gebhart/patrepeval huggingface dataset:
Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection (2015)

Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17) effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg) cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.
Prospects for immunisation against Marburg and Ebola viruses (2010)

For more than 30 years the filoviruses, Marburg virus and Ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. The filoviruses are endemic primarily in resource-poor regions in Central Africa and are also potential agents of bioterrorism. Although no vaccines or antiviral drugs for Marburg or Ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines against filoviruses in nonhuman primate models. Due to the generally remote locations of filovirus outbreaks, a single-injection vaccine is desirable. Among the prospective vaccines that have shown efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant VSV (rVSV), were shown to provide complete protection to nonhuman primates when administered as a single injection. The rVSV-based vaccine has also shown utility when administered for postexposure prophylaxis against filovirus infections. A VSV-based Ebola vaccine was recently used to manage a potential laboratory exposure.
Preparation of Silica-Encapsulated Hollow Gold Nanosphere Tags Using Layer-by-Layer Method for Multiplex Surface-Enhanced Raman Scattering Detection (2011)

The use of silica shells offers many advantages in surface-enhanced Raman scattering (SERS)-based biological sensing applications due to their optical transparency, remarkable stability in environmental media, and improved biocompatibility. Here, we report a novel layer-by-layer method for the preparation of silica-hollow gold nanosphere (HGN) SERS tags. Poly(acrylic acid) was used to stabilize Raman reporter-tagged HGNs prior to the adsorption of a coupling agent, after which a silica shell was deposited onto the particle surface using Stöber's method. Importantly, competitive adsorption of the Raman reporter molecules and coupling agents, which results in unbalanced loading of reporter molecules on individual nanoparticles, was avoided using this method. As a result, the loading density of reporter molecules could be maximized. In addition, HGNs exhibited strong enhancement effects from the individual particles because of their ability to localize the surface electromagnetic fields through pinholes in the hollow particle structures. The proposed layer-by-layer silica-encapsulated HGN tags showed strong SERS signals as well as excellent multiplexing capabilities.
Chalcogenides of aluminium(III) and gallium(III) derived from Lewis base adducts of alane and gallane (1998)

Reductive cleavage of (ER)2 by [GaH3L], L = NMe3 or P(C6H11)3, afforded [Ga(TePh)3(NMe3)], [Ga(SeEt)3(NMe3)] and [Ga(TePh)3{P(C6H11)3}]; the latter was also prepared by the reaction of [GaH2Cl{P(C6H11)3}] with LiTePh. They have slightly disordered tetrahedral metal centres, established in the solid for [Ga(TePh)3(NMe3)] and [Ga(TePh)3{P(C6H11)3}], and in the structure of the aluminium analogue, [Al(SePh)3(NMe3)], which was also determined. Reaction of [GaH2Cl{P(C6H11)3}] with Li2Se afforded dinuclear trans-[{GaCl(µ-Se)[P(C6H11)3]}2] (minor product) which is centrosymmetric with distorted tetrahedral metal centres associated with a planar Ga2Se2 ring system. Treatment of trans-[{AlH(µ-Se)(NMe3)}2] with tmen (=N,N,N′,N′-tetramethylethane-1,2-diamine), or [{AlH3(tmen)}∞] with elemental selenium, afforded polymeric [{[AlH(µ-Se)]2(tmen)}∞]. Cleavage of (EPh)2 by trans-[{AlH(µ-Se)(NMe3)}2] gave trans-[{Al(µ-Se)(EPh)(NMe3)}2], E = S, Se or Te, also as centrosymmetric dinuclear species with planar Al2Se2 ring systems. Reaction of trans-[{AlH(µ-Se)(NMe3)}2] with 2 equivalents of NH(SiMe3)2 or 6-methyl-2-trimethylsilylaminopyridine gave the secondary amine metallated products trans-[{Al(µ-Se)[N(SiMe3)2](NMe3)}2] (structurally authenticated as a centrosymmetric dinuclear species) and [{Al(µ-Se)(NC5H3NSiMe3-2-Me-6)}2].
Endoplasmic reticulum membrane localization of Rce1p and Ste24p, yeast proteases involved in carboxyl-terminal CAAX protein processing and amino-terminal a-factor cleavage (1998)

Proteins terminating in the CAAX motif, for example Ras and the yeast a-factor mating pheromone, are prenylated, trimmed of their last three amino acids, and carboxyl-methylated. The enzymes that mediate these activities, collectively referred to as CAAX processing components, have been identified genetically in Saccharomyces cerevisiae. Whereas the Ram1p/Ram2p prenyltransferase is a cytosolic soluble enzyme, sequence analysis predicts that the other CAAX processing components, the Rce1p and Ste24p proteases and the Ste14p methyltransferase, contain multiple membrane spans. To determine the intracellular site(s) at which CAAX processing occurs, we have examined the localization of the CAAX proteases Rce1p and Ste24p by subcellular fractionation and indirect immunofluorescence. We find that both of these proteases are associated with the endoplasmic reticulum (ER) membrane. In addition to having a role in CAAX processing, the Ste24p protease catalyzes the first of two cleavage steps that remove the amino-terminal extension from the a-factor precursor, suggesting that the first amino-terminal processing step of a-factor maturation also occurs at the ER membrane. The ER localization of Ste24p is consistent with the presence of a carboxyl-terminal dilysine ER retrieval motif, although we find that mutation of this motif does not result in mislocalization of Ste24p. Because the ER is not the ultimate destination for a-factor or most CAAX proteins, our results imply that a mechanism must exist for the intracellular routing of CAAX proteins from the ER membrane to other cellular sites.
Inhibitors of human immunodeficiency virus integrase. (1993)

In an effort to further extend the number of targets for development of antiretroviral agents, we have used an in vitro integrase assay to investigate a variety of chemicals, including topoisomerase inhibitors, antimalarial agents, DNA binders, naphthoquinones, the flavone quercetin, and caffeic acid phenethyl ester as potential human immunodeficiency virus type 1 integrase inhibitors. Our results show that although several topoisomerase inhibitors--including doxorubicin, mitoxantrone, ellipticines, and quercetin--are potent integrase inhibitors, other topoisomerase inhibitors--such as amsacrine, etoposide, teniposide, and camptothecin--are inactive. Other intercalators, such as chloroquine and the bifunctional intercalator ditercalinium, are also active. However, DNA binding does not correlate closely with integrase inhibition. The intercalator 9-aminoacridine and the polyamine DNA minor-groove binders spermine, spermidine, and distamycin have no effect, whereas the non-DNA binders primaquine, 5,8-dihydroxy-1,4-naphthoquinone, and caffeic acid phenethyl ester inhibit the integrase. Caffeic acid phenethyl ester was the only compound that inhibited the integration step to a substantially greater degree than the initial cleavage step of the enzyme. A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein is proposed.
Angiotensin-converting enzyme: immunologic, structural, and developmental aspects. (1983)

Immunization of dog and rat high pure rabbit pulmonary angiotensin-converting enzyme elicited, in some individuals, antibodies that inhibited their own converting enzyme. Active immunization with an immunologically related enzyme is thus a plausible approach for developing biologically based inhibitors of enzymes that are either in or accessible to the circulation. Rabbit testicular peptidyldipeptide hydrolase was purified to homogeneity and found to be a considerably smaller (Mr approximately 100,000) glycoprotein than pulmonary converting enzyme (Mr approximately 140,000). The two enzymes differed at their amino- and carboxy-termini. However, they exhibited identical catalytic properties, and antibodies prepared against either inhibited both similarly. In competition radioimmunoassays, antibodies against the pulmonary enzyme preferred it to the testicular species, whereas those against the latter did not distinguish between the two molecules. The testicular isozyme thus resembles an internal part of the pulmonary polypeptide, which includes its active site. In a reticulocyte lysate, mRNA from the lungs of immature and mature rabbits comparably primed the synthesis of a polypeptide (Mr approximately 129,000) that reacted with anticonverting enzyme antibodies. In contrast, an immunoreactive species was programed only by mRNA from the testis of mature animals, and this protein was much smaller (Mr approximately 85,000). Maturation dependence and a shorter polypeptide chain, the regulatory and structural properties that distinguish the testicular isozyme, are thus each pretranslationally determined.
Association of (Pro)renin Receptor Gene Polymorphism With Blood Pressure in Japanese Men: The Ohasama Study (2009)

We demonstrated for the first time that polymorphism of the (P)RR gene IVS5+169C>T is associated with ABP in Japanese men. This association suggests that (P)RR has a role in blood pressure regulation.
The Role of the Immune Response in Age-Related Macular Degeneration (2013)

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries; with the aging population, the negative health impacts and costs of the disease will increase dramatically over the next decade. Although the exact cause of AMD is unknown, genetic studies have implicated the complement system as well as other immune responses in disease pathogenesis and severity. Furthermore, histologic studies have shown the presence of macrophages, lymphocytes, and mast cells, as well as fibroblasts, in both atrophic lesions and with retinal neovascularization. This review summarizes discussions from the fifth annual conference of the Arnold and Mabel Beckman Initiative for Macular Research by the Inflammation and Immune Response Task Force. These deliberations focused on the role of inflammatory immune responses, including complement, inflammasomes, adaptive immune responses, and para-inflammation, unanswered questions and studies to address these questions, and potential immune-related therapeutic targets for AMD.
Effect of Neutralizing Sera on Factor X-Mediated Adenovirus Serotype 5 Gene Transfer (2008)

The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based vectors in vitro. Neutralizing activity correlated well with the ability to inhibit Ad5-mediated liver transduction, suggesting that prescreening patient sera in this manner accurately predicts the efficacy of Ad5-based gene therapies. Neutralization in vitro can be partially bypassed by pseudotyping with Ad45 fiber protein, indicating that a proportion of neutralizing antibodies are directed against the Ad5 fiber.
A survival prediction nomogram for liposomal irinotecan (nal-IRI)+5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. (2018)

e16204 Background: NAPOLI-1 (NCT01494506) was a global phase 3 study in pts with mPDAC previously treated with gemcitabine-based therapy that showed a significant improvement in overall survival (OS) in pts treated with nal-IRI+5-FU/LV vs 5-FU/LV alone. A nomogram assists in predicting individualized risk for prespecified events, such as OS, death, or adverse events. A post hoc analysis of NAPOLI-1 was conducted to develop a nomogram to predict OS for nal-IRI+5-FU/LV in the post-gemcitabine setting. Methods: In NAPOLI-1, pts received nal-IRI+5-FU/LV, nal-IRI, or 5-FU/LV. Univariate and multivariate analyses identified baseline factors that were significantly predictive of OS. A multivariable Cox regression model was created to develop a nomogram that assigned points equal to the weighted sum of relative significance of each variable. The predictive accuracy of the nomogram, as measured by the concordance index (c-index), was evaluated by internal bootstrap validation. Results: Data from pts in the univariate analysis (n = 417) and multivariate analysis (n = 399; n = 18 pts excluded for missing data) were used. Eight of 21 variables were retained in the multivariate analysis and re-tested through stratification (all factors significant at the P < 0.01 level, except BMI [P= 0.08]). Conclusions: Key predictors of OS in NAPOLI-1 were nal-IRI+5-FU/LV treatment, KPS, NLR, albumin level, baseline CA19-9, stage 4 at diagnosis, BMI, and presence of liver metastasis. Clinical trial information: NCT01494506.Stratified Multivariate Cox Regression of OS (N = 399)a Wald P-value HR 95% CI Karnofsky Performance Status (KPS) ≥ 90 vs 60–80 < 0.0001 0.58 0.46, 0.74 Albumin ≥4 g/dL vs < 4 g/dL 0.0013 0.68 0.54, 0.86 Neutrophil-to-lymphocyte ratio (NLR) > 5 vs ≤5 0.0001 0.61 0.47, 0.79 No liver metastasis vs Presence of liver metastases < 0.0001 0.59 0.45, 0.76 CA19-9 > median ≤ 1542 U/mL) vs > 1542 U/ml < 0.0001 0.63 0.50, 0.79 Stage < 4 vs Stage 4 at diagnosis < 0.0001 0.62 0.49, 0.78 Body mass index (BMI) > 25 vs ≤25 kg/m2 0.030 0.75 0.58, 0.97 nal-IRI+5-FU/LV vs 5-FU/LV or nal-IRI 0.0001 0.59 0.45, 0.77 aModel excluded pts with missing values.
Tunable Laser Diode System for Noninvasive Blood Glucose Measurements (2005)

Optical sensing of glucose would allow more frequent monitoring and tighter glucose control for people with diabetes. The key to a successful optical noninvasive measurement of glucose is the collection of an optical spectrum with a very high signal-to-noise ratio in a spectral region with significant glucose absorption. Unfortunately, the optical throughput of skin is low due to absorption and scattering. To overcome these difficulties, we have developed a high-brightness tunable laser system for measurements in the 2.0-2.5 microm wavelength range. The system is based on a 2.3 microm wavelength, strained quantum-well laser diode incorporating GaInAsSb wells and AlGaAsSb barrier and cladding layers. Wavelength control is provided by coupling the laser diode to an external cavity that includes an acousto-optic tunable filter. Tuning ranges of greater than 110 nm have been obtained. Because the tunable filter has no moving parts, scans can be completed very quickly, typically in less than 10 ms. We describe the performance of the present laser system and avenues for extending the tuning range beyond 400 nm.
ANIMAL CELL CYCLES AND THEIR CONTROL (1992)

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
Genes encoding two different beta-glucosidases of Thermoanaerobacter brockii are clustered in a common operon (1997)

A 5.9-kb fragment of chromosomal DNA coding for beta-glucosidase activity of the thermophilic anaerobe Thermoanaerobacter brockii was sequenced. Two genes, cglT and xglS, encoding a cellodextrin-cleaving beta-glucosidase and a xylodextrin-degrading xylo-beta-glucosidase, respectively, were located directly adjacent to each other. The 5' region contained two additional genes, cglF and cglG, whose products exhibited similarity to integral membrane proteins of metabolite transport systems. The two beta-glucosidases, CglT and XglS, with deduced molecular masses of 52 and 81 kDa, belong to different families of glycosyl hydrolases. Both enzymes were overexpressed in Escherichia coli and could be detected after protein gel electrophoresis and activity staining. The enzyme CglT was purified by fast protein liquid chromatography and identified by N-terminal sequencing. The enzyme was thermostable at 60 degrees C for at least 24 h, and the temperature optimum was 75 degrees C. The ki for glucose inhibition was calculated to 200 mM. The enzyme released glucose from the nonreducing end of beta-1,4-cello oligomers as well as from various disaccharides. CglT was active on glucosides, galactosides and on fucosides, while XglS cleaved beta-glucosides and beta-xylosides as well. The cglT gene was also expressed in Bacillus subtilis, and the enzyme was mainly intracellular during exponential growth but was efficiently released into the supernatant after cultures entered the stationary phase.
Class 1 outer membrane protein of Neisseria meningitidis: epitope analysis of the antigenic diversity between strains, implications for subtype definition and molecular epidemiology (1993)

The VR1 and VR2 regions of the class 1 protein have been sequenced from a number of meningococcal strains, including non-subtypable strains and strains of apparently identical subtype. The amino acid sequences have been used to construct synthetic peptides for mapping subtype-specific epitopes. The majority of epitopes was found to be located in VR2 at the apex of a predicted surface-exposed loop. A single amino acid change within an epitope, or an amino acid deletion outside an epitope, were both associated with loss of subtype specificity, resulting from a change in the predicted conformation at the apex of the loop structure. Analysis of the sequence information combined with knowledge of defined epitopes also revealed considerable additional information not demonstrated by current subtyping procedures.
Automatic line matching across views (2002)

The paper presents a new method for matching individual line segments between images. The method uses both grey-level information and the multiple view geometric relations between the images. For image pairs epipolar geometry facilitates the computation of a cross-correlation based matching score for putative line correspondences. For image triplets cross-correlation matching scores are used in conjunction with line transfer based on the trifocal geometry. Algorithms are developed for both short and long range motion. In the case of long range motion the algorithm involves evaluating a one parameter family of plane induced homographies. The algorithms are robust to deficiencies in the line segment extraction and partial occlusion. Experimental results are given for image pairs and triplets, for varying motions between views, and for different scene types. The three view algorithm eliminates all mismatches.
The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide–dependent deacetylase (2002)

The yeast silent information regulator (Sir)2 protein links cellular metabolism and transcriptional silencing through its nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase activity. We report that mitochondria from mammalian cells contain intrinsic NAD-dependent deacetylase activity. This activity is inhibited by the NAD hydrolysis product nicotinamide, but not by trichostatin A, consistent with a class III deacetylase. We identify this deacetylase as the nuclear-encoded human Sir2 homologue hSIRT3, and show that hSIRT3 is located within the mitochondrial matrix. Mitochondrial import of hSIRT3 is dependent on an NH2-terminal amphipathic alpha-helix rich in basic residues. hSIRT3 is proteolytically processed in the mitochondrial matrix to a 28-kD product. This processing can be reconstituted in vitro with recombinant mitochondrial matrix processing peptidase (MPP) and is inhibited by mutation of arginines 99 and 100. The unprocessed form of hSIRT3 is enzymatically inactive and becomes fully activated in vitro after cleavage by MPP. These observations demonstrate the existence of a latent class III deacetylase that becomes catalytically activated upon import into the human mitochondria.
Synthesis and Pharmacological Evaluation of New Pyrazolidine-3,5-diones as AT1 Angiotensin II Receptor Antagonists (2000)

On the basis of the structure of the non-peptide receptor antagonist irbesartan, a new series of AT(1) ligands was designed. In these compounds the central imidazolone nucleus of irbesartan was replaced by a pyrazolidine-3,5-dione structure. The key intermediate N-alkylpyrazolidine-3,5-diones were synthesized according to a new and general method. The most active compounds possess a spirocyclopentane ring at position 4, a linear butyl chain at position 1, and the [2'-(5-tetrazolyl)biphenyl-4-yl]methyl or [2'-(benzoylaminosulfonyl)biphenyl-4-yl]methyl group at position 2. Affinity toward the AT(1) and AT(2) receptors was assessed by the ability of the compounds to competitively displace [(3)H]AII from its specific binding sites. The most active compounds, 28 and 48, displayed high affinity for the AT(1) receptor, good selectivity AT(1) versus AT(2), and potent in vitro antagonist activity.