gebhart/patrepeval huggingface dataset:
A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction in Murine Polymicrobial Sepsis (2020)

Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. Peptide-based therapeutics are an alternative drug modality that provide a rapid pharmacokinetic profile, reducing the incidence of precipitating irAEs. We recently reported that the potent, peptide-based PD-1 checkpoint antagonist, LD01, improves T-cell responses. The goal of the current study was to determine whether LD01 treatment improved survival, bacterial clearance, and host immunity in the cecal-ligation and puncture (CLP)-induced murine polymicrobial sepsis model. LD01 treatment of CLP-induced sepsis significantly enhanced survival and decreased bacterial burden. Altered survival was associated with improved macrophage phagocytic activity and T-cell production of interferon-γ. Further, myeloperoxidase levels and esterase-positive cells were significantly reduced in LD01-treated mice. Taken together, these data establish that LD01 modulates host immunity and is a viable therapeutic candidate for alleviating immunosuppression that characterizes sepsis and other infectious diseases.
The Antimicrobial Efficacy of Hypoxia Mimicking Cobalt Oxide Doped Phosphate-Based Glasses against Clinically Relevant Gram Positive, Gram Negative Bacteria and a Fungal Strain (2018)

Bioactive phosphate glasses are of considerable interest for a range of soft and hard tissue engineering applications. The glasses are degradable and can release biologically important ions in a controlled manner. The glasses can also potentially be used as an antimicrobial delivery system. In the given study, novel cobalt-doped phosphate-based glasses, (P<sub>2</sub>O<sub>5</sub>)<sub>50</sub>(Na<sub>2</sub>O)<sub>20</sub>(CaO)<sub>30-<i>x</i></sub>(CoO)<sub><i>x</i></sub> where 0 ≤ <i>x</i> (mol %) ≤ 10, were manufactured and characterized. As the cobalt oxide concentration increased, the rate of dissolution was observed to decrease. The antimicrobial potential of the glasses was studied using direct and indirect contact methods against both <i>Escherichia coli</i> (NCTC 10538) <i>Staphylococcus aureus</i> (ATCC 6538) and <i>Candida albicans</i> (ATCC 76615). The results showed strong, time dependent, and strain specific antimicrobial activity of the glasses against microorganisms when in direct contact. Antimicrobial activity (<i>R</i>) ≥ 2 was observed within 2 h against <i>Escherichia coli</i>, whereas a similar effect was achieved in 6 h against <i>Staphylococcus aureus</i> and <i>Candida albicans</i>. However, when in indirect contact, the dissolution products from the bioactive glasses failed to show an antimicrobial effect. Following direct exposure to the glasses for 7 days, osteoblast-like SAOS-2 cells showed a 5-fold increase in VEGF mRNA while THP-1 monocytic cells showed a 4-fold increase in VEGF mRNA expression when exposed to 10% CoO-doped glass compared with the cobalt free control glass. Endothelial cells stimulated with conditioned medium taken from cell cultures of THP-1 monocytes exposed to 10% CoO doped glass showed clear tubelike structure (blood vessel) formation after 4 h.
In Vitro Activity of Rifabutin and Rifampin against Antibiotic-Resistant Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae (2021)

We recently reported that the antimicrobial activity of rifabutin against Acinetobacter baumannii is best modeled by the use of RPMI for <i>in vitro</i> susceptibility testing. Here, we define the effects of medium on the susceptibility and frequency of resistance emergence in a panel of A. baumannii, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa clinical isolates. Only A. baumannii was hypersusceptible to rifabutin <i>in vitro</i> and <i>in vivo</i> using a Galleria mellonella infection model. <i>In vitro</i>, the frequency of resistance emergence was greater when the bacteria were selected on RPMI versus tryptic soy agar (TSA) or Mueller-Hinton II (MHII) agar plates. However, the frequency of resistance emergence was lower <i>in vivo</i> than in the RPMI <i>in vitro</i> condition. <b>IMPORTANCE</b> Rifabutin has been recently described as a potential adjunctive therapy for antibiotic-resistant A. baumannii infections due to hypersensitivity in iron-depleted media, which may more closely mimic an <i>in vivo</i> environment. Here, we report that this hyperactivity is specific for A. baumannii, rather than being a general effect for other pathogens.
Distortion matrix concept for deep imaging in optical coherence tomography (2021)

In optical imaging, light propagation is affected by the medium inhomogeneities. Adaptive optics has been employed to compensate for sample-induced aberrations but the field-of-view is often limited to a single isoplanatic patch. Here, we propose a noninvasive approach based on the distortion matrix concept. This matrix basically connects any focusing point with the distorted part of its wave-front in reflection. Its time reversal and entropy analysis allow to correct for high-order aberrations over multiple isoplanatic areas. We demonstrate a Strehl ratio enhancement up to 2500 and a diffraction-limited resolution until a depth of ten scattering mean free paths through an opaque cornea.
Byzantine agreement in constant expected time (1985)

We present a novel cryptographic algorithm for Byzantine agreement in a network with l=O(n) faulty processors and in the most adversarial setting. Our algorithm requires, once and for all, O(t) rounds of preprocessing. Afterwards it allows us to reach each individual Byzantine agreement in constant expected time. Our solution does not make use of any trusted party.
Power-Dependent Attenuation And Power Transfer Effects In Optical Nonlinear Waveguides (1987)

We present a theoretical analysis of some new properties of TE waves in waveguides consisting of an optical linear thin film deposited onto the surface of a substrate exhibiting both positive and negative nonlinearities at two different wavelengths. The semi-infinite substrate is characterized by an intensity dependent refractive index ns= nso+ n2S, where S is the local power density and n2 is the nonlinear coefficient. The data set used in our calculations concerns a particular structure consisting of a film of Corning 7059 glass deposited onto the surface of a Schott GG 495 glass filter. Color filters made with glasses doped with crystallites of the mixed semiconductor CdSxSel_x exhibit third order nonlinearity with n2 of about 10-14m2/W. It is also known1 that the sign of the nonlinearity in these glasses changes in the vicinity of a band gap. The material parameters for positive nonlinearity at &lambda; = 0.4765 pm and negative nonlinearity at &lambda;= 0.4880 mm are the following: Corning glass film refractive indices nf= 1.597 and 1.595; substrate refractive indices nse 1.573 and 1.569; imaginary parts of dielectric constant of the substrate c&quot; = 2.8 x 10 and 6.5 x 10-5 respectively.
Measuring lifeline emergency response using temporal network models (2014)

used in literature to analyze infrastructure interdependencies within the social, political and economic sphere although it is comprehensive, it is not proper to describe the infrastructures emergency management. During an emergency, the response phase is very condensed in time, and the failures that occur are usually amplified through cascading effects in the long-term period. Because of these peculiarities, interdependencies need to be modeled also taking into account the effect of the time dimension. The methodology proposed in this paper is based on a modified version of the Input-output Inoperability Model which has been applied to an emergency response situation. The lifelines are modeled using graph theory, while the perturbations, representing a natural or man-made disaster, are applied to the elements of the network and propagated following predefined rules. The cascading effect between interdependent networks has been simulated using a spatial multilayer approach, while the use of an adjacency tensor allows taking into account the temporal dimensions and its effects. Finally, the numerical results of the simulations with the proposed model give the probabilities of failure for each node of the system
Electronic spectra of dinuclear cobalt carbonyl complexes (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectronic spectra of dinuclear cobalt carbonyl complexesHarmon B. Abrahamson, Claude C. Frazier, David S. Ginley, Harry B. Gray, Jane. Lilienthal, David R. Tyler, and Mark S. WrightonCite this: Inorg. Chem. 1977, 16, 6, 1554–1556Publication Date (Print):June 1, 1977Publication History Published online1 May 2002Published inissue 1 June 1977https://pubs.acs.org/doi/10.1021/ic50172a062https://doi.org/10.1021/ic50172a062research-articleACS PublicationsRequest reuse permissionsArticle Views231Altmetric-Citations52LEARN 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
Self-focusing and optical damage in Cr:LiSAF and Cr:LiCAF (1993)

The Cr-doped Colquiriites, Cr:LiSAF, and Cr:LiCAF, are new solid-state laser materials with high gain cross-sections, very large gain bandwidths, and relatively long fluorescence lifetimes (approximately 100 microsecond(s) ) making them amenable to flashlamp pumping. These laser materials are capable of providing tunable high power laser radiation in the near IR and are very suitable for ultrashort pulse generation and amplification. For these high power laser applications, however, a knowledge of the optical damage thresholds and mechanisms in these materials is essential. We present results of measurements of bulk damage thresholds, of basic material properties, and of the nonlinear refractive indices of these materials. We have also observed optical damage due to self-focusing in a femtosecond chirped pulse Cr:LiSAF regenerative amplifier. We discuss these observations and give an estimate of the critical power of self-focusing for these materials.
Compact Catalytic Membrane Reactors for Reforming Applications Based on an IntegratedSandwichedCatalyst Layer (2011)

This chapter contains sections titled: Introduction Experimental Results and Discussion Conclusion References
Biotech Application of Exopolysaccharides from Curvularia brachyspora: Optimization of Production, Structural Characterization, and Biological Activity (2023)

<i>C. brachyspora</i>, a widespread dematiaceous fungus, was evaluated in this study to optimize the production of exopolysaccharides (CB-EPS). Optimization was performed using response surface methodology, and the best production yielded 75.05% of total sugar at pH 7.4, with 0.1% urea, after 197 h. The obtained CB-EPS showed typical signals of polysaccharides, which was confirmed by FT-IR and NMR. The HPSEC analysis indicated a polydisperse polymer, showing a non-uniform peak, with an average molar mass (M<i><sub>w</sub></i>) of 24,470 g/mol. The major monosaccharide was glucose (63.9 Mol%), followed by mannose (19.7 Mol%), and galactose (16.4 Mol%). Methylation analysis encountered derivatives that indicated the presence of a β-d-glucan and a highly branched glucogalactomannan. CB-EPS was tested on murine macrophages to verify its immunoactivity, and the treated cells were able to produce TNF-α, IL-6, and IL-10. However, the cells did not produce superoxide anions or nitric oxide nor stimulated phagocytosis. The results demonstrated an indirect antimicrobial activity of macrophages by stimulating cytokines, showing another biotech applicability for the exopolysaccharides produced by <i>C. brachyspora</i>.
ChemInform Abstract: SIMPLE AND CLEAR PROCESS FOR THE JOINING OF METAL‐METAL BONDS. METAL CARBONYL SYNTHESES. 6 (1981)

Abstract Einwirkung von Tetrafluoroborsäure auf den Rh‐Komplex (I) ergibt in einer Fällungsreaktion das sa1zartige, thermisch bis ca. 85°C stabile, außerordentlich baseempfindliches u‐Hydrido‐Komplexsalz (II).
Prediction range estimation from noisy Raman spectra with robust optimization (2010)

Inferences need to be drawn in biological systems using experimental multivariate data. The number of samples collected in many such experiments is small, and the data are noisy. We present and study the performance of a robust optimization (RO) model for such situations. We adapt this model to generate a minimum and a maximum estimation of analyte concentration for a given sample, producing a prediction range. The calibration model was applied to sets of Raman spectra. In particular we used normal Raman measurements of pyridine/deuterated pyridine mixtures and spectra from a more complex glucose detection system based on surface-enhanced Raman spectroscopy. The results from the RO model were compared with prediction intervals estimated from partial least squares (PLS) method. We find that the RO prediction ranges included the actual concentration value of the sample more consistently than the 99% prediction intervals built with PLS methods.
P393 Patient-reported symptom measures differ in their association with mucosal healing in adults with moderately to severely active ulcerative colitis: Results from ULTRA 1 and 2 (2014)

68% had inflammatory (B1) disease behavior; 30% had prior resections. Over 7 years, 117 pts completed, while 478 discontinued (36% due to AEs; 28% due to pt decision; 17% due to no improvement/disease deterioration). Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% during years 1 7, respectively. Over 71% of pts were exposed to CZP for >1 year; the average number of CZP injections was 41. No new safety signals were identified during this study. The most common AE was CD exacerbation (30%); most common OI was herpes simplex (3.4%). The observed annual remission rates ranged from 68% 76% (Year 1 to 7, table). The remission rates analyzed by LOCF and NRI methods were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7, respectively. FC levels had no trends toward change; CRP levels were relatively stable. The geometric mean CZP plasma concentrations ranged from 6 10 ug/mL up to year 6; CZP concentrations were typically lower in pts who were anti-CZP antibody positive vs. negative throughout the study (e.g. 3μg/ml vs. 9μg/ml at Wk 54, 3μg/ml vs. 10μg/ml at Wk 210, respectively). Conclusions: The P3 study demonstrates that the long-term safety of CZP is consistent with short-term studies.[1, 2] Additionally, the observed rates of clinical remission were sustainable for 7 years. PRECiSE3 Remission Rates Over 7 Years, observed cases
TVGN-489: A novel approach for the production of SARS-CoV-2-specific cytotoxic T lymphocytes to treat COVID-19 (2021)

Abstract SARS-COV-2 (COVID-19) has resulted in over 2 million deaths. While vaccination is expected to decrease mortality, there remains a need for curative therapies for active infections. Uncertainties regarding the duration of post-vaccination immunity and the rapidity of mutational evolution by this virus suggest that it is unwise to rely on preventative measures alone. Dysregulation of endogenous cellular immunity has been implicated in the failure to control COVID-19 infections suggesting that allogeneic T cell therapy using nature’s curative approach to viral infections could successfully be applied to vulnerable patients. Allogeneic virus-specific cytotoxic T lymphocytes (CTLs) have a long track record of safety and efficacy in treating viral infections occurring after allogeneic stem cell transplantation. We hypothesize that this approach can be applied to the treatment of Covid-19. Covid-19 specific CTLs were produced by priming and enriching T cells from convalescent patients using COVID-19 peptides predicted or demonstrated to bind to specific HLA alleles. Utilizing the globally common HLA-A*02:01 allele as the restriction element, 7 peptides from 4 COVID-19 gene/ORF products were identified and used as a pool for serial restimulation and enrichment on a peptide pulsed, HLA-A*02:01 antigen presenting cell monolayer. This preclinical effort produced CTLs of high purity (&amp;gt;95% CD3+/CD8+, &amp;gt;60% positive by tetramer staining) and potency (60% lysis of peptide pulsed targets at an effector to target ratio of 3:1) in sufficient quantities for clinical application. Trials using these TVGN-489 CTLs and those produced with other SARS-COV-2 peptides and HLA restriction elements will hopefully be launched shortly.
Quantitative Analysis of Film Coating in a Fluidized Bed Process by In-Line NIR Spectrometry and Multivariate Batch Calibration (2000)

A method is described which enables real-time analysis of film coating on pharmaceutical pellets during an industrial manufacturing process. Measurements were conducted on the solid particulate material by near-infrared (NIR) spectrometry utilizing a diffuse reflectance fiber-optic probe positioned inside a fluidized bed process vessel. Time series of NIR spectra from 11 batches generated a three-way data matrix that was unfolded and modeled by partial least squares (PLS) in a multivariate batch calibration. The process conditions were deliberately varied according to an experimental design. This yielded good predictability of the coating thickness with a best model fit, R2 = 0.97, for one PLS-projection, and a root-mean-square error of calibration = 2.2 microm (range tested 0-50 microm). The regression vector was shown to be highly influenced by responses that are both direct (aliphatic C-H stretch overtones) and indirect (aromatic C-H stretch overtones), from film component and core material, respectively. The impact of different data pre-treatment methods on the normalization of the regression vector is reported. Justification of the process calibration approach is emphasized by good correlation between values predicted from NIR data and reference image analysis data on dissected pellets and a theoretical nonlinear coating thickness growth model. General aspects of in-line NIR on solids and multivariate batch calibration are discussed.
On the sojourn time of a batch in the $M^{[X]}/M/1$ Processor Sharing\n Queue (2020)

In this paper, we analyze the sojourn of an entire batch in a processor\nsharing $M^{[X]}/M/1$ processor queue, where geometrically distributed batches\narrive according to a Poisson process and jobs require exponential service\ntimes. By conditioning on the number of jobs in the systems and the number of\njobs in a tagged batch, we establish recurrence relations between conditional\nsojourn times, which subsequently allow us to derive a partial differential\nequation for an associated bivariate generating function. This equation\ninvolves an unknown generating function, whose coefficients can be computed by\nsolving an infinite lower triangular linear system. Once this unknown function\nis determined, we compute the Laplace transform and the mean value of the\nsojourn time of a batch in the system.\n
Hyperactive mTOR in Lung Mesenchyme Induces Endothelial Dysfunction and Pulmonary Vascular Remodeling (2022)

Abstract Pulmonary vascular remodeling is the key structural abnormality in pulmonary hypertension (PH). Mechanistic target of rapamycin (mTOR) has long been suspected to play a role in the development of pulmonary vascular remodeling. However, underlying cellular and molecular mechanisms leading to this pathophysiological condition remain incompletely understood. To elucidate the crosstalk between lung mesenchyme with activated mTOR and endothelial cells (ECs), we focused on a monogenic lung disease, pulmonary lymphangioleiomyomatosis (LAM). LAM is a progressive cystic lung disease caused by a mutational inactivation of tuberous sclerosis complex (TSC1/TSC2), which results in constitutive mTOR activation in mesenchymal LAM cells. ECs derived from LAM lung explants showed increased proliferation, migration, and defective angiogenesis compared to age- and sex-matched ECs from control human lung. In LAM cells, we found increased WNT2 ligand expression. We also identified corresponding Frizzled 4 (FZD) receptors on ECs isolated from distal LAM lung, suggesting cellular crosstalk between LAM cells and ECs. In endothelial-fibroblast cocultures, treatment of normal ECs with WNT2 ligands recapitulated LAM EC phenotype and morphology. We observed transcriptomic upregulation in metabolic, angiogenic and growth pathways in ECs of young mice, while 1-year-old Tsc2 KO mice spontaneously developed pulmonary vascular remodeling with concurrent elevation in right ventricular systolic pressure. Our study demonstrates that LAM cells are not just a pathological mesenchymal cell state but a signaling hub that contributes to dysregulated cellular response in the surrounding vasculature, eventual pulmonary vascular remodeling and PH.
Supplementary Data S1a and S1b from Optimizing precision medicine for breast cancer brain metastases with functional drug response assessment. (2023)

&lt;p&gt;S1a. Breast cancer brain metastases cohort (Group A) selectionS1b. Clinical characteristics of breast cancer brain metastases cohort (Group A)&lt;/p&gt;