gebhart/patrepeval huggingface dataset:
Coordinated amino acid changes in homologous protein families (1988)

In the tobamovirus coat protein family, amino acid residues at some spatially close positions are found to be substituted in a coordinated manner [Altschuh et al. (1987) J. Mol. Biol., 193, 693]. Therefore, these positions show an identical pattern of amino acid substitutions when amino acid sequences of these homologous proteins are aligned. Based on this principle, coordinated substitutions have been searched for in three additional protein families: serine proteases, cysteine proteases and the haemoglobins. Coordinated changes have been found in all three protein families mostly within structurally constrained regions. This method works with a varying degree of success depending on the function of the proteins, the range of sequence similarities and the number of sequences considered. By relaxing the criteria for residue selection, the method was adapted to cover a broader range of protein families and to study regions of the proteins having weaker structural constraints. The information derived by these methods provides a general guide for engineering of a large variety of proteins to analyse structure-function relationships.
HLA–B27 misfolding and the unfolded protein response augment interleukin‐23 production and are associated with Th17 activation in transgenic rats (2009)

The IL-23/IL-17 axis is strongly activated in the colon of B27/Hubeta(2)m-transgenic rats with spondylarthritis-like disease. HLA-B27 misfolding and UPR activation in macrophages can result in enhanced induction of the pro-Th17 cytokine IL-23. These results suggest a possible link between HLA-B27 misfolding and immune dysregulation in this animal model, with implications for human disease.
Molecular Cloning of a Novel Human CC Chemokine Liver and Activation-regulated Chemokine (LARC) Expressed in Liver (1997)

Partial overlapping cDNA sequences likely to encode a novel human CC chemokine were identified from the GenBank Expressed Sequence Tag data base. Using these sequences, we isolated full-length cDNA encoding a protein of 96 amino acid residues with 20-28% identity to other CC chemokines. By Northern blot, this chemokine was mainly expressed in liver among various tissues and strongly induced in several human cell lines by phorbol myristate acetate. We thus designated this chemokine as LARC from Liver and Activation-Regulated Chemokine. We mapped the LARC gene close to the chromosomal marker D2S159 at chromosome 2q33-q37 by somatic cell and radiation hybrid mappings and isolated two yeast artificial chromosome clones containing the LARC gene from this region. To prepare LARC, we subcloned the cDNA into a baculovirus vector and expressed it in insect cells. The secreted protein started at Ala-27 and was significantly chemotactic for lymphocytes. At a concentration of 1 microg/ml, it also showed a weak chemotactic activity for granulocytes. Unlike other CC chemokines, however, LARC was not chemotactic for monocytic THP-1 cells or blood monocytes. LARC tagged with secreted alkaline phosphatase-(His)6 bound specifically to lymphocytes, the binding being competed only by LARC and not by other CC or CXC chemokines. Scatchard analysis revealed a single class of receptors for LARC on lymphocytes with a Kd of 0.4 nM and 2100 sites/cell. Collectively, LARC is a novel CC chemokine, which may represent a new group of CC chemokines localized on chromosome 2.
Immunization of patients with sjögren's syndrome with pneumococcal polysaccharide vaccine (1980)

Thirty-two patients with Sjögren's syndrome were randomly selected to receive either multivalent pneumococcal polysaccharide vaccine or saline placebo in a double-blind study. Among placebo treated patients, levels of antipneumococcal antibodies remained constant. Immunized patients developed significant elevations of antibody concentrations against all 12 capsular serotypes measured. Levels fell, but persisted above baseline, for 8 of the serotypes 6 months after immunization. During the 6-month study no clinical or serologic evidence of disease exacerbation occurred in either group. We conclude that pneumococcal vaccine can be safely and successfully administered to patients with Sjögren's syndrome.
100-mW kink-free blue-violet laser diodes with low aspect ratio (2003)

400-nm-band GaN-based laser diodes (LDs) operating with a kink-free output power of over 100 mW and having a low aspect ratio of 2.3 have been successfully fabricated for the first time. A new ridge structure, in which the outside of the ridge is covered with a stacked layer of Si on SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> and the ridge width is as narrow as 1.5 μm, is applied to realize high kink-free output power with a wide beam divergence angle parallel to the junction plane. A new layer structure around the active layer is demonstrated to be quite effective for obtaining a narrow beam divergence angle perpendicular to the junction plane, maintaining low threshold current. Ten LDs with low aspect ratio have been operated stably for over 1000 h under 30-mW continuous-wave operation at 60°C. Relative intensity noise measured under optical feedback with high-frequency modulation is as low as -125 dB/Hz. These results indicate that this LD is suitable for next-generation high-density optical storage systems.
Gestation Effects on the Hematological and Biochemical Profile of Nubian Ibex (Capra Nubiana) (2012)

The aim of this study was to investigate effect of gestation periods on thehaematological and biochemical parameters in adult captive wild (Capra nubiana),a group of 21Nubian ibexwas selected for the study. the mean values of the different (RBC) and (WBC) showed significant changes during gestation. (RBC), (PCV) and (Hb) increased while total (WBC) and segmented neutrophils increased after the second gestation period in the second period. The numbers of total leucocytes and segmented neutrophilsincreased after the second period. The concentration of the (AST) was declined during progression of gestation, On the other hand the concentration of (ALT) was increased and arrived maximum concentration at second period of gestation.
Hydrocarbon biosynthesis by bacteria : genes and hydrocarbon products. (2010)

University of Minnesota Ph.D. dissertation. December 2010. Major: Microbiology, Immunology and Cancer Biology. 1 computer file (PDF); xvi, 190 pages, appendices A-F. Ill. (some col.)
Targeting the PI3K and MAPK pathways to treat Kaposi’s sarcoma-associated herpes virus infection and pathogenesis (2007)

Cells require the ability to appropriately respond to signals in their extracellular environment. To initiate, inhibit and control these processes, the cell has developed a complex network of signaling cascades. The phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways regulate several responses including mitosis, apoptosis, motility, proliferation, differentiation and many others. It is not surprising, therefore, that many viruses target the PI3K and MAPK pathways as a means to manipulate cellular function. Recently, Kaposi's sarcoma-associated herpes virus (KSHV) has been added to the list. KSHV manipulates the PI3K and MAPK pathways to control such divergent processes as cell survival, cellular migration, immune responses, and to control its own reactivation and lytic replication. Manipulation of the PI3K and MAPK pathways also plays a role in malignant transformation. Here, the authors review the potential to target the PI3K and MAPK signaling pathways to inhibit KSHV infection and pathogenesis.
Physiology and genetics of the dimorphic fungusYarrowia lipolytica (1997)

The ascomycetous yeast Yarrowia lipolytica (formerly Candida, Endomycopsis, or Saccharomyces lipolytica) is one of the more intensively studied 'non-conventional' yeast species. This yeast is quite different from the well-studied yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe with respect to its phylogenetic evolution, physiology, genetics, and molecular biology. However, Y. lipolytica is not only of interest for fundamental research, but also for biotechnological applications. It secretes several metabolites in large amounts (i.e. organic acids, extracellular proteins) and the tools are available for overproduction and secretion of foreign proteins. This review presents a comprehensive overview on the available data on physiology, cell biology, molecular biology and genetics of Y. lipolytica.
Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization (2000)

Brain derived neurotrophic factor, BDNF, is a neurotrophin best characterized for its survival and differentiative effects on neurons expressing the trk B receptor tyrosine kinase. Although many of these neurons are lost in the BDNF(-)(/)(- )mouse, the early postnatal lethality of these animals suggests a wider function for this growth factor. Here, we demonstrate that deficient expression of BDNF impairs the survival of endothelial cells in intramyocardial arteries and capillaries in the early postnatal period, although the embryonic vasculature can remodel into arteries, capillaries and veins. BDNF deficiency results in a reduction in endothelial cell-cell contacts and in endothelial cell apoptosis, leading to intraventricular wall hemorrhage, depressed cardiac contractility and early postnatal death. Vascular hemorrhage is restricted to cardiac vessels, reflecting the localized expression of BDNF and trk B by capillaries and arterioles in this vascular bed. Conversely, ectopic BDNF overexpression in midgestational mouse hearts results in an increase in capillary density. Moreover, BDNF activation of endogenous trk B receptors supports the survival of cardiac microvascular endothelial cells cultured from neonatal mice. These results establish an essential role for BDNF in maintaining vessel stability in the heart through direct angiogenic actions on endothelial cells.
cDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue (1991)

Prolyl endopeptidase is a cytoplasmic serine protease. The enzyme was purified from porcine kidney, and oligonucleotides based on peptide sequences from this protein were used to isolate a cDNA clone from a porcine brain library. This clone contained the complete coding sequence of prolyl endopeptidase and encoded a polypeptide with a molecular mass of 80,751 Da. The deduced amino acid sequence of prolyl endopeptidase showed no sequence homology with other known serine proteases. [3H]Diisopropyl fluorophosphate was used to identify the active-site serine of prolyl endopeptidase. One labeled peptide was isolated and sequenced. The sequence surrounding the active-site serine was Asn-Gly-Gly-Ser-Asn-Gly-Gly. This sequence is different from the active-site sequences of other known serine proteases. This difference and the lack of overall homology with the known families of serine proteases suggest that prolyl endopeptidase represents a new type of serine protease.
147 Platelet cox-1 knockout mouse as a model of the effects of aspirin in the cardiovascular system (2017)

Introduction Aspirin acts as an anti-thrombotic drug by inhibiting platelet cyclooxygenase-1 (COX-1) and blocking the production of thromboxane A2, but it also has off-platelet actions that may limit its effectiveness. Since mice have very marked differences in aspirin pharmacokinetics they cannot be used to explore the effects of low dose aspirin in humans. To address these questions, we developed platelet COX-1 knockout mice (platelet-COX-1 -/- ) to recapitulate the effect of low-dose aspirin in humans. Methods and Results Cox-1 fl/fl mice were paired with Pf4-Cre mice to delete COX-1 in the MK lineage. The absence of COX-1 in platelets was confirmed by Western blot analysis, confocal immunofluorescence microscopy and by analysing the distribution of the COX-1 signal and mass with an high-throughput confocal imaging system. The production of thromboxane B2 (TxB 2 ) induced by collagen, A23187 and the PAR-4 activating peptide in platelet rich plasma and whole blood was significantly decreased in platelet-COX-1 -/- mice. This effect was not further reduced by the addition of aspirin in vitro . Further eicosanomic analysis was performed using LC-MS/MS of samples from untreated and A23187-stimulated whole blood. 11- and 15-hydroxyeicosatetraenoic acid (HETE), alongside TxB 2 formation were inhibited after platelet COX-1 deletion. Production of 12-HETE, coming from 12-lipoxygenase (LOX), and 5-HETE coming from leukocyte 5-LOX, was unchanged in platelet-COX-1 -/- mice. To better dissect the effects of aspirin in vivo , we used a thrombosis model caused by ferric chloride injury in the mouse carotid artery. Platelet COX-1 -/- mice, that recapitulate the effects of low-dose aspirin, formed unstable thrombi that were embolizing before producing a stable vessel occlusion. Interestingly, when a high dose of aspirin (10 mg/kg) was injected into the mice, the thrombus was stable and formed earlier than in the vehicle-treated mice. Conclusions We have produced the first platelet-COX-1 -/- mouse and characterised its phenotype and eicosanomic profile. This model is allowing us to mechanistically dissect the platelet and non-platelet effects of aspirin and so better model the effects of clinically important anti-thrombotic therapy.
Determination of density of follicles on various regions of the face by cyanoacrylate biopsy: correlation with sebum output (1994)

The density of follicles on various regions of the human face has received scant attention. We used cyanoacrylate follicular biopsies to determine the number of follicles on the forehead, cheek, chin and nose of 12 healthy adult white women. Sebum output was assessed on the same regions by means of Sebutape. The density of follicles and sebum output followed a centrolateral decreasing gradient. There was no correlation between these two parameters. These regional patterns are important for studies of the pathogenesis of common disorders of the face and their response to treatment.
Handbook of Aqueous Solubility Data (2010)

Over the years, researchers have reported solubility data in the chemical, pharmaceutical, engineering, and environmental literature for several thousand organic compounds. Until the first publication of the Handbook of Aqueous Solubility Data, this information had been scattered throughout numerous sources. Now newly revised, the second edition of
RNA Interference Trigger Variants: Getting the Most Out of RNA for RNA Interference-Based Therapeutics (2012)

The manifestation of RNA interference (RNAi)-based therapeutics lies in safe and successful delivery of small interfering RNAs (siRNAs), the molecular entity that triggers and guides sequence-specific degradation of target mRNAs. Optimizing the chemistry and structure of siRNAs to achieve maximum efficacy is an important parameter in the development of siRNA therapeutics. The RNAi protein machinery can tolerate a variety of non-canonical modifications made to siRNAs, each of which imparts advantageous properties. Here, we review these modifications to siRNAs in pre-clinical and clinical studies.
Characterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe (2013)

Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathology of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing molecular pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochemical characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and molecular pathway studies that involve GTPases.
State of the art in anti-cancer mAbs (2017)

Following Milstein's discovery, the monoclonal antibodies (mAbs) became a basic tool for biomedical science. In cancer field, since the first mAb was approved by the FDA a great improvement took place making of them a therapeutic option for many cancer types in the current clinical practice. Today, mAbs are being developed to target different molecules with different mechanisms of action and its target potential is unlimited. However, this huge and fast growing new field needs to be organized to better understand the treatment options we have to confront different cancer diseases. Current cancer targeted immunotherapies aim to achieve different goals like the regulation of osteoclast function, the delivery of cytotoxic drugs into tumor cells and the blockade of oncogenic pathways, neo-angiogenesis and immune checkpoints. Here, we reviewed the most relevant therapeutic mAbs for solid tumors available in current clinical practice.
Reduced driving voltage optical duobinary transmitter and its impact on transmission performance over standard single-mode fiber (2002)

We have investigated the impact of reducing the electrical driving voltage in a 10-Gb/s optical duobinary transmitter from 100% to 25% of the full swing 2 V/sub /spl pi// of the Mach-Zehnder modulator. Reduction in the driving voltage enhances the signal extinction ratio and reduces the complexity of the transmitter while maintaining the high tolerance of this modulation technique to chromatic dispersion. Transmission at 10 Gb/s with 25% of the full swing over a 182-km unrepeatered span of uncompensated standard single-mode fiber has been achieved with low sensitivity penalty.
Free radical-induced generation of isoprostanes in vivo. Evidence for the formation of D-ring and E-ring isoprostanes. (1994)

We recently reported the discovery that a series of novel prostaglandin (PG)F2-like compounds (F2-isoprostanes) are produced in vivo independent of the cyclooxygenase as products of free radical-catalyzed lipid peroxidation. F2-isoprostanes are initially formed in situ from arachidonic acid esterified to phospholipids and then released preformed. We have now investigated whether PGD2/E2-like isoprostanes are also produced by rearrangement of the PGG2-like intermediates involved in isoprostane formation. Using a variety of approaches utilizing mass spectrometry, compelling evidence was obtained for the presence of D2/E2-isoprostane-containing phosphospholipids in the liver (85 +/- 33 ng/g of liver) and free D2/E2-isoprostanes in the circulation (215 +/- 90 pg/ml) of rats treated with CCl4 to induce lipid peroxidation. In untreated rats, levels of D2/E2-isoprostanes esterified in liver phospholipids were much lower (0.90 +/- 0.10 ng/g), and free compounds could not be detected in the circulation (< 5 pg/ml). Interestingly, one of the E2-isoprostanes that would be expected to be formed in abundance, 8-epi-PGE2, was found to be a potent renal vasoconstrictor, and these effects could be abrogated by SQ29548, a thromboxane receptor antagonist. Further understanding of the biological consequences of the formation of these novel compounds and factors that influence their formation may provide valuable insights into the pathophysiology of oxidant injury.
Hoops for games (1997)

Place hoops on the floor in front of each child. On the instruction ‘in/out’ the children jump in and out of the hoops. Repeat ‘in/out’ several times then ‘shake it all about’! (the whole body).
Complement Regulation (1998)

Because of its strong potential for generating inflammation and causing tissue destruction the complement system has to be kept strictly under control. Cells of the host need special protection against the cytolytic complement system. This paper will describe how inappropriate activation of complement in the fluid phase is prevented and how viable human blood cells defend themselves against being destroyed and cleared away by the complement system. Since disturbances in complement regulation occasionally result in disease a brief reference will be made to two of the syndromes caused by complement regulator deficiency, hereditary angioedema (HAE) and paroxysmal nocturnal hemoglobinuria (PNH).
Effects of the Nd (1983)

Human skin fibroblasts were subjected to treatment with a Neodymium:YAG laser at 1060 nm with varying levels of energy determined by a reproducible method of dosimetry. DNA synthesis in the cells was measured by the incorporation of [3H]thymidine, and collagen production was monitored by the synthesis of nondialyzable [3H]hydroxyproline after incubation of cells with [3H]proline. Using energy levels equal to 1.7 X 10(3) J/cm2, a significant reduction in DNA synthesis was noted, while the cells remained viable as tested by the trypan blue exclusion test. With energy levels higher or equal to 2.3 X 10(3) J/cm2, the suppression of DNA synthesis was accompanied by cell nonviability. The collagen production, when measured immediately following the treatment with 1.7 X 10(3) J/cm2, was markedly reduced, and similar effects were observed with higher energy levels. However, when the cells were tested for collagen production at 20 hours following laser treatment, there was a significant decrease in collagen production at energy levels as low as 1.1 X 10(3) J/cm2, a dose that did not affect DNA synthesis or cell viability. Thus, the results indicate that the Nd:YAG laser can selectively suppress collagen production without affecting cell proliferation. These observations suggest that laser treatment could potentially be used to reduce collagen deposition in conditions such as keloids and hypertrophic scars.
Molecular Differentiation of High- and Moderate-Grade Human Prostate Cancer by cDNA Microarray Analysis (2003)

The prognosis of men with moderate-grade prostate cancer is uncertain. At present, there are few if any reliable molecular markers that can distinguish moderate-grade tumors from those that behave more aggressively. To better understand the molecular basis of human prostate cancer and potentially provide information toward more accurate prognosis, we measured and analyzed gene expression profiles of 13 high- and moderate-grade human prostate tumors using cDNA microarrays. The expression of 136 genes was observed to differ significantly (P < 0.001) between normal prostate and tumors using one-sample t testing and Wilcoxon ranking. Hierarchical clustering of genes demonstrated a relatively similar pattern of differential expression across the tumors. However, importantly, permutation t tests (two-tailed P < 0.001) revealed 21 genes whose expression profiles segregated moderate- and high-grade tumors from each other, which was significantly (P < 0.03) greater than what was expected by chance. These results were compared in silico with prostate cancer profiling efforts performed by other groups, including a meta-analysis of four data sets, which validated many of the dysregulated genes. We suggest that these data provide insight into the molecular nature of clinically aggressive prostate cancer.