gebhart/patrepeval huggingface dataset:
CTLA-4 blockade: therapeutic potential in cancer treatments (2010)

Enhancing or prolonging T-cell activation by monoclonal antibodies (mAbs) blocking negative signaling receptors such as CTLA4 is one approach to overcoming tumor-induced immune tolerance. Ipilimumab and tremelimumab inhibit CTLA4, prolonging antitumor immune responses and leading to durable anti-tumor effects. Treatment with these mAbs has demonstrated clinically important and durable tumor responses and disease control rates in patients with unresectable advanced melanoma. Durable objective responses have been reported across a spectrum of doses and schedules, with relative safety in this patient population. Although the phase III tremelimumab melanoma study was closed for "futility", the 1-year survival rate of >50% for tremelimumab and the median survival of 11.7 months (compared with 10.7 months for chemotherapy) are notable. Results of the phase III studies testing CTLA4-blockade with ipilimumab are eagerly anticipated. The further development of these agents includes testing in the neoadjuvant melanoma setting (ipilimumab) as well the adjuvant high-risk melanoma setting (ipilimumab). Future progress with CTLA-4 blockade therapy will also likely come from the use of combinations of agents that target several critical regulatory pathways of the immune system and modulate the immune response in the host in a synergistic and controlled fashion.
Intracerebroventricular antisense knockdown of Gαi2 results in ciliary stasis and ventricular dilatation in the rat (2007)

Our results establish that Galphai2 has an essential regulatory role in ciliary function and CSF homeostasis.
Conception assistée par ordinateur (CAO) - Moteur asynchrone (2001)

La conception des machines asynchrones recouvre un domaine d’activité très vaste qui va de la machine de quelques watts de puissance destinée à des applications informatiques jusqu’au moteur de quelques mégawatts implanté dans des procédés industriels lourds. Il n’est pas possible de couvrir, dans l
Spectral embedding of regularized block models (2019)

Spectral embedding is a popular technique for the representation of graph data. Several regularization techniques have been proposed to improve the quality of the embedding with respect to downstream tasks like clustering. In this paper, we explain on a simple block model the impact of the complete graph regularization, whereby a constant is added to all entries of the adjacency matrix. Specifically, we show that the regularization forces the spectral embedding to focus on the largest blocks, making the representation less sensitive to noise or outliers. We illustrate these results on both on both synthetic and real data, showing how regularization improves standard clustering scores.
Visualization of time-dependent inactivation of human tumor cathepsin B isozymes by a peptidyl fluoromethyl ketone using a fluorescent print technique. (1988)

A peptidyl fluoromethyl ketone (Z-Phe-Ala CH2F) was found to be an effective compound in a time dependent inactivation of cathepsin B isozymes from a number of tissues including human tumors. The effect was visualized by employing an activity-specific fluorescent print technique preceded by isoelectric focusing. The technique could yield additional information of selective inhibition of isozymes as observed with rat pancreas. The fluoromethyl ketone is 30-fold more potent than the known inhibitor of cathepsin B, Z-Phe-AlaCHN2 in parallel evaluation. Furthermore, the fluoromethyl ketone may have in vivo potential in the inhibition of cathepsin B, in view of the results of toxicological studies. The findings demonstrate that the application of enzyme-directed overlay membranes, impregnated with specific substrates, following isoelectric focusing could be very useful in the study of proteases and their involvement in the oncogenic process.
Light-Weight, Single-Phase, Liquid-Cooled Cold Plate (Presentation) (2013)

This presentation, 'Light-Weight, Low-Cost, Single-Phase Liquid-Cooled Cold Plate,' directly addresses program goals of increased power density, specific power, and lower cost of power electronics components through improved thermal management.
Competitive Analog Antagonists of Bradykinin in the Canine Hindlimb (1987)

Six structural analogs of bradykinin were tested to determine whether they antagonize the vasodilator response to bradykinin. The dog hindlimb preparation was used as a bioassay. Mongrel dogs were anesthetized and the femoral arteries were isolated and fitted with a noncanulating electromagnetic flow probe. An indwelling catheter was also placed for administration of saline, bradykinin, or the various analogs. The vasodilatory responses of the hindlimb circulation to bolus doses of bradykinin from 1 of 20 ng were tested during vehicle or analog administration at 1 and 10 micrograms/min. Bradykinin analogs which were characterized by amino acid replacement by beta-(2-thienyl)-L-alanine (Thi) at positions 5 and 8, D-phenylalanine (D-Phe) at position 7, and an additional replacement of hydroxyproline at position 2 or 3 were effective antagonists of bradykinin. The decapeptide bradykinin analog (BKA06) D-Arg-(Hyp3-Thi5-D-Phe7-Thi)-BK was the most potent analog tested, producing a full log dose shift in the dose-response curve to bradykinin at the 10 micrograms/min (4 nmole/min) infusion rate. None of the analogs we tested produced vasodilation or had any effect upon systemic blood pressure at the concentrations tested. Our results suggest that these structural analogs of bradykinin may be effective pharmacologic tools to study the role of endogenous kinins in the control of vascular resistance and circulatory homeostasis.
Lower extremity cooling reduces ischemia-reperfusion injury following Zone 3 REBOA in a porcine hemorrhage model (2018)

External cooling during prolonged Zone 3 REBOA decreased ischemic muscle injury and resulted in lower compartment pressures following reperfusion. Hypothermia may be a viable option to extend the tolerable duration of Zone 3 occlusion, beyond what is currently achievable. Future survival studies are required to assess functional outcomes.
A Theoretical Study of Curing Reactions of Maleimide Resins through Michael Additions of Amines (2000)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTA Theoretical Study of Curing Reactions of Maleimide Resins through Michael Additions of AminesSatoshi Okumoto and Shinichi YamabeView Author Information Matsushita Electric Works, Ltd., 1048, Kadoma, Osaka 571-8686, Japan Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8528, Japan Cite this: J. Org. Chem. 2000, 65, 5, 1544–1548Publication Date (Web):February 16, 2000Publication History Received1 April 1999Published online16 February 2000Published inissue 1 March 2000https://pubs.acs.org/doi/10.1021/jo9905773https://doi.org/10.1021/jo9905773brief-reportACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views586Altmetric-Citations20LEARN 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 (1)»Supporting Information Supporting Information SUBJECTS:Addition reactions,Amines,Molecules,Noncovalent interactions,Reaction mechanisms Get e-Alerts
A Novel Type of Geosmin Biosynthesis in Myxobacteria (2005)

The biosynthesis of geosmin (1) and (1(10)E,5E)-germacradien-11-ol (2), two volatile terpenoid compounds emitted by the myxobacteria Myxococcus xanthus and Stigmatella aurantiaca, was investigated in feeding experiments with different labeled precursors. In these experiments, the volatiles released by the cell cultures grown on agar plates were collected with a closed-loop stripping apparatus (CLSA) and analyzed by GC-MS. [(2)H(10)]Leucine and [4,4,4,5,5,5-(2)H(6)]dimethylacrylate were fed to wild-type strains and bkd mutant strains, which are impaired in the degradation of leucine to isovaleryl-CoA. [(2)H(10)]Leucine was incorporated into 1 and 2 only by the wild-type strains via the biosynthetic pathway that involves leucine degradation and branching into the mevalonate pathway. Dimethylacrylyl-CoA (DMA-CoA) is an intermediate in the leucine degradation and in the recently discovered pathway from HMG-CoA to isovaleryl-CoA. The corresponding free acid, [4,4,4,5,5,5-(2)H(6)]dimethylacrylic acid, was incorporated into 1 and 2 only by the mutants impaired in leucine degradation. [4,4,6,6,6-(2)H(5)]Mevalonic acid lactone (12) was synthesized and fed to M. xanthus and S. aurantiaca wild-type strains and a double mutant strain of M. xanthus. This strain does not degrade leucine and is impaired in the reduction of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid. The mass spectral analysis of labeled 1 and 2 obtained in these feeding experiments led to a biosynthetic scheme to 1 with intermediate 2. This pathway differs from that observed in the liverwort Fossombronia pusilla and thus suggests microbial geosmin biosynthesis following a route different from that in liverworts. Our results are supported by a 1,2-hydride shift of the tertiary hydrogen atom at C-4a into the ring opposite to that in F. pusilla.
On the Geometry and Shape of Brain Sub-Manifolds (1997)

This paper develops mathematical representations for neuro-anatomically significant substructures of the brain and their variability in a population. The focus of the paper is on the neuro-anatomical variation of the geometry and the "shape" of two-dimensional surfaces in the brain. As examples, we focus on the cortical and hippocampal surfaces in an ensemble of Macaque monkeys and human MRI brains. The "shapes" of the substructures are quantified via the construction of templates; the variations are represented by defining probabilistic deformations of the template. Methods for empirically estimating probability measures on these deformations are developed by representing the deformations as Gaussian random vector fields on the embedded sub-manifolds. The Gaussian random vector fields are constructed as quadratic mean limits using complete orthonormal bases on the sub-manifolds. The complete orthonormal bases are generated using modes of vibrations of the geometries of the brain sub-manifolds. The covariances are empirically estimated from an ensemble of brain data. Principal component analysis is presented for characterizing the "eigen-shape" of the hippocampus in an ensemble of MRI-MPRAGE whole brain images. Clustering based on eigen-shape is presented for two sub-populations of normal and schizophrenic.
The Development of Intellectual Abilities in Pediatric Temporal Lobe Epilepsy (2006)

These data suggest a critical period during the first year of life for the subsequent development of intellectual abilities and highlight the importance of early treatment in this population.
Diagnostic and therapeutic potential of RNASET2 in Crohn’s disease: Disease-risk polymorphism modulates allelic-imbalance in expression and circulating protein levels and recombinant-RNASET2 attenuates pro-inflammatory cytokine secretion (2022)

Ribonuclease T2 gene (RNASET2) variants are associated in genome wide association studies (GWAS) with risk for several autoimmune diseases, including Crohn's disease (CD). In T cells, a functional and biological relationship exists between TNFSF15-mediated enhancement of IFN-γ production, mucosal inflammation and RNASET2. Disease risk variants are associated with decreased mRNA expression and clinical characteristics of severe CD; however, functional classifications of variants and underlying molecular mechanisms contributing to pathogenesis remain largely unknown. In this study we demonstrate that allelic imbalance of RNASET2 disease risk variant rs2149092 is associated with transcriptional and post-transcriptional mechanisms regulating transcription factor binding, promoter-transactivation and allele-specific expression. RNASET2 mRNA expression decreases in response to multiple modes of T cell activation and recovers following elimination of activator. In CD patients with severe disease necessitating surgical intervention, preoperative circulating RNASET2 protein levels were decreased compared to non-IBD subjects and rebounded post-operatively following removal of the inflamed region, with levels associated with allelic carriage. Furthermore, overexpression or treatment with recombinant RNASET2 significantly reduced IFN-γ secretion. These findings reveal that RNASET2 cis- and trans-acting variation contributed regulatory complexity and determined expression and provide a basis for linking genetic variation with CD pathobiology. These data may ultimately identify RNASET2 as an effective therapeutic target in a subset of CD patients with severe disease.
Pathology of dengue virus infection. (2014)

This chapter describes the diagnosis, pathology and pathogenesis of dengue, focusing on histopathology, immunohistochemistry, molecular and other diagnostic modalities. Of the many pathogens within the clinical differential diagnosis, leptospirosis and viral haemorrhagic fevers including yellow fever will be highlighted because these diseases can have similar clinical pathological presentations and significant geographical overlap. Lastly, knowledge gaps are briefly highlighted where pathological studies could provide insight into the morbidity and mortality seen in the expanding dengue pandemic.
Ultrakurzzeitphysik: Laser‐optimierte Femtochemie: Quantenkontrolle durch lernfähige Femtosekunden‐Laser (2001)

Abstract Mithilfe der Femtosekunden‐Spektroskopie lassen sich atomare Bewegungen in Molekülen zeitaufgelöst beobachten. Seit kurzem ist es mit speziell geformten Femtosekunden‐Laserpulsen sogar möglich, über diese bloße Beobachtung hinauszugehen, „von außen”︁ steuernd einzugreifen und den Ablauf molekularer Dynamik „mikroskopisch”︁ gezielt zu beeinflussen. Durch den Einsatz lernender Algorithmen mit experimenteller Rückkopplung lassen sich komplexe Licht‐Materie‐Wechselwirkungen in vielen Anwendungsbereichen optimieren. In diesem Artikel wird schwerpunktmäßig die Quantenkontrolle der Femtochemie, also die Steuerung chemischer Prozesse auf einer Femtosekunden‐Zeitskala, diskutiert.
Influence of hypoxia on adrenergic modulation of triggered activity in isolated adult canine myocytes. (1991)

Although findings from several reports suggest that nonreentrant or focal mechanisms contribute to the genesis of arrhythmias during early ischemia, the contribution of triggered activity arising from early or delayed afterdepolarizations has not been resolved. We have previously demonstrated that beta- but not alpha-adrenergic stimulation induces afterdepolarizations and triggered activity in isolated normoxic myocytes. In the present study, the influence of the extent of cellular derangements as well as increases in [K+]o on alpha- and beta-adrenergic-mediated afterdepolarizations and triggered activity was evaluated. Adult canine myocytes were exposed to one of the following experimental conditions with simultaneous intracellular transmembrane action potential recordings: 1) low PO2 (less than 10 mm Hg, obtained using a specially designed hypoxic chamber) and low (6.8) pH; 2) low PO2, low pH, and high extracellular potassium ([K+]o) (10 mM); or 3) severe metabolic inhibition with cyanide (10(-6) M). Cells from each group were superfused with either the alpha-agonist phenylephrine (10(-5) or 10(-7) M, with 10(-5) M nadolol) or the beta-agonist isoproterenol (10(-6) M). Moderate changes in the action potentials were observed under conditions 1 and 2 (moderate hypoxia), whereas marked but reversible changes were observed with cyanide (severe metabolic inhibition). During moderate hypoxia in normal [K+]o, delayed afterdepolarizations or triggered activity were elicited by both alpha- (12 of 13 cells) and beta-adrenergic (five of five cells) stimulation. Increasing [K+]o during moderate hypoxia completely abolished the afterdepolarizations induced by alpha-adrenergic stimulation and prevented the occurrence of triggered activity. In contrast, the influence of beta-adrenergic stimulation was only attenuated by an increase in [K+]o. Exposure to cyanide completely prevented the induction of afterdepolarizations and triggered activity by both alpha- and beta-adrenergic stimulation. Our findings indicate that moderate hypoxia in normal [K+]o is associated with the development of adrenergic-mediated afterdepolarizations and triggered activity. In contrast, accumulation of [K+]o or severe impairment of cellular metabolism is accompanied by inhibition of adrenergic-mediated afterdepolarizations and triggered activity.
Assessment of MULTALL As CFD Code for the Analysis of Tube-Axial Fans (2020)

Abstract This work deals with the application of the open source CFD code MULTALL to the analysis of tube-axial-fans. The code has been widely validated in the literature for high-speed turbomachine flows but not applied yet to low speed tutbomachines. The aim of this work is to assess the degree of reliability of MULTALL as a tool for simulating the internal flow in industrial axial-flow fan rotors. To this end, the predictions of the steady-state air flow field in the annular sector of a 315mm tube-axial fan obtained by MULTALL 18.3 are compared with those obtained by two state-of-the-art CFD codes and experimental data of the global aerodynamic performance of the fan and the pitch-wise averaged velocity distribution downstream of the rotor. All the steady-state RANS calculations were performed on either fully structured hexahedron or hexa-dominant grids using classical formulations of algebraic turbulence models. The pressure curve and the trend of the aeraulic efficiency in the stable operation range of the fan predicted by MULTALL show very good agreement with both the experimental data and the other CFD results. Although the estimation of the fan efficiency predicted by MULTALL can be noticeably improved by the more sophisticated state-of-the-art CFD codes, the analysis of the velocity distribution at the rotor exit supports the use of MULTALL as a reliable CFD analysis tool for designers of low-speed axial fans.
Evaluation of a Newly Developed Vacuum Dried Microtiter Plate for Rapid Biocide Susceptibility Testing of Clinical Enterococcus faecium Isolates (2020)

We investigated the suitability of a newly developed biocide susceptibility test system based on microtiter plates containing vacuum dried biocides as a fast and reliable screening method. The evaluated substances included the cationic biocides benzalkonium chloride (BAC), chlorhexidine dihydrochloride (CHX), cetylpyridinium chloride, didecyldimethylammonium chloride, and octenidine dihydrochloride. Testing a selection of <i>Escherichia coli</i> and enterococci, the biocide microtiter plates provided results comparable to those obtained from broth microdilution according to ISO 20776-1. Broad MIC ranges allowed for testing gram-positive and gram-negative species with the same plate design. In the second part of our study, we applied the established method to analyze the susceptibility of 90 clinical <i>Enterococcus faecium</i> isolates from a German university hospital, as previous studies have indicated a link between reduced susceptibility to substances such as CHX and BAC and vancomycin resistance. We therefore determined MIC and minimum bactericidal concentrations (MBC) for 48 non-clonal vancomycin susceptible and 42 non-clonal vancomycin resistant isolates, but MIC<sub>95</sub> and MBC<sub>95</sub> were quite similar in both groups. Our easy to handle and ready to use test system enables the routine surveillance of bacterial tolerance towards disinfectants in hospitals. As a result, hygiene measures can be adapted and nosocomial infections controlled despite increasing prevalence of antibiotic-resistant bacteria.
Direct Torque Control of Brushless DC Drives With Reduced Torque Ripple (2005)

The application of direct torque control (DTC) to brushless ac drives has been investigated extensively. This paper describes its application to brushless dc drives, and highlights the essential differences in its implementation, as regards torque estimation and the representation of the inverter voltage space vectors. Simulated and experimental results are presented, and it is shown that, compared with conventional current control, DTC results in reduced torque ripple and a faster dynamic response.
Front Cover: Synthesis of Cytotoxic Iron‐Containing Macrocycles Through Unexpected C(sp2)−C(sp2) Bonds Formation (Eur. J. Inorg. Chem. 23/2023) (2023)

The Front Cover shows a representation of stomach cancer cells being destroyed by an iron(II) complex bearing a tetradentate ligand. Gastric cancer is associated with a high mortality rate and high lethality and is frequently resistant to standard chemotherapies and immunotherapy. A cutting-edge reaction between Fe3(CO)12 and brominated or mercurated pincer derivatives promotes the formation of carbon−carbon bonds, and a 16-electron iron(II) complex with a tetradentate ligand originating from the dimerization of 6-phenyl-2,2′-bipyridine and a protonated 14-membered macrocycle from 2,6-diphenyl-pyridine were obtained. These new compounds are cytotoxic towards stomach cancer cells. Thanks to the presence of the iron center, the biological activity dramatically increased, and the complex was 5-fold more toxic than cisplatin on AGS cells. The cover was designed by Carolina Torres-Gutiérrez (the first author) and Hortensia Segura Silva. More information can be found in the Research Article by R. Le Lagadec and co-workers.