gebhart/patrepeval huggingface dataset:
The Genome of Salmonella enterica Serovar Typhi (2007)

The generation of complete genome sequences provides a blueprint that facilitates the genetic characterization of pathogens and their hosts. The genome of Salmonella enterica serovar Typhi (S. Typhi) harbors ~5 million base pairs encoding some 4000 genes, of which >200 are functionally inactive. Comparison of S. Typhi isolates from around the world indicates that they are highly related (clonal) and that they emerged from a single point of origin ~30,000-50,000 years ago. Evidence suggests that, as well as undergoing gene degradation, S. Typhi has also recently acquired genes, such as those encoding the Vi antigen, by horizontal transfer events.
1.3‐Dipolare Cycloadditionen, XXIII. Einige Beobachtungen zur Addition organischer Azide an CC‐Dreifachbindungen (1965)

Abstract Wenngleich elektronenarme Azide sich bevorzugt an elektronenreiche Alkine anlagern, lassen sich aus Tosylazid mit Acetylendicarbonsäureester, Propiolsäureester, Phenylpropiolsäureester und Phenylacetylen die 1‐Tosyl‐1.2.3‐triazole erhalten. Phenylazid tritt mit Methyl‐propiolat zu 88% 1‐Phenyl‐triazol‐4‐carbonester und 12% des isomeren 5‐Carbonesters zusammen. 4‐Nitro‐phenylazid addiert sich rascher als 4‐Methoxy‐phenylazid an Äthoxy‐acetylen zum 1‐Aryl‐5‐äthoxy‐triazol. Benz‐in, das als gespanntes Cycloalkin betrachtet werden kann, nimmt glatt Phenylazid und 4‐Methoxy‐phenylazid auf.
Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). (1994)

The results of several experimental studies of focal ischemia and anecdotal observations suggest that leukocytes may contribute to the injury initiated by an arterial occlusion. The timing and the nature of leukocyte responses in evolving brain infarcts (either human or experimental) are incompletely characterized. This is a study of experimental brain lesions in 96 Wistar rats that underwent occlusion of a large intracranial artery for variable intervals ranging between 30 minutes and 7 days. The experimental model, based on the occlusion of a middle cerebral artery ostium via the insertion of a nylon monofilament through the external carotid artery, does not require opening the skull; therefore, the inflammatory response is not influenced by the effects of craniotomy and changes in intracranial pressure are only those induced by the ischemic lesion. All 96 animals having the same type of arterial occlusion developed an ischemic brain lesion (limited to the territory of the corresponding artery) that evolved into an area of extensive neuronal necrosis over a period of 6 to 12 hours followed by pan-necrosis (infarct) approximately 60 hours later. In this study, leukocytes (in particular polymorphonuclear cells) were detected in the microvessels (capillaries and venules) of the ischemic hemisphere as early as 30 minutes after the arterial occlusion. Numbers of intravascular neutrophils peaked at 12 hours, whereas intraparenchymal granulocytes were most numerous at 24 hours; a few granulocytes were visible in the brain infarct as late as day 7. Circulating monocytes were first detected within the capillaries/venules of the ischemic area after 4 to 6 hours. Platelet aggregates were more abundant in the arterial than the venous side of the circulation, and luminal obstruction of arteries by platelet aggregates became noticeable only 48 hours after the arterial occlusion. Fibrin thrombi were conspicuous for their absence. These observations provide the background for studies that will attempt to unravel the relationship between the biological responses of leukocytes and neuronal necrosis secondary to focal ischemia.
Directed evolution approach to a structural genomics project: Rv2002 from Mycobacterium tuberculosis (2003)

One of the serious bottlenecks in structural genomics projects is overexpression of the target proteins in soluble form. We have applied the directed evolution technique and prepared soluble mutants of the Mycobacterium tuberculosis Rv2002 gene product, the wild type of which had been expressed as inclusion bodies in Escherichia coli. A triple mutant I6TV47MT69K (Rv2002-M3) was chosen for structural and functional characterizations. Enzymatic assays indicate that the Rv2002-M3 protein has a high catalytic activity as a NADH-dependent 3alpha, 20beta-hydroxysteroid dehydrogenase. We have determined the crystal structures of a binary complex with NAD(+) and a ternary complex with androsterone and NADH. The structure reveals that Asp-38 determines the cofactor specificity. The catalytic site includes the triad Ser-140Tyr-153Lys-157. Additionally, it has an unusual feature, Glu-142. Enzymatic assays of the E142A mutant of Rv2002-M3 indicate that Glu-142 reverses the effect of Lys-157 in influencing the pKa of Tyr-153. This study suggests that the Rv2002 gene product is a unique member of the SDR family and is likely to be involved in steroid metabolism in M. tuberculosis. Our work demonstrates the power of the directed evolution technique as a general way of overcoming the difficulties in overexpressing the target proteins in soluble form.
Polarization-sensitive interferometric synthetic aperture microscopy (2015)

Three-dimensional optical microscopy suffers from the well-known compromise between transverse resolution and depth-of-field. This is true for both structural imaging methods and their functional extensions. Interferometric synthetic aperture microscopy (ISAM) is a solution to the 3D coherent microscopy inverse problem that provides depth-independent transverse resolution. We demonstrate the extension of ISAM to polarization sensitive imaging, termed polarization-sensitive interferometric synthetic aperture microscopy (PS-ISAM). This technique is the first functionalization of the ISAM method and provides improved depth-of-field for polarization-sensitive imaging. The basic assumptions of polarization-sensitive imaging are explored, and refocusing of birefringent structures is experimentally demonstrated. PS-ISAM enables high-resolution volumetric imaging of birefringent materials and tissue.
Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21. (1991)

PTPG, the gene for protein-tyrosine phosphatase gamma (PTP gamma), maps to a region of human chromosome 3, 3p21, that is frequently deleted in renal cell carcinoma and lung carcinoma. One of the functions of protein-tyrosine phosphatases is to reverse the effect of protein-tyrosine kinases, many of which are oncogenes, suggesting that some protein-tyrosine phosphatase genes may act as tumor suppressor genes. A hallmark of tumor suppressor genes is that they are deleted in tumors in which their inactivation contributes to the malignant phenotype. In this study, one PTP gamma allele was lost in 3 of 5 renal carcinoma cell lines and 5 of 10 lung carcinoma tumor samples tested. Importantly, one PTP gamma allele was lost in three lung tumors that had not lost flanking loci. PTP gamma mRNA was expressed in kidney cell lines and lung cell lines but not expressed in several hematopoietic cell lines tested. Thus, the PTP gamma gene has characteristics that suggest it as a candidate tumor suppressor gene at 3p21.
The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease (2007)

Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (alpha(M)beta(2), CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen-Mac-1 interaction in fibrinogen-gamma(390-396A) knock-in mice or pharmacologically impeding fibrinogen-Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (gamma(377-395)) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen-Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the gamma(377-395) fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation.
Co-Culture with Bifidobacterium catenulatum Improves the Growth, Gut Colonization, and Butyrate Production of Faecalibacterium prausnitzii: In Vitro and In Vivo Studies (2020)

<i>Faecalibacterium prausnitzii</i> is a major commensal bacterium in the human gut. It produces short-chain fatty acids that promote intestinal health. However, the bacterium is extremely oxygen-sensitive, making it difficult to develop as a probiotic. To facilitate practical application of <i>F. prausnitzii</i>, we investigated factors that affect its growth and mammalian gut colonization. We evaluated cross-feeding interactions between <i>F. prausnitzii</i> and seven <i>Bifidobacterium</i> strains, and the anti-inflammatory properties of bacterial metabolites produced in co-culture, in vitro and in vivo. Co-culture of <i>F. prausnitzii</i> and <i>Bifidobacterium catenulatum</i>, with fructooligosaccharides as an energy source, resulted in the greatest viable cell-count and butyrate production increases. Further, the co-culture supernatant reduced the amount of proinflammatory cytokines produced by HT-29 cells and RAW 264.7 macrophages, an effect that was similar to that of butyrate. Furthermore, feeding mice both <i>Faecalibacterium</i> and <i>Bifidobacterium</i> enhanced <i>F. prausnitzii</i> gut colonization. Finally, feeding the co-culture supernatant decreased interleukin 8 levels in the colon and increased butyrate levels in the cecum in the dextran sodium sulfate-induced colitis mouse model. These observations indicate that the <i>Faecalibacterium</i>-<i>Bifidobacterium</i> co-culture exerts an anti-inflammatory effect by promoting <i>F. prausnitzii</i> survival and short-chain fatty acid production, with possible implications for the treatment of inflammatory bowel disease.
Use of dexmedetomidine in children after cardiac and thoracic surgery* (2006)

Our data suggest that dexmedetomidine is a well-tolerated and effective agent for both spontaneously breathing and mechanically ventilated patients following congenital cardiac and thoracic surgery.
Sites of stromelysin cleavage in collagen types II, IX, X, and XI of cartilage. (1991)

Human recombinant stromelysin-1 was shown to cleave four types of collagen (types II, IX, X, and XI) prepared from bovine and rat cartilages at specific sites. Stromelysin-1 cleaved salt-soluble native molecules of type IX collagen into two main triple-helical fragments, COL1 and COL2,3. Protein microsequencing identified the exact cleavage sites in the NC2 domain of all three chains, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Stromelysin-1 also acted as a "telopeptidase," in that it efficiently clipped intact molecules of types II and XI collagens at sites just inside their terminal cross-linking hydroxylysine residues. Native molecules of type X collagen were cleaved by stromelysin-1 within their triple helical domains at a COOH-terminal site that reduced the alpha 1(X) chain size by 10 kDa. These findings suggest an important role for stromelysin in the turnover and remodeling of the collagenous matrix of cartilage both normally and in degenerative joint disease.
Taxonomy, physiology and growth of Lactococcus lactis: a review (2001)

Lactococcus lactis species is one of the most important groups of lactic acid bacteria that are used in the dairy industry. The major functions of this species in dairy fermentation are the production of lactic acid from lactose, hydrolysis of casein and citric acid fermentation. Thus their metabolic end products and enzymes directly or indirectly have significant influence in determining the texture and flavour of the final products. In recent years, genetics and physiological properties of lactococci have considerable changed. Therefore, both for basic research and for application purposes in this paper the general view of the new taxonomic classification of Lactococcus lactis, the role of their plasmids and the physiology and nutritional requirements during growth are discussed.
Translocation of a small cytosolic calcium-binding protein (MRP-8) to plasma membrane correlates with human neutrophil activation. (1992)

To further understand the mechanisms involved in phagocyte activation in general and in NADPH oxidase activation in particular, a polyclonal antibody was raised in rabbit against a partially purified oxidase preparation. The enzyme was solubilized from zymosan-activated human neutrophils and resting cells and separated by preparative isoelectric focusing electrophoresis. A polyclonal antibody was raised in rabbit against the pI 5.0 fraction, which had the maximum superoxide-producing capacity. Analysis of the polyclonal antibody revealed marked differences between activated and resting neutrophils. The antibody recognized in particular an 8-kDa protein (p8) in resting human neutrophil cytosol and in the membrane of zymosan-activated cells. A polyclonal antibody (anti-p8) was raised against the pure cytosolic p8 protein. This anti-p8 reacted not only with p8, but also with cytosolic proteins of 14 kDa and 6 kDa. N-terminal amino acid sequence analysis of p8 revealed homology with the calcium-binding myeloid related protein (MRP-8). Upon neutrophil activation, translocation of the 8- and 14-kDa proteins to the membrane was observed with stimuli known to depend on extracellular calcium. In calcium-depleted medium, the absence of translocation correlated with a depression of superoxide production, supporting a role for the calcium-binding protein in cellular activation.
Apolipoprotein B-containing Lipoprotein Particle Assembly (2004)

We previously proposed that the N-terminal 1000-residue betaalpha(1) domain of apolipoprotein B (apoB) forms a bulk lipid pocket homologous to that of lamprey lipovitellin. In support of this "lipid pocket" hypothesis, we demonstrated that apoB:1000 (residues 1-1000) is secreted by a stable transformant of McA-RH7777 cells as a monodisperse particle with high density lipoprotein 3 (HDL(3)) density. In contrast, apoB:931 (residues 1-931), missing only 69 residues of the sequence homologous to lipovitellin, was secreted as a particle considerably more dense than HDL(3). In the present study we have determined the stoichiometry of the lipid component of the apoB:931 and apoB:1000 particles. The secreted [(3)H]glycerol-labeled apoB:1000 particles, isolated by nondenaturing gradient gel electrophoresis, contained 50 phospholipid (PL) and 11 triacylglycerol (TAG) molecules/particle. In contrast, apoB:931 particles contained only a few molecules of PL and were devoid of TAG. The unlabeled apoB:1000 particles, isolated by immunoaffinity chromatography, contained 56 PL, 8 TAG, and 7 cholesteryl ester molecules/particle. The surface to core lipid ratio of apoB:1000-containing particles was approximately 4:1 and was not affected by oleate supplementation. Although very small amounts of microsomal triglyceride transfer protein (MTP) were associated with apoB:1000 particles, it never approached a 1:1 molar ratio of MTP to apoB. These results support a model in which (i) the first 1000 amino acid residues of apoB are competent to complete the lipid pocket without a structural requirement for MTP; (ii) a portion, or perhaps all, of the amino acid residues between 931 and 1000 of apoB-100 are critical for the formation of a stable, bulk lipid-containing nascent lipoprotein particle, and (iii) the lipid pocket created by the first 1000 residues of apoB-100 is PL-rich, suggesting a small bilayer type organization and has a maximum capacity on the order of 50 molecules of phospholipid.
Moving Least Squares Coordinates (2010)

Abstract We propose a new family of barycentric coordinates that have closed‐forms for arbitrary 2D polygons. These coordinates are easy to compute and have linear precision even for open polygons. Not only do these coordinates have linear precision, but we can create coordinates that reproduce polynomials of a set degree m as long as degree m polynomials are specified along the boundary of the polygon. We also show how to extend these coordinates to interpolate derivatives specified on the boundary.
Iron overload and gene expression in HepG2 cells: analysis by differential display (2000)

The aim of the present study was to evaluate the effect of iron overload on gene expression in HepG2 cells by differential display. Iron-treated cells showed a 50% decrease in apolipoprotein B100 (Apo B100) and a 2- and 3-fold increase in semaphorin cd100 and aldose reductase mRNA, respectively, with parallel variations in Apo B100 and aldose reductase proteins. These effects were time-dependent. Vitamin E prevented the increase in aldose reductase expression, but had no effect on Apo B100 and semaphorin cd100. Treatment with hydrogen peroxide and 4-hydroxy-2,3-nonenal increased only aldose reductase mRNA. These data suggest that iron can affect mRNA levels by lipid peroxidation-dependent and -independent pathways.
Thresholds for cellular disruption and activation of the stress response in renal epithelia (1999)

Renal ischemia causes a rapid fall in cellular ATP, increased intracellular calcium (Ca(i)), and dissociation of Na(+)-K(+)-ATPase from the cytoskeleton along with initiation of a stress response. We examined changes in Ca(i), Na(+)-K(+)-ATPase detergent solubility, and activation of heat-shock transcription factor (HSF) in relation to graded reduction of ATP in LLC-PK(1) cells to determine whether initiation of the stress response was related to any one of these perturbations alone. Ca(i) increased first at 75% of control ATP. Triton X-100 solubility of Na(+)-K(+)-ATPase increased below 70% control ATP. Reducing cellular ATP below 50% control consistently activated HSF. Stepped decrements in cellular ATP below the respective thresholds caused incremental increases in Ca(i), Na(+)-K(+)-ATPase solubility, and HSF activation. ATP depletion activated both HSF1 and HSF2. Proteasome inhibition caused activation of HSF1 and HSF2 in a pattern similar to ATP depletion. Lactate dehydrogenase release remained at control levels irrespective of the degree of ATP depletion. Progressive accumulation of nonnative proteins may be the critical signal for the adaptive induction of the stress response in renal epithelia.
C31G, a new agent for oral use with potent antimicrobial and antiadherence properties (1988)

C31G, an equimolar mixture of alkyl dimethyl glycine and alkyl dimethyl amine oxide, was evaluated for antimicrobial and antiadherence properties. The efficacy of C31G, its two components, and several commercial mouth rinses was determined in assays measuring inhibition of glycolysis, inhibition of bacterial adherence, and MICs. Inhibition of glycolysis was determined by using a saliva sediment model, with glycolytic activity expressed as the change in pH relative to that of a control. Adherence studies were undertaken with Streptococcus sobrinus 6715 to measure inhibition of adherence to nichrome wires. MICs were determined against selected microorganisms by standard methods. C31G demonstrated broad-spectrum antimicrobial properties, with activity against both gram-positive and gram-negative organisms and Candida albicans, a yeast. C31G inhibited both glycolysis by salivary bacteria and adherence of Streptococcus strains to wire mesh. C31G was more effective in the assays conducted than any commercial formulation tested and was as effective as chlorhexidine. A synergistic effect was demonstrated between the individual components of C31G, and no loss of activity was noted when it was formulated into a mouth rinse vehicle.
Aerosol Particle Size Distribution and Genetic Characteristics of Aerosolized Influenza A H1N1 Virus Vaccine Particles (2011)

Influenza has increasingly become a global issue that threatens human lives worldwide. While an aerosol-type influenza vaccine has been licensed for the treatment of seasonal influenza via intranasal administration, the physical and genetic characteristics of aerosols containing vaccine particles have not yet been reported in either a native or artificial environment. In this study, we aerosolized a conventional vaccine solution containing inactivated split influenza particles and measured the size distribution of the aerosol particles after nebulization. We also tested a novel method for detecting a minimal amount of the viral particles in the aerosols by amplifying the viral genomic RNAs in the vaccine solution via reverse transcription-PCR. In the results, we found via TEM that the morphology of the viral particles in the vaccine solution was not significantly deteriorated by the inactivation process. The aerosolized vaccine particles exhibited a mode diameter of 130 nm. In addition, the viral RNAs were successfully amplified from the inactivated split virus vaccine solution even after the nebulization process. Taken together, the current experimental results provide basic information regarding the general characteristics of the inactivated influenza viral particles in the vaccine, including genetic properties, and may contribute to the effective use of the vaccine solution in medical protocols.
The Utility and Limitations of Neurosphere Assay, CD133 Immunophenotyping and Side Population Assay in Glioma Stem Cell Research (2010)

The newly proposed glioma stem cell (GSC) hypothesis may re-model the way we diagnose and treat the tumor, which highlights the need for a complete knowledge on the genetic and epigenetic "blueprints" of GSCs. To identify the true "stemness" signatures, pure GSC populations are primarily needed. Reliable in vitro methods enriching for GSCs and thereby identifying the key stem-like characteristics constitute the preliminary step forward. We discuss in this review the current widely used methods for enriching and isolating GSCs, namely neurosphere assay, CD133 Immunophenotyping and side population assay, and detail their limitations and potential pitfalls that could complicate interpretation of corresponding results.
Nonsurgical closure of patent ductus arteriosus: clinical application of the Rashkind PDA Occluder System. (1987)

The first successful application of a transcatheter closure technique for patent ductus arteriosus (PDA) suitable for use in infants and children was performed by us in 1977. Since that time, there has been continued improvement and simplification of the equipment as well as in the implantation technique. Following a Food and Drug Administration protocol, a multicenter study was conducted to test the safety and effectiveness of this interventional method. The clinical results from three major regional test centers (Philadelphia, Houston, and New Haven) are presented. One hundred forty-six patients from a test population of 156 were treated for PDA with use of the Rashkind PDA Occluder Systems. Successful closure was accomplished in 94 (66%) of the total cases. Ten patients (7%) retained residual ductal murmurs despite correct placement of the occlusion devices; five additional patients (3%) were considered failures due to the presence of abnormal Doppler flow patterns after the procedure. Postrelease embolizations occurred in 19 (15%) instances. One patient required emergency surgical intervention after attempted retrieval of an embolized occluder. With the improvements in the manufacturing of the double-disk occluder systems as well as the perfection of the transvenous delivery technique, the incidences of closure failure and postrelease complications have decreased. Since January 1984, 78% of all transcatheter closure attempts were successful, with 10% embolization.