gebhart/patrepeval huggingface dataset:
α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (2008)

Background: Although α1 adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by cardiovascular-related side effects that are caused by the subtype nonselective nature of many current drugs. To overcome this problem, it was hypothesized that an α1a/1d subtype selective antagonist would be efficacious yet produce less side effects, and hence would bring greater benefit for the therapy of BPH/LUTS. Unfortunately, such highly selective α1a/1d antagonists were not available, making the validation of the new hypothesis impossible. Objective/method: This review disclosed several series of α1a/1d subtype selective antagonists that have been discovered and developed by Johnson & Johnson recently. These compounds show equal and potent affinity for both α1a and α1d subtypes with good selectivity versus the α1b subtype. Some analogues also possess favorable pharmacokinetic properties. Conclusion: Although discovery of α1a/1d subtype selective antagonists paves the way for future research, the effectiveness of α1a/1d subtype selective antagonist in BPH/LUTS patients still needs to be proven in clinical trials. This patent review will focus on the latest progress in this field from 2006 to present.
20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells (2010)

20-hydroxyvitamin D(2) [20(OH)D(2)] inhibits DNA synthesis in epidermal keratinocytes, melanocytes, and melanoma cells in a dose- and time-dependent manner. This inhibition is dependent on cell type, with keratinocytes and melanoma cells being more sensitive than normal melanocytes. The antiproliferative activity of 20(OH)D(2) is similar to that of 1,25(OH)(2)D(3) and of newly synthesized 1,20(OH)(2)D(2) but significantly higher than that of 25(OH)D(3). 20(OH)D(2) also displays tumorostatic effects. In keratinocytes 20(OH)D(2) inhibits expression of cyclins and stimulates involucrin expression. It also stimulates CYP24 expression, however, to a significantly lower degree than that by 1,25(OH)(2)D(3) or 25(OH)D(3). 20(OH)D(2) is a poor substrate for CYP27B1 with overall catalytic efficiency being 24- and 41-fold lower than for 25(OH)D(3) with the mouse and human enzymes, respectively. No conversion of 20(OH)D(2) to 1,20(OH)(2)D(2) was detected in intact HaCaT keratinocytes. 20(OH)D(2) also demonstrates anti-leukemic activity but with lower potency than 1,25(OH)(2)D(3). The phenotypic effects of 20(OH)D(2) are mediated through interaction with the vitamin D receptor (VDR) as documented by attenuation of cell proliferation after silencing of VDR, by enhancement of the inhibitory effect through stable overexpression of VDR and by the demonstration that 20(OH)D(2) induces time-dependent translocation of VDR from the cytoplasm to the nucleus at a comparable rate to that for 1,25(OH)(2)D(3). In vivo tests show that while 1,25(OH)(2)D(3) at doses as low as 0.8 μg/kg induces calcium deposits in the kidney and heart, 20(OH)D(2) is devoid of such activity even at doses as high as 4 μg/kg. Silencing of CY27B1 in human keratinocytes showed that 20(OH)D(2) does not require its transformation to 1,20(OH)(2)D(2) for its biological activity. Thus 20(OH)D(2) shows cell-type dependent antiproliferative and prodifferentiation activities through activation of VDR, while having no detectable toxic calcemic activity, and is a poor substrate for CYP27B1.
Intravenous immunoglobulins for the treatment of infections in patients with haematological cancers (2011)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: We will evaluate the efficacy of intravenous immunoglobulin (IVIG) in the treatment of infections in patients with haematological malignancies with respect to the duration of infections, study mortality, infection‐related mortality, adverse events, infection and duration of hospitalisation.
The Projectile Perforation Resistance of Materials: Scaling the Impact Resistance of Thin Films to Macroscale Materials (2023)

From drug delivery to ballistic impact, the ability to control or mitigate the puncture of a fast-moving projectile through a material is critical. While puncture is a common occurrence, which can span many orders of magnitude in the size, speed, and energy of the projectile, there remains a need to connect our understanding of the perforation resistance of materials at the nano- and microscale to the actual behavior at the macroscale that is relevant for engineering applications. In this article, we address this challenge by combining a new dimensional analysis scheme with experimental data from micro- and macroscale impact tests to develop a relationship that connects the size-scale effects and materials properties during high-speed puncture events. By relating the minimum perforation velocity to fundamental material properties and geometric test conditions, we provide new insights and establish an alternative methodology for evaluating the performance of materials that is independent of the impact energy or the specific projectile puncture experiment type. Finally, we demonstrate the utility of this approach by assessing the relevance of novel materials, such as nanocomposites and graphene for real-world impact applications.
Innovative approaches of experimentally guided CFD modeling for data centers (2015)

This study illustrates basic guidelines for integrating empirical measurements to state of the art modeling approaches; that can be used to improve the accuracy of physics based data center CFD models. Experimental measurements gathered in a new research dedicated data center laboratory are used to guide an advanced approach to CFD modeling, the intent is to come up with a validated predictive model of the data center. One of the goals of this study is to provide scientists and engineers with a clear set of design guidelines; that allow for the introduction of important physical details into the model which have previously been largely overlooked. This approach will establish a valid baseline for future designs of data centers as well as future research projects in the data center laboratory. The current CFD model incorporates important physical parameters that affect the accuracy of the results. These include the plenum floor jacks' hydraulic resistance, the impact of cutouts, exact locations of supply vents, CRAH (computer room air handler) unit blower jet effects and momentum transfer through the perforated tiles. Other details of the CRAH unit such as the detailed supply vents, blower specifications, turning vent and angle of flow are included; also rack detailed structure including the mounting rails, cable penetration and PDUs (power distribution units). CFD modeling results are compared to the measured tiles flow rates from several different experimental conditions. The models were refined based on the experimental data and comparisons of the CFD versus experimental tiles flow data showed an overall average error of –3%.
Surface Characterization and Biocompatibility of Restorative Resin Containing Nanoparticles (2008)

Composite resins that are used to restore hard tissues have several drawbacks including the accumulation of biofilm on teeth and restorations. Recently, quaternary ammonium poly(ethylene imine) (QA-PEI) nanoparticles were developed for additional antibacterial activity of restorative composite resins. QA-PEI nanoparticles were synthesized from cross-linked poly(ethylene imine) that was N-alkylated with octyl halide, followed by quaternary methylation with methyl iodide. QA-PEI particles that were embedded in restorative composite resin at 1% w/w resulted in the complete growth inhibition of Streptococcus mutans. Moreover, the antibacterial activity was retained for at least 3 months. The active substances on the surface of the restorative composite resin that were incorporated with QA-PEI particles were detected by X-ray photoelectron spectroscopy (XPS) and confocal microscopy measurements. The in vitro cytotoxicity tests showed a similar effect on the viability of the cell line that was tested with composites including modified and unmodified dental composite resins. In vivo toxicity studies, which were assessed on Wistar rats by the implantation of modified composite specimens, revealed no inflammation response 1 week after the implantation of restorative composite resin that was embedded with up to 2% w/w QA-PEI.
Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study (2021)

We describe for the first time early high-resolution IL-33 concentration kinetics in individual patients after trauma and correlate systemic IL-33 release to clinical data. These findings provide insight into a potentially important axis of danger signaling in humans.
Data from Functional Kinomics Identifies Candidate Therapeutic Targets in Head and Neck Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; To identify novel therapeutic drug targets for p53-mutant head and neck squamous cell carcinoma (HNSCC).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; RNAi kinome viability screens were performed on HNSCC cells, including autologous pairs from primary tumor and recurrent/metastatic lesions, and in parallel on murine squamous cell carcinoma (MSCC) cells derived from tumors of inbred mice bearing germline mutations in &lt;i&gt;Trp53&lt;/i&gt;, and p53 regulatory genes: &lt;i&gt;Atm&lt;/i&gt;, &lt;i&gt;Prkdc&lt;/i&gt;, and &lt;i&gt;p19&lt;sup&gt;Arf&lt;/sup&gt;&lt;/i&gt;. Cross-species analysis of cell lines stratified by p53 mutational status and metastatic phenotype was used to select 38 kinase targets. Both primary and secondary RNAi validation assays were performed on additional HNSCC cell lines to credential these kinase targets using multiple phenotypic endpoints. Kinase targets were also examined via chemical inhibition using a panel of kinase inhibitors. A preclinical study was conducted on the WEE1 kinase inhibitor, MK-1775.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Our functional kinomics approach identified novel survival kinases in HNSCC involved in G&lt;sub&gt;2&lt;/sub&gt;–M cell-cycle checkpoint, SFK, PI3K, and FAK pathways. RNAi-mediated knockdown and chemical inhibition of the WEE1 kinase with a specific inhibitor, MK-1775, had a significant effect on both viability and apoptosis. Sensitivity to the MK-1775 kinase inhibitor is in part determined by p53 mutational status, and due to unscheduled mitotic entry. MK-1775 displays single-agent activity and potentiates the efficacy of cisplatin in a p53-mutant HNSCC xenograft model.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; WEE1 kinase is a potential therapeutic drug target for HNSCC. This study supports the application of a functional kinomics strategy to identify novel therapeutic targets for cancer. &lt;i&gt;Clin Cancer Res; 20(16); 4274–88. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Octa: Omissions and Conflicts in Target-Aspect Sentiment Analysis (2020)

Sentiments in opinionated text are often determined by both aspects and target words (or targets). We observe that targets and aspects interrelate in subtle ways, often yielding conflicting sentiments. Thus, a naive aggregation of sentiments from aspects and targets treated separately, as in existing sentiment analysis models, impairs performance. We propose Octa, an approach that jointly considers aspects and targets when inferring sentiments. To capture and quantify relationships between targets and context words, Octa uses a selective self-attention mechanism that handles implicit or missing targets. Specifically, Octa involves two layers of attention mechanisms for, respectively, selective attention between targets and context words and attention over words based on aspects. On benchmark datasets, Octa outperforms leading models by a large margin, yielding (absolute) gains in accuracy of 1.6% to 4.3%.
Structural damping studies at cryogenic temperatures (1994)

Results of an engineering study to measure changes in structural damping properties of two cryogenic wind tunnel model systems and two metallic test specimens at cryogenic temperatures are presented. Data are presented which indicate overall, a trend toward reduced structural damping at cryogenic temperatures (-250 degrees F) when compared with room temperature damping properties. The study was focused on structures and materials used for model systems tested in the National Transonic Facility (NTF). The study suggests that the significant reductions in damping at extremely cold temperatures are most likely associated with changes in mechanical joint compliance damping rather than changes in material (solid) damping.
Protein−Protein Recognition between Acyltransferases and Acyl Carrier Proteins in Multimodular Polyketide Synthases (2009)

Acyltransferase (AT) domains of multimodular polyketide synthases are the primary gatekeepers for stepwise incorporation of building blocks into a growing polyketide chain. Each AT domain has two substrates, an alpha-carboxylated CoA thioester (e.g., malonyl-CoA or methylmalonyl-CoA) and an acyl carrier protein (ACP). Whereas the acyl-CoA specificity of AT domains has been extensively investigated, little is known about their ACP specificity. Guided by recent high-resolution structural insights, we have systematically probed the protein-protein interactions between AT domains, ACP domains, and the linkers that flank AT domains. Representative AT domains of the 6-deoxyerythronolide B synthase (DEBS) have greater than 10-fold specificity for their cognate ACP substrates as compared to other ACP domains from the same synthase. Both of the flanking (N- and C-terminal) linkers of an AT domain contributed to the efficiency and specificity of transacylation. As a frame of reference, the activity and specificity of a stand-alone AT domain from the "AT-less" disorazole synthase (DSZS) were also quantified. The activity (k(cat)/K(M)) of this AT was >250-fold higher than the corresponding values for DEBS AT domains. Although the AT from DSZS discriminated modestly against ACP domains from DEBS, it exhibited >40-fold higher activity in trans in the presence of these heterologous substrates than their natural AT domains. Our results highlight the opportunity for regioselective modification of a polyketide backbone by in trans complementation of inactivated AT domains. They also reinforce the need for more careful consideration of protein-protein interactions in the engineering of these assembly line enzymes.
Vibration Detection and Localization Using Modified Digital Coherent Telecom Transponders (2021)

We demonstrate a vibration detection and localization scheme based on bidirectional transmission of telecom signals with digital coherent detection at the receivers. Optical phase is extracted from the digital signal processing blocks of the coherent receiver, from which the vibration component is extracted by bandpass filtering, and the position along the cable closest to the vibration's epicenter is recovered by correlation. We demonstrate our scheme first using offline experiment with 200-Gb/s DP-16QAM, and we report field trial results over installed fiber to detect real-world vibration events.
New basic esters of 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylic acid endowed with spasmolytic properties. Synthesis and pharmacological-pharmacokinetic evaluation. (1993)

In order to obtain new analogs of flavoxate endowed with higher stability and possibly higher potency, a new series of basic esters of 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylic acid (MFCA) has been prepared and investigated. Derivatives in which the structure of flavoxate was modified by branching and lengthening of the estereal alkyl chain were synthesized, together with the conformationally restricted N-piperidinyl derivatives. Esters containing in their structure various alicyclic tertiary amines which are present in natural or synthetic drugs endowed with spasmolytic properties, mainly of anticholinergic nature, were also prepared. The stability in aqueous solution, acute toxicity in mouse, and in vitro spasmolytic properties of the new compounds were investigated in comparison with flavoxate. Based on the results obtained from this screening procedure, 3 compounds were selected for further investigation. In this phase, further pharmacological and stability testing as well as preliminary animal pharmacokinetic investigations were carried out. The obtained results suggested the choice of 1,1-dimethyl-2-(1-piperidinyl)ethyl 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylate HCl (Rec 151 2053, terflavoxate, CAS 86433-39-8) as a candidate for preclinical development. The deeper pharmacological characterization of this compound, carried out mainly in comparison with flavoxate, terodiline, and oxybutynin confirmed its good spasmolytic activity.
Simulation and Control of Deformable Autonomous Airships in Turbulent Wind (2020)

Abstract. Fixed wing and multirotor UAVs are common in the field of robotics. Solutions for simulation and control of these vehicles are ubiquitous. This is not the case for airships, a simulation of which needs to address unique properties, i) dynamic deformation in response to aerodynamic and control forces, ii) high susceptibility to wind and turbulence at low airspeed, iii) high variability in airship designs regarding placement, direction and vectoring of thrusters and control surfaces. We present a flexible framework for modeling, simulation and control of airships, based on the Robot operating system (ROS), simulation environment (Gazebo) and commercial off the shelf (COTS) electronics, both of which are open source. Based on simulated wind and deformation, we predict substantial effects on controllability, verified in real world flight experiments. All our code is shared as open source, for the benefit of the community and to facilitate lighter-than-air vehicle (LTAV) research. https://github.com/robot-perception-group/airship_simulation
Trace level doping of lithium-rich cathode materials (2016)

Lithium ion batteries have revolutionized portable electronics and have the potential to electrify the transportation sector.
Blastogenic responses and the release of interleukins 1 and 2 by spleen cells obtained from rat skin allograft recipients administered with 15-deoxyspergualin. (1987)

15-Deoxyspergualin(DSG) is an analogue of spergualin isolated from Bacillus laterosporus0'.In mice, DSG strongly inhibits antibody formation and delayed-type hypersensitivity to sheep red blood cells2).In rats, DSGinhibits the rejection of skin2), heart3) and islet cell4) allografts.The mechanisms responsible for these immunosuppressive actions of DSGhave not been elucidated.To investigate these mechanisms, we administered DSGor cyclosporin A (Cy A), a
Synthesis of clean hydrogen gas from waste plastic at zero net cost (2023)

Hydrogen gas (H2) is the primary storable fuel for pollution-free energy production, with over 90 million tonnes used globally per year. More than 95% of H2 is synthesized through metal-catalyzed steam methane reforming that produces 11 tonnes of CO2 per tonne H2. “Green H2” from water electrolysis using renewable energy produces sub-stoichiometric CO2, but costs 2-3x more, making it presently economically unviable. Here we report catalyst-free conversion of waste plastic into clean “flash H2” along with high purity graphene. The scalable procedure evolves no CO2 when deconstructing polyolefins and produces H2 in purities up to 94% at high mass yields. Sale of the graphene byproduct at just 5% of its current value yields H2 production at negative cost. Life-cycle assessment demonstrates a 39-84% reduction in emissions compared to other H2 production methods, suggesting the flash H2 process to be an economically viable, clean H2 production route.
Control and Characterization of Cyclopentene Unimolecular Dissociation on Si(100) with Scanning Tunneling Microscopy (2009)

Dissociation of individual cyclopentene molecules on the Si(100) surface is induced and investigated using cryogenic ultrahigh vacuum scanning tunneling microscopy (STM). Using a secondary feedback loop during elevated tunneling current and sample biasing conditions, the cyclopentene dissociation products are isolated and then characterized with atomic-scale spatial resolution. Using multibias STM and density functional theory, the cyclopentene dissociation products are shown to consist of a C(5)H(7) fragment and an individual H atom. The C(5)H(7) fragment contains a C=C double bond and is bound to the Si(100) surface via a single Si-C covalent bond, while the individual H atom can be induced to hop between two sites on a single silicon dimer with the STM tip. This study shows that the use of feedback control during STM-induced single molecule reactions allows transient reaction products to be captured and thus more thoroughly studied. While demonstrated here for cyclopentene on Si(100), this feedback-controlled approach can likely be applied to a wide array of chemical reactions on semiconductor surfaces.
High-Throughput Microfluidic Sorting of Live Magnetotactic Bacteria (2018)

Magnetic nanoparticles (MNPs) are useful for many biomedical applications, but it is challenging to synthetically produce them in large numbers with uniform properties and surface functionalization. Magnetotactic bacteria (MTB) produce magnetosomes with homogenous sizes, shapes, and magnetic properties. Consequently, there is interest in using MTB as biological factories for MNP production. Nonetheless, MTB can only be grown to low yields, and wild-type strains produce low numbers of MNPs/bacterium. There are also limited technologies to facilitate the selection of MTB with different magnetic contents, such as MTB with compromised and enhanced biomineralization ability. Here, we describe a magnetic microfluidic platform combined with transient cold/alkaline treatment to temporarily reduce the rapid flagellar motion of MTB without compromising their long-term proliferation and biomineralization ability for separating MTB on the basis of their magnetic contents. This strategy enables live MTB to be enriched, which, to the best of our knowledge, has not been achieved with another previously described magnetic microfluidic device that makes use of ferrofluid and heat. Our device also facilitates the high-throughput (25,000 cells/min) separation of wild-type <i>Magnetospirillum gryphiswaldense</i> (MSR-1) from nonmagnetic Δ<i>mamAB</i> MSR-1 mutants with a sensitivity of up to 80% and isolation purity of up to 95%, as confirmed with a gold-standard fluorescent-activated cell sorter (FACS) technique. This offers a 25-fold higher throughput than other previously described magnetic microfluidic platforms (1,000 cells/min). The device can also be used to isolate <i>Magnetospirillum magneticum</i> (AMB-1) mutants with different ranges of magnetosome numbers with efficiencies close to theoretical estimates. We believe this technology will facilitate the magnetic characterization of genetically engineered MTB for a variety of applications, including using MTB for large-scale, controlled MNP production.<b>IMPORTANCE</b> Our magnetic microfluidic technology can greatly facilitate biological applications with magnetotactic bacteria, from selection and screening to analysis. This technology will be of interest to microbiologists, chemists, and bioengineers who are interested in the biomineralization and selection of magnetotactic bacteria (MTB) for applications such as directed evolution and magnetogenetics.