gebhart/patrepeval huggingface dataset:
The crystal structure of staphylococcal nuclease refined at 1.7 Å resolution (1991)

The crystal structure of staphylococcal nuclease has been determined to 1.7 A resolution with a final R-factor of 16.2% using stereochemically restrained Hendrickson-Konnert least-squares refinement. The structure reveals a number of conformational changes relative to the structure of the ternary complex of staphylococcal nuclease 1,2 bound with deoxythymidine-3',5'-diphosphate and Ca2+. Tyr-113 and Tyr-115, which pack against the nucleotide base in the nuclease complex, are rotated outward creating a more open binding pocket in the absence of nucleotide. The side chains of Ca2+ ligands Asp-21 and Asp-40 shift as does Glu-43, the proposed general base in the hydrolysis of the 5'-phosphodiester bond. The significance of some changes in the catalytic site is uncertain due to the intrusion of a symmetry related Lys-70 side chain which hydrogen bonds to both Asp-21 and Glu-43. The position of a flexible loop centered around residue 50 is altered, most likely due to conformational changes propagated from the Ca2+ site. The side chains of Arg-35, Lys-84, Tyr-85, and Arg-87, which hydrogen bond to the 3'- and 5'-phosphates of the nucleotide in the nuclease complex, are unchanged in conformation, with packing interactions with adjacent protein side chains sufficient to fix the geometry in the absence of ligand. The nuclease structure presented here, in combination with the stereochemically restrained refinement of the nuclease complex structure at 1.65 A, provides a wealth of structural information for the increasing number of studies using staphylococcal nuclease as a model system of protein structure and function.
Autogenous regulation and kinetics of induction of Pseudomonas aeruginosa recA transcription as analyzed with operon fusions (1988)

A promoterless chloramphenicol acetyltransferase gene (cat) was used to construct recA-cat operon fusions to quantitatively examine the transcriptional regulation of the Pseudomonas aeruginosa recA gene in P. aeruginosa PAO. Wild-type P. aeruginosa containing the recA8-cat fusion was treated with methyl methanesulfonate (MMS) and showed immediate induction of chloramphenicol acetyltransferase (CAT) specific activity, whereas a recA::Tn501 mutant of P. aeruginosa containing recA8-cat showed no induction with MMS. This indicated that a functional copy of recA was required for derepression of recA transcription and that P. aeruginosa recA protein was a positive regulatory factor promoting its own expression. Compared with that in the wild type, the uninduced level of CAT in recA8-cat-containing cells was reduced by approximately one-half in the recA::Tn501 mutant, indicating that recA+-dependent spontaneous induction contributes to the uninduced levels of recA expression in P. aeruginosa. MMS (0.012%) caused recA-directed CAT synthesis to increase almost immediately, with maximum CAT activity, fourfold higher than uninduced levels, attained at 60 min postinduction. The kinetics of recA8-cat fusion activity were shown to be directly related to the MMS doses used. Another fusion called recAa1-cat, where cat was located between the two transcriptional terminators of the P. aeruginosa recA gene, also showed dose-dependent induction by MMS, but the CAT activity from recAa1-cat was only one-half of that obtained with recA8-cat under the same conditions. Treatment of recA+ P. aeruginosa containing recA8-cat with UV irradiation produced an immediate effect on recA8-cat transcription and showed little UV dose dependency at doses of 5 J/m2 or greater. Treatment with 10 J/m2 produced peak levels of recA-directed CAT activity, fivefold higher than background levels, by 60 min postirradiation; CAT activity remained at peak levels during the 120 min of the experiment. In contrast, nalidixic acid had a weak effect on recA8-cat expression in P. aeruginosa, although the response was dose dependent. Nalidixic acid (800 micrograms/ml) produced maximal CAT activity that was only twofold higher than background levels.
Hearts from transgenic pigs constructed with CD59/DAF genomic clones demonstrate improved survival in primates (1999)

We have previously created transgenic pigs bearing the human complement regulatory proteins CD59 and decay-accelerating factor (DAF) by either the intercellular transfer or the cDNA transgenic method. To achieve more physiologic protein expression, we constructed a new line of transgenic pigs with CD59 and DAF human genomic clones. We transplanted these CD59/DAF transgenic pig hearts into baboons immunosuppressed with cyclosporine, methylprednisone or leflunomide/mofetil mycophenolate. The four wild-type hearts survived for 20-80 min, whereas the four CD59/DAF hearts functioned for 85-130 h. Immunohistochemical staining showed levels of CD59 and DAF protein expression similar to that in human hearts. Wild-type and transgenic hearts demonstrate a similar level of IgM deposition, although transgenic hearts suffered less hyperacute rejection and thus less membrane attack complex deposition. The histology of the transgenic grafts after explant was consistent with acute vascular rejection, with a high level of IgG deposit compared with wild-type control. We conclude that this new line of CD59/DAF transgenic pigs express high levels of the transgene products, which conferred longer survival because of better protection from hyperacute rejection. Similar to previous transgenic pigs, however, these animals suffered from delayed xenograft rejection.
A long-range regulatory element of Hoxc8 identified by using the pClasper vector. (1996)

Hox genes are located in highly conserved clusters. The significance of this organization is unclear, but one possibility is that regulatory regions for individual genes are dispersed throughout the cluster and shared with other Hox genes. This hypothesis is supported by studies on several Hox genes in which even large genomic regions immediately surrounding the gene fail to direct the complete expression pattern in transgenic mice. In particular, previous studies have identified proximal regulatory regions that are primarily responsible for early phases of mouse Hoxc8 expression. To locate additional regulatory regions governing expression during the later periods of development, a yeast homologous recombination-based strategy utilizing the pClasper vector was employed. Using homologous recombination into pClasper, we cloned a 27-kb region around the Hoxc8 gene from a yeast artificial chromosome. A reporter gene was introduced into the coding region of the isolated gene by homologous recombination in yeast. This large fragment recapitulates critical aspects of Hoxc8 expression in transgenic mice. We show that the regulatory elements that maintain the anterior boundaries of expression in the neural tube and paraxial mesoderm are located between 11 and 19 kb downstream of the gene.
Effects of the timing of the administration of Mycoplasma hyopneumoniae bacterin on the development of lesions associated with porcine circovirus type 2 (2006)

To determine whether there is an effect of the timing of vaccination on porcine circovirus type 2 (PCV-2) replication and PCV-2-associated lesions, 78 pigs were randomly assigned to eight groups: group 1 (10 pigs) was vaccinated with a commercial Mycoplasma hyopneumoniae vaccine at two and four weeks of age, group 2 (nine pigs) was vaccinated at four and six weeks of age, group 3 (10 pigs) at six and eight weeks of age and group 4 (10 pigs) at eight and 10 weeks of age; group 5 (nine pigs) was vaccinated once with a double dose at four weeks of age, and group 6 (10 pigs) was vaccinated once with a double dose at eight weeks of age. Groups 7 and 8, both of 10 pigs, were not vaccinated. At eight weeks of age, the pigs in groups 1 to 7 were inoculated with PCV-2. Fourteen days after they had been inoculated, the pigs in groups 1, 4 and 5 had significantly (P<0.05) more copies of the PCV-2 genome in their serum than the unvaccinated pigs. Microscopically, 14 of the 68 inoculated pigs had normal lymphoid tissues, 40 had mild PCV-2-associated lymphoid lesions and 14 had moderate lesions. The mean overall lymphoid lesions (lymphoid depletion, granulomatous inflammation, and quantity of PCV-2 antigen in spleen, tonsil, and five lymph nodes) were significantly (P<0.05) more severe in groups 4 and 5 than in groups 2, 3, 7 and 8.
The lethal myospheroid gene of Drosophila encodes a membrane protein homologous to vertebrate integrin beta subunits. (1988)

A mutant of Drosophila melanogaster carrying the lethal(1) myospheroid mutation [l(1)mys] has a defective musculature and a phenotype that suggests a defect of basement membranes. The genomic region that is interrupted by an insertion in a mutant carrying l(1)mys was used to isolate cDNA clones, and their sequences are presented here. The cDNA sequence predicts a cysteine-rich integral membrane protein that displays 45% sequence identity to chicken integrin and the human fibronectin receptor beta subunit and much greater similarity over localized segments. These similarities extend to other vertebrate integrin beta subunits, and we conclude that the myospheroid protein is an integrin beta subunit of Drosophila. This implies evolutionary conservation of a group of transmembrane proteins that are receptors for extracellular matrix and, coupled with the myospheroid phenotype, indicates an important role for the interaction of cells with extracellular matrix during development.
From indomethacin to a selective COX-2 inhibitor. Development of indolalkanoic acids as potent and selective cyclooxygenase-2 inhibitors. (1997)

It has been known since the early 1970's that nonsteroidal antiinflammatory drugs (NSAIDs) exert their antinflammatory effects through the blocking of the synthesis of prostaglandins (PGs) by inhibiting cyc100xygenase (COX).! Cyc100xygenase was believed to be a single enzyme present constitutively in many tissues. It is believed to be involved in the maintenance of essential physiological function such as platelet aggregation, cytoprotection in the stomach and maintenance of normal kidney function. While inhibiting the production of proinflammatory prostaglandins at the inflammatory sites, NSAIDs also reduce the cytoprotective PGs in the gastrointestinal (GI) tract, leading to mechanism-based GI toxicity.2 The recent discovery of an inducible isoform of cyc100xygenase (COX-2) that is associated primarily with inflammation5 has led to the hypothesis that NSAID-induced toxicity in the GI tract may be caused by the inhibition of the beneficial constitutive isoform of cyclooxygenase (COX-I) in these tissues, while the antiinflammatory effect of NSAIDs is due to the inhibition of the inducible isoform (COX-2) at the inflammation site. A selective COX-2 inhibitor has the potential therefore to be an effective antiinflammatory drug with reduced GI toxicity compared to current NSAIDs. The recent identification of Dup 697, Nimesulide and Flosulide as selective COX-2 inhibitors has led to extensive efforts by several laboratories to design better compounds based on these three structures. We have pursued the aryl sulfonamide class of compounds which led to the identification of L-745,337 as a potent and selective COX-2 inhibitor. All these selective COX-2 inhibitors are methylsulfones and therefore it was also of interest to
Comparative Genomic Analyses of the Bacterial Phosphotransferase System (2005)

We report analyses of 202 fully sequenced genomes for homologues of known protein constituents of the bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS). These included 174 bacterial, 19 archaeal, and 9 eukaryotic genomes. Homologues of PTS proteins were not identified in archaea or eukaryotes, showing that the horizontal transfer of genes encoding PTS proteins has not occurred between the three domains of life. Of the 174 bacterial genomes (136 bacterial species) analyzed, 30 diverse species have no PTS homologues, and 29 species have cytoplasmic PTS phosphoryl transfer protein homologues but lack recognizable PTS permeases. These soluble homologues presumably function in regulation. The remaining 77 species possess all PTS proteins required for the transport and phosphorylation of at least one sugar via the PTS. Up to 3.2% of the genes in a bacterium encode PTS proteins. These homologues were analyzed for family association, range of protein types, domain organization, and organismal distribution. Different strains of a single bacterial species often possess strikingly different complements of PTS proteins. Types of PTS protein domain fusions were analyzed, showing that certain types of domain fusions are common, while others are rare or prohibited. Select PTS proteins were analyzed from different phylogenetic standpoints, showing that PTS protein phylogeny often differs from organismal phylogeny. The results document the frequent gain and loss of PTS protein-encoding genes and suggest that the lateral transfer of these genes within the bacterial domain has played an important role in bacterial evolution. Our studies provide insight into the development of complex multicomponent enzyme systems and lead to predictions regarding the types of protein-protein interactions that promote efficient PTS-mediated phosphoryl transfer.
FP 14.7: A Fully Integrated 2.7V 0.35pm CMOS VCO for (1998)

Figure 2 presents the circuit diagram. M1 and M2 (each 143.4pd0.36~m) form the differential negative resistor; they are biased with 2mA at a VGST of only about 140mV. The varactor diodes D1 and D2 are PMOS p++ source/drain diffusions in the nwell. Their layout and wiring are optimized for maximum quality factor. Figure 1 shows the measured quality factor of a varactor test structure. A quality of 5 to 6 is available in the 45GHz region. A buffer (M3 and M4 each 72.1pd0.4pm) is included to drive the off-chip loads. In a fully-integrated wireless application the VCO needs to drive only smaller on-chip loads. The buffer transistors are therefore biased from a 3.3V supply to obtain the necessary driving capability from reasonably sized buffer devices. The current bias transistor M5 (247.2yd0.4pm) is connected at the center tap of the inductor and does not load the tank. The parasitics of M1 and M2 represent 67% of the total tank capacitor. The parasitics of M3 and M4 contribute 15% and the fixed part of the varactor capacitance contributes 18%. The calculated quality factor of the tank capacitor is about 8.5.
Über Umlagerung von Phenol‐allyläthern in C‐Allyl‐phenole (1912)

d e s A c e t e s s i g e s t e r s und verwandter Verbindungen hat sich ein bemerkenswerter Unterschied gezeigt, der zwischen den 0-Alkylderivaten mit den gewiihnlichen gesLttigten A l k g l e n (Methyl, Athyl, Propyl usw.) einerseits und den %All yl'derivaten andererseits besteht.Wahrend die ersteren so gut wie gar keine Neigung zeigen, sich in die isomeren C-Derivate umzulagern, tritt diese Neigung bei den 0 -A 11 y lderivaten i n stitrkstem Mn5e hervor.0-A l l y 1-acetessigester wird beim Destillieren uber etwas Salmiak fast vollstiindig in 0-Allyla c e t essiges t e r verwandelt : 0-Allyl-acetylaceton CH, .C(OCaH5):CH.CO .CHS lagert sich unter denselben Bedingungen glatt in C-All y 1-a c e t y l a c e t o n CHa .CO.CH (CaHj).CO .C& um.Ganz Entsprechendes wurde bei den Oxymethylenverbindungen beobachtet.Wiihrend beispielsweise beim O x y m e t h y l e n -c a m p h e r der 0-Metbylather CHj .C(OG Ho) : CH.COa CIHs -+ CH3.CO .CH(CgH5).COa Ca Hs;
Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease (2000)

Fewer patients receiving initial treatment for PD with pramipexole developed dopaminergic motor complications than with levodopa therapy. Despite supplementation with open-label levodopa in both groups, the levodopa-treated group had a greater improvement in total UPDRS compared with the pramipexole group. JAMA. 2000;284:1931-1938.
Some Interesting Properties of Metals Confined in Time and Nanometer Space of Different Shapes (2001)

The properties of a material depend on the type of motion its electrons can execute, which depends on the space available for them (i.e., on the degree of their spatial confinement). Thus, the properties of each material are characterized by a specific length scale, usually on the nanometer dimension. If the physical size of the material is reduced below this length scale, its properties change and become sensitive to its size and shape. In this Account we describe some of the observed new chemical, optical, and thermal properties of metallic nanocrystals when their size is confined to the nanometer length scale and their dynamical processes are observed on the femto- to picosecond time scale.
Proposed American Standards for Mutations (1997)

The idea for an American Standard for Mutations came about because aviculturists who are interested in raising Psittacula mutations want and need to communicate more effectively with each other. The many problems with identification and naming of mutations can be reduced and someday eliminated by the adoption of a standard for notation and nomenclature. Interest in Indian Ring-necked Parakeet mutations is at an all time high. Enthusiasm with the purchase of a beautiful mutation often gives way to frustration when it comes to locating a suitable mate. The problem isn't a lack of birds, but rather a lack of consistency in nomenclature and understanding of inheritance modes. Different breeders are using various names for the same mutations. Understandably, those new to the mutation field are put off' by the confusion and contradiction in terms. Many do not understand the inheritance modes and promises are made to buyers that cannot he fulfilled. Some people feel they have been cheated, although in most cases this was unintentional due to lack of knowledge on the part of both buyer and seller. So who would you believe? We desperately need the American Standard for Mutations so anybody and everybody has a standardized reference. An American Standard will help the many new mutation enthusiasts and long-time breeders by providing a concise reference guide. The American Standard is a work in progress. As long as there are new mutations popping up, the American Standard will continue to grow. The information in the Proposed American Standard is intended as a framework for discussion and hopefully adoption by all interested parties. The Standard can also be adopted/adapted for use by breeders of other bird species that have mutations. While the American Standard for Mutations will provide us all with a common language and written identification of mutation types, it can't offer any guarantees. The phrase caveat emptor still applies. Individual aviculturists will have to educate themselves on what the various mutations should look like and make their purchase decisions accordingly. All questions, comments, and suggestions should be directed to Psittacula Sightings in care of the AFA Watchbird magazine.
Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"? (2011)

Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.
Reduction of exacerbations by the PDE4 inhibitor roflumilast - the importance of defining different subsets of patients with COPD (2011)

ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729.
The Expression, Purification, and Immunogenicity of a New Chimeric Virus-like Particle (2009)

Virus-like particles (VLPs) are highly immunogenic. In this study, gene fragments encoding hepatitis A virus (HAV) vp1 (aa 24-171), a hepatitis E virus (HEV) ORF2 gene fragment encoding aa 431-615, and gene fragments encoding a nine-peptide linker were spliced together. The spliced gene fragments were then inserted into the expression vector pBV220, resulting in the recombinant plasmid pBV-EA342, which expressed a 342-amino acid fusion protein. The fusion protein was expressed in Escherichia coli and specifically reacted to human hepatitis A- and E-positive sera. VLPs were formed during the renaturation of the EA342 fusion protein. The chimeric HAV and HEV VLPs were able to immunize KM mice, and they induced strong anti-HAV and anti-HEV humoral immune responses. These results are promising for future studies.
Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo (2005)

Va14Ja18 natural T (iNKT) cells are innate, immunoregulatory lymphocytes that recognize CD1d-restricted lipid Ags such as alpha-galactosylceramide (alpha GalCer). The immunoregulatory functions of iNKT cells are dependent upon either IFN-gamma or IL-4 production by these cells. We hypothesized that alpha GalCer presentation by different CD1d-positive cell types elicits distinct iNKT cell functions. In this study we report that dendritic cells (DC) play a critical role in alpha GalCer-mediated activation of iNKT cells and subsequent transactivation of NK cells. Remarkably, B lymphocytes suppress DC-mediated iNKT and NK cell activation. Nevertheless, alpha GalCer presentation by B cells elicits low IL-4 responses from iNKT cells. This finding is particularly interesting because we demonstrate that NOD DC are defective in eliciting iNKT cell function, but their B cells preferentially activate this T cell subset to secrete low levels of IL-4. Thus, the differential immune outcome based on the type of APC that displays glycolipid Ags in vivo has implications for the design of therapies that harness the immunoregulatory functions of iNKT cells.
Alteration of ASIC1 expression in clear cell renal cell carcinoma (2015)

ASIC1 is downregulated in CCRCC. ASIC1 expression may be potentially used as a novel biomarker and even a CCRCC therapeutic target. Further efforts will be made to clarify the mechanism of ASIC1 in occurrence, progression, and metastasis of CCRCC.