Miracle-dz/UniFAR-FTUs huggingface dataset:
Ectopic Expression of Activated Notch or SOX2 Reveals Similar and Unique Roles in the Development of the Sensory Cell Progenitors in the Mammalian Inner Ear

Hearing impairment or vestibular dysfunction in humans often results from a permanent loss of critical cell types in the sensory regions of the inner ear, including hair cells, supporting cells, or cochleovestibular neurons. These important cell types arise from a common sensory or neurosensory progenitor, although little is known about how these progenitors are specified. Studies have shown that Notch signaling and the transcription factor Sox2 are required for the development of these lineages. Previously we and others demonstrated that ectopic activation of Notch can direct nonsensory cells to adopt a sensory fate, indicating a role for Notch in early specification events. Here, we explore the relationship between Notch and SOX2 by ectopically activating these factors in nonsensory regions of the mouse cochlea, and demonstrate that, similar to Notch, SOX2 can specify sensory progenitors, consistent with a role downstream of Notch signaling. However, we also show that Notch has a unique role in promoting the proliferation of the sensory progenitors. We further demonstrate that Notch can only induce ectopic sensory regions within a certain time window of development, and that the ectopic hair cells display specialized stereocilia bundles similar to endogenous hair cells. These results demonstrate that Notch and SOX2 can both drive the sensory program in nonsensory cells, indicating these factors may be useful in cell replacement strategies in the inner ear.
Plasma norepinephrine, epinephrine, and dopamine beta-hydroxylase activity during exercise in man.

Many experimental studies have utilized the activity of dopamine-beta-hydroxylase (DBH) as an index of sympathetic activity, since this enzyme is not submitted to uptake mechanisms or to enzymatic metabolism as are the circulating catecholamines norepinephrine (NE) and epinephrine (E). However, large discrepancies have been found between the results of these studies. The hypothesis which is examined in this study is that these discrepancies might arise from the different intensities in the stimuli utilized. In order to examine this possibility, plasma DBH activity was measured in seven subjects at rest and in three different conditions known to increase sympathetic activity to varying degrees, i.e., during hand-grip, standing, and supra-maximal bicycle exercise. Plasma NE and E concentrations were also measured during these stimuli. The results of this study show that DBH activity increases above resting levels only during supramaximal dynamic exercise, while plasma NE and E concentrations increase during each experimental condition. Furthermore, the increases in NE and E are related to each other and are also related to heart rate when all experimental conditions are considered. On the contrary, the variations in plasma DBH (expressed as a percentage of the resting value) are not related to other sympathetic indices or to heart rate. Since NE and E vary little from subject to subject at rest and increase discretely in response to the various stimuli, these plasma catecholamine concentrations therefore appear to represent the most accurate indices of sympathetic activity.
Characterizing Nonlinear Heartbeat Dynamics Within a Point Process Framework

Human heartbeat intervals are known to have nonlinear and nonstationary dynamics. In this paper, we propose a model of R-R interval dynamics based on a nonlinear Volterra-Wiener expansion within a point process framework. Inclusion of second-order nonlinearities into the heartbeat model allows us to estimate instantaneous heart rate (HR) and heart rate variability (HRV) indexes, as well as the dynamic bispectrum characterizing higher order statistics of the nonstationary non-Gaussian time series. The proposed point process probability heartbeat interval model was tested with synthetic simulations and two experimental heartbeat interval datasets. Results show that our model is useful in characterizing and tracking the inherent nonlinearity of heartbeat dynamics. As a feature, the fine temporal resolution allows us to compute instantaneous nonlinearity indexes, thus sidestepping the uneven spacing problem. In comparison to other nonlinear modeling approaches, the point process probability model is useful in revealing nonlinear heartbeat dynamics at a fine timescale and with only short duration recordings.
Characterization and genetic mapping of fructose phosphotransferase mutations in Pseudomonas aeruginosa

Pseudomonas aeruginosa transports and phosphorylates fructose via a phosphoenolpyruvate-dependent fructose phosphotransferase system (PTS). Mutant strains deficient in both PTS activity and glucose-6-phosphate dehydrogenase activity were isolated and were used to select mannitol-utilizing revertant strains singly deficient in PTS activity. These mutants were unable to utilize fructose as a carbon source and failed to accumulate exogenously provided [14C]fructose, and crude cell extracts lacked phosphoenolpyruvate-dependent fructose PTS activity. Thus, the PTS was essential for the uptake and utilization of exogenously provided fructose by P. aeruginosa. Mutations at a locus designated pts, which resulted in a loss of PTS activity, exhibited 57% linkage to argF at 55 min on the chromosome in plasmid R68.45-mediated conjugational crosses. The pts mutations in four independently isolated mutant strains exhibited from 11 to 20% linkage to argF, and one of these mutations exhibited 3% linkage to lys-9015 in phage F116L-mediated transductional crosses.
Attenuation of Murine Collagen-Induced Arthritis by a Novel, Potent, Selective Small Molecule Inhibitor of IκB Kinase 2, TPCA-1 (2-[(Aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide), Occurs via Reduction of Proinflammatory Cytokines and Antigen-Induced T Cell Proliferation

Demonstration that IκB kinase 2 (IKK-2) plays a pivotal role in the nuclear factor-κB-regulated production of proinflammatory molecules by stimuli such as tumor necrosis factor (TNF)-α and interleukin (IL)-1 suggests that inhibition of IKK-2 may be beneficial in the treatment of rheumatoid arthritis. In the present study, we demonstrate that a novel, potent (IC50 = 17.9 nM), and selective inhibitor of human IKK-2, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), inhibits lipopolysaccharide-induced human monocyte production of TNF-α, IL-6, and IL-8 with an IC50 = 170 to 320 nM. Prophylactic administration of TPCA-1 at 3, 10, or 20 mg/kg, i.p., b.i. d. , resulted in a dose-dependent reduction in the severity of murine collagen-induced arthritis (CIA). The significantly reduced disease severity and delay of disease onset resulting from administration of TPCA-1 at 10 mg/kg, i.p., b.i. d. were comparable to the effects of the antirheumatic drug, etanercept, when administered prophylactically at 4 mg/kg, i.p., every other day. Nuclear localization of p65, as well as levels of IL-1β, IL-6, TNF-α, and interferon-γ, were significantly reduced in the paw tissue of TPCA-1- and etanercept-treated mice. In addition, administration of TPCA-1 in vivo resulted in significantly decreased collagen-induced T cell proliferation ex vivo. Therapeutic administration of TPCA-1 at 20 mg/kg, but not at 3 or 10 mg/kg, i.p., b.i. d. , significantly reduced the severity of CIA, as did etanercept administration at 12.5 mg/kg, i.p., every other day. These results suggest that reduction of proinflammatory mediators and inhibition of antigen-induced T cell proliferation are mechanisms underlying the attenuation of CIA by the IKK-2 inhibitor, TPCA-1.
Pain education in pre-registration professional health courses: a protocol for a scoping review

Introduction Pain is a global health concern causing significant health and social problems with evidence that patients experiencing pain are receiving inadequate care. The content of pain education in pre-registration professional health courses is thought to be lacking both in the UK and internationally which is unacceptable considering the prevalence of pain. Evaluating the effect of education is complex in that the outcome (improved healthcare) is some distance from the educational approach. Best evidence medical education has been proposed as a continuum between ‘opinion-based teaching’ and ‘evidence-based teaching’. Searching for evidence to inform best practice in health education is complex. A scoping review provides a practical and comprehensive strategy to locate and synthesise literature of varied methodology including reports from a variety of sources. The aim of this article is to describe a protocol for a scoping review that will locate, map and report research, guidelines and policies for pain education in pre-registration professional health courses. The extent, range and nature of reports will be examined, and where possible titles for potential systematic review will be identified. Methods and analysis Reports will be included for review that are directly relevant to the development of the pain curriculum in pre-registration professional health courses, eg nursing, medicine, physiotherapy. The search strategy will identify reports that include [pain] AND [pre-registration education or curriculum] AND [health professionals] in the title or abstract. Two authors will independently screen retrieved studies against eligibility criteria. A numerical analysis regarding the extent, nature and distribution of reports will be given along with a narrative synthesis to describe characteristics of relevant reports. Ethics and dissemination Formal ethical approval was not required to undertake this scoping review. Findings will be published in scientific peer-reviewed journals and via conference presentations.
The Effects of Acupuncture on Hypertension

Hypertension is a chronic medical condition that can lead to additional physiological complications including stroke, heart attack, and chronic kidney disease. Due to this, development of new and alternative methods to treat hypertension is necessary. This project emphasizes the treatment of hypertension by the stringent use of acupuncture. Acupuncture show’s promise as an alternative method to eliminate this disease from an inflicted individual. In this work, numerous studies were utilized to promote the use of acupuncture as an unconventional yet superior healing method for hypertension. Two studies demonstrate that acupuncture treatment of allotted patients with hypertension experienced a decline in blood pressure following the treatment. One study shows how acupuncture directly affects the neuroendocrine system leading to a decrease in sympathetic neural activity and ultimately a decrease blood pressure. These observations indicate that acupuncture is an effective treatment against hypertension.
Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication

Mean effect sizes for changes in depression were calculated for 2,318 patients who had been randomly assigned to either antidepressant medication or placebo in 19 double-blind clinical trials. As a proportion of the drug response, the placebo response was constant across different types of medication (75%), and the correlation between placebo effect and drug effect was . 90. These data indicate that virtually all of the variation in drug effect size was due to the placebo characteristics of the studies. The effect size for active medications that are not regarded to be antidepressants was as large as that for those classified as antidepressants, and in both cases, the inactive placebos produced improvement that was 75% of the effect of the active drug. These data raise the possibility that the apparent drug effect (25% of the drug response) is actually an active placebo effect. Examination of pre–post effect sizes among depressed individuals assigned to no-treatment or wait-list control groups suggest that approximately one quarter of the drug response is due to the administration of an active medication, one half is a placebo effect, and the remaining quarter is due to other nonspecific factors.
Economic burden of refractory chronic spontaneous urticaria on Kuwait’s health system

Background Chronic spontaneous urticaria (CSU) is a common problem worldwide. We evaluated the direct medical costs of treating patients with refractory CSU and the budget effect of omalizumab use in these patients in Kuwait. Methods The prevalence of CSU was estimated using the Delphi method. Medical records of patients with refractory CSU in Kuwait were reviewed. Costs were calculated from a health system perspective. One-way sensitivity analyses were conducted on the price and utilization of each cost component. Results Before omalizumab use, the total direct costs of treating 1,293 patients with refractory CSU were estimated to be USD 3,650,733 per year. This estimation was principally generated by outpatient visits. After omalizumab use, the cost was sensitive to price variation and estimated to be USD 15,828,612 per year. All other direct costs were reduced. Conclusion The economic burden of refractory CSU in Kuwait is high. Omalizumab use is costly, but its administration reduces all other direct costs.
A Remote Sensing Image Fusion Algorithm Based on Ordinal Fast Independent Component Analysis

Data fusion on remote sensing is hot in current image processing. A new approach, that is the ordinal fast independent component analysis for remote image fusion between Landsat ETM+ panchromatic and CBERS multi-spectral images, is proposed to eliminate high-order image data redundancy for two different remote sensing images. The independent components are done factor analysis, and then the fused image is obtained by applying image fusion rule. Visual and statistical analysis proves that the concept of fusion based on the ordinal fast independent component analysis is promising, and it significantly increases the signal-to-noise ratio and improves the fusion quality.
Subspace Information Criterion for Non-quadratic Regularizers — Model Selection for Sparse Regressors Subspace Information Criterion for Non-quadratic Regularizers

Non-quadratic regularizers, in particular the 1 norm regularizer can yield sparse solutions that generalize well. In this work we propose the Generalized Subspace Information Criterion (GSIC) that allows to predict the generalization error for this useful family of regularizers. We show that under some technical assumptions GSIC is an asymptotically unbiased estimator of the generalization error. GSIC is demonstrated to have a good performance in experiments with the 1 norm regularizer as we compare with the Network Information Criterion and cross-validation in relatively large sample cases. However in the small sample case, GSIC tends to fail to capture the optimal model due to its large variance. Therefore, also a biased version of GSIC is introduced, which achieves reliable model selection in the relevant and challenging scenario of high dimensional data and few samples.
LEARNING IN DEEP SCATTERING CONVOLUTION NETWORKS

This paper addresses the problem of automatic scattering feature selection for signal classification. While features derived from group invariant scattering networks are quite effective for signal classification. We argue that scattering networks are not always the appropriate choice as they are not learned for the objective at hand. In this paper, we explore jointly learning a deep scattering convolution network with a support vector machine by casting the problem as a multiple kernel learning problem. The convolution paths of the network are kernelized respectively to be selected in a large-margin context. We deduce scattering paths from the corresponding kernels after solving the kernel learning problem. Experiments on several datasets demonstrate the effectiveness of the proposed method over state-of-the-art techniques.
Wideband Radar for Ballistic Missile Defense and Range- Doppler Imaging of Satellites

Lincoln Laboratory led the nation in the development of high-power wideband radar with a unique capability for resolving target scattering centers and producing three-dimensional images of individual targets. The Laboratory fielded the first wideband radar, called ALCOR, in 1970 at Kwajalein Atoll. Since 1970 the Laboratory has developed and fielded several other wideband radars for use in ballistic-missile-defense research and space-object identification. In parallel with these radar systems, the Laboratory has developed high-capacity, high-speed signal and data processing techniques and algorithms that permit generation of target images and derivation of other target features in near real time. It has also pioneered new ways to realize improved resolution and scatterer-feature identification in wideband radars by the development and application of advanced signal processing techniques. Through the analysis of dynamic target images and other wideband observables, we can acquire knowledge of target form, structure, materials, motion, mass distribution, identifying features, and function. Such capability is of great benefit in ballistic missile decoy discrimination and in space-object identification.
A Piecewise Fuzzy Lyapunov Function Approach to Stability Analysis of Discrete T-S Fuzzy System

Stability analysis of discrete T-S fuzzy system with the common Lyapunov function approach and the fuzzy Lyapunov function approach is computationally attractive but conservative. Based on the definition of a discrete piecewise fuzzy Lyapunov function at each overlapping rules group, this paper introduces a new sufficient stability condition that only needs satisfying the stability condition of the fuzzy Lyapunov function approach in each maximal overlapped-rules group (MORG). A simulation example shows the condition is less conservative and easier to check than earlier approaches.
A Simplified Model of Coaxial, Multilayer High-Temperature Superconducting Power Cables with Cu Formers for Transient Studies

Bypassing transient current through copper (Cu) stabilizer layers reduces heat generation and temperature rise of high-temperature superconducting (HTS) conductors, which could protect HTS cables from burning out during transient conditions. The Cu layer connected in parallel with HTS tape layers impacts current distribution among layers and variations of phase resistance in either steady-state or transient conditions. Modeling the multilayer HTS power cable is important for transient studies. However, existing models of HTS power cables have only proposed HTS cables without the use of a Cu-former layer. To overcome this problem, the authors proposed a multilayer HTS power cable model that used a Cu-former layer in each phase for transient study. It was observed that resistance of the HTS conductor increased significantly in the transient state due to a quenching phenomenon, which made the transient current mainly flow into the Cu-former layers. Since resistance of the Cu-former layer has a significant impact on the transient current, detailed modeling of the Cu-former layer is described in this study. The feasibility of the developed HTS cable model is evaluated in the PSCAD/EMTDC program.
A FDTD scattered field formulation for dispersive media

This paper presents a scattered field formulation for the finite difference time domain technique applied to dispersive media characterized by the Debye equation with two relaxation constants. The 3D formulation is based on the auxiliary differential equation (ADE) approach. For verification purposes, numerical results for a one dimensional problem involving reflections from a dispersive dielectric half-space are presented and compared with the exact solution.
Discovery That Theonellasterol a Marine Sponge Sterol Is a Highly Selective FXR Antagonist That Protects against Liver Injury in Cholestasis

Background The farnesoid-x-receptor (FXR) is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated genes and biological functions. Principal Findings Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation assay shows that theonellasterol is a selective FXR antagonist, devoid of any agonistic or antagonistic activity on a number of human nuclear receptors including the vitamin D receptor, PPARs, PXR, LXRs, progesterone, estrogen, glucorticoid and thyroid receptors, among others. Exposure of HepG2 cells to theonellasterol antagonizes the effect of natural and synthetic FXR agonists on FXR-regulated genes, including SHP, OSTα, BSEP and MRP4. A proof-of-concept study carried out to investigate whether FXR antagonism rescues mice from liver injury caused by the ligation of the common bile duct, a model of obstructive cholestasis, demonstrated that theonellasterol attenuates injury caused by bile duct ligation as measured by assessing serum alanine aminostrasferase levels and extent of liver necrosis at histopathology. Analysis of genes involved in bile acid uptake and excretion by hepatocytes revealed that theonellasterol increases the liver expression of MRP4, a basolateral transporter that is negatively regulated by FXR. Administering bile duct ligated mice with an FXR agonist failed to rescue from liver injury and downregulated the expression of MRP4. Conclusions FXR antagonism in vivo results in a positive modulation of MRP4 expression in the liver and is a feasible strategy to target obstructive cholestasis.
Combined Complexity of Probabilistic Query Evaluation

Query evaluation over probabilistic databases (probabilistic query evaluation or PQE) is known to be intractable in many cases, even in data complexity, i.e., when the query is fixed. Although some restrictions of the queries and instances have been proposed to lower the complexity, these known tractable cases usually do not apply to combined complexity, i.e., when the query is not fixed. My thesis investigates the question of which queries and instances ensure the tractability of PQE in combined complexity. My first contribution is to study PQE of conjunctive queries on binary signatures, which we rephrase as a probabilistic graph homomorphism problem. We restrict the query and instance graphs to be trees and show the impact on the combined complexity of diverse features such as edge labels, branching, or connectedness. While the restrictions imposed in this setting are quite severe, my second contribution shows that, if we are ready to increase the complexity in the query, then we can evaluate a much more expressive language on more general instances. Specifically, we show that PQE for a particular class of Datalog queries on instances of bounded treewidth can be solved with linear complexity in the instance and doubly exponential complexity in the query. To prove this result, we use techniques from tree automata and knowledge compilation. The third contribution is to show the limits of some of these techniques by proving general lower bounds on knowledge compilation and tree automata formalisms.