gebhart/patrepeval huggingface dataset:
Kinetics and Thermodynamics of Virus Binding to Receptor. (1995)

We have studied the kinetics and thermodynamics of a virus interacting with its receptor using human rhinovirus serotype 3 (HRV3), soluble intercellular adhesion molecule-1 (ICAM-1, CD54) containing Ig superfamily domains 1-5 (sICAM-1), and surface plasmon resonance. There were two classes of binding sites for sICAM-1 on HRV3, each comprising about 50% of the total sites, with association rate constants of 2450 +/- 300 and 134 +/- 11 M-1 s-1. These rates are low, consistent with binding to a relatively inaccessible site in the rhinovirus canyon. By contrast, three monoclonal antibodies bound to sICAM-1 with a single rate constant of 17,000-48,000 M-1 s-1. The dissociation rate constant for HRV3 was 1.7 +/- 0.1 x 10(-3) s-1, giving calculated dissociation constants of 0.7 +/- 0.1 and 12.5 +/- 1.2 microM. Agreement was good with saturation binding in solution, which showed two sites of similar abundance with KD of 0.55 +/- 0.2 and 5.7 +/- 2.0 microM. A bivalent chimera of ICAM-1 with the IgA1 Fc region bound with KD = 50 and 410 nM, showing 17-fold enhanced affinity. Lowering pH from 8.0 to 6.0 reduced affinity by approximately 50-fold, primarily by reducing the on rate. Thermodynamic measurements showed that binding of ICAM-1 to HRV3 is endothermic, by contrast to binding to monoclonal antibody. The heat that is absorbed of 3.5 and 6.3 kcal/mol for the two classes of ICAM-1 binding sites may contribute to receptor-mediated disruption of virions, which has an activation energy of about 42 kcal/mol.
First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy (2011)

Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538).
SCTP versus TCP for MPI (2005)

SCTP (Stream Control Transmission Protocol) is a recently standardized transport level protocol with several features that better support the communication requirements of parallel applications; these features are not present in traditional TCP (Transmission Control Protocol). These features make SCTP a good candidate as a transport level protocol for MPI (Message Passing Interface). MPI is a message passing middleware that is widely used to parallelize scientific and compute intensive applications. TCP is often used as the transport protocol for MPI in both local area and wide area networks. Prior to this work, SCTP has not been used for MPI. We compared and evaluated the benefits of using SCTP instead of TCP as the underlying transport protocol for MPI. We re-designed LAM-MPI, a public domain version of MPI, to use SCTP.We describe the advantages and disadvantages of using SCTP, the necessary modifications to the MPI middleware to use SCTP, and the performance of SCTP as compared to the stock implementation that uses TCP.
Obesity, diabetes, and neoplasia in yellow A vy /‐ mice: ectopic expression of the agouti gene (1994)

The viable yellow A(vy) mutation results in a mottled yellow mouse that is obese, slightly larger than its nonyellow sibs, and more susceptible to tumor formation in those tissues sensitized by the strain genome. The mutation exhibits variable expressivity resulting in a continuum of coat color phenotypes, from clear yellow to pseudoagouti. The mouse agouti protein is a paracrine signaling molecule that induces hair follicle melanocytes to switch from the synthesis of black pigment to yellow pigment. Molecular cloning studies indicate that the obesity and growth effects of the A(vy) mutation result from ectopic expression of the normal agouti gene product. This review seeks to summarize the current state of knowledge regarding the obesity, stimulation of somatic growth, and enhancement of tumor formation caused by the A(vy) mutation, and to interpret these pleiotropic effects in terms of the normal function of the agouti protein.
Synthesis and single enzyme activity of a clicked lipase–BSA hetero-dimer (2006)

Click chemistry is used to construct a novel lipase-BSA hetero-dimer, in which the latter protein acts as a foot enabling the anchoring of the enzyme onto the surface for single enzyme studies.
Antisense Morpholino-Oligomers Directed against the 5′ End of the Genome Inhibit Coronavirus Proliferation and Growth† (2004)

Conjugation of a peptide related to the human immunodeficiency virus type 1 Tat represents a novel method for delivery of antisense morpholino-oligomers. Conjugated and unconjugated oligomers were tested to determine sequence-specific antiviral efficacy against a member of the Coronaviridae, Mouse hepatitis virus (MHV). Specific antisense activity designed to block translation of the viral replicase polyprotein was first confirmed by reduction of luciferase expression from a target sequence-containing reporter construct in both cell-free and transfected cell culture assays. Peptide-conjugated morpholino-oligomers exhibited low toxicity in DBT astrocytoma cells used for culturing MHV. Oligomer administered at micromolar concentrations was delivered to >80% of cells and inhibited virus titers 10- to 100-fold in a sequence-specific and dose-responsive manner. In addition, targeted viral protein synthesis, plaque diameter, and cytopathic effect were significantly reduced. Inhibition of virus infectivity by peptide-conjugated morpholino was comparable to the antiviral activity of the aminoglycoside hygromycin B used at a concentration fivefold higher than the oligomer. These results suggest that this composition of antisense compound has therapeutic potential for control of coronavirus infection.
Identification and characterization of SPRK, a novel src-homology 3 domain-containing proline-rich kinase with serine/threonine kinase activity. (1994)

Protein kinase play important roles in the growth and differentiation of cells. We have isolated cDNA clones from the human megakaryocytic cell line CMK11-5 that encode a novel protein kinase, which we call SPRK (src-homology 3 (SH3) domain-containing proline-rich kinase). The gene sequence predicts an 847-amino acid protein kinase with a unique domain arrangement. An amino-terminal glycine-rich region is followed by an SH3 domain and a kinase domain that is similar to both tyrosine and serine/threonine kinases. Adjacent to the kinase domain are two closely spaced leucine/isoleucine zipper motifs and a stretch of basic amino acids that resembles karyophilic nuclear localization signals. The COOH-terminal half of SPRK is basic, and proline accounts for 24% of the COOH-terminal 216 amino acids. The sprk gene is widely expressed as a 4-kilobase transcript in adult and fetal human tissues. Transfection of 293 cells with a vector encoding an epitope-tagged SPRK results in the expression of a 95-kDa protein. The epitope-tagged SPRK becomes phosphorylated on serine and threonine residues in an in vitro kinase assay, whereas SPRK variants with point mutations in the predicted ATP-binding site fail to become phosphorylated. These data indicate that SPRK has serine/threonine kinase activity. The SH3 domain of SPRK is interrupted by a unique 5-amino acid insert whose location in the SH3 consensus sequence is the same as that of the inserts found in the SH3 domains of neuronal SRC and of the p85 subunit of phosphatidylinositol 3-kinase.
Basic fibroblast growth factor induces angiogenesis in vitro. (1986)

Fibroblast growth factors (FGFs) are potent mitogens for vascular and capillary endothelial cells in vitro and can stimulate the formation of blood capillaries (angiogenesis) in vivo. A crucial event in this process is the invasion of the perivascular extracellular matrix by sprouting endothelial cells. Using a recently developed in vitro model of angiogenesis, we show here that highly purified basic pituitary FGF can induce capillary endothelial cells to invade a three-dimensional collagen matrix and to organize themselves to form characteristic tubules that resemble blood capillaries. We also show that basic FGF concomitantly stimulates endothelial cells to produce a urokinase-type plasminogen activator, a protease that has been implicated in the neovascular response. The results demonstrate that basic FGF can stimulate processes that are characteristic of angiogenesis in vivo, including endothelial cell migration, invasion, and production of plasminogen activator.
CYP52 (Cytochrome P450alk) Multigene Family in Candida maltosa: Identification and Characterization of Eight Members (1995)

Previously, we characterized three genes and presented evidence for an n-alkane-inducible cytochrome P450 (P450alk) multigene family in an n-alkane-assimilating and diploid-type yeast, Candida maltosa. In the present report, we isolated and characterized additional members of this gene family, including a total of thirteen P450alk-related sequences (eight genes and five of their alleles). Two sets, each consisting of two genes, were tandemly arranged in the genome. A gene replacement experiment showed that at least one gene had only a single allele in the genome. The determined nucleotide and the deduced amino acid sequences indicated that all had a characteristic constituent for P450s and exhibited amino acid identities from 94% to 37% to each other. Six genes showed relatively higher similarities to each other than to the other two genes and were thus classified into a subfamily. All the members of this subfamily were assigned to the same single chromosome, showing a good correlation between sequence similarity and chromosomal linkage. Although all the genes except for one were induced by n-alkane, their inducibilities by some other aliphatic carbon sources showed variabilities.
Audio-visual imposture (2006)

A GMM based audio visual speaker verification system is described and an Active Appearance Model with a linear speaker transformation system is used to evaluate the robustness of the verification. An Active Appearance Model (AAM) is used to automatically locate and track a speaker's face in a video recording. A Gaussian Mixture Model (GMM) based classifier (BECARS) is used for face verification. GMM training and testing is accomplished on DCT based extracted features of the detected faces. On the audio side, speech features are extracted and used for speaker verification with the GMM based classifier. Fusion of both audio and video modalities for audio visual speaker verification is compared with face verification and speaker verification systems. To improve the robustness of the multimodal biometric identity verification system, an audio visual imposture system is envisioned. It consists of an automatic voice transformation technique that an impostor may use to assume the identity of an authorized client. Features of the transformed voice are then combined with the corresponding appearance features and fed into the GMM based system BECARS for training. An attempt is made to increase the acceptance rate of the impostor and to analyzing the robustness of the verification system. Experiments are being conducted on the BANCA database, with a prospect of experimenting on the newly developed PDAtabase developed within the scope of the SecurePhone project.
Characterization of the structure–function relationship at the ligament-to-bone interface (2008)

Soft tissues such as ligaments and tendons integrate with bone through a fibrocartilaginous interface divided into noncalcified and calcified regions. This junction between distinct tissue types is frequently injured and not reestablished after surgical repair. Its regeneration is also limited by a lack of understanding of the structure-function relationship inherent at this complex interface. Therefore, focusing on the insertion site between the anterior cruciate ligament (ACL) and bone, the objectives of this study are: (i) to determine interface compressive mechanical properties, (ii) to characterize interface mineral presence and distribution, and (iii) to evaluate insertion site-dependent changes in mechanical properties and matrix mineral content. Interface mechanical properties were determined by coupling microcompression with optimized digital image correlation analysis, whereas mineral presence and distribution were characterized by energy dispersive x-ray analysis and backscattered scanning electron microscopy. Both region- and insertion-dependent changes in mechanical properties were found, with the calcified interface region exhibiting significantly greater compressive mechanical properties than the noncalcified region. Mineral presence was only detectable within the calcified interface and bone regions, and its distribution corresponds to region-dependent mechanical inhomogeneity. Additionally, the compressive mechanical properties of the tibial insertion were greater than those of the femoral. The interface structure-function relationship elucidated in this study provides critical insight for interface regeneration and the formation of complex tissue systems.
Thyroid hormone action: Effect of triiodothyronine on mitochondrial adenine nucleotide translocase in vivo and in vitro (1995)

Adenine nucleotide translocase (AdNT) levels were measured as the exchange of extramitochondrial against intramitochondrial adenosine diphosphate (ADP) in liver, spleen, and testes mitochondria isolated from normal and hypothyroid rats using the "back-exchange" and atractyloside-stop method of Pfaff and Klingenberg. The results provide confirmation of previous reports that mitochondria from hypothyroid rats show a markedly diminished AdNT activity, which is restored to normal levels within 72 hours by intraperitoneal injection of 10 to 20 micrograms triiodothyronine (T3)/100 g body weight. The latter dose was found in dose-response studies to result in maximal stimulation of AdNT in liver mitochondria. Qualitatively similar results on AdNT activity were obtained in liver mitochondria within 30 to 60 minutes following intravenous injection into hypothyroid rats of a more physiological dose of T3 (40 ng/100 g body weight). AdNT in mitochondria isolated from spleen and testes (organs that do not exhibit a calorigenic response after administration of thyroid hormone to the whole animal) failed to respond to thyroidectomy and to administration of T3. More recently, we have observed that in vitro replacement of T3 also stimulates AdNT activity in hypothyroid liver mitochondria. The enzyme adenosine triphosphate (ATP) synthase was examined as another possible candidate for direct hormonal stimulation of mitochondria. Simultaneous determinations on the same rats after intraperitoneal injection of T3 (20 micrograms/100 g body weight) showed little or no effect on ATP synthase until after 37 to 85 hours, whereas enhanced activity of the translocator was regularly observed at 17 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Use of Viral Fusogenic Membrane Glycoproteins as Novel Therapeutic Transgenes in Gliomas (2001)

Malignant gliomas are the most common primary brain tumors in adults and, with few exceptions, have a dismal prognosis despite the therapeutic use of surgery, radiation therapy, and chemotherapy. Because CNS gliomas rarely metastasize, they represent an attractive target for gene therapy through local gene delivery. Here we report on the use of two different fusogenic membrane glycoproteins (FMGs), the measles virus proteins F and H (MV-F and MV-H) and a mutated form of the retroviral envelope protein of the gibbon ape leukemia virus (GALV.fus), as a novel class of therapeutic transgenes in gliomas. Transfection of U87 and U118 cells with MV-F and MV-H cDNA or GALV.fus cDNA led in 48 hr to massive syncytial formation followed by cell death. FMG-mediated cytotoxicity in the U87 and U118 cell lines was superior to the cytotoxicity caused by transfection with HSV-tk cDNA followed by ganciclovir (GCV) treatment at all time points. At high-density cell seeding, addition of tumor cells transfected with MV-F and H killed at least 1 log more cells than by HSV-tk + GCV treatment, indicating higher bystander effect. Similar results were obtained with GALV.fus. The mechanism of syncytial death in cultured glioma cell lines was predominantly apoptotic. Transfection of U87 cells with F + H or GALV.fus expression constructs completely suppressed their tumorigenicity. Treatment of established U87 xenografts in nude mice with a combination of F and H adenoviruses at 1:1 ratio led to complete tumor regression, significantly higher antitumor effect, and prolongation of survival as compared with control animals treated with a GFP adenovirus. In summary, the viral fusogenic membrane glycoproteins (GALV and the MV-F + MV-H combination) are potent therapeutic transgenes with potential utility in the gene therapy of gliomas.
Meningococcal Disease (2001)

Reports of illness resembling meningococcal disease date back to the 16th century. The description reported by Vieusseux in 1805 is generally thought to be the first definitive identification of the disease,1 and the causative organism, Neisseria meningitidis, was first isolated in 1887.2 Yet meningococcal disease remains a leading cause of bacterial meningitis and sepsis in the United States and a major cause of epidemics in sub-Saharan Africa. Short of abolishing tobacco use, which is thought to be responsible for almost one third of cases,3 routine vaccination of high-risk populations is likely to be the most effective public health strategy . . .
C-Terminal Heat Shock Protein 90 Inhibitor Decreases Hyperglycemia-induced Oxidative Stress and Improves Mitochondrial Bioenergetics in Sensory Neurons (2012)

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in which hyperglycemia-induced mitochondrial dysfunction and enhanced oxidative stress contribute to sensory neuron pathology. KU-32 is a novobiocin-based, C-terminal inhibitor of the molecular chaperone, heat shock protein 90 (Hsp90). KU-32 ameliorates multiple sensory deficits associated with the progression of DPN and protects unmyelinated sensory neurons from glucose-induced toxicity. Mechanistically, KU-32 increased the expression of Hsp70, and this protein was critical for drug efficacy in reversing DPN. However, it remained unclear if KU-32 had a broader effect on chaperone induction and if its efficacy was linked to improving mitochondrial dysfunction. Using cultures of hyperglycemically stressed primary sensory neurons, the present study investigated whether KU-32 had an effect on the translational induction of other chaperones and improved mitochondrial oxidative stress and bioenergetics. A variation of stable isotope labeling with amino acids in cell culture called pulse SILAC (pSILAC) was used to unbiasedly assess changes in protein translation. Hyperglycemia decreased the translation of numerous mitochondrial proteins that affect superoxide levels and respiratory activity. Importantly, this correlated with a decrease in mitochondrial oxygen consumption and an increase in superoxide levels. KU-32 increased the translation of Mn superoxide dismutase and several cytosolic and mitochondrial chaperones. Consistent with these changes, KU-32 decreased mitochondrial superoxide levels and significantly enhanced respiratory activity. These data indicate that efficacy of modulating molecular chaperones in DPN may be due in part to improved neuronal mitochondrial bioenergetics and decreased oxidative stress.
Polarized-electroabsorption spectroscopy of a soluble derivative of poly(p-phenylenevinylene) oriented by gel processing in polyethylene: Polarization anisotropy, the off-axis dipole moment, and excited-state delocalization (1994)

We present the polarized electric field modulation spectra of dilute blends of the conjugated polymer poly[2-methoxy,5-(2'-ethyl-hexoxy)-p-phenylenevinylene] (MEH-PPV) oriented in ultrahigh-molecular-weight polyethylene (PE). The photoluminescence and electric-field-modulation spectra of tensile drawn MEH-PPV/PE blends are highly anisotropic, with preferred polarization parallel to the draw axis; the field-induced absorption and photoluminescence demonstrate polarization anisotropies in excess of 150:1 and 60:1, respectively. Because of the orientation, the enhanced order and the dilution of the MEH-PPV conjugated polymer in the polyethylene matrix, the MEH-PPV/PE blend is an ideal system in which to investigate the intrinsic linear and nonlinear optical properties of oriented conjugated polymer chains. The absorption is directly proportional to the imaginary part of ${\mathrm{\ensuremath{\chi}}}^{(1)}$(\ensuremath{\omega}), and the electroabsorption is directly proportional to the imaginary part of ${\mathrm{\ensuremath{\chi}}}^{(3)}$(\ensuremath{\omega},0,0) of the ordered MEH-PPV \ensuremath{\pi}-electron system. The optical data obtained from the oriented blends are therefore directly relevant to existing theoretical models which do not account for disorder. Using a model for the off-axis transition dipole moment of the conjugated polymer, which is based on the measured off-axis transition dipole moment of trans-stilbene and the geometric structure of MEH-PPV, we demonstrate that the observed anisotropy of 150:1 in the field-induced absorption requires that the instantaneous excited-state wave functions are delocalized over a minimum of 50 unit cells (400 \AA{}).
Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation (2006)

The human prion protein (PrP) has a common polymorphism at residue 129, which can be valine or methionine. This polymorphism has a strong influence on susceptibility to prion diseases and on prion-strain properties. Previous work has shown that this amino acid variation has no measurable effect on the native structure of cellular PrP (PrPC). Here, it is shown that the polymorphism does not change the efficiency of conversion to the beta-PrP conformation or affect the binding of copper(II) ions. However, in a partially denatured conformation, the polymorphic variation has a profound influence on the ability of the protein to form amyloid fibrils spontaneously.
Characterization of Endocrine Progenitor Cells and Critical Factors for Their Differentiation in Human Adult Pancreatic Cell Culture (2003)

We have reproduced a previously described method for the in vitro generation of endocrine cells in adult human pancreatic tissue culture. The aim of this study was to characterize the nature of pancreatic progenitor cells and to identify the factors necessary for their differentiation in this model. During monolayer expansion, two types of cells proliferated sequentially; first cytokeratin 19 (CK19)-positive ductal epithelial cells and then nestin-positive fibroblastoid cells. After the bromodeoxyuridine-labeled cells were traced in differentiated islet buds, some of the proliferating ductal cells had differentiated into endocrine cells, whereas nestin-positive cells could not give rise to endocrine tissue. Serum-free culture was found to be an absolute requirement for the endocrine differentiation to occur. Also, overlay of the cells with Matrigel was essential, whereas nicotinamide had a potentiating effect. The in vitro-generated islet buds released insulin in response to glucose nearly as efficiently as native islets. When transplanted under the kidney capsule of nude mice, only one of five grafts demonstrated further growth with foci of both endocrine and exocrine differentiation. Our results support the previous notion that pancreatic progenitor cells represent a subpopulation of ductal epithelial cells. No evidence was found for the development of endocrine cells from nestin-positive stem cells.