gebhart/patrepeval huggingface dataset:
Glycolysis is required for LPS-Induced activation and adhesion of Human CD14+CD16− Monocytes (2019)

Monocytes in humans consist of 3 subsets; CD14&lt;sup&gt;+&lt;/sup&gt;CD16&lt;sup&gt;−&lt;/sup&gt;(classical), CD14&lt;sup&gt;+&lt;/sup&gt;CD16&lt;sup&gt;+&lt;/sup&gt; (intermediate) and CD14&lt;sup&gt;dim&lt;/sup&gt;CD16&lt;sup&gt;+&lt;/sup&gt; (non-classical), which exhibit distinct and heterogeneous responses to activation. During acute inflammation CD14&lt;sup&gt;+&lt;/sup&gt;CD16&lt;sup&gt;−&lt;/sup&gt; monocytes are significantly elevated and migrate to the sites of injury via the adhesion cascade. The field of immunometabolism has begun to elucidate the importance of the engagement of specific metabolic pathways in immune cell function. Yet, little is known about monocyte metabolism and the role of metabolism in mediating monocyte activation and adherence to vessels. Accordingly, we aimed to determine whether manipulating the metabolism of CD14&lt;sup&gt;+&lt;/sup&gt;CD16&lt;sup&gt;− &lt;/sup&gt;monocytes alters their ability to become activated and adhere. We discovered that LPS stimulation increased the rate of glycolysis in human CD14&lt;sup&gt;+&lt;/sup&gt;CD16&lt;sup&gt;− &lt;/sup&gt;monocytes. Inhibition of glycolysis with 2-deoxy-D-glucose blunted LPS-induced activation and adhesion of monocytes. Mechanistically, we found that increased glycolysis was regulated by mTOR-induced glucose transporter (GLUT)-1. Furthermore, enhanced glycolysis increased accumulation of reactive oxygen species (ROS) and activation of p38 MAPK, which lead to activation and adhesion of monocytes. These findings reveal that glycolytic metabolism is critical for the activation of CD14&lt;sup&gt;+&lt;/sup&gt;CD16&lt;sup&gt;−&lt;/sup&gt; monocytes and contributes to our understanding of the interplay between metabolic substrate preference and immune cell function.
Expression of bcl-2 and the progression of human and rodent prostatic cancers. (1996)

The frequency of bcl-2 protein expression was evaluated using immunocytochemical staining during the progression of human and rat prostate cancer from an androgen-sensitive nonmetastatic to an androgen-independent metastatic phenotype. Previous studies (A. S. Shabaik et al., J. Urol. Pathol., 3: 17-27, 1995) demonstrated that 0 of 20 high-grade prostatic intraepithelial neoplasias and only 3 (7%) of 41 pathologically localized stage B human prostatic cancers had detectable bcl-2 staining. In the present study, 5 (17%) of 30 lymph node metastases from pathologically disseminated D1 disease and 14 (52%) of 27 bone metastases from pathologically disseminated D2 disease expressed detectable bcl-2 protein. These data demonstrate that there is a statistically significant (P < 0.05) association between expression of bcl-2 and the progression of human prostatic cancer cells to a metastatic phenotype. Such bcl-2 expression is not absolutely required, however, for either androgen independence or metastatic ability by human prostatic cancer cells. Likewise, within a series of eight distinct Dunning R3327 rat prostatic cancer sublines, which differ widely in their progressional state, there is also a significant association (P < 0. 05) between bcl-2 expression and progression (four of six androgen-independent rat sublines expressed bcl-2 protein). Again in this rodent system, bcl-2 expression is not an absolute requirement for either androgen independence or metastatic ability. For example, the androgen-independent highly metastatic Dunning AT-3 subline, while expressing bax protein, does not express bcl-2 protein. If such AT-3 cells are genetically engineered to express bcl-2, these expressing cells are now cross-resistant to a variety of mechanistically diverse noxious insults (e.g., viral infection or exposure to antimetabolites, alkylating agents, or agents which elevate the intracellular free Ca2+). The ability of bcl-2 to inhibit the programmed death of AT-3 cells induced by these agents involves a late step in the death process, since the early induction of expression of a series of genes associated with apoptosis is not impaired by bcl-2 expression. These data demonstrate that the development of androgen independence and/or metastatic ability can be associated with the expression of bcl-2 protein but that bcl-2-independent mechanisms also exist for such progression.
Mechanisms to Suppress ILC2-induced Airway Inflammation (2016)

Abstract Epithelial cell–derived cytokines such as IL-33 and IL-25 activate group 2 innate lymphoid cells (ILC2s), which are known to be important sources of type 2 cytokines such as IL-5 and IL-13 in a variety of asthma mouse models. Recently, human studies have also reported the involvement of ILC2s in asthma, as ILC2s are increased in peripheral blood and bronchoalveolar lavage fluid in patients with asthma. Compared with positive regulators such as IL-25 and IL-33, the mechanisms to suppress the ILC2s-induced inflammation remain unclear. Because ILC2s express various cytokine receptors, the function of ILC2s would likely be influenced by cytokines present around ILC2s in the lungs. We reported that IL-2, IL-7, and thymic stromal lymphopoietin (TSLP) induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) and promoted the proliferation of ILC2s and type 2 cytokine production when combined with IL-33. TSLP enhanced the expression of Bcl-xL, an antiapoptotic molecule, and caused corticosteroid-resistant airway inflammation via ILC2s in mice. Furthermore, pimozide, a STAT5 inhibitor, counteracted the TSLP-induced corticosteroid resistance and suppressed airway inflammation. As a negative regulator, we have found that IFN-γ and IL-27 suppressed the proliferation and type 2 cytokine production of ILC2s in vitro and in vivo. Interestingly, ILC2s-induced eosinophilic inflammation was more severe in IFN-γ receptor–deficient mice than in control mice. These findings suggest the importance of environmental cytokines for the regulation of ILC2s, and this would lead to a new approach to control airway inflammation in asthma.
MEDIPLEX: A phase 1 study of durvalumab (D) combined with pexidartinib (P) in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). (2019)

2579 Background: Targeting tumor associated macrophages is an emerging strategy to increase the responsiveness of PDAC and CRC to anti-PD(L)1. Pexidartinib (P) is an orally active, small-molecule kinase inhibitor that targets the colony-stimulating factor-1 receptor (CSF1R) on macrophages. Methods: Adult pts with advanced/ metastatic PDAC or CRC were treated with a fixed dose of D (1500mg q4w, IV) and ascending doses of P (400, 600, 800 and 1000mg/d, orally). Dose escalation was conducted according to a Likelihood Continual Reassessment Method with a 28-day window to evaluate dose-limiting toxicity (DLT), a stopping rule advised dose escalation termination in case of a high probability ( &gt; 90%) for the next 6 pts to be assigned to the same dose. Following the determination of RP2D, 14 pts with PDAC and 14 pts with CRC who consented to serial tumor biopsies were enrolled in expansion cohorts to assess preliminary anti-tumor activity and biomarkers. Results: 19 pts (12M, 7F, median age, 56 y [range, 43-76y]) were enrolled in 4 dose escalation cohorts (P 400, 600 and 800mg/d: 3 pts each and P 1000mg/d: 10 pts). Pharmacokinetic analysis showed dose-dependent increase in the exposure of P from 400 to 1000 mg. Two DLTs (AST/ALT elevations including one with bilirubin increase) were seen at dose level P 1000mg/d. The most frequent ( &gt; 2pts) related (to either D, P or both) AEs were: fatigue, maculopapular rash/pruritus/dry skin, hair color changes, anorexia, edema (periorbital, limbs or face), AST/ALT increases, bilirubin increases, nausea, vomiting and diarrhea. The most frequent (≥2pts) Grade ≥ 3 AEs related to P were: AST/ALT increase, ALP increase, neutrophil or white blood cell count decrease, and fatigue. Clinical benefit rate at 2 months was 21% (4 SD /19pts), 2 pts with MSI-H CRC had SD for more than 6 months including 1 pt still receiving single agent D after &gt; 18 months. The RP2D for the combination was P 800mg/d + D 1500mg q4w. Enrolment in the expansion cohorts was completed in January 2019. Conclusions: Toxicity was consistent with the expected profiles of the individual drugs and no unexpected events were seen with the combination. Updated data will be presented at the meeting. Clinical trial information: NCT02777710.
Hydrogen production from biodiesel industry waste by using a co-culture of Enterobacter aerogenes and Clostridium butyricum (2016)

Valorization of crude glycerol (CG), a waste of biodiesel production process, was investigated for increased hydrogen production by co-culture system using Enterobacter aerogenes NRRL B-407 and Clostridium butyricum NRRL B-41122. The ability of E. aerogenes was evaluated as a replacement of expensive reducing agent to maintain anaerobic conditions for the growth of C. butyricum. The co-culture resulted in increased hydrogen production, reaching a maximum of 19.46 ± 0.95 mmol-H2/L-medium in comparison to monoculture of E. aerogenes (15.64 ± 0.47) and C. butyricum (17.44 ± 0.38) in the presence of reducing agent. The effect of inoculum ratio was investigated and hydrogen yield was 0.95 mmol-H2/mol-glycerol at 1:11 inoculum ratio with more than 85% of substrate utilization was comparable to other mixed and co-culture studies. In addition to hydrogen, value added by-products such as 1,3-propandiol, acetic acid, butyric acid and ethanol have also been produced. Co-culture indicated the possibility of valorization of CG as a stable functional consortium with higher conversion efficiency for increased hydrogen along with high value by-product production. Additionally, the study provided the evidence of medium composition controlled metabolic pathway shift during CG bioconversion. Valorization of low cost CG with efficient co-culture of hydrogen production can aid biodiesel in-house energy source.
Supplementary Figure Legends from Metalloprotease-Mediated Tumor Cell Shedding of B7-H6, the Ligand of the Natural Killer Cell–Activating Receptor NKp30 (2023)

&lt;p&gt;PDF file - 70KB&lt;/p&gt;
PD-118057 contacts the pore helix of hERG1 channels to attenuate inactivation and enhance K + conductance (2009)

Human ether-a-go-go-related gene 1 (hERG1) K(+) channels mediate repolarization of cardiac action potentials. Unintended block of hERG1 channels by some drugs can prolong the QT interval and induce arrhythmia. Recently, hERG1 channel agonists were discovered and, based on their mechanisms of action can be classified into two types. RPR260243 [(3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5 trifluorophenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid], a type 1 agonist, binds to residues located near the intracellular end of S5 and S6 transmembrane segments and activates hERG1 channels by a dual mechanism of slowed deactivation and attenuated P-type inactivation. As defined here, type 2 agonists such as PD-118057 [2-(4-[2-(3,4-dichloro-phenyl)-ethyl]-phenylamino)-benzoic acid] attenuate inactivation but do not slow deactivation. At 10 muM, PD-118057 shifted the half-point for inactivation of wild-type hERG1 channels by +19 mV and increased peak outward current by 136%. Scanning mutagenesis and functional characterization of 44 mutant channels expressed in Xenopus oocytes was used to identify the major structural determinants of the binding site for PD-118057. Single mutations of residues in the pore helix (F619) or the S6 segment (L646) of hERG1 eliminated agonist activity. Mutation of a nearby residues in the S6 segment (C643, M645) enhanced drug activity, presumably by reducing steric hindrance for drug binding. Molecular modeling indicates that PD-118057 binds to a hydrophobic pocket formed by L646 of one hERG1 subunit and F619 of an adjacent subunit. We conclude that direct interaction of PD-118057 with the pore helix attenuates fast P-type inactivation and increases open probability of hERG1 channels.
Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity (2017)

An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% (<i>n</i> = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden (<i>n</i> = 42), a higher proportion of weight loss (<i>n</i> = 37), or cough (<i>n</i> = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients.
Novel N-Substituted 3-Aryl-4-(diethoxyphosphoryl)azetidin-2-ones as Antibiotic Enhancers and Antiviral Agents in Search for a Successful Treatment of Complex Infections (2021)

A novel series of N-substituted <i>cis</i>- and <i>trans</i>-3-aryl-4-(diethoxyphosphoryl)azetidin-2-ones were synthesized by the Kinugasa reaction of N-methyl- or N-benzyl-(diethyoxyphosphoryl)nitrone and selected aryl alkynes. Stereochemistry of diastereoisomeric adducts was established based on vicinal H3-H4 coupling constants in azetidin-2-one ring. All the obtained azetidin-2-ones were evaluated for the antiviral activity against a broad range of DNA and RNA viruses. Azetidin-2-one <i>trans</i>-<b>11f</b> showed moderate inhibitory activity against human coronavirus (229E) with EC<sub>50</sub> = 45 µM. The other isomer <i>cis</i>-<b>11f</b> was active against influenza A virus H1N1 subtype (EC<sub>50</sub> = 12 µM by visual CPE score; EC<sub>50</sub> = 8.3 µM by TMS score; MCC > 100 µM, CC<sub>50</sub> = 39.9 µM). Several azetidin-2-ones <b>10</b> and <b>11</b> were tested for their cytostatic activity toward nine cancerous cell lines and several of them appeared slightly active for Capan-1, Hap1 and HCT-116 cells values of IC<sub>50</sub> in the range 14.5-97.9 µM. Compound <i>trans</i>-<b>11f</b> was identified as adjuvant of oxacillin with significant ability to enhance the efficacy of this antibiotic toward the highly resistant <i>S. aureus</i> strain HEMSA 5. Docking and molecular dynamics simulations showed that enantiomer (3<i>R</i>,4<i>S</i>)-<b>11f</b> can be responsible for the promising activity due to the potency in displacing oxacillin at β-lactamase, thus protecting the antibiotic from undesirable biotransformation.
Diabetic Retinopathy and Macular Edema Quality-of-Life Item Banks: Development and Initial Evaluation Using Computerized Adaptive Testing (2017)

Purpose: The purpose of this study was to assess the psychometric properties of diabetic retinopathy (DR) and diabetic macular edema (DME) quality-of-life (QoL) item banks and determine the utility of the final calibrated item banks by simulating a computerized adaptive testing (CAT) application. Methods: In this clinical, cross-sectional study, 514 participants with DR/DME (mean age ± SD, 60.4 ± 12.6 years; 64% male) answered 314 items grouped under nine QoL item pools: Visual Symptoms (SY); Ocular Comfort Symptoms (OS); Activity Limitation (AL); Mobility (MB); Emotional (EM); Health Concerns (HC); Social (SC); Convenience (CV); and Economic (EC). The psychometric properties of the item pools were assessed using Rasch analysis, and CAT simulations determined the average number of items administered at high and moderate precision levels. Results: The SY, MB, EM, and HC item pools required minor amendments, mainly involving removal of six poorly worded, highly misfitting items. AL and CV required substantial modification to resolve multidimensionality, which resulted in two new item banks: Driving (DV) and Lighting (LT). Due to unresolvable psychometric issues, the OS, SC, and EC item pools were not pursued further. This iterative process resulted in eight operational item banks that underwent CAT simulations. Correlations between CAT and the full item banks were high (range, 0.88–0.99). On average, only 3.6 and 7.2 items were required to gain measurement at moderate and high precision, respectively. Conclusions: Our eight psychometrically robust and efficient DR/DME item banks will enable researchers and clinicians to accurately assess the impact and effectiveness of treatment therapies for DR/DME in all areas of QoL.
An H.264 full HD 60i double speed encoder IP supporting both MBAFF and Field-Pic structure (2011)

HD video sequences are widely used in today's multimedia systems and many of these are encoded with H.264 codec. However, it is still challenging to develop a high-performance H.264 encoder because the H.264 encoding process needs a large amount of computations and memory accesses. In this paper, a novel H.264 encoder is described. This encoder can encode video sequences of full HD 60i at double speed. Both MBAFF and Field-Pic structure are supported as coding tool for interlaced video sequences. The memory bandwidths are reduced by using a hierarchical motion estimation method and a pipeline configuration with consideration of MBAFF. The encoder is implemented with 1637 K logic gates and 336.5 KB on-chip SRAM in the 65 nm CMOS technology.
Studies on Delayed Hypersensitivity to Protein Antigen: Antigen‐specific Suppression of Delayed Hypersensitivity by Chemically Modified Antigen (1979)

Abstract An extensively modified protein antigen (methylated bacterial α‐amylase, M‐BαA) which was neither reactive with anti‐BαA antibody nor able to induce a humoral anti‐BαA response, retained the ability to prime native BαA‐specific T cells which were responsible for the enhanced anti‐BαA response to subsequent immunization with BαA and delayed hypersensitivity (DH). The splenic T cell‐rich fraction from mice primed with M‐BαA collaborated with a native BαA‐primed B cell‐rich fraction to give a good adoptive IgG anti‐BαA response in syngeneic irradiated mice, whereas M‐BαA‐primed B cell fractions failed to cooperate with native BαA‐primed T cell fractions. Splenic T cells from mice given a subcutaneous (s.c.) injection of M‐BαA in complete Freund's adjuvant (CFA) exhibited DH in syngeneic cyclophosphamide‐treated mice. In the present study, native and methylated BαA were tested for their ability to generate suppressor T cells capable of inhibiting the development of DH. An intraperitoneal (i.p.) injection of either native or methylated BαA in incomplete Freund's adjuvant (IFA) interferred with the development of DH to M‐BαA by an s.c. injection of the same antigen in CFA. Transfer of spleen cells from mice given an i.p. injection of either of these antigens 5 days previously, suppressed antigen‐specifically induction and expression of DH in the syngeneic recipient mice. The suppressive activity was sensitive to treatment with anti‐θ antiserum plus complement. These results indicate that the early phase of inhibition of DH after an i.p. injection is in part mediated by suppressor T cells and that M‐BαA cross‐reacts with native BαA at the suppressor T cell level as well as the level of effector T cells in DH.
High-bandwidth data memory systems for superscalar processors (1991)

article Free Access Share on High-bandwidth data memory systems for superscalar processors Authors: Gurindar S. Sohi View Profile , Manoj Franklin View Profile Authors Info & Claims ACM SIGOPS Operating Systems ReviewVolume 25Issue Special IssueApr. 1991 pp 53–62https://doi.org/10.1145/106974.106980Published:01 April 1991Publication History 196citation1,396DownloadsMetricsTotal Citations196Total Downloads1,396Last 12 Months79Last 6 weeks8 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
ChemInform Abstract: CARBON DIFFUSIVITY IN MOLYBDENUM CARBIDE (MO2C)FROM 800 TO 1000°C (1985)

Abstract Der Diffusionskoeffizient von C in Mo 2 C wird aus der Kinetik der Carbidbildung bestimmt.
A Dynamic Semi-Analytic Channel-to-Channel Model of Two-Phase Water Distribution for a Unit Fuel Cell (2009)

The critical task of controlling the water accumulation within the gas diffusion layer (GDL) and the channels of a polymer-electrolyte-membrane (PEM) fuel cell is shown to benefit from a partial-differential-equation (PDE) approach. Starting from first principles, a model of a fuel cell is represented as a boundary value problem for a set of three coupled nonlinear second-order PDEs for mass transport across the GDL of each electrode. These three PDEs are approximated, with justification founded in linear systems theory and a time-scale decomposition approach, by a semianalytic model that requires less than one-third the number of states to be numerically integrated. A set of numerical transient, analytic transient, and analytic steady-state solutions for the semianalytic model are presented, and an experimental verification of the cell voltage prediction due to liquid-water accumulation is demonstrated. The semianalytic model derived and the associated analysis represent our main contribution for which future expansion of along-the-channel dynamics and statistical consideration of cell-to-cell variations can be implemented for application to control, estimation, and diagnostic algorithms.
The Effect of Theophylline on Glucose and Fluid Transport across the Rat Jejunum (1976)

Conference Article| April 01 1976 The Effect of Theophylline on Glucose and Fluid Transport across the Rat Jejunum HENRY J. LEESE; HENRY J. LEESE 1Department of Biology, University of York, York YO1 5DD, U.K. Search for other works by this author on: This Site PubMed Google Scholar JAINE PRENDERGAST; JAINE PRENDERGAST 2Department of Biology, University of York, York YO1 5DD, U.K. Search for other works by this author on: This Site PubMed Google Scholar BARBARA S. READ BARBARA S. READ 3Department of Biology, University of York, York YO1 5DD, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1976) 4 (2): 272–274. https://doi.org/10.1042/bst0040272 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation HENRY J. LEESE, JAINE PRENDERGAST, BARBARA S. READ; The Effect of Theophylline on Glucose and Fluid Transport across the Rat Jejunum. Biochem Soc Trans 1 April 1976; 4 (2): 272–274. doi: https://doi.org/10.1042/bst0040272 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1976 Biochemical Society1976 Article PDF first page preview Close Modal You do not currently have access to this content.