gebhart/patrepeval huggingface dataset:
Comparative genomics of the emerging human pathogen Photorhabdus asymbiotica with the insect pathogen Photorhabdus luminescens (2009)

Our results suggest that North American isolates of Pa have acquired virulence against man via the acquisition of a plasmid and specific virulence factors with similarity to those shown to play roles in pathogenicity against humans in other bacteria.
Methodology for <i>in Situ</i> Protection of Aldehydes and Ketones Using Trimethylsilyl Trifluoromethanesulfonate and Phosphines: Selective Alkylation and Reduction of Ketones, Esters, Amides, and Nitriles (2013)

A methodology for selective transformations of ketones, esters, Weinreb amides, and nitriles in the presence of aldehydes has been developed. The use of a combination of PPh(3)-trimethylsilyl trifluoromethanesulfonate (TMSOTf) promotes selective transformation of aldehydes to their corresponding, temporarily protected, O,P-acetal type phosphonium salts. Because, hydrolytic work-up following ensuing reactions of other carbonyl moieties in the substrates liberates the aldehyde moiety, a sequence involving aldehyde protection, transformation of other carbonyl groups, and deprotection can be accomplished in a one-pot manner. Furthermore, the use of PEt(3) instead of PPh(3) enables ketones to be converted in situ to their corresponding O,P-ketal type phosphonium salts and, consequently, selective transformations of esters, Weinreb amides, and nitriles in the presence of ketones can be performed. This methodology is applicable to various dicarbonyl compounds, including substrates that possess heteroaromatic skeletons and hydroxyl protecting groups.
Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays. (1986)

A chemical selection procedure has been used to prepare a hybrid hybridoma cell line (P4C1) following fusion of two previously established hybridomas secreting antiperoxidase and antisubstance P, respectively. P4C1 secretes bispecific monoclonal antibody alongside the two parental antibodies, with no visible inactive heterologous heavy-light chain pairs. The bispecific monoclonal antibody is thus easy to purify in excellent yields. The advantage of its monovalency for one antigen and simultaneous binding of a marker enzyme has been explored for its potential use in competitive immunoassays. Its use in immunocytochemistry led to major improvements in sensitivity, signal-to-noise ratio, simplification of staining procedures, and ultrastructural preservation of subcellular elements. Particularly remarkable was that, unlike conventional procedures, the immunoreaction with the bispecific monoclonal antibody was homogeneously distributed across the entire thickness of a 50-micron section.
Cloning and tissue‐specific expression of the brain calcium channel β‐subunit (1991)

A cDNA clone encoding a protein with high homology to the beta-subunit of the rabbit skeletal muscle dihydropyridine-sensitive calcium channel was isolated from a rat brain cDNA library. This rat brain beta-subunit cDNA hybridizes to a 3.4 kb message that is expressed in high levels in the cerebral hemispheres and hippocampus but is significantly reduced in cerebellum. The open reading frame encodes 597 amino acids with a predicted mass of 65 679 Da which is 82% homologous with the skeletal muscle beta-subunit. The brain cDNA encodes a unique 153 amino acid C-terminus and predicts the absence of a muscle-specific 50 amino acid internal segment. It also encodes numerous consensus phosphorylation sites suggesting a role in calcium channel regulation. The corresponding human beta-subunit gene was localized to chromosome 17. Hence the encoded brain beta-subunit, which has a primary structure highly similar to its isoform in skeletal muscle, may have a comparable role as an integral regulatory component of a neuronal calcium channel.
Calcimimetic Compound Upregulates Decreased Calcium-Sensing Receptor Expression Level in Parathyroid Glands of Rats with Chronic Renal Insufficiency (2004)

The reduced expression level of the calcium-sensing receptor (CaR) is attributed to the hyposensitivity of parathyroid cells to extracellular calcium concentration [Ca2+]o, which plays a crucial role in the pathogenesis of secondary hyperparathyroidism (SHPT) in patients and rats with chronic renal insufficiency (CRI). Calcimimetic compounds have been demonstrated to improve the decreased sensitivity of CaR to extracellular calcium concentration and to suppress both parathyroid hormone (PTH) oversecretion and parathyroid cell proliferation. However, the effect of calcimimetics on the reduced CaR expression level in parathyroid cells in CRI remains unclarified. The aim of this investigation was to examine the effect of the calcimimetic compound NSP R-568 (R-568) on the CaR expression in the parathyroid cells of rats with experimental CRI. Subtotally nephrectomized rats were fed a high-phosphorus diet for 8 (n = 12; Nx-8 group) or 9 wk (n = 11; Nx-9 group) to induce severe SHPT. Another group of uremic rats were fed a high-phosphorus diet for 8 wk and then orally administered R-568 (100 micromol/kg body wt) once a day for 7 d (n = 11; Nx+R-568 group). Sham-operated rats that were fed a standard diet for 9 wk were used as controls (n = 8). R-568 treatment induced a significant reduction in plasma PTH level with significant decrease in serum calcium and without change in serum phosphorus concentration. Serum 1,25(OH)2D3 level was not affected by R-568 administration. CaR mRNA and protein levels in the Nx-8 and Nx-9 groups significantly decreased compared with those in the controls; however, no significant difference in these parameters was observed between the Nx-8 and Nx-9 groups. In the Nx+R-568 group, CaR mRNA and protein levels significantly increased compared with those in either the Nx-8 or Nx-9 group. R-568 was effective in reducing the number of proliferating cell nuclear antigen-positive cells along with parathyroid gland growth suppression in the Nx+R-568 group compared with that in the Nx-9 group. The results suggest that the calcimimetic compound R-568 upregulates decreased CaR expression, and the upregulation possibly has an enhancement effect on PTH secretion and parathyroid cell hyperplasia through the improved sensitivity of CaR to [Ca2+]o.
Interferometry in flow to sort unstained X‐ and Y‐chromosome‐bearing bull spermatozoa (2002)

Interferometry can be combined with flow cytometry and used to obtain significantly enriched fractions of X- and Y-bearing sperm without staining and UV light. Sorting speeds and purities at this point, however, are much lower than with the conventional method.
Nucleosides and Nucleotides. 184. Synthesis and Conformational Investigation of Anti-Fixed 3-Deaza-3-halopurine Ribonucleosides1,2 (1999)

A versatile synthetic route to 3-deaza-3-haloinosines 6−8 and 46, -adenosines 15−17 and 64, and -guanosines 25, 26, and 52 is described. 3-Deaza-3-chloro-, -bromo-, and -iodopurine ribonucleosides can be synthesized by treating the 3-deazapurine ribonucleosides with N-halosuccinimides. For the synthesis of 3-deaza-3-fluoropurine ribonucleosides, 5-formylimidazole-4-carboxamide ribosides 34 and 35 prepared from 5-iodoimidazole-4-carboxamide derivatives 29 and 31 were used as the key intermediates. The reaction of 34 and 35 with lithium (trimethylsilyl)acetylide and sodium cyanide, respectively, followed by appropriate manipulations gave 3-deaza-3-fluoroinosine derivative 46 and 3-deaza-3-fluoroguanosine derivative 52. 3-Deaza-3-fluoroadenosine (64) was also synthesized by selective reductive deamination of 4,6-diamino-7-fluoroimidazo[4,5-c]pyridine derivative 51, followed by deprotection. A conformational analysis using 1H NMR and NOE experiments showed that the introduction of halogens (chloro, bromo, and iodo) into the 3-position of 3-deazapurine ribonucleosides forced fixation of the glycosyl torsion angle in the anti region, but did not abnormally influence sugar puckering. On the other hand, 3-deaza-3-fluoropurine ribonucleosides should rotate freely around the glycosyl bond.
Non‐mRNA 3′ end formation: how the other half lives (2013)

The release of nascent RNA from transcribing RNA polymerase complexes is required for all further functions carried out by RNA molecules. The elements and processing machinery involved in 3' end formation therefore represent key determinants in the biogenesis and accumulation of cellular RNA. While these factors have been well-characterized for messenger RNA, recent work has elucidated analogous pathways for the 3' end formation of other important cellular RNA. Here, we discuss four specific cases of non-mRNA 3' end formation-metazoan small nuclear RNA, Saccharomyces cerevisiae small nuclear RNA, Schizosaccharomyces pombe telomerase RNA, and the mammalian MALAT1 large noncoding RNA-as models of alternative mechanisms to generate RNA 3' ends. Comparison of these disparate processing pathways reveals an emerging theme of evolutionary ingenuity. In some instances, evidence for the creation of a dedicated processing complex exists; while in others, components are utilized from the existing RNA processing machinery and modified to custom fit the unique needs of the RNA substrate. Regardless of the details of how non-mRNA 3' ends are formed, the lengths to which biological systems will go to release nascent transcripts from their DNA templates are fundamental for cell survival.
Failure diagnosis: a case study on modeling and analysis by Petri nets (2004)

Failure diagnosis in the context of DES was first formulated by Sampath et al. Where the notion of diagnosability and the associated diagnoser are proposed. Ushio et al. extended Sampath's study to systems modeled by Petri nets. This paper further assumes some of the transitions in a Petri net model are observable in the sense that its occurrence can be observed. The main contribution of this study shows how diagnosers and verifiers for systems modeled by Petri net are constructed accordingly. As shown by examples, the additional information from observed transitions adds diagnosability to the system.
Oxysterol Activators of Liver X Receptor and 9-cis-Retinoic Acid Promote Sequential Steps in the Synthesis and Secretion of Tumor Necrosis Factor-α from Human Monocytes (2002)

Liver X receptor alpha (LXRalpha), is a nuclear hormone receptor that is activated by oxysterols and plays a crucial role in regulating cholesterol and lipid metabolism in liver and cholesterol efflux from lipid-loaded macrophages. Here we show that treatment of human peripheral blood monocytes or monocytic THP-1 cells with the LXR ligand 22(R)-hydroxycholesterol (22(R)-HC), in combination with 9-cis-retinoic acid (9cRA), a ligand for the LXR heterodimerization partner retinoid X receptor (RXR), results in the specific induction of the potent pro-apoptotic and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Promoter analysis, inhibitor studies, and order-of-addition experiments demonstrated that TNF-alpha induction by 22(R)-HC and 9cRA occurs by a novel two-step process. The initial step involves 22(R)-HC-dependent induction of TNF-alpha mRNA, and intracellular accumulation of TNF-alpha protein, mediated by binding of LXRalpha/RXRalpha to an LXR response element at position -879 of the TNF-alpha promoter. Subsequent cell release of TNF-alpha protein occurs via a separable 9cRA-dependent, LXRalpha-independent step that requires de novo transcription and protein synthesis. Our findings reveal a potentially new dimension of the physiological role of LXRalpha and identify a unique multistep pathway of TNF-alpha production that may be of consequence to the normal function of LXR in monocyte/macrophages and in disease conditions such as atherosclerosis.
Activation of STAT3 by the Hepatitis C Virus Core Protein Leads to Cellular Transformation (2002)

The signal transducer and activator of transcription (STAT) family proteins are transcription factors critical in mediating cytokine signaling. Among them, STAT3 is often constitutively phosphorylated and activated in human cancers and in transformed cell lines and is implicated in tumorigenesis. However, cause of the persistent activation of STAT3 in human tumor cells is largely unknown. The hepatitis C virus (HCV) is a major etiological agent of non-A and non-B hepatitis, and chronic infection by HCV is associated with development of liver cirrhosis and hepatocellular carcinoma. HCV core protein is proposed to be responsible for the virus-induced transformation. We now report that HCV core protein directly interacts with and activates STAT3 through phosphorylation of the critical tyrosine residue. Activation of STAT3 by the HCV core in NIH-3T3 cells resulted in rapid proliferation and up-regulation of Bcl-XL and cyclin-D1. Additional expression of STAT3 in HCV core-expressing cells resulted in anchorage-independent growth and tumorigenesis. We propose that the HCV core protein cooperates with STAT3, which leads to cellular transformation.
High mobility AlGaN/GaN heterostructures grown by plasma-assisted molecular beam epitaxy on semi-insulating GaN templates prepared by hydride vapor phase epitaxy (2002)

We report on an extensive study of the growth and transport properties of the two-dimensional electron gas (2DEG) confined at the interface of AlGaN/GaN heterostructures grown by molecular beam epitaxy (MBE) on thick, semi-insulating GaN templates prepared by hydride vapor phase epitaxy (HVPE). Thick (∼20 μm) GaN templates are characterized by low threading dislocation densities (∼5×108 cm−2) and by room temperature resistivities of ∼108 Ω cm. We describe sources of parasitic conduction in our structures and how they have been minimized. The growth of low Al containing (x⩽0.05) AlxGa1-xN/GaN heterostructures is investigated. The use of low Al containing heterostructures facilitates the study of the 2DEG transport properties in the previously unexplored regime of carrier density ns⩽2×1012 cm−2. We detail the impact of MBE growth conditions on low temperature mobility. Using an undoped HVPE template that was residually n type at room temperature and characterized an unusually low dislocation density of ∼2×108 cm−2, we have grown an Al0.05Ga0.95N/GaN heterostructure with a record mobility of 75 000 cm2/V s at sheet density of 1.5×1012 cm−2 and T=4.2 K. The same heterostructure design grown on a semi-insulating HVPE template yielded a peak mobility of 62 000 cm2/V s at a density of ns=1.7×1012 cm−2 and T=4.2 K. The observation of the fractional quantum Hall effect at filling factor ν=5/3 in the AlGaN/GaN system is reported. It is also demonstrated that thick semi-insulating GaN templates grown by HVPE are a viable substrate for the growth of high electron mobility transistors. Typical Al0.25Ga0.75N/GaN heterostructures exhibit room temperature density of 1.0×1013 cm−3 and mobility of ∼1500 cm2/V s. The dc and rf characteristics of transistors grown by MBE on a HVPE template are presented.
Human Glioma Growth Is Controlled by MicroRNA-10b (2011)

MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas.
Why Men Die Younger (2000)

Abstract It is generally accepted that, on average, women live longer than men. Few, however, are aware that there is an underlying and consistent pattern of factors contributing to the sex mortality differential. This paper attempts to synthesize the evidence supporting and refuting the hypotheses for the sex mortality differential. The extent of the sex mortality differential is examined. It has existed since at least 1750; it occurs at all age groups, even prenatally, in nearly all animal species studied and for almost every major cause of death. Evidence supports both the biological/genetic and the social/cultural/environmental/behavioral schools of hypotheses, as well as interactions between the two, but the determining component may revolve around the differing chromosomes and hormones between the sexes. Behavioral distinctions, especially cigarette smoking, also affect the sex mortality differential.
Growth Factors and Cancer (1991)

Signaling pathways that mediate the normal functions of growth factors are commonly subverted in cancer. Oncogenes identified by a variety of approaches have been shown to function at critical steps in mitogenic signaling. Progression through the cell cycle requires the coordinated actions of members of two complementary classes of growth factors, and oncogenes appear to replace the actions of one set of these growth factors. Growth factors can also influence normal cell differentiation, and constitutive activation of growth-promoting pathways in cancer cells can modulate the cell phenotype as well. Paracrine actions of growth factors and cytokines may also influence the stepwise series of genetic events that lead to malignancy. New approaches for cancer therapy are being developed that intervene at various steps in growth factor signaling pathways.
FIBRINOGEN AND FIBRIN (1984)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Murine Leukemia Virus Particle Assembly Quantitated by Fluorescence Microscopy: Role of Gag-Gag Interactions and Membrane Association (2003)

In order to track the assembly of murine leukemia virus (MLV), we used fluorescence microscopy to visualize particles containing Gag molecules fused to fluorescent proteins (FPs). Gag-FP chimeras budded from cells to produce fluorescent spots, which passed through the same pore-size filters and sedimented at the same velocity as authentic MLV. N-terminal myristylation of Gag-FPs was necessary for particle formation unless wild-type Gag was coexpressed. By labeling nonmyristylated Gag with yellow FP and wild-type Gag with cyan FP, we could quantitate the coincorporation of two proteins into single particles. This experiment showed that nonmyristylated Gag was incorporated into mixed particles at approximately 50% the efficiency of wild-type Gag. Mutations that inhibit Gag-Gag interactions (K. Alin and S. P. Goff, Virology 216:418-424, 1996; K. Alin and S. P. Goff, Virology 222:339-351, 1996) were then introduced into the capsid (CA) region of Gag-FPs. The mutations P150L and R119C/P133L inhibited fluorescent particle formation by these Gag-FPs, but Gag-FPs containing these mutations could be efficiently incorporated into particles when coexpressed with wild-type Gag. When these mutations were introduced into nonmyristylated Gag-FPs, no incorporation into particles in the presence of wild-type Gag was detected. These data suggest that two independent mechanisms, CA interactions and membrane association following myristylation, cooperate in MLV Gag assembly and budding.
Gene replacement by homologous recombination in the multicellular green alga Volvox carteri (1997)

With only two different cell types, the haploid green alga Volvox represents the simplest multicellular model system. To facilitate genetic investigations in this organism, the occurrence of homologous recombination events was investigated with the intent of developing methods for gene replacement and gene disruption. First, homologous recombination between two plasmids was demonstrated by using overlapping nonfunctional fragments of a recombinant arylsulfatase gene (tubulin promoter/arylsulfatase gene). After bombardment of Volvox reproductive cells with DNA-coated gold microprojectiles, transformants expressing arylsulfatase constitutively were recovered, indicating the presence of the machinery for homologous recombination in Volvox. Second, a well characterized loss-of-function mutation in the nuclear nitrate reductase gene (nitA) with a single G --> A nucleotide exchange in a 5'-splice site was chosen as a target for gene replacement. Gene replacement by homologous recombination was observed with a reasonably high frequency only if the replacement vector containing parts of the functional nitrate reductase gene contained only a few nucleotide exchanges. The ratio of homologous to random integration events ranged between 1:10 and 1:50, i.e., homologous recombination occurs frequently enough in Volvox to apply the powerful tool of gene disruption for functional studies of novel genes.
Distinct Functional Lineages of Human Vα24 Natural Killer T Cells (2002)

CD1d-restricted autoreactive natural killer (NK)T cells have been reported to regulate a range of disease conditions, including type I diabetes and immune rejection of cancer, through the secretion of either T helper (Th)2 or Th1 cytokines. However, mechanisms underlying Th2 versus Th1 cytokine secretion by these cells are not well understood. Since most healthy subjects express <1 NKT cell per 1,000 peripheral blood lymphocytes (PBLs), we devised a new method based on the combined used of T cell receptor (TCR)-specific reagents alpha-galactosylceramide (alphaGalCer) loaded CD1d-tetramers and anti-V(alpha)24 monoclonal antibody, to specifically identify and characterize these rare cells in fresh PBLs. We report here that CD4(+) and CD4(-)CD8(-) (double negative [DN]) NKT cell subsets represent functionally distinct lineages with marked differences in their profile of cytokine secretion and pattern of expression of chemokine receptors, integrins, and NK receptors. CD4(+) NKT cells were the exclusive producers of interleukin (IL)-4 and IL-13 upon primary stimulation, whereas DN NKT cells had a strict Th1 profile and prominently expressed several NK lineage receptors. These findings may explain how NKT cells could promote Th2 responses in some conditions and Th1 in others, and should be taken into consideration for intervention in relevant diseases.