gebhart/patrepeval huggingface dataset:
A large accumulation of non-muscle myosin occurs at first entry into M phase in rat vascular smooth-muscle cells (1991)

Vascular smooth-muscle cells (VSMCs) from rat aortae contained very little non-muscle myosin heavy chain (MHC) immediately after dispersal, and the protein did not accumulate if the cells were held in G0/G1 phase by withholding serum or were held in first S phase by the addition of bromodeoxyuridine (BrdU). However, non-muscle MHC accumulated by greater than 20-fold per cell during first M phase, when over 80% of the cells divided between 48 h and 72 h after addition of serum. Delaying the addition of serum caused a delay in the accumulation of the non-muscle MHC until the cells subsequently entered M phase. If the cells were held in M phase at the metaphase/anaphase boundary by nocadazole, the accumulation of non-muscle myosin still occurred, although division was blocked. When the cells were pulse-labelled with [35S]methionine, it was found that non-muscle MHC was one of the major proteins being made and that its synthesis occurred at similar rates throughout the cell cycle. This implied that the rate of degradation of the protein before first M phase was much faster than in M phase, when the protein accumulated rapidly. This was confirmed by direct measurements of the rate at which [35S]methionine-labelled non-muscle MHC disappeared from the cells, which gave a half-life for the protein of about 8 h before M phase but about 5 days in post-mitotic cells, i.e. an increase of approx. 15-fold. These data are consistent with the hypothesis that there is a mechanism in VSMCs which shortens the half-life of the protein before first M phase and that the accumulation of non-muscle MHC which results from the increase in half-life at first M phase may be necessary for division of these cells.
A Review on Position/Speed Sensorless Control for Permanent-Magnet Synchronous Machine-Based Wind Energy Conversion Systems (2013)

Owing to the advantages of higher efficiency, greater reliability, and better grid compatibility, the direct-drive permanent-magnet synchronous generator (PMSG)-based variable-speed wind energy conversion systems (WECSs) have drawn the highest attention from both academia and industry in the last few years. Applying mechanical position/speed sensorless control to direct-drive PMSG-based WECSs will further reduce the cost and complexity, while enhancing the reliability and robustness of the WECSs. This paper reviews the state-of-the-art and highly applicable mechanical position/speed sensorless control schemes for PMSG-based variable-speed WECSs. These include wind speed sensorless control schemes, generator rotor position and speed sensorless vector control schemes, and direct torque and direct power control schemes for a variety of direct-drive PMSG-based WECSs.
Fibroblast precursors in normal and irradiated mouse hematopoietic organs. (1976)

Using the in vitro colony assay, clonogenic fibroblast precursor cells (CFU-F) were detected in the bone marrow, spleen and thymus from adult mice. The survival curve for CFU-F of mouse bone marrow irradiated in vitro has a D0 of 220 r. Regeneration of bone marrow CFU-F after whole-body irradiation with 150 r is characterized by a marked secondary loss and post-irradiation lag and dip, lasting 6 days, followed by return to normal values by about the 25th day. This pattern of post-radiation recovery of CFU-F is similar to that of the CFU-s. In addition, during the first 6 hours following irradiation the number of CFU-F increased approximately twofold.
Peptidyl carbamates incorporating amino acid isosteres as novel elastase inhibitors (1986)

The design and synthesis of 13 novel peptidyl carbamates are described. When tested for inhibitory activity toward porcine pancreatic elastase, trypsin, and chymotrypsin, six compounds were found to specifically inhibit elastase without affecting the other two serine proteases. All the active inhibitors had an amino acid isostere at the P1 position. Kinetic studies indicated that the inhibition was competitive with Ki values ranging from 4.23 X 10(-5) to 2.4 X 10(-6) M. The degree of inhibition was found to be dependent on the specificity of the peptide chain for the extended subsites on the enzyme as well as on the nature of P1'. Preliminary work on one inhibitor indicates that the inhibition is reversible and proceeds via the rapid formation of a strong enzyme-inhibitor complex, followed by slow acylation of the serine residue on the active site of the enzyme. Peptidyl carbamates represent a novel class of elastase inhibitors.
Pharmacotherapy of Abdominal Aortic Aneurysms (2006)

Aortic aneurysms account for 10,000 deaths annually in the UK, due to rupture. At present the only effective therapeutic strategy to treat abdominal aortic aneurysms is to surgically repair them; this carries an elective mortality of up to 10%. Recent advances in vascular biology have led to a greater understanding of the pathophysiological process that causes aortic aneurysms to expand and rupture. Key pathological processes include widespread aortic inflammation, proteolytic degradation of the extracellular matrix, neovascularisation and generation of reactive oxygen species. Identification of these processes has lead to pharmacological strategies to prevent aneurysm expansion and rupture. Many of these strategies have undergone proof of concept in animal models and some have now entered clinical trials. This review outlines current thinking regarding the molecular events leading to aneurysm expansion and explains how these processes may be inhibited. Experimental data on agents retarding aneurysm expansion in animal models are discussed. A significant proportion of the review details pharmacological agents that have undergone or are undergoing clinical trials. Pharmacological treatment for abdominal aneurysms is urgently required given the number of small aneurysms being diagnosed by screening programmes. This is a rapidly evolving field and one in which translation from experimental research to clinical practice is anticipated within 5 years.
Longitudinal Studies on the Rate of Decline in Renal Function with Age (1985)

Serial creatinine clearances (5 to 14 studies) were obtained for 446 normal volunteers in the Baltimore Longitudinal Study of Aging followed between 1958 and 1981. When those subjects with possible renal or urinary tract disease and subjects on diuretics and antihypertensives were removed from the study, leaving a group of 254 "normal" subjects, the mean decrease in creatinine clearance was 0.75 ml/min/year. The slopes of the creatinine clearance vs. time fell into a normal (Gaussian) distribution around this mean. One third of all subjects followed had no absolute decrease in renal function (positive slope of creatinine clearance vs. time) and there was a small group of patients who showed a statistically significant increase (P less than 0.05) in creatinine clearance with age.
Influenza A Virus PB1-F2 Protein Contributes to Viral Pathogenesis in Mice (2006)

The influenza virus PB1-F2 protein is a novel protein previously shown to be involved in induction of cell death. Here we characterize the expression and the function of the protein within the context of influenza viral infection in tissue culture and a mouse model. We show that the C-terminal region of the protein can be expressed from a downstream initiation codon and is capable of interaction with the full-length protein. Using this knowledge, we generated influenza viruses knocked out for the expression of PB1-F2 protein and its downstream truncation products. Knocking out the PB1-F2 protein had no effect on viral replication in tissue culture but diminished virus pathogenicity and mortality in mice. The viruses replicated to similar levels in mouse lungs by day 3 postinfection, suggesting that the knockout did not impair viral replication. However, while the PB1-F2 knockout viruses were cleared after day 5, the wild-type viruses were detectable in mouse lungs until day 7, implying that expression of PB1-F2 resulted in delayed clearance of the viruses by the host immune system. Based on our findings and on the fact that the PB1 genomic segment was always newly introduced into some pandemic influenza viruses of the last century, we speculate that the PB1-F2 protein plays an important role in pathogenesis of influenza virus infection and may be an important contributor to pathogenicity of pandemic influenza viruses.
DNA hypermethylation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomas (2001)

The three human leukocyte antigen (HLA) class I antigens, HLA-A, HLA-B and HLA-C, play important roles in the elimination of transformed cells by cytotoxic T cells. Frequent loss of expression of these antigens at the cell surface has been observed in many human cancers. Various mechanisms for post-transcriptional regulation have been proposed and tested but the molecular mechanisms for transcriptional regulation are not clear. We show by immunohistochemistry that the HLA class I antigens are absent in 26 of 29 (89%) samples of human esophageal squamous cell carcinomas (ESCC). Eleven of the 26 ESCC samples lost mRNA expression for at least one of the HLA genes, as shown by RT-PCR. DNA from the 29 pairs of ESCC and neighboring normal epithelium were examined for CpG island hypermethylation, homozygous deletion, microsatellite instability (MSI) and loss of heterozygosity (LOH). DNA from normal epithelial tissues had no detectable methylation of the CpG islands of any of these gene loci. Thirteen of 29 ESCC samples (45%) exhibited methylation of one or more of the three HLA loci and six samples (21%) exhibited methylation of all three loci. The HLA-B gene locus was most frequently methylated (38%). HLA-B mRNA expression in an ESCC cell line, where HLA-B was hypermethylated and did not express mRNA, was activated after treatment with 5-aza-2'-deoxycytidine. Homozygous deletion of these three gene loci was not observed. Relatively low rates of LOH and MSI were observed for the microsatellite markers D6S306, D6S258, D6S273 and D6S1666, close to the HLA-A, -B and -C loci, although a high ratio of LOH was observed at a nearby locus (represented by the markers D6S1051 and D6S1560), where the tumor suppressor gene p21(Waf1) resides. A strong correlation between genetic alterations and mRNA inactivation was observed in the ESCC samples. Our results indicate that HLA class I gene expression was frequently down-regulated in ESCC at both the protein and mRNA levels and that hypermethylation of the promoter regions of the HLA-A, -B and -C genes is a major mechanism of transcriptional inactivation.
Generation of Bis-Cationic Heterocyclic Inhibitors of Bacillus subtilis HPr Kinase/Phosphatase from a Ditopic Dynamic Combinatorial Library (2003)

Ditopic dynamic combinatorial libraries were generated and screened toward inhibition of the bifunctional enzyme HPr kinase/phosphatase from Bacillus subtilis. The libraries were composed of all possible combinations resulting from the dynamic interconversion of 16 hydrazides and five monoaldehyde or dialdehyde building blocks, resulting in libraries containing up to 440 different constituents. Of all possible acyl hydrazones formed, active compounds containing two terminal cationic heterocyclic recognition groups separated by a spacer of appropriate structure could be rapidly identified using a dynamic deconvolution procedure. Thus, parallel testing of sublibraries where one specific component was excluded basically revealed all the essential components. A potent ditopic inhibitor, based on 2-aminobenzimidazole, was identified from the process.
Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy (2014)

Immune-deficient mice, reconstituted with human stem cells, have been used to analyze human immune responses in vivo. Although they have been used to study immune responses to xenografts, allografts, and pathogens, there have not been models of autoimmune disease in which the mechanisms of the pathologic process can be analyzed. We have found that reconstituted "humanized" mice treated with anti-CTLA-4 Ab (ipilimumab) develop autoimmune disease characterized by hepatitis, adrenalitis, sialitis, anti-nuclear Abs, and weight loss. Induction of autoimmunity involved activation of T cells and cytokine production, and increased infiltration of APCs. When anti-CTLA-4 mAb-treated mice were cotreated with anti-CD3 mAb (teplizumab), hepatitis and anti-nuclear Abs were no longer seen and weight loss did not occur. The anti-CD3 blocked proliferation and activation of T cells, release of IFN-γ and TNF, macrophage infiltration, and release of IP-10 that was induced with anti-CTLA-4 mAb. We also found increased levels of T regulatory cells (CD25(+)CD127(-)) in the spleen and mesenteric lymph nodes in the mice treated with both Abs and greater constitutive phosphorylation of STAT5 in T regulatory cells in spleen cells compared with mice treated with anti-CTLA-4 mAb alone. We describe a model of human autoimmune disease in vivo. Humanized mice may be useful for understanding the mechanisms of biologics that are used in patients. Hepatitis, lymphadenopathy, and other inflammatory sequelae are adverse effects of ipilimumab treatment in humans, and this study may provide insights into this pathogenesis and the effects of immunologics on autoimmunity.
Multiple emitter location and signal parameter estimation (1986)

Processing the signals received on an array of sensors for the location of the emitter is of great enough interest to have been treated under many special case assumptions. The general problem considers sensors with arbitrary locations and arbitrary directional characteristics (gain/phase/polarization) in a noise/interference environment of arbitrary covariance matrix. This report is concerned first with the multiple emitter aspect of this problem and second with the generality of solution. A description is given of the multiple signal classification (MUSIC) algorithm, which provides asymptotically unbiased estimates of 1) number of incident wavefronts present; 2) directions of arrival (DOA) (or emitter locations); 3) strengths and cross correlations among the incident waveforms; 4) noise/interference strength. Examples and comparisons with methods based on maximum likelihood (ML) and maximum entropy (ME), as well as conventional beamforming are included. An example of its use as a multiple frequency estimator operating on time series is included.
Deficiency of acetylcholine receptors in a case of end‐plate acetylcholinesterase deficiency: A histochemical investigation (1992)

A young boy is described who, since early infancy, suffered from weakness of predominantly proximal limb muscles. Electromyography revealed impairment of neuromuscular transmission. There were no antibodies against acetylcholine receptors. The amplitude of miniature end-plate potentials was reduced. Neuromuscular junctions showed somewhat coarse postsynaptic junctional folds and degeneration products in the synaptic clefts and in postsynaptic areas. Using qualitative and semiquantitative histochemical methods, at light- and electronmicroscopical levels, acetylcholinesterase (AChE) activity and acetylcholine receptors (AChRs) were demonstrated to be deficient. This patient demonstrates that the clinical picture of congenital myasthenia may closely resemble a congenital myopathy. The findings provide evidence that AChR deficiency offers protection from some of the effects of AChE deficiency. The clinical features of AChE deficiency depend, not only on the level of residual enzyme activity, but also on the degree of AChR reduction, if present.
1-Alkylcarbonyloxymethyl Prodrugs of 5-Fluorouracil (5-FU): Synthesis, Physicochemical Properties, and Topical Delivery of 5-FU (1998)

1-Alkylcarbonyloxymethyl (1-ACOM) prodrugs of 5-fluorouracil (5-FU) have been synthesized and characterized by their solubilities in isopropyl myristate (SIPM) and pH 4.0 buffer (SH2O), by their partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K) and by their abilities to deliver total 5-FU species into (Cs) and through (Ji) hairless mouse skin from an IPM vehicle. All of the prodrugs were much more lipophilic (SIPM) than 5-FU (> 60 times), and two members of the series (alkyl = C1 and C2, acetyl- and propionyloxymethyl) were also more soluble in water than 5-FU. The two more water-soluble members gave larger Ji values than the other members of the series, with C2 exhibiting the best biphasic solubility and the largest Ji value (16 times that of 5-FU). The ability of the 1-ACOM-5-FU prodrugs to deliver total 5-FU species into skin (Cs) was greater than the delivery of 5-FU by 5-FU, except for the last two members of series (alkyl = C7 and C9, octanoyl- and decanoyl-oxymethyl). However, the ratios of normalized Cs to Ji for the series was less than that exhibited by 5-FU, except for C7 and C9. Also, except for C9, significant amounts of intact prodrug as percentages of total 5-FU species were found in the receptor phases during the course of the diffusion cell experiments, ranging from 55% for C1 to 12% for C7.
Direct synthesis of fluoro-bicyclic compounds with fluorine (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect synthesis of fluoro-bicyclic compounds with fluorineShlomo Rozen and Chava GalCite this: J. Org. Chem. 1988, 53, 12, 2803–2807Publication Date (Print):June 1, 1988Publication History Published online1 May 2002Published inissue 1 June 1988https://pubs.acs.org/doi/10.1021/jo00247a026https://doi.org/10.1021/jo00247a026research-articleACS PublicationsRequest reuse permissionsArticle Views268Altmetric-Citations23LEARN 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-Scanned Digicon: a Digital Image Tube for Astronomical Spectroscopy (1975)

We have successfully fabricated, tested, and operated a digital image tube consisting of a magnetically focused image intensifier tube in which a self-scanned linear array of 1024 silicon photodiodes operating in the EBS mode serves as the photoelectron image detector, amplifier, and intermediate image storage device. Integral on-chip MOS shift registers driven by an external clock sequentially interrogate the photodiodes through MOS FET multiplex switch arrays. Each output frame is a sequence of 256 analog pulses on each of four video lines. Laboratory and observing tests show that the output signal is photoelectron shot noise limited over at least a range of 1-10(5) detected photoelectrons per picture element, indicating that single photon detection is achieved. High-resolution astronomical spectroscopy has been carried out in the coudé spectrograph of the 2.7-m telescope at McDonald Observatory. Examples are shown.
Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition (2020)

Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the innate and adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the notable exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight of the S trimer (17% for the HEK293 glycoform) they shield approximately 40% of the protein surface.
Cytokine regulation of the human burst-forming unit-megakaryocyte (1990)

The human burst-forming unit-megakaryocyte (BFU-MK) is a primitive megakaryocytic progenitor cell. A marrow cell population enriched for BFU-MK (CD34+ DR-) was obtained by monoclonal antibody labeling and fluorescence-activated cell sorting. CD34+DR- cells were assayed in a serum-depleted, fibrin clot culture system. Recombinant granulocyte- macrophage colony-stimulating factor (rGM-CSF), recombinant interleukin- 3 (rIL-3), and megakaryocyte colony-stimulating factor (MK-CSF), partially purified from human plasma, were each individually capable of promoting BFU-MK-derived colony formation. Recombinant erythropoietin, rG-CSF, rIL-4, rIL-6, and thrombocytopiesis stimulating factor, partially purified from human embryonic kidney cell conditioned media, had no stimulatory effect on BFU-MK-derived colony formation when added alone or in various combinations with either GM-CSF, IL-3, or MK-CSF, GM-CSF and IL-3, GM-CSF and MK-CSF, but not IL-3 and MK-CSF had additive actions in promoting BFU-MK-derived colony formation, rIL-1 alpha had no influence alone on BFU-MK cloning efficiency, but had a dose-dependent, synergistic effect with IL-3, but not with GM-CSF or MK- CSF. The synergistic relationship between IL-1 alpha and IL-3 was abrogated by addition of an IL-1 alpha neutralizing antibody but not by a GM-CSF neutralizing antiserum, suggesting that IL-1 alpha acts directly on the BFU-MK and not by stimulating marrow auxiliary cells to secondarily release additional cytokines. Information presented here indicates that the regulatory influence, acting on the different stages of megakaryocyte development, are stage-specific and accomplished by multiple cytokines.