gebhart/patrepeval huggingface dataset:
Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells (1997)

We measured the cellular uptake of 125I-labeled full-length Tat (amino acids 1 to 86) (125I-Tat(1-86)) and 125I-Tat(1-72) (first exon) in human fetal astrocytes, neuroblastoma cells, and human fetal neurons and demonstrated that the uptake of 125I-Tat(1-72) without the second exon was much lower than that of 125I-Tat(1-86) (P < 0.01). This suggests an important role for the C-terminal region of Tat for its cellular uptake. 125I-Tat uptake could be inhibited by dextran sulfate and competitively inhibited by unlabeled Tat but not by overlapping 15-mer peptides, suggesting that Tat internalization is charge and conformationally dependent. Interestingly, one of 15-mer peptides, Tat(28-42), greatly enhanced 125I-Tat uptake. These findings are important for understanding the neuropathogenesis of human immunodeficiency virus type 1 infection and in the potential application of Tat for drug delivery to cells.
7-Azetidinylquinolones as Antibacterial Agents. 3. Synthesis, Properties and Structure-Activity Relationships of the Stereoisomers Containing a 7-(3-Amino-2-methyl-1-azetidinyl) Moiety (1995)

A series of stereochemically pure 7-(3-amino-2-methyl-1-azetidinyl)-1,4- dihydro-6-fluoro-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to determine the effects of chirality on potency and in vivo efficacy relative to the racemic mixtures (for part 2, see: J. Med. Chem. 1994, 37, 4195-4210). A series of chiral 9-fluoro-2,3-dihydro-3-methyl-7-oxo-10-(substituted-1- azetidinyl)-7H-pyrido[1,2,3- de]-1,4-benzoxazine-6-carboxylic acids was synthesized to study the effect of the azetidine moiety on tricyclic quinolone antibacterial agents. A series of amino acid prodrugs of chiral naphthyridines 24a and 24b and quinolone 33a (cetefloxacin) was prepared and evaluated for antibacterial activity, solubility, and pharmacokinetic behavior. The absolute configuration of the new azetidinylquinolones was established by X-ray analysis of one of the diastereomeric salts of the resolved azetidinols (15) and of compound 25a (E-4767), which showed the best in vitro and in vivo overall profile. Structure-activity relationship studies indicated that the absolute stereochemistry at the asymmetric centers of both the azetidine and the oxazine rings was critical to increase in vitro activity and oral efficacy. The 3S configuration in the pyridobenzoxazine series and the (2S,3R) configuration of the 3-amino-2-methylazetidine moiety for all new compounds conferred the best antibacterial activity.
Implementation of a real-time computerized sepsis alert in nonintensive care unit patients* (2010)

The sepsis alert developed at Barnes-Jewish Hospital was shown to increase early therapeutic and diagnostic interventions among nonintensive care unit patients at risk for sepsis.
Influence of Base Composition on Membrane Binding and Cellular Uptake of 10-mer Phosphorothioate Oligonucleotides in Chinese Hamster Ovary (CH R C5) Cells (1994)

A key problem in antisense therapeutics is the relatively poor cell uptake of oligonucleotides and subsequent transport to the cytoplasm and nucleus. Although the chemical characteristics of oligonucleotides seem likely to affect their uptake by cells, little is known about this issue. In this article we explore the effect of base composition on oligonucleotide uptake. We show that phosphorothioate homo-G oligomers have a distinctly greater cellular uptake than other phosphorothioate homooligomers. This is probably due to a greater initial association with the plasma membrane, because homo-G oligomers show the greatest binding to liposome membranes, when tested at physiological ionic strength. Under different buffer conditions appreciable differences in membrane binding to liposomes were detected for the various homooligonucleotides.
Molecular genetic analysis of herpesviruses and their potential use as vectors for gene therapy applications. (1999)

Molecular genetic experiments with large human herpesviruses have provided a means whereby large heterologous DNA fragments can be cloned, propagated and established in cells permissive for infection with herpesviruses. Some of these cells include neuronal cells and B-lymphocytes infected with herpes simplex virus (HSV) and Epstein-Barr virus (EBV), respectively as well as human T-lymphocytes with herpesvirus saimiri. These large DNA viruses have the potential to deliver fragments of human heterologous DNA > 150 kbp to specific cells. Additionally, EBV recombinants can maintain these large pieces of DNA in the infected B-cells as episomal DNA. The maintenance of these episomes requires a specific EBV nuclear protein, EBNA1, constitutively expressed during infection with EBV. Additionally, these vectors can be used for transfection, where large amounts of protein can be generated transiently in vitro. Herpesvirus amplicon systems are also being used to package pieces of DNA > 150 kbp and to infect cells that can stably maintain DNA as episomes. Moreover, other herpesvirus vector systems can be utilized as a source for the propagation of specific DNA fragments of interest, including wild-type genes to correct genetic defects in human cells. Other herpesvirus systems include defective infectious single cycle (DISC-HSV) mutants of HSV, which are now undergoing trials for the treatment of genital herpesvirus infections and certain types of cancers. The use of herpesviruses as an agent to deliver heterologous gene products has the potential to make a significant difference to the development of therapeutic approaches to human diseases.
Nicotinic receptors and schizophrenia (2004)

The incidence of smoking is very high in non-schizophrenic subjects presenting various psychiatric disorders (35 to 54%). However, the incidence of smoking is extremely high in schizophrenic patients: 80% to 90%, versus 25% to 30% of the general population. Various studies have demonstrated that the use of tobacco transiently restores the schizophrenic patient's cognitive and sensory deficits. Smoking cessation also appears to exacerbate the symptoms of the disease. Post-mortem binding studies have revealed a disturbance of nicotinic receptor expression, affecting the alpha(7) and alpha(4)beta(2) subunits, in various cerebral areas. Genetic linkage studies have also shown that the alpha(7) subunit is involved in schizophrenia. This review assesses the involvement of the nicotinic system in schizophrenia and suggests ways in which this system may participate in the pathophysiology of this disease.
Picosecond InP optoelectronic switches (1982)

Proton bombardment is used to increase the response speed of InP optoelectronic switches. Photoconductivity measurements indicate response times following bombardment of &amp;lt;100 ps, with the electron mobility estimated to be ⩾600 cm2/Vs. This mobility is over an order of magnitude larger than that observed in similar high-resistivity devices of comparable speed fabricated in germanium or silicon-on-sapphire.
Shoogle: multimodal excitatory interaction on mobile devices (2007)

No abstract available.
Purification of the saxitoxin receptor of the sodium channel from rat brain. (1981)

The saxitoxin (STX) receptor has been purified 740-fold from rat brain by a combination of ion exchange chromatography, wheat germ agglutinin chromatography, and sedimentation on sucrose gradients to a specific activity of 1488 pmol/mg of protein. The best fractions were estimated to be 47% pure from their specific activity or 66% pure on the basis of NaDodSO4 gel electrophoresis. Two polypeptides, alpha (Mr approximately equal to 270,000 +/- 10,000) and beta (Mr approximately equal to 38,300 +/- 2000) (mean +/- SD) copurify with STX binding activity. Two polypeptides of the same apparent Mr are specifically covalently labeled by photoreactive derivatives of 125I-labeled scorpion toxin in rat brain synaptosomes and are likely to be identical to alpha and beta. The solubilized STX receptor has a Mr of 316,000 +/- 63,000, limiting its composition to one alpha polypeptide and one or more beta polypeptides per soluble receptor. Our results suggest that the alpha and beta polypeptides contain both the STX binding site and the scorpion toxin binding site of the mammalian sodium channel.
Substrate Recognition Drives the Evolution of Serine Proteases (2002)

A method is introduced to identify amino acid residues that dictate the functional diversity acquired during evolution in a protein family. Using over 80 enzymes of the chymotrypsin family, we demonstrate that the general organization of the phylogenetic tree and its functional branch points are fully accounted for by a limited number of residues that cluster around the active site of the protein and define the contact region with the P1-P4 residues of substrate.
Exploiting the Basis of Proline Recognition by SH3 and WW Domains: Design of N-Substituted Inhibitors (1998)

Src homology 3 (SH3) and WW protein interaction domains bind specific proline-rich sequences. However, instead of recognizing critical prolines on the basis of side chain shape or rigidity, these domains broadly accepted amide N-substituted residues. Proline is apparently specifically selected in vivo, despite low complementarity, because it is the only endogenous N-substituted amino acid. This discriminatory mechanism explains how these domains achieve specific but low-affinity recognition, a property that is necessary for transient signaling interactions. The mechanism can be exploited: screening a series of ligands in which key prolines were replaced by nonnatural N-substituted residues yielded a ligand that selectively bound the Grb2 SH3 domain with 100 times greater affinity.
Swept source / Fourier domain polarization sensitive optical coherence tomography with a passive polarization delay unit (2012)

Polarization sensitive optical coherence tomography (PS-OCT) is a functional imaging method that provides additional contrast using the light polarizing properties of a sample. This manuscript describes PS-OCT based on ultrahigh speed swept source / Fourier domain OCT operating at 1050nm at 100kHz axial scan rates using single mode fiber optics and a multiplexing approach. Unlike previously reported PS-OCT multiplexing schemes, the method uses a passive polarization delay unit and does not require active polarization modulating devices. This advance decreases system cost and avoids complex synchronization requirements. The polarization delay unit was implemented in the sample beam path in order to simultaneously illuminate the sample with two different polarization states. The orthogonal polarization components for the depth-multiplexed signals from the two input states were detected using dual balanced detection. PS-OCT images were computed using Jones calculus. 3D PS-OCT imaging was performed in the human and rat retina. In addition to standard OCT images, PS-OCT images were generated using contrast form birefringence and depolarization. Enhanced tissue discrimination as well as quantitative measurements of sample properties was demonstrated using the additional contrast and information contained in the PS-OCT images.
FcγR polymorphisms: Implications for function, disease susceptibility and immunotherapy (2003)

Leukocyte Fcgamma receptors (FcgammaR) confer potent cellular effector functions to the specificity of IgG. FcgammaR-induced leukocyte functions, including antibody-dependent cellular cytotoxicity, phagocytosis, superoxide generation, degranulation, cytokine production and regulation of antibody production, are essential for host defense and immune regulation. The efficacy of IgG-induced FcgammaR function displays inter-individual heterogeneity due to genetic polymorphisms of three FcgammaR subclasses, FcgammaRIIa (CD32a), FcgammaRIIIa (CD16a), and FcgammaRIIIb (CD16b). FcgammaR polymorphisms have been associated with infectious and autoimmune disease, or with disease severity. FcgammaR polymorphisms may furthermore serve as markers for therapeutic efficacy and side-effects of treatment with monoclonal antibodies. In this review, FcgammaR function and the relevance of FcgammaR polymorphisms as prognostic markers for inflammatory disease and antibody-based immunotherapy are discussed.
Parvoviral vectors for the gene therapy of cancer. (1996)

Gene transfer vectors based on the replication-defective (adeno-associated virus, AAV) and autonomous parvoviruses are emerging as promising vehicles for gene therapeutic approaches for the treatment of cancer. AAV-based vectors are nonpathogenic, possess an extremely wide host and tissue range, stably integrate into cellular DNA, and transduce both proliferating and nonproliferating cells. Unlike AAV, autonomous parvoviruses such as the minute virus of mice (MVM) do not integrate. However, their tropism for transformed tissues and innate oncolytic properties may permit rapid in situ therapies. In this article, we briefly review basic parvovirus biology as it relates to vector development. In addition, parvoviral vectors are discussed within the context of applications for gene transfer approaches to cancer treatment including genetic marking studies, hematopoietic progenitor chemoprotection, interruption of oncogene expression, and modulation of antitumor immunity.
[Expressions of transforming growth factor-beta1, desmin and CD34 in the penile corpus cavernosum of rats]. (2010)

With the increase of age, the expression of TGF-beta1 is significantly up-regulated, while those of Desmin and CD34 significantly down-regulated in the corpus cavernosum tissues, and it is negatively correlated with the latter two. TGF-beta1 is an important influencing factor on ED.
Prolactin receptor signal transduction (2001)

Within the immune system, multiple isoforms of the human prolactin receptor (PRLr) serve to mediate the effects of its ligand (PRL). Now numbering four, these isoforms are structurally and functionally distinct, demonstrating significant differences in ligand affinities, kinetics of transduction and the transduction proteins activated. The proximal transduction pathways activated during PRLr-associated signaling include the tyrosine kinases Jak2, Fyn and Tec, the phosphatase SHP-2, the guanine nucleotide exchange factor Vav, and the signaling suppressor SOCS. Differential activation of these pathways may contribute to the pleiotropism of PRL action in tissues of the immune system.
Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderminducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis (1991)

In amphibian embryos, formation of the basic body plan depends on positional differences in the mesoderm. Although peptide growth factors involved in mesoderm induction have tentatively been identified, additional signals are required to generate pattern in this tissue. We have isolated a Xenopus cDNA for a Wnt-1 related gene, designated Xwnt-8, which is activated in response to mesoderm-inducing growth factors. Xwnt-8 transcripts are transiently expressed, being most abundant during gastrulation at which time expression is confined primarily to ventral mesodermal cells. Embryos dorsoanteriorized by exposure to lithium exhibit greatly reduced levels of Xwnt-8 mRNA, supporting a correlation between Xwnt-8 expression and a ventral mesodermal cell fate. Surprisingly, ectopic expression of Xwnt-8 in embryos causes a dorsoanterior-enhanced phenotype. These findings suggest that Xwnt-8 may be a secondary signalling agent which is produced in response to mesoderm-inducing factors and is involved in the early steps of mesodermal patterning.
Engineering and Medical Applications of Diatoms (2005)

Biologists, and diatomists in particular, have long studied the properties of single-cell algae, and engineers are just discovering how to exploit features unique to these organisms. Their uniform nanopore structure, microchannels, chemical inertness, and silica microcrystal structure suggest many nanoscale applications. This paper proposes three potential research initiatives taking advantage of diatom morphology and mechanical and chemical properties: (1) embedding diatom frustules in a metal-film membrane; (2) magnetizing frustules for pinpoint drug delivery; and (3) producing silica nanopowders from frustules. The potential benefits of each initiative and its technical challenges are outlined.
Maximum entropy and the foundations of direct methods (1984)

A revision of the classical statistical methods of phase determination is presented which widens their theoretical foundations and consolidates their practical implementation, thus bringing about a major increase of their power. In a brief introductory survey (§ 1), the basic concepts and mathematical techniques of direct methods are analysed. Closer scrutiny (§ 2) reveals that severe inadequacies still impair the effectiveness of these methods. The asymptotic character of the series used to approximate joint distributions of structure factors demands that great caution be exercised to guarantee their accuracy, and this requirement can only be fulfilled if they are used within a multisolution algorithm in which the prior distribution of atoms is constantly updated so as to incorporate at every stage all the phase information assumed to that point. Further limitations follow from the traditional practice of approximating joint distributions by products of marginal distributions of single invariants. A scheme for simultaneously overcoming both difficulties is then proposed. The pivotal element of this scheme is a device, based on Jaynes's maximum-entropy principle, for exploiting the prior knowledge of some structure factors in the construction of the joint distributions of others conditional to that knowledge. Jaynes's maximum-entropy formalism is presented and systematically applied to the construction of the requisite non-uniform prior distributions of atoms in § 3. The problem of effectively approximating conditional distributions of very large numbers of structure factors is solved in § 4 by a novel technique of 'maximum-entropy inversion' of Karle-Hauptman matrices, and the result obtained is shown to generalize the most sophisticated probabilistic formulae hitherto obtained. This procedure is proved in § 5 to coincide with an enhancement of the standard method of asymptotic expansions by means of Daniels's saddlepoint approximation. Its relationship to determinantal methods is investigated in § 6. A numerical algorithm for implementing these ideas is presented in § 7, together with an application to data from the small protein Crambin, and a unified strategy for its use ab initio is described and discussed in § 8. It is concluded that the phase-determination strategy proposed here will expedite the realization of the full potential of probabilistic direct methods, and is likely to bring macromolecular structures within their reach.
Obtaining Absorptive Line Shapes in Two-Dimensional Infrared Vibrational Correlation Spectra (2003)

Absorptive line shapes in two-dimensional infrared (2D IR) vibrational spectra are important for an intuitive interpretation of molecular structure and dynamics. We obtain an absorptive 2D IR correlation spectrum by summing complementary spectra from experiments sampling vibrational coherences that oscillate with conjugate frequencies in the initial evolution time period. The 2D correlation spectrum of a coupled vibrational system reveals certain spectral features with tilted line shapes that are explained in terms of unequal contributions of Liouville-space pathways.
Age-Dependent Acceleration of Ischemic Injury in Endothelial Nitric Oxide Synthase-Deficient Mice: Potential Role of Impaired VEGF Receptor 2 Expression (2006)

Morbidity and mortality of peripheral arterial occlusive disease significantly increases with age, often exhibiting more severe disease pathology and decreased treatment effectiveness. Therapeutic angiogenesis with angiogenic growth factors may represent a valuable treatment option for the severely ill, older adult patient population. Aging is considered an independent cardiovascular risk factor, but pathomechanistically it is not well understood. Diminished endothelial nitric oxide (EDNO) production has been considered as a major contributor to the aging process. To investigate the effect of age on postischemic revascularization independent of changes in EDNO, we used endothelial nitric oxide synthase-deficient (ecNOS-KO) mice. We found an age-dependent acceleration in ischemic injury following unilateral femoral artery ligation in these animals compared to C57BL/J6 mice. Postischemic revascularization, quantified by measuring von Willebrand factor expression, was significantly impaired, suggesting that factors other than progressive EDNO deterioration are also involved in the age-dependent severe disease phenotype. Ischemia led to an increase in the expression of vascular endothelial growth factor receptor-2, KDR, in younger ecNOS-KO; however, this increase in KDR expression was absent in the older animals. Lack of increased KDR expression may provide a mechanistic explanation for the severe ischemic injury and perhaps can be used as a clinical marker to identify severe, vascular endothelial growth factor refractory patient population.
Structure–function relationships in peptoids: Recent advances toward deciphering the structural requirements for biological function (2009)

Oligomers of N-substituted glycine, or peptoids, are versatile tools to probe biological processes and hold promise as therapeutic agents. An underlying theme in the majority of recent peptoid research is the connection between peptoid function and peptoid structure. For certain applications, well-folded peptoids are essential for activity, while unstructured peptoids appear to suffice, or even are superior, for other applications. Currently, these structure-function connections are largely made after the design, synthesis, and characterization process. However, as guidelines for peptoid folding are elucidated and the known biological activities are expanded, we anticipate these connections will provide a pathway toward the de novo design of functional peptoids. In this perspective, we review several of the peptoid structure-function relationships that have been delineated over the past five years.
Helicobacter pylori isolated from the domestic cat: public health implications (1994)

Helicobacter pylori has been directly linked with active chronic gastritis, peptic ulceration, and gastric adenocarcinoma in humans. Although a substantial portion of the human population is colonized with H. pylori, the patterns of transmission of the organism remain in doubt, and reservoir hosts have not been identified. This study documents the isolation of H. pylori from domestic cats obtained from a commercial vendor. The isolation of H. pylori from these cats was confirmed by morphologic and biochemical evaluations, fatty acid analysis, and 16S rRNA sequence analysis. H. pylori was cultured from 6 cats and organisms compatible in appearance with H. pylori were observed in 15 additional cats by histologic examination. In most animals, H. pylori was present in close proximity to mucosal epithelial cells or in mucus layers of the glandular or surface epithelium. Microscopically, H. pylori-infected cat stomachs contained a mild to severe diffuse lymphoplasmacytic infiltrate with small numbers of neutrophils and eosinophils in the subglandular and gastric mucosae. Lymphoid follicles were also noted, particularly in the antrum, and often displaced glandular mucosal tissue. Thus, the domestic cat may be a potential model for H. pylori disease in humans. Also, the isolation of H. pylori from domestic cats raises the possibility that the organism may be a zoonotic pathogen, with transmission occurring from cats to humans.