gebhart/patrepeval huggingface dataset:
A phase I pharmacokinetic (PK) trial of XAA296A (Discodermolide) administered every 3 wks to adult patients with advanced solid malignancies (2004)

2025 Background: XAA296A is a natural product isolated from the marine sponge Discoderma dissoluta. It stabilizes microtubules more potently than paclitaxel and has activity against paclitaxel-refractory xenografts. Methods: In this phase I trial, XAA296A was administered IV as a fixed infusion rate of 0.77mg/ml/min once every 3 weeks. Results: 26 pts (17 M, 9 F) have been treated at the following dose levels (mg/m2): 0.6 (3 pts); 1.2 (3 pts); 2.4 (4 pts); 4.8 (4 pts); 9.6 (4 pts); 14.4 (6 pts) and 19.2 (2 pts). The median age = 59.5 (19–79). All patients had KPS ≥70%. 9/ 26 received prior taxane therapy. No drug related DLTs have occurred to date. G1 pain and burning at site of injection was noticed at initial dose levels but resolved with central administration of XAA296A. One patient had G4 anemia during third cycle. Number of patients with G2/3 adverse events with suspected relationship to XAA296A (all cycles): Anemia (5,1), Nausea (6, 0), Vomiting (3, 1), Fatigue (5, 1), Diarrhea (4, 0), Mucositis (2, 0), Stomatitis (1,0), Pruritus (1,0), ↑Alk phos (1,0), ↑ Creatinine (1,0), Myalgias (1,0). No neuropathy or neutropenia has been observed. One patient with appendix carcinoma had stable disease for 4 cycles. PK of XAA296A was evaluated in 24 pts after the 1st and 2nd dose using noncompartmental approach. Concentrations were determined by an LC/MS/MS method. XAA296A concentrations showed Cmax at the end of infusion, thereafter declining rapidly in a multiphasic manner. By 24 h post-dose, blood concentrations had decreased to <10% of Cmax, but then showed nonlinear PK, evidenced by a convexity of the terminal phase on a semi-log scale. This was observed in the majority of concentration-time profiles, suggesting prolonged recycling of drug between tissue and the systemic circulation. AUClast, Cmax, and MRTlast ranged from 103–15211 ng*h/ml, 29–482 ng/ml, and 32–162 h, respectively. Conclusions: XAA296A is a novel microtubule stabilizer which has minimal toxicities in this phase I trial. In addition, it demonstrates nonlinear PK characterized by a second broad peak at the terminal phase. Dose accrual is continuing to define the phase II dose. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp.
New Homogeneous Standards by Atomic Layer Deposition for Synchrotron X-Ray Fluorescence and Absorption Spectroscopies (2012)

Gains in predictive accuracy for predicting cardiovascular outcomes were less impressive than gains in performance observed in the data mining literature.
SU‐FF‐T‐45: Sensitivity of the 50 KVp Xoft Axxent Electronic Brachytherapy Skin Applicator to Flattening Filter Design, Source‐Filter Position, Applicator Alignment and Surface Collimation (2009)

Purpose: The Xoft Axxent Electronic Brachytherapy Skin Applicator and miniature x‐ray source combination can be used for superficial skin or surface treatments. The applicator is a 25 mm SSD cone (1.0–5.0 cm diameter) with an embedded flattening filter. The applicator and source are decoupled, which could lead to variations in dose profile. Several potential problems are investigated for this system. Method and Materials: Dose profiles of the 35 mm diameter cone were measured in solid water using GAFChromic EBT film and in water using a stereotactic diode. Two flattening filter designs were examined. The effect of rotating the source or applicator independently, tilting the applicator with respect to the surface, modifying the source‐filter distance, and skin collimation from 10 to 30 mm by means of tungsten aperture cutouts were examined. Results: The stepped disk filter design had flatness and asymmetry of 8.3% and 3.1%. The chamfered filter was 14.8% and 0.7% respectively. Rotation of the source and applicator produced a minimal change in flatness and asymmetry, with less than 2% change in flatness or asymmetry. The stepped‐disk filter flatness changed by up to 7% with filter source displacement. Tipping the applicator off of the perpendicular axis by 6 degrees changed the symmetry by 14%. Beam profiles for cutouts ranging from 1.0–3.0 showed little change in flatness and asymmetry, and the sharp edges of the PTW were retained. Conclusion: The stepped filter design is superior. The source‐filter is sufficiently concentric to prevent profile shifts, but the dose is very sensitive to the filter‐source distance, as predicted by the geometric model. Small tilts of up to 2 degrees, or a 1 mm gap on one side of the cone, can be tolerated. Skin collimation preserves both profile and penumbra. Research Sponsored by Xoft, Inc.
A hierarchical interface design methodology and models for SoC IP integration (2003)

A key aspect of an IP core's marketability is its ability to be easily integrated across a wide variety of interfaces. In this paper, we propose an efficient hierarchical interface design methodology and models so that a designer can quickly design an IP core's interface, which can be easily integrated into any interface/bus architecture. The proposed methodology and models have been applied to design an MP3 decoder with different interfaces: an ISA bus interface and a PCI bus interface. The results demonstrate that the methodology and models result in easy IP integration and only a little performance overhead.
Simulations of Submicron MOSFETs in 2H-, 4H- and 6H-SiC (2002)

In this paper, we present numerical studies of the high frequency performance of a submicron MOSFET in 2H-, 4H- and 6H-SiC. The studies are based on simulations where commercial two-dimensional drift-diffusion and hydrodynamic carrier transport models have been used. The results have been compared with those obtained from full band Monte Carlo simulations. The Monte Carlo carrier transport model is based on data from a full potential band structure calculation using the Local Density Approximation to the Density Functional Theory. In 6H-SiC the bulk transport properties in the direction perpendicular to the c-axis, are slightly lower than in 2H- and 4H-SiC. However, in the direction parallel to the c-axis the transport properties are considerably less favourable than in the other two polytypes. The effects of these differences, on surface mobility, device performance and carrier energy, have been studied.
Study of DNA deformation under flow using optical tweezers (2004)

The stretching and unwinding of polymers under flow is important for understanding the rheological properties of dilute polymer solutions. Scaling theory based on the blob picture of single polymer chains predicts several regimes for the overall shape of a hydrodynamically deformed macromolecule. We studied the shape of a DNA molecule stretched out by steady uniform flow at different velocities using optical trapping of single DNA molecules (tethered on polystyrene beads) and single molecule fluorescence imaging. The results show a gradual transition from a non-draining regime at low velocities to a free-draining regime at high velocities, thus verifying the predictions of the free draining-shell (F-shell) blob model.
Estudo preliminar sobre a transmissão de Leishmaniose Tegumentar Americana (LTA) em Monte Negro, Rondônia (2007)

Projeto PRONEX. CNPq/FAPESP (03-10391-5) e FINEP -040311.
HYALURONIDASE ACTIVITY IN SEMINAL PLASMA AS A METHOD OF ASSESSING BULL SPERM INTEGRITY (1975)

Ministry of Agriculture, Fisheries and Food, Cattle Breeding Centre, Shinfield, Reading RG2 9BZ (Received 4th November 1974) One of the earliest visual signs of sperm damage is the loss of acrosomal integrity. Consequently, assay of the release into the seminal plasma of hyaluronidase, which is localized in the acrosome (Mancini, Alonsa, Bacquet, Avarez & Nemirosky, 1964; Gould & Bernstein, 1973) should provide an early and sensitive indication of damage sustained by the spermatozoa during processing of semen for artificial insemination (A.I.). Previous biochemical tests of sperm viability have included the assay of phenylalanine α-ketoglutarate transaminase released into boar seminal plasma (Gemert, Hendrike & Van der Horst, 1972). A correlation was found between high enzyme activity in seminal plasma and poor fertility. The release of glutamic oxaloacetic transaminase has been considered an indication of cell damage (Brown, Crabo, Graham & Pace, 1971) and assay of this non-acrosomal enzyme has been investigated
Electrostatic lubrication of moulds (2002)

A prototype dry electrostatic powder lubrication system for lubrication of powder metallurgy moulds was designed. The system uses contact electrification to charge the powder and an electric field to aid in uniform coating of the internal surfaces of the mould. The system was mounted on a 200 ton press and the sequence used in lubrication of the mould was compatible with the press sequence in which the parts are produced. Parts which were made using the prototype system and reduced lubricant powder concentration in the metal powder formulation had increased green density and strength while still maintaining equivalent surface finish and mould lubrication for successful moulding of parts.
Lateral distribution of muons in IceCube cosmic ray events (2013)

In cosmic ray air showers, the muon lateral separation from the center of the shower is a measure of the transverse momentum that the muon parent acquired in the cosmic ray interaction. IceCube has observed cosmic ray interactions that produce muons laterally separated by up to 400 m from the shower core, a factor of 6 larger distance than previous measurements. These muons originate in high ${p}_{T}$ ($>2\text{ }\text{ }\mathrm{GeV}/\mathrm{c}$) interactions from the incident cosmic ray, or high-energy secondary interactions. The separation distribution shows a transition to a power law at large values, indicating the presence of a hard ${p}_{T}$ component that can be described by perturbative quantum chromodynamics. However, the rates and the zenith angle distributions of these events are not well reproduced with the cosmic ray models tested here, even those that include charm interactions. This discrepancy may be explained by a larger fraction of kaons and charmed particles than is currently incorporated in the simulations.
Favorskii reactions. I. Nature of the rate-determining step (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFavorskii reactions. I. Nature of the rate-determining stepFrederick G. Bordwell, Robert R. Frame, Richard G. Scamehorn, Jerry G. Strong, and Seymour. MeyersonCite this: J. Am. Chem. Soc. 1967, 89, 25, 6704–6711Publication Date (Print):December 1, 1967Publication History Published online1 May 2002Published inissue 1 December 1967https://pubs.acs.org/doi/10.1021/ja01001a054https://doi.org/10.1021/ja01001a054research-articleACS PublicationsRequest reuse permissionsArticle Views264Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Differential Mapping of the Amino Acids Mediating Agonist and Antagonist Coordination with the Human Thromboxane A2 Receptor Protein. (2005)

Abstract Despite the well-documented involvement of thromboxane A2 receptor (TPR) signaling in the pathogenesis of thrombotic diseases, there are currently no rationally-designed antagonists available for clinical use. To a large extent this derives from a lack of knowledge regarding the topography of the TPR ligand binding pocket. On this basis, the purpose of the current study was to identify the specific amino acid residues in the TPR protein which regulate ligand coordination and binding. The sites selected for mutation reside within or in close proximity to a region we previously defined as a TPR ligand binding site, i.e., the C-terminus of the second extracellular loop and the leading edge of the fifth transmembrane domain. Mutation of these residues caused varying effects on the TPR-ligand coordination process. Specifically, the D193A mutant lacked both SQ29,548 (antagonist) binding and U46619 (agonist)-induced calcium mobilization. Three other mutants, F184Y, T186A and S191T, discriminated between SQ29,548 binding and the U46619-mediated functional response. Furthermore, these mutants also revealed a divergence in the binding of two structurally different antagonists, SQ29,548 and BM13.505. Conversely, two separate mutants which exhibited SQ29,548 binding activity yielded either a normal (F196Y) or reduced (S201T) U46619 response. Finally, mutation of other residues directly adjacent to those described above, e.g., E190A and F200A, produced no detectable effects on either SQ29,548 binding or the U46619-induced functional response. In summary, these results identify key amino acids involved in TPR ligand coordination and demonstrate that TPR-specific ligands do not necessarily interact with the same residues in the ligand-binding pocket.
Stavudine plus didanosine and nevirapine in antiretroviral-naive HIV-infected adults: preliminary safety and efficacy results. VIRGO Study Team. (1998)

The objective of this open-label trial is to evaluate the virological and immunological effects of triple therapy with stavudine (40 mg twice daily if > or = 60 kg, 30 mg twice daily if < 60 kg)/didanosine (400 mg once daily if > or = 60 kg, 300 mg once daily if < 60 kg)/nevirapine (200 mg daily from day 1 to 14, then 200 mg twice daily) in 60 antiretroviral-naive HIV-infected adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV RNA > or = 5000 copies/ml. At present, 59 patients have begun receiving the trial regimen. Characteristics of patients at baseline were as follows: 46 men/13 women, CDC stage A, 75%; mean CD4 cell count, 429 cells/mm3; mean HIV RNA, 4.6 log10 copies/ml). Mean decrease of viral load was -1.9 log10 at week 4 (n = 39), -1.9 log10 at week 16 (n = 20), with HIV RNA below the detectable level (< 500 copies/ml) in 62% of patients at week 4 and 85% at week 16. Mean CD4 cell count increase was +118 cells/mm3 at week 4. Cutaneous intolerance occurred within the first 4 weeks in 11/59 (19%) patients after a mean of 14 days (range, 3-24 days) and led to nevirapine discontinuation in 3/11 patients. Preliminary results of this ongoing trial show that combination therapy with stavudine/didanosine/nevirapine is a convenient (seven pills in two daily intakes) triple-therapy regimen with rapid immunological and antiviral effects. Rash, frequent in the first weeks of therapy, usually can be managed without stopping nevirapine. Long-term suppression of plasma HIV RNA with this combination needs to be confirmed but may support use of nevirapine as a component of first-line anti-HIV therapy along with two nucleosides.
Wavelength dependence and power requirements of a wavelength converter based on XPM in an optical fiber (2000)

Summary form only given. All-optical wavelength conversion can play an important role in future ultra-high-speed networks due to the significant increase in flexibility and potential reduction in need for optical buffers. We have recently demonstrated a different cross phase modulation (XPM) based scheme to wavelength convert 40 Gb/s RZ data. The basic idea of this scheme is to utilize XPM in a dispersion shifted fiber. Continuous wave (CW) light is launched into the fiber along with the data pulses. The pulses will impose a phase modulation which generates sidebands on the CW light. After suppression of the original CW wavelength, and filtering out one of the sidebands, the wavelength converted data remains at the output. Here we report on pulse measurements in the wavelength converter in order to assess its fundamental operating characteristics.
A comparison of the effects of ibuprofen and rofecoxib on rabbit fibula osteotomy healing (2009)

Continuous COX-2 inhibition as modeled by rofecoxib treatment appears to be more deleterious to fracture repair than cyclical cyclooxygenase inhibition as modeled by ibuprofen treatment. Ibuprofen treatment appeared to delay bone healing based upon the persistence of cartilage within the fracture callus and diminished shear modulus. Despite the ibuprofen-induced delay, rofecoxib treatment produced worse fracture (osteotomy) healing than ibuprofen treatment.
A model for calculation of RCS pressure during reflux boiling under reduced inventory conditions and its assessment against PKL data (1991)

There has been recent interest in the United States concerning the loss of residual heat removal system (RHRS) under reduced coolant inventory conditions for pressurized water reactors. This issue is also of interest in the Federal Republic of Germany and an experiment was performed in the integral PKL-HI experimental facility at Siemens-KWU to supply applicable data. Recently, an NRC-sponsored effort has been undertaken at the Idaho-National Engineering Laboratory to identify and analyze the important thermal-hydraulic phenomena in pressurized water reactors following the long term loss-of-RHRS during reduced inventory operation. The thermal-hydraulic response of a closed reactor coolant system during such a transient is investigated in this report. Some of the specific processes investigated include: reflux condensation in the steam generators, the corresponding pressure increase in the reactor coolant system, and void fraction distributions on the primary side of the system. Mathematical models of these and other physical processes Experiment B4.5.
Optimization of the Probe Coverage in DNA Biosensors by a One‐Step Coadsorption Procedure (2013)

Abstract Analytical performance (selectivity, sensitivity, limit of detection) of a sensor is ultimately connected to the interfacial architecture of the sensing surface that needs to be optimized. Self‐assembly of a mixed monolayer of thiolated probes and diluent onto gold surfaces used in the design of biosensing platforms is nowadays commonly performed by a two‐step immobilization procedure. In this work, the merits of a one‐step coadsorption procedure are emphasized, and it is shown that the ionic strength is a very efficient tool to fine control the surface concentration of the immobilized probe. Probe densities were obtained by alternating current voltammetry or fluorescence measurements depending on the type of labeling of the probes. With unlabeled DNA sequences, chronocoulometric measurements were performed in the presence of dissolved hexaammineruthenium(III) cations. The maximum probe density achievable at high ionic strength by the one‐step coadsorption procedure is limited by steric constraints and depends on the structure of the sequence. Various thiolated DNA sequences (single‐stranded DNA, double‐stranded DNA, linear, hairpin, quadruplex) coadsorbed with a common diluent, 4‐mercaptobutan‐1‐ol, were used to discuss the structural factors affecting the maximum surface densities obtained for the different types of probe. Application of the one‐step coadsorption procedure to the optimization of the analytical performance of a protein aptasensor is illustrated by building a sensor for the detection of thrombin on the basis of the thrombin binding aptamer sequence.
CD155 (PVR/Necl5) Mediates a Costimulatory Signal in CD4+ T Cells and Regulates Allergic Inflammation (2015)

Although Th1 and Th2 cells are known to be involved in allergic inflammatory diseases, the molecular mechanisms underlying their differentiation are incompletely understood. In this study, we identified CD155 as a costimulatory molecule on CD4(+) T cells. Importantly, CD155-mediated signaling induced Th1 development in both humans and mice, as evidenced by production of IFN-γ and upregulation of Tbx21 transcription; these effects were independent of IL-12 but dependent on NF-κB-induced autocrine IFN-γ that triggered positive feedback via STAT1 activation. Mice genetically deficient in CD155 or treated with anti-CD155 Ab exhibited attenuated Th1-type contact hypersensitivity. Thus, CD155 plays an important regulatory role in helper T cell differentiation and allergic diseases.
Measurements of the Ultra-Heavy Galactic Cosmic-Ray Abundances between Z=30 and Z=40 with the TIGER Instrument (2003)

The Trans-Iron Galactic Element.Recorder (TIGER) instrument was launched in December 2001 from McMurdo, Antarctica. TIGER is a cosmic-ray telescope that uses four scintillation counters, two Cherenkov detectors and a scintillating fiber hodoscope to determine the charge (Z) and energy of a particle. During the 31.8 day flight it measured ~100 ultra-heavy galactic cosmic-ray (GCR) events\nwith Z > 30 and demonstrated charge resolution sufficient to resolve the individual elemental abundances in this region. The abundances of the Ultra-Heavy GCRs in this range can be used to distinguish between GCR source models. We present our measurements and discuss the implications for the GCR source.
Singular perturbation approximation of bounded real and of positive real transfer matrices (2005)

In this work the problem of model reduction of bounded real and of positive real transfer matrices is considered. Singular perturbation approximation of bounded real balanced and of stochastically balanced systems are proposed and their properties are shown. In particular it is shown that the reduced order models remain bounded real and positive real respectively and bounds on the approximation error are obtained. An example, showing the suitability of the proposed method, concludes the paper.
Electron‐transfer coupling in microbial fuel cells. 2. performance of fuel cells containing selected microorganism—mediator—substrate combinations (1984)

Abstract Various phenoxazine, phenothiazine, phenazine, indophenol and bipyridilium derivatives were tested for their effectiveness as redox mediators in microbial fuel cells containing Alcaligenes eutrophus, Bacillus subtilis, Escherichia coli , or Proteus vulgaris as the active biological agent, and glucose or succinate as the oxidisable substrate. A ferricyanide‐Pt cathode was used. The open‐circuit cell e.m.f.′s increased in the order of increasing negative formal redox potentials at pH 7(E 7 m ) of the redox compounds. Several of the redox agents worked well as mediators, maintaining steady currents over several hours, and thionine was found to be particularly effective in maintaining relatively high cell voltages when current was drawn from the cell. A number of the compounds tested did not function well, either because they were incompletely or slowly reduced by the microorganisms or because of their instability. P. vulgaris , with thionine as mediator and glucose as substrate, showed the best performance in a fuel cell. This system was examined in some detail under various conditions of external load to establish the effects of organism concentration, mediator concentration, and substrate addition. Coulombic outputs from these cells were calculated by integration of the current‐time plots. Coulombic yields of 30–60% were obtained, on the basis of (theoretical) complete oxidation of added substrate to CO 2 and water.