gebhart/patrepeval huggingface dataset:
Selection and Characterization of HIV-1 Variants Resistant to the (+) and (-) Enantiomers of 2′-Deoxy-3′-Oxa-4′-Thiocytidine (Dotc) (1999)

Human immunodeficiency virus type 1 (HIV-1) variants were selected for resistance against the (+) and (-) enantiomers of a novel nucleoside analogue, 2′-deoxy-3′-oxa-4′-thiocytidine (dOTC), using the infectious molecular clone HXB2D grown in the MT-4 line of human T cells. The variants selected with (+) dOTC were approximately 6–7-fold less sensitive than wild-type virus to this drug. Cloning and sequencing of the complete reverse transcriptase (RT) coding region of these variants identified the M184I mutation and further selection with virus containing the M184I substitution led to the appearance of an M184V mutation. In contrast, selection experiments performed with (-) dOTC yielded variants capable of growing in drug concentrations as high as 100 μM, but phenotypic analysis of these viruses revealed near wild-type 50% inhibitory concentration (IC 50 ) values for this compound. Site-directed mutagenesis experiments in which the M184I and M184V mutations were introduced into HXB2D confirmed the importance of these mutations when viruses were grown in MT4 cells. However, wild-type IC 50 values in regard to both (–) and (+) dOTC were obtained when these recombinant viruses were grown in cord blood mononuclear cells (CBMC). Clinical isolates of HIV-1 resistant to lamivudine and containing the M184V substitution also displayed low-level resistance to both (–) and (+) dOTC when grown in CBMC. Finally, cell-free RT assays were performed in the presence of either (–) dOTC triphosphate, (+) dOTC triphosphate, or the triphosphate of a racemic mixture of (+) and (–) dOTC with wild-type and mutated M184V-containing recombinant RT. The data demonstrate chain termination effects of these compounds with regard to both wild-type and mutated enzyme and that the latter was approximately twofold less sensitive than the former to these drugs.
Diamond-MESFETs --- Synthesis and Integration (2006)

We report the utilization of synthetic diamond grown by chemical-vapour-deposition (CVD) for use as metal-semiconductor field-effect-transistors (MESFETs). The lack of a shallow n-type donor means that diamond-based electronic devices are unipolar (p-type). The devices presented in this paper are based on delta-doping. Delta-doping stands for the use of very thin (<5 mm) highly doped (N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">A</sub> 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">20</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> ) buried layers. This approach poses a huge challenge in terms of synthesis as well as processing. First successful attempts of fully integrating working delta-doped diamond MESFETs are presented
Abstract 2506: Exploring the complex etiology of oncogenic fusions in childhood cancer (2019)

Background, Rationale and Experimental ApproachOncogenic fusions are generated via chromosomal rearrangements resulting in an exchange of coding or regulatory DNA sequences. These mutations play an important role in disease onset and subsequent cancer progression, however the exact timing and mechanisms by which they arise are unknown. Through the SickKids clinical sequencing program, KiCS, we explored how and when canonical fusions arise by studying the whole-genomes of childhood cancers with diagnostic or driver fusions. Our investigation began with the pediatric bone cancer, Ewing sarcoma, and later expanded to include other solid, blood, and brain cancers such as papillary thyroid carcinoma, myeloid leukemia, and ependymoma among others.ResultsThe starting point of our investigation was ES, where we sequenced the whole-genomes of 124 cases. Ewing sarcoma (ES) represents the prototypical fusion-driven sarcoma as it is characterized and driven by the EWSR1-ETS fusion. In ~42% of cases, we found that the ES fusion gene arises by chromoplexy, a sudden burst of complex, loop-like rearrangements, rather than by simple reciprocal translocations as previously thought. We show that these rearrangements rapidly and dramatically altered the chromosomal landscape of ES tumors, producing the driver EWSR1-ETS fusion and disrupting numerous other genes in a short time. Remarkably, these complex rearrangements are enriched for genes, including those with a clear role in oncogenesis, and are associated with the earliest replicating portions of the genome. We then sequenced the genomes of 30 other childhood cancers with oncogenic fusions to study their timing and formation mechanisms. In doing so, we have identified several novel fusions in many cancer types, which have been validated by RNA sequencing and cytogenetics. In some cases, the presence of these chromoplectic fusions indicates these patients may benefit from targeted therapy due to the generation of druggable fusions. .ConclusionsOur findings provide fundamental insights into the pathogenesis of gene fusions in human cancer. They reveal complex DNA rearrangements to be a mutational process underpinning gene fusions in cancer that influences tumorigenesis.Citation Format: Nathaniel D. Anderson, Richard de Borja, Matthew D. Young, Fabio Fuligni, Andrej Rosic, Nicola D. Roberts, Nischalan Pillay, Jeffrey A. Toretsky, Yoshida Akihiko, Tatsuhiro Shibata, Markus Metzler, Gino Somers, Stephen W. Scherer, Adrienne M. Flanagan, Peter J. Campbell, Joshua D. Schiffman, Mary Shago, Ludmil B. Alexandrov, Jay S. Wunder, Irene L. Andrulis, David Malkin, Sam Behjati, Adam Shlien. Exploring the complex etiology of oncogenic fusions in childhood cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2506.
Numerical Investigation of Influence of Spot Geometry in Laser Peen Forming of Thin-Walled Ti-6Al-4V Specimens (2022)

The aviation industry demands thin-walled structures of high dimensional accuracy. Varying radii and individual use-cases, e.g. for repair purpose, require flexible forming techniques. Laser peen forming (LPF) represents such a forming process providing precise energy input by a pulsed laser over a wide energy range. Among adjustable parameters such as laser intensity and focus size, the spot shape, i.e. square and circular, is usually fixed for a specific laser system. As the spot shape is a crucial parameter, this work focuses on the effect of the spot shape on structural deformation after LPF application. Therefore, models for laser peen forming of thin-walled Ti-6Al-4V strips for LPF systems with circular and square focus shapes are set up. Geometric conditions on both focus shapes ensure equal energy input during the laser processing. The numerical simulation relies on the so called eigenstrain method, leading to a cost-efficient calculation of resulting deformation after the dynamic LPF process. Square-based peening pattern exhibit higher deflection. For increasing spot size, the deflection difference between square and circle-based patterns increase slightly.
How to Eat Your Entropy and Have it Too - Optimal Recovery Strategies for Compromised RNGs. (2014)

Abstract. Random number generators (RNGs) play a crucial role in many cryptographic schemes and proto-cols, but their security proof usually assumes that their internal state is initialized with truly random seeds and remains secret at all times. However, in many practical situations these are unrealistic assumptions: The seed is often gathered after a reset/reboot from low entropy external events such as the timing of manual key presses, and the state can be compromised at unknown points in time via side channels or penetration attacks. The usual remedy (used by all the major operating systems, including Windows, Linux, FreeBSD, MacOS, iOS, etc.) is to periodically replenish the internal state through an auxiliary input with additional randomness harvested from the environment. However, recovering from such attacks in a provably correct and computationally optimal way had remained an unsolved challenge so far. In this paper we formalize the problem of designing an efficient recovery mechanism from state compromise, by considering it as an online optimization problem. If we knew the timing of the last compromise and the amount of entropy gathered since then, we could stop producing any outputs until the state becomes truly random again. However, our challenge is to recover within a time proportional to this optimal solution even in the hardest (and most realistic) case in which (a) we know nothing about the timing of the last state compromise, and the amount of new entropy injected since then into the state, and (b) any premature production of outputs
Optical response of phase change material for metasurface(Conference Presentation) (2016)

Phase change materials are used as the recording layer in optical data storage, electronic storage and nanolithography due to the enormous physical difference between crystalline and amorphous states. In recent years, they are demonstrated to exploit in various tunable plasmonic devices, such as perfect absorber, planar lenses, plasmonic antenna, Fano resonance and so on. However, in these researches, the phase change material merely plays a role as a refractive index switchable substrate. In this paper, we study the intrinsic optical properties of phase change material Ge2Sb2Te5 (GST) in the near-infrared regime. A clear insight into the dipole resonance system of GST is provided. The reflection phase retardation and intensity of each unit cells depending on the phase state and geometry are estimated. Further, we introduce the concept of reconfigurable gradient metasurface, which has different anomalous reflection angles by switching the combination of nanorods with different geometries and phase states. The research has great potential in the area of tunable metamaterial device (metadevice) in the future.
Angular correction of the radiation emitted from a laser with an inhomogeneous active medium (1977)

An experimental comparison was made of a plane-parallel resonator containing a telescopic angular selector with an unstable telescopic resonator. The resonator with a telescopic angular selector made it possible to achieve for the first time a considerable reduction in the angular divergence of the radiation emitted from a moving stimulated emission zone.
CMOS active pixel image sensor with in-pixel CDS for high-speed cameras (2005)

This paper presents a high-speed CMOS image sensor whose frame rate exceeds 2000 frames/sec (fps). The pixel includes a photodiode, a charge-transfer amplifier, and circuitry for correlated double sampling (CDS) and global electronic shuttering. Reset noise, which is the major random noise factor, is reduced by the CDS combined with the charge-transfer amplifier. The total number of devices in the pixel is 11 transistors and 2 MOS capacitors. Test circuits were fabricated using the 0.25 um CMOS process. The sensitivity of the 20 x 20 um<sup>2</sup> pixel using the floating diffusion capacitor of 6.2 fF and the photodiode area of 15 x 12.7 um^2 is 34 V/lux-sec. At 1000 fps, noise level is 2.43 mVrms (dark). The noise level and the sensitivity are greatly improved compared to the non-charge-transfer pixel without global shutter (3Tr-type) implemented with the same technology, and to a previous version of the APS with in-pixel CDS.
The electrical resistance of a graph captures its commute and cover times (1989)

View an n-vertex, m-edge undirected graph as an electrical network with unit resistors as edges. We extend known relations between random walks and electrical networks by showing that resistance in this network is intimately connected with the lengths of random walks on the graph. For example, the commute time between two vertices s and t (the expected length of a random walk from s to t and back) is precisely characterized by the effective resistance Rst between s and t: commute time = 2mRst. Additionally, the cover time (the expected length of a random walk visiting all vertices) is characterized by the maximum resistance R in the graph to within a factor of log n: mR ≤ cover time ≤ O (mR log n). For many graphs, the bounds on cover time obtained in this manner are better than those obtained from previous techniques such as the eigenvalues of the adjacency matrix. In particular, using this approach, we improve known bounds on cover times for various classes of graphs, including high-degree graphs, expanders, and multi-dimensional meshes. Moreover, resistance seems to provide an intuitively appealing and tractable approach to these problems.
Synthesis of Heavily Glycosylated PeptideαThioester (2010)

Abstract Erythropoietin (EPO) needs to be heavily glycosylated to exhibit its bioactivity in vivo. In order to synthesize heavily glycosylated EPO analogues, corresponding glycosylated peptide αthioesters are essential to prepare glycosylated whole EPO peptide backbones through native chemical ligation. After construction of the peptide αthioester corresponding to the 1–32 amino acid sequence in EPO, we aimed to incorporate three complex-type biantennary sialyloligosaccharides to this peptide αthioester by the haloacetamide method. The reaction afforded the desired heavily glycosylated peptide αthioester. Keywords: ErythropoietinGlycopeptideNative Chemical Ligation ACKNOWLEDGEMENTS Financial support from the Japan Society for the Promotion of Science (Grant-in-Aid for Creative Scientific Research no.17GS0420 and 18550155) is acknowledged.
The Novel Primary Response Gene MyD118 and the Proto-Oncogenes myb, myc, and bcl-2 Modulate Transforming Growth Factor β1-induced Apoptosis of Myeloid Leukemia Cells (1994)

Cell numbers are regulated by a balance among proliferation, growth arrest, and programmed cell death. A profound example of cell homeostasis, controlled throughout life, is the complex process of blood cell development, yet little is understood about the intracellular mechanisms that regulate blood cell growth arrest and programmed cell death. In this work, using transforming growth factor beta 1 (TGF beta 1)-treated M1 myeloid leukemia cells and genetically engineered M1 cell variants, the regulation of growth arrest and apoptosis was dissected. Blocking of early expression of MyD118, a novel differentiation primary response gene also shown to be a primary response gene induced by TGF beta 1, delayed TGF beta 1-induced apoptosis, demonstrating that MyD118 is a positive modulator of TGF beta 1-mediated cell death. Elevated expression of bcl-2 blocked the TGF beta 1-induced apoptotic pathway but not growth arrest induced by TGF beta 1. Deregulated expression of either c-myc or c-myb inhibited growth arrest and accelerated apoptosis, demonstrating for the first time that c-myb plays a role in regulating apoptosis. In all cases, the apoptotic response was correlated with the level of MyD118 expression. Taken together, these findings demonstrate that the primary response gene MyD118 and the c-myc, c-myb, and bcl-2 proto-oncogenes interact to modulate growth arrest and apoptosis of myeloid cells.
Supplementary Table S3 from Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets (2023)

&lt;p&gt;Summary of clinically informative (TARGET) genes.&lt;/p&gt;
Structure Elucidation and Computationally Guided Synthesis of SSZ‐43: A One‐Dimensional 12‐Ring Zeolite with Unique Sinusoidal Channels (2022)

The structure of zeolite SSZ-43 was determined by 3D electron diffraction, synchrotron X-ray powder diffraction, and high-resolution transmission electron microscopy. The SSZ-43 framework forms one-dimensional, sinusoidal 12-ring channels from 5<sup>4</sup> 6<sup>1</sup> butterfly units commonly found in other zeolites, but with unique 6.5×6.5 Å apertures and 12-ring 6.5×8.9 Å windows perpendicular to the channels. SSZ-43 crystals are intergrowths of two polytypes: ≈90 % orthorhombic polytype A with ABAB stacking of the 12-rings, and ≈10 % monoclinic polytype B with ABCABC stacking. Molecular modeling performed on the idealized Si-SSZ-43 structure along with empirical relationships for zeolite selectivity in boron- and aluminum-containing synthesis gels were used in a combined approach to design new di-quaternary ammonium organic structure-directing agents (OSDAs). Experimental trials demonstrated that the new OSDAs produced SSZ-43 over a broader range of compositions than previous mono-quaternary OSDAs.
Perlecan Domain I Promotes Fibroblast Growth Factor 2 Delivery in Collagen I Fibril Scaffolds (2005)

Perlecan, a heparan sulfate proteoglycan, is widely distributed in developing and adult tissues and plays multiple, important physiological roles. Studies with knockout mouse models indicate that expression of perlecan and heparan sulfate is critical for proper skeletal morphogenesis. Heparan sulfate chains bind and potentiate the activities of various growth factors such as fibroblast growth factor 2 (FGF-2). Previous studies indicate that important biological activities are associated with the heparan sulfate-bearing domain I of perlecan (PlnDI; French et al. J. Bone Miner. Res. 17 , 48, 2002). In the present study, we have used recombinant, glycosaminoglycan-bearing PlnDI to reconstitute three-dimensional scaffolds of collagen I. Collagen I fibrils bound PlnDI much better than native collagen I monomers or heat-denatured collagen I preparations. Heparitinase digestion demonstrated that recombinant PlnDI was substituted with heparan sulfate and that these heparan sulfate chains were critically important not only for efficient integration of PlnDI into scaffolds, but also for FGF-2 binding and retention. PlnDI-containing collagen I scaffolds to which FGF-2 was bound sustained growth of both MG63, an osteoblastic cell line, and human bone marrow stromal cells (hBMSCs) significantly better than scaffolds lacking either PlnDI or FGF-2. Collectively, these studies demonstrate the utility of PlnDI in creating scaffolds that better mimic natural extracellular matrices and better support key biological activities.
Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study (2021)

Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an <i>ex vivo</i> MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. <i>Ex vivo</i> diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.
Dioxygenases without Requirement for Cofactors and Their Chemical Model Reaction:  Compulsory Order Ternary Complex Mechanism of 1H-3-Hydroxy-4-oxoquinaldine 2,4-Dioxygenase Involving General Base Catalysis by Histidine 251 and Single-Electron Oxidation of the Substrate Dianion (2004)

1H-3-Hydroxy-4-oxoquinaldine 2,4-dioxygenase (Hod) is a cofactor-less dioxygenase belonging to the alpha/beta hydrolase fold family, catalyzing the cleavage of 1H-3-hydroxy-4-oxoquinaldine (I) and 1H-3-hydroxy-4-oxoquinoline (II) to N-acetyl- and N-formylanthranilate, respectively, and carbon monoxide. Bisubstrate steady-state kinetics and product inhibition patterns of HodC, the C69A protein variant of Hod, suggested a compulsory-order ternary-complex mechanism, in which binding of the organic substrate precedes dioxygen binding, and carbon monoxide is released first. The specificity constants, k(cat)/K(m,A) and k(cat)/K(m,O)()2, were 1.4 x 10(8) and 3.0 x 10(5) M(-1) s(-1) with I and 1.2 x 10(5) and 0.41 x 10(5) M(-1) s(-1) with II, respectively. Whereas HodC catalyzes formation of the dianion of its organic substrate prior to dioxygen binding, HodC-H251A does not, suggesting that H251, which aligns with the histidine of the catalytic triad of the alpha/beta hydrolases, acts as general base in catalysis. Investigation of base-catalyzed dioxygenolysis of I by electron paramagnetic resonance (EPR) spectroscopy revealed formation of a resonance-stabilized radical upon exposure to dioxygen. Since in D(2)O spectral properties are not affected, exchangeable protons are not involved, confirming that the dianion is the reactive intermediate that undergoes single-electron oxidation. We suggest that in the ternary complex of the enzyme, direct single-electron transfer from the substrate dianion to dioxygen may occur, resulting in a radical pair. Based on the estimated spin distribution within the radical anion (observed in the model reaction of I), radical recombination may produce a C4- or C2-hydroperoxy(di)anion. Subsequent intramolecular attack would result in the 2,4-endoperoxy (di)anion that may collapse to the reaction products.
New Percutaneous Access Method for Minimally Invasive Anterior Lumbosacral Surgery (2004)

Preliminary cadaver, animal, and human studies were performed to determine the feasibility of axial anterior lumbosacral spine access using a percutaneous, presacral approach. Custom instruments were directed under fluoroscopic guidance along the midline of the anterior sacrum to the surface of the sacral promontory where an axial bore was created into the lower lumbar vertebral bodies and discs. Imaging and gross dissection were performed in cadavers and animals. The procedure was used for lumbosacral biopsy in human subjects guided by intraoperative imaging and clinical monitoring. All procedures were technically successful. This study demonstrates the feasibility of the axial access technique to the anterior lower lumbar spine.
Semi-Supervised Recurrent Neural Network for Adverse Drug Reaction\n Mention Extraction (2017)

Social media is an useful platform to share health-related information due to\nits vast reach. This makes it a good candidate for public-health monitoring\ntasks, specifically for pharmacovigilance. We study the problem of extraction\nof Adverse-Drug-Reaction (ADR) mentions from social media, particularly from\ntwitter. Medical information extraction from social media is challenging,\nmainly due to short and highly information nature of text, as compared to more\ntechnical and formal medical reports.\n Current methods in ADR mention extraction relies on supervised learning\nmethods, which suffers from labeled data scarcity problem. The State-of-the-art\nmethod uses deep neural networks, specifically a class of Recurrent Neural\nNetwork (RNN) which are Long-Short-Term-Memory networks (LSTMs)\n\\cite{hochreiter1997long}. Deep neural networks, due to their large number of\nfree parameters relies heavily on large annotated corpora for learning the end\ntask. But in real-world, it is hard to get large labeled data, mainly due to\nheavy cost associated with manual annotation. Towards this end, we propose a\nnovel semi-supervised learning based RNN model, which can leverage unlabeled\ndata also present in abundance on social media. Through experiments we\ndemonstrate the effectiveness of our method, achieving state-of-the-art\nperformance in ADR mention extraction.\n