gebhart/patrepeval huggingface dataset:
Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer (2020)

<b>Background:</b> Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Sacituzumab govitecan (SG) is a novel antibody-drug-conjugate (ADC) targeting trophoblast-antigen-2 (Trop-2), a cell surface glycoprotein highly expressed in many epithelial tumors, to deliver SN-38, the active metabolite of irinotecan. This study aimed to evaluate Trop-2 expression in EOC tissues and the preclinical activity of SG against primary EOC cell lines and xenografts. <b>Methods:</b> Trop-2 expression was assessed in 90 formalin-fixed-paraffin-embedded tumors and nine primary tumor cell lines by immunohistochemistry (IHC) and flow cytometry, respectively. Trop-2 expression and cell viability after exposure to SG in primary tumor cell lines, non-targeting control ADC, and SG-parental antibody hRS7 were evaluated using flow-cytometry-based-assays. Antibody-dependent-cell-cytotoxicity (ADCC) against Trop-2+ and Trop-2- EOC cell lines was tested <i>in vitro</i> using 4 h Chromium-release-assays. <i>In vivo</i> activity of SG was evaluated against Trop-2+ EOC xenografts. <b>Results:</b> Moderate-to-strong staining was seen in 47% (42/90) of ovarian tumors by IHC while 89% (8/9) of the primary EOC cell lines overexpressed Trop-2 by flow cytometry. EOC Trop-2+ were significantly more sensitive to SG compared to control ADC (<i>p</i> < 0.05). Both SG and hRS7 mediated high ADCC activity against Trop-2+ cell lines. SG also induced significant bystander killing of Trop-2- tumor cells admixed with Trop-2+ EOC cells. In <i>in vivo</i> experiments SG treatment demonstrated impressive anti-tumor activity against chemotherapy-resistant EOC xenografts. <b>Conclusion:</b> SG demonstrates remarkable preclinical activity against biologically aggressive and chemotherapy-resistant EOC cell lines and a significant bystander effect against EOC cell lines with heterogenous Trop-2 expression. Clinical trials are warranted.
Physical Model for Real-Time Simultaneous Estimation of Intake Mass and Cylinder Pressure in an SI Engine (2016)

Stringent emission regulations require spark ignited (SI) engines to operate at stoichiometry to enable the use of a three way catalyst (TWC). Thus, accurate prediction of the intake charge mass flow rate is paramount. Current speed-density air mass-flow prediction techniques require extensive calibration for predicting volumetric efficiency, while mass air flow (MAF) meter based approaches suffer from a loss of accuracy during transients. This work aims to provide an alternative, i.e. a model based air charge estimation algorithm that can reduce calibration effort and provide a universal solution across engine platforms. An additional objective is to minimize the number of required sensors and associated cost. The foundation is established with a 0-D physics-based air charge model, where air flow through intake and exhaust valves is modeled on a crank-angle basis, without the need to measure in-cylinder pressure. The proposed algorithm solves differential equations for cylinder pressure and mass flow rate in/out of the cylinder to simultaneously obtain instantaneous pressure and mass-flow estimations, hence eliminating the need to install cylinder pressure transducers. An additional benefit is the robustness of the new model, due to its ability to self-compensate for an error in the intake runner pressure or initial estimation of the cylinder pressure. The model has been validated with GT-Power simulations and steady-state engine tests with multiple actuator sweeps. Transient tests and real-time implementations were performed as well.
Large-area microfabrication of three-dimensional, helical polymer structures (2004)

A technique has been developed to fabricate polymeric helixes with sub-micron dimensions. These helixes are made using a double-templating process, in which an inorg. thin film deposited using glancing angle deposition acts as the master. The shape, pitch, handedness and no. of turns of the polymer helixes can be tuned by altering the deposition parameters of the master film. The structure of this pos. master is copied into a neg. intermediate template of photoresist, which itself acts as a master for the templating of polymer helixes. This process is demonstrated with four multifunctional acrylates. The master, intermediate template and polymer helixes are characterized using SEM, and the polymer helixes are characterized using energy dispersive x-ray spectroscopy. It is shown that a large no. of polymer helical microstructures, which are anchored to both a thick substrate and a thin capping layer, can be made in parallel over areas of mm2 to cm2.
Der Einfluss des neuen nichtsteroidalen Mineralocorticoid Antagonisten BR-4628 auf die Natriumausscheidung bei sekundärer biliärer Leberzirrhose (2010)

Einleitung: Bei der Leberzirrhose kommt es häufig zu einer Störung der renalen Natriumausscheidung. Zur Therapie der renalen Natrium- und Wasserausscheidung bei dekompensierter Leberzirrhose und Aszites gibt es bisher kein befriedigendes Konzept. Durch den Einsatz von Schleifendiuretika gelingt es häufig nicht, eine balancierte Natrium- und Wasserausscheidung zu erreichen.
Fast and accurate global geodesic registrations using knee MRI from the Osteoarthritis Initiative (2012)

Registration is important for many applications in medical image analysis. Affine registration of knee MR images can suffer failures due to large anatomical and articulated pose variations. This work is demonstrated using 2743 MR images from the Osteoarthritis Initiative (OAI) public access dataset. With such large datasets any manual interventions to aid registration success are not feasible and so full automation with high accuracy is of paramount importance. Additionally, computing exhaustive pairwise registrations across the OAI dataset is very computationally expensive. We present a sparse geodesic registration method that increases accuracy of pairwise registration and also enables fast online computation of registration. We then propose two novel methods to reduce registration error over the graph. Firstly we use all precomputed transformations to infer transformation errors for each edge, through assuming global registration cycle consistency across a sparse graph. In conjunction with this, we suggest fusing multiple successful registrations as a strategy to mitigate small errors in each transformation in the graph. It is shown that, in combination, these techniques achieve more accurate pairwise registration results than both geodesic registration and direct pairwise registration. This paper addresses accuracy of registrations, speed of online computation and is demonstrated on a large scale dataset.
Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair (2016)

Faithful meiotic chromosome segregation and fertility require meiotic recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on the meiotic kinase, Mek1. Mek1 is thought to mediate repair template bias by specifically suppressing sister-directed repair. Instead, we found that when Mek1 persists on closely paired (synapsed) homologues, DNA repair is severely delayed, suggesting that Mek1 suppresses any proximal repair template. Accordingly, Mek1 is excluded from synapsed homologues in wild-type cells. Exclusion requires the AAA+-ATPase Pch2 and is directly coupled to synaptonemal complex assembly. Stage-specific depletion experiments further demonstrate that DNA repair in the context of synapsed homologues requires Rad54, a repair factor inhibited by Mek1. These data indicate that the sister template is distinguished from the homologue primarily by its closer proximity to inhibitory Mek1 activity. We propose that once pairing or synapsis juxtaposes homologues, exclusion of Mek1 is necessary to avoid suppression of all templates and accelerate repair progression.
NONLINEAR SIGNAL DETECTION IN THE TIME DOMAIN: LEVEL CROSSING STATISTICS AND NOISE-MEDIATED MINIMIZATION OF THE MEASUREMENT ERROR (2004)

We study the problem of detecting a small dc signal by quantifying its effect on the mean difference ΔT in residence times in the stable steady states of a bistable dynamical measurement device, in the presence of a noise-floor and a known time-sinusoidal bias signal. Errors in the measurement process occur due to a finite observation time that is present in most practical scenarios; in turn, noise degrades the measurement. Adjusting the bias signal amplitude to a slightly subthreshold operating regime, leads to a non-monotonic dependence of the (suitably defined) error on the noise intensity; at a critical noise intensity, the error is minimized. This phenomenon, reminiscent of the well-known Stochastic Resonance effect [1–4], appears to be most pronounced for subthreshold bias signals in the strongly nonlinear response regime. The results can be applied to a variety of nonlinear systems, including neurons, that operate in the time-domain.
New Aromatic Nitro Compounds from Salegentibacter sp. T436, an Arctic Sea Ice Bacterium: Taxonomy, Fermentation, Isolation and Biological Activities. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Flexible Route to Mannose 6-Phosphonate Functionalized Derivatives (2002)

A new approach for the synthesis of a mannose 6-phosphonate isosteric analog of mannose 6-phosphate is reported. The mannosylphosphonate has been prepared in a multistep synthesis involving an homologation reaction of the methyl f - D -mannopyranoside followed by an Arbuzov reaction between a bromohomomannosyl derivative and the tris (trimethylsilyl)phosphite. This approach, avoiding the deprotection of dialkylphosphonate, allowed us to prepare the mannose 6-phosphonate in good yield. The described method was successfully extended to the preparation of a mannose 6-phosphonate linked to a cholesteryl moiety. This strategy affords a more general route for a wide range of functionalized mannose 6-phosphonate derivatives.
Micro-optical Spectroscopy of Stacking Faults in Colloidal Photonic Crystal Films (2007)

We report on direct measurements of the influence of stacking faults on the optical properties of thin colloidal crystal films. Spatially resolved micro‐optical spectroscopy is used to demonstrate that variations in the stacking sequence of close‐packed spheres give rise to unique optical spectra, which can be convoluted by large area spatially averaged measurements. FDTD simulations are in excellent agreement with the measured spectra.
Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both? (2007)

Microcirculatory dysfunction in ST-elevation myocardial infarction can be cause, consequence or both according to non-traditional and traditional concepts.
Cementation of Colloidal Particles on Electrodes in a Galvanic Microreactor (2013)

We have studied the processes leading to the cementation of colloidal particles during their autonomous assembly on corroding copper electrodes within a Cu-Au galvanic microreactor. We determined the onset of particle immobilization through particle tracking, monitored the dissolution of copper as well as the deposition of insoluble products of the corrosion reactions in situ, and showed that particle immobilization initiated after reaction products (RPs) began to deposit on the electrode substrate. We further demonstrated that the time and the extent of RP precipitation and thus the strength of the particle-substrate bond could be tuned by varying the amount of copper in the system and the microreactor pH. The ability to cement colloidal particles at locations undergoing corrosion illustrates that the studied colloidal assembly approach holds potential for applications in dynamic material property adaptation.
Total Synthesis and Initial Structure−Function Analysis of the Potent V-ATPase Inhibitors Salicylihalamide A and Related Compounds (2002)

Salicylihalamide A is the first member of a growing class of macrocyclic salicylate natural products that induce a variety of interesting phenotypes in cultured mammalian cells. Salicylihalamide A was reported to be a unique and highly differential cytotoxin and a potent inhibitor of the mammalian vacuolar (H(+))-ATPase. The total synthesis of both enantiomers of salicylihalamide A, a revision of the absolute configuration assigned to the natural product, and extensive structure-function studies with synthetic salicylihalamide variants are reported. These studies were possible only due to a highly efficient synthetic strategy that features (1) a remarkably E-selective ring-closing olefin metathesis to construct the 12-membered benzolactone skeleton 29, (2) a mild stereocontrolled elaboration to E-alkenyl isocyanate 41, and (3) addition of carbon, oxygen, and sulfur nucleophiles to isocyanate 41 to obtain salicylihalamide A and congeners. We demonstrate for the first time that salicylihalamide A is a potent inhibitor of fully purified reconstituted V-ATPase from bovine brain, and have identified several similarly potent side chain modified derivatives, including salicylihalamide dimers 43-45. In combination, these studies have laid the foundation for ongoing studies aimed at a comprehensive understanding of salicylihalamide's mode-of-action, of potential relevance to the development of lead compounds for the treatment of osteoporosis and cancer.
Photoelectron spectra of sterically congested alkenes and dienes (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotoelectron spectra of sterically congested alkenes and dienesPhillip D. Mollere, K. N. Houk, David S. Bomse, and Thomas Hellman MortonCite this: J. Am. Chem. Soc. 1976, 98, 16, 4732–4736Publication Date (Print):August 1, 1976Publication History Published online1 May 2002Published inissue 1 August 1976https://pubs.acs.org/doi/10.1021/ja00432a007https://doi.org/10.1021/ja00432a007research-articleACS PublicationsRequest reuse permissionsArticle Views107Altmetric-Citations26LEARN 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-Alertsclose Get e-Alerts
On networks with side information (2009)

In this paper, we generalize the lossless coded side information problem from the three-node network of Ahlswede and Korner to more general network scenarios. We derive inner and outer bounds on the achievable rate region in the general network scenario and show that they are tight for some families of networks. Our approach demonstrates how solutions to canonical source coding problems can be used to derive bounds for more complex networks and reveals an interesting connection between networks with side information, successive refinement, and network coding.
Functional connectivity changes in multiple sclerosis patients: A graph analytical study of MEG resting state data (2011)

Multiple sclerosis (MS) is characterized by extensive damage in the central nervous system. Within this field, there is a strong need for more advanced, functional imaging measures, as abnormalities measured with structural imaging insufficiently explain clinicocognitive decline in MS. In this study we investigated functional connectivity changes in MS using resting-state magnetoencephalography (MEG). Data from 34 MS patients and 28 age and gender-matched controls was assessed using synchronization likelihood (SL) as a measure of functional interaction strength between brain regions, and graph analysis to characterize topological patterns of connectivity changes. Cognition was assessed using extensive neuropsychological evaluation. Structural measures included brain and lesion volumes, using MRI. Results show SL increases in MS patients in theta, lower alpha and beta bands, with decreases in the upper alpha band. Graph analysis revealed a more regular topology in the lower alpha band in patients, indicated by an increased path length (λ) and clustering coefficient (γ). Attention and working memory domains were impaired, with decreased brain volumes. A stepwise linear regression model using clinical, MRI and MEG parameters as predictors revealed that only increases in lower alpha band γ predicted impaired cognition. Cognitive impairments and related altered connectivity patterns were found to be especially predominant in male patients. These results show specific functional changes in MS as measured with MEG. Only changes in network topology were related to poorer cognitive outcome. This indicates the value of graph analysis beyond traditional structural and functional measures, with possible implications for diagnostic and/or prognostic purposes in MS.
The role of KIR and HLA polymorphism in HIV acquisition: association and in vitro functional studies (VIR1P.1159) (2015)

Abstract Polymorphism in the genes that encode the HLA antigens and the KIR receptors on NK cells influence both adaptive and innate immunity. We analyzed the role of HLA and KIR polymorphisms in HIV acquisition by comparing 405 HIV+ and 523 HIV- men in the Chicago MACS cohort. We found no significant association with any HLA allele, in contrast to the well established strongly protective effect of HLA-B*57:01 for HIV disease progression. The inhibitory KIR ligands are HLA class I epitopes and fall into the groups: HLA-C1,C2, HLA-Bw4, and HLA-A3/A11. Association analyses of individual KIR genes in the presence/absence of their cognate HLA ligand revealed that one KIR/HLA ligand genotype combination was protective for HIV acquisition. The HLA ligand genotype C1/C1 was protective compared to C1/C2 and C2/C2 but only with genotype KIR2DL3+/KIR2DL2- (OR = 1.76, p = 0.007). This KIR genotype marks homozygosity for the centromeric KIR A haplotype, which is more inhibitory, has fewer genes, and less diverse than KIR B haplotypes. Since C2 is the ligand for the KIR2DL1 receptor, and C1 is the ligand for the KIR2DL3 receptor, the protective association observed with C1/C1 homozygotes suggests that a lack of signaling via the strongly inhibitory KIR2DL1 receptor in addition to signaling via the KIR2DL3 receptor is protective. In vitro assays of NK cells from KIR2DL3 homozygous individuals demonstrate that C1/C1 vs C1/C2 and C2/C2 (C2+) genotypes are more active in terms of cytokine release.
Glycan FRET Probes for Screening Catalytic Antibodies Against Cryptococcus Neoformans Capsule (2020)

Catalytic monoclonal antibodies (mAbs) against the capsule of Cryptococcus neoformans have been identified but characterization of their Michaelis-Menten kinetics against oligosaccharides has so far not been possible. To address this, we report the design and synthesis of two glycan based Förster resonance energy transfer (FRET) probes that express a major structural unit of the cryptococcal polysaccharide. These probes allowed the kinetic analysis of four catalytic antibodies with glycosidase activity, including 2H1, an antibody which was not known previously to be catalytic. This is only the second report of an antibody with naturally occurring catalytic activity against glycans and the most efficient identified to date. The probe’s capability as a diagnostic for catalysis was demonstrated by accurately predicting glycosidase activity on the native capsule. Furthermore, we used molecular docking studies to reveal the antibody-glycan interactions, with the first structural insights into these interactions between anti-GXM mAbs and their epitopes. Through modelling we see no classical catalytic residues in the antigen binding site, signifying the possibility of further glycan hydrolyzing mechanisms yet to be discovered.
Automatically Finding Good Clusters with Seed K-Means (2003)

In finding biologically relevant groups of genes with gene expression data obtained by microarray technologies, the k-means clustering method is one of the most popular approaches due to its easiness to use and simplicity to implement. However, the randomness of k-means clustering method in choosing initial points to start with makes it impossible to obtain reliable results without much iteration of the entire clustering process [2]. Our goal here is to introduce a novel clustering method, which we call it seed k-means clustering, where a novel algorithm is employed to automatically find good initial seeds for k-means clustering.
Serum and urinary carnosinase-1 correlate with kidney function and inflammation (2022)

The carnosinase dipeptidase 1 (CNDP1) gene has been reported as a susceptibility locus for the development of diabetic kidney disease (DKD). While the (CTG)<sub>5</sub> allele affords protection in the Caucasian population, we have previously shown that this allele is less frequently present in the Chinese population and therefore a protective role for the (CTG)<sub>5</sub> allele is difficult to demonstrate. In the present study, we sought to assess if carnosinase-1 (CN-1) concentrations in serum and/or urine are associated with progression of DKD and to what extent CN-1 influences diabetes-associated inflammation. From a total of 622 individuals that enrolled in our study, 247 patients had type 2 diabetes without DKD, 165 patients had DKD and 210 subjects served as healthy controls. Uni- and multivariate regression analyses were performed to identify potential factors predicting urinary albumin creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and CN-1 concentration in serum and urine. The results indicated that serum CN-1 indeed correlated with eGFR (p = 0.001). In addition, urinary CN-1 associated with eGFR and tubular injury indicator: urinary cystatin C (Cys-C) and urinary retinol-binding protein (RBP). Interestingly, serum CN-1 also positively correlated with inflammatory indicators: neutrophils and lymphocytes. With regard to this, a STZ injected C57BL/6 mice model with surgically made skin wound was established for the generation of skin inflammation. This animal model further proved that the expression of CN-1 in liver and kidney increased remarkably in diabetic mice with skin wound as compared to those without. In conclusion, serum and urinary CN-1 significantly related to the surrogates of impaired renal function in diabetic patients; besides, CN-1 expression might also be associated with the process of inflammation.