gebhart/patrepeval huggingface dataset:
Abstract LB-295: Identification of the first class of proteasome inhibitors that impair 26S proteasome assembly in vitro. (2010)

Abstract The Ubiquitin-Proteasome System (UPS) is the main non-lysosomial proteolytic machinery in the eukaryotic cells. Prior to their degradation proteins are adressed to the catalytic 26S proteasome complex composed of a 20S “core” that contains proteolytic activities, assembled with one or two 19S regulatory particles that bind proteins to be degraded. Due to its central role of in regulating cell cycle progression and signal transduction the UPS has been proposed as a suitable target for antineoplastic strategies. To date only catalytic inhibitors of proteasome, targeting proteolytic activities of the 20S core particle, have been characterized and/or have emerged as potent anticancer drugs (1). However, the capacity of the UPS to degrade proteins not only depends of the catalytic activities of the 20S core, but also of the 26S proteasome assembly, a dynamic and tightly controlled cellular process. Thus, compounds impairing 26S proteasome assembly could represent a novel class of proteasome inhibitors. With the aim of identifying such molecules we first set up a robust biochemical screening assay allowing us to follow 26S proteasome assembly in vitro. First, 26S proteasome was purified from Hela cells using affinity chromatography followed by gel filtration. Then, experimental conditions were determined for in vitro 26S disassembly into its constitutive sub-complexes (19S+20S) ands its re-assembly as an active and functional 26S entity. The differential CTL-activity between 26S and 20S proteasomes (2) was then used as the readout to follow the reassembly of 26S in vitro, prior to be confirmed using in gel overlay experiments and western-blotting. Using this biochemical assay: 1) we screened naturals compounds endowed with antiproliferative properties and described as inhibitors of the ubiquitine-proteasome pathway (3). 2) we identified structurally-related natural molecules, epidithiodioxopiperazine and diketodithiopiperazine derivatives, as the first class of molecules inhibiting proteasome assembly without significantly affecting neither 26S nor 20S catalytic activity in vitro. Our research efforts now concentrate in showing that: 1) these molecules inhibit proteasome assembly in cells, and that 2) this inhibition can be correlated with their antiproliferative effects. References Sterz J. et al. Extert Opin. Invest. Drugs, 2008, 17 Rivett AJ et al., Experimental Gerontology, 2002, 37 Vandenberghe I. et al., Biochem. Pharmacol., 2008, 76 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-295.
Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention (2015)

Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg) and arenaviruses (Lassa and Junín viruses), are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1) and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms.
Current Trends in Medicinal Chemistry (2013)

A 5 years old female, mixed-breed goat was presented to clinic for evaluation of postmortem lesions because it showed evidence of paratuberculosis. At necropsy examination, whitish-yellow lobulated mass (11 × 8 × 4 cm) was found on the ileal mesentery. Histopathologically, the tumor consisted of well-differentiated fat cells with no pleomorphism and anaplasia. The cells have monovacuolated and multivacuolated cytoplasm. Mitotic figures were not observed in the mature adipocytes. On the basis of the gross and microscopical findings, the mesenteric lipoma was diagnosed.
Table S1 from Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and αPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer (2023)

&lt;p&gt;Supplementary Table 1&lt;/p&gt;
Restoring an elliptical chamber during rebuilding a wrap around anterior infarction (2005)

Left ventricular geometry is distorted after anterior infarction caused by occlusion of a wrap around left anterior descending artery. Loss of the apex creates a spherical left ventricular (LV) chamber, whose rebuilding requires reconstruction techniques that exclude the non-functional inferior wall. The described technique of tailoring the apex defines a way to create an oblique elliptical rim for subsequent patch placement to complete the restoration procedure. This method of ventricular rebuilding differs from methods that follow the inferior wall scar, which result in a restoration procedure that leaves a spherical or box-like apical region.
Multiple haplotype-resolved genomes reveal population patterns of gene and protein diplotypes (2014)

To fully understand human biology and link genotype to phenotype, the phase of DNA variants must be known. Here we present a comprehensive analysis of haplotype-resolved genomes to assess the nature and variation of haplotypes and their pairs, diplotypes, in European population samples. We use a set of 14 haplotype-resolved genomes generated by fosmid clone-based sequencing, complemented and expanded by up to 372 statistically resolved genomes from the 1000 Genomes Project. We find immense diversity of both haploid and diploid gene forms, up to 4.1 and 3.9 million corresponding to 249 and 235 per gene on average. Less than 15% of autosomal genes have a predominant form. We describe a 'common diplotypic proteome', a set of 4,269 genes encoding two different proteins in over 30% of genomes. We show moreover an abundance of cis configurations of mutations in the 386 genomes with an average cis/trans ratio of 60:40, and distinguishable classes of cis- versus trans-abundant genes. This work identifies key features characterizing the diplotypic nature of human genomes and provides a conceptual and analytical framework, rich resources and novel hypotheses on the functional importance of diploidy.
Sleep architecture changes during a trek from 1400 to 5000 m in the Nepal Himalaya (2009)

The aim of this study was to examine sleep architecture at high altitude and its relationship to periodic breathing during incremental increases in altitude. Nineteen normal, sea level-dwelling volunteers were studied at sea level and five altitudes in the Nepal Himalaya. Morning arterial blood gases and overnight polysomnography were performed in 14 subjects at altitudes: 0, 1400, 3500, 3900, 4200 and 5000 m above sea level. Subjects became progressively more hypoxic, hypocapnic and alkalinic with increasing altitude. As expected, sleep architecture was affected by increasing altitude. While time spent in Stage 1 non-rapid eye movement sleep increased at 3500 m and higher (P < 0.001), time spent in slow-wave sleep (SWS) decreased as altitude increased. Time spent in rapid eye movement (REM) sleep was well preserved. In subjects who developed periodic breathing during sleep at one or more altitudes (16 of 19), arousals because of periodic breathing predominated, contributing to an increase in the total arousal index. However, there were no differences in sleep architecture or sleeping oxyhaemoglobin saturation between subjects who developed periodic breathing and those who did not. As altitude increased, sleep architecture became progressively more disturbed, with Stage 1 and SWS being affected from 3500 m, while REM sleep was well preserved. Periodic breathing was commonplace at all altitudes, and while associated with increases in arousal indices, did not have any apparent effect on sleep architecture.
Liver disease in patients undergoing head and neck surgery: Incidence and risk for postoperative complications (2016)

2c. Laryngoscope, 127:102-109, 2017.
Highly durable 4-kHz ArF excimer laser G42A for sub-90-nm lithography (2004)

Mass production in 193 nm lithography is now starting and its target node is moving from 90 nm to 65 nm. The main performance requirement of ArF excimer laser in this situation is high power with ultra narrow spectrum for higher throughput. The other hand, higher reliability and lower cost of ownership (CoO) are strongly hoped in mass production because CoO of ArF excimer laser is still higher than that of KrF excimer laser. We have already reported the 4 kHz ArF excimer laser for mass production, model G42A, which has an 20 W of average power, spectral bandwidth less than 0.3 pm (FWHM) and a spectral purity less than 0.75 pm (E95). We applied some technologies to G42A for achieving the high reliability and long lifetime. As a result, G42A showed the stable performance during the lifetime of over 10 billion pulses. In this paper, we report the long-term stability of G42A. And also, we introduce the reliability data of G40A series, which is the previous 4 kHz ArF excimer laser model.
Quantitation of the fourth complement component by electrophoresis in agarose gel containing antibodies. (1970)

Electrophoresis in agarose gel containing antibodies can be used for quantitation of C4 in serum and plasma. The normal range of the C4 concentration in serum and plasma varied between 40 and 200% of the standard pools. Low C4 values were found in systemic lupus erythematosus, in acquired haemolytic anaemia and in hereditary angioneurotic oedema. Differences in C4 values were found between normal sera and the corresponding EDTA plasma, when tested after dilution in calcium-free and EDTA buffers, respectively. After storage of the samples for 1 day at 20°C or 37°C the C4 values decreased, most markedly in plasma; no further decrease was found on prolongation of storage, and the difference between serum and plasma C4 values disappeared. The plasma C4 levels gradually fell on storage at 4°C, but a clear difference between serum and plasma was still demonstrable after 5 days. The method described is simple and quick and can be used routinely in large scale investigations.
Axonal Neurofilaments Control Multiple Fiber Properties But Do Not Influence Structure or Spacing of Nodes of Ranvier (2007)

In the vertebrate nervous system, axon calibers correlate positively with myelin sheath dimensions and electrophysiological parameters including action potential amplitude and conduction velocity. Neurofilaments, a prominent component of the neuronal cytoskeleton, are required by axons to support their normal radial growth. To distinguish between fiber features that arise in response to absolute axon caliber and those that are under autonomous control, we investigated transgenic mice in which neurofilaments are sequestered in neuronal cell bodies. The neurofilament deficient axons in such mice achieve mature calibers only 50% of normal and have altered conduction properties. We show here that this primary axonal defect also induces multiple changes in myelin sheath composition and radial dimensions. Remarkably, other fundamental fiber features, including internodal spacing and the architecture and composition of nodes of Ranvier, remain unaltered. Thus, many fiber characteristics are controlled through mechanisms operating independently of absolute axon caliber and the neurofilament cytoskeleton.
ImageAssist: Tools for Enhancing Touchscreen-Based Image Exploration Systems for Blind and Low Vision Users (2023)

Blind and low vision (BLV) users often rely on alt text to understand what a digital image is showing. However, recent research has investigated how touch-based image exploration on touchscreens can supplement alt text. Touchscreen-based image exploration systems allow BLV users to deeply understand images while granting a strong sense of agency. Yet, prior work has found that these systems require a lot of effort to use, and little work has been done to explore these systems’ bottlenecks on a deeper level and propose solutions to these issues. To address this, we present ImageAssist, a set of three tools that assist BLV users through the process of exploring images by touch — scaffolding the exploration process. We perform a series of studies with BLV users to design and evaluate ImageAssist, and our findings reveal several implications for image exploration tools for BLV users.
Survival with AGS-003, an autologous dendritic cell–based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results (2015)

#NCT00678119.
Optimizing a reconfigurable material via evolutionary computation (2015)

Rapid prototyping by combining evolutionary computation with simulations is becoming a powerful tool for solving complex design problems in materials science. This method of optimization operates in a virtual design space that simulates potential material behaviors and after completion needs to be validated by experiment. However, in principle an evolutionary optimizer can also operate on an actual physical structure or laboratory experiment directly, provided the relevant material parameters can be accessed by the optimizer and information about the material's performance can be updated by direct measurements. Here we provide a proof of concept of such direct, physical optimization by showing how a reconfigurable, highly nonlinear material can be tuned to respond to impact. We report on an entirely computer controlled laboratory experiment in which a 6×6 grid of electromagnets creates a magnetic field pattern that tunes the local rigidity of a concentrated suspension of ferrofluid and iron filings. A genetic algorithm is implemented and tasked to find field patterns that minimize the force transmitted through the suspension. Searching within a space of roughly 10^{10} possible configurations, after testing only 1500 independent trials the algorithm identifies an optimized configuration of layered rigid and compliant regions.
Anomalous heavy doping in chemical-vapor-deposited titanium trisulfide nanostructures (2021)

Trichalcogenide semiconductors could provide a platform for quasi-one-dimensional electronic devices, on condition that their tunable doping capability is established. This work presents a synthetic strategy towards degenerately doped titanium trisulfide nanostructures that feature ultralow carrier activation barriers and exceptional ambient stability. The anomalous electrical conductivity of the synthesized nanostructures is revealed both experimentally and computationally to be associated with high-density S22- vacancies, which are generated spontaneously during the chemical vapor deposition process and act effectively as the electron dopants. These results hence portend the tantalizing possibility of constructing nanoscale electronics with defect-engineered trichalcogenide semiconductors.
Dye sensitized solar cells with cobalt and iodine-based electrolyte: the role of thiocyanate-free ruthenium sensitizers (2014)

Isomeric Ru(<sc>ii</sc>) sensitizers, with varied steric impediment on TiO<sub>2</sub>, show high efficiency using Co<sup>2+/3+</sup> electrolyte, with higher efficiency for the more symmetric isomers.
FAM190A Rearrangements Provide a Multitude of Individualized Tumor Signatures and Neo-antigens in Cancer (2011)

We found FAM190A transcripts to have internal rearrangements in 40% (19/48) of unselected human cancers. Most of these tumors (84%) had in-frame structures, 94% of which involved deletion of exon 9. The FAM190A gene is located at 4q22.1 in a region of common fragility, FRA4F. Although normally stable in somatic cells, common fragile sites can be hotspots of rearrangement in cancer. The genomic deletion patterns observed at some sites, including FRA4F at 4q22.1, are proposed to be the result of selection for disrupted tumor-suppressor genes. Our evidence, however, indicated additional patterns for FAM190A. We found genomic deletions accounted for some FAM190A in-frame structures, and cases pre-selected for FAM190A genomic deletions had a yet higher prevalence of FAM190A rearrangements. Our evidence of widespread in-frame heterozygous and homozygous rearrangements affecting this gene in tumors of multiple types leads speculation on structural grounds that the mutant forms may retain, provide new, or possibly convey dominant-negative functions. Although a functionally uncharacterized gene, it is evolutionary conserved across vertebrates. In addition to its potential oncogenic role, the in-frame deletions predict the formation of cancer-specific FAM190A peptide sequences (neo-antigens) with potential diagnostic and therapeutic usefulness.
Effect of Substrate Miscut on the Direct Growth of Semipolar (10-1-1) GaN on (100) MgAl2O4 by Metalorganic Chemical Vapor Deposition (2006)

We report on the the direct growth of semipolar (10-1-1) GaN templates on (100) MgAl2O4 substrates miscut in the <011> direction. (10-1-1) GaN deposited on nominally on-axis substrates did not coalesce. An intentional substrate miscut broke the four-fold symmetry of the substrate surface and resulted in coalesced layers. The minimum full-width at half maximum (FWHM) of the on-axis (10-1-1) X-ray rocking curve was 0.4° for a 1.5° miscut. The FWHM of the off-axis (000-2) rocking curve remained constant for miscuts <3.0°. 93% and 99% of the volume of the samples were aligned in a single epitaxial variant for 1.5° and 3.0° substrate miscuts, respectively.
Emission Intensity Dependence and Single-Exponential Behavior In Single Colloidal Quantum Dot Fluorescence Lifetimes (2003)

We present measurements of photoluminescence decay dynamics from single colloidal CdSe quantum dots. We find that the decays fluctuate in time with decay rates that correlate with time-averaged emission intensities. Moreover, the decays measured by selecting only those photons collected while the single quantum dot emission intensity was near its maximum yields single-exponential dynamics. We find that the “maximum-intensity” decays are nearly identical across different independently synthesized samples of nearly the same size. The combination of single-exponential kinetics and decays that are reproducible across samples leads us to speculate that it is the radiative lifetime that is measured and that the quantum yield of a single dot near its maximum emission intensity is close to unity. The variations in decay rates with time and their correlation with emission intensity indicate these intensity time trajectories primarily reflect fluctuations in nonradiative relaxation pathways.
Rescue of Skeletal Muscles of γ-Sarcoglycan- Deficient Mice with Adeno-Associated Virus-Mediated Gene Transfer (2000)

In humans, a subset of cases of Limb-girdle muscular dystrophy (LGMD) arise from mutations in the genes encoding one of the sarcoglycan (alpha, beta, gamma, or delta) subunits of the dystrophin-glycoprotein complex. While adeno-associated virus (AAV) is a potential gene therapy vector for these dystrophies, it is unclear if AAV can be used if a diseased muscle is undergoing rapid degeneration and necrosis. The skeletal muscles of mice lacking gamma-sarcoglycan (gsg-/- mice) differ from the animal models that have been evaluated to date in that the severity of the skeletal muscle pathology is much greater and more representative of that of humans with muscular dystrophy. Following direct muscle injection of a recombinant AAV [in which human gamma-sarcoglycan expression is driven by a truncated muscle creatine kinase (MCK) promoter/enhancer], we observed significant numbers of muscle fibers expressing gamma-sarcoglycan and an overall improvement of the histologic pattern of dystrophy. However, these results could be achieved only if injections into the muscle were prior to the development of significant fibrosis in the muscle. The results presented in this report show promise for AAV gene therapy for LGMD, but underscore the need for intervention early in the time course of the disease process.
Quantization-Aided Secrecy: FD C-RAN Communications with Untrusted Radios (2021)

In this work, we study a full-duplex (FD) cloud radio access network (C-RAN) from the aspects of infrastructure sharing and information secrecy, where the central unit utilizes FD remote radio units (RU)s belonging to the same operator, i.e., the trusted RUs, as well as the RUs belonging to other operators or private owners, i.e., the untrusted RUs. Furthermore, the communication takes place in the presence of untrusted external receivers, i.e., eavesdropper nodes. The communicated uplink (UL) and downlink (DL) waveforms are quantized in order to comply with the limited capacity of the fronthaul links. In order to provide information secrecy, we propose a novel utilization of the quantization noise shaping in the DL, such that it is simultaneously used to comply with the limited capacity of the fronthaul links, as well as to degrade decoding capability of the individual eavesdropper and the untrusted RUs for both the UL and DL communications. In this regard, expressions describing the achievable secrecy rates are obtained. An optimization problem for jointly designing the DL and UL quantization and precoding strategies are then formulated, with the purpose of maximizing the overall system weighted sum secrecy rate. Due to the intractability of the formulated problem, an iterative solution is proposed, following the successive inner approximation and semi-definite relaxation frameworks, with convergence to a stationary point. Numerical evaluations indicate a promising gain of the proposed approaches for providing information secrecy against the untrusted infrastructure nodes and/or external eavesdroppers in the context of FD C-RAN communications.