gebhart/patrepeval huggingface dataset:
LITESPARK-004 (MK-6482-004) phase 2 study of belzutifan, an oral hypoxia-inducible factor 2α inhibitor (HIF-2α), for von Hippel-Lindau (VHL) disease: Update with more than two years of follow-up data. (2022)

4546 Background: VHL disease is associated with malignant or benign tumors, including renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNETs), and hemangioblastomas. Alterations in the VHL gene cause aberrant stabilization and accumulation of HIF-2α, leading to activation of genes associated with tumor growth. Antitumor activity observed in the ongoing open-label phase 2 study, LITESPARK-004 (NCT03401788), led to the approval of belzutifan for the treatment of patients (pts) with VHL disease who require therapy for associated RCC, CNS hemangioblastomas, or pNETs not requiring immediate surgery. Updated results are presented after &gt; 2 years of follow-up. Methods: Pts (≥18 years) with germline VHL alterations, ≥1 measurable nonmetastatic RCC tumor, no tumor of &gt; 3 cm that necessitated immediate surgery, no prior anticancer systemic treatment, and an ECOG PS score of 0 or 1 received oral belzutifan 120 mg once daily until disease progression, unacceptable toxicity, or pt withdrawal. The primary end point was objective response rate (ORR) in VHL disease–associated RCC per RECIST v1.1 by independent central review (ICR). Secondary end points were safety, ORR in non-RCC neoplasms, and duration of response (DOR) in renal and nonrenal neoplasms, per RECIST v1.1 by ICR. Results: Of 61 pts, 50 were on treatment as of July 15, 2021; the primary reasons for discontinuation were disease progression in RCC neoplasms (n = 4) and pt decision to withdraw (n = 4). Twenty pts (33%) had ≥1 pNET and 50 (82%) had ≥1 CNS hemangioblastoma evaluable by ICR at baseline. At baseline, 97% of pts (n = 59) had prior VHL-related surgery; 38 pts had ≥1 VHL-related surgery within 3 years before starting belzutifan. Median time from first dose to database cutoff date was 29.3 mo (range, 27.6-37.5). ORR in RCC was 59% (n = 36), with 2 CRs (3%) and 34 PRs (56%). Median DOR was not reached (range, 8.3+ to 27.6+ mo). ORR in CNS hemangioblastomas was 38% (n = 19; 3 CRs; 16 PRs); median DOR was not reached (range, 3.7+ to 28.0+ mo). ORR in pNETS was 90% (n = 18; 3 CRs; 15 PRs); median DOR was not reached (range, 11.0+ to 31.0+ mo). Three pts (5%) underwent VHL-related surgeries after starting belzutifan. Grade 3 treatment-related adverse events (TRAEs) were reported in 10 pts (16%); the most common was anemia (n = 6 [10%]). No pt had a grade 4 or 5 TRAE. Two pts (3%) stopped treatment because of TRAEs (grade 1 dizziness and grade 2 intracranial hemorrhage). Conclusions: After a median follow-up of 29.3 mo, belzutifan continued to show antitumor activity in VHL disease–related neoplasms, including RCC, pNETs, and CNS hemangioblastomas, whereas the safety profile remained consistent with that of previous reports. These results support the use of belzutifan as a systemic treatment for VHL disease. Clinical trial information: NCT03401788.
A New Route for Dioxygen Activation Uncovered from Quantum Mechanics Investigations of X‐Ray‐Diffraction‐Captured Intermediates of the Ferroxidase Reaction of Ferritins from Gram‐Negative Bacteria (2020)

Abstract Following the recent reassessment from X‐ray‐diffraction‐caught short‐path uptake to wide permeation of the S20A mutant Escherichia coli ferritin by ferrous ions, what happens when dioxygen gets to the diiron system is investigated. It is shown that the previously X‐ray‐caught situation of an unbound‐dioxygen diferrous state actually is an ephemeral state that changes into a P‐type peroxodiferric state, while a water molecule moves to bridge the two ferric ions, in what appears to be a remarkable redox process. All this stems from density functional theory (DFT)‐based quantum mechanics‐molecular mechanics and broken symmetry (BS) calculations that are extended to X‐ray‐diffraction‐caught oxodiferric and I‐type peroxodiferric systems from other subunits of the same crystal structure, validating them while determining antiferromagnetic coupling with all such diiron systems except the oxodiferric one. The latter converged, on BS, to ferromagnetic coupling under a wide variety of hybrid DFT functionals and basis sets. The trend of the Heisenberg J coupling reflects and substantiates the structures of the diiron core.
Evaluation of fracture behavior in metal/ceramic joint by acoustic emission (1999)

Fracture behavior of Al/sapphire bulk joint fabricated by SAB (surface activated room temperature bonding) was investigated by AE (acoustic emission) method. Direct bonding at atomic level without formation of reaction products restricted the sources of AE generation into interfacial debonding and aluminum fracture itself. In order to reveal the effects of bonding conditions on fracture behavior by non-destructive method, specimens having different bonded area fraction were prepared. The sequential process of interfacial defect growth and propagation of main crack was elucidated by AE source characterization and real time observation of interface through transparent sapphire. Classification of AE signals was carried out by means of source characterization, which well agreed to observed results. While the coalescence of unbonded dominated in Al 2nine (99.5%)-bonded at 40 MPa, both coalescence of unbonded and ligament Al fracture resulted in crack propagation in Al 5nine (99.999%)-bonded at 20MPa.
Conformal transformation applied to plasmonics beyond the quasistatic limit (2010)

A general strategy has been proposed recently to design and study analytically plasmonic devices, such as kissing nanowires, which show unprecedented broadband and nanofocusing properties. These nanostructures result from a conformal transformation applied to infinite plasmonic systems. The conformal transformation tool is powerful since the whole problem is solved in the original frame under the quasistatic approximation. However, this strategy is quite restrictive in perspective of applications since it can only apply to nanostructures of a few tens of nanometers (typically 20 nm). In this study, we extend the range of validity of this approach by taking into account radiation damping. The radiative losses are shown to map directly onto the power dissipated by a fictive absorbing particle in the original frame. Whereas only the surface plasmon mode was considered in previous studies, here lossy surface waves are also taken into account. Their counterpart in the transformed frame is shown to contribute predominantly to the radiative losses. The radiative reaction is then taken into account to predict the optical response of the nanostructure beyond the quasistatic limit. Radiative losses are shown to limit the light harvesting process but improve its broadband feature. The field enhancement induced by the nanostructure decreases with the structure dimension but remains significant $(\ensuremath{\sim}{10}^{3})$ over a major part of the near-infrared and visible spectra. Our analytical model is compared to numerical simulations and a quantitative agreement is found for dimension up to 200 nm.
Vertical profiles of environmental parameters measured on discrete water samples collected with Niskin bottles at station TARA_031 during the Tara Oceans expedition 2009-2013 (2014)

The Tara Oceans Expedition (2009-2013) was a global survey of ocean ecosystems aboard the Sailing Vessel Tara. It carried out extensive measurements of evironmental conditions and collected plankton (viruses, bacteria, protists and metazoans) for later analysis using modern sequencing and state-of-the-art imaging technologies. Tara Oceans Data are particularly suited to study the genetic, morphological and functional diversity of plankton. The present data set includes properties of seawater, particulate matter and dissolved matter that were measured from discrete water samples collected with Niskin bottles during the 2009-2013 Tara Oceans expedition. Properties include pigment concentrations from HPLC analysis (10 depths per vertical profile, 25 pigments per depth), the carbonate system (Surface and 400m; pH (total scale), CO2, pCO2, fCO2, HCO3, CO3, Total alkalinity, Total carbon, OmegaAragonite, OmegaCalcite, and dosage Flags), nutrients (10 depths per vertical profile; NO2, PO4, N02/NO3, SI, quality Flags), DOC, CDOM, and dissolved oxygen isotopes. The Service National d'Analyse des Paramètres Océaniques du CO2, at the Université Pierre et Marie Curie, determined CT and AT potentiometrically. More than 200 vertical profiles of these properties were made across the world ocean. DOC, CDOM and dissolved oxygen isotopes are available only for the Arctic Ocean and Arctic Seas (2013).
Agents for Plan Monitoring and Repair (2003)

A key aspect to the successful planning and execution of tasks in an agent-enabled organization is the timely access to up-to-date information. Agents making decisions on behalf of human users need to access and verify information from multiple heterogeneous information sources, such as internal organizational databases (personal schedules, staff lists), real-time sensors (traffic and weather updates), as well as many types of public information (airline schedules, restaurant listings, etc). To address the problems of accessing and verifying information from heterogeneous sources, we developed a set of techniques for learning to recognize the content of the required information. The capability makes it possible to automatically access and maintain wrappers to extract data from online sources. It also provides semantic interoperability among software agents: to verify information from other agents, identify semantic mismatches in data, as well as automatically determine the type of information being communicated by an agent.
Monolayer of metallo-supramolecular complexes (1998)

Self-assembled thin films of metallo-supramolecular complexes were prepared and characterized by synchrotron based X-ray reflectivity and fluorescence techniques.
Density of the Ratio of Two Normal Random Variables and Applications (2006)

In reply to a question raised in the literature, and to settle an argument debated in the last decades, we give the exact closed form expression of the density of X/Y, where X and Y are normal random variables, in terms of Hermite and confluent hypergeometric functions. All cases will be considered: standardized and nonstandardized variables, independent or correlated variables. Examples in applied disciplines are presented, and generalizations to ratios of variables from scale mixtures of bivariate normal distributions show the potential of further new applications in applied statistics and operations research.
Monte Carlo simulations of secondary electron emission due to ion beam milling (2017)

The authors present a Monte Carlo simulation study of secondary electron (SE) emission resulting from focused ion beam milling of a copper target. The basis of this study is a simulation code which simulates ion induced excitation and emission of secondary electrons, in addition to simulating focused ion beam sputtering and milling. This combination of features permits the simulation of the interaction between secondary electron emission, and the evolving target geometry as the ion beam sputters material. Previous ion induced SE Monte Carlo simulation methods have been restricted to predefined target geometries, while the dynamic target in the presented simulations makes this study relevant to image formation in ion microscopy, and chemically assisted ion beam etching, where the relationship between sputtering, and its effects on secondary electron emission, is important. The authors focus on a copper target and validate the simulation method against experimental data for a range of noble gas ions, ion energies, ion/substrate angles, and the energy distribution of the secondary electrons. The authors then provide a detailed account of the emission of secondary electrons resulting from ion beam milling; the authors quantify both the evolution of the yield as high aspect ratio valleys are milled, as well as the emission of electrons within these valleys that do not escape the target, but which are important to the secondary electron contribution to chemically assisted ion induced etching.
RepSeq Data Representativeness and Robustness Assessment by Shannon Entropy (2018)

High-throughput sequencing (HTS) has the potential to decipher the diversity of T cell repertoires and their dynamics during immune responses. Applied to T cell subsets such as T effector and T regulatory cells, it should help identify novel biomarkers of diseases. However, given the extreme diversity of TCR repertoires, understanding how the sequencing conditions, including cell numbers, biological and technical sampling and sequencing depth, impact the experimental outcome is critical to proper use of these data. Here, we assessed the representativeness and robustness of TCR repertoire diversity assessment according to experimental conditions. By comparative analyses of experimental datasets and computer simulations, we found that (i) for small samples, the number of clonotypes recovered is often higher than the number of cells per sample, even after removing the singletons; (ii) high-sequencing depth for small samples alters the clonotype distributions, which can be corrected by filtering the datasets using Shannon entropy as a threshold; and (iii) a single sequencing run at high depth does not ensure a good coverage of the clonotype richness in highly polyclonal populations, which can be better covered using multiple sequencing. Altogether, our results warrant better understanding and awareness of the limitation of TCR diversity analyses by HTS and justify the development of novel computational tools for improved modeling of the highly complex nature of TCR repertoires.
Amyloid protein SAA is associated with high density lipoprotein from human serum. (1977)

Human serums contain a protein antigenically related to protein AA, the principal protein of a major class of amyloid substance. The serum antigen, SAA, occurs mainly in a high molecular weight form, 1 to 2 X 10(5). This work shows that the bulk of the SAA sediments at density 1.12 g/cm3 and floats at density 1.21 g/cm3, as does the high density lipoprotein HDL3. SAA is associated with the apolipoproteins ApoA-I and ApoA-II. The total cholesterol:total protein ratio of the fraction with density 1.12-1.21 g/cm3 is 0.2:1, consistent with that of SAA constituent of the HDL3 fraction into low molecular weight species of the order of 13,000. The quantity of SAA may vary from 0.1% or more of the total protein of HDL3.
Initiation, Elongation, and Termination of Bacterial Cellulose Synthesis (2018)

Cellulose is the major component of the plant cell wall and composed of β-linked glucose units. Use of cellulose is greatly impacted by its physical properties, which are dominated by the number of individual cellulose strand within each fiber and the average length of each strand. Our work described herein provides a complete mechanism for cellulose synthase accounting for its processivity and mechanism of initiation. Using ionic liquids and gel permeation chromatography, we obtain kinetic constants for initiation, elongation, and termination (release of the cellulose strand from the enzyme) for two bacterial cellulose synthases (<i>Gluconacetobacter hansenii</i> and <i>Rhodobacter sphaeroides</i>). Our results show that initiation of synthesis is primer-independent. After initiation, the enzyme undergoes multiple cycles of elongation until the strand is released. The rate of elongation is much faster than that of steady-state turnover. Elongation requires cyclic addition of glucose (from uridine diphosphate-glucose) and then strand translocation by one glucose unit. Translocations greater than one glucose unit result in termination requiring reinitiation. The rate of the strand release, relative to the rate of elongation, determines the processivity of the enzyme. This mechanism and the measured rate constants were supported by kinetic simulation. With the experimentally determined rate constants, we are able to simulate steady-state kinetics and mimic the size distribution of the product. Thus, our results provide for the first time a mechanism for cellulose synthase that accounts for initiation, elongation, and termination.
Methods for absorbing neutrons (2023)

A conduction cooled neutron absorber may include a metal matrix composite that comprises a metal having a thermal neutron cross-section of at least about 50 barns and a metal having a thermal conductivity of at least about 1 W/cmK. Apparatus for providing a neutron flux having a high fast-to-thermal neutron ratio may include a source of neutrons that produces fast neutrons and thermal neutrons. A neutron absorber positioned adjacent the neutron source absorbs at least some of the thermal neutrons so that a region adjacent the neutron absorber has a fast-to-thermal neutron ratio of at least about 15. A coolant in thermal contact with the neutron absorber removes heat from the neutron absorber.
New Methods in Iris Recognition (2007)

This paper presents the following four advances in iris recognition: 1) more disciplined methods for detecting and faithfully modeling the iris inner and outer boundaries with active contours, leading to more flexible embedded coordinate systems; 2) Fourier-based methods for solving problems in iris trigonometry and projective geometry, allowing off-axis gaze to be handled by detecting it and "rotating" the eye into orthographic perspective; 3) statistical inference methods for detecting and excluding eyelashes; and 4) exploration of score normalizations, depending on the amount of iris data that is available in images and the required scale of database search. Statistical results are presented based on 200 billion iris cross-comparisons that were generated from 632500 irises in the United Arab Emirates database to analyze the normalization issues raised in different regions of receiver operating characteristic curves.
A hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia (2012)

Using N-ethyl-N-nitrosourea-induced mutagenesis, we established a mouse model with a novel form of neutropenia resulting from a point mutation in the transcriptional repressor Growth Factor Independence 1 (Gfi1). These mice, called Genista, had normal viability and no weight loss, in contrast to mice expressing null alleles of the Gfi1 gene. Furthermore, the Genista mutation had a very limited impact on lymphopoiesis or on T- and B-cell function. Within the bone marrow (BM), the Genista mutation resulted in a slight increase of monopoiesis and in a block of terminal granulopoiesis. This block occurred just after the metamyelocytic stage and resulted in the generation of small numbers of atypical CD11b(+) Ly-6G(int) neutrophils, the nuclear morphology of which resembled that of mature WT neutrophils. Unexpectedly, once released from the BM, these atypical neutrophils contributed to induce mild forms of autoantibody-induced arthritis and of immune complex-mediated lung alveolitis. They additionally failed to provide resistance to acute bacterial infection. Our study demonstrates that a hypomorphic mutation in the Gfi1 transcriptional repressor results in a novel form of neutropenia characterized by a split pattern of functional responses, reflecting the distinct thresholds required for eliciting neutrophil-mediated inflammatory and anti-infectious responses.
Effectiveness of foam disinfectants in reducing sink-drain gram-negative bacterial colonization (2019)

An easy-to-use foaming application of a hydrogen peroxide- and peracetic acid-based disinfectant suppressed sink-drain colonization for at least 3 days. Intermittent application of the foaming disinfectant could potentially reduce the risk for dissemination of pathogens from sink drains.
Performance evaluation of a new cache replacement scheme using SPEC (2002)

Presents a new neural network-based algorithm called KORA (Khalid-Obaidat Replacement Algorithm), that uses a backpropagation neural network (BPNN) for the purpose of guiding the line/block replacement decisions in a cache. The KORA algorithm attempts to approximate the replacement decisions made by the optimal scheme (OPT). The key to our algorithm is to identify and subsequently discard the dead lines in cache memories. This allows our algorithm to provide better cache performance as compared to the conventional LRU (least recently used), MRU (most recently used) and FIFO (first-in, first-out) replacement policies. Extensive trace-driven simulations were performed for 30 different cache configurations using different SPEC (Standard Performance Evaluation Corp.) programs. Simulation results have shown that KORA can provide a substantial improvement in the miss ratio over the conventional algorithms. Our work opens up new dimensions for research in the development of new and improved page replacement schemes for virtual memory systems and disk caches.
Silicon-Nanocrystal-Coated Silica Microsphere Thermooptical Switch (2006)

We report on a low-switching-energy, all-optical fiber switch that consists of a silica microsphere resonator coated with a silica layer containing silicon nanocrystals. A signal at 1450 nm and a pump at 488 nm are coupled into the microsphere through a tapered fiber. When a pump pulse is launched into the sphere, it is absorbed by the nanocrystal layer, causing the sphere to heat up and change its refractive index. The index change can be exploited to switch the signal by shifting the microsphere resonance. A resonance wavelength shift of 5 pm, sufficient to fully switch the signal, was observed with a pump pulse energy of only 85 nJ. The rise time of the switch was ~25 ms (limited by the pump peak power) and its fall time was ~30 ms (limited by the sphere's thermal time constant). The product of the switching peak power (3.4 mu W) and the device's characteristic dimension (a diameter of 150 mum) is 5.1times10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-10</sup> Wm, one of the lowest values reported for an all-optical fiber switch
Soy-Induced Fecal Metabolome Changes in Ovariectomized and Intact Female Rats: Relationship with Cardiometabolic Health (2018)

Phytoestrogens are plant-derived compounds found in a variety of foods, most notably, soy. These compounds have been shown to improve immuno-metabolic health, yet mechanisms remain uncertain. We demonstrated previously that dietary phytoestrogen-rich soy (SOY) rescued metabolic dysfunction/inflammation following ovariectomy (OVX) in female rats; we also noted remarkable shifts in gut microbiota in SOY vs control diet-fed rats. Importantly, specific bacteria that significantly increased in those fed the SOY correlated positively with several favorable host metabolic parameters. One mechanism by which gut microbes might lead to such host effects is through production of bacterial metabolites. To test this possibility, we utilized non-targeted gas chromatography-mass spectrometry (GCMS) to assess the fecal metabolome in those previously studied animals. Partial least square discriminant analysis (PLSDA) revealed clear separation of fecal metabolomes based on diet and ovarian state. In particular, SOY-fed animals had greater fecal concentrations of the beneficial bacterial metabolite, S-equol, which was positively associated with several of the bacteria upregulated in the SOY group. S-equol was inversely correlated with important indicators of metabolic dysfunction and inflammation, suggesting that this metabolite might be a key mediator between SOY and gut microbiome-positive host health outcomes.
Superiority of sirolimus eluting stent compared with intracoronary β radiation for treatment of in-stent restenosis: a matched comparison (2005)

In this non-randomised matched cohort SES achieved acute and follow up results superior to IRT for treatment of ISR even if cases of failed IRT are included. Failed IRT is a predictor of impaired SES effectiveness.