gebhart/patrepeval huggingface dataset:
Preclinical evaluation of AMG 160, a next-generation bispecific T cell engager (BiTE) targeting the prostate-specific membrane antigen PSMA for metastatic castration-resistant prostate cancer (mCRPC). (2019)

301 Background: mCRPC is a disease of high unmet medical need, especially for patients who fail novel hormonal therapies and chemotherapy. BiTE molecules provide an off the shelf therapy that activates a patient’s own immune system and redirects T cells to kill tumor cells. The BiTE mechanism of action is distinct from other immunotherapies and may unlock immune response in mCRPC. PSMA is a compelling BiTE target that is highly expressed on PCa compared to normal tissue and has increased expression in mCRPC. Methods: AMG 160 is a fully human, half-life extended (HLE) BiTE that targets PSMA on tumor cells and CD3 on T cells. AMG 160 comprises two tandem single chain variable fragments fused to an Fc domain. Results: AMG 160 binds human and non-human primate (NHP) PSMA and CD3, leading to T cell activation and proliferation and cytokine production. AMG 160 redirects T cells to kill PSMA-positive cancer cell lines in vitro, including those with low PSMA levels or androgen-independent signaling. Weekly dosing of AMG 160 induces significant antitumor activity in established PCa xenograft model. The pharmacokinetics (PK) and pharmacodynamics of AMG 160 were tested in NHP. AMG 160 treatment led to BiTE target engagement in vivo, including transient T cell activation and cytokine release in blood, and mixed cellular infiltrates in multiple organs known to express PSMA. AMG 160 treatment was well tolerated. Cytokine release associated with the first dose could be attenuated using a step dose regimen. The half-life of AMG 160 in NHP was about one week. Based on allometric scaling, the PK profile of AMG 160 may be projected to enable dosing every other week in humans. Conclusions: AMG 160 is a potent HLE BiTE with specificity for PSMA-positive tumor cells. A Phase 1 study is planned to evaluate the safety and efficacy of AMG 160 in patients with mCRPC.
Polymerization of Liquid-Crystalline Monomers with Biphenyl Moiety (1998)

Abstract To explore the effect of orientation of monomers and polymerization procedure on polymerization behavior, thermal polymerization and photopolymerization of vinyl monomers having a biphenyl structure were conducted at various temperatures. It was found that the initial rate of polymerization and conversion increased with temperature despite phases of the monomer. It was also observed that Arrhenius plots for the initial rates of photopolymerization fell on a straight line, while those of thermal polymerization changed the slope at the smecticisotropic or nematic-isotropic phase transition temperature. The number-average molecular weight of the polymer produced in the thermal polymerization in the smectic phase was higher than that in the isotropic phase, whereas that of the polymer obtained by photopolymerization in the smectic phase was lower than that in the isotropic phase. These results suggest that polymerization behavior is affected by the initiation method in the polymerization of liquid-crystalline monomers.
Electron Paramagnetic Resonance and Optical Spectra of Pentacyanocobaltate(II) (1971)

Electron paramagnetic resonance (EPR) and optical spectral studies have been carried out on the pentacyanocobaltate(II) ion in ethylene glycol–water solutions, and in electron-irradiated powder samples of K3Co(CN)6. Both EPR and optical spectra observed for the ion in the powder samples are essentially similar to those obtained from the ethylene glycol–water solutions. There was no observable linewidth variation with nuclear spin states MI, no dependence on the different solvent media used, and no dependence on the concentration ratio Co2+/CN−, in both X-band and K-band spectra. The results indicate that the structure of Co(CN)53− in solutions and in polycrystalline media is a slightly distorted square pyramid with no solvent bound in the sixth coordination site. The two strong hyperfine components with exceptionally large spacings occurring at the low-field end of the X-band spectrum are identified as the so-called angular anomalies. An effective method of simulation of the first-derivative EPR spectra of polycrystalline samples has also been developed.
Towards New Robust Zn(II) Complexes for the Ring‐Opening Polymerization of Lactide Under Industrially Relevant Conditions (2019)

The synthesis of bio-based and biodegradable plastics is a hot topic in research due to growing environmental problems caused by omnipresent plastics. As a result, polylactide, which has been known for years, has seen a tremendous increase in industrial production. Nevertheless, the manufacturing process using the toxic catalyst Sn(Oct)<sub>2</sub> is very critical. As an alternative, five zinc acetate complexes have been synthesized with Schiff base-like ligands that exhibit high activity in the ring-opening polymerization of non-purified lactide. The systems bear different side arms in the ligand scaffold. The influence of these substituents has been analyzed. For a detailed description of the catalytic activities, the rate constants <i>k</i> <sub>app</sub> and <i>k</i> <sub>p</sub> were determined using in-situ Raman spectroscopy at a temperature of 150 °C. The polymers produced have molar masses of up to 71 000 g mol<sup>-1</sup> and are therefore suitable for a variety of applications. Toxicity measurements carried out for these complexes proved the nontoxicity of the systems.
Multivariate entropy analysis with data-driven scales (2012)

A data-adaptive algorithm for the entropy-based analysis of structural regularities (complexity) in multivariate signals is proposed. This is achieved by combining multivariate sample entropy with a multivariate extension of empirical mode decomposition, both data-driven multiscale techniques. The proposed analysis across data-adaptive scales makes the approach robust to nonstationarity, a critical issue with information theoretic measures. Simulations on synthetic and real-world physiological data support the approach and validate the hypothesis of increased complexity for unconstrained as compared to constrained (due to e.g. ageing or illness) biological systems.
Long-Range Electron Transfer in Heme Proteins (1991)

The kinetics of long-range electron transfer (ET) have been measured in Ru(NH3)4L(His 39) derivatives (L is NH3, pyridine, or isonicotinamide) of Zn-substituted Candida krusei cytochrome c and Ru(NH3)4L(His 62) derivatives (L is NH3 or pyridine) of Zn-substituted Saccharomyces cerevisiae cytochrome c. The rates of both excited-state electron transfer and thermal recombination are approximately 3 times greater in Ru(His 39)cytochrome c (Zn) than the rates of the corresponding reactions in Ru(His 33)cytochrome c (Zn), but analogous ET reactions in Ru(His 62)cytochrome c (Zn) are roughly 2 orders of magnitude slower than in the His 33-modified protein. Analysis of driving-force dependences establishes that the large variations in the ET rates are due to differences in donor-acceptor electronic couplings. Examination of potential ET pathways indicates that hydrogen bonds could be responsible for the enhanced electronic couplings in the Ru(His 39) and Ru(His 33) proteins.
A double dissociation between striate and extrastriate visual cortex for pattern motion perception revealed using rTMS (2009)

The neural mechanisms underlying the integration and segregation of motion signals are often studied using plaid stimuli. These stimuli consist of two spatially coincident dynamic gratings of differing orientations, which are either perceived to move in two unique directions or are integrated by the visual system to elicit the percept of a checkerboard moving in a single direction. Computations pertaining to the motion of the individual component gratings are thought to take place in striate cortex (V1) whereas motion integration is thought to involve neurons in dorsal stream extrastriate visual areas, particularly V5/MT. By combining a psychophysical task that employed plaid stimuli with 1 Hz offline repetitive transcranial magnetic stimulation (rTMS), we demonstrated a double dissociation between striate and extrastriate visual cortex in terms of their contributions to motion integration. rTMS over striate cortex increased coherent motion percepts whereas rTMS over extrastriate cortex had the opposite effect. These effects were robust directly after the stimulation administration and gradually returned to baseline within 15 minutes. This double dissociation is consistent with previous patient data and the recent hypothesis that both coherent and transparent motion percepts are supported by the visual system simultaneously and compete for perceptual dominance.
Capsular Localization of theCryptococcus neoformansPolysaccharide Component Galactoxylomannan (2008)

Cryptococcus neoformans capsular polysaccharide is composed of at least two components, glucuronoxylomannan (GXM) and galactoxylomannans (GalXM). Although GXM has been extensively studied, little is known about the location of GalXM in the C. neoformans capsule, in part because there are no serological reagents specific to this antigen. To circumvent the poor immunogenicity of GalXM, this antigen was conjugated to protective antigen from Bacillus anthracis as a protein carrier. The resulting conjugate elicited antibodies that reacted with GalXM in mice and yielded an immune serum that proved useful for studying GalXM in the polysaccharide capsule. In acapsular cells, immune serum localized GalXM to the cell wall. In capsulated cells, immune serum localized GalXM to discrete pockets near the capsule edge. GalXM was abundant on the nascent capsules of budding daughter cells. The constituent sugars of GalXM were found in vesicle fractions consistent with vesicular transport for this polysaccharide. In addition, we generated a single-chain fraction variable fragment antibody with specificity to oxidized carbohydrates that also produced punctate immunofluorescence on encapsulated cells that partially colocalized with GalXM. The results are interpreted to mean that GalXM is a transient component of the polysaccharide capsule of mature cells during the process of secretion. Hence, the function of GalXM appears to be more consistent with that of an exopolysaccharide than a structural component of the cryptococcal capsule.
Robust Gradient Estimation Schemes Using Radial Basis Functions (2008)

Utilization of Radial Basis Functions (RBFs) for gradient estimation is tested over various noisy flow fields. A novel mathematical formulation which minimizes the energy functional associated with the analytical surface fit for Gaussian (GA) and Generalized Multiquadratic (GMQ) RBFs is presented. Error analysis of the wall gradient estimation was performed at various resolutions, interpolation grid sizes, and noise levels in synthetically generated Poiseuille and Womersley flow fields for RBFs along with standard finite difference schemes. To test the effectiveness of the methods with DPIV (Digital Particle Image Velocimetry) data, the methods were compared using the velocities obtained by processing images generated from DNS data of an open turbulent channel. Random, bias and total error were computed in all cases. In the absence of noise all tested methods perform well, with error contained under 10% at all resolutions. In the presence of noise the RBFs perform robustly with a total error that can be contained under 10–15% even with 10% noise using various interpolation grid sizes, For turbulent flow data, although the total error is approximately 5% for finite difference schemes in the absence of noise, the error can go as high as 150% in the presence of as little as 1% noise. With DPIV processed data the error is 25–40% for TPS and MQ methods optimization of the fitting parameters that minimize the energy functional associated with the analytical surface using RBFs results in robust gradient estimators are obtained that are applicable to steady, unsteady and turbulent flow fields.
Plastid Marker Gene Excision in Greenhouse-Grown Tobacco by Agrobacterium-Delivered Cre Recombinase (2014)

Uniform transformation of the thousands of plastid genome (ptDNA) copies in a cell is driven by selection for plastid markers. When each of the plastid genome copies is uniformly altered, the marker gene is no longer needed. Plastid markers have been efficiently excised by site-specific recombinases expressed from nuclear genes either by transforming tissue culture cells or introducing the genes by pollination. Here we describe a protocol for the excision of plastid marker genes directly in tobacco (Nicotiana tabacum) plants by the Cre recombinase. Agrobacterium encoding the recombinase on its T-DNA is injected at an axillary bud site of a decapitated plant, forcing shoot regeneration at the injection site. The excised plastid marker, the bar (au) gene, confers a visual aurea leaf phenotype; thus marker excision via the flanking recombinase target sites is recognized by the restoration of normal green color of the leaves. The bar (au) marker-free plastids are transmitted through seed to the progeny. PCR and DNA gel blot (Southern) protocols to confirm transgene integration and plastid marker excision are also provided herein.
Design for Variability, Performance, and Yield (2008)

This chapter contains sections titled: Introduction Impact of Variations on Design Some Parametric Fluctuations with New Implications for Design Process Variations in Interconnects Impact of Deep-Submicron Integration in SRAMs Impact of Layout Styles on Manufacturability, Yield, and Scalability Design for Variations Summary References
<title>Numerical holography with digital recording devices</title> (1998)

We describe here anew 3D numerical holographic method which allows intensity and phase contrast imaging. This technique involves a CCD camera as recording device and a numerical method for the reconstruction. We demonstrate here that, in spite of their low resolution, the recording capacities of standard CCD cameras are large enough for the holographic imaging of a few millimeter size objects. 9
Antifungal Management Practices and Evolution of Infection in Organ Transplant Recipients with Cryptococcus Neoformans Infection (2005)

A majority of the organ transplant recipients with cryptococcosis receive maintenance antifungal therapy for 6 months with low risk of relapse. These data can assist in trials to assess the optimal therapeutic approach and duration of therapy for cryptococcosis in transplant recipients.
Phase I/II Trial of an Allogeneic Cellular Immunotherapy in Hormone-Naive Prostate Cancer (2006)

This non-patient-specific prostate cancer immunotherapy has a favorable safety profile and is immunologically active. Continued clinical investigation at higher doses and with longer boosting schedules is warranted.
p16(INK4a) and p53 deficiency cooperate in tumorigenesis. (2002)

The combined impact of mutations in p16(INK4a) and p53 was examined in cellular growth,transformation, and tumor formation. In cultured cells, p16(INK4a) loss enhanced growth at high density and conferred susceptibility to oncogene-induced transformation. In vivo, mice doubly deficient for p16(INK4a) and p53 showed an increased rate of tumor formation with particular susceptibility to aggressive angiosarcomas. Furthermore, p16(INK4a) silencing by promoter methylation was detected in tumors derived from p16(INK4a+/-) and (+/+) mice, independent of p53 status. These data suggest at least one general feature of malignancy, resistance to density-mediated growth arrest depends on p16(INK4a) rather than p53. This cooperation between p16(INK4a) and p53 loss in tumorigenesis is consistent with the view that these genes function in distinct anticancer pathways.
Experimental Implementation of the Optimal Linear-Optical Controlled Phase Gate (2011)

We report on the first experimental realization of optimal linear-optical controlled phase gates for arbitrary phases. The realized scheme is entirely flexible in that the phase shift can be tuned to any given value. All such controlled phase gates are optimal in the sense that they operate at the maximum possible success probabilities that are achievable within the framework of postselected linear-optical implementations with vacuum ancillas. The quantum gate is implemented by using bulk optical elements and polarization encoding of qubit states. We have experimentally explored the remarkable observation that the optimum success probability is not monotone in the phase.
A holistic and optimal approach for data center cooling management (2011)

Efficient and reliable operation of today's data centers, which host IT equipment with ever-increasing power density, relies heavily on the cooling system to meet the thermal management needs of the IT equipment with minimal environmental footprint. The dynamic IT workload, together with the spatial variance of cooling efficiencies, creates both temporal and spatial non-uniformities within the data centers. Most data centers use zonal cooling actuators, such as computer room air conditioners (CRAC), to alleviate the local "hot spots". Without proper localized cooling actuation mechanisms, the cooling capacity is usually over-provisioned that leads to waste of energy. To address this problem, we introduce adaptive vent tiles (AVT) for local cooling adjustment, and develop a holistic multivariable model based on the mass and energy balance principles to capture the effects of both zonal and local cooling actuation on the inlet temperatures of the racks that host the IT equipment. A model predictive controller is then proposed to minimize the total cooling power while meeting the thermal requirements of the racks. The zonal and local cooling actuation is coordinated in such a unified framework for the provisioning, transport and distribution of the cooling resources in the data centers. The proposed holistic cooling approach is validated in a production data center. Experimental results indicate that up to 36% of CRAC units blower power can be saved, compared with the state of the art control solution.
SYN-004 (ribaxamase), an oral beta-lactamase, mitigates antibiotic-mediated dysbiosis in a porcine gut microbiome model (2017)

Damage of the microbiome can lead to overgrowth of pathogenic organisms and antibiotic exposure can promote selection for antibiotic-resistant micro-organisms. Ribaxamase has the potential to become the first therapy designed to protect the gut microbiome from antibiotic-mediated dysbiosis and reduce emergence of antibiotic resistance.
Analysis of Threats Motivating DomainKeys Identified Mail (DKIM) (2006)

This document provides an analysis of some threats against Internet
mail that are intended to be addressed by signature-based mail
authentication, in particular DomainKeys Identified Mail. It discusses
the nature and location of the bad actors, what their capabilities
are, and what they intend to accomplish via their attacks.
Characterization of novel inhibitors of histone deacetylases (2005)

611 Reversible modification of histones and other cellular proteins by acetylation is widely accepted to be one of the key mechanisms regulating gene expression and protein activity. Recent studies suggest that histone deacetylases (HDACs) play important roles in the regulation of cell proliferation and differentiation. HDAC inhibitors have been demonstrated to inhibit cancer cell growth in vitro and in vivo, and several of them are currently being studied as potential anticancer agents in clinical trials. We studied 10 newly synthesized HDAC inhibitors (structurally different analogues of hydroxamic acid (1), mercaptoacetamide (2), and biphenylalanine (7)) using several cancer cell lines (SQ-20B, PC-3, MCF-7, HeLa, and Jurkat). To characterize these inhibitors, we analyzed their effects on cell proliferation, cell cycle, and pertinent protein expression. The values of HDAC inhibitors IC50 were determined for these cancer cells and normal human cells after 24 and 48 hours of treatment. Cytotoxicity assays revealed Jurkat cells most sensitive at nM ranges to all the inhibitors tested, while little toxicity was observed in normal cells. Induction of p21Cip1 expression was observed within 2-12 h of treatment depending on the cell line. FACS analysis demonstrated that cells were predominantly accumulated in either G1 or G2 phase of the cell cycle, albeit concentration-dependent. Currently, using PC-3 and MCF-7 cell lines in which the expression of HDACs was suppressed by RNA interference (RNAi), we are investigating target-specificities of these HDAC inhibitors on HDAC family members. These studies could provide valuable instruments for further elucidation of specific HDAC functions in normal and tumor cells, and potentially result in development of more efficient therapeutics for cancer treatment.
Caspase-1 (interleukin-1β-converting enzyme) is inhibited by the human serpin analogue proteinase inhibitor 9 (1999)

The regulation of caspases, cysteine proteinases that cleave their substrates after aspartic residues, is poorly understood, even though they are involved in tightly regulated cellular processes. The recently discovered serpin analogue proteinase inhibitor 9 (PI9) is unique among human serpin analogues in that it has an acidic residue in the putative specificity-determining position of the reactive-site loop. We measured the ability of PI9 to inhibit the amidolytic activity of several caspases. The hydrolysis of peptide substrates by caspase-1 (interleukin-1β-converting enzyme), caspase-4 and caspase-8 is inhibited by PI9 in a time-dependent manner. The rate of reaction of caspase-1 with PI9, as well as the rate of substrate hydrolysis of the initial caspase-PI9 complex, shows a hyperbolic dependence on the concentration of PI9, indicative of a two-step kinetic mechanism for inhibition with an apparent second-order rate constant of 7×102 M-1˙s-1. The hydrolysis of a tetrapeptide substrate by caspase-3 is not inhibited by PI9. The complexes of caspase-1 and caspase-4 with PI9 can be immunoprecipitated but no complex with caspase-3 can be detected. No complex can be immunoprecipitated if the active site of the caspase is blocked with a covalent inhibitor. These results show that PI9 is an inhibitor of caspase-1 and to a smaller extent caspase-4 and caspase-8, but not of the more distantly related caspase-3. PI9 is the first example of a human serpin analogue that inhibits members of this class of cysteine proteinases.
The Engine Testbed: An Experimental System for Model-Based Monitoring, Prediction and Fault Isolation (1998)

The complexity of the new generation of physical systems combined with the growing demand for their reliability and safety, is now being met by automatic control and monitoring, and the use of functional redundancy techniques that exploit static and dynamic relations between observed variables in a system for fault detection and isolation. Our work in monitoring and diagnosis of complex physical systems is based on functional redundancy and uses model-based and qualitative reasoning methods to achieve robustness, reliability, and efficiency in developing integrated methodologies for monitoring, prediction, and diagnosis of such systems