gebhart/patrepeval huggingface dataset:
Re-evaluation of P-Chiral, N-Phosphoryl Sulfonamide Brønsted Acids in the Asymmetric Synthesis of 1,2,3,4-Tetrahydroquinoline-2-carboxylate Esters via Biomimetic Transfer Hydrogenation (2023)

Abstract Enantioenriched heterocyclic and rigidified bioisosteres of amino acids are valuable building blocks in drug discovery, particularly in the design of peptidomimetic drugs. The rigidified bioisostere of phenylalanine, 1,2,3,4-tetrahydroquinoline-2-carboxylic acid, is found in several biologically active compounds. However, only a small number of successful methodologies have been reported for its asymmetric synthesis. To develop an environmentally benign and metal-free organocatalytic process for the preparation of this compound, a number of novel P-chiral, N-phosphoryl sulfonamide Brønsted acids were synthesized and evaluated in a biomimetic transfer hydrogenation reaction of quinoline-2-carboxylates to give the (R)-1,2,3,4-tetrahydroquinoline-2-carboxylates.
Engineering antigen-specific T cells for in vivo imaging: A study of the dynamic biological interactions in anti-tumor immunity (2007)

5532A Immunotherapy with adoptive transfer of antigen-specific T cells has anti-tumor activity in melanoma, but questions remain regarding the biology of the T cell responses, especially the kinetics of its anti-tumor effects. We engineered lymphocytes to express a transgenic T cell receptor (TCR) specific to a melanoma antigen and a PET reporter gene to be used in an adoptive transfer model to study TCR transgenic cells targeting melanoma tumors in vivo. A tetracistronic lentiviral vector was engineered to express the alpha and beta chains of a hybrid murine/human TCR specific for the endogenous melanoma antigen tyrosinase (Tyr), along with a modified HSV1-tk with higher affinity for nucleotide analogues (sr39tk) used as PET reporter gene, which was fused to the GFP marker. The transgenes were interspaced with picornavirus-derived highly efficient self-cleaving 2A-like sequences to allow balanced protein expression. The hybrid TCR chains contained murine constant regions and human variable regions specific for human HLA-A2.1, allowing the specific recognition of HLA-A2.1-restricted peptides. Transduction of ex vivo activated splenocytes with concentrated lentivirus stocks (titer range of 1.5-3.2 x 10e8 infection units/ml) demonstrated correct expression of Tyr-specific TCR as assessed by flow-cytometry with anti-Vbeta12 staining and Tyr (368-376) tetramer assays, with transduction efficiency of 12-32% at M.O.I.=15 . The functionality of sr39tk was confirmed with 3H-penciclovir uptake and ganciclovir cell killing assays, demonstrating its use as both PET reporter and suicide gene. The cleavage efficiency of the 2A-like sequences was assessed by immunoblotting, which indicated more than 90% correct cleavage of the protein products. Transduced murine splenocytes stimulated with EL4 murine lymphoma stably transduced with HLA-A2.1/Kb (EL4-A2.1/Kb) pulsed with Tyr (368-376) showed higher IFN-gamma-producing cells in comparison to control cells in an ELISPOT assay (30.4 vs. 1.6 spots/1x10e5 cells, P
Verteporfin- and sodium porfimer-mediated photodynamic therapy enhances pancreatic cancer cell death without activating stromal cells in the microenvironment (2019)

The goal of our study was to determine the susceptibility of different pancreatic cell lines to clinically applicable photodynamic therapy (PDT). The efficacy of PDT of two different commercially available photosensitizers, verteporfin and sodium porfimer, was compared using a panel of four different pancreatic cancer cell lines, PANC-1, BxPC-3, CAPAN-2, and MIA PaCa-2, and an immortalized non-neoplastic pancreatic ductal epithelium cell line, HPNE. The minimum effective concentrations and dose-dependent curves of verteporfin and sodium porfimer on PANC-1 were determined. Since pancreatic cancer is known to have significant stromal components, the effect of PDT on stromal cells was also assessed. To mimic tumor-stroma interaction, a co-culture of primary human fibroblasts or human pancreatic stellate cell (HPSCs) line with PANC-1 was used to test verteporfin-PDT-mediated cell death of PANC-1. Two cytokines (TNF-α and IL-1β) were used for stimulation of primary fibroblasts (derived from human esophageal biopsies) or HPSCs. The increased expression of smooth muscle actin (α-SMA) confirmed the activation of fibroblasts or HPSC upon treatment with TNF-α and IL-1β. Cell death assays showed that both sodium porfimer- and verteporfin-mediated PDT-induced cell death in a dose-dependent manner. However, verteporfin-PDT treatment had a greater efficiency with 60 × lower concentration than sodium porfimer-PDT in the PANC-1 incubated with stimulated fibroblasts or HPSC. Moreover, activation of stromal cells did not affect the treatment of the pancreatic cancer cell lines, suggesting that the effects of PDT are independent of the inflammatory microenvironment found in this two-dimensional culture model of cancers.
The Influence of Lyophilized EmuGel Silica Microspheres on the Physicomechanical Properties, In Vitro Bioactivity and Biodegradation of a Novel Ciprofloxacin-Loaded PCL/PAA Scaffold (2016)

A new composite poly(caprolactone) (PCL) and poly(acrylic acid) (PAA) (PCL:PAA 1:5) scaffold was synthesized via dispersion of PCL particles into a PAA network. Silica microspheres (Si) (2⁻12 μm) were then prepared by a lyophilized micro-emulsion/sol-gel (Emugel) system using varying weight ratios. The model drug ciprofloxacin (CFX) was used for <i>in situ</i> incorporation into the scaffold. The physicochemical and thermal integrity, morphology and porosity of the system was analyzed by X-Ray Diffraction (XRD), Attenuated Total Refelctance Fourier Transform Infrared (ATR-FTIR), Differential Scanning Calorimetry (DSC), SEM, surface area analysis and liquid displacement, respectively. The mechanical properties of the scaffold were measured by textural analysis and <i>in vitro</i> bioactivity, biodegradation and pH variations were evaluated by XRD, FTIR and SEM after immersion in Simulated Body Fluid (SBF). The <i>in vitro</i> and <i>in vivo</i> studies of the prepared scaffold were considered as future aspects for this study. CFX release was determined in phosphate buffer saline (PBS) (pH 7.4; 37 °C). The incorporation of the Si microspheres and CFX into the scaffold was confirmed by XRD, FTIR, DSC and SEM, and the scaffold microstructure was dependent on the concentration of Si microspheres and the presence of CFX. The system displayed enhanced mechanical properties (4.5⁻14.73 MPa), <i>in vitro</i> bioactivity, biodegradation and controlled CFX release. Therefore, the PCL/PAA scaffolds loaded with Si microspheres and CFX with a porosity of up to 87% may be promising for bone tissue engineering.
In vivo assessment of behavioral recovery and circulatory exchange in the peritoneal parabiosis model (2016)

Abstract The sharing of circulation between two animals using a surgical procedure known as parabiosis has created a wealth of information towards our understanding of physiology, most recently in the neuroscience arena. The systemic milieu is a complex reservoir of tissues, immune cells and circulating molecules that is surprisingly not well understood in terms of its communication across organ systems. While the model has been used to probe complex physiological questions for many years, critical parameters of recovery and exchange kinetics remain incompletely characterized, limiting the ability to design experiments and interpret results for complex questions. Here we provide evidence that mice joined by parabiosis gradually recover much physiology relevant to the study of brain function. Specifically, we describe the timecourse for a variety of recovery parameters, including those for general health and metabolism, motor coordination, activity and sleep behavior. Finally, we describe the kinetics of chimerism for several lymphocyte populations as well as the uptake of small molecules into the brains of mice following parabiosis. Our characterization provides an important resource to those attempting to understand the complex interplay between the immune system and the brain as well as other organ systems.
Optimization of the porous structure and polarity of polymethacrylate‐based monolithic capillary columns for the LC‐MS separation of enzymatic digests (2007)

The porous structure as well as the polarity of methacrylate ester-based monolithic stationary phases has been optimized to achieve the separation of various peptides originating from enzymatic digestion. The porous structure, determined by the size of both pores and microglobules, was varied through changes in the composition of porogenic solvents in the polymerization mixture, while the polarity was controlled through the incorporation of butyl, lauryl, or octadecyl methacrylate in the polymer backbone. Both the morphology and the chemistry of the monoliths had a significant effect on the retention and efficiency of the capillary columns. The best resolution of peptidic fragments obtained by digestion of Cytochrome c with trypsin in solution was obtained in a gradient LC-MS mode using a monolithic capillary column of poly(lauryl methacrylate-co-ethylene dimethacrylate) featuring small pores and small microglobules. Raising the temperature from 25 to 60 degrees C enabled separations to be carried out at 40% higher flow rates. Separations carried out at 60 degrees C with a steeper gradient proceeded without loss of performance in half the time required for a comparable separation at room temperature. Our preparation technique affords monolithic columns with excellent column-to-column and run-to-run repeatability of retention times and pressure drops.
Dendritic Cells, Antibodies Reactive with oxLDL, and Inflammation (2011)

Periodontitis appears to promote chronic inflammatory diseases, including atherosclerosis, but relevant mechanisms need clarification. Oral bacteria induce antibodies that bind not only bacteria, but also oxLDL. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans induce remarkable IgG responses that are dominated by IgG2, and IgG2 is IFN-γ-dependent and is promoted by dendritic cells (DCs). LDL-reactive antibodies induced by P. gingivalis and A. actinomycetemcomitans include anti-phosphorylcholine (α-PC) and β2-glycoprotein-1-dependent anticardiolipin (α-CL), and these antibodies may link chronic inflammatory diseases at a mechanistic level. Antibody-mediated uptake of oxLDL or bacteria dramatically enhances DC-IL-12, and DC-IL-12 induces NK-cell-IFN-γ responses that promote Th-1 responses and sustained inflammation. DCs may be derived from monocytes, and this is striking in cultures of aggressive periodontitis (AgP) monocytes, where DC numbers are about double control levels. Moreover, serum α-CL levels in individuals with AgP are frequently elevated, and these antibodies promote atherosclerosis in persons with antiphospholipid syndrome. Elevated serum levels of soluble-intercellular adhesion molecule, soluble-vascular cell adhesion molecule, and soluble-E-selectin are atherosclerosis-associated indicators of vascular inflammation, and these markers are elevated in the subset of AgP patients with high α-CL. We reason that periodontitis patients with elevated antibodies reactive with oxLDL could be a subgroup at high risk for cardiovascular sequelae.
Evaluate of tension-free hernia repair to recurrent inguinal hernia:a report of 32 cases (2009)

Objective To discuss the value of tension-free hernia repair in recurrent inguinal hernia.Methods From 1/1999 to 10/2007,38 patients with recurrent inguinal hernia udrwent reopration clinical were reviewed.The primary surgery had been traditional herniorrhaphy without prothesis in 37 cases(including 18 cases of Bassini、17 cases of Ferguson、2 cases of Mcway) and 1 case of lension-free hernia.Interval from the initial surgery to recurrence was 2months to 15 Years,average 52 months.38 cases with recurrent inguinal hernia were treated lension-free hernia repair including mesh plug-patch in 33 cases and Polypropylene-prolene Hernia System(PHS) in 5 cases.Results All cases were operatied successfully.The average postoperative slay was 8-10 days the the postoperative complications were 4 case of urinary retentions,2 cases of scrotal hydrocrlrs and 1 case of postoperative pain.The follow-up period ranged from 2-14 months and no recurrent was observed.Conclusion Tension-free hernia repair is the therapy of choice patients suffering recurrent inguinal hernia.
Reduktion der kleinen Untereinheit der Ribonucleotid‐Reductase mit Diimid: Beweise für die Bildung eines gemischtvalenten FeIIFeIII‐Zentrums (1991)

Das Dieisen(III)‐Zentrum des Proteins R2 , einer Untereinheit der Ribonucleotid‐Reductase, läßt sich mit Diimid effizient zum gemischtvalenten Fe II Fe III ‐Zustand reduzieren, der EPR‐spektroskopisch nachgewiesen werden kann. Der Vergleich mit den Spektren des gemischtvalenten Zustands von Hämerythrin legt nahe, daß beide Fe‐Atome nur schwach antiferromagnetisch gekoppelt und über eine Hydroxobrücke verbunden sind.
Neuropeptide Y, left ventricular mass and function in patients with end stage renal disease (2003)

Elevated NPY is independently associated with LV concentric hypertrophy and systolic dysfunction in ESRD. It remains to be seen whether these links contribute to the high cardiovascular mortality in these patients.
Absence of central tolerance in Aire-deficient mice synergizes with immune-checkpoint inhibition to enhance antitumor responses (2020)

The endogenous anti-tumor responses are limited in part by the absence of tumor-reactive T cells, an inevitable consequence of thymic central tolerance mechanisms ensuring prevention of autoimmunity. Here we show that tumor rejection induced by immune checkpoint blockade is significantly enhanced in Aire-deficient mice, the epitome of central tolerance breakdown. The observed synergy in tumor rejection extended to different tumor models, was accompanied by increased numbers of activated T cells expressing high levels of Gzma, Gzmb, Perforin, Cxcr3, and increased intratumoural levels of Cxcl9 and Cxcl10 compared to wild-type mice. Consistent with Aire's central role in T cell repertoire selection, single cell TCR sequencing unveiled expansion of several clones with high tumor reactivity. The data suggest that breakdown in central tolerance synergizes with immune checkpoint blockade in enhancing anti-tumor immunity and may serve as a model to unmask novel anti-tumor therapies including anti-tumor TCRs, normally purged during central tolerance.
Interview with Donald E Ingber (2014)

Dr Ingber is a founder of the emerging field of biologically inspired engineering, and at the Wyss Institute, he oversees a multifaceted effort to identify the mechanisms that living organisms use to self-assemble from molecules and cells, and to apply these design principles to develop advanced materials and devices for healthcare and to improve sustainability.In addition, Dr Ingber has made major contributions to mechanobiology, tissue engineering, angiogenesis, systems biology and nanobiotechnology.He was the first to recognize that tensegrity architecture is a fundamental principle that governs molecular self assembly and how living cells self-organize themselves to respond biochemically to mechanical forces.His work on tensegrity has inspired development of DNA self-assembly-based nanotechnologies, and his insights into mechanobiology have led to the creation of shear-activated nanotherapeutics that selectively target clot-busting drugs to sites of vascular occlusion; he also has developed engineered tissues and cancer therapeutics that have entered human clinical trials.
Poster reception---Alef parallel SAT solver for HPC hardware (2006)

Solvers for the Boolean satisfiability problem (SAT) are an enabling technology for a diverse set of applications, including formal verification of both hardware and software, mathematics, and planning. However, solver performance, measured in terms of speed and maximum problem size, is a limiting factor to the application of SAT to real-world problems. We are developing a parallel SAT solver, Alef, to take advantage of HPC hardware.The Alef parallel SAT solver utilizes algorithms and heuristics that improve its performance over existing approaches. We are developing the solver to run well on commercially available HPC hardware. Our analysis shows that our algorithms combined with the low message latency of supercomputers are likely to produce a significant performance improvement over existing solvers in terms of speed and maximum problem size. Our poster will describe the algorithms we are using, illustrate our approach to problem partitioning, and present our performance analysis to date.
Computational Raman spectroscopy of organometallic reaction products in lithium and sodium-based battery systems (2014)

A common approach to understanding surface reaction mechanisms in rechargeable lithium-based battery systems involves spectroscopic characterization of the product mixtures and matching of spectroscopic features to spectra of pure candidate reference compounds. This strategy, however, requires separate chemical synthesis and accurate characterization of potential reference compounds. It also assumes that atomic structures are the same in the actual product mixture as in the reference samples. We propose an alternative approach that uses first-principles computations of spectra of the possible reaction products and by-products present in advanced battery systems. We construct a library of computed Raman spectra for possible products, achieving excellent agreement with reference experimental data, targeting solid-electrolyte interphase in Li-ion cells and discharge products of Li-air cells. However, the solid-state crystalline structure of Li(Na) metal-organic compounds is often not known, making the spectra computations difficult. We develop and apply a novel technique of simplifying spectra calculations by using dimer-like representations of the solid state structures. On the basis of a systematic investigation, we demonstrate that molecular dimers of Li(Na)-based organometallic material provide relevant information about the vibrational properties of many possible solid reaction products. Such an approach should serve as a basis to extend existing spectral libraries of molecular structures relevant for understanding the link between atomic structures and measured spectroscopic data of materials in novel battery systems.
A brain detoxifying enzyme for organophosphorus nerve poisons (2005)

Organophosphorus (OP) insecticides and chemical warfare agents act primarily by inhibiting acetylcholinesterase. There are many secondary targets for OP toxicants as observed for example with the major insecticide chlorpyrifos and its bioactivated metabolite chlorpyrifos oxon (CPO). Therefore, it was surprising that the predominant mouse brain protein labeled in vitro by [(3)H-ethyl]CPO (1 nM) (designated CPO-binding protein or CPO-BP) is not one of these known OP toxicant targets. CPO-BP is a 50-kDa membrane-bound serine hydrolase measured by derivatization with [(3)H]CPO and SDS/PAGE or filtration binding assay. It appears to undergo rapid diethylphosphorylation by [(3)H]CPO followed by either dephosphorylation and reactivation or aging on loss of an ethyl group. CPO and several other OP toxicants potently inhibit CPO-BP in vivo (i.p., 2 h) (50% inhibition at 2-25 mg/kg) and in vitro (50% inhibition at 8-68 nM). Using three chemical labeling reagents, i.e., [(3)H]CPO and the activity-based proteomic probes fluorophosphonate-biotin and fluorophosphonate-rhodamine, mouse brain CPO-BP is identified as serine hydrolase KIAA1363 of unknown function. Brains from KIAA1363(-/-) mice show greatly reduced levels of CPO labeling and hydrolytic metabolism compared to brains from wild-type mice. KIAA1363 therefore is the principal enzyme for metabolizing low levels of CPO in brain and may play a more general role in detoxification of OP nerve poisons.
Synchronization in DMT based VDSL modems (2002)

In digital transceivers, synchronization is a crucial issue in restoring correctly the transmitted data. In Discrete Multi Tone (DMT) systems, the received continuous-time signal is sampled and demodulated using a Fast Fourier Transform (FFT) operating on blocks of samples (DMT symbols). Aligning the DMT symbols with the FFT window should be done correctly. Clock synchronization should be guaranteed. This paper treats the design of a programmable solution for synchronization in DMT based VDSL modems using Texas Instrument processor family TMS320C64x. We present the hardware needed and the cost of the implementation for this function.
Magnetic nonequivalence in 1,2-disubstituted ethanes: An organic experiment in NMR spectroscopy (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMagnetic nonequivalence in 1,2-disubstituted ethanes: An organic experiment in NMR spectroscopyRobert E. Colborn Cite this: J. Chem. Educ. 1990, 67, 5, 438Publication Date (Print):May 1, 1990Publication History Received3 August 2009Published online1 May 1990Published inissue 1 May 1990https://doi.org/10.1021/ed067p438RIGHTS & PERMISSIONSArticle Views173Altmetric-Citations4LEARN 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 InReddit PDF (2 MB) Get e-Alerts Get e-Alerts
900-mW high brightness buried ridge lasers by selective area epitaxy (2002)

A study has been made of high power single lateral mode buried ridge lasers fabricated by selective area epitaxy. Several ridge thicknesses have been evaluated simultaneously in a single fabrication run. These lasers operate purely in the fundamental mode to output powers in excess of 450 mW, after which they are subject to beam steering or higher order mode operation. For weakly guided lasers, the output remains in a narrow lobe [full-width at half-maximum (FWHM)] = 4/spl deg/-6/spl deg/, stable at a given current value, up to output powers of 900 mW in CW tests.