gebhart/patrepeval huggingface dataset:
Abstract 43: Discovery of ARV-110, a first in class androgen receptor degrading PROTAC for the treatment of men with metastatic castration resistant prostate cancer (2021)

Abstract Prostate cancer is the second leading cause of cancer death in men in the United States. The androgen receptor (AR) plays critical roles in both early disease and advanced prostate cancer. Current therapeutic approaches targeting the androgen/AR axis are initially effective, but castration resistant prostate cancer (CRPC) inevitably develops. CRPC is tightly linked with increased AR activity via gene overexpression, amplification, and gain-of-function mutations. To address these mechanisms of AR-dependent prostate tumor growth, we have developed a novel therapeutic agent, ARV-110, a proteolysis targeting chimera (PROTAC®) that induces a protein-protein interaction between the AR and E3 ubiquitin ligase complexes, leading to the ubiquitination of AR and its subsequent degradation via the proteasome. In vitro, ARV-110 robustly degrades AR in various prostate cancer cell lines with a half-maximal degradation concentration (DC50) of ~1 nM. Whole cell lysate proteomics and ubiquitin proteomics demonstrated high selectivity for AR in VCaP cells. ARV-110 potently downregulates androgen responsive genes, inhibits proliferation and induces apoptosis in AR dependent prostate cancer cells. In vivo, ARV-110 is orally bioavailable and robustly degrades AR with a &amp;gt;90% observed maximum degradation (Dmax) at efficacious doses. ARV-110 significantly and dose-dependently inhibits tumor growth in murine LNCaP and VCaP xenograft models, including enzalutamide-resistant VCaP and enzalutamide-insensitive patient-derived xenograft models. These preclinical data supported the clinical development of ARV-110 for the treatment of men with metastatic CRPC. The discovery, chemical structure and initial clinical data of ARV-110 will be presented Citation Format: Lawrence B. Snyder, Taavi K. Neklesa, Xin Chen, Hanqing Dong, Caterina Ferraro, Deborah A. Gordon, Jennifer Macaluso, Jennifer Pizzano, Jing Wang, Ryan R. Willard, Nicholas Vitale, Ron Peck, Marcia Dougan Moore, Craig M. Crews, John Houston, Andrew P. Crew, Ian Taylor. Discovery of ARV-110, a first in class androgen receptor degrading PROTAC for the treatment of men with metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 43.
Direct Radiator Loudspeaker Enclosures (1951)

Direct radiator loudspeaker mechanisms are usually mounted in cabinets. Most of the considerations concerning the design of cabinets for direct radiator loudspeaker mechanisms have involved the volume or over-all dimensions of the cabinet which, together with the loudspeaker mechanism determines the performance of the combination of the loudspeaker mechanism and cabinet in the low frequency range. There is another important factor in the design of direct radiator loudspeaker cabinets, namely, the exterior configuration of the cabinet. The configuration of the outside of the cabinet markedly influences the response in the mid and high frequency ranges due to diffraction effects. These effects are usually overlooked, and the anomalies in response are unjustly attributed to the loudspeaker mechanism. Therefore, in order to determine the effects of diffraction, it appeared desirable to obtain the performance of a direct radiator loudspeaker mechanism in such fundamental shapes as the sphere, hemisphere, cylinder, cube, rectangular parallelopiped, cone, double cone, pyramid and double pyramid, and variations and combinations of these fundamental shapes. The result of these tests indicates that the outside configuration of the housing introduces variations in the response frequency characteristic of as much as 12 db.
Hospital Quality Improvement Activities and the Effects of Interventions on Pneumonia: A Multistate Study of Medicare Beneficiaries (2004)

This article evaluates the relative effectiveness of quality improvement interventions on increasing the time to antibiotic administration after a diagnosis of pneumonia. Clinical data were abstracted from the medical records of 17,040 Medicare beneficiaries discharged from one of 215 acute-care hospitals across 15 states. Thirteen Quality Improvement Organizations collected data on hospital quality improvement interventions from each hospital in this study. Medicare discharges between January 1997 and January 2002 define the study period. Most hospitals implemented multiple interventions to improve pneumonia care. Only 3 individual interventions were found to be effective in increasing time to antibiotic administration. Data feedback and benchmarking and medical records checklists had a positive effect on time to antibiotic administration. Administrative support by itself had a negative effect on the quality indicator. Although several combinations of interventions were also found effective, generalizations about the use of multiple interventions in quality improvement are difficult to make from retrospective studies.
Monolithic array of optoelectronic broad-band switches (1984)

The response of monolithic arrays of GaAs photoconductors to optical intensity modulation signals and their feasibility of operating as crosspoint arrays in integrated broadband switch matrices are investigated. It is found that individual photoconductors can switch signals at frequencies of up to 1.3 GHz with isolation better than 70 dB and switching time less than 10 ns. In a 2/spl times/2 monolithic array, 65-dB switch isolation and 80-dB crosstalk isolation between channels are achieved in the frequency range 0-130 MHz. The responsivity is essentially uniform within this frequency range and has a value of 0.84 A/W at 820 nm. At higher frequencies electromagnetic coupling between output lines limits the performance with the layout used. This monolithic array thus demonstrates compact broadband matrix switching of signals in the frequency range up to 100 MHz using the optoelectronic switching principle.
IARPA Babel Mongolian Language Pack IARPA-babel401b-v2.0b (2020)

Introduction <br> <br>IARPA Babel Mongolian Language Pack IARPA-babel401b-v2.0b was developed by Appen for the IARPA (Intelligence Advanced Research Projects Activity) Babel program. It contains approximately 204 hours of Halh Mongolian conversational and scripted telephone speech collected in 2014 along with corresponding transcripts. <br> <br>The Babel program focused on underserved languages and sought to develop speech recognition technology that could be rapidly applied to any human language to support keyword search performance over large amounts of recorded speech. <br>Data <br> <br>The Halh Mongolian speech in this release represents that spoken by native speakers in Mongolia. The gender distribution among speakers is approximately equal; speakers' ages range from 16 years to 61 years. Calls were made using different telephones (e.g., mobile, landline) from a variety of environments including the street, a home or office, a public place, and inside a vehicle. <br> <br>Audio data is presented as 8kHz 8-bit a-law encoded audio in sphere format and 48kHz 24-bit PCM encoded audio in wav format. <br> <br>Transcripts are encoded in UTF-8 in both Mongolian Cyrillic and a romanization scheme developed by Appen; they cover approximately 77% of the speech data. Further information about transcription methodology is contained in the documentation accompanying this release. <br> <br>Evaluation data is available from NIST in support of OpenKWS. <br>Samples <br> <br>Please view the following samples: <br> <br> Audio Sample (SPH) <br> Transcript Sample (TXT) <br> Romanized Transcript Samples (TXT) <br> <br>Updates <br> <br>None at this time. <br>Copyright <br>Portions © 2015 U.S. Government <br> <br>The U.S. Government acquired this data from Appen Pty Ltd, which assigned the copyright to the data to the U.S. Government.
Force-Induced Formation of Twisted Chiral Ribbons (2020)

We demonstrate that an achiral stretching force transforms disk-shaped colloidal membranes composed of chiral rods into twisted ribbons with handedness opposite the preferred twist of the rods. Using an experimental technique that enforces torque-free boundary conditions we simultaneously measure the force-extension curve and the ribbon shape. An effective theory that accounts for the membrane bending energy and uses geometric properties of the edge to model the internal liquid crystalline degrees of freedom explains both the measured force-extension curve and the force-induced twisted shape.
WLC07-2: Simultaneous Routing and Resource Allocation in Multihop Wireless Networks using Optimization (2006)

Wireless multihop networks hope to provide increased total capacity and enhanced coverage at possibly low cost. In this paper, we are interested in the jointly optimal routing and power allocation, i.e. cross-layer design between the physical and the network layer. We formulate this as a convex mathematical programming problem, with objective function to minimize the total power, and propose a distributed solution method. Based on the theoretical results we implement a heuristic solution algorithm and study the performance on a set of test problems. We manage to establish convergence for the standard solution method and also for a more practically realistic model where the information passing between the nodes is limited.
Determination and Analysis of the Putative AcaCD-Responsive Promoters of Salmonella Genomic Island 1 (2016)

The integrative genomic island SGI1 and its variants confer multidrug resistance in numerous Salmonella enterica serovariants and several Proteus mirabilis and Acinetobacter strains. SGI1 is mobilized by the IncA/C family plasmids. The island exploits not only the conjugation apparatus of the plasmid, but also utilizes the plasmid-encoded master regulator AcaCD to induce the excision and formation of its transfer-competent form, which is a key step in the horizontal transfer of SGI1. Triggering of SGI1 excision occurs via the AcaCD-dependent activation of xis gene expression. AcaCD binds in Pxis to an unusually long recognition sequence. Beside the Pxis promoter, upstream regions of four additional SGI1 genes, S004, S005, S012 and S018, also contain putative AcaCD-binding sites. Furthermore, SGI1 also encodes an AcaCD-related activator, FlhDCSGI1, which has no known function. Here, we have analysed the functionality of the putative AcaCD-dependent promoter regions and proved their activation by either AcaCD or FlhDCSGI1. Moreover, we provide evidence that both activators act on the same binding site in Pxis and that FlhDCSGI1 is able to complement the acaCD deletion of the IncA/C family plasmid R16a. We determined the transcription start sites for the AcaCD-responsive promoters and showed that orf S004 is expressed probably from a different start codon than predicted earlier. Additionally, expression of S003 from promoter PS004 was ruled out. Pxis and the four SGI1 promoters examined here also lack obvious -35 promoter box and their promoter profile is consistent with the class II-type activation pathway. Although the role of the four additionally analysed AcaCD/FlhDCSGI1-controlled genes in transfer and/or maintenance of SGI1 is not yet clear, the conservation of the whole region suggests the existence of some selection for their functionality.
Mechanism of mRNA transport in the nucleus (2005)

The mechanism of transport of mRNA-protein (mRNP) complexes from transcription sites to nuclear pores has been the subject of many studies. Using molecular beacons to track single mRNA molecules in living cells, we have characterized the diffusion of mRNP complexes in the nucleus. The mRNP complexes move freely by Brownian diffusion at a rate that assures their dispersion throughout the nucleus before they exit into the cytoplasm, even when the transcription site is located near the nuclear periphery. The diffusion of mRNP complexes is restricted to the extranucleolar, interchromatin spaces. When mRNP complexes wander into dense chromatin, they tend to become stalled. Although the movement of mRNP complexes occurs without the expenditure of metabolic energy, ATP is required for the complexes to resume their motion after they become stalled. This finding provides an explanation for a number of observations in which mRNA transport appeared to be an enzymatically facilitated process.
Nuclear Security Applications of Antineutrino Detectors: Current Capabilities and Future Prospects (2010)

Antineutrinos are electrically neutral, nearly massless fundamental particles produced in large numbers in the cores of nuclear reactors and in nuclear explosions. In the half century since their discovery, major advances in the understanding of their properties, and in detector technology, have opened the door to a new discipline—Applied Antineutrino Physics. Because antineutrinos are inextricably linked to the process of nuclear fission, there are many applications of interest in nuclear nonproliferation. This paper presents a comprehensive survey of applied antineutrino physics relevant for nonproliferation, summarizes recent advances in the field, describes the overlap of this nascent discipline with other ongoing fundamental and applied antineutrino research, and charts a course for research and development for future applications. It is intended as a resource for policymakers, researchers, and the wider nuclear nonproliferation community.
Design of Tension Leg Platforms: A Knowledge Based Approach (1992)

Tension leg platforms (TLPs) are floating compliant platforms designed for deep water offshore hydrocarbon production. Only a few TLPs have actually been built, but others are currently being designed and constructed. Important field experience about their response behavior due to the environmental loading is not generally available, although many technical articles on analysis methods have been published. The knowledge based computer approach can compensate for missing design information through either the introduction of best estimates, simplified mathematical models, empirical models or the use of existing computer models. The preliminary design model developed in this study focuses on general aspects of the TLP platform configuration and its tethers. A constrained optimization model developed by Nordgren (1987) is incorporated into the knowledge based computer model. TLP response behavior, tether characteristics, and the requirement of minimum cost are combined in a strategy to identify the optimum TLP configuration for a given offshore site. The computer model is interactive and the results at any point can be viewed in a detailed spreadsheet and there is an option to plot an engineering drawing of the corresponding TLP. The example presented illustrates the promise of this approach for use in the design process.
Thrombus Imaging Using Technetium-99m-Labeled High-Potency GPIIb/IIIa Receptor Antagonists. Chemistry and Initial Biological Studies (1996)

Platelet-specific compounds which are radiolabeled with γ-emitting radionuclides may be particularly useful for the noninvasive in vivo detection of thrombi. The synthesis of peptides which are potent inhibitors of platelet aggregation and which contain a chelator for the radionuclide technetium-99m are described. The target compounds were designed such that stable, oxotechnetium(V) species could be prepared where the site of metal coordination was well defined. A strategy was employed where the pharmacophore -Arg-Gly-Asp-(RGD), or RGD mimetic, was constrained in a ring which was formed by the S-alkylation of a cysteine residue with an N-terminal chloroacetyl group. Binding affinities were enhanced by the replacement of arginine with the arginine mimetics S-(3-aminopropyl)cysteine and 4-amidinophenylalanine. Further enhancements could be obtained by the synthesis of oligomers which contained two or more rings containing receptor binding regions. The increase in binding affinity seen was more than that expected from a simple stoichiometric increase of pharmacophore. The most potent compounds described had IC50s of approximately 0.03 μM for the inhibition of human platelet aggregation. Two of the more potent peptides (P280 and P748) were labeled with technetium-99m and assessed in a canine thrombosis model. The 99mTc complexes of the peptides prepared in this work hold promise as thrombus imaging agents due to their high receptor binding affinity, ease of preparation, and expected rapid pharmacokinetics.
SLAC: A Sparsely Labeled Dataset for Action Classification and Localization (2017)

This paper describes a procedure for the creation of large-scale video datasets for action classification and localization from unconstrained, realistic web data. The scalability of the proposed procedure is demonstrated by building a novel video benchmark, named SLAC (Sparsely Labeled ACtions), consisting of over 520K untrimmed videos and 1.75M clip annotations spanning 200 action categories. Using our proposed framework, annotating a clip takes merely 8.8 seconds on average. This represents a saving in labeling time of over 95% compared to the traditional procedure of manual trimming and localization of actions. Our approach dramatically reduces the amount of human labeling by automatically identifying hard clips, i.e., clips that contain coherent actions but lead to prediction disagreement between action classifiers. A human annotator can disambiguate whether such a clip truly contains the hypothesized action in a handful of seconds, thus generating labels for highly informative samples at little cost. We show that our large-scale dataset can be used to effectively pre-train action recognition models, significantly improving final metrics on smaller-scale benchmarks after fine-tuning. On Kinetics, UCF-101 and HMDB-51, models pre-trained on SLAC outperform baselines trained from scratch, by 2.0%, 20.1% and 35.4% in top-1 accuracy, respectively when RGB input is used. Furthermore, we introduce a simple procedure that leverages the sparse labels in SLAC to pre-train action localization models. On THUMOS14 and ActivityNet-v1.3, our localization model improves the mAP of baseline model by 8.6% and 2.5%, respectively.
Histological and histomorphometric analysis of strontium chloride coated commercially pure titanium implant compared with hydroxyapatite coating (2015)

Background: In recent years, the immediate loading of dental implants has become more accepted as a standard protocol for the treatment of the edentulous area. Success in implant dentistry depends on several parameters that may improve phenomenon of osseointegration and new bone formation in close contact with the implant. The aim of study was to evaluate the effect of strontium chloride coating of screw shape commercially pure titanium dental implant osseointegration at bone - implant interface by histomorphometric analysis and compare with hydroxyapatite coating at 2 time periods (2 weeks and 6 weeks). Materials and methods: Electrophoretic Deposition Technique (EPD) was used to obtain a uniform coating layer on commercially pure titanium screws. The tibia of 4 white New Zealand rabbits was chosen as implantation sites. Each tibia of rabbit received two screws, one strontium chloride coated and one hydroxyapatite coated and a total 30 histological sections were obtained for each coating material in each period of time. Histomorphometric analysis was performed to measure new bone formed ratio between implant and original bone, after 2 and 6 weeks healing periods. Results: There was increased in new bone formation ratio for the strontium chloride coated implants than hydroxyapatite coated implants and over the two periods of time. There was an increase in the new bone formation ratio at bone-implant interface with time. Conclusion: Coating commercially pure titanium implant with strontium chloride was more efficient in increasing osseointegration at bone implant interface than hydroxyapatite , which was demonstrated by higher new bone formation and maturation at the two periods of time 2 weeks and 6 weeks after implantation. Keywords: Histomorphometric, commercially pure titanium, strontium chloride, hydroxyapatite.
Novel Mutations Found in Individuals with Adult-Onset Pompe Disease (2020)

Pompe disease, or glycogen storage disease II is a rare, progressive disease leading to skeletal muscle weakness due to deficiency of the acid α-1,4-glucosidase enzyme (GAA). The severity of disease and observed time of onset is subject to the various combinations of heterozygous <i>GAA</i> alleles. Here we have characterized two novel mutations: c.2074C>T and c.1910_1918del, and a previously reported c.1082C>G mutation of uncertain clinical significance. These mutations were found in three unrelated patients with adult-onset Pompe disease carrying the common c.-32-13T>G mutation. The c.2074 C>T nonsense mutation has obvious consequences on <i>GAA</i> expression but the c.1910_1918del (deletion of 3 amino acids) and c.1082C>G missense variants are more subtle DNA changes with catastrophic consequences on GAA activity. Molecular and clinical analyses from the three patients corresponded with the anticipated pathogenicity of each mutation.
Desorption/Ionization Fluence Thresholds and Improved Mass Spectral Consistency Measured Using a Flattop Laser Profile in the Bioaerosol Mass Spectrometry of Single Bacillus Endospores (2005)

Bioaerosol mass spectrometry is being developed to analyze and identify biological aerosols in real time. Mass spectra of individual Bacillus endospores were measured with a bipolar aerosol time-of-flight mass spectrometer in which molecular desorption and ionization were produced using a single laser pulse from a Q-switched, frequency-quadrupled Nd:YAG laser that was modified to have an approximately flattop profile. The flattened laser profile allowed the minimum fluence required to desorb and ionize significant numbers of ions from single aerosol particles to be determined. For Bacillus spores, this threshold had a mean value of approximately 1 nJ/microm(2) (0.1 J/cm(2)). Thresholds for individual spores, however, could apparently deviate by 20% or more from the mean. Threshold distributions for clumps of MS2 bacteriophage and bovine serum albumin were subsequently determined. Finally, the flattened profile was observed to increase the reproducibility of single-spore mass spectra. This is consistent with the general conclusions of our earlier paper on the fluence dependence of single-spore mass spectra and is particularly significant because it is expected to enable more robust differentiation and identification of single bioaerosol particles.
Strenuous Walking Exercise and Spontaneous Fracture of the Femoral Neck in the Elderly (2000)

Spontaneous fractures of the hip which developed after strenuous walking exercise in 8 elderly people are reported. All patients had Singh hip index 4 or below at the time of initial examination and walked from 8,000 to 10,000 steps per day. This presentation aims to arouse the attention of physicians, recreational sports coaches, and elderly people to the deleterious effects of strenuous walking exercise on bone, and it looks for an optimal level of walking exercise according to the elderly patient"s bone quality. Walking exercise should be stopped immediately if pain in the hip develops and continues without relief for several days or more. The optimal walking frequency per day should be prescribed on the basis of the Singh index or T-score of BMD. If the BMD is 1/3 to 1/2 of normal, walking frequency should be adjusted to 1/3 to 1/2 of those of the normal adult with good bone quality.
Supplementary Figure 1 from Endoplasmic Reticulum Stress Triggers XBP-1–Mediated Up-regulation of an EBV Oncoprotein in Nasopharyngeal Carcinoma (2023)

Supplementary Figure 1 from Endoplasmic Reticulum Stress Triggers XBP-1–Mediated Up-regulation of an EBV Oncoprotein in Nasopharyngeal Carcinoma