gebhart/patrepeval huggingface dataset:
Discovery of RG7834: The First-in-Class Selective and Orally Available Small Molecule Hepatitis B Virus Expression Inhibitor with Novel Mechanism of Action (2018)

Chronic hepatitis B virus (HBV) infection is a serious public health burden, and current therapies cannot achieve satisfactory cure rate. There are high unmet medical needs of novel therapeutic agents with differentiated mechanism of action (MOA) from the current standard of care. RG7834, a compound from the dihydroquinolizinone (DHQ) chemical series, is a first-in-class highly selective and orally bioavailable HBV inhibitor which can reduce both viral antigens and viral DNA with a novel mechanism of action. Here we report the discovery of RG7834 from a phenotypic screening and the structure-activity relationship (SAR) of the DHQ chemical series. RG7834 can selectively inhibit HBV but not other DNA or RNA viruses in a virus panel screening. Both in vitro and in vivo profiles of RG7834 are described herein, and the data support further development of this compound as a chronic HBV therapy.
Biopolymer-based dielectric materials for space environments (2012)

The potential of bio-dielectrics for space applications was explored using deoxyribonucleic acid (DNA)-based biopolymers. Un-doped DNA, as well as titanium dioxide (TiO<sub>2</sub>) nanoparticle (rutile form)-doped DNA were processed and evaluated. Characterized parameters were temperature stability, resistivity, dielectric constant, dielectric loss and radiation tolerance. The dielectric constant and dielectric loss of un-doped DNA and TiO<sub>2</sub>-doped DNA were measured for both pre- and post- exposure to approximately100 krad Gamma-ray radiation. There was little change in the dielectric constant and dielectric loss of the un-doped DNA sample with exposure to radiation. However, there was a significant reduction in the dielectric constant of the TiO<sub>2</sub>-doped DNA sample.
A Newly Identified CG301269 Improves Lipid and Glucose Metabolism Without Body Weight Gain Through Activation of Peroxisome Proliferator–Activated Receptor α and γ (2011)

We demonstrate that CG301269 exhibits beneficial effects on glucose and lipid metabolism by simultaneous activation of both PPARα and PPARγ. Our data suggest that CG301269 would be a potential lead compound against obesity and related metabolic disorders.
Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma (1991)

Twenty-two consecutive patients with malignant diffuse pleural mesothelioma were treated with recombinant gamma-interferon by the intrapleural route. Diagnosis was made by thoracoscopic examination and all cases were confirmed by the French Mesothelioma Panel of Pathologist. Patients were staged based on thoracoscopic examination and computed tomography (CT) scan: 12 patients were classified as Stage I and 10 were Stage II. A solution of gamma-interferon (40 X 106 U) was infused twice a week over 2 months. Every patient experienced fever. One patient had a Grade 2 leukopenia and one patient suffered from pleural empyema. Response evaluation was based on the following: (1) CT scan performed 2 weeks after treatment ended, and (2) repeat thoracoscopic examination with histopathologic verification in nine patients who had demonstrated a stabilization or a regression of the disease on CT scan. From the original group, 19 patients could be evaluated. Four complete thoracoscopic histopathologic responses and one partial response were observed in Stage I patients (56%). One partial response was observed in Stage II patients.
Thermococcus kodakarensis encodes three MCM homologs but only one is essential (2011)

The minichromosome maintenance (MCM) complex is thought to function as the replicative helicase in archaea and eukaryotes. In eukaryotes, this complex is an assembly of six different but related polypeptides (MCM2-7) but, in most archaea, one MCM protein assembles to form a homohexameric complex. Atypically, the Thermococcus kodakarensis genome encodes three archaeal MCM homologs, here designated MCM1-3, although MCM1 and MCM2 are unusual in having long and unique N-terminal extensions. The results reported establish that MCM2 and MCM3 assemble into homohexamers and exhibit DNA binding, helicase and ATPase activities in vitro typical of archaeal MCMs. In contrast, MCM1 does not form homohexamers and although MCM1 binds DNA and has ATPase activity, it has only minimal helicase activity in vitro. Removal of the N-terminal extension had no detectable effects on MCM1 but increased the helicase activity of MCM2. A T. kodakarensis strain with the genes TK0096 (MCM1) and TK1361 (MCM2) deleted has been constructed that exhibits no detectable defects in growth or viability, but all attempts to delete TK1620 (MCM3) have been unsuccessful arguing that that MCM3 is essential and is likely the replicative helicase in T. kodakarensis. The origins and possible function(s) of the three MCM proteins are discussed.
Recore:  A Fast and Versatile Method for Scaffold Hopping Based on Small Molecule Crystal Structure Conformations (2007)

Replacing central elements of known active structures is a common procedure to enter new compound classes. Different computational methods have already been developed to help with this task, varying in the description of possible replacements, the query input, and the similarity measure used. In this paper, a novel approach for scaffold replacement and a corresponding software tool, called Recore, is introduced. In contrast to prior methods, our main objective was to combine the following three properties in one tool: to avoid structures with strained conformations, to enable the exploration of large search spaces, and to allow interactive use through short response times. We introduce a new technique employing 3D fragments generated by combinatorial enumeration of cuts. It allows focusing on fragments suitable for scaffold replacement while retaining conformational information of the corresponding crystal structures. Based on this idea, we present an algorithm utilizing a geometric rank searching approach. Given a geometric arrangement of two or three exit vectors and additional pharmacophore features, the algorithm finds fragments fulfilling all these constraints ordered by increasing deviation from the query constraints. For the validation of the approach, three different design scenarios have been used. The results obtained show that our approach is able to propose new valid scaffold topologies.
Termitomycamides A to E, Fatty Acid Amides Isolated from the Mushroom Termitomyces titanicus, Suppress Endoplasmic Reticulum Stress (2010)

Five fatty acid amides, termitomycamides A to E (1 to 5), were isolated from the giant edible mushroom Termitomyces titanicus. The structures of 1-5 were determined by the interpretation of spectral data and/or synthesis. Compounds 2 and 5 showed protective activity against endoplasmic reticulum stress-dependent cell death.
Graphene Oxide-Polycarbonate Track-Etched Nanosieve Platform for Sensitive Detection of Human Immunodeficiency Virus Envelope Glycoprotein (2017)

Solid-state nanopores within graphene-based materials are on the brink of fundamentally changing the sensing of desired bioanalytes through ion trafficking across nanoporous membranes. Here, we report on a two-electrode electrochemical biosensor comprised of a graphene oxide-polycarbonate track-etched nanosieve platform for the rapid and sensitive detection of the Human Immunodeficiency Virus Type 1 (HIV-1) envelope glycoprotein ectodomain (gp140<sub>MS</sub>). We have covalently linked an engineered high-affinity one-domain soluble CD4 fused to a human domain targeting HIV-1 coreceptor binding site and ferrocene (Fc) (2Dm2m) to the nanosieve platform. An exponential decrease in the ionic current resulted from a partial blockade of the nanosieve due to the specific interactions of gp140<sub>MS</sub> with the 2Dm2m protein, which was immobilized on the nanosieve platform by biolinkage as a function of applied voltages of 0.1-2.0 V. There was no change in current when a nonspecific antigen bovine serum albumin was tested under identical conditions. This platform had high sensitivity, and when the receptor-binding phenomenon was tested to identify the minimum concentration of target analyte, the lowest detection limit was as short as 8.3 fM and with sensitivity and response times of 0.87 mA mM<sup>-1</sup> cm<sup>-1</sup> and 12 s, respectively. In addition to this remarkable sensitivity, our nanobiorecognition platform has the advantage of superior stability due to the few layered graphene oxide laminates. It also exhibits exceptional biomolecule binding and higher reusability, sustainability, and ease of fabrication in a soft mechanism. Real samples of HIV positive and negative patients were successfully tested to confirm the virus by the developed platform. To the best of our knowledge, this is the first time prosperous pervious remembrance surface has been employed in a nanobiosensing application. In light of the recent great trend of using graphene-based nanopore surfaces created by sophisticated ion-beam methods in sensing and sequencing, this hybrid-surface nanolayer fabricated by the simple vacuum filtration of a few layered graphene oxide laminates may serve as a good alternative in terms of ease of fabrication without expensive instrumental prerequisites.
Enzymatic formation of a resorcylic acid by creating a structure‐guided single‐point mutation in stilbene synthase (2014)

A novel C17 resorcylic acid was synthesized by a structure-guided Vitis vinifera stilbene synthase (STS) mutant, in which threonine 197 was replaced with glycine (T197G). Altering the architecture of the coumaroyl binding and cyclization pocket of the enzyme led to the attachment of an extra acetyl unit, derived from malonyl-CoA, to p-coumaroyl-CoA. The resulting novel pentaketide can be produced strictly by STS-like enzymes and not by Chalcone synthase-like type III polyketide synthases; due to the unique thioesterase like activity of STS-like enzymes. We utilized a liquid chromatography mass spectrometry-based data analysis approach to directly compare the reaction products of the mutant and wild type STS. The findings suggest an easy to employ platform for precursor-directed biosynthesis and identification of unnatural polyketides by structure-guided mutation of STS-like enzymes.
A Diels-Alder Approach to 4,4′-Ihiobis-(Phihalic Acid) Derivatives (1987)

Abstract Reactions of 3,3′-thiobis(2,5-dihydrothiophene 1,1 dioxide) (2) with several dienophiles afforded Diels Alder adducts 4–7. Compound 7 was aromatized to give 4,4′-thio-bis(dimethyl phthalate) (9), a potential intermediate to sulfur- bridged polyimides.
Capture and Visualization of Hydrogen Sulfide by a Fluorescent Probe (2011)

Reaction-based sensing: A fluorescent probe for the detection of hydrogen sulfide was prepared and evaluated on the basis of H2S-mediated benzodithiolone formation. The probe showed good selectivity and sensitivity for hydrogen sulfide. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Immunoglobulins in Serum and Nasal Secretions Following Infection with Type 1 Parainfluenza Virus and Injection of Inactivated Vaccines (1967)

Summary The antibody response in serum and nasal secretions was studied in volunteers following infection with type 1 parainfluenza virus and injection with type 1 virus inactivated vaccines. Although both methods of immunization stimulated a serum antibody response, virus infection was more effective in stimulating a local antibody response than was vaccination. Antibody in nasal secretions was found to be associated with γA-immunoglobulins. No significant differences were observed in the immunoglobulin distribution of serum antibody following infection and vaccination.
Mechanistic Insights into the Voltammetric Determination of Riboflavin at Poly (Serine) Modified Graphite and Carbon Nanotube Composite Paste Electrode (2021)

Abstract Intense present work is directed on the fabrication and application of Poly (serine) modified graphite carbon nanotube composite paste electrode (PSR/CNTPE) for determining the Riboflavin (RF). The surface qualities of the projected sensor were observed by Field Emission Scanning Electron Microscopy (FE‐SEM) and the conductivity by Electrochemical Impedance Spectroscopy (EIS) method. The electrochemical redox activity of the PSR/CNTPE to RF was investigated through Cyclic Voltammetry (CV) and Differential Pulse Voltammetry (DPV). Outcomes displays that Poly (serine) in CNTPE enhanced the catalytic performance of the electrode towards the redox reaction of RF. The voltammetric response of PSR/CNTPE exhibited linear dependence for extended concentration range of RF from 6 μM to 50 μM with lower detection limit of 3.4×10 −8 M.The PSR/CNTPE revealed to be reproducible, highly stable and successfully validated for the pharmaceutical, beverage and milk samples. The fabricated electrode was conducive and displayed two well‐separated oxidation signals for the solution containing two vitamins RF and Folic Acid (FA). The projected sensor is an adequate candidate for electrochemical sensing of RF.
Show me a good time (2010)

In order to study the effect supporting awareness of a colleague's activity on a collaborator's communication intentions, we developed ActivitySpotter. It is a research tool and awareness display that determines a user's current activity through a semantic analysis of documents s/he accesses and shares this information with collaborators. We ran a user study on 22 participants to investigate how accurately ActivitySpotter represents user activity and whether different representations of activity (presence only, topic keywords, or activity labels) influence awareness differently and lead users to change their contact intention. Our findings suggest that activity content awareness can help users glean more about what their collaborators are doing, especially if they are more socially distant, and can afford screen space to have the display showing. This increase in awareness also positively influences users' intentions to communicate in a socially appropriate manner.
Structural Properties of Nickel Metal-Induced Laterally Crystallized Silicon Films and Their Improvement Using Excimer Laser Annealing (2003)

Structural properties of nickel metal-induced laterally crystallized (Ni-MILC) silicon films are studied in detail mainly using transmission electron microscopy (TEM). Laterally grown crystalline grains can be as large as 17 µm, though the grains consist of small misorientated subgrains and, in addition, some subgrains are divided further into overlapping upper and lower subgrains. The excimer laser annealing (ELA) method definitely improves the Ni-MILC silicon film quality, enlarges the subgrains and removes the overlapping structure. As a result, fairly good polycrystalline silicon (polysilicon) thin film transistors (TFTs) are easily fabricated through a low-temperature process. It is difficult, however, to completely eliminate the subgrains by simply applying the ELA method to Ni-MILC silicon films.
Label-free detection of anticancer drug paclitaxel in living cells by confocal Raman microscopy (2013)

Confocal Raman microscopy, a non-invasive, label-free, and high spatial resolution imaging technique is employed to trace the anticancer drug paclitaxel in living Michigan Cancer Foundation-7 (MCF-7) cells. The Raman images were treated by K-mean cluster analysis to detect the drug in cells. Distribution of paclitaxel in cells is verified by calculating the correlation coefficient between the reference spectrum of the drug and the whole Raman image spectra. A time dependent gradual diffusion of paclitaxel all over the cell is observed suggesting a complementary picture of the pharmaceutical action of this drug based on rapid binding of free tubulin to crystallized paclitaxel.
PET reconstruction from deconvolved FORE data (2003)

Fully 3D PET data is often rebinned into 2D data sets in order to avoid time consuming fully 3D reconstruction. Then, conventional 2D reconstruction techniques are employed to obtain images from the rebinned data. In a common scenario, 2D filtered back projection (FBP) is applied to Fourier rebinned (FORE) data. This approach is suboptimal because FBP is based on an idealized mathematical model of the data. Specifically, FBP cannot account fully for variations in the system and the statistical structure of the data and noise. FORE data contains some blur in all 3 dimensions in comparison to conventional 2D PET data. In this work, we propose methods for approximating this blur due to FORE through its point spread function (PSF). We also explore simple methods for deconvolving the rebinned data with this PSF to restore it to a more ideal state prior to FBP. Our results show that deconvolution of the approximate transaxial PSF yields little improvement, while deconvolution of the axial PSF leads to significant gains in contrast levels.
Noise properties of pulse-width modulated power converters: open-loop effects (2000)

The pulse-width modulation (PWM) process in DC-DC and DC-AC power converters introduces characteristic nonlinear behavior. When PWM is performed in the presence of noise, specific effects are seen on the duty ratio and consequently on the output of the converter. Small-signal concepts do not model nonlinear noise issues. Here, the probability density function of the duty ratio and its implications are obtained analytically, given external noise that follows a Gaussian distribution. The results are verified with Monte Carlo simulation and confirmed by experiments. For a DC-DC converter, noise is shown to introduce a DC shift at the output. The degree of nonlinear effect on a converter depends on the noise derivative level. For an inverter, noise can produce significant DC offset at the output. Closed-form expressions from the analysis can be used to evaluate noise sensitivity of a design.
Analysis of Q-factors of structural imperfections in triangular cross-section nanobeam photonic crystal cavities (2015)

We present comprehensive and quantitative analysis of the effect of structural imperfections on quality (Q)-factors in triangular cross-section nanobeam photonic crystal cavities. We investigated statistically the optical losses due to the various imperfections in the air holes&#x2019; positions, radii, alignments, and surface roughness, among other factors. It is revealed that the Q-factor decreases significantly from an ideally designed value due to such imperfections, with the main influence being the asymmetric alignment of the air hole line relative to the center of the nanobeam in the currently used fabrication process. Our analysis provides important information for achieving higher Q-factors in the cavities.
Synthesis and Evaluation of 14-Nor-A-secotaxoids (2002)

A series of 14-nor-A-secotaxoids has been prepared from 10-deacetyl-14β-hydroxybaccatin III (3a) and some unexpected and new reactivity of the taxane system has been revealed. The observation that the final compounds were considerably less active than taxol and their 1,10-oxygen-bridged analogues shows that the 1,10-oxygen tether can partially compensate for the opening of ring A, and suggests that 14-nor-A-secotaxoids warrant further investigation as simplified taxol mimics.
From caging to grasping (2012)

This paper digs into the relationship between cages and grasps of a rigid body. In particular, it considers the use of cages as waypoints to grasp an object. We introduce the concept of pregrasping cages, caging configurations from which an object can be grasped without first breaking the cage. For two-fingered manipulators, all cages are pregrasping cages and, consequently, useful waypoints to grasp an object. A contribution of this paper is to show that the same does not hold for more than two fingers. A second contribution is to show how to overcome that limitation. We explore the natural generalization of the well-understood squeezing/stretching characterization of two-finger cages to arbitrary workspace dimension, arbitrary object shapes without holes, and arbitrary number of point fingers, and exploit it to give sufficient conditions for a cage to be a pregrasping cage. As a product of that generalization, we introduce grasping functions: scalar functions defined on the finger formation that control the process of going from a cage to a grasp. We finish the paper by establishing an analogy between the role of grasping functions in grasping and that of Lyapunov functions in stability theory.
GUIDELINES FOR PLACEMENT OF LONGITUDINAL BARRIERS ON SLOPES. VOLUME II: FULL-SCALE CRASH TESTS. FINAL REPORT (1984)

This research was undertaken to investigate longitudinal barrier impact performance when placed on nonlevel terrain. Tasks performed in this study included: a determination of typical conditions for which longitudinal barriers are placed on nonlevel terrain; an evaluation of the impact behavior of widely used barrier systems when placed on nonlevel terrain; and the development of guidelines for selection and placement of barriers on nonlevel terrain. This volume, 2nd of 3, describes crash tests conducted to evaluate barrier impact performance when placed on nonlevel terrain. Seven full-scale crash tests were conducted to evaluate the impact behavior of three widely used roadside barriers when placed on a 6:1 side slope. Four tests involved a standard W-beam rail on metal posts (G4(1S) system). Two tests involved a three-cable barrier mounted on metal posts (G1 system). One test involved the thrie beam rail on metal posts (G9 system). Barrier offsets of 6 ft (1.8 m) and 12 ft (3.7 m) from the edge of the shoulder were evaluated. Vehicle override of the barrier occurred in the 25 degree, 60 mph (96.5 km/h) tests of the W-beam and thrie beam systems. The vehicle was contained and smoothly redirected for the same conditions when impacting the cable barrier.
Effects of microstructure on the speed and attenuation of elastic waves (1982)

A unified theory pertaining to the sensitivity of the propagation of an elastic wave to changes in the microstructural details of a material is discussed. In contrast to nearly all previous treatments a first principles approach, using developments from other multiple scattering problems and adapting them to the elastic wave case, is followed. We then present several simple, standard approximations. In the process the validity of the commonly made assumption that ..cap alpha.. = n anti sigma is clarified, and the effective speed, illustrating its complementary character to the attenuation, is computed. The principal objective is to present the formal analysis necessary to treat systematically the dependency of the wave propagation on microstructural statistics.