gebhart/patrepeval huggingface dataset:
Inositol Phosphorylceramide, a Novel Substance and the Chief Member of a Major Group of Yeast Sphingolipids Containing a Single Inositol Phosphate (1974)

Abstract About one-third of the nondeacylatable phospholipids in Saccharomyces cerevisiae have been shown to be a group of sphingolipids with a single phosphoinositol moiety. This group of lipids was obtained richly concentrated in high yield by several simple steps involving differential solubility. Four components of this group were further purified by liquid chromatography on base-treated porous silica beads. The major component of this group proved to be the novel substance, inositol phosphorylceramide, the ceramide consisting of hydroxysphinganine and a hydroxy C-26 fatty acid. Two other inositol phosphorylceramides were purified which differed from the major component in their ceramide moieties. Two glycolipids are minor members of this group of monoinositol-containing sphingolipids and one of these was purified, and had a composition consistent with its formulation as a mannosylinositol phosphorylceramide. The major inositol phosphorylceramide could be cleaved quantitatively by alkali to give an inositol monophosphate and could be cleaved by periodate to give a C-15 fragment. Periodate treatment followed by borohydride reduction and HCl hydrolysis gave a significant yield of phosphoserinol. These facts suggest strongly that the phosphoinositol moiety is attached to position 1 of the hydroxysphinganine. Data obtained with cells uniformly labeled with [3H]-inositol suggest that all significant ( g 1% lipid 3H) inositol-containing lipids in yeast have now been chemically characterized.
T cell depletion in bone marrow transplantation for leukemia: current results and future directions. (1988)

T cell depletion reduces the incidence and severity of graft-versus-host disease (GVHD) following bone marrow transplantation in man. Graft-versus-host disease of more than grade 2 severity is decreased from about 45% to about 10% in recipients of HLA-identical transplants. However, T cell depletion also increases the frequency of graft failure and leukemia relapse. Graft failure increases from about 1 to 10% following HLA-identical transplants. In patients with acute leukemia in first remission or with chronic myelogenous leukemia in chronic phase, leukemia relapse increases from about 20% to about 40%. Thus, although T cell depletion decreases GVHD, it increases graft failure and leukemia relapse such that survival is not convincingly improved. Several approaches to these problems are possible including increased pre- or post-transplant immune suppression, more effective antileukemia therapy or selective T cell depletion. Preliminary results of these approaches are discussed and new directions suggested.
MYC-Induced Cancer Cell Energy Metabolism and Therapeutic Opportunities (2009)

Although cancers have altered glucose metabolism, termed the Warburg effect, which describes the increased uptake and conversion of glucose to lactate by cancer cells under adequate oxygen tension, changes in the metabolism of glutamine and fatty acid have also been documented. The MYC oncogene, which contributes to the genesis of many human cancers, encodes a transcription factor c-Myc, which links altered cellular metabolism to tumorigenesis. c-Myc regulates genes involved in the biogenesis of ribosomes and mitochondria, and regulation of glucose and glutamine metabolism. With E2F1, c-Myc induces genes involved in nucleotide metabolism and DNA replication, and microRNAs that homeostatically attenuate E2F1 expression. With the hypoxia inducible transcription factor HIF-1, ectopic c-Myc cooperatively induces a transcriptional program for hypoxic adaptation. Myc regulates gene expression either directly, such as glycolytic genes including lactate dehydrogenase A (LDHA), or indirectly, such as repression of microRNAs miR-23a/b to increase glutaminase (GLS) protein expression and glutamine metabolism. Ectopic MYC expression in cancers, therefore, could concurrently drive aerobic glycolysis and/or oxidative phosphorylation to provide sufficient energy and anabolic substrates for cell growth and proliferation in the context of the tumor microenvironment. Collectively, these studies indicate that Myc-mediated altered cancer cell energy metabolism could be translated for the development of new anticancer therapies.
Multimode Light Microscopy and the Dynamics of Molecules, Cells, and Tissues (1993)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
PCR-Based Detection of Coxiella burnetii from Clinical Samples (2003)

Q fever is caused by Coxiella burnetii, an organism widely found in nature and responsible for infections in arthropods, pets, domestic and wild animals, as well as humans (1,2). Conventional diagnosis of Q fever is mainly based on serological tests, such as immunofluorescence, enzyme-linked immunosorbent assay, and complement fixation (3). Isolation of C. burnetii is performed in cell culture, animals or embryonated chicken eggs, however, the procedure is time-consuming and hazardous and therefore restricted to specialized laboratories. The highly sensitive polymerase chain reaction (PCR) was shown to be a useful tool for the detection of C. burnetii-specific genomic DNA sequences in biological samples (4–9). A PCR assay designated Trans-PCR, which targets a repetitive, transposon-like element (5–8) proved to be specific and sensitive. However, the numerous DNA extraction steps required are time-consuming and carry a high risk of carryover contamination, thus reducing the assay’s sensitivity.
Framework for Network Co-Simulation (2014)

The Framework for Network Co-Simulation (FNCS) uses a federated approach to integrate simulations which may have differing time scales. Special consideration is given to integration with a communication network simulation such that inter-simulation messages may be optionally routed through and delayed by such a simulation. In addition, FNCS uses novel time synchronization algorithms to accelerate co-simulation including the application of speculative multithreading. FNCS accomplishes all of these improvements with minimal end user intervention. Simulations can be integrated using FNCS while maintaining their original model input files simply by linking with the FNCS library and making appropriate calls into the FNCS API.
Colicin A receptor: role of two Escherichia coli outer membrane proteins (OmpF protein and btuB gene product) and lipopolysaccharide (1982)

ompF cells were completely resistant to colicin A, whereas btuB cells were partially resistant. The OmpF protein, in the presence of added lipopolysaccharide, inactivated colicin A. This inactivation was enhanced by added btuB gene product, btuB gene product with lipopolysaccharide did not inactivate colicin A. These data, together with the observation that vitamin B12 protected btuB+ cells from the killing effect of colicin A, suggest that the colicin A receptor in Escherichia coli K-12 is composed of the OmpF protein, the btuB gene product, and lipopolysaccharide.
Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. (1980)

During the period 1955 to 1974 inclusive, 826 patients developed Crohn's disease and were registered citizens of Stockholm County at the time of definite diagnosis. These patients were followed up and investigated with reference to the occurrence of and outcome after treatment for anal fistulae. These fistulae were recorded in 184 patients (23%). The incidence of anal fistulae increased the further distally the intestinal lesion was located. Healing followed local operation for anal fistula before curative intestinal resection in approximately 60% of the patients with small intestinal and combined ileocolic disease. However, patients with colonic Crohn's disease did not heal after such treatment. When curative intestinal resection was the primary procedure, 47% of the patients healed spontaneously. Small intestinal and combined ileocolic disease was associated with a good prognosis--90% were healed at follow-up, while patients with colonic disease had a poor prognosis. The combination of rectal Crohn's disease and anal fistula invariably led to proctocolectomy.
Peptibodies: A flexible alternative format to antibodies (2012)

Peptibodies or peptide-Fc fusions are an attractive alternative therapeutic format to monoclonal antibodies. They consist of biologically active peptides grafted onto an Fc domain. This approach retains certain desirable features of antibodies, notably an increased apparent affinity through the avidity conferred by the dimerization of two Fcs and a long plasma residency time. Peptibodies can be made in E. coli using recombinant technology. The manufacturing process involves fermentation and downstream processing, including refolding and multiple column chromatographic steps, that result in overall yields and quality suitable for commercial development. Romiplostim, marketed under the brand name Nplate®, is the first peptibody to be approved by the United States Food and Drug Administration and the European Medicines Agency and is indicated for the treatment of immune thrombocytopenic purpura. AMG 386, a peptibody antagonist to angiopoietins 1 and 2, is being evaluated in Phase 3 clinical testing in combination with chemotherapy in women with ovarian cancer. AMG 819, a peptibody targeting nerve growth factor for pain has also progressed to clinical trials. These peptibodies illustrate the versatility of the modality.
8.4: Distinguished Paper : A Full Color Eyewear Display Using Holographic Planar Waveguides (2008)

Abstract A full color eyewear display with over 85% see‐through transmittance and 2500cd/m 2 brightness was developed. Very low color crosstalk, less than 0.008 Δu'v' uniformity and 120% NTSC color gamut were achieved. Waveguides with two in‐ and out‐coupling hologram elements enabled simple configuration with side‐mounted microdisplays.
More Than Just a Surface Thing: Rice Infection by Magnaporthe grisea (1999)

The common names for plant diseases are as provocative as they are venerable: the blotches, blights, and bunts; the scabs, smuts, and rusts; mildews, powdery or downy. Many of the names are centuries old, appearing in the Bible and utilized by the ancient Romans to describe agricultural diseases
DOT1L/KMT4 Recruitment and H3K79 Methylation Are Ubiquitously Coupled with Gene Transcription in Mammalian Cells (2008)

The histone H3 lysine 79 methyltransferase DOT1L/KMT4 can promote an oncogenic pattern of gene expression through binding with several MLL fusion partners found in acute leukemia. However, the normal function of DOT1L in mammalian gene regulation is poorly understood. Here we report that DOT1L recruitment is ubiquitously coupled with active transcription in diverse mammalian cell types. DOT1L preferentially occupies the proximal transcribed region of active genes, correlating with enrichment of H3K79 di- and trimethylation. Furthermore, Dot1l mutant fibroblasts lacked H3K79 di- and trimethylation at all sites examined, indicating that DOT1L is the sole enzyme responsible for these marks. Importantly, we identified chromatin immunoprecipitation (ChIP) assay conditions necessary for reliable H3K79 methylation detection. ChIP-chip tiling arrays revealed that levels of all degrees of genic H3K79 methylation correlate with mRNA abundance and dynamically respond to changes in gene activity. Conversion of H3K79 monomethylation into di- and trimethylation correlated with the transition from low- to high-level gene transcription. We also observed enrichment of H3K79 monomethylation at intergenic regions occupied by DNA-binding transcriptional activators. Our findings highlight several similarities between the patterning of H3K4 methylation and that of H3K79 methylation in mammalian chromatin, suggesting a widespread mechanism for parallel or sequential recruitment of DOT1L and MLL to genes in their normal "on" state.
Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes (2020)

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
Interaction of the C-terminal region of p105 with the nuclear localisation signal of p50 is required for inhinition of NF-ϰB binding activity (1993)

DNA binding of the homodimeric p50 subunit of NF-kappa B was inhibited by a bacterially expressed protein containing the ankyrin repeats present in the C-terminus of the p105 precursor but not by the I kappa B protein MAD-3. However p50 was retained on protein affinity matrices containing either the C-terminal ankyrin repeats of p105 or MAD-3. To investigate the interaction between p50 and proteins containing ankyrin repeats we have used a number of approaches to probe the accessibility of the p50 nuclear localisation signal in the protein complex. A monoclonal antibody recognising a linear epitope either very close to, or including, the nuclear localisation signal of the p50 protein could immunoprecipitate p50 homodimers but was unable to precipitate the protein when it was bound to the C-terminal region of p105. A close association between the nuclear localisation signal of p50 and the C-terminal region of p105 was also suggested by protease accessibility experiments. While the nuclear localisation signal of free p50 is extremely susceptible to cleavage with trypsin the same site is masked in the presence of the C-terminal ankyrin repeats of p105 and, to a lesser extent MAD-3. Removal of the nuclear localisation signal by trypsin digestion generates a protein that is fully competent for DNA binding but is refractile to inhibition by the C-terminal ankyrin repeats of p105. Addition of DNA destabilises complexes between p50 and ankyrin repeat containing proteins, increasing the susceptibility of the nuclear localisation signal to trypsin cleavage. The data suggest that there is a rapid exchange of p50 between complexes containing DNA or I kappa B proteins via a metastable complex containing DNA, p50 and I kappa B.
Mobile, Game-Based Training for Myoelectric Prosthesis Control (2018)

Myoelectric prostheses provide upper limb amputees with hand and arm movement control using muscle activity of the residual limb, but require intensive training to effectively operate. The result is that many amputees abandon their prosthesis before mastering control of their device. In the present study, we examine a novel, mobile, game-based approach to myoelectric prosthesis training. Using the non-dominant limb in a group of able-bodied participants to model amputee pre-prosthetic training, a significant improvement in factors underlying successful myoelectric prosthesis use, including muscle control, sequencing, and isolation were observed. Participants also reported high levels of usability, and motivation with the game-based approach to training. Given fiscal or geographic constraints that limit pre-prosthetic amputee care, mobile myosite training, as described in the current study, has the potential to improve rehabilitation success rates by providing myosite training outside of the clinical environment. Future research should include longitudinal studies in amputee populations to evaluate the impact of pre-prosthetic training methods on prosthesis acceptance, wear time, abandonment, functional outcomes, quality of life, and return to work.
CD101: a novel long‐acting echinocandin (2016)

CD101 is a novel echinocandin drug being developed to treat severe fungal infections including invasive candidiasis. We have performed a series of studies to evaluate the antifungal properties of CD101 against both echinocandin-susceptible and -resistant Candida strains. Antifungal susceptibility testing performed on a collection of 95 Candida strains including 30 caspofungin-resistant isolates containing fks mutations demonstrated comparable antifungal potency of CD101 relative to micafungin (MCF) across different Candida species. Comparable kinetic inhibition of glucan synthase activity was also observed for CD101 and MCF on both wild-type (WT) and resistant fks mutant Candida strains. Similarly, both drugs yielded nearly identical values for a mutant prevention concentration. In a murine model of invasive candidiasis, CD101 displayed better or at least comparable efficacy relative to MCF in treating WT or fks mutant Candida albicans. An exceptional long-lived pharmacokinetic profile was observed in mice following a single dose of CD101. Collectively, CD101 has great potential not only in treating invasive Candida infections but also in preventing emergence of resistance to currently approved echinocandin drugs.
Demonstration of an 8&#x00D7;8-bit RSFQ multi-port register file (2013)

As a part of the 8-bit RSFQ processor datapath development, we have designed, fabricated, and experimentally demonstrated an 8×8-bit RSFQ multi-port register file. The register file provides input data operands and stores Arithmetic Logic Unit (ALU) results. It can perform two simultaneous non-destructive “read” operations and one “write” operation and is capable of storing eight 8-bit words. The distinct feature of the design is an extensive use of passive transmission lines (PTLs) for very complex interconnects inside the register file. The register file is designed for integration with recently demonstrated 20-GHz 8-bit RSFQ ALU. It is fabricated with the standard HYPRES's 1.0-um 4.5-kA/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> process. The circuit is placed on a 1 cm × 1 cm chip and consists of ~4,000 Josephson junctions.
Antigenic determinants of high mobility group chromosomal proteins 1 and 2 (1982)

The antigenic determinants of nonhistone high mobility group chromosomal proteins 1 (HMG-1) and 2 (HMG-2) were studied with rabbit antisera elicited against HMG-1 and against HMG-2 and monoclonal antibodies elicited by HMG-1. The monoclonal antibodies did not distinguish between the two proteins, suggesting that they have specificity toward a shared determinant. Whereas anti-HMG-1 did not, anti-HMG-2 did distinguish between the proteins, suggesting that the anti-HMG-2 serum contains antibodies against peptides which differ between the proteins. Peptides were generated from HMG-1 and HMG-2 by controlled digestion with trypsin and pepsin. Analysis of the digests by ELISA and by sodium dodecyl sulfate electrophoresis followed by diazobenzyloxymethyl transfer, antibody binding and autoradiography revealed that most of the antibodies are against sequential determinants some of which are smaller than 3000 in molecular weight.
Role of nitric oxide in tumor microcirculation. Blood flow, vascular permeability, and leukocyte-endothelial interactions. (1997)

The present study was designed to define the role of nitric oxide (NO) in tumor microcirculation, through the direct intravital microcirculatory observations after administration of NO synthase (NOS) inhibitor and NO donor both regionally and systemically. More specifically, we tested the following hypotheses: 1) endogenous NO derived from tumor vascular endothelium and/or tumor cells increases and/or maintains tumor blood flow, decreases leukocyte-endothelial interactions, and increases vascular permeability, 2) exogenous NO can increase tumor blood flow via vessel dilatation and decrease leukocyte-endothelial interactions, and 3) NO production and tissue responses to NO are tumor dependent. To this end, a murine mammary adenocarcinoma (MCaIV) and a human colon adenocarcinoma (LS174T) were implanted in the dorsal skinfold chamber in C3H and severe combined immunodeficient mice, respectively, and observed by means of intravital fluorescence microscopy. Both regional and systemic inhibition of endogenous NO by N omega-nitro-L-arginine methyl ester (L-NAME; 100 mumol/L superfusion or 10 mg/kg intravenously) significantly decreased vessel diameter and local blood flow rate. The diameter change was dominant on the arteriolar side. Superfusion of NO donor (spermine NO, 100 mumol/L) increased tumor vessel diameter and flow rate, whereas systemic injection of spermine NO (2.62 mg/kg) had no significant effect on these parameters. Rolling and stable adhesion of leukocytes were significantly increased by intravenous injection of L-NAME. In untreated animals, both MCaIV and LS174T tumor vessels were leaky to albumin. Systemic NO inhibition significantly attenuated tumor vascular permeability of MCaIV but not of LS174T tumor. Immunohistochemical studies, using polyclonal antibodies to endothelial NOS and inducible NOS, revealed a diffuse pattern of positive labeling in both MCaIV and LS174T tumors. Nitrite and nitrate levels in tumor interstitial fluid of MCaIV but not of LS174T were significantly higher than that in normal subcutaneous interstitial fluid. These results support our hypotheses regarding the microcirculatory response to NO in tumors. Modulation of NO level in tumors is a potential strategy for altering tumor hemodynamics and thus improving oxygen, drug, gene vector, and effector cell delivery to solid tumors.
Metabolism and Influence of Glycine-Extended Gastrin on Gastric Acid Secretion in Man (1996)

Glycine-extracted gastrins are the immediate precursors of the bioactive carboxyamidated gastrins. The effect on gastric acid secretion and the pharmacokinetics of glycine-extended gastrin-17 were studied in 8 normal subjects. The elimination in plasma after bolus injection was biexponential, the half-lives being 4.1 +/- 0.2 and 21.8 +/- 0.9 min, and clearance and apparent volume of distribution being 7.9 +/- 0.6 ml/kg/min and 69.5 +/- 2.7 ml/kg, respectively. Infusion of the peptide at three consecutive dose rates did not stimulate gastric acid secretion, although plasma concentrations reached supraphysiological levels. Nor did glycine-extended gastrin-17 influence submaximal acid secretion induced by amidated gastrin-17. In contrast to amidated gastrins, the concentration of glycine-extended gastrins in peripheral venous plasma did not increase significantly after a meal. The postprandial rise in amidated gastrin was unaffected by concomitant infusion of glycine-extended gastrin-17. A reduction in glycine-extended gastrin-17 concentrations in plasma during constant-rate infusion of the peptide was observed after a protein meal (p < 0.05). This reduction was reflected by an increase in glycine-extended gastrin-17 is without immediate effect on gastric output in man. The postprandial increase in clearance might be due to increased splanchnic blood flow with subsequently increased peptide elimination.