gebhart/patrepeval huggingface dataset:
Pharmacokinetic-Pharmacodynamic Interactions Between Two Selective Monoamine Oxidase Inhibitors: Moclobemide and Selegiline (1996)

The objectives of this study were to assess potential pharmacokinetic and pharmacodynamic interactions between moclobemide and selegiline. Two groups of 12 healthy male and female subjects were treated with 200 mg moclobemide or 5 mg selegiline b.i.d. for 16 days. On study day 8, the alternative active drug or placebo was added to the respective treatments. Concentration-time profiles of moclobemide and two of its main metabolites and 3,4-dihydrox/phenylglycol (DHPG, a norepinephrine metabolite), 5-hydroxy-indoleacetic acid (HIAA, a serotonin metabolite), and 3,4-dihydroxyphenylacetic acid (DOPAC, a dopamine metabolite) in plasma as well as MAO-B activity and serotonin concentration in platelets were determined at steady state during monotreatment and combined treatment. The pharmacokinetic parameters of moclobemide and its metabolites changed on multiple dosing but were not influenced to a relevant extent by concomitant administration of selegiline. The measured pharmacodynamic parameters, expressed as the maximum effect on a study day and the area under the effect-time curve, characterized the drugs' influence on peripheral neurotransmitter metabolism. The most reliable variables to assess inhibition of MAO-A and -B in humans proved to be DHPG in plasma and serotonin in platelets and MAO-B activity in platelets, respectively. Several variables (DHPG, platelet serotonin) suggested that selegiline has some MAO-A inhibitory activity. This became particularly apparent upon addition of selegiline to moclobemide treatment; i.e., the effects of combined moclobemide and selegiline treatment were statistically greater than those of moclobemide monotreatment. Moclobemide alone exerted a slight inhibition of platelet MAO-B activity. The reported pharmacodynamic interactions are not considered to be clinically relevant. However, due to the previously found supraadditive tyramine potentiation upon simultaneous treatment, moclobemide and selegiline should only be combined when applying dietary restrictions with respect to tyramine.
Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment (2021)

Our results suggest significant mechanistic overlap between AD and COVID-19, strongly centered on neuroinflammation and microvascular injury. These results help improve our understanding of COVID-19-associated neurological manifestations and provide guidance for future development of preventive or treatment interventions.
A comparative study elucidating the substantial functional defects of electroporated T cells relative to a mechanical SQZ-based approach (2018)

Background: Ex vivo manipulation of primary cells is critical to the success of cell-based therapies, however, limitations of existing ex vivo delivery approaches may dramatically restrict the use of cell engineering to treat disease. Methods: We used a genome-wide approach to study optimized electroporation treatment and microfluidic cell squeezing to identify the impact of delivery technique on gene expression profiles in human T cells. To validate the microarray results, we used a multiplex cytokine analysis comprised of 42 key T cell cytokines to assess perturbation of cytokine secretion. Finally, in a direct comparison of therapeutic functionality, the efficacy of T cells edited for PD-1 via electroporation and cell squeezing was assessed using therapeutic treatment of the Eg.7 OVA tumor model. Results: We identified striking disruptions in transcript expression after treatment with electroporation (17% of genes mis-regulated, FDR q < 0.1), whereas cells treated with microfluidic squeezing had similar expression profiles to untreated control cells (0% of genes mis-regulated, FDR q < 0.1). These genetic disruptions result in concomitant perturbation of cytokine secretion including a 648-fold increase in IL-2 secretion (p < 0.01) and a 30-fold increase in IFNγ secretion (p < 0.05) in electroporated cells. Squeezing cells did not result in the non-specific secretion of any of the 42 cytokines tested. Ultimately, the effects at the transcript and protein level resulted in functional deficiencies in vivo with electroporated T cells failing to demonstrate sustained antigen-specific effector responses and tumor control. Conclusions: This work demonstrates that the delivery mechanism used to insert biomolecules affects functionality and warrants further study. The significant differences in outcomes from the two techniques underscores the importance of understanding the impact of intracellular delivery methods on cell function for research and clinical applications. Hence, for both research and therapeutic applications, the functional and safety consequences of the selected intracellular delivery technique and its impact on cell phenotype should be carefully evaluated. Legal entity responsible for the study: SQZ Biotechnologies. Funding: SQZ Biotechnologies. Disclosure: J. Hanson, J. Cole, L. Cassereau, J. Bugge, T. Ditommaso, J. Gilbert, H. Bernstein, A. Sharei: Employed by SQZ Biotech.
The Value of FLG Null Mutations in Predicting Treatment Response in Atopic Dermatitis: An Observational Study in Finnish Patients (2016)

The contribution of filaggrin null mutations to predicting atopic dermatitis (AD) treatment response is not clear, nor have such mutations been studied in the Finnish population. This study tested the association of the 4 most prevalent European FLG null mutations, the 2 Finnish enriched FLG null mutations, the FLG 12-repeat allele, and 50 additional epidermal barrier gene variants, with risk of AD, disease severity, clinical features, risk of other atopic diseases, age of onset, and treatment response in 501 patients with AD and 1,710 controls. AD, early-onset AD, palmar hyperlinearity, and asthma showed significant associations with the combined FLG null genotype. Disease severity and treatment response were independent of patient FLG status. Carrier frequencies of R501X, 2282del4, and S3247X were notably lower in Finns compared with reported frequencies in other populations. This data confirms FLG mutations as risk factors for AD in Finns, but also questions their feasibility as biomarkers in predicting treatment response.
Phage-displayed peptides as biosensor reagents (2000)

This study investigated the potential to utilize phage-displayed peptides as reagents in sensor applications. A library of random 12-mers displayed on phage was panned against staphylococcal enterotoxin B (SEB), a causative agent of food poisoning. Nine SEB binding phage clones were isolated, all of which share the consensus sequence Trp His Lys at their amino terminus. Binding of several of these phage was shown to be inhibited when they were assayed in a competitive enzyme-linked immunosorbent assay (ELISA) format with synthesized peptide corresponding to the peptide-encoding region of one of the clones. Whole phage were labeled with the dye Cy5, and incorporated into fluoroimmunoassays. Labeled phage were able to detect SEB down to a concentration of 1.4 ng/well in a fluorescence-based immunoassay. When incorporated into an automated fluorescence-based sensing assay, Cy5-labeled phage bound to probes coated with SEB generated a robust signal of about 10,000 pA, vs a signal of 1,000 pA using a control fiber coated with streptavidin. These results demonstrate the potential for development of phage-based sensor reagents.
ChemInform Abstract: Direct Synthesis of Acyl Azides from Carboxylic Acids Using 2‐Azido‐1,3‐dimethylimidazolinium Chloride. (2010)

Abstract The title reaction is also used for the racemization‐free amidation of amino acid derivatives such as (III).
A prolate-spheroidal impulse-radiating antenna system to launch and focus 100-ps pulses for melanoma treatment (2010)

This paper briefly reviews the design of a prolate-spheroidal impulse-radiating antenna system, to launch and focus fast (100 ps) high-voltage (> 100 kV) pulses, as a non-invasive tool for melanoma (skin cancer) treatment. The experiments on a graded five-layer dielectric lens, designed to match the pulses into a biological target medium, are outlined. The design of a switch system to launch high-voltage spherical TEM pulses is also summarized.
Application of giant magnetoresistive elements in thin film tape heads (1994)

We studied the applicability of Ni/sub 80/Fe/sub 20//Cu/Ni/sub 80/Fe/sub 20//Fe/sub 50/Mn/sub 50/ GMR multilayers for thin film tape heads. A method involving crossed anisotropies is applied for avoiding noise in the GMR response. We compare and analyse the sensitivities of AMR and GMR heads.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Comparison of L-DACS and FBMC performance in over-water air-ground channels (2015)

The demand for air transportation is continuously growing. Likewise, unmanned aircraft systems (UAS) are proliferating at a tremendous pace. Both current and future air-to-ground (AG) communications systems will be deployed in the L-band (960-1164 MHz), and possibly in other bands. Aiming toward modernization, Eurocontrol recently defined two L-Band Digital Aeronautical Communication Systems (L-DACS). Primary goals of LDACS are high data rate transmission and high reliability. There are two L-DACS technology candidates, LDACS1 and LDACS2. The LDACS1 scheme employs a fairly broadband (0.5 MHz) transmission using Orthogonal Frequency-Division Multiplexing (OFDM) together with adaptive coding and modulation. The LDACS2 scheme follows a more traditional approach which is based on GSM (Global System for Mobile Communications), i.e., on second generation cellular mobile radio technology. In this paper, we investigate and compare the physical layer characteristics of L-DACS1 and L-DACS2 and then via simulations we illustrate the performance of these two communication systems in an air-to-ground channel. The air-to-ground channel we employ is one based upon a recent extensive measurement campaign. Results for error probability vs. signal to noise ratio are the focus. We also propose a new filterbank multicarrier (FBMC) based air-ground communication air interface which is consistent with previous requirements of L-DACS. We compare the FBMC performance with that of the LDACS schemes and show that FBMC has higher spectral efficiency via better time-frequency localized prototype subcarrier filters. This enables use of some guard subcarriers as data carrying subcarriers, increasing throughput. The BER results of our FBMC based L-DACS system are equivalent to those of L-DACS1 and better than those of L-DACS2. The simulation results also show the sensitivity of L-DACS2 systems to channel phase shifts and show the necessity of channel equalization for L-DACS2 receivers.
Molecular profiling of reticular gigantocellularis neurons indicates that eNOS modulates environmentally dependent levels of arousal (2018)

Neurons of the medullary reticular nucleus gigantocellularis (NGC) and their targets have recently been a focus of research on mechanisms supporting generalized CNS arousal (GA) required for proper cognitive functions. Using the retro-TRAP method, we characterized transcripts enriched in NGC neurons which have projections to the thalamus. The unique expression and activation of the endothelial nitric oxide (eNOS) signaling pathway in these cells and their intimate connections with blood vessels indicate that these neurons exert direct neurovascular coupling. Production of nitric oxide (NO) within eNOS-positive NGC neurons increases after environmental perturbations, indicating a role for eNOS/NO in modulating environmentally appropriate levels of GA. Inhibition of NO production causes dysregulated behavioral arousal after exposure to environmental perturbation. Further, our findings suggest interpretations for associations between psychiatric disorders and mutations in the eNOS locus.
Refined Solution Structure of the LpxC−TU-514 Complex and pKa Analysis of an Active Site Histidine:  Insights into the Mechanism and Inhibitor Design, (2005)

Lipopolysaccharide, the major constituent of the outer monolayer of the outer membrane of Gram-negative bacteria, is anchored into the membrane through the hydrophobic moiety lipid A, a hexaacylated disaccharide. The zinc-dependent metalloamidase UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) catalyzes the second and committed step in the biosynthesis of lipid A. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds. Recent NMR and X-ray studies of the LpxC from Aquifex aeolicus have provided the first structural information about this family of proteins. Insight into the catalytic mechanism and the design of effective inhibitors could be facilitated by more detailed structural and biochemical studies that define substrate-protein interactions and the roles of specific residues in the active site. Here, we report the synthesis of the (13)C-labeled substrate-analogue inhibitor TU-514, and the subsequent refinement of the solution structure of the A. aeolicus LpxC-TU-514 complex using residual dipolar couplings. We also reevaluate the catalytic role of an active site histidine, H253, on the basis of both its pK(a) as determined by NMR titration and pH-dependent kinetic analyses. These results provide a structural basis for the design of more potent LpxC inhibitors than those that are currently available.
Urinary albumin/creatinine ratio tertiles predict risk of diabetic retinopathy progression: a natural history study from the Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort (2022)

isrctn.org ISRCTN91419926.
Uncoupled glycerol distribution as the origin of the accumulation of 3-hydroxypropionaldehyde during the fermentation of glycerol byEnterobacter agglomerans CNCM 1210 (1998)

Batch fermentation of glycerol to 1,3-propanediol (1,3PPD) by Enterobacter agglomerans CNCM 1210 showed the lethal accumulation of 3-hydroxypropionaldehyde (3-HPA) when performed under initial substrate content higher than 40 g/L. Assigned to the inhibition by the NAD/NADH ratio of the 3-HPA converting enzyme: 1,3PPD dehydrogenase, intracellular assays were conducted in an attempt to identify the metabolic mechanisms involved in the increase of that ratio. An overflow metabolism through the 1,3PPD formation pathway was established, while a catabolic limitation in the oxidative branch at the level of glyceraldehyde-3-phosphate dehydrogenase occurred. Uncoupled activities of synthesis and consumption of reducing equivalents are thus suspected to provoke the increase of the NAD/NADH ratio and the subsequent accumulation of 3-HPA. Copyright 1998 John Wiley & Sons, Inc.
Supplementary Figures S1-S7 from LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody–Drug Conjugates (2023)

&lt;p&gt;Figures S1-S7 show LRRC15 RNA and protein expression in cancer, and demonstrate the anti-tumor efficacy of the LRRC15-targeted ADC ABBV-085 in vitro and in vivo as a monotherapy and in combination with standard-of-care therapies.&lt;/p&gt;
Supplementary Figure 5. Anti-tumor response of all groups of mice treated with carfilzomib or selinexor alone and in combination. from Synergistic Myeloma Cell Death via Novel Intracellular Activation of Caspase-10–Dependent Apoptosis by Carfilzomib and Selinexor (2023)

&lt;p&gt;Changes in mean tumor volume of all groups of mice treated with selinexor and carfilzomib, alone and in combination.&lt;/p&gt;
High-Temperature Polymer Dielectrics For Capacitive Energy-Storage Applications (2011)

Founded in 1683 in Leiden, the Netherlands, Brill is a leading international academic publisher in the Humanities, Social Sciences, International Law, and Biology. With offices in the Netherlands, Germany, Austria, the USA and Asia, Brill today publishes more than 360 journals and 2,000 new books and reference works each year as well as a large number of databases and primary source research collections.
Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence (2009)

This is the first report documenting that MGB-2 expression characterizes less aggressive forms of EOC and is correlated with a favorable outcome. These findings suggest that the determination of MGB-2, especially at molecular level, in EOC tissue obtained after primary surgery can provide additional prognostic information about the risk of recurrence.
BeyondRgenes: dissecting disease-resistance pathways using genomics and proteomics (2006)

Breeding for disease resistance in crops has mainly been accomplished by incorporating single resistance (R) genes. There are advantages to quantitative resistance in terms of durability but breeding for this type of resistance is difficult. New technologies in genomics and proteomics are providing insights into disease-resistance pathways. Structural genomics can identify genomic regions that carry genes controlling these pathways and provide a means for identifying and cloning the genes involved. High-throughput molecular breeding can be used to rapidly assess a large number of lines and select for multiple-resistance quantitative trait loci. This makes breeding for complex resistance types feasible. Functional genomics can identify genes involved in the resistance pathway. By merging structural and functional genomics it will be possible to correlate complex patterns of gene expression with genomic regions and identify key elements that control entire pathways. To fully understand the pathways it is necessary to look at post-translational modification of proteins, as this is a fundamental mechanism involved in transducing the signal from the cell membrane to the nucleus to activate the resistance. Phosphoproteomics will help to discover proteins involved in the signalling pathways.
Tailoring the Surface Chemistry of PEDOT:PSS to Promote Supported Lipid Bilayer Formation (2023)

Abstract This communication reports on a versatile and substrate‐agnostic method to tune the surface chemistry of conducting polymers with the aim of bridging the chemical mismatch between bioelectronic devices and biological systems. As a proof of concept, the surface of poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is grafted with a short‐chain oligoethylene glycol monolayer to favor the formation of cell‐derived supported lipid bilayers (SLBs). This method is tuned to optimize the affinity between the supported lipid bilayer and the conducting polymer, leading to significant improvements in bilayer quality and therefore electronic readouts. To validate the impact of surface functionalization on the system's ability to transduce biological phenomena into quantifiable electronic signals, the activity of a virus commonly used as a surrogate for SARS‐CoV‐2 (mouse hepatitis virus) is monitored with and without surface treatment. The functionalized devices exhibit significant improvements in electronic output, stemming from the improved SLB quality, therefore strengthening the case for the use of such an approach in membrane‐on‐a‐chip systems.
First observation and amplitude analysis of theB−→D+K−π−decay (2015)

The ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}{D}^{+}{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{\ensuremath{-}}$ decay is observed in a data sample corresponding to $3.0\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ of $pp$ collision data recorded by the LHCb experiment during 2011 and 2012. Its branching fraction is measured to be $\mathcal{B}({B}^{\ensuremath{-}}\ensuremath{\rightarrow}{D}^{+}{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{\ensuremath{-}})=(7.31\ifmmode\pm\else\textpm\fi{}0.19\ifmmode\pm\else\textpm\fi{}0.22\ifmmode\pm\else\textpm\fi{}0.39)\ifmmode\times\else\texttimes\fi{}1{0}^{\ensuremath{-}5}$ where the uncertainties are statistical, systematic and from the branching fraction of the normalization channel ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}{D}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}{\ensuremath{\pi}}^{\ensuremath{-}}$, respectively. An amplitude analysis of the resonant structure of the ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}{D}^{+}{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{\ensuremath{-}}$ decay is used to measure the contributions from quasi-two-body ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}{D}_{0}^{*}(2400{)}^{0}{K}^{\ensuremath{-}}$, ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}{D}_{2}^{*}(2460{)}^{0}{K}^{\ensuremath{-}}$, and ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}{D}_{J}^{*}(2760{)}^{0}{K}^{\ensuremath{-}}$ decays, as well as from nonresonant sources. The ${D}_{J}^{*}(2760{)}^{0}$ resonance is determined to have spin 1.
Enantio-, Diastereo-, and Regioselective Zirconium-Catalyzed Carbomagnesation of Cyclic Ethers with Higher Alkyls of Magnesium. Utility in Synthesis and Mechanistic Implications (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantio-, Diastereo-, and Regioselective Zirconium-Catalyzed Carbomagnesation of Cyclic Ethers with Higher Alkyls of Magnesium. Utility in Synthesis and Mechanistic ImplicationsMary T. Didiuk, Charles W. Johannes, James P. Morken, and Amir H. HoveydaCite this: J. Am. Chem. Soc. 1995, 117, 27, 7097–7104Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/ja00132a009https://doi.org/10.1021/ja00132a009research-articleACS PublicationsRequest reuse permissionsArticle Views891Altmetric-Citations58LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Topological transformations of a nematic drop (2023)

Morphogenesis of living systems involves topological shape transformations which are highly unusual in the inanimate world. Here we demonstrate that a droplet of a nematic liquid crystal changes its equilibrium shape from a simply-connected tactoid, which is topologically equivalent to a sphere, to a torus, which is not simply-connected. The topological shape transformation is caused by the interplay of nematic elastic constants, which facilitates splay and bend of molecular orientations in tactoids but hinders splay in the toroids. The elastic anisotropy mechanism might be helpful in understanding topology transformations in morphogenesis and paves the way to control and transform shapes of droplets of liquid crystals and related soft materials.
A Novel Synthesis of 1-IsochromanolsviaHetero Diels-Alder Reaction of Carbonyl Compounds with 1-Trimethylsilyloxy-benzocyclobutene as a Precursor of α-Oxy-o-Quinodimethane Under Mild Condition (1996)

Abstract Reaction of 1-trimethylsilyloxybenzocyclobutene(1) with carbonyl compounds catalyzed by tris(dimethylamino)sulfur (trimethylsilyl)difluoride (TASF) at room temperature gave 1-isochromanol derivatives as corresponding hetero Diels-Alder adducts in good yields.