s k' O(d) k more precise.
The promise and potential hazards of adenovirus gene therapy

Gene therapy has been heralded as the “medicine of the 21st century”. With this has come an expectation which has yet to be met by experience. Thus the past decade has seen some 4000 patients entered into a variety of gene therapy trials with very few documented successes. Much of the “hype and hope” surrounding clinical gene therapy reflects the gap between the need to carefully perform phase I clinical trials to assess toxicity and tolerability and the public expectation that this approach is the panacea to chronic disease. Recent publicity highlights the current dilemma. The death in the USA of an 18 year old with ornithine transcarbamylase (OTC) deficiency after intrahepatic arterial injection of an adenovirus vector carrying a wild-type version of the defective enzyme has precipitated a flurry of reports and congressional hearings focusing on the ethics of such trials and on the very nature of clinical research itself.1 In contrast, a recent report provides one of the first clear cut gene therapy successes—the reconstitution of immune responses in two children with the SCID-X1 disorder by retroviral delivery of the wild-type gene to bone marrow.2 These two examples are interesting in that the therapies target rare monogenic diseases where returning the wild-type gene is the only rational therapeutic option while also posing the most rigorous test of the gene therapy approach—the ability to provide long term correction of gene defects. It is however in the area of the common ills such as heart disease and cancer that gene therapy promises so much and, despite current concerns, there is no doubt that with the necessary technical developments gene therapy will significantly improve the treatment of the major contemporary causes of premature mortality. It is generally accepted that the major impediment to the successful application of gene therapy …
Unscrambling the genomic chaos of osteosarcoma reveals extensive transcript fusion, recurrent rearrangements and frequent novel TP53 aberrations

In contrast to many other sarcoma subtypes, the chaotic karyotypes of osteosarcoma have precluded the identification of pathognomonic translocations. We here report hundreds of genomic rearrangements in osteosarcoma cell lines, showing clear characteristics of microhomology-mediated break-induced replication (MMBIR) and end-joining repair (MMEJ) mechanisms. However, at RNA level, the majority of the fused transcripts did not correspond to genomic rearrangements, suggesting the involvement of trans-splicing, which was further supported by typical trans-splicing characteristics. By combining genomic and transcriptomic analysis, certain recurrent rearrangements were identified and further validated in patient biopsies, including a PMP22-ELOVL5 gene fusion, genomic structural variations affecting RB1, MTAP/CDKN2A and MDM2, and, most frequently, rearrangements involving TP53. Most cell lines (7/11) and a large fraction of tumor samples (10/25) showed TP53 rearrangements, in addition to somatic point mutations (6 patient samples, 1 cell line) and MDM2 amplifications (2 patient samples, 2 cell lines). The resulting inactivation of p53 was demonstrated by a deficiency of the radiation-induced DNA damage response. Thus, TP53 rearrangements are the major mechanism of p53 inactivation in osteosarcoma. Together with active MMBIR and MMEJ, this inactivation probably contributes to the exceptional chromosomal instability in these tumors. Although rampant rearrangements appear to be a phenotype of osteosarcomas, we demonstrate that among the huge number of probable passenger rearrangements, specific recurrent, possibly oncogenic, events are present. For the first time the genomic chaos of osteosarcoma is characterized so thoroughly and delivered new insights in mechanisms involved in osteosarcoma development and may contribute to new diagnostic and therapeutic strategies.
Real-time remote sensing driven river basin modeling using radar altimetry

Abstract. Many river basins have a weak in-situ hydrometeorological monitoring infrastructure. However, water resources practitioners depend on reliable hydrological models for management purposes. Remote sensing (RS) data have been recognized as an alternative to in-situ hydrometeorological data in remote and poorly monitored areas and are increasingly used to force, calibrate, and update hydrological models. In this study, we evaluate the potential of informing a river basin model with real-time radar altimetry measurements over reservoirs. We present a lumped, conceptual, river basin water balance modeling approach based entirely on RS and reanalysis data: precipitation was obtained from the Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA), temperature from the European Centre for Medium-Range Weather Forecast's (ECMWF) Operational Surface Analysis dataset and reference evapotranspiration was derived from temperature data. The Ensemble Kalman Filter was used to assimilate radar altimetry (ERS2 and Envisat) measurements of reservoir water levels. The modeling approach was applied to the Syr Darya River Basin, a snowmelt-dominated basin with large topographical variability, several large reservoirs and scarce hydrometeorological data that is located in Central Asia and shared between 4 countries with conflicting water management interests. The modeling approach was tested over a historical period for which in-situ reservoir water levels were available. Assimilation of radar altimetry data significantly improved the performance of the hydrological model. Without assimilation of radar altimetry data, model performance was limited, probably because of the size and complexity of the model domain, simplifications inherent in model design, and the uncertainty of RS and reanalysis data. Altimetry data assimilation reduced the mean absolute error of the simulated reservoir water levels from 4.7 to 1.9 m, and overall model RMSE from 10.3 m to 6.7 m. Model performance was variable for the different reservoirs in the system. The RMSE ranged from 10% to 76% of the mean seasonal reservoir level variation. Because of its easy accessibility and immediate availability, radar altimetry lends itself to being used in real-time hydrological applications. As an impartial source of information about the hydrological system that can be updated in real time, the modeling approach described here can provide useful medium-term hydrological forecasts to be used in water resources management.
Oestrogen receptor α agonist improved long-term ovariectomy-induced spatial cognition deficit in young rats.

Ovariectomy is known as 'surgical menopause' with decreased levels of oestrogen in female rodents and its reported risks and adverse effects include cognitive impairment. In the brain, oestrogen exerts effects through its receptors, oestrogen receptor α (ERα) and β (ERβ). However, the role of ERα or ERβ in ovariectomy-induced cognitive impairment needs further investigation. Here, we observed that bilaterally ovariectomized 3-month-old rats showed obvious spatial learning and memory deficits in the Morris water maze with significant loss of neurons and synapses in the hippocampus. In addition to the rapid decline in serum oestradiol levels, the expression of ERα, but not ERβ, was decreased in the hippocampus starting 1 wk after ovariectomy. Prompt 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT) treatment (1 mg/kg.d), an agonist of ERα, improved the spatial learning and memory ability of ovariectomized rats and rescued ovariectomy-induced neuron loss by up-regulating the level of BCLxl, an important anti-apoptosis protein. Furthermore, PPT treatment also improved ovariectomy-induced hippocampal synapse loss and up-regulated the levels of synaptic proteins (synapsin I, NR2A and GluR1) and the activates of CaMK Πα, ERK and Akt. Thus, these results demonstrated that ERα plays an important role in neuroprotection and that prompt ERα rescue is effective to improve hippocampal-dependent cognition deficit after long-term ovariectomy.
First combination of Tevatron and LHC measurements of the top-quark mass

We present a combination of measurements of the mass of the top quark, $m_{\rm top}$, performed by the CDF and D0 experiments at the Tevatron collider and the ATLAS and CMS experiments at the Large Hadron Collider (LHC). The Tevatron data correspond to an integrated luminosity of up to 8.7 fb${^{-1}}$ of proton-antiproton collisions from Run II of the Tevatron at a centre-of-mass energy of 1.96 TeV. The LHC data correspond to an integrated luminosity of up to 4.9 fb${^{-1}}$ of proton-proton collisions from the run at a centre-of-mass energy of 7 TeV. The combination includes measurements in the $t\bar t\to$ lepton+jets, $t\bar t\to$ dilepton, $t\bar t\to$ all jets and $t\bar t\to$ $E_{\rm T}^{\rm miss}$+jets final states. The resulting combined measurement of $m_{\rm top}$ is $173.34 \pm 0.27 \mbox{(stat)} \pm 0.71 \mbox{(syst)}$ GeV, with a total uncertainty of $0.76$ GeV.
Static-priority periodic scheduling on multiprocessors

Presents a new sufficient condition for the schedulability of preemptable, periodic, hard-real-time task sets using the very simple static-priority weight-monotonic scheduling scheme. Like a previous condition due to S. Baruah et al. (1996), our condition actually determines pfair schedulability. Pfairness requires that the schedule, in addition to being periodic, schedules each task at an approximately even rate. Our condition improves on the previous one in two important ways. First, it can determine that task sets with both high utilization and many tasks are schedulable, while the previous condition cannot. Second, our condition applies to both uniprocessors and multiprocessors, while the previous condition applies only to uniprocessors. We present simulations that show that our condition is highly accurate for many cases of interest.