gebhart/patrepeval huggingface dataset:
Mutational landscape of uterine and ovarian carcinosarcomas. (2016)

5589 Background: Carcinosarcomas (CS) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. While an increasing body of evidence supports the origin of both CS elements from a common epithelial cell that undergoes sarcomatous dedifferentiation, limited information is currently available about the role of somatic mutations (SNV) and copy number variations (CNV) in these rare tumors. The objective of our study was to evaluate the genetic landscape of uterine and ovarian CSs by whole-exome-sequencing (WES). Methods: We analyzed the mutational landscape of 63 fresh frozen CS biopsies and 5 primary CS cell lines by WES, most of which were matched to normal DNA from the same patients. We also performed multi region WES in separate carcinoma and sarcoma areas to resolve the genetic architecture and evolutionary histories of CS. Finally, in transfection experiments we validated somatic histone 2A and 2B mutations as potential drivers of epithelial-mesenchymal transition (EMT). Results: Our results demonstrated the presence of two major genetic types of uterine CSs and provided evidence that both subtypes, as well as ovarian CS, arise from sarcomatous transformation of carcinomas. We found an excess of mutations in histones H2A and H2B. We also found frequent deletions comprising TP53 and MBD3, and frequent amplification of chromosome segments containing PIK3CA, CCNE1, TERT and c-MYC. Amplifications of the histone cluster and TERT were significantly more frequent in CS than their epithelial counterparts. Stable transgenic expression H2A and H2Bin USC cell lines demonstrated that mutant, but not wild type H2A and H2B increased expression of markers of epithelial-mesenchymal transition (EMT), suggesting a role in sarcomatous transformation. Comparison of the phylogenetic relationships of carcinomatous and sarcomatous elements of the same tumors demonstrated separate lineages resulting in these two components. Conclusions: Our results provide new insight into the origins and development of uterine and ovarian CS and defined the genetic landscape of this type of malignant tumor. These findings also suggest new therapeutic targets for these highly aggressive neoplasms.
The critical protein interactions and structures that elicit growth deregulation in cancer and viral replication (2010)

One of the greatest challenges in biomedicine is to define the critical targets and network interactions that are subverted to elicit growth deregulation in human cells. Understanding and developing rational treatments for cancer requires a definition of the key molecular targets and how they interact to elicit the complex growth deregulation phenotype. Viral proteins provide discerning and powerful probes to understand both how cells work and how they can be manipulated using a minimal number of components. The small DNA viruses have evolved to target inherent weaknesses in cellular protein interaction networks to hijack the cellular DNA and protein replication machinery. In the battle to escape the inevitability of senescence and programmed cell death, cancers have converged on similar mechanisms, through the acquisition and selection of somatic mutations that drive unchecked cellular replication in tumors. Understanding the dynamic mechanisms through which a minimal number of viral proteins promote host cells to undergo unscheduled and pathological replication is a powerful strategy to identify critical targets that are also disrupted in cancer. Viruses can therefore be used as tools to probe the system-wide protein-protein interactions and structures that drive growth deregulation in human cells. Ultimately this can provide a path for developing system context-dependent therapeutics. This review will describe ongoing experimental approaches using viruses to study pathways deregulated in cancer, with a particular focus on viral cellular protein-protein interactions and structures.
Re: Downregulation of Ral GTPase-Activating Protein Promotes Tumor Invasion and Metastasis of Bladder Cancer (2013)

No AccessJournal of UrologyInvestigative Urology1 Oct 2013Re: Downregulation of Ral GTPase-Activating Protein Promotes Tumor Invasion and Metastasis of Bladder Cancer Anthony AtalaM.D. Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.06.057AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Downregulation of Ral GTPase-Activating Protein Promotes Tumor Invasion and Metastasis of Bladder Cancer." The Journal of Urology, 190(4), p. 1437 © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 190Issue 4October 2013Page: 1437Supplementary Materials Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Metrics Author Information Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...
Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2-Specific Human Chimeric Monoclonal Antibodies (2015)

Presently, the seroprevalence of human papillomavirus (HPV) minor capsid antigen L2-reactive antibody is not well understood, and no serologic standard exists for L2-specific neutralizing antibodies. Therefore, we screened a total of 1,078 serum samples for HPV16 L2 reactivity, and these were obtained from four prior clinical studies: a population-based (n = 880) surveillance study with a high-risk HPV DNA prevalence of 10.8%, a cohort study of women (n = 160) with high-grade cervical intraepithelial neoplasia (CIN), and two phase II trials in women with high-grade vulvar intraepithelial neoplasia (VIN) receiving imiquimod therapy combined with either photodynamic therapy (PDT) (n = 19) or vaccination with a fusion protein comprising HPV16 L2, E7, and E6 (TA-CIN) (n = 19). Sera were screened sequentially by HPV16 L2 enzyme-linked immunosorbent assay (ELISA) and then Western blot. Seven of the 1,078 serum samples tested had L2-specific antibodies, but none were detectably neutralizing for HPV16. To develop a standard, we substituted human IgG1 sequences into conserved regions of two rodent monoclonal antibodies (MAbs) specific for neutralizing epitopes at HPV16 L2 residues 17 to 36 and 58 to 64, creating JWW-1 and JWW-2, respectively. These chimeric MAbs retained neutralizing activity and together reacted with 33/34 clinically relevant HPV types tested. In conclusion, our inability to identify an HPV16 L2-specific neutralizing antibody response even in the sera of patients with active genital HPV disease suggests the subdominance of L2 protective epitopes and the value of the chimeric MAbs JWW-1 and JWW-2 as standards for immunoassays to measure L2-specific human antibodies.
Ocular dominance plasticity: inhibitory interactions and contrast equivalence (2017)

Abstract Brief monocular occlusion results in a transient change in ocular dominance, such that the previously patched eye makes a stronger contribution to the binocular percept after occlusion. The previously unpatched eye therefore makes a correspondingly weaker contribution to the binocular sum. To shed light on the mechanism underlying this change we investigate how the relationship between the perception of fusion, suppression, and diplopia changes after short-term monocular deprivation. Results show that fusible stimuli seen by the unpatched eye are actively suppressed as a result of patching and that this can be reversed by an interocular contrast imbalance. This suggests that dichoptic inhibition plays an important role in ocular dominance changes due to short-term occlusion, possibly by altering the contrast gain prior to binocular summation. This may help explain why this form of plasticity affects the perception of both fusible and rivalrous stimuli.
High Power Density Silicon Combustion Systems for Micro Gas Turbine Engines (2002)

As part of an effort to develop a micro-scale gas turbine engine for power generation and micro-propulsion applications, this paper presents the design, fabrication, experimental testing, and modeling of the combustion system. Two radial inflow combustor designs were examined; a single-zone arrangement and a primary and dilution-zone configuration. Both combustors were micro-machined from silicon using Deep Reactive Ion Etching (DRIE) and aligned fusion wafer bonding. Hydrogen-air and hydrocarbon-air combustion was stabilized in both devices, each with chamber volumes of 191 mm3. Exit gas temperatures as high as 1800 K and power densities in excess of 1100 MW/m3 were achieved. For the same equivalence ratio and overall efficiency, the dual-zone combustor reached power densities nearly double that of the single-zone design. Because diagnostics in micro-scale devices are often highly intrusive, numerical simulations were used to gain insight into the fluid and combustion physics. Unlike large-scale combustors, the performance of the micro-combustors was found to be more severely limited by heat transfer and chemical kinetics constraints. Important design trades are identified and recommendations for micro-combustor design are presented.
Supporting concurrent memory access in TCF-aware processor architectures (2017)

The Thick Control Flow (TCF) model packs together self-similar computations to simplify parallel programming and to eliminate redundant usage of associated software and hardware resources. While there are processor architectures supporting native execution ofprograms written for the model, none of them support concurrent memory access that can speed up execution of many algorithms by a logarithmic factor. In this paper, we propose an architectural solution implementing concurrent memory access for TCF-aware processors. The solution is based on bounded size step caches and two-phase structure of the TCF-aware processors. Step caches capture and hold the references made during the on-going step of an execution that are independent by the definition of TCF execution and therefore avoid coherence problems. The 2-phase structure reduces some concurrent accesses to a frontend operation followed by broadcast in the spreading network. According to our evaluation, a concurrent memory access-aware B-backend unit TCF processor executes certain algorithms up to B times faster than the baseline TCF processor.
Role of Proximal Tubules in the Pathogenesis of Kidney Disease (2011)

The proximal tubules make up a significant portion of the kidneys; proximal tubule epithelial cells are the most populous cell type in the kidney, and carry out diverse regulatory and endocrine functions where numerous transporters are located. Under normal circumstances, more than two thirds of filtered salt and water, and all filtered bicarbonate is reabsorbed in the proximal tubule. A number of inherited and acquired acid-base and tubule disorders are linked to impaired transporters in the proximal tubule cells. Equally important is the intrinsic immune characteristics of proximal tubule cells that give them the ability to also function as immune responders to a wide range of immunologic, ischemic or toxic injury. It is therefore not surprising that proximal tubule-related phenomena are closely related to the pathogenesis of a vast array of kidney diseases. Many kidney diseases, acute and chronic, first manifest with proximal tubule disorders. Recent insight into molecular characteristics of transport functions in the proximal tubules, and the recognition that proximal tubule cells possess intrinsic immune responses have contributed to an improved understanding of important areas in nephrology, such as Fanconi's syndrome, renal tubular acidosis, phosphate wasting syndromes, Dent's disease, cystinuria and other amino acid transport disorders, acute kidney injury, and the role of proximal tubules in progressive kidney disease. Megalin/ cubilin-mediated endocytosis by proximal tubule cells of increased quantities of filtered proteins (protein overloading) in glomerular diseases appears to evoke cell stress responses resulting in increased inflammatory cytokines leading to tubulointerstitial inflammation and fibrosis. Finally, the proximal tubule may be the site of both active vitamin D synthesis through the action of 1-α-hydroxylase, and the site where erythropoietin synthesis takes place. Thus, proximal tubule injury also contributes to two distressing consequences of chronic kidney disease: mineral-bone disorder and anemia.
Stratlets: Low Reynolds Number Point-Force Solutions in a Stratified Fluid (2010)

We present fundamental solutions of low Reynolds number flows in a stratified fluid, including the case of a point force (Stokeslet) and a doublet. Stratification dramatically alters the flow by creating toroidal eddies, and velocity decays much faster than in a homogeneous fluid. The fundamental length scale is set by the competition of buoyancy, diffusion and viscosity, and is O(100 μm–1 mm) in aquatic environments. Stratification can therefore affect the swimming of small organisms and the sinking of marine snow particles, and diminish the effectiveness of mechanosensing in the ocean.
Topology Control for Effective Interference Cancellation in Multiuser MIMO Networks (2012)

In multiuser multiple-input-multiple-output (MIMO) networks, receivers decode multiple concurrent signals using successive interference cancellation (SIC). With SIC, a weak target signal can be deciphered in the presence of stronger interfering signals. However, this is only feasible if each strong interfering signal satisfies a signal-to-noise-plus-interference ratio (SINR) requirement. This necessitates the appropriate selection of a subset of links that can be concurrently active in each receiver's neighborhood; in other words, a subtopology consisting of links that can be simultaneously active in the network is to be formed. If the selected subtopologies are of small size, the delay between the transmission opportunities on a link increases. Thus, care should be taken to form a limited number of subtopologies. We find that the problem of constructing the minimum number of subtopologies such that SIC decoding is successful with a desired probability threshold is NP-hard. Given this, we propose MUSIC, a framework that greedily forms and activates subtopologies in a way that favors successful SIC decoding with a high probability. MUSIC also ensures that the number of selected subtopologies is kept small. We provide both a centralized and a distributed version of our framework. We prove that our centralized version approximates the optimal solution for the considered problem. We also perform extensive simulations to demonstrate that: 1) MUSIC forms a small number of subtopologies that enable efficient SIC operations; the number of subtopologies formed is at most 17% larger than the optimum number of topologies, discovered through exhaustive search (in small networks); 2) MUSIC outperforms approaches that simply consider the number of antennas as a measure for determining the links that can be simultaneously active. Specifically, MUSIC provides throughput improvements of up to four times, as compared to such an approach, in various topological settings. The improvements can be directly attributable to a significantly higher probability of correct SIC based decoding with MUSIC.
A Displaced Sensor Array Configuration for Estimating Angles of Arrival of Narrowband Sources under Grazing Incidence Conditions (2007)

This paper proposes a displaced sensor array (DSA) configuration for estimating the angles of arrival of narrow-band sources arriving at grazing incidence directions. Unlike the conventional uniform linear array (ULA) where all the array elements are aligned along one axis, the proposed DSA configuration comprises two displaced ULAs aligned on two parallel axes in the vertical plane. The steering vectors of the two parallel arrays differ from each other by only two multiplicative phase terms that represent the space factors due to the vertical separation and horizontal displacement of the two arrays. This makes the computational load of using MUSIC algorithm with the proposed DSA configuration identical to that of ULA. Simulation results obtained for cases involving narrow-band sources arriving at grazing incidence angles show that the proposed DSA configuration outperforms ULA in terms numerical accuracy and angular resolution.
Real Time 3D Cytomorphological Imaging using Digital Holographic Microscopy and Fluorescence Microscopy for Space Biology (2010)

A microscope operating in Digital Holographic Microscopy (DHM) and classical widefield epi-fluorescence microscopy in a time sequential manner is developed to study morphological alterations of mouse myoblast cells under simulated microgravity in real time.
Improving Computer Architecture Simulation Methodology by Adding Statistical Rigor (2005)

Due to cost, time, and flexibility constraints, computer architects use simulators to explore the design space when developing new processors and to evaluate the performance of potential enhancements. However, despite this dependence on simulators, statistically rigorous simulation methodologies are typically not used in computer architecture research. A formal methodology can provide a sound basis for drawing conclusions gathered from simulation results by adding statistical rigor and, consequently, can increase the architect's confidence in the simulation results. This paper demonstrates the application of a rigorous statistical technique to the setup and analysis phases of the simulation process. Specifically, we apply a Plackett and Burman design to: 1) identify key processor parameters, 2) classify benchmarks based on how they affect the processor, and 3) analyze the effect of processor enhancements. Our results showed that, out of the 41 user-configurable parameters in SimpleScalar, only 10 had a significant effect on the execution time. Of those 10, the number of reorder buffer entries and the L2 cache latency were the two most significant ones, by far. Our results also showed that instruction precomputation - a value reuse-like microarchitectural technique - primarily improves the processor's performance by relieving integer ALU contention.
An Efficient Convolutional Neural Network Computation using AVX-512 Instructions (2019)

Recently, Convolutional Neural Networks (CNNs) are widely used for image processing. Since the computation cost is high, it is necessary to accelerate the computation. Therefore, in this paper, we propose an efficient implementation using Intel AVX-512 instructions on the multicore CPUs. AVX-512 instructions suppose 512-bit vector operations, in which 16 32-bit floating point number operations can be executed simultaneously. In this implementation, to reduce the computation, we use an idea of the fused filter that combines a convolutional layer and its following pooling layer. As a result, we achieve a speed-up factor of 1.62 over an existing library implementation using Intel Math Kernel Library for Deep Neural Networks.
Rapid biological agent identification by surface-enhanced Raman spectroscopy (1999)

The Chemical Weapons Convention prohibits the development, production, stockpiling, and use of warfare agents (chemical and biological), and requires their destruction. Yet their use persists and has been included in the terrorist's arsenal. Currently, a number of analytical methods are being developed to perform rapid measurements of trace agents to ensure treaty compliance, as well as safe environments for military personal and the public at large. We have been investigating the ability of surface-enhanced Raman spectroscopy to detect bacterial nucleic acid-base pairs with sufficient sensitivity and selectivity to eliminate the need for enumeration used in polymerase chain reactions and culture growth, required by other measurement techniques. The design of a small volume, fiber optic coupled, electrolytic sample cell is presented along with analysis of DNA and RNA separated from non-toxic bacteria.
Diffusion of minority carriers against electric field (high injection level) (2017)

A one-dimensional analytic model describing the motion of minority carriers against the electric field direction under the conditions of high injection level is developed. The results of the model can also be used to estimate the motion of carriers against the field in the case of an arbitrary injection level. The model makes it possible to describe, in good agreement with the results of computer simulation, the modulation of the collector layer resistance in a high voltage SiC bipolar transistor.
Computation of flow in a carotid artery in a Cartesian coordinate system using voxel information (2002)

Computation of fiow
Novel Research Horizons for Presenilins and γ-Secretases in Cell Biology and Disease (2010)

Presenilins are the catalytic subunits of larger tetrameric &#x03B3;-secretase complexes. The degradome of these aspartyl proteases consists of at least 60 different substrates. &#x03B3;-Secretase is key to regulated intramembrane proteolysis, releasing protein fragments that potentially transduce signals at both sides of the cell membrane. Characteristic for this novel form of cellular signaling is its irreversible nature, providing direction to biological processes. We discuss recent insights in structure-function and assembly of the &#x03B3;-secretase complexes and emerging insights in the regulation of the activity of these enzymes. This novel knowledge will help to develop better drugs for Alzheimer's disease and cancer. We critically evaluate literature that proposes presenilin functions outside of the &#x03B3;-secretase complex.
Probing Substrate Promiscuity of Amylosucrase from Neisseria polysaccharea (2013)

Abstract The amylosucrase from Neisseria polysaccharea ( Np AS) naturally catalyzes the synthesis of a variety of products from sucrose and shows signs of plasticity of its active site. To explore further this promiscuity, the tolerance of amylosucrase towards different donor and acceptor substrates was investigated. The selection of alternate donor substrates was first made on the basis of preliminary molecular modeling studies. From 11 potential donors harboring selective derivatizations that were experimentally evaluated, only p ‐nitrophenyl‐α‐ D ‐glucopyranoside was used by the wild‐type enzyme, and this underlines the high specificity of the −1 subsite of Np AS for glucosyl donor substrates. The acceptor substrate promiscuity was further explored by screening 20 hydroxylated molecules, including D ‐ and L ‐monosaccharides as well as polyols. With the exception of one compound, all were successfully glucosylated, and this showcases the tremendous plasticity of the +1 subsite of Np AS, which is responsible for acceptor recognition. The products obtained from the transglucosylation reactions of three selected acceptors were characterized, and they revealed original structures and enzyme enantiopreference, which were more particularly analyzed by in silico docking analyses.
Response to “Comment on ‘Threshold voltage control of oxide nanowire transistors using nitrogen plasma treatment’” [Appl. Phys. Lett. 98, 176101 (2011)] (2011)

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Processing of pigmented‐flesh potatoes (Solanum tuberosum L.) on the retention of bioactive compounds (2011)

Summary Retention of bioactive compounds in white‐ (WFP), yellow‐ (YFP), red‐ (RFP) and purple (PFP)‐fleshed potatoes after drum‐drying (DD) and Refractance Window™ drying (RW) was compared with freeze‐drying (FD). Processing, generally, did not influence total phenolics. Total carotenoid was high in YFP, but decreased with DD. Both DD and RW decreased lutein concentration in YFP. The RFP and PFP had the highest total anthocyanin, and their concentrations were decreased by DD. RW decreased total anthocyanin in PFP only. Total antioxidant activity in WFP was higher with DD but lower with RW. In contrast, DD and RW drying had no significant effect on total antioxidants in YFP, RFP and PFP. Therefore, drying generally decreased antioxidants, with FD and RW retaining the highest concentration of bioactive compounds.