gebhart/patrepeval huggingface dataset:
Comparative pharmacokinetics and interspecies scaling of 3'-azido-3'-deoxythymidine(AZT) in several mammalian species. (1990)

Interspecies variation in drug disposition can be considered to be a function of species body weight. Therefore, it is possible to establish allometric relationships between pharmacokinetic parameters and species body weight. Interspecies scaling of pharmacokinetic data yielded from laboratory animals can often provide reliable predictions of pharmacokinetic parameters and drug disposition in humans. Significant correlations between 3'-azido-3'-deoxythymidine (AZT) pharmacokinetic parameters (total clearance, renal clearance, nonrenal clearance and steady-state volume of distribution) from mice, rats, dogs, monkeys and humans and body weight were found. Plasma AZT concentration versus chronological time profiles were markedly different for each species. However, when chronological time was converted to pharmacokinetic (physiologic) time these profiles were superimposible. These results demonstrate that interspecies pharmacokinetic scaling can be used to estimate plasma AZT concentrations in humans and can be used to design initial dosage regimens.
Antibiotic-Induced Changes to the Host Metabolic Environment Inhibit Drug Efficacy and Alter Immune Function (2017)

Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect either treatment efficacy or immune function. Here, we quantify local metabolic changes in the host microenvironment following antibiotic treatment for a peritoneal Escherichia coli infection. Antibiotic treatment elicits microbiome-independent changes in local metabolites, but not those distal to the infection site, by acting directly on host cells. The metabolites induced during treatment, such as AMP, reduce antibiotic efficacy and enhance phagocytic killing. Moreover, antibiotic treatment impairs immune function by inhibiting respiratory activity in immune cells. Collectively, these results highlight the immunomodulatory potential of antibiotics and reveal the local metabolic microenvironment to be an important determinant of infection resolution.
Pdx-1 Regulation of the INGAP Promoter Involves Sequestration of NeuroD Into a Non-DNA-Binding Complex (2009)

These data reveal a dynamic interaction between Pdx-1, NeuroD, and Pan-1 for the regulation of INGAP promoter activity. Modulating molecular regulators of DNA expression may be a consideration in diabetic therapies that translate exogenous stimuli into new endogenous beta-cell mass.
Resolving Multiple Protein–Peptide Binding Events: Implication for HLA‐DQ2 Mediated Antigen Presentation in Celiac Disease (2012)

Techniques that can effectively separate protein-peptide complexes from free peptides have shown great value in major histocompatibility complex (MHC)-peptide binding studies. However, most of the available techniques are limited to measuring the binding of a single peptide to an MHC molecule. As antigen presentation in vivo involves both endogenous ligands and exogenous antigens, the deconvolution of multiple binding events necessitates the implementation of a more powerful technique. Here we show that capillary electrophoresis coupled to fluorescence detection (CE-FL) can resolve multiple MHC-peptide binding events owing to its superior resolution and the ability to simultaneously monitor multiple emission channels. We utilized CE-FL to investigate competition and displacement of endogenous peptides by an immunogenic gluten peptide for binding to HLA-DQ2. Remarkably, this immunogenic peptide could displace CLIP peptides from the DQ2 binding site at neutral but not acidic pH. This unusual ability of the gluten peptide supports a direct loading mechanism of antigen presentation in extracellular environment, a property that could explain the antigenicity of dietary gluten in celiac disease.
Gene Regulation During Axon and Tissue Regeneration in the Retina of Zebrafish (2006)

This chapter contains sections titled: Introduction The Zebrafish Retina Retina Injury Experimental Models of Retinal Injury Gene Regulation in the Injured Zebrafish Retina Phase 1: Programmed Cell Death (Apoptosis) and Immune Response Phase 2: Stem Cell Activation and Proliferation Phase 3: Cellular Migration and Differentiation Approaches to Identifying Transcriptional Regulators in the Injured Retina: The Example of α1-Tubulin Optic Nerve Regeneration Experimental Models of Optic Nerve Regeneration Gene Regulation Following Optic Nerve Lesion Environmental Factors Influencing Fish Optic Nerve Regeneration Intrinsic Mechanisms of Optic Nerve Regeneration Approaches to Identifying Transcriptional Regulators of Optic Nerve Regeneration in Zebrafish: The Example of α1-Tubulin Genetic Strategies for Retinal Regeneration: Perspectives and Challenges Concluding Remarks
Molecular-modelling and biophysical studies on modified and unmodified oligonucleotides (1984)

We report crystallographic data for a dinucleoside monophosphate d(T[plT) (as its cyanoethyl derivative) with the cis-syn cyclobutane geometry generated by UV irradiation. The molecule crystallizes in the orthorhombic space group P2 1 2 1 2 1 (Z = 4) with two '.;ater
Stereospecific total synthesis of dl-austamide (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereospecific total synthesis of dl-austamideAlan J. Hutchison and Yoshito KishiCite this: J. Am. Chem. Soc. 1979, 101, 22, 6786–6788Publication Date (Print):October 1, 1979Publication History Published online1 May 2002Published inissue 1 October 1979https://pubs.acs.org/doi/10.1021/ja00516a067https://doi.org/10.1021/ja00516a067research-articleACS PublicationsRequest reuse permissionsArticle Views955Altmetric-Citations75LEARN 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
Dihydrofolate reductase as an oncogene: a microRNA binding site SNP leads to cellular transformation and drug resistance (2008)

2458 Dihydrofolate Reductase (DHFR) is an E2F1-regulated enzyme that isessential for DNA synthesis and repair. Elevated levels of DHFR have been correlated with methotrexate resistance leading to poor prognosis in many cancers. We have previously demonstrated that a microRNA miR24 has a conserved binding site in DHFR 3’UTR and a miRSNP (microRNA binding site SNP) 829C→τ in DHFR 3’ UTR results in loss of miR24 function and leads to DHFR over expression and methotrexate resistance (Mishra et. al. 2007, PNAS). Of interest, we observed that DHFR over expressing CHO cells grow at a faster rate and form foci in monolayer cultures, which is a hallmark of transformation. Over expression of DHFR because of the SNP resulted in transformation of rat kidney cells (RK3) cells and murine fibroblast cells (NIH3T3) in vitro and in vivo in nude mice. To test the hypothesis that DHFR can be a potential proto-oncogene and when over expressed can act as an oncogene DHFR was over expressed in NIH3T3 and RK3 cells by a vector containing the DHFR coding region. Over-expression of DHFR transformed the immortalized non-transformed mammalian cells assayed by foci formation, anchorage independentgrowth and tumor formation in nude mice. Whereas the control vector alone transfected cells were not transformed.  We also over expressed DHFR in human mammary epithelial cells (MCF10A) and demonstrated that they now form colonies in soft agar. We next showed that DHFR over expression can make a breast cancer cell line (MDA-MB-231) more tumorigenic in nude mice. Using a clone of MDAMB231 cells that form subcutaneous tumors in a xenograft model only when co-injected with Matrigel, we demonstrated that DHFR over expression in these cells causes tumor formation without matrigel. Animals injected with DHFR over expressing breast cancer cells developed tumors (5/5) where as injection of control breast cancer cells did not result in tumor growth (0/5). To determine whether increased DHFR levels could be detected in aggressive human tumors, we isolated DNA from 51 metastatic human colorectal tumor samples and 7 peripheral blood mononuclear cells of non-cancer patients (as control) and examined them for DHFR gene copy number by Q-PCR. Interestingly, DHFR gene copy number was increased in the human colorectal cancer samples: 46 out of 51 samples had 1.6 to 18-fold increase in gene copy number of DHFR (mean 6.8). Our study demonstrates a novel role for dihydrofolate reductase, an essential DNA synthesis enzyme, as a proto-oncogene regulated by a microRNA miR24. This work also suggests a link between deregulated DNA synthesis and acquisition of a neoplastic phenotype.
Evidence for Two Classes of Cytokines That Stimulate Hepatic Lipogenesis: Relationships among Tumor Necrosis Factor, Interleukin-1 and Interferon-Alpha* (1990)

Tumor necrosis factor (TNF) increases serum triglycerides in rats by increasing de novo hepatic fatty acid synthesis and very low density lipoprotein production. We have recently shown that several other cytokines increase hepatic fatty acid synthesis in the mouse. We now explore the mechanism by which these cytokines increase de novo lipogenesis and the interactions between cytokines in fed mice. TNF administration results in increased hepatic levels of citrate, the primary allosteric activator of acetyl-CoA carboxylase, which is the major rate-limiting enzyme for fatty acid synthesis. The TNF-induced increase in citrate occurs within 15 min of administration, early enough to account for the acute rise in hepatic fatty acid synthesis seen by 30 min after TNF administration. IL-1, which also increases hepatic fatty acid synthesis, produces similar increases in hepatic citrate levels. In contrast, another potent stimulator of hepatic fatty acid synthesis, interferon-alpha (IFN alpha), has no effect on hepatic citrate levels. There were no acute effects of TNF or IL-1 on the activation state of acetyl-CoA carboxylase. A trend toward an increase in the activation state of acetyl-CoA carboxylase was seen after IFN alpha administration. Low doses of TNF and IL-1 given in combination show no synergy while maximal doses are not additive. In contrast, when a low dose of either TNF or IL-1 is combined with a low dose of IFN alpha, there is synergy in stimulating hepatic fatty acid synthesis. A maximal dose of TNF or IL-1 and a high dose of IFN alpha produce a further increase in hepatic fatty acid synthesis. These data support the concept that there are two classes of cytokines that stimulate hepatic fatty acid synthesis, those that can increase hepatic citrate levels and those that cannot.
Amount and Type of Dietary Fat, Postprandial Glycemia, and Insulin Requirements in Type 1 Diabetes: A Randomized Within-Subject Trial (2019)

This study provides clinical guidance for mealtime insulin dosing recommendations for dietary fat in T1D.
Theory of collective proton motion at interfaces with densely packed protogenic surface groups (2012)

We present a theoretical study of collective proton transport at a 2D array of end-grafted protogenic surface groups with sulfonic acid head groups. The graft positions of the surface groups form a regular hexagonal lattice. We consider the interfacial array at a high packing density of the surface groups and under minimal hydration with one water molecule added per head group. For these conditions, the stable interfacial conformation consists of a bicomponent lattice of hexagonally ordered sulfonate anions and interstitial hydronium cations. Hydronium ion motion occurs as a travelling solitary wave. We analyse the microscopic parameters of the solitons and study the influence of different potential profiles on the proton motion created by rotation and tilting of sidechains and sulfonate anions. Using soliton solutions of the equation of motion, we establish relations between the energy and mobility of the solitons and the microscopic structural and interaction parameters of the array.
SPAD Developed in 55 nm Bipolar-CMOS-DMOS Technology Achieving Near 90% Peak PDP (2023)

We present a single-photon avalanche diode (SPAD) developed in 55 nm bipolar-CMOS-DMOS (BCD) technology, which achieves high photon detection probability (PDP) while its breakdown voltage is lower than 20 V. To enhance the PDP performance, the SPAD junction is optimized with lightly-doped-drain and high-voltage-well layers which are provided in the BCD process. In addition, the dielectric layers over the SPAD are properly etched to reduce multilayer reflections so that the photon collection efficiency can be maximized. The SPAD achieves a peak PDP of 89.4% at 450 nm wavelength with the excess bias voltage of 7 V, while its breakdown voltage is 16.1 V. At the same bias condition, the device shows a dark count rate (DCR) of 38.2 cps/μm2. It also achieves a timing jitter of 55 ps at 940 nm with the 7 V excess bias. This new high-performance SPAD implemented in such an advanced node BCD technology operating at a low breakdown voltage is expected to have a major impact on several single-photon applications, especially biomedical sensing and imaging.
Surface Functionalization of Two-Dimensional MXene Nanosheets to Tailor Sulfur-Host Architecture for Metal-Sulfur Batteries (2022)

Practicality of lithium-sulfur batteries is severely hindered by the notorious polysulfide-shuttle phenomenon, leading to rapid capacity fade. This issue is aggravated with increase in sulfur loading, causing low-coulombic efficiency and cycle life. Herein, we present a facile strategy to combine hydrophobic sulfur and hydrophilic , conductive Ti 3 C 2 T z -MXene via one-step surface functionalization using di(hydrogenated tallow) benzylmethyl ammonium chloride (DHT). The latter renders the Ti 3 C 2 T z surface hydrophobic , making it readily dispersible in sulfur dissolved in a carbon disulfide (CS 2 ) solvent. By evaporating the solvent, we conformally coat the DHT-Ti 3 C 2 T z (DMX) with sulfur. The developed composite, with higher available active area, enables effective trapping of lithium polysulfides (LiPs) on the electroactive sites within the cathode, leading to improvement in electrochemical performance at higher sulfur loadings. The DMX/S cathodes function with high sulfur loading of ∼10.7 mg·cm −2 and deliver a stable areal capacity of ∼7 mAh·cm −2 for 150 cycles in the standard ether electrolyte. Moreover, a DMX/S cathode in a pouch-cell configuration retains ∼770 mAh·g −1 after ∼200 cycles at 0.2C (85.5% retention). Postmortem spectroscopic studies elucidate the nature of the LiPs-MXene interaction and the effect of surface functionalization towards improved performance. To further demonstrate the applicability of such uniquely functionalized MXene sheets, we study them as a host to confine sulfur (S 8 ) triggering a quasi-solid state redox mechanism enabling the use of commercialization-friendly carbonate electrolyte in metal-sulfur batteries. We demonstrate that the multilayer MXene structure provides tunable spacing for S 8 confinement and its unique interlayer spacing prevents adverse polysulfide-carbonate reactions resulting in stable battery cycling.
Low-Cost Magnesium Alloy Sheet Component Development and Demonstration Project (2022)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Most of the applications of magnesium in lightweighting commercial cars and trucks are die castings rather than sheet metal, and automotive applications of magnesium sheet have typically been experimental or low-volume serial production. The overarching objective of this collaborative research project organized by the United States Automotive Materials Partnership (USAMP) was to develop new low-cost magnesium alloys, and demonstrate warm-stamping of magnesium sheet inner and outer door panels for a 2013 MY Ford Fusion at a fully accounted integrated component cost increase over conventional steel stamped components of no more than $2.50/lb. saved ($5.50/kg saved). The project demonstrated the computational design of new magnesium (Mg) alloys from atomistic levels, cast new experimental alloy ingots and explored thermomechanical rolling processes to produce thin Mg sheet of desired textures. A new commercial Mg alloy sheet material was sourced and pretreated with protective coil coatings, and its properties fully characterized. The Mg sheet was successfully warm-formed using novel lubricants into intermediate size benchmark parts and full-size automotive door inner and outer panels. The project also explored conventional welding processes for joining of Mg sheet, developed novel corrosion treatments for multi-metal assembly coatings, performed computer simulations of door panel forming using two new material cards based on crystal plasticity theory, and concluded with a door static and dynamic performance analysis. An overall cost driver and sensitivity assessment task compared the final cost penalty depending on the cost of the primary magnesium sheet.&lt;/div&gt;&lt;/div&gt;
Atomic Layer Deposited Cu2s As a Superior Electrode Material With High Capacity and Excellent Cycleability for Lithium-Ion Batteries (2013)

Abstract not Available.
Regenerative Therapy Prevents Heart Failure Progression in Dyssynchronous Nonischemic Narrow QRS Cardiomyopathy (2015)

In narrow QRS HF, a regenerative approach demonstrated functional and structural benefit, introducing the prospect of device-autonomous resynchronization therapy for refractory disease.
Abstract P3-09-02: Pateint Derived Breast Cancer Organoids as a Model for Testing Personalized Therapies (2023)

Abstract Introduction: Breast cancer is one of the most frequently diagnosed cancer in women with a high mortality rate. More than 20 different subtypes of breast cancer are identified. Advancement in patient-derived organoid technology makes it possible to preserve cellular, structural, and tissue microenvironment which mimics the tissue in vivo. Method: We developed patient derived breast organoids both from normal and cancer biopsies recapitulate the structure of breast tissue. Breast biopsies were enzymatically digested to yield a single cell suspension. About 1 × 105 cells were encapsulated in a specialized hydrogel mixture. Immune enhanced breast tumor organoids (iTOs) included 2 × 105 patient matched PMBCs. Results: Histological analyses of the breast organoids shows the characteristics of the breast tissue with well-defined acini in H&amp;E. In tumor organoids acini were somewhat perturbed compared to normal breast organoids. Immuno-fluorescence staining shows the expression of breast biomarkers including EGF receptor 2 (HER2), Progesterone receptor (PR), Estrogen receptor (ER). Zona occludin 1 and 2 and keratin 19 expression in luminal cells and expression of Keratin 14 and P63 in basal cells suggested correct polarization in the organoids. Immunofluorescence staining of (iTOs), with T cell markers including CD3, CD4, and CD8 indicated that immune cells remained viable in the iTOs. Drug responses to Doxorubicin, Paclitaxel and a combination of Doxorubicin-Paclitaxel showed significant inhibition of cell growth in normal and tumor organoids (p&amp;lt; 0.04, n=11) except for Paclitaxel failed to inhibit tumor cell growth. However, immunotherapy with nivolumab (anti PD-1) showed no significant effect on cell growth. Conclusions: Pateint Derived Breast cancer organoids recapitulate the histological features of breast tissue in culture and response to chemotherapies. In the future, patient-derived tumor organoids can provide a platform for personalized medicine. Citation Format: Nadeem Wajih, Richard Erali, Steven Forsythe, Shay Soker, Konstantinos Votanopoulos. Pateint Derived Breast Cancer Organoids as a Model for Testing Personalized Therapies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-09-02.
Splice Variants of Intersectin Are Components of the Endocytic Machinery in Neurons and Nonneuronal Cells (1999)

We recently identified and cloned intersectin, a protein containing two Eps15 homology (EH) domains and five Src homology 3 (SH3) domains. Using a newly developed intersectin antibody, we demonstrate that endogenous COS-7 cell intersectin localizes to clathrin-coated pits, and transfection studies suggest that the EH domains may direct this localization. Through alternative splicing in a stop codon, a long form of intersectin is generated with a C-terminal extension containing Dbl homology (DH), pleckstrin homology (PH), and C2 domains. Western blots reveal that the long form of intersectin is expressed specifically in neurons, whereas the short isoform is expressed at lower levels in glia and other nonneuronal cells. Immunofluorescence analysis of cultured hippocampal neurons reveals that intersectin is found at the plasma membrane where it is co-localized with clathrin. Ibp2, a protein identified based on its interactions with the EH domains of intersectin, binds to clathrin through the N terminus of the heavy chain, suggesting a mechanism for the localization of intersectin at clathrin-coated pits. Ibp2 also binds to the clathrin adaptor AP2, and antibodies against intersectin co-immunoprecipitate clathrin, AP2, and dynamin from brain extracts. These data suggest that the long and short forms of intersectin are components of the endocytic machinery in neurons and nonneuronal cells.
Non‐negativity constraints for elimination of multiple solutions in fitting of multivariate kinetic models to spectroscopic data (2005)

Abstract Multiple solutions arise when fitting complicated multi‐step kinetic models to spectroscopic data. For consecutive reactions of the type A→B→C this well‐known ambiguity is due to the presence of multiple equivalent global minima in the response surfaces associated with the non‐linear least squares fitting of rate constants to spectroscopic data. Several methods have been described to overcome the ambiguity when fitting consecutive reactions with univariate data but few attempts to solve the problem have been described for multivariate data. Additionally, for complicated multi‐step reaction schemes there may be several local minima that make selection of the initial parameter guesses difficult. This paper reports a general approach to overcome these types of ambiguities in multivariate kinetic fitting methods using non‐negativity constraints for the determination of the pure component spectra estimated during the model‐fitting process. Under many conditions these constraints reduce or eliminate entirely the incorrect local minima. The effectiveness and reliability of the new constraints were tested with several simulated and real data sets. Copyright © 2005 John Wiley &amp; Sons, Ltd.