Miracle-dz/UniFAR-FTUs huggingface dataset:
Dose-Dependent EEG Effects of Zolpidem Provide Evidence for GABAA Receptor Subtype Selectivity in Vivo

Zolpidem is a nonbenzodiazepine GABAA receptor modulator that binds in vitro with high affinity to GABAA receptors expressing α1 subunits but with relatively low affinity to receptors expressing α2, α3, and α5 subunits. In the present study, it was investigated whether this subtype selectivity could be detected and quantified in vivo. Three doses (1.25, 5, and 25 mg) of zolpidem were administered to rats in an intravenous infusion over 5 min. The time course of the plasma concentrations was determined in conjunction with the change in the β-frequency range of the EEG as pharmacodynamic endpoint. The concentration-effect relationship of the three doses showed a dose-dependent maximum effect and a dose-dependent potency. The data were analyzed for one- or two-site binding using two pharmacodynamic models based on 1) the descriptive model and 2) a novel mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for GABAAreceptor modulators that aims to separates drug- and system-specific properties, thereby allowing the estimation of in vivo affinity and efficacy. The application of two-site models significantly improved the fits compared with one-site models. Furthermore, in contrast to the descriptive model, the mechanism-based PK/PD model yielded dose-independent estimates for affinity (97 ± 40 and 33,100 ± 14,800 ng · ml−1). In conclusion, the mechanism-based PK/PD model is able to describe and explain the observed dose-dependent EEG effects of zolpidem and suggests the subtype selectivity of zolpidem in vivo.
BMP Signaling Modulates Hepcidin Expression in Zebrafish Embryos Independent of Hemojuvelin

Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription of the iron regulatory hormone hepcidin by activating the bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers of Hjv's function. Using the zebrafish model, we evaluated the effects of hjv and its interacting proteins on hepcidin expression during embryonic development. We found that hjv is strongly expressed in the notochord and somites of the zebrafish embryo and that morpholino knockdown of hjv impaired the development of these structures. Knockdown of hjv or other hjv-related genes, including zebrafish orthologs of furin or neogenin, however, failed to decrease hepcidin expression relative to liver size. In contrast, overexpression of bmp2b or knockdown of matriptase-2 enhanced the intensity and extent of hepcidin expression in zebrafish embryos, but this occurred in an hjv-independent manner. Furthermore, we demonstrated that zebrafish hjv can activate the human hepcidin promoter and enhance BMP responsive gene expression in vitro, but is expressed at low levels in the zebrafish embryonic liver. Taken together, these data support an alternative mechanism for hepcidin regulation during zebrafish embryonic development, which is independent of hjv.
Improving Simulations of Convective Systems from TRMM LBA: Easterly and Westerly Regimes

Abstract The 3D Goddard Cumulus Ensemble model is used to simulate two convective events observed during the Tropical Rainfall Measuring Mission Large-Scale Biosphere–Atmosphere (TRMM LBA) experiment in Brazil. These two events epitomized the type of convective systems that formed in two distinctly different environments observed during TRMM LBA. The 26 January 1999 squall line formed within a sheared low-level easterly wind flow. On 23 February 1999, convection developed in weak low-level westerly flow, resulting in weakly organized, less intense convection. Initial simulations captured the basic organization and intensity of each event. However, improvements to the model resolution and microphysics produced better simulations as compared to observations. More realistic diurnal convective growth was achieved by lowering the horizontal grid spacing from 1000 to 250 m. This produced a gradual transition from shallow to deep convection that occurred over a span of hours as opposed to an abrupt appearance of.
Acid-induced Dissociation of VacA, the Helicobacter pylori Vacuolating Cytotoxin, Reveals Its Pattern of Assembly

In this study, we describe the ultrastructural changes associated with acid activation of Helicobacter pylori vacuolating cytotoxin (VacA). Purified VacA molecules imaged by deep-etch electron microscopy form ∼30-nm hexagonal “flowers,” each composed of an ∼15-nm central ring surrounded by six ∼6-nm globular “petals. ” Upon exposure to acidic pH, these oligomeric flowers dissociate into collections of up to 12 teardrop-shaped subunits, each measuring ∼6 × 14 nm. Correspondingly, glycerol density gradient centrifugation shows that at neutral pH VacA sediments at ∼22 S, whereas at acidic pH it dissociates and sediments at ∼5 S. Immunoblot and EM analysis of the 5-S material demonstrates that it represents ∼90-kD monomers with 6 × 14–nm “teardrop” morphology. These data indicate that the intact VacA oligomer consists of 12 ∼90-kD subunits assembled into two interlocked six-membered arrays, overlap of which gives rise to the flower-like appearance. Support for this interpretation comes from EM identification of small numbers of relatively “flat” oligomers composed of six teardrop-shaped subunits, interpreted to be halves of the complete flower. These flat forms adsorb to mica in two different orientations, corresponding to hexameric surfaces that are either exposed or sandwiched inside the dodecamer, respectively. This view of VacA structure differs from a previous model in which the flowers were interpreted to be single layers of six monomers and the flat forms were thought to be proteolysed flowers. Since acidification has been shown to potentiate the cytotoxic effects of VacA, the present results suggest that physical disassembly of the VacA oligomer is an important feature of its activation.
ICP: Design and evaluation of an Interest control protocol for content-centric networking

Content-centric networking (CCN) brings a paradigm shift in the present Internet communication model by addressing named-data instead of host locations. With respect to TCP/IP, the transport model is connectionless with a unique endpoint at the receiver, driving a retrieval process natively point to multi-point. Another salient feature of CCN is the possibility to embed storage capabilities into the network, adding a new dimension to the transport problem. The focus of this work is on the design of a receiver-driven Interest control protocol for CCN, whose definition, to the best of our knowledge, still lacks in literature. ICP realizes a window-based Interest flow control, achieving full efficiency and fairness under proper parameters setting. In this paper, we provide an analytical characterization of average rate, expected data transfer delay and queue dynamics in steady state on a single and multi-bottleneck network topology. Our model accounts for the impact of on-path caches. Protocol performance is also assessed via packet-level simulations and design guidelines are drawn from previous analysis.
Confidence measures for spoken dialogue systems

This paper provides improved confidence assessment for detection of word-level speech recognition errors, out of domain utterances and incorrect concepts in the CU Communicator system. New features from the speech understanding component are proposed for confidence annotation at the utterance and concept levels. We consider a neural network to combine all features in each level. Using the data collected from a live telephony system, it is shown that 53.2% of incorrectly recognized words, 53.2% of out of domain utterances and 50.1% of incorrect concepts are detected at a 5% false rejection rate. In addition, the confidence measures are used to improve the word recognition accuracy. Several hypotheses from different speech recognizers are compiled into a word-graph. The word-graph is searched for the hypothesis with the best confidence. We report a 14.0% relative word error rate reduction after this confidence rescoring.
Leveraging E-Identities: The Impact of Percieved Diversity on Team Social Integration and Performance

Virtual teams (VTs) are increasingly being employed by organizations, presenting managers and researchers with challenges that collocated teams do not face. VTs are likely to be diverse and lack opportunities to readily communicate personal information to build relationships. Research on team diversity shows mixed results regarding the impact of diversity on team integration and performance, with both positive and negative impacts observed. This study asks the question: Can we minimize the negative impact of perceived deep-level diversity on performance while still leveraging the benefits of actual deep-level diversity? We examine how technology can be used to influence perceptions of deep-level diversity in order to attenuate the negative impact of diversity. Results show that diversity in general, deep-level, attributes can be influenced via the use of eidentity profiles, providing support for the idea that we can minimize social tension due to deeplevel diversity, while still reaping the benefits from actual diversity.
Key differences on the compaction response of natural and glass fiber preforms in liquid composite molding

In the present work, the effects of fiber structure and fluid absorption on the compaction behavior of jute woven fabrics and sisal mats were analyzed and compared with the response of glass fiber mats. It was found that the fiber content that can be achieved with a certain compaction pressure is lower in the case of natural fiber preforms. In addition, due to the hollow structure of these natural fibers, jute and sisal preforms suffered larger permanent deformation than glass fiber preforms after the compressive loading cycle. In addition, it was found that fluid absorption reduced the compaction pressure in natural reinforcements due to fiber softening. These phenomena were not observed in glass fiber mats.
An enhanced treatment program with markedly reduced mortality after a transtibial or higher non-traumatic lower extremity amputation

Background and purpose — Historically, high 30-day and 1-year mortality post-amputation rates (> 30% and 50%, respectively) have been reported in patients with a transtibial or higher non-traumatic lower extremity amputation (LEA). We evaluated whether allocating experienced staff and implementing an enhanced, multidisciplinary recovery program would reduce the mortality rates. We also determined factors that influenced mortality rates. Patients and methods — 129 patients with a LEA were consecutively included over a 2-year period, and followed after admission to an acute orthopedic ward. Mortality was compared with historical and concurrent national controls in Denmark. Results — The 30-day and 1-year mortality rates were 16% and 37%, respectively, in the intervention group, as compared to 35% and 59% in the historical control group treated in the same orthopedic ward. Cox proportional harzards models adjusted for age, sex, residential and health status, the disease that caused the amputation, and the index amputation level showed that 30-day and 1-year mortality risk was reduced by 52% (HR =0.48, 95% CI: 0.25–0.91) and by 46% (HR =0.54, 95% CI: 0.35–0.86), respectively, in the intervention group. The risk of death was increased for patients living in a nursing home, for patients with a bilateral LEA, and for patients with low health status. Interpretation — With similarly frail patient groups and instituting an enhanced program for patients after LEA, the risks of death by 30 days and by 1 year after LEA were markedly reduced after allocating staff with expertise.
Dissociation of Response Variability from Firing Rate Effects in Frontal Eye Field Neurons during Visual Stimulation, Working Memory, and Attention

Recent studies suggest that trial-to-trial variability of neuronal spiking responses may provide important information about behavioral state. Observed changes in variability during sensory stimulation, attention, motor preparation, and visual discrimination suggest that variability may reflect the engagement of neurons in a behavioral task. We examined changes in spiking variability of frontal eye field (FEF) neurons in a change detection task requiring monkeys to remember a visually cued location and direct attention to that location while ignoring distracters elsewhere. In this task, the firing rates (FRs) of FEF neurons not only continuously reflect the location of the remembered cue and select targets, but also predict detection performance on a trial-by-trial basis. Changes in FEF response variability, as measured by the Fano factor (FF), showed clear dissociations from changes in FR. The FF declined in response to visual stimulation at all tested locations, even in the opposite hemifield, indicating much broader spatial tuning of the FF compared with the FR. Furthermore, despite robust spatial modulation of the FR throughout all epochs of the task, spatial tuning of the FF did not persist throughout the delay period, nor did it show attentional modulation. These results indicate that changes in variability, at least in the FEF, are most effectively driven by visual stimulation, while behavioral engagement is not sufficient. Instead, changes in variability may reflect shifts in the balance between feedforward and recurrent sources of excitatory drive.
Inactivation of Mammalian Target of Rapamycin Increases STAT1 Nuclear Content and Transcriptional Activity in α4- and Protein Phosphatase 2A-dependent Fashion*

Target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth, primarily via regulation of protein synthesis. In Saccharomyces cerevisiae, TOR can also suppress the transcription of stress response genes by a mechanism involving Tap42, a serine/threonine phosphatase subunit, and the transcription factor Msn2. A physical association between mammalian TOR (mTOR) and the transcription factor signal transducer and activator of transcription-1 (STAT1) was recently identified in human cells, suggesting a similar role for mTOR in the transcription of interferon-γ-stimulated genes. In the current study, we identified a macromolecular protein complex composed of mTOR, STAT1, the Tap42 homologue α4, and the protein phosphatase 2A catalytic subunit (PP2Ac). Inactivation of mTOR enhanced its association with STAT1 and increased STAT1 nuclear content in PP2Ac-dependent fashion. Depletion of α4, PP2A, or mTOR enhanced the induction of early (i.e. IRF-1) and late (i.e. caspase-1, hiNOS, and Fas) STAT1-dependent genes. The regulation of IRF-1 or caspase-1 by mTOR was independent of other known mTOR effectors p70 S6 kinase and Akt. These results describe a new role for mTOR and α4/PP2A in the control of STAT1 nuclear content, and the expression of interferon-γ-sensitive genes involved in immunity and apoptosis.
Efficiency of antlion trap construction

SUMMARY Assessing the architectural optimality of animal constructions is in most cases extremely difficult, but is feasible for antlion larvae, which dig simple pits in sand to catch ants. Slope angle, conicity and the distance between the head and the trap bottom, known as off-centring, were measured using a precise scanning device. Complete attack sequences in the same pits were then quantified, with predation cost related to the number of behavioural items before capture. Off-centring leads to a loss of architectural efficiency that is compensated by complex attack behaviour. Off-centring happened in half of the cases and corresponded to post-construction movements. In the absence of off-centring, the trap is perfectly conical and the angle is significantly smaller than the crater angle, a physical constant of sand that defines the steepest possible slope. Antlions produce efficient traps, with slopes steep enough to guide preys to their mouths without any attack, and shallow enough to avoid the likelihood of avalanches typical of crater angles. The reasons for the paucity of simplest and most efficient traps such as theses in the animal kingdom are discussed.
Three‐Dimensional Echocardiography and 2D‐3D Speckle‐Tracking Imaging in Chronic Pulmonary Hypertension: Diagnostic Accuracy in Detecting Hemodynamic Signs of Right Ventricular (RV) Failure

Background Our aim was to compare three‐dimensional (3D) and 2D and 3D speckle‐tracking (2D‐STE, 3D‐STE) echocardiographic parameters with conventional right ventricular (RV) indexes in patients with chronic pulmonary hypertension (PH), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. Methods and Results Seventy‐three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (RV–fractional area change–tricuspid annular plane systolic excursion) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes and global and regional ejection fraction (3D‐RVEF) were determined. RV strains were calculated by 2D‐STE and 3D‐STE. RV 3D global‐free‐wall longitudinal strain (3DGFW‐RVLS), 2D global‐free‐wall longitudinal strain (GFW‐RVLS), apical‐free‐wall longitudinal strain, basal‐free‐wall longitudinal strain, and 3D‐RVEF were lower in patients with precapillary PH (P<0.0001) and postcapillary PH (P<0.01) compared to controls. 3DGFW‐RVLS (hazard ratio 4.6, 95% CI 2.79 to 8.38, P=0.004) and 3D‐RVEF (hazard ratio 5.3, 95% CI 2.85 to 9.89, P=0.002) were independent predictors of mortality. Receiver operating characteristic curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D‐RVEF (AUC 0.89), −17% for 3DGFW‐RVLS (AUC 0.88), −18% for GFW‐RVLS (AUC 0.88), −16% for apical‐free‐wall longitudinal strain (AUC 0.85), 16 mm for tricuspid annular plane systolic excursion (AUC 0.67), and 38% for RV‐FAC (AUC 0.62). Conclusions In chronic PH, 3D, 2D‐STE and 3D‐STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices.
Study of loading rate effect on dynamic fracture toughness of high strength steel under impact loading

Dynamic fracture toughness (DFT) of a high strength steel, 30CrMnSiA, is determined using a hybrid experimental- numerical method, with a focus on improved understanding of the loading rate effect on DFT under impact loading. The experiments are conducted on the Hopkinson pressure bar (HPB) apparatus with striker velocities ranging from 9.2 to 24.1 m/s to obtain a series of loading rates. Linear-elastic transient finite element analyses are performed to calculate histories of dynamic stress intensity factor (DSIF). The results show that with the increase of striker velocity, the crack tip loading rate increases on the order of 10 6 MPa m 1/2 s −1 , while the fracture initiation time and the DFT both reduce. Fracture surface examination is
How Accurate Is MOLLI T1 Mapping In Vivo? Validation by Spin Echo Methods

T1 mapping is a promising quantitative tool for assessing diffuse cardiomyopathies. The purpose of this study is to quantify in vivo accuracy of the Modified Look-Locker Inversion Recovery (MOLLI) cardiac T1 mapping sequence against the spin echo gold standard, which has not been done previously. T1 accuracy of MOLLI was determined by comparing with the gold standard inversion recovery spin echo sequence in the calf muscle, and with a rapid inversion recovery fast spin echo sequence in the heart. T1 values were obtained with both conventional MOLLI fitting and MOLLI fitting with inversion efficiency correction. In the calf (n = 6), conventional MOLLI fitting produced inconsistent T1 values with error ranging from 8.0% at 90° to 17.3% at 30°. Modified MOLLI fitting with inversion efficiency correction improved error to under 7.4% at all flip angles. In the heart (n = 5), modified MOLLI fitting with inversion correction reduced T1 error to 5.5% from 14.0% by conventional MOLLI fitting. This study shows that conventional MOLLI fitting can lead to significant in vivo T1 errors when not accounting for the lower adiabatic inversion efficiency often experienced in vivo.
A bag-of-regions approach to sketch-based image retrieval

This paper presents a system for retrieving photographs using free-hand sketched queries. Regions are extracted from each image by gathering nodes of a hierarchical image segmentation into a bag-of-regions (BoR) representation. The BoR represents object shape at multiple scales, encoding shape even in the presence of adjacent clutter. We extract a shape representation from each region, using the Gradient Field HoG (GF-HOG) descriptor which enables direct comparison with the sketched query. The retrieval pipeline yields significant performance improvements over the previous GF-HOG results reliant on single-scale Canny edge maps, and over leading descriptors (SIFT, SSIM) for visual search. In addition, our system enables localization of the sketched object within matching images.
Interfacial layer properties of HfO2 films formed by plasma-enhanced atomic layer deposition on silicon

The interfacial oxide layers, generated on Si substrates during the initial stage of HfO 2 atomic layer deposition (ALD), have been investigated depending on the oxygen reactants, oxygen plasma and water. In the plasma-enhanced ALD (PEALD) using oxygen plasma, a 2-nm-thick interfacial layer, which was intermixed with Hf-Si-O and SiO 2 having a dielectric constant (k) of 6.5, was formed, while water made a 1.5-nm-thick interfacial layer composed mainly of SiO 2 . Additionally, by utilizing oxygen plasma, the k of the HfO 2 film itself was increased up to 22.2 resulting in a higher effective k, and a much lower leakage current density was also obtained.
Analysis of Stroke Organization in the Backstroke as a Function of Skill

Many studies have demonstrated the importance of technical ability in stroke organization of swimmers. Chatard, Collomb, Maglischo, and Maglischo (1990) suggested that skilled swimmers, compared to those less skilled, were characterized by a higher stroke frequency and superposition of both arm actions, this motor pattern being more economical in terms of energy cost. Chollet, Chalies, and Chatard (2000) used an index ofcoordination to accurately quantify the lag time between the propulsive phases of each arm in crawl, showing that the lag time decreased with increased performance level.This lower relative duration oflag time (-4.2%) was associated with longer propulsive pull and push stroke phases (+4.1%) and shorter nonpropulsive entry and catch phases (-3.4%). However, such observations have been limited to front crawl swimming. Research devoted to stroke organization in the backstroke is scarce; little information exists in the literature describing the stroke pattern. Costill,Maglischo, and Richardson (1992) and Maglischo (1993) stated that the ideal coordination in high-level swimmers would conform to the opposite model, a mode of coordination providing continuous propulsive actions in which one arm begins the pull phase while the