Miracle-dz/UniFAR-FTUs huggingface dataset:
Cupular structure and its receptor relationship.

The general shape of the cupula conformsto the receptor area from which it arises. In the vertical canals of the frog, the cristae have an overall dumbbell shape; the cupula has corresponding enlarged masses which project from the expanded receptor ends while the central portion, which is about one third as thick, completes the diaphragm. The horizontal canal crista has a single enlarged end (club shaped) and consequently has a single cupular mass extending along one side of the ampulla up to the apex. A thinner portion extends to the opposite ampullar wall. In the vertical canals the enlarged masses end before the summit such that the thinner center reaches the apex.The cupula forms a tight diaphragm across the ampulla which is most easily displaced at the center. The central zone of the crista serves to position hair cells about one third the distance to the center of the ampulla while the ends of the crista are more peripherally located in relation to the diaphragm. A graded response to diaphragmatic displacement results. The apex of the cupula is most labile to detachment but not initial displacement. This region can act as a relief valve such that once displacement of the diaphragm has reached its maximum for the base of the cupula, the apical end is displaced and ultimately detached. This mechanism serves to prevent damage to the receptor structure and its cupular relationship.The cupula is composed of two components: filamentous material (protein) and an amorphous substance (mucopolysaccharide). The protein is related to supporting cells and the distal end of the kinocilium. The mucopolysaccharide is secreted from cuboidal cells which surround the receptor area and may serve as a binding substance.From the saddle-shaped receptor surface ciliary tufts consisting of 3 or 4 rows of short stereocilia project into the lumen and a single row of 5 or 6 of these processes continues across the subcupular space (60–70 µm) accompanied by a single kinocilium. The kinocilium continues into the filamentous and mucopolysaccharide matrix of the cupula to form a linkage between the receptor cells and the cupula. Scattered binding filaments are found between the kinocilium and adjacent stereocilia which are similar to those described in the saccule and utricle.
Erythrocyte Membrane Failure by Electromechanical Stress

We envision that electrodeformation of biological cells through dielectrophoresis as a new technique to elucidate the mechanistic details underlying membrane failure by electrical and mechanical stresses. Here we demonstrate the full control of cellular uniaxial deformation and tensile recovery in biological cells via amplitude-modified electric field at radio frequency by an interdigitated electrode array in microfluidics. Transient creep and cyclic experiments were performed on individually tracked human erythrocytes. Observations of the viscoelastic-to-viscoplastic deformation behavior and the localized plastic deformations in erythrocyte membranes suggest that electromechanical stress results in irreversible membrane failure. Examples of membrane failure can be separated into different groups according to the loading scenarios: mechanical stiffening, physical damage, morphological transformation from discocyte to echinocyte, and whole cell lysis. These results show that this technique can be potentially utilized to explore membrane failure in erythrocytes affected by other pathophysiological processes.
Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation.

BACKGROUND Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts. RESULTS Gene expression changes unequivocally discriminated between benign and malignant states, and a dual epigenetic and immune signature emerged defining this transition. To our knowledge, we discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was distinguished by a 122-epigenetic gene signature ("epigenetic" cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of "viral mimicry" were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures ("immune" clusters) were identified. CONCLUSION The TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of protein-coding and -noncoding RNA transcripts may be a better predictor for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell's epigenome with the immune milieu with potential for future therapeutic targeting. FUNDING National Institutes of Health (CA154683, CA158557, CA177940, CA087497-13), Tisch Cancer Institute, Melanoma Research Foundation, the Dow Family Charitable Foundation, and the Icahn School of Medicine at Mount Sinai.
Increased Interleukin-23 in Hashimoto’s Thyroiditis Disease Induces Autophagy Suppression and Reactive Oxygen Species Accumulation

Hashimoto’s thyroiditis (HT) represents the most common organ-specific autoimmune disease. Inflammatory factors and reactive oxygen species (ROS) play detrimental roles during the pathogenesis of HT. In this study, we found that thyroid follicular cells (TFCs) from HT patients expressed an elevated level of interleukin-23 (IL-23), which contributed to autophagy suppression and ROS accumulation. Additionally, IL-23-induced autophagy suppression and ROS accumulation in human TFCs was attributed to AKT/mTOR/NF-κB signaling pathway activation. Inhibition of either IL-23 by a specific neutralization antibody, or mTOR by rapamycin, or NF-κB by IKK-16, significantly reversed the autophagy suppression and ROS accumulation. These results demonstrate a key role for IL-23 in HT pathogenesis and provide a potential therapeutic strategy against IL-23 or its signaling pathway in HT.
The influence of symptoms of anxiety and depression on medication nonadherence and its causes: a population based survey of prescription drug users in Sweden

Purpose The purpose of this study was to evaluate the associations between self-reported symptoms of anxiety and/or depression, nonadherent (NA) behaviors, and reasons for NA to medication regimens. Methods A population based cross-sectional study with questionnaire was performed in the general Swedish population. The participants were 2,802 prescription drug users aged 18–84 years. The questionnaire covered use of prescription drugs, symptoms of anxiety and/or depression, based on the Hospital Anxiety and Depression Scale (HADS), various NA behavior types, intentional and unintentional, and various reasons for NA. Results Symptoms of anxiety and depression, independently and in combination, were associated with unintentional and intentional NA, with a stronger association with intentional NA. Regarding the reasons given for NA, for example anxiety, independently or in combination with depression, was associated with a fear of developing adverse drug reactions (ADRs). Depression, independently or in combination with anxiety, on the other hand, was associated with the actual development of ADRs. Conclusion A cross-sectional design such as this does not allow assessment of causality derived from the results. However, the results indicate that patients experiencing symptoms of psychological distress are at increased risk of NA, especially intentional NA, and could therefore benefit from extra attention from the health care professional. Patients with symptoms of anxiety and/or depression should be identified and monitored for the development and/or fear of ADRs, in order to improve adherence to medication regimens.
Analytical solutions to piezoelectric bimorphs based on improved FSDT beam model

This paper presents an efficient and accurate coupled beam model for piezoelectric bimorphs based on improved first-order shear deformation theory (FSDT). The model combines the equivalent single layer approach for the mechanical displacements and a layerwise modeling for the electric potential. General electric field function is proposed to reasonably approximate the through-the-thickness distribution of the applied and induced electric potentials. Layerwise defined shear correction factor (k) accounting for nonlinear shear strain distribution is introduced into both the shear stress resultant and the electric displacement integration. Analytical solutions for free vibrations and forced response under electromechanical loads are obtained for the simply supported piezoelectric bimorphs with series or parallel arrangement, and the numerical results for various length-to-thickness ratios are compared with the exact two-dimensional piezoelasticity solution. Excellent predictions with low error estimates of local and global responses as well as the modal frequencies are observed.
On ensemble components selection in data streams scenario with reoccurring concept-drift

In this article we consider the problem of data stream classification with recurring concept-drift. The proposed method determines when to add or remove a component from an ensemble. The algorithm discussed in this article is an extension of the ASE (Automatically Sized Ensemble) algorithm which guarantees that, with the assumed probability, adding a new component increases the accuracy not only for the current data chunk, but also for the entire data stream. The new approach improves the adaptation of the ASE algorithm to non-stationary environments, particularly when the data stream is generated by different data distributions that appear and disappear alternately. The procedure uses a Kullback-Leibler discrepancy to measure the suitability of elements for the considered data distribution.
Propagation Characteristics of Lamb Waves in Stringer-Stiffened Panels

Stringer-stiffened plate-like structure is a typical engineering structure and its structural integrity is critical. A guided Lamb wave-based damage identification scheme and an online structural health monitoring (SHM) system with an integrated PZT-sensor network were developed. In the previous studies, the specimens were relatively simple. In this paper, the abovementioned method was extended to the stiffened plate-like structure—a flat plate reinforced by stringer. FE dynamic simulation was applied to investigate the Lamb wave propagation characteristics due to the existence of stringer with the consideration of its material and geometric configurations.
Race and Sex Differences in QRS Interval and Associated Outcome Among Patients with Left Ventricular Systolic Dysfunction

Background Prolonged QRS duration is associated with increased mortality among heart failure patients, but race or sex differences in QRS duration and associated effect on outcomes are unknown. Methods and Results We investigated QRS duration and morphology among 2463 black and white patients with heart failure and left ventricular ejection fraction ≤35% who underwent coronary angiography and 12‐lead electrocardiography at Duke University Hospital from 1995 through 2011. We used multivariable Cox regression models to assess the relationship between QRS duration and all‐cause mortality and investigate race‐QRS and sex‐QRS duration interaction. Median QRS duration was 105 ms (interquartile range [IQR], 92–132) with variation by race and sex (P<0.001). QRS duration was longest in white men (111 ms; IQR, 98–139) followed by white women (108 ms; IQR, 92–140), black men (100 ms; IQR, 91–120), and black women (94 ms; IQR, 86–118). Left bundle branch block was more common in women than men (24% vs 14%) and in white (21%) versus black individuals (12%). In black patients, there was a 16% increase in risk of mortality for every 10 ms increase in QRS duration up to 112 ms (hazard ratio, 1.16; 95% CI, 1.07, 1.25) that was not present among white patients (interaction, P=0.06). Conclusions Black individuals with heart failure had a shorter QRS duration and more often had non‐left bundle branch block morphology than white patients. Women had left bundle branch block more commonly than men. Among black patients, modest QRS prolongation was associated with increased mortality.
Quantifying Uncertainty in Discrete-Continuous and Skewed Data with Bayesian Deep Learning

Deep Learning (DL) methods have been transforming computer vision with innovative adaptations to other domains including climate change. For DL to pervade Science and Engineering (S&EE) applications where risk management is a core component, well-characterized uncertainty estimates must accompany predictions. However, S&E observations and model-simulations often follow heavily skewed distributions and are not well modeled with DL approaches, since they usually optimize a Gaussian, or Euclidean, likelihood loss. Recent developments in Bayesian Deep Learning (BDL), which attempts to capture uncertainties from noisy observations, aleatoric, and from unknown model parameters, epistemic, provide us a foundation. Here we present a discrete-continuous BDL model with Gaussian and lognormal likelihoods for uncertainty quantification (UQ). We demonstrate the approach by developing UQ estimates on "DeepSD'', a super-resolution based DL model for Statistical Downscaling (SD) in climate applied to precipitation, which follows an extremely skewed distribution. We find that the discrete-continuous models outperform a basic Gaussian distribution in terms of predictive accuracy and uncertainty calibration. Furthermore, we find that the lognormal distribution, which can handle skewed distributions, produces quality uncertainty estimates at the extremes. Such results may be important across S&E, as well as other domains such as finance and economics, where extremes are often of significant interest. Furthermore, to our knowledge, this is the first UQ model in SD where both aleatoric and epistemic uncertainties are characterized.
Nanoindentation Studies Reveal Material Properties of Viruses

Over the last years, a paradigm shift has occurred from approaching viruses solely as disease‐bringing agents toward regarding them as functional nanoparticles, and a perfect example of Nature's capability to self‐assemble complex, multicomponent materials at the nanoscale. Viruses are now used as templates for constructing specific nanocontainers, either by changing the properties of the viruses themselves or by copying their compact, shelled structure into engineered materials, which are able to encapsulate various agents. To exploit the mechanisms used by nature to create functional nanocontainers, we need to understand what their material and biomechanical properties are. Nanoindentation, a technique based on atomic force microscopy, is perfectly suited to determine these characteristics. Here, we discuss the advances this research field has achieved, exploring prokaryotic (bacteriophages) as well as eukaryotic viruses. The material properties of viral shells (capsids) and of more complex viral assemblies are analyzed and compared. We discuss the Young's modulus of capsids, the maximal forces viruses can withstand, and explore the occurrence of material fatigue in nanosize objects. Finally, the impact of internalized materials and of specific alterations to the capsid proteins on the particle's mechanical strength is analyzed.
Effects of timolol on MYOC, OPTN, and WDR36 RNA levels.

OBJECTIVES To evaluate if timolol affects expression of 3 open-angle glaucoma genes and to study its ability to modulate dexamethasone-induced up-regulation of MYOC. METHODS We used quantitative polymerase chain reaction assay of glaucoma gene transcript levels from human trabecular meshwork (HTM) cultures exposed to 3 different doses of timolol. Three HTM cell cultures were grown with or without 1 of 3 timolol doses in the presence or absence of dexamethasone. RESULTS All 3 concentrations of timolol reduced MYOC RNA levels in 1 HTM culture compared with an untreated control and showed negligible effects in the other 2 cultures. Timolol had no effect on dexamethasone-induced MYOC transcript levels in any of the 3 cultures. Timolol, dexamethasone, and dexamethasone plus timolol had a negligible effect on OPTN and WDR36 RNA levels. CONCLUSIONS Timolol can reduce MYOC RNA levels in HTM cultures from some individuals. Timolol does not alter OPTN or WDR36 levels or ameliorate MYOC induction by dexamethasone in vitro. CLINICAL RELEVANCE It remains to be determined whether timolol could reduce production of misfolded myocilin protein by HTM cells in individuals with MYOC missense mutations. A broader survey of interindividual variation in response to timolol as well as mechanistic studies are still needed before potential therapeutic implications can be explored.
Focusing processor policies via critical-path prediction

Although some instructions hurt performance more than others, current processors typically apply scheduling and speculation as if each instruction was equally costly. Instruction cost can be naturally expressed through the critical path: if we could predict it at run-time, egalitarian policies could be replaced with cost-sensitive strategies that will grow increasingly effective as processors become more parallel. This paper introduces a hardware predictor of instruction criticality and uses it to improve performance. The predictor is both effective and simple in its hardware implementation. The effectiveness at improving performance stems from using a dependence-graph model of the microarchitectural critical path that identifies execution bottlenecks by incorporating both data and machine-specific dependences. The simplicity stems from a token-passing algorithm that computes the critical path without actually building the dependence graph. By focusing processor policies on critical instructions, our predictor enables a large class of optimizations. It can (i) give priority to critical instructions for scarce resources (functional units, ports, predictor entries); and (ii) suppress speculation on non-critical instructions, thus reducing "useless" misspeculations. We present two case studies that illustrate the potential of the two types of optimization, we show that (i) critical-path-based dynamic instruction scheduling and steering in a clustered architecture improves performance by as much as 21% (10% on average); and (ii) focusing value prediction only on critical instructions improves performance by as much as 5%, due to removing nearly half of the misspeculations.
Specialization Patterns in International Trade

The pattern of specialization is key to understanding how trade affects the production structure of an economy. To measure specialization, I compute concentration indexes for the value of exports and imports and decompose the overall concentration into the extensive product margin (number of products traded) and intensive product margin (value of products traded). Using detailed product- level trade data for 130 countries, I find that exports are more concentrated than imports, specialization occurs mainly in the intensive product margin, and larger economies have more diversified exports and imports because they trade more products. Based on these facts, I assess the ability of the Eaton-Kortum model, the workhorse model of modern Ricardian trade theory, to account for the observed patterns. The results show that specialization through comparative advantage induced by technological differences can explain the qualitative and quantitative facts. The key determinants of specialization are: the degree of absolute and comparative advantage, the elasticity of substitution and geography.
STIMATION VIA LSH S AMPLERS ( LSS )

The softmax function has multiple applications in large-scale machine learning. However, calculating the partition function is a major bottleneck for large state spaces. In this paper, we propose a new sampling scheme using locality-sensitive hashing (LSH) and an unbiased estimator that approximates the partition function accurately in sub-linear time. The samples are correlated and unnormalized, but the derived estimator is unbiased. We demonstrate the significant advantages of our proposal by comparing the speed and accuracy of LSH-Based Samplers (LSS) against other state-of-the-art estimation techniques.
Impact of data quality and surface-to-column representativeness on the PM 2.5 / satellite AOD relationship for the contiguous United States

Abstract. Satellite-derived aerosol optical depth (AOD) observations have been used to estimate particulate matter smaller than 2.5 μm (PM2.5). However, such a relationship could be affected by the representativeness of satellite-derived AOD to surface aerosol particle mass concentration and satellite AOD data quality. Using purely measurement-based methods, we have explored the impacts of data quality and representativeness on the AOD-inferred PM2.5 / AOD relationship for the contiguous United States (CONUS). This is done through temporally and spatially collocated data sets of PM2.5 and AOD retrievals from Aqua/Terra Moderate Resolution Imaging Spectroradiometer (MODIS), Multi-angle Imaging Spectroradiometer (MISR), and Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP). These analyses show that improving data quality of satellite AOD, such as done with data assimilation-grade retrievals, increases their correlation with PM2.5. However, overall correlation is relatively low across the CONUS. Also, integrated extinction observed within 500 m above ground level (a.g.l.), as measured by CALIOP, is not well representative of the total column AOD. Surface aerosol in the eastern CONUS is better correlated with total column AOD than in the western CONUS. The best correlation values are found for estimated dry mass CALIOP extinction at 200–300 m a.g. l. and PM2.5, but additional work is needed to address the ability of using actively sensed AOD as a proxy for PM2.5 concentrations.
AN ANALYTICAL MODEL TO STUDY TRANSIENT THERMAL STRESSES IN GRAPHITE TARGET RODS HIT BY OFF-AXIS BEAM FOR CNGS FACILITY

An analytical method to determine the transient stresses induced by a fast extracted proton beam hitting off-axis a graphite rod was fully developed. An exact solution for the temperature field was first determined, by means of Fourier-Bessel expansions Quasi-static thermal stresses were then computed as a function of the calculated temperature distribution, making use of Goodier’s method for the thermoelastic problem. Finally, the contribution of dynamic stresses due to longitudinal and bending waves was also determined by using mode-summation modal analysis.