gebhart/patrepeval huggingface dataset:
Daclizumab High-Yield Process (DAC HYP) has no Effect on Activity of the Cytochrome P450 (CYP) Enzymes: Results of a Drug Cocktail Interaction Study in Subjects with Multiple Sclerosis (MS) (P1.148) (2015)

OBJECTIVE: To determine whether dosage adjustments are needed for drugs that are substrates of CYPs 1A2, 2C9, 2C19, 2D6, or 3A when given concomitantly with DAC HYP. BACKGROUND: DAC HYP, a humanized IgG1 monoclonal antibody specific for the alpha subunit (CD25) of the high-affinity IL-2 receptor, is being developed for treatment of MS. DAC HYP treatment results in a detectable increase in serum IL-2 levels, and changes in cytokine levels may influence expression of the CYPs. DESIGN/METHODS: Twenty subjects with MS received an oral cocktail of probe substrates of CYP3A (midazolam 5mg), CYP2C9 (warfarin 10mg/vitamin K 10mg), CYP2C19 (omeprazole 40mg), CYP1A2 (caffeine 200mg) and CYP2D6 (dextromethorphan 30mg) at 2 sequential occasions: 7 days before and 7 days after administration of DAC HYP 150mg SC every 4 weeks for 3 doses. Serial PK blood samples up to 96 hours and 12-hour urine samples were collected in both occasions. The AUC for midazolam, caffeine, S-warfarin, and omeprazole and the urine dextromethorphan to dextrorphan ratio were calculated. Statistical analyses were conducted on log-transformed parameters using a linear mixed-effects model. RESULTS: The 90[percnt] confidence intervals (CIs) about the geometric mean ratio (probe substrate with DAC HYP/probe substrate alone) for midazolam AUCinf (0.89-1.15), omeprazole AUCinf (0.88-1.13), S-warfarin AUCinf (0.95- 1.06), and caffeine AUC0-12 (0.93-1.15) were within the no-effect boundary of 0.80-1.25. The geometric mean ratio for urine dextromethorphan to dextrorphan ratio was 1.01, with the 90[percnt] CI (0.76-1.34) extending slightly outside the no-effect boundary, likely due to high variability with urine collections and CYP2D6 activity. CONCLUSIONS: DAC HYP treatment in MS patients had no effect on CYPs 1A2, 2C9, 2C19, 2D6, and 3A activities. Hence, no dosage adjustments are needed for concomitant drugs that are substrates of these CYPs. Study Supported by: Biogen Idec and AbbVie Biotherapeutics.
Fluid-Loss Control Improves Performance of Viscoelastic Surfactant Fluids (2007)

Abstract Viscoelastic surfactant (VES) fluids have been widely used as gravel-packing, frac-packing and fracturing fluids for more than a decade because the fluids exhibit excellent rheological properties and maintain low formation damage characteristics compared with crosslinked-polymer fluids. Due to its non-wall-building property, VES fluid has much higher fluid leak-off into the reservoir matrix than wall-building polymer fluid. For frac-packing this has limited VES use to reservoirs with permeability of less than 1000 md and, in most cases, less than 250 md. Excessive fluid leak-off also significantly increases the cost of treatment. This paper will introduce new technology for controlling the fluid loss of VES fluids to about 300°F. New fluid loss control agents have been developed that, through chemisorption and surface charge attraction, associate with VES micelles to produce a pseudo-filtercake of viscous VES fluid that significantly reduces the rate of fluid loss. Use of this technology will reduce the VES fluid volume required for a given treatment by up to two-thirds and extends the permeability range of VES fluids to about 2000 md. The fluid loss control agents are slowly water-soluble particles that are used at relatively low concentrations. The particles will be dissolved and/or flowed back with the producing fluid. The rate of the pseudo-filtercake clean-up is enhanced by use of internal VES breakers. The results of rheology, leak-off, and core flow tests will be presented for the VES fluid systems at temperatures 150°F and 250°F.
Heat capacity and torsional oscillator studies of molecular hydrogen in porous Vycor glass (1990)

We have measured the heat capacity of para-hydrogen in a series of samples of porous Vycor glass at temperatures in the range 0.6 to 12 K. For hydrogen in the samples with large pores a freezing transition is observed; in the small-pore samples there is no feature that can be associated with a liquid-solid transition. At low temperatures the heat capacity of hydrogen in Vycor is found to decrease as the amount of hydrogen in the pores increases. We discuss possible explanations for this behavior. For hydrogen in small-pore Vycor we have made a search for superfluidity down to 0.08 K. No sharp transition is observed down to this temperature.
Heating and Sterilization Technology for Long‐duration Space Missions (2009)

Long-duration space missions require a high-quality, shelf-stable food supply but must also contend with packaging waste after use. We have developed a package, adapted from a military pouch, that enables heating of foods to serving temperature. After the food is consumed, the package may be reused for containment and sterilization of waste, and, potentially, for packaging and sterilizing foods grown on a Mars base. Packages are equipped with electrodes to permit ohmic heating of internal constituents. Heat transfer within the package was modeled using the energy transport equation, coupled with the Laplace equation for electric field strength distribution. The model was verified by temperature measurements during a sample experimental run, and it was used to optimize the package design. Waste sterilization within the package was also studied and confirmed. Mass transfer (electrode component migration) was studied by inductively coupled plasma mass spectrometry; the findings have shown concentrations within products to be well below current daily dietary exposure levels. Microbiological studies for sterilization indicated the need for package redesign to ensure parallel electrode configuration, as well as the use of supplemental external heaters along the nonelectrode walls of the package. Temperature profiles during heating of these packages have been determined.
A Model for Network-Based Identification and Pharmacological Targeting of Aberrant, Replication-Permissive Transcriptional Programs Induced by Viral Infection (2022)

Precise characterization and targeting of host cell transcriptional machinery hijacked by viral infection remains challenging. Here, we show that SARS-CoV-2 hijacks the host cell transcriptional machinery to induce a phenotypic state amenable to its replication. Specifically, analysis of Master Regulator (MR) proteins representing mechanistic determinants of the gene expression signature induced by SARS-CoV-2 in infected cells revealed coordinated inactivation of MRs enriched in physical interactions with SARS-CoV-2 proteins, suggesting their mechanistic role in maintaining a host cell state refractory to virus replication. To test their functional relevance, we measured SARS-CoV-2 replication in epithelial cells treated with drugs predicted to activate the entire repertoire of repressed MRs, based on their experimentally elucidated, context-specific mechanism of action. Overall, >80% of drugs predicted to be effective by this methodology induced significant reduction of SARS-CoV-2 replication, without affecting cell viability. This model for host-directed pharmacological therapy is fully generalizable and can be deployed to identify drugs targeting host cell-based MR signatures induced by virtually any pathogen.
Regioselective Nucleophilic Additions to Cross-Conjugated Dienone System Bearing β-Fluorine:  A Versatile Approach to Highly Substituted 2-Cyclopentenones (2001)

[reaction: see text] 3-Fluoro-5-methylene-2-cyclopentenone is treated with appropriate nucleophiles and Lewis acids to undergo regioselective 1,2-addition, exocyclic 1,4-addition, and endocyclic 1,4-addition, leading to 3-substituted 4-methylene-2-cyclopentenones, 5-substituted 3-fluoro-2-cyclopentenones, and 3-substituted 5-methylene-2-cyclopentenones in good yields, respectively.
Predictive thermal model for indirect temperature measurement inside atomic cell of nuclear magnetic resonance gyroscope (2009)

This paper describes a methodology for predicting temperatures inside a micro-device at critical locations where thermal sensors cannot be placed. The device under study is a nuclear magnetic resonance gyroscope, an instrument that is highly sensitive to temperature variations. A physical thermal model of the device is developed and validated using experimental measurements from a prototype. A compact thermal model which approximates the behavior of the physical system is obtained through a sequential selection algorithm (with RMS error of approximately 0.15degC). The compact thermal model can be solved rapidly and is therefore suitable for real-time feedback control of the temperature inside the atomic cell.
Chronic High Dose Intraperitoneal Bisphenol A (BPA) Induces Substantial Histological and Gene Expression Alterations in Rat Penile Tissue Without Impairing Erectile Function (2013)

While rats treated chronically with a high IP dose of BPA developed hypogonadism and a corporal histo- and molecular-pathology usually associated with ED, no changes were detected in erectile function as measured by EFS and cavernosometry. Further studies using alternate routes of BPA administration with various doses and length of exposure are needed to expand these findings.
Fine structure of neutral and charged excitons in self-assembled In(Ga)As/(Al)GaAs quantum dots (2002)

The fine structure of excitons is studied by magnetophotoluminescence spectroscopy of single self-assembled In(Ga)As/(Al)GaAs quantum dots. Both strength and orientation of the magnetic field are varied. In a combination with a detailed theoretical analysis, these studies allow us to develop a comprehensive picture of the exciton fine structure. Symmetry of the dot structures as well as its breaking cause characteristic features in the optical spectra, which are determined by the electron-hole exchange and the Zeeman interaction of the carriers. The symmetry breaking is either inherent to the dot due to geometry asymmetries, or it can be obtained by applying a magnetic field with an orientation different from the dot symmetry axis. From data on spin splitting and on polarization of the emission we can identify neutral as well as charged exciton complexes. For dots with weakly broken symmetry, the angular momentum of the neutral exciton is no longer a good quantum number and the exchange interaction lifts degeneracies within the fine-structure manifold. The symmetry can be restored by a magnetic field due to the comparatively strong Zeeman interactions of electron and hole. For dots with a strongly broken symmetry, bright and dark excitons undergo a strong hybridization, as evidenced by pronounced anticrossings when states within the manifold are brought into resonance. The fine structure can no longer be described within the frame developed for structures of higher dimensionality. In particular, the hybridization cannot be broken magnetically. For charged excitons, the exchange interaction vanishes, demonstrating that the exchange splitting of a neutral exciton can be switched off by injecting an additional carrier.
The impact of technology scaling on lifetime reliability (2004)

The relentless scaling of CMOS technology has provided a steady increase in processor performance for the past three decades. However, increased power densities (hence temperatures) and other scaling effects have an adverse impact on long-term processor lifetime reliability. This paper represents a first attempt at quantifying the impact of scaling on lifetime reliability due to intrinsic hard errors, taking workload characteristics into consideration. For our quantitative evaluation, we use RAMP (Srinivasan et al., 2004), a previously proposed industrial-strength model that provides reliability estimates for a workload, but for a given technology. We extend RAMP by adding scaling specific parameters to enable workload-dependent lifetime reliability evaluation at different technologies. We show that (1) scaling has a significant impact on processor hard failure rates - on average, with SPEC benchmarks, we find the failure rate of a scaled 65nm processor to be 316% higher than a similarly pipelined 180nm processor; (2) time-dependent dielectric breakdown and electromigration have the largest increases; and (3) with scaling, the difference in reliability from running at worst-case vs. typical workload operating conditions increases significantly, as does the difference from running different workloads. Our results imply that leveraging a single microarchitecture design for multiple remaps across a few technology generations will become increasingly difficult, and motivate a need for workload specific, microarchitectural lifetime reliability awareness at an early design stage.
Preliminary Design of DSMs for ITER Upper Ports #02 and #08 Integration (2020)

Since 2014, Budker Institute of Nuclear Physics (BINP) SB RÀS has been working on the design of ITER upper port-plugs (UPPs) #02 and #08. The design of upper diagnostic shielding modules (DSMs) for UP #02 and UP #08 has been performed using CATIA v5.0. DSMs represent a welded structure made of stainless steel SS316L(N)-IG. Cooling water channels to be performed use the unique gundrilling technology. The main conception of structural design of DSMs is in good agreement with ITER recommendations. The engineering calculations of DSM structure were done to demonstrate the sufficient strength of the considered design under thermal (normal operation and baking), electromagnetic (vertical displacement event (VDE) II), and seismic (SL-2) loads. To prove the satisfaction of upper DSMs design to ITER requirements, the load combination dead weight (DW) + normal operation (NO) + SL-1 + VDE II numerical simulations were performed. Further studies of the modular design will be optimized for the use of standardized boron carbide shielding trays.
A direct GHz-clocked phase and intensity modulated transmitter applied to quantum key distribution (2018)

Quantum key distribution (QKD), a technology that enables perfectly secure communication, has evolved to the stage where many different protocols are being used in real-world implementations. Each protocol has its own advantages, meaning that users can choose the one best-suited to their application, however each often requires different hardware. This complicates multi-user networks, in which users may need multiple transmitters to communicate with one another. Here, we demonstrate a direct-modulation based transmitter that can be used to implement most weak coherent pulse-based QKD protocols with simple changes to the driving signals. This also has the potential to extend to classical communications, providing a low chirp transmitter with simple driving requirements that combines phase shift keying with amplitude shift keying. We perform QKD with concurrent time-bin and phase modulation, alongside phase randomisation. The acquired data is used to evaluate secure key rates for time-bin encoded BB84 with decoy states and a finite key-size analysis, giving megabit per second secure key rates, 1.60 times higher than if purely phase-encoded BB84 was used.
The Synthesis of XNOR Recurrent Neural Networks with Stochastic Logic (2019)

The emergence of XNOR networks seek to reduce the model size and computational cost of neural networks for their deployment on specialized hardware requiring real-time processes with limited hardware resources. In XNOR networks, both weights and activations are binary, bringing great benefits to specialized hardware by replacing expensive multiplications with simple XNOR operations. Although XNOR convolutional and fully-connected neural networks have been successfully developed during the past few years, there is no XNOR network implementing commonly-used variants of recurrent neural networks such as long short-term memories (LSTMs). The main computational core of LSTMs involves vector-matrix multiplications followed by a set of non-linear functions and element-wise multiplications to obtain the gate activations and state vectors, respectively. Several previous attempts on quantization of LSTMs only focused on quantization of the vector-matrix multiplications in LSTMs while retaining the element-wise multiplications in full precision. In this paper, we propose a method that converts all the multiplications in LSTMs to XNOR operations using stochastic computing. To this end, we introduce a weighted finite-state machine and its synthesis method to approximate the non-linear functions used in LSTMs on stochastic bit streams. Experimental results show that the proposed XNOR LSTMs reduce the computational complexity of their quantized counterparts by a factor of 86x without any sacrifice on latency while achieving a better accuracy across various temporal tasks.
Ceramic dielectric resonators for high-field magnetic resonance imaging (2007)

In this study, high permittivity ceramic resonators were used to produce the Bl field in a 14.1 Tesla NMR device with a proton frequency of 600 MHz. Magnetic field distributions in the setup are analyzed using the finite-difference time-domain simulations. The NMRI images obtained by using the new setup are demonstrated.
Visualizing Dermal Permeation of Sodium Channel Modulators by Mass Spectrometric Imaging (2014)

Determining permeability of a given compound through human skin is a principal challenge owing to the highly complex nature of dermal tissue. We describe the application of an ambient mass spectrometry imaging method for visualizing skin penetration of sodium channel modulators, including novel synthetic analogs of natural neurotoxic alkaloids, topically applied ex vivo to human skin. Our simple and label-free approach enables successful mapping of the transverse and lateral diffusion of small molecules having different physicochemical properties without the need for extensive sample preparation.
Recent Progress Toward the Synthesis of Trifluoromethyl‐ and Difluoromethyl‐Substituted Cyclopropanes (2016)

This Minireview describes recent advances toward the synthesis of trifluoromethyl- and difluoromethyl-substituted cyclopropanes. Synthetic methodologies using [2+1] cycloaddition, ring-contraction, and ring-closure cyclopropanations since 2010 are reported.
Nonlinear 2D-feedback optical systems: new approaches for adaptive wavefront correction (1994)

The appearance of nonlinear and optoelectronic phase correctors with very high resolution requires changes to traditional adaptive system design. New approaches based on the 2D feedback system concept are discussed.
Supplemental Figure 1 from Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma (2023)

&lt;p&gt;Order of study arm enrollment is displayed graphically&lt;/p&gt;
Inhibition of Ty1 Transposition by Mating Pheromones in Saccharomyces cerevisiae (1991)

The Ty1 elements in the yeast Saccharomyces cerevisiae are a family of retrotransposons which transpose via a process similar to that of retroviral replication. We report here that the Ty1 transposition process can be blocked posttranscriptionally by treatment of cells with mating pheromones. When haploid yeast cells are treated with appropriate mating pheromones, the transposition frequency of a marked Ty1 element driven by the GAL1 promoter is greatly diminished. Ty1 viruslike particles (VLPs), the putative intermediates for transposition, can be isolated from mating pheromone-treated cells. These VLPs accumulate to normal levels but are aberrant in that they produce very few reverse transcripts of Ty1 RNA both in vivo and in vitro and contain subnormal amounts of p90-TYB and related proteins. In addition, a TYA phosphoprotein product accumulates in treated cells, and some species of TYB proteins have decreased stability. We also show that decreased transposition in mating pheromone-treated cells is not a consequence of simply blocking cell division, since Ty1 transposes at a nearly normal rate in yeast cells arrested in G2 by the drug nocodazole.
Supplementary Figure 1 from Expression of G Protein-Coupled Receptor 19 in Human Lung Cancer Cells Is Triggered by Entry into S-Phase and Supports G<sub>2</sub>–M Cell-Cycle Progression (2023)

&lt;p&gt;PDF file - 337K, Reduced cellular proliferation upon Gpr19 siRNA treatment. Thumbnail visualization of confluence measurement for NCI-H1703 cells and phase contrast microscopy pictures of NCI-H1703 and DMS 53 cells subject to siRNA transfection&lt;/p&gt;
Human miRNA miR-675 inhibits DUX4 expression and may be exploited as a potential treatment for Facioscapulohumeral muscular dystrophy (2021)

Facioscapulohumeral muscular dystrophy (FSHD) is a potentially devastating myopathy caused by de-repression of the DUX4 gene in skeletal muscles. Effective therapies will likely involve DUX4 inhibition. RNA interference (RNAi) is one powerful approach to inhibit DUX4, and we previously described a RNAi gene therapy to achieve DUX4 silencing in FSHD cells and mice using engineered microRNAs. Here we report a strategy to direct RNAi against DUX4 using the natural microRNA miR-675, which is derived from the lncRNA H19. Human miR-675 inhibits DUX4 expression and associated outcomes in FSHD cell models. In addition, miR-675 delivery using gene therapy protects muscles from DUX4-associated death in mice. Finally, we show that three known miR-675-upregulating small molecules inhibit DUX4 and DUX4-activated FSHD biomarkers in FSHD patient-derived myotubes. To our knowledge, this is the first study demonstrating the use of small molecules to suppress a dominant disease gene using an RNAi mechanism.
Salt-Sensitive Hypertension After Exposure to Angiotensin Is Associated With Inability to Upregulate Renal Epoxygenases (2003)

The current study was designed to determine whether angiotensin II infusion could lead to persistent salt-sensitive hypertension and to examine involvement of renal microvascular epoxygenases in this process. Six groups were studied: rats maintained on a normal salt diet for 4 weeks (NS); rats maintained on a high salt diet for 4 weeks (HS); and all other animals receiving angiotensin II (ANG) infusion and being fed a normal or high salt diet for 2 weeks; then the angiotensin II infusion was stopped and diets were either maintained or switched (ANG/NS-NS, ANG/NS-HS, ANG/HS-HS, ANG/HS-NS). Angiotensin II infusion resulted in a rise in blood pressure and an increase in urinary albumin excretion over the 2-week period. After angiotensin II withdrawal, blood pressure returned to normal in animals receiving a normal salt diet from weeks 2 to 4 (ANG/NS-NS and ANG/HS-NS groups). In contrast, blood pressure remained elevated in the group maintained on a high salt diet throughout the entire 4-week period (ANG/HS-HS group). Renal microvascular CYP2C11 and CYP2C23 protein levels were decreased by 50% to 60% in the ANG/HS-HS group compared with the NS group. Likewise, renal microvascular CYP2J protein was significantly decreased in the ANG/HS-HS group versus the NS group. Renal microvascular CYP2C11 and CYP2C23 mRNA levels were reduced in the ANG/HS-HS group compared with both the NS and HS groups. These results support the hypothesis that angiotensin II infusion induces persistent salt-sensitive hypertension after withdrawal of angiotensin II that may be due to downregulation of CYP2C and CYP2J epoxygenases in renal microvessels.
Experiments on tympanic membrane reconstruction influencing the middle ear transfer function after middle ear reconstruction with the 'Vibrant-Soundbridge'-simulation of reduced middle ear ventilation (2018)

The middle ear transfer function should be measured in a temporal bone study after vibroplasty on the stapes head and under simulation of atmospheric pressure fluctuations (pressurization via external ear canal). Subsequently, materials used for tympanic membrane reconstruction (sheep ear cartilage varying in thickness, perichondrium, 3-D printed tympanic membrane models) were analyzed on their material properties.