gebhart/patrepeval huggingface dataset:
Screening for crystalline salts via mechanochemistry (2005)

Neat grinding and solvent-drop grinding methods are found to be effective screening tools for indicating the potential for crystalline salt formation involving a given acid-base pair, as demonstrated with two model pharmaceuticals.
Exploring infrared wavelength matrix-assisted laser desorption/ionization of proteins with delayed-extraction time-of-flight mass spectrometry (1998)

We report a study of the application of delayed extraction (DE) to infrared-wavelength matrix-assisted time-of-flight mass spectrometry (IR-MALDI-TOF-MS) of proteins. The shapes of the spectral peaks obtained with DE-IR-MALDI-MS are compared with those obtained from the same samples and matrix using continuous extraction (CE) IR-MALDI-MS. Application of DE results in significant improvements in the peak resolution, revealing spectral features (in proteins with molecular masses < 12 kDa) that were not resolved in the corresponding CE-IR-Maldi mass spectra. Particularly significant is a series of peaks on the high mass side of the protonated protein peaks that arise through replacement of protons by adventitious sodium ions in the sample. We deduced that these sodium replacement species are a significant contributor to the broad tails (and resulting peak asymmetries) that are a feature of the DE-IR-MALDI mass spectra of proteins with molecular masses > or = 17 kDa. The peak width reduction observed in IR-MALDI by DE suggests that, as in UV-MALDI, the initial velocity distribution for ions produced in the MALDI process contributes to the peak broadness in the CE mass spectra. In a systematic comparison between DE UV-MALDI and DE IR-MALDI, we determined that photochemical matrix adduction is present in UV-MALDI but absent in IR-MALDI. In addition, we find that protein ions produced by IR irradiation are less internally excited (i.e., cooler), exhibiting less fragmentation, more Na+ replacement and/or unspecified noncovalent adduction, and more heme adduction with apomyoglobin. Thus, IR-MALDI appears to be a softer means for producing gas-phase protein ions than is UV-MALDI. It will be of considerable practical interest to determine whether large protein ions produced by IR-MALDI are sufficiently cool to survive transport through reflecting TOF mass spectrometers (without loss of small neutral species such as H2O, NH3, and CO2) and the extended time periods required for detection by quadrupole ion trap and Fourier transform ion cyclotron resonance mass analyzers.
Expression of a receptor for IgM by human T cells in vitro (1975)

The capacity of human peripheral blood lymphocytes (PBL) to bind antigen-IgG antibody (EA(IgG)) and antigen-IgM antibody (EA(IgM)) complexes was investigated using a rosette technique with ox erythrocytes coated with rabbit IgG or IgM antibody. It was found that while EA(IgG)-rosette-forming cells (RFC) were detected on PBL freshly drawn from normal individuals, EA(IgM)-RFC were present only in suspensions kept in culture for 24 h in mediá supplemented with sera containing very low or no amounts of IgM. Experiments of simultaneous detection of EA(IgG)-RFC or EA(IgM)-RFC and other membrane markers for human T or B cells together with experiments on purified T or B cell populations indicated that EA(IgG)-RFC were formed by both T and B cells, while T cells only were capable of EA(IgM) rosette formation. The specificity of the receptors for IgG and IgM was determined by studying the inhibitory capacity of purified human IgM and IgG in the rosette assay. The receptor for IgG was inhibited by IgG and not by IgM, while the reverse was true for the receptor for IgM.
Identification of type 2 diabetes subgroups through topological analysis of patient similarity (2015)

Type 2 diabetes (T2D) is a heterogeneous complex disease affecting more than 29 million Americans alone with a rising prevalence trending toward steady increases in the coming decades. Thus, there is a pressing clinical need to improve early prevention and clinical management of T2D and its complications. Clinicians have understood that patients who carry the T2D diagnosis have a variety of phenotypes and susceptibilities to diabetes-related complications. We used a precision medicine approach to characterize the complexity of T2D patient populations based on high-dimensional electronic medical records (EMRs) and genotype data from 11,210 individuals. We successfully identified three distinct subgroups of T2D from topology-based patient-patient networks. Subtype 1 was characterized by T2D complications diabetic nephropathy and diabetic retinopathy; subtype 2 was enriched for cancer malignancy and cardiovascular diseases; and subtype 3 was associated most strongly with cardiovascular diseases, neurological diseases, allergies, and HIV infections. We performed a genetic association analysis of the emergent T2D subtypes to identify subtype-specific genetic markers and identified 1279, 1227, and 1338 single-nucleotide polymorphisms (SNPs) that mapped to 425, 322, and 437 unique genes specific to subtypes 1, 2, and 3, respectively. By assessing the human disease-SNP association for each subtype, the enriched phenotypes and biological functions at the gene level for each subtype matched with the disease comorbidities and clinical differences that we identified through EMRs. Our approach demonstrates the utility of applying the precision medicine paradigm in T2D and the promise of extending the approach to the study of other complex, multifactorial diseases.
Curcumin modulates dopaminergic receptor, CREB and phospholipase c gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats (2010)

Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, B(max) showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes.
Expression of raf family proto-oncogenes in normal mouse tissues. (1990)

We have determined RNA expression patterns of raf family proto-oncogenes in a variety of normal NFS/n mouse tissues, and several murine cell lines. Tissues were collected from male and female adults, and 16 day old fetuses. Raf-1 transcripts of 3.1 kb were found to be expressed in all tissues examined with highest levels in striated muscle, cerebellum and fetal brain. In contrast, A-raf showed wider variation in its range of expression, with the 2.6 kb transcripts being most abundant in epididymis and ovary. B-raf was found to have a very restricted expression pattern, with high levels in fetal brain and adult cerebrum. In addition to the 10 and 13 kb transcripts common to all B-raf expressing tissues, alternate sized B-raf RNAs were detected in testes, placenta and fetal membranes. We found no effect of gender on raf expression in non-sex related tissues, nor does tissue germline of origin correlate with levels of expression for any of the three genes.
Quantitative studies of the pathway to acute carrageenan inflammation. (1976)

A 12-step scheme representing initiation and development of acute carrageenan inflammation in the rat has been devised. Simultaneous quantitative temporal measurement of the number of inflammatory cells mobilized and edema volume produced as carrageenan pleurisy developed helped elucidate several of the early steps, In the pleurisy a 20-min lag phase preceded both the mobilization of neutrophils and edema formation. Temporal histological studies suggested that the lag phase represents the time needed for the neutrophil chemotactic factor to be generated and/or released (steps 2 and 3) in addition to the time required for these cells to move through the walls of the capillaries into the pleural space (steps 4 and 5). The neutrophil chemotactic factor is unknown. The complement system is not involved since cobra venom factor-treated animals produced a normal edematous and cellular response to carrageenan in spite of severely depressed complement levels. The mobilized neutrophils are believed to phagocytize the carrageenan(step6). In this process lysosomal enzymes are released (step 7). Drug inhibition studies suggest that lysosomal enzymes are not the edemagenic agents in carrageenan inflammation. In the scheme these enzymes are responsible for activation of the prostaglandin biosynthetic chain (step 8). Prostaglandin biosynthesis (step 9) leads to the release of an intermediate (step 10), as yet unidentified, which is responsible for increased tissue permeability (step 11) and edema formation (step 12). Histamine, serotonin, bradykinin, arachidonic acid, and prostaglandin's E1 and E2 are not deemagenic in the rat pleural cavity and therefore cannot be responsible for edema formation. Aspirin and indomethacin reduce the edema produced by carrageenan in a dose-related manner without affecting the magnitude or the time course of neutrophil mobilization. These findings led to the concept that edema formation is not the result of inflammatory cell mobilization but is rather a consequence of cellular activity, presumably phagocytosis, after mobilization.
Endothelin-induced Apoptosis of A375 Human Melanoma Cells (1998)

Endothelin-1 (ET-1) inhibited serum-dependent growth of asynchronized A375 human melanoma cells, and the growth inhibitory effect was markedly enhanced when ET-1 was applied to the cells synchronized at G1/S boundary by double thymidine blocks. Flow cytometric analysis revealed that ET-1 did not inhibit the cell cycle progression after the release of the block but caused a significant increase of the hypodiploid cell population that is characteristic of apoptotic cell death. ET-1-induced apoptosis was confirmed by the appearance of chromatin condensation on nuclear staining and DNA fragmentation on gel electrophoresis. The increase in the hypodiploid cell peak was manifest within 16 h of exposure to 5 nM ET-1. Within the same time range, ET-1 caused actin reorganization and drastic morphological changes of the surviving cells from epithelioid to an elongated bipolar shape. These phenotypical changes were preceded by ET-1-induced increase and nuclear accumulation of the tumor suppressor protein p53. All of these effects of ET-1 were mediated by ETB via a pertussis toxin-sensitive G protein. Flow cytometric analysis with fluorescent dye-labeled ET-1 revealed up-regulation of ETB expressed by the cells in G1/early S phases, and overexpression of the receptor protein by cDNA microinjection conferred the responsiveness (both apoptosis and morphological changes) to ET-1 irrespective of the position of the cell in the cell cycle. These results indicated the presence of ETB-mediated signaling pathways to apoptotic cell machinery and cytoskeletal organization. Furthermore, the densities of ETB expressed by individual A375 melanoma cells appeared to be regulated by a cell cycle-dependent mechanism, and the receptor density can be a limiting factor to control the apoptotic and cytoskeletal responses of the cells to ET-1. Although the molecular mechanisms remain to be elucidated, these findings added a new dimension to the diverse biological activities of ETs and also indicated a novel mechanism to control the responsiveness of the cell to the peptides.
Crystal structure of an active form of RAS protein, a complex of a GTP analog and the HRAS p21 catalytic domain. (1990)

Normal RAS proteins play a key role of molecular switch in the transduction of the growth signal from extracellular to intracellular space. The state of the switch is "on" when GTP is bound and "off" when GDP is bound to the protein. The crystal structure of a complex between a nonhydrolyzable GTP analog and the catalytic domain of a RAS protein has been determined by a rotation-translation search method. The orientations and positions of four independent molecules have been determined using a single molecule as a probe in the search. The crystal structure reveals that the gamma phosphate of the GTP analog induces extensive conformational changes on two loop regions of the protein.
Pathogenicity of avian reoviruses: examination of six isolates and a vaccine strain (1982)

Six avian reovirus isolates and a vaccine reovirus strain were compared for invasiveness, virulence, and pathological characteristics upon infection of day-old specific-pathogen-free chicks by the footpad, subcutaneous, and oral routes of inoculation. No significant differences were noted regarding the ability of individual isolates to infect target tissues. However, virulence (measured as the 50% lethal dose) among the isolates varied markedly from 2 x 10(5) to less than 10 PFU per chick for the most virulent isolate; between the parental wild-type virus and the derivative vaccine virus strain, a million-fold (10(6)) difference in virulence was demonstrated. All strains revealed, with considerable variation, arthrogenic potential.
Veterinary Epidemiology: Principles and Methods (1987)

<b>Veterinary Epidemiology: Principles and Methods</b> was published in 1987 by Iowa State University Press, Ames IA. Rights for this work have been reverted to the authors by the original publisher. The authors have chosen to license this work with a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license. (See: https://creativecommons.org/licenses/by-nc-nd/4.0) For any reuse or distribution, you must make clear to others the license terms of this work. Any of these conditions can be waived if you get permission from the copyright holder. Nothing in this license impairs or restricts the author's moral rights. IN ADDITION: the authors allow non-commercial distribution of translated and reformatted versions with attribution and without additional permission. <b>Table of contents</b> <br><b>I: Basic principles</b> <br>1. Epidemiologic concepts <br>2. Sampling methods <br>3. Measurement of disease frequency and production <b>II: Studying disease in animal populations</b> <br>4. Descriptive epidemiology <br>5. Disease causation <br>6. Surveys and analytic observational studies <br>7. Design of field trials <br>8. Theoretical epidemiology: systems analysis and modeling. <b>III: Animal health economics</b> <br>9. Animal health economics <b>IV: Applied epidemiology</b> <br>10. Rationale, strategies, and concepts of animal disease control <br>11. Monitoring disease and production <br>12. Field investigations <b>About the book</b> <br>The purpose of this textbook is to provide an introductory, yet comprehensive, source of information on epidemiology for veterinary students, researchers, and practitioners. There has not been a textbook that presents analytic epidemiology as a science, basic to veterinary medicine's efforts in health management (herd health) as well as in clinical medicine.
Low aspect ratio nanophotonic filled cavities with Q-matching for scalable thermophotovoltaic power conversion (2013)

Selective thermal emitters with a metallic 2D photonic crystal structure, such as shown in Fig. 1a), have been demonstrated to control the thermal emission spectrum of selective emitters for thermophotovoltaic applications. Traditionally, tungsten has been the metal of choice for thermal emitters due to their natural thermal emission selectivity to wavelengths > 2μm and high melting temperatures. However, due to the unweldable nature of tungsten, system integration of tungsten is difficult. As a result, weldable tantalum nanophotonic cavities have been demonstrated as effective thermal emitters with long wavelength emissivity below that of tungsten, allowing for improved selectivity performance compared to tungsten. However, the aspect ratios (AR) of the tantalum cavities have been demonstrated with a depth to radius aspect ratio of 11.2. The high aspect ratios in relation to tungsten (AR = 2.9) are due to the smaller material absorption at optical wavelengths around 2 μm, which causes Q <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">abs</sub> per unit length to be reduced thus affecting the Q matching condition. The aspect ratio is determined based on Q-matching, where the radiative Q (Q <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rad</sub> ) and absorption Q (Q <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">abs</sub> ) of the cavity must be equal for maximum absorption. The high cavity aspect ratio significantly hinders the fabrication methods available to manufacture the tantalum devices. For example, because of the high aspect ratio cavities, low-cost and scalable fabrication methods such as surface deposition of tantalum via sputtering or evaporation are not possible due to poor step coverage. Thus, previous methods used expensive and difficult to prepare 2" diameter tantalum wafers with custom etching methods. Accordingly, low aspect ratio cavities are key for a low-cost and scalable deployment of thermophotovoltaic devices.
Cucurbitane Glycosides from Unripe Fruits of <i>Siraitia grosvenori</i> (2007)

Studies on the constituents of the unripe fruits of Siraitia grosvenori led to the isolation of three new cucurbitane triterpene glycosides, 11-oxomogroside III (10), 11-dehydroxymogroside III (11), and 11-oxomogroside IV A (12). Their structures were determined on the basis of detailed analyses of 1D, 2D-NMR spectroscopic methods. All of the compounds isolated from the unripe fruits of S. grosvenori were tested for cytotoxic activities against tumor cells, HCT-116 and SMMC-7721.
Molecular Cloning and Characterization of DEFCAP-L and -S, Two Isoforms of a Novel Member of the Mammalian Ced-4 Family of Apoptosis Proteins (2001)

We report the deduced amino acid sequences of two alternately spliced isoforms, designated DEFCAP-L and -S, that differ in 44 amino acids and encode a novel member of the mammalian Ced-4 family of apoptosis proteins. Similar to the other mammalian Ced-4 proteins (Apaf-1 and Nod1), DEFCAP contains a caspase recruitment domain (CARD) and a putative nucleotide binding domain, signified by a consensus Walker's A box (P-loop) and B box (Mg(2+)-binding site). Like Nod1, but different from Apaf-1, DEFCAP contains a putative regulatory domain containing multiple leucine-rich repeats (LRR). However, a distinguishing feature of the primary sequence of DEFCAP is that DEFCAP contains at its NH(2) terminus a pyrin-like motif and a proline-rich sequence, possibly involved in protein-protein interactions with Src homology domain 3-containing proteins. By using in vitro coimmunoprecipitation experiments, both long and short isoforms were capable of strongly interacting with caspase-2 and exhibited a weaker interaction with caspase-9. Transient overexpression of full-length DEFCAP-L, but not DEFCAP-S, in breast adenocarcinoma cells MCF7 resulted in significant levels of apoptosis. In vitro death assays with transient overexpression of deletion constructs of both isoforms using beta-galactosidase as a reporter gene in MCF7 cells suggest the following: 1) the nucleotide binding domain may act as a negative regulator of the killing activity of DEFCAP; 2) the LRR/CARD represents a putative constitutively active inducer of apoptosis; 3) the killing activity of LRR/CARD is inhibitable by benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone and to a lesser extent by Asp-Glu-Val-Asp (OMe)-fluoromethyl ketone; and 4) the CARD is critical for killing activity of DEFCAP. These results suggest that DEFCAP is a novel member of the mammalian Ced-4 family of proteins capable of inducing apoptosis, and understanding its regulation may elucidate the complex nature of the mammalian apoptosis-promoting machinery.
Identification of Unique Truncated KC/GROβ Chemokines with Potent Hematopoietic and Anti-Infective Activities (2000)

SK&F 107647, a previously described synthetic immunomodulatory peptide, indirectly stimulates bone marrow progenitor cells and phagocytic cells, and enhances host defense effector mechanisms in bacterial and fungal infection models in vivo. In vitro, SK&F 107647 induces the production of a soluble mediator that augments colony forming cell (CFU-GM) formation in the presence of CSFs. In this paper we purified and sequenced the stromal cell-derived hematopoietic synergistic factors (HSF) secreted from both murine and human cell lines stimulated with SK&F 107647. Murine HSF is an N-terminal 4-aa truncated form of the CXC chemokine, KC, while human HSF was identified as an N-terminal 4-aa truncated form of the CXC chemokine, GRO beta. In comparison to their full-length forms, truncated KC and truncated GRO beta were 10 million times more potent as synergistic growth stimulants for CFU-GM. Enhanced potency of these novel truncated chemokines relative to their full-length forms was also demonstrated in respiratory burst assays, CD11b Ag expression, and intracellular killing of the opportunistic pathogen, Candida albicans. Administration of truncated KC significantly enhanced survival of mice lethally infected with C. albicans. The results reported herein delineate the biological mechanism of action of SK&F 107647, which functions via the induction of unique specific truncated forms of the chemokines KC and GRO beta. To our knowledge, this represents the first example where any form of KC or GRO beta were purified from marrow stromal cells. Additionally, this is the first demonstration of in vivo efficacy of a CXC chemokine in an animal infectious fungal disease model.
Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis (2020)

The cell type specific sequences of transcriptional programs during lung regeneration have remained elusive. Using time-series single cell RNA-seq of the bleomycin lung injury model, we resolved transcriptional dynamics for 28 cell types. Trajectory modeling together with lineage tracing revealed that airway and alveolar stem cells converge on a unique Krt8 + transitional stem cell state during alveolar regeneration. These cells have squamous morphology, feature p53 and NFkB activation and display transcriptional features of cellular senescence. The Krt8+ state appears in several independent models of lung injury and persists in human lung fibrosis, creating a distinct cell-cell communication network with mesenchyme and macrophages during repair. We generated a model of gene regulatory programs leading to Krt8+ transitional cells and their terminal differentiation to alveolar type-1 cells. We propose that in lung fibrosis, perturbed molecular checkpoints on the way to terminal differentiation can cause aberrant persistence of regenerative intermediate stem cell states.