gebhart/patrepeval huggingface dataset:
Different disulfide bridge connectivity drives alternative folds in highly homologous<i>Brassicaceae</i>trypsin inhibitors (2015)

Low-molecular-mass trypsin inhibitors from Arabidopsis thaliana, Brassica napus var. oleifera, and Sinapis alba L. (ATTI, RTI, and MTI, respectively) display more than 69% amino acid sequence identity. Among others, the amino acid sequence Cys-Ala-Pro-Arg-Ile building up the inhibitor reactive site, and the eight Cys residues forming four disulfide bridges are conserved. However, the disulfide bridge connectivity of RTI and MTI (C1-C3, C2-C4, C5-C6, and C7-C8) is different from that of ATTI Cys (C1-C8, C2-C5, C3-C6, and C4-C7). Despite the different disulfide bridge connectivity, the reactive site loop of ATTI, RTI, and MTI is solvent exposed permitting trypsin recognition. Structural considerations here reported suggest that proteins showing high amino acid sequence identity and common functional properties could display different three-dimensional structures. This may reflect high inhibitor plasticity in relation to plant–pathogen interactions, plant tissue development as well as the different redox potential of cell compartments. © 2015 IUBMB Life, 67(12):966–970, 2015
A feature of the behavior of He<sup>+</sup> in the nightside high‐latitude ionosphere during equinox (1981)

At high latitudes during solstice the ray path through the atmosphere to about 400‐km altitude near midnight is either so small that production of O + , He + , and H + continues at all times or so large that production of these species is negligible. The latter condition will produce an ionospheric ‘hole’ if the plasma stagnates or circulates in the nightside winter pole. Near equinox, however, the shadow height near midnight may ensure that photoproduction of O + is negligible, while the ray path at higher altitudes may be short enough that significant production of He + and H + takes place. Observations made by Atmosphere Explorer D and calculations suggest that an ionospheric hole should also be observable at equinox but will not be so pronounced as that observed during winter. However, the dominance of He + in the hole between 500 and 1000 km is unique to equinoctial conditions. We note that stagnation of the plasma rather than slow passage across the polar cap is required, since at equinox the field tubes must reach the nightside before the shadow height ensures that the photoproduction of O + ceases. Stagnation times between 3 and 6 hours are required for He + to be dominant at altitudes around 600 km.
<i>In vitro and in vivo</i>activity of the chloroaryl-substituted imidazole viniconazole against<i>Trypanosoma cruzi</i> (2013)

Chagas disease (CD) is caused by the intracellular protozoan parasite Trypanosoma cruzi and affects more than 10 million people in poor areas of Latin America. There is an urgent need for alternative drugs with better safety, broader efficacy, lower costs and shorter time of administration. Thus the biological activity of viniconazole, a chloroaryl-substituted imidazole was investigated using in vitro and in vivo screening models of T. cruzi infection. Ultrastructural findings demonstrated that the most frequent cellular damage was associated with plasma membrane (blebs and shedding events), Golgi (swelling aspects) and the appearance of large numbers of vacuoles suggesting an autophagic process. Our data demonstrated that although this compound is effective against bloodstream and intracellular forms (16 and 24 μ m, respectively) in vitro, it does not present in vivo efficacy. Due to the urgent need for novel agents against T. cruzi, the screening of natural and synthetic products must be further supported with the aim of finding more selective and affordable drugs for CD.
Magnetic field angle dependence of out-of-plane precession in spin torque oscillators having an in-plane magnetized free layer and a perpendicularly magnetized reference layer (2016)

Abstract Out-of-plane (OP) precession in spin torque oscillators having an in-plane (IP) magnetized free layer and a perpendicularly magnetized reference layer was studied. The bias voltage ( V B ) and magnetic field angle (θ) dependence of the OP precession were investigated. The absolute values of the critical magnetic fields ( and ) between which OP precession is excited increased as V B increased and as θ changed from the IP to the OP direction. The IP components of converged to a constant value regardless of θ. This result indicates that excitation of OP precession is suppressed entirely by the IP component of the magnetic field, and the contribution of the OP component can be ignored. The experimentally observed precession behavior was successfully modeled by macrospin simulations.
Establishment of a stable SARS-CoV-2 replicon system for application in high-throughput screening (2021)

Abstract Experiments with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited by the need for biosafety level 3 (BSL3) conditions. A SARS-CoV-2 replicon system rather than an in vitro infection system is suitable for antiviral screening since it can be handled under BSL2 conditions and does not produce infectious particles. However, the reported replicon systems are cumbersome because of the need for transient transfection in each assay. In this study, we constructed a bacterial artificial chromosome vector (the replicon-BAC vector) including the SARS-CoV-2 replicon and a fusion gene encoding Renilla luciferase and neomycin phosphotransferase II, examined the antiviral effects of several known compounds, and then established a cell line stably harboring the replicon-BAC vector. Several cell lines transiently transfected with the replicon-BAC vector produced subgenomic replicon RNAs (sgRNAs) and viral proteins, and exhibited luciferase activity. In the transient replicon system, treatment with remdesivir or interferon-β but not with camostat or favipiravir suppressed the production of viral agents and luciferase, indicating that luciferase activity corresponds to viral replication. VeroE6/Rep3, a stable replicon cell line based on VeroE6 cells, was successfully established and continuously produced viral proteins, sgRNAs and luciferase, and their production was suppressed by treatment with remdesivir or interferon-β. Molnupiravir, a novel coronavirus RdRp inhibitor, inhibited viral replication more potently in VeroE6/Rep3 cells than in VeroE6-based transient replicon cells. In summary, our stable replicon system will be a powerful tool for the identification of SARS-CoV-2 antivirals through high-throughput screening.
ChemInform Abstract: Multicomponent Solution Phase Synthesis of Dehydroamino Acid Derivatives Based on the Passerini Reaction. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Joint optimal placement of PMU and conventional measurements in power systems (2010)

We consider the problem of joint optimal placement of Phasor Measurement Units (PMU) and conventional measurements to ensure full observability in power systems. The problem is first formulated as a nonlinear integer programming problem and then recast in to an equivalent integer linear programming (ILP) problem by introducing auxiliary variables and constraints. The ensuing ILP problem is solved for the IEEE 14, 57 and 118 bus systems considering zero-injection buses. The results provide a far more economical solution to system observability compared to those obtained solely with PMU placement.
Robustness and Reliability of Synergy-Based Myocontrol of a Multiple Degree of Freedom Robotic Arm (2015)

In this study, we test the feasibility of the synergy- based approach for application in the realistic and clinically oriented framework of multi-degree of freedom (DOF) robotic control. We developed and tested online ten able-bodied subjects in a semi-supervised method to achieve simultaneous, continuous control of two DOFs of a robotic arm, using muscle synergies extracted from upper limb muscles while performing flexion-extension movements of the elbow and shoulder joints in the horizontal plane. To validate the efficacy of the synergy-based approach in extracting reliable control signals, compared to the simple muscle-pair method typically used in commercial applications, we evaluated the repeatability of the algorithm over days, the effect of the arm dynamics on the control performance, and the robustness of the control scheme to the presence of co-contraction between pairs of antagonist muscles. Results showed that, without the need for a daily calibration, all subjects were able to intuitively and easily control the synergy-based myoelectric interface in different scenarios, using both dynamic and isometric muscle contractions. The proposed control scheme was shown to be robust to co-contraction between antagonist muscles, providing better performance compared to the traditional muscle-pair approach. The current study is a first step toward user-friendly application of synergy-based myocontrol of assistive robotic devices.
A phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (CKS). (2020)

11518 Background: CKS is a mesenchymal neoplasm associated with HHV8 infection. Though recombinant INFa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation in CKS therapy. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated progressive CKS. Methods: CKS pts with progressive disease after &gt; 1 line of systemic therapy and measurable disease received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint was overall response rate (ORR) evaluated clinically, radiologically (RECIST) and metabolically (FDG-PET). Secondary endpoints include 6-months progression free survival rate (PFS) and safety. Exploratory endpoints included PD-L1/MMR by IHC, DNAseq (596 genes)/RNAseq (whole transcriptome) of tumor and matched blood specimens to explore CKS genomic traits and IO correlates: TMB and MSI status, MMR and PD-L1 protein expression, and immune gene transcript expression (PD-1, PD-L1, CTLA-4, and others) (Tempus Labs, Chicago, IL, USA). Results: Fifteen patients were enrolled and evaluable (Apr18-Jan20). Median age 72.5 (61-81), all male. At a median FU of 15.7 mo ORR as per RECIST was 66% (9 pts PR, 1 pt CR, 2 pts SD, 3 pts NE). Clinical ORR was 87% and metabolic ORR was 60%. Median PFS was not reached, 6mo PFS rate was 85% and 1y PFS rate was 75%. The safety profile was as expected with all pts experiencing G1 toxicity, 3 pts with G2 toxicity (1 hepatic, 2 asymptomatic lipase increase) and 2 pts with G3 toxicity (1 colitis, 1 asymptomatic lipase increase). One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in 3 pts. Correlative results are available for 8 pts showing a trend for copy number loss in genes with tumor-suppressive activity (FOXA1, ELF3), no PDL1 expression, low TMB, microsatellite stability, but marked overexpression of CTLA-4, PD-1, PDL-1, CD40, OX40 and LAG3 RNA immune transcripts. Conclusions: The interim analysis of this prospective phase II study of nivolumab and low-dose ipilimumab demonstrates promising activity in progressive CKS, with 66% ORR and a 6mo PFS rate of 85%. Toxicity profile is as expected in this class of drugs. Correlative studies are preliminary, but warrant further investigation into genomic traits and immune gene expression profiles. Clinical trial information: NCT03219671. Clinical trial information: NCT03219671 .
92418 Molecular imaging of the tumor microenvironment to predict response to combination treatment with immunotherapy in triple negative breast cancer (2021)

ABSTRACT IMPACT: Insights from this project will provide clinical guidance in treatment of immunotherapy in triple negative breast cancer and identify early imaging biomarkers of treatment response. OBJECTIVES/GOALS: Significant research that addresses monitoring and predicting patient response of triple negative breast cancer (TNBC) to immunotherapy is needed. Using positron emission tomography (PET) imaging to probe the tumor microenvironment (hypoxia, T-cell activation), we aim to predict early response to immunotherapy for in mouse models of TNBC tumors. METHODS/STUDY POPULATION: Female Balb/c mice with 4T1-luciferase mammary carcinoma cell tumors were administered paclitaxel (PTX; 10 mg/kg), anti-PD1 (200 µg), both, or vehicle (saline) intraperitoneally. Treatment was given on days 0, 2, and 5 for cohort 1 (n=16) who underwent granzyme B specific (GZP) PET imaging (T-cell activation) and days 0, 2, 5, and 8 for cohort 2 (n=12) who underwent [18F]-fluoromisonidazole (FMISO)-PET imaging (hypoxia). Bioluminescence (BLI) imaging and caliper measurements were performed to track tumor size changes at multiple timepoints and tumors were collected for histological validation on day 20. Mean standard uptake value (SUVmean) was calculated as percent of day 0, and statistical analyses were performed with unpaired t-tests and Wilcoxon-rank sum tests. RESULTS/ANTICIPATED RESULTS: Non-responders to treatment had a significantly higher tumor volume compared to responders starting on day 6 (p&lt;0.05). Although no significant differences in BLI between control and single-agent therapies were found, BLI data revealed that treatment with combination PTX and anti-PD1 significantly decreased viability signal between days 3 and 6 (p=0.04). SUVmean from GZP-PET was over 250% higher in responders compared to non-responders by day 6 (p=0.03). SUVmean from FMISO-PET was 80% less in responders compared to nonresponders, indicating less tumor hypoxia (p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Non-invasive PET imaging of the tumor microenvironment can provide data on T cell activation and hypoxic response predicting response to combination immunotherapy and chemotherapy. Utilizing advanced imaging to understand biologically distinct features of the TNBC tumor microenvironment can aid in personalizing anti-cancer therapies.
TAR- and Tat-Independent Replication of Human Immunodeficiency Virus Type 1 in Human Hepatoma Cells (1996)

The molecular mechanisms involved in the regulation of human immunodeficiency virus type 1 (HIV-1) replication may differ in various cell types and with various exogenous stimuli. TAR/Tat interactions play important roles in HIV-1-long terminal repeat (LTR)-directed transcription, and have become specific targets in molecular therapies for blocking HIV-1 replication. As we previously reported, astrocytic glial cells, which can support HIV-1 replication in cell culture and may be infected in vivo, provide an intracellular milieu in which TAR mutant HIV-1 viruses may replicate. In further studies of this molecular model, several divergent human cell types were analyzed for both TAR- and Tat-independent HIV-1 replication. Human hepatoma cell lines, which can be productively infected by HIV-1 after the hepatoma cells are transduced with the human CD4 receptor gene, were found to support high levels of HIV-1 replication. In these studies, utilizing a transient transfection system with wild-type and various TAR, Tat, or combined TAR/Tat mutant HIV-1 proviral constructs, we demonstrate TAR-independent replication in unstimulated human hepatoma cells. Remarkably, in human hepatoma cells, HIV-1 replication is not only independent of TAR but also can be independent of Tat expression. It is further demonstrated, using electrophoretic mobility shift assays (EMSAs) and an in situ UV cross-linking system, that human hepatoma cells contain novel endogenous cellular proteins that bind to the proviral HIV-1 5' LTR in the downstream region, between nucleotides +38 to +125 on proviral DNA. This alternative regulatory pathway of TAR- and Tat-independent viral production may provide a new system to dissect further the interactions of Tat/TAR and determine the role of the TAR element, in its DNA form, in HIV-1 replication.
Compact cavity dumped broadband laser oscillator (2009)

Recent development of optically-pumped semiconductor laser (OPSL) technology provide a Ti:sapphire pump source reducing cost and complexity while maintaining a high standard of performance and reliability. In this paper we report on the performance of a compact (930 x 330 x 170 mm³), cavity-dumped ultrafast Ti:Sapphire laser oscillator pumped by an OPSL and using negative dispersion mirrors. The system generates broadband pulses of more than 45nJ pulse energy from single shot to 2 MHz repetition rate. At higher repetition rates the pulse energy decreases as it is typical for cavity dumped laser systems, but with 10 nJ at 27 MHz (division ratio of 1:2) the pulse energy is at the level of the Mantis in standard configuration (8 nJ). FWHM spectrum of the Mantis is specified &gt;70nm and bandwidth over 100nm could be achieved by fine adjustment of the dispersion with intracavity wedges. Compressed pulse duration down to 12.5fs was measured. The system is based on the standard Coherent Mantis laser with a cavity dumper extension, making the footprint only 350 mm longer. It can be user configured either as standard oscillator or as a cavity dumped oscillator.
Connecting gene expression data from connectivity map and <i>in silico</i> target predictions for small molecule mechanism-of-action analysis (2014)

Integrating gene expression profiles with certain proteins can improve our understanding of the fundamental mechanisms in protein-ligand binding. This paper spotlights the integration of gene expression data and target prediction scores, providing insight into mechanism of action (MoA). Compounds are clustered based upon the similarity of their predicted protein targets and each cluster is linked to gene sets using Linear Models for Microarray Data. MLP analysis is used to generate gene sets based upon their biological processes and a qualitative search is performed on the homogeneous target-based compound clusters to identify pathways. Genes and proteins were linked through pathways for 6 of the 8 MCF7 and 6 of the 11 PC3 clusters. Three compound clusters are studied; (i) the target-driven cluster involving HSP90 inhibitors, geldanamycin and tanespimycin induces differential expression for HSP90-related genes and overlap with pathway response to unfolded protein. Gene expression results are in agreement with target prediction and pathway annotations add information to enable understanding of MoA. (ii) The antipsychotic cluster shows differential expression for genes LDLR and INSIG-1 and is predicted to target CYP2D6. Pathway steroid metabolic process links the protein and respective genes, hypothesizing the MoA for antipsychotics. A sub-cluster (verepamil and dexverepamil), although sharing similar protein targets with the antipsychotic drug cluster, has a lower intensity of expression profile on related genes, indicating that this method distinguishes close sub-clusters and suggests differences in their MoA. Lastly, (iii) the thiazolidinediones drug cluster predicted peroxisome proliferator activated receptor (PPAR) PPAR-alpha, PPAR-gamma, acyl CoA desaturase and significant differential expression of genes ANGPTL4, FABP4 and PRKCD. The targets and genes are linked via PPAR signalling pathway and induction of apoptosis, generating a hypothesis for the MoA of thiazolidinediones. Our analysis show one or more underlying MoA for compounds and were well-substantiated with literature.
&lt;title&gt;Optical parallel selectionist systems&lt;/title&gt; (1993)

There are at least two major classes of computers in nature and technology: connectionist and selectionist. A subset of connectionist systems (Turing Machines) dominates modern computing, although another subset (Neural Networks) is growing rapidly. Selectionist machines have unique capabilities which should allow them to do truly creative operations. It is possible to make a parallel optical selectionist system using methods describes in this paper.
Anomalous Crystal Growth on TiO<sub>2</sub> Thin Film Induced by the AFM Tip (2008)

Tip-induced nucleation and crystallization have been observed in polymer thin films. This work shows for the first time that it is possible to induce a rapid crystal growth on amorphous inorganic thin film using the AFM tip. The force applied on the AFM tip exerts an enormous pressure on the surface of an amorphous titania thin film. The movement of the tip displaced the spin-coated titania sol and deformed the film. The V-shaped grooves left by the passage of the tip measured 65 nm in width and penetrated 5 nm into the 15 nm thick film. Heat treatment in air at 723 K crystallizes the TiO2. Large TiO2 crystallized on the grooves compared to the surrounding film indicating an anomalous rapid crystal growth. It is speculated that the enormous tip pressure caused a local densification and structural rearrangement of the titania that presage nucleation resulting in a faster crystallization.
Photolithography at the Limits of Optical Resolution (1993)

The continuous miniaturization in microelectronics requires advanced materials and processes that allow millions of electronic components to be integrated on a single chip of less than 1 cm2. The resolution of structures in the half and even quarter micron region is performed by the photolithographic process, i.e. the patternwise exposure of light-sensitive photoresist layers that alter solubility in developers when exposed to light. A recently developed bilayer photoresist consists of specifically functionalized anhydride-containing polymers and photoactive dissolution inhibitors. Within the CARL (Chemical Amplification of Resist Lines) process, the anhydride moieties in the resist enable room-temperature silylation with bisamino-siloxanes in aqueous based solvents that enhances oxygen-plasma etch resistance and creates widened structures. Thus, the resolution capability of optical exposure tools can be used to the full extent, and even structures beyond the optical resolution limit become accessible. Copolymerization of maleic anhydride with Boc-maleimide or tert-butyl methacrylate yields polymers for highly sensitive acid-catalyzed deep UV resists.
Measurement of the Domain Growth Kinetics in Multidomain Nematic Liquid Crystal Polymers by Means of the Worm Like Path Model for Multiple Scattering (1995)

Abstract The rate of domain growth in nematic side chain polymer samples is measured using the worm like path model for multiple scattering of light. The worm like path model which describes multiple scattaering in terms of the optical persistence length is found to apply both to multiple scattering in liquid crystal polymer films as well as to model polystyrene despersions. The required value of the optical persistence length can be calculated from the single scattering process so that there are no adjustable parameters in this model. The rate of domain growth in liquid crystal polymer samples is found to obey a scaling law where the growth exponent is about 0.85, contrary to the expected value of ½. In addition, an unexpected effect of the layer thickness on the rate of growth is observed, even for layer thickness much larger than the domain size.