gebhart/patrepeval huggingface dataset:
Distinct functional classes of PDGFRB pathogenic variants in primary familial brain calcification (2021)

Platelet-derived growth factor receptor beta (PDGFRB) is one of the genes associated with primary familial brain calcification (PFBC), an inherited neurological disease (OMIM:173410). Genetic analysis of patients and families revealed at least 13 PDGFRB heterozygous missense variants, including two novel ones described in the present report. Limited experimental data published on five of these variants had suggested that they decrease the receptor activity. No functional information was available on the impact of variants located within the receptor extracellular domains. Here, we performed a comprehensive molecular analysis of PDGFRB variants linked to PFBC. Mutated receptors were transfected in various cell lines to monitor receptor expression, signaling, mitogenic activity and ligand binding. Four mutants caused a complete loss of tyrosine kinase activity in multiple assays. One of the novel variants, p.Pro154Ser, decreased the receptor expression and abolished binding of platelet-derived growth factor (PDGF-BB). Others showed a partial loss of function related to reduced expression or signaling. Combining clinical, genetic and molecular data, we consider nine variants as pathogenic or likely pathogenic, three as benign or likely benign and one as a variant of unknown significance. We discuss the possible relationship between the variant residual activity, incomplete penetrance, brain calcification and neurological symptoms. In conclusion, we identified distinct molecular mechanisms whereby PDGFRB variants may result in a receptor loss of function. This work will facilitate genetic counseling in PFBC.
Asbestos and Zeolites: from A to Z via a Common Ion (2021)

Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.
21203 Study on evaporation enhancement of water film on wafer by EPA (2014)

Influence of isopropyl alcohol (IPA) supplying to the washing water on a rotating disk was experimentally investigated. Disappearance processes of liquid film and droplet formation behavior on a rotating disk were observed by using a high speed video camera. As a result, it was confirmed that removal of water film and the evaporations of droplets were enhanced by the IPA supply on the rotating disk.
Data from Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors to cross-resistance.&lt;/p&gt;Experimental Design:&lt;p&gt;We collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 patients with mCRPC receiving sequential AR signaling inhibitors (abiraterone and enzalutamide) in a randomized phase II clinical trial (NCT02125357). We utilized deep targeted and whole-exome sequencing to compare baseline and posttreatment somatic genomic profiles in circulating tumor DNA (ctDNA).&lt;/p&gt;Results:&lt;p&gt;Patient ctDNA abundance was correlated across plasma collections and independently prognostic for sequential therapy response and overall survival. Most driver alterations in established prostate cancer genes were consistently detected in ctDNA over time. However, shifts in somatic populations after treatment were identified in 53% of patients, particularly after strong treatment responses. Treatment-associated changes converged upon the &lt;i&gt;AR&lt;/i&gt; gene, with an average 50% increase in &lt;i&gt;AR&lt;/i&gt; copy number, changes in &lt;i&gt;AR&lt;/i&gt; mutation frequencies, and a 2.5-fold increase in the proportion of patients carrying AR ligand binding domain truncating rearrangements.&lt;/p&gt;Conclusions:&lt;p&gt;Our data show that the dominant &lt;i&gt;AR&lt;/i&gt; genotype continues to evolve during sequential lines of AR inhibition and drives acquired resistance in patients with mCRPC.&lt;/p&gt;&lt;/div&gt;
435. Skin Delivery of a RSV Vaccine with Surface Electroporation Provides Full Protection from Lower Respiratory Disease in the Cotton Rat (2016)

Respiratory syncytial virus (RSV) is a massive medical burden in infants and children worldwide, and an effective and safe RSV vaccine remains an unmet need. Here we report a novel vaccination strategy to deliver a pDNA vaccine encoding RSV-F using a surface electroporation device (SEP) to target epidermal cells in clinically relevant experimental models. We demonstrate the ability of this strategy to target epidermal Langerhans cells, and elicit robust cellular and humoral immune responses. In the cotton rat challenge model we demonstrate complete resistance to pulmonary infection after delivering a single low dose of vaccine. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine there was no enhanced lung inflammation upon virus challenge after pDNA vaccination. In summary the data presented outlines the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine strategy against RSV.
Subcellular Regulation of the Ionized Calcium Pool in Isolated Growth-Plate Chondrocytes (1989)

low total endogenous calcium content, as in the reserve and proliferative zone chondrocyte, cells buffer their ionized calcium pool at a low steady state between 150 and 300 nM. The endoplasmic reticulum appears to be primarily effective in the regulation of the ionized calcium pool under these conditions. With calcium loading of 20 to 30 nmol Ca+2/mg protein, as in the hypertrophic zone chondrocyte, the cells buffer their ionized calcium pool at a higher steady state between 600 and 700 nM. The mitochondria appear to be primarily effective in buffering the cytosolic ionized calcium pool after calcium loading. These data suggest that in the growth plate as the chondrocyte approaches the mineralization front, there is an accumulation of intracellular calcium that results in the saturation of the capacity of the endoplasmic reticulum to buffer the ionized calcium pool at a low steady state. Under these conditions of calcium loading, there is an increase in the intracellular ionized calcium concentration and a shift toward mitochondrial buffering of this calcium pool. This study has clinical relevance because in the cartilaginous tissues of the growth plate and in fracture callus, the matrix mineralizes as a prerequisite step in the formation of bone. Intracellular calcium accumulation and calcium release appear to play a role in matrix mineralization. An understanding of how the chondrocyte regulates intracellular calcium homeostasis in states of calcium accumulation is important in the overall understanding of bone development and fracture healing.
Gold particle generation by spray pyrolysis (1996)

Phase‐pure, micrometer‐sized, spherical gold particles (see Figure) have been generated for the first time by spray pyrolysis of gold nitrate at temperatures well below the melting point of gold. The effects of reaction atmosphere, temperature, and residence time on the morphology of the final product are described. The resulting gold powder is shown to be suitable for a variety of microelectronics applications. magnified image
Conclusions and Future Directions (2021)

This conclusion provides an overview of the key concepts discussed in this book. The book focuses on the advances made by a team of university researchers supported by an FY12 Office of the Secretary of Defense MURI grant on Transformational Electromagnetics, managed by AFOSR. This team sought to exploit metamaterials (MTMs), in the broadest definition of the term, as electromagnetic interaction structures in high-power microwave (HPM) sources, as well as in HPM antennas and components. Whereas the use of conventional media (metals) in vacuum electron device (VED) design is nearly a century old, the use of MTMs is not even a decade old. One can even imagine the design flexibility, combined with the opportunities for lower size, weight, and power (SWAP) that MTM enables, driving new ideas for space-based electromagnetic systems in both commercial and nation-state space programs.
Tunable resonance hyper-Raman spectroscopy of second-order nonlinear optical chromophores (2004)

Two-photon-resonant hyper-Raman spectra are reported for three "push-pull" conjugated organic chromophores bearing -NO(2) acceptor groups, two dipolar and one octupolar. The excitation source is an unamplified picosecond mode-locked Ti:sapphire laser tunable from 720 to 950 nm. The linear resonance Raman spectra of the same molecules are measured using excitation from the laser second harmonic. Excitation on resonance with the lowest-lying band in the linear absorption spectrum yields nearly identical resonance Raman and resonance hyper-Raman spectra. However, excitation into a region that appears to contain more than one electronic transition gives rise to different intensity patterns in the linear and nonlinear spectra, indicating that different transitions contribute differently to the one-photon and two-photon oscillator strength. The promise of the hyper-Raman technique for examining electronic transitions that are both one- and two-photon allowed is discussed.
Adaptive linearization of transmitter in the presence of I/Q Imbalance using distributed spatio-temporal neural network (2012)

For distortion-free data transmission, digital predistortion (DPD) is now a widely accepted method to linearize the power amplifier (PA) in a transmitter. DPD requires inverse modeling of PA and processing input through inverse model before feeding it to PA. However, when modulator in transmitter also have I/Q imbalance and local oscillator (LO) leakage, they cause extra intermodulation distortion (IMD) to appear at the PA output and conventional models such as Volterra series, memory polynomial, Weiner-Hammerstein and look up table methods are not able to model the inverse modeling properly and even worsen the spectral regrowth. This paper focuses on an adaptive distributed spatiotemporal neural network (DSTNN) for adaptive predistortion which has been shown to be robust to all the linear imperfections (i.e., gain/phase errors) as well as nonlinearity (i.e., IMD) to finally mitigate all the imperfections in the transmitter system in one step, due to its unique nonlinear mapping which does not depend on quadrature relation between I and Q components. DSTNN provides one-step solution for online adaptive application, which low cost in terms of floating point operations and does not require complex matrix operations such as matrix inversion.
Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection (2018)

Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine (P<0.05) observed in controls and increased the mitochondria membrane potential (P<0.05), maximal respiratory capacity (P<0.05), and intracellular ATP levels (P<0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning.
Data from Inhibition of Mitochondrial Matrix Chaperones and Antiapoptotic Bcl-2 Family Proteins Empower Antitumor Therapeutic Responses (2023)

&lt;div&gt;Abstract&lt;p&gt;Rational therapeutic approaches based on synthetic lethality may improve cancer management. On the basis of a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL, and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and obatoclax) or selective (ABT199, WEHI-539, and A1210477), along with the established mitochondrial matrix chaperone inhibitor gamitrinib-TPP. Drug combinations were tested in various therapy-resistant tumors &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; in murine model systems of melanoma, triple-negative breast cancer, and patient-derived orthotopic xenografts (PDX) of human glioblastoma. We found that combining BH3 mimetics and gamitrinib-TPP blunted cellular proliferation in a synergistic manner by massive activation of intrinsic apoptosis. In like manner, suppressing either Bcl-2, Bcl-xL, or Mcl-1 recapitulated the effects of BH3 mimetics and enhanced the effects of gamitrinib-TPP. Mechanistic investigations revealed that gamitrinib-TPP activated a PERK-dependent integrated stress response, which activated the proapoptotic BH3 protein Noxa and its downstream targets Usp9X and Mcl-1. Notably, in the PDX glioblastoma and BRAFi-resistant melanoma models, this drug combination safely and significantly extended host survival. Our results show how combining mitochondrial chaperone and Bcl-2 family inhibitors can synergize to safely degrade the growth of tumors recalcitrant to other treatments. &lt;i&gt;Cancer Res; 77(13); 3513–26. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Epitaxial film thickness in the low-temperature growth of Si(100) by plasma enhanced chemical vapor deposition (1996)

The limiting epitaxial thickness of Si films grown at a low substrate temperature by plasma enhanced chemical vapor deposition has been determined. The specific process used was electron cyclotron resonance plasma deposition. The limiting epitaxial thickness was found to decrease with the ratio of energetic ion-to-adatom arrivals on the substrate surface. The measured epitaxial thicknesses are similar to those obtained in previous investigations using molecular beam epitaxy. Hydrogen surface coverage does not appear to be a factor in limiting epitaxial thickness. The maximum epitaxial thickness remains to be determined for this process and substrate temperature range.
Measurement of lepton differential distributions and the top quark mass in $$t\bar{t}$$ t t ¯ production in pp collisions at $$\sqrt{s}=8$$ s = 8 TeV with the ATLAS detector (2017)

This paper presents single lepton and dilepton kinematic distributions measured in dileptonic <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>t</mml:mi> <mml:mover><mml:mrow><mml:mi>t</mml:mi></mml:mrow> <mml:mrow><mml:mo>¯</mml:mo></mml:mrow> </mml:mover> </mml:mrow> </mml:math> events produced in 20.2 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mtext>fb</mml:mtext> <mml:mrow><mml:mo>-</mml:mo> <mml:mn>1</mml:mn></mml:mrow> </mml:msup> </mml:math> of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow><mml:msqrt><mml:mi>s</mml:mi></mml:msqrt> <mml:mo>=</mml:mo> <mml:mn>8</mml:mn></mml:mrow> </mml:math> TeV <i>pp</i> collisions recorded by the ATLAS experiment at the LHC. Both absolute and normalised differential cross-sections are measured, using events with an opposite-charge <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>e</mml:mi> <mml:mi>μ</mml:mi></mml:mrow> </mml:math> pair and one or two <i>b</i>-tagged jets. The cross-sections are measured in a fiducial region corresponding to the detector acceptance for leptons, and are compared to the predictions from a variety of Monte Carlo event generators, as well as fixed-order QCD calculations, exploring the sensitivity of the cross-sections to the gluon parton distribution function. Some of the distributions are also sensitive to the top quark pole mass; a combined fit of NLO fixed-order predictions to all the measured distributions yields a top quark mass value of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow><mml:msubsup><mml:mi>m</mml:mi> <mml:mi>t</mml:mi> <mml:mi>pole</mml:mi></mml:msubsup> <mml:mo>=</mml:mo> <mml:mn>173.2</mml:mn> <mml:mo>±</mml:mo> <mml:mn>0.9</mml:mn> <mml:mo>±</mml:mo> <mml:mn>0.8</mml:mn> <mml:mo>±</mml:mo> <mml:mn>1.2</mml:mn></mml:mrow> </mml:math> GeV, where the three uncertainties arise from data statistics, experimental systematics, and theoretical sources.
A Cooperative Online Learning-Based Load Balancing Scheme for Maximizing QoS Satisfaction in Dense HetNets (2021)

This paper proposes a cooperative multi-agent online reinforcement learning-based (COMORL) bias offset (BO) control scheme for cell range expansion (CRE) in dense heterogeneous networks (HetNets). The proposed COMORL scheme controls BOs for CRE to maximize the number of user equipments (UEs) that satisfy their quality of service (QoS) requirements, especially in terms of delay and data rates. For this purpose, we developed a QoS satisfaction indicator that measures a violation of delay requirements by considering both QoS requirements and signal-to-interference-plus-noise ratio (SINR). In addition, we formulated a Markov decision process (MDP) model that is solved with a cooperative multi-agent online reinforcement learning algorithm. The proposed COMORL scheme maximizes the global utility for load-coupled base stations. Our simulation results verify the proposed COMORL scheme’s effectiveness in terms of throughput, delay satisfaction ratio, and fairness. Specifically, we verify that the proposed COMORL scheme achieves a maximum of approximately 27% and 30% improvement of the delay satisfaction ratio, which is how many UEs satisfy their delay requirement among all of the UEs in a serving BS under medium and full traffic loads, respectively, in a dynamic scenario in comparison to the max-SINR scheme.
Location-Dependent Excitatory Synaptic Interactions in Pyramidal Neuron Dendrites (2012)

Neocortical pyramidal neurons (PNs) receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.
Ultrahigh mid-infrared electric field enhancement via nanoantenna plasmonic resonance coupled to a novel hyperbolic metalens (2021)

Concentrating optical energy to areas much smaller than the diffraction limit, with high field enhancement in mid-infrared (MIR) using noble metals such as gold (Au) or silver (Ag), is not feasible because of high losses, lack of tunability, low resolution, and low-intensity enhancement. Our methods are based on appropriate metamaterial selection, coupling system (a hyperbolic metalens and a nanoantenna), and optimizations of their geometries. Doped indium arsenide (InAs) is used as an alternative to plasmonic metals when designing a Fresnel zone plate (FZP). A hyperbolic metamaterial (HMM), placed under FZP, is formed by stacking layers of doped and undoped InAs. By combining the focal spot of the metalens with the excited plasmons of a nanoantenna, the resulting structure exhibits an ultrahigh field-intensity enhancement factor of about 1012 with a high absorption cross-section and a focusing resolution of up to 10−3 λ at the operating wavelength of 7.8 μm.