gebhart/patrepeval huggingface dataset:
Kinetic Mechanism of Aminoglycoside Phosphotransferase Type IIIa (1995)

Bacterial resistance to aminoglycoside-aminocyclitol antibiotics is mediated primarily by covalent modification of the drugs by a variety of enzymes. One such modifying enzyme, the 3'-aminoglycoside phosphotransferase, which is produced by Gram-positive cocci such as Enterococcus and Streptococcus inactivates a broad range of aminoglycosides by ATP-dependent phosphorylation of specific hydroxyl residues on the antibiotics. Through the use of dead-end and product inhibitor studies, we present the first detailed examination of the kinetic mechanism for the 3'-aminoglycoside phosphotransferase-IIIa. Initial velocity patterns deduced from steady-state kinetics indicate a sequential mechanism with ordered binding of ATP first followed by aminoglycoside. Dead-end inhibition by AMP and adenylyl-imidodiphosphate is competitive versus ATP and noncompetitive versus kanamycin A. Dead-end inhibition by tobramycin, a kanamycin analogue lacking a 3'-OH, is competitive versus both kanamycin A and uncompetitive versus ATP, indicative of ordered substrate binding where ATP must add prior to aminoglycoside addition. Product inhibition by kanamycin phosphate is noncompetitive versus ATP when kanamycin A is held at subsaturating concentrations (Km(kanA)), whereas no inhibition is observed when the concentration of kanamycin A is held at 10Km(kanA). This is consistent with kanamycin phosphate being the first product released followed by ADP release. The patterns of inhibition observed support a mechanism where ATP binding precedes aminoglycoside binding followed by a rapid catalytic step. Product release proceeds in an ordered fashion where kanamycin phosphate is released quickly followed by a slow release of ADP. Aminoglycoside substrates, such as kanamycin A, show substrate inhibition that is uncompetitive versus ATP. This indicates binding of the aminoglycosides to the slowly dissociating (E-ADP) complex at high drug concentrations. These experiments are consistent with a Theorell-Chance kinetic mechanism for 3'-aminoglycoside phosphotransferase-IIIa.
City name recognition over the telephone (1993)

The authors present a neural-network-based speech recognition system for telephone speech. A neural network classifier provides phoneme probabilities for each frame of the utterance. A dynamic programming algorithm finds the most probable sequence of words. The classifier was trained on a spoken name corpus which contained the test vocabulary and many other words. The test set consisted of 262 utterances containing 44 cities and 2 states. The best result obtained on the test set was 92.9% word accuracy (90.1% on just the city names). Removing phoneme duration constraints reduced recognition accuracy to 82%. Performance fell to 82.4% using a network trained on a large vocabulary, fluent-speech corpus. Several other experiments are reported which did not produce significant changes in system performance.< <ETX>&gt;</ETX>
New Societal Approaches to Empowering Antibiotic Stewardship (2016)

Substantial concern regarding the ever-worsening crisis of antibiotic resistance has been raised by the World Health Organization, US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control, European Medicines Agency, Institute of Medicine, World Economic Forum, and the US Presidential Advisory Council on Science and Technology. The question is no longer whether to act, but how.

Antibiotic stewardship is the term used to describe efforts to optimize selection of antibiotic therapy. Formal antibiotic stewardship programs are essential to help society address antimicrobial resistance by reducing the estimated more than 50% of antibiotic use that is unnecessary or inappropriate.1 The US government has recently emphasized the need for implementation of antibiotic stewardship programs at all hospitals.2 To be effective, antibiotic stewardship programs must incorporate best practices, which include dedicating sufficient resources to the program, appointing a single leader to be accountable for performance, having appropriate antibiotic expertise, implementing action plans, monitoring bacterial resistance, reporting antibiotic usage to staff, and providing education
Development of Novel, Bioresorbable, Small-Diameter Electrospun Vascular Grafts (2015)

This study proposes a production method capable of producing vascular grafts from fully synthetic, resorbable polymers that both meet basic minimum mechanical requirements for potential vascular grafts, and have a compliance similar to that of the intended vasculature being replaced. All of the electrospun vascular grafts in this work meet the minimum mechanical requirements for compliance, burst pressure, and suture retention strength, and could be potential candidates for off-the-shelf tissue engineered vascular grafts. Each polymer investigated in this paper has FDA approval for medical use and has been shown to be successful in various tissue engineering applications. Only recently has an electrospun small-diameter graft been fabricated with compliance and burst pressure greater than that of the human saphenous vein. We show a significant advancement in burst pressure, compliance, and suture retention strength in the novel electrospun grafts presented in this work which demonstrates the potential use of these tissue engineered vascular grafts for coronary artery bypass graft and other smalldiameter graft indications.
Rabies Virus-Based Vectors Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Protein Induce a Strong, Cross-Reactive Cytotoxic T-Lymphocyte Response against Envelope Proteins from Different HIV-1 Isolates (2001)

Novel viral vectors that are able to induce both strong and long-lasting immune responses may be required as effective vaccines for human immunodeficiency virus type 1 (HIV-1) infection. Our previous experiments with a replication-competent vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from a laboratory-adapted HIV-1 strain (NL4-3) and a primary HIV-1 isolate (89.6) showed that RV-based vectors are excellent for B-cell priming. Here we report that cytotoxic T-lymphocyte (CTL) responses against HIV-1 gp160 are induced by recombinant RVs. Our results indicated that a single inoculation of mice with an RV expressing HIV-1 gp160 induced a solid and long-lasting memory CTL response specific for HIV-1 envelope protein. Moreover, CTLs from immunized mice were not restricted to the homologous HIV-1 envelope protein and were able to cross-kill target cells expressing HIV-1 gp160 from heterologous HIV-1 strains. These studies further suggest promise for RV-based vectors to elicit a persistent immune response against HIV-1 and their potential utility as efficacious anti-HIV-1 vaccines.
Optical transceivers for 100 gigabit Ethernet and its transport [100 gigabit ethernet transport (2010)

A new generation of optical transceivers for 100 Gigabit Ethernet client interconnection and line system transmission are now being developed and deployed for data center and transport applications. This article provides an overview and status of the 100 G Form-factor Pluggable Multi-Source Agreement for client applications and the Optical Internetworking Forum 100 G Transponder Module Implementation Agreement for long distance DWDM transmission applications.
A Totally Synthetic Polyoxime Malaria Vaccine Containing Plasmodium falciparum B Cell and Universal T Cell Epitopes Elicits Immune Responses in Volunteers of Diverse HLA Types (2001)

This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types. The polyoxime, designated (T1BT(*))(4)-P3C, was constructed by chemoselective ligation, via oxime bonds, of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein. The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant, using instead a core modified with the lipopeptide P3C as an endogenous adjuvant. This totally synthetic vaccine formulation can be characterized by mass spectroscopy, thus enabling the reproducible production of precisely defined vaccines for human use. The majority of the polyoxime-immunized volunteers (7/10) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites. In addition, these seven volunteers all developed T cells specific for the universal epitope, termed T(*), which was originally defined using CD4(+) T cells from protected volunteers immunized with irradiated P. falciparum sporozoites. The excellent correlation of T(*)-specific cellular responses with high anti-repeat Ab titers suggests that the T(*) epitope functioned as a universal Th cell epitope, as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes. The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic, multicomponent synthetic vaccines for malaria, as well as for other pathogens.
The D ysfunctional Att itude Scale: A Validation Study (1979)

Doctor of Philosophy (PhD)
In Vivo Delivery Systems for Therapeutic Genome Editing (2016)

Therapeutic genome editing technology has been widely used as a powerful tool for directly correcting genetic mutations in target pathological tissues and cells to cure of diseases. The modification of specific genomic sequences can be achieved by utilizing programmable nucleases, such as Meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly-interspaced short palindromic repeat-associated nuclease Cas9 (CRISPR/Cas9). However, given the properties, such as large size, negative charge, low membrane penetrating ability, as well as weak tolerance for serum, and low endosomal escape, of these nucleases genome editing cannot be successfully applied unless in vivo delivery of related programmable nucleases into target organisms or cells is achieved. Here, we look back at delivery strategies having been used in the in vivo delivery of three main genome editing nucleases, followed by methodologies currently undergoing testing in clinical trials, and potential delivery strategies provided by analyzing characteristics of nucleases and commonly used vectors.
Proteolytic cleavage at arginine residues within the hydrophilic disulphide loop of the Escherichia coli Shiga‐like toxin I A subunit is not essential for cytotoxicity (1993)

Escherichia coli Shiga-like toxin I is a type II ribosome-inactivating protein composed of an A subunit with RNA-specific N-glycosidase activity, non-covalently associated with a pentamer of B subunits possessing affinity for galabiose-containing glycolipids. The A subunit contains a single intrachain disulphide bond encompassing a hydrophilic sequence containing two trypsin-sensitive arginine residues. By analogy with other bacterial toxins it has been proposed that proteolytic nicking, deemed essential for a cytotoxic effect, occurs within this disulphide-bonded loop to generate the A1 and A2 fragments. Reduced A1 is then believed to translocate an internal membrane to inactivate protein synthesis in the cytosol. In this report, the disulphide-loop arginines of the SLT I A subunit were mutated to block the specific proteolysis presumed to occur. However, the mutant generated remained an effective toxin having similar catalytic activity to wild-type toxin and only a marginally reduced cytotoxicity towards cultured cells. We conclude that the disulphide-loop arginine residues are not the unique and essential processing sites previously assumed, but that processing may occur at alternative accessible sites to compensate for loss of target sites within the loop.
Insecticidal Baits on Field Plot Perimeters Suppress Reticulitermes12 (1978)

Journal Article Insecticidal Baits on Field Plot Perimeters Suppress Reticulitermes Get access G. R. Esenther, G. R. Esenther Search for other works by this author on: Oxford Academic PubMed Google Scholar R. H. Beal R. H. Beal Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 71, Issue 4, 1 August 1978, Pages 604–607, https://doi.org/10.1093/jee/71.4.604 Published: 01 August 1978 Article history Received: 04 November 1977 Published: 01 August 1978
Microfluidic System for Planar Patch Clamp Electrode Arrays (2006)

We present a microfluidic system integrated with disposable cell interface partitions for simultaneous patch clamp recordings. Glass-supported poly(dimethylsiloxane) (PDMS) partitions, having a 2 microm air-blown aperture, were reversibly sealed to a microfluidic system including PDMS channels with isolation valves and microfabricated Ag/AgCl electrodes. Gigaseal recordings from RBL-1 cells were obtained with a 24% success rate. Simultaneous whole cell recordings from valve-isolated electrodes were obtained.
An Epidemic of Mild Pneumonia Due to an Unusual Strain of Chlamydia psittaci (1985)

An epidemic of mild pneumonia was discovered during a chest radiographic survey of adolescents and young adults in two communities 110 kilometers apart in northern Finland. Antibodies to chlamydial antigens were found in 32 of 34 persons with pneumonitis. Microimmunofluorescence antibody tests suggest that the etiologic agent is closely related or identical to TW-183, an unusual strain of Chlamydia psittaci isolated from the eye of a child in Taiwan. The point prevalence of pneumonitis with antibody to TW-183 in school children at the time of the survey was high-15 and 19 patients per 1,000 students in the two communities. There was no evidence of avian transmission in the epidemic.
The Chick Embryo Chorioallantoic Membrane as a Model for in vivo Research on Anti-Angiogenesis (2000)

Anti-angiogenesis, i.e. inhibition of blood vessel growth, is being investigated as a way to prevent the growth of tumors and other angiogenesis-dependent diseases. Pharmacological inhibition interferes with the angiogenic cascade or the immature neovasculature with synthetic or semi-synthetic substances, endogenous inhibitors or biological antagonists. The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane commonly used in vivo to study both new vessel formation and its inhibition in response to tissues, cells, or soluble factors. Angiogenesis or anti-angiogenesis is evaluated quantitatively or semiquantitatively. The fields of application of CAM in the study of anti-angiogenesis, including our personal experience, are illustrated in this paper.
Surface Tension of Liquid Fluorocompounds (2006)

This work aims at studying the surface tension of some linear, cyclic, aromatic, and α-substituted perfluorocarbons. Despite its fundamental interest, information about this property for these compounds is scarce, and the available data are old and present strong discrepancies among each other. The measurements were carried out in the temperature range (283 to 327) K with the Du Noüy ring method. The analysis of the experimental data shows that the molecular structure is an important factor in the surface behavior of the studied compounds since the aromatic fluorocompounds present the highest surface tensions, followed by the cyclic and substituted fluorocompounds. The linear n-perfluoroalkanes exhibit the lowest surface tension values, slightly increasing with the carbon number. The surface thermodynamic functions such as surface entropy and enthalpy were derived from surface tension values and are also reported. The experimental data were compared against the Faizullin correlation, and it is shown that this correlation describes the measured surface tensions with deviations inferior to 4 %.
DNA Fragment Sizing by Single Molecule Detection in Submicrometer-Sized Closed Fluidic Channels (2002)

The fabrication of fluidic channels with dimensions smaller than 1 microm is described and characterized in respect to their use for detection of individual DNA molecules. The sacrificial layer technique is used to fabricate these devices as it provides CMOS-compatible materials exhibiting low fluorescence background. It also allows creating microfluidics circuitry of submicrometer dimensions with great control. The small dimensions facilitate single molecule detection and minimize events of simultaneous passage of more than one molecule through the measurement volume. The behavior of DNA molecules inside these channels under an applied electrical field was first studied by fluorescence correlation spectroscopy using M13 double-stranded DNA. A linear relationship between the flow speed and applied electric field across the channel was observed. Speeds as high as 5 mm/s were reached, corresponding to only a few milliseconds of analysis time per molecule. The channels were then used to characterize a mixture of nine DNA fragments. Both the distribution and relative proportions of the individual fragments, as well as the overall concentration of the DNA sample, can be deduced from a single experiment. The amount of sample required for the analysis was approximately 10,000 molecules, or 76 fg. Other potential applications of these submicrometer structures for DNA analysis are discussed.
Bile Salt Induction of Apoptosis in Goblet Cells of the Normal Human Colonic Mucosa: Relevance to Colon Cancer (1995)

Substantial evidence indicates that bile salts have a role in the etiology of colon cancer. The mechanism of action of bile salts, however, is largely unknown. We show here that bile salt sodium deoxycholate (NaDOC), at high physiologic individual ingests a high fat diet over severa! concentrations, induces apoptosis (programmed cell death) in a select colonic epithelial subpopulation (immature and mature goblet cells). Induction of apoptosis by NaDOC was determined using light and electron microscopy.
The colonic goblet cells of four normal human subjects showed substantial induction of apoptosis (45% to 63% of goblet cells were apoptotic) upon treatment with 1 mM NaDOC for three hours. In contrast, the normal appearing colonic mucosa from six colon cancer patients showed relatively low induction of apoptosis (only 1% to 23% of goblet cells were apoptotic) after the same treatment. Among six patients with non- malignant polyps, four resembled the cancer patients in that the frequency of apoptotic cells in the normal portion of their colon was low after NaDOC treatment (2% to 21 %); the other two had frequencies similar to that of normal individuals (61% and 63%).
These new findings suggest a novel hypothesis related to the role of bile salts in colon carcinogenesis. It is known that a high fat diet produces high levels of bile salts in the intestinal tract, and that bile salts cause DNA damage. Studies have also shown that cells with unrepaired DNA damage are subject to apoptosis. We hypothesize that when an apoptosis-resistant cells can be selected. When such a population becomes established, cells with carcinogen caused DNA damage remain viable instead of entering the apoptosis pathway. Such cells may then replicate and undergo mutation at sites of damage. These mutations may then lead to colon cancer.
Olfactory receptor surface expression is driven by association with the β 2 -adrenergic receptor (2004)

Olfactory receptors (ORs) comprise more than half of the large class I G protein-coupled receptor (GPCR) superfamily. Although cloned over a decade ago, little is known about their properties because wild-type ORs do not efficiently reach the cell surface following heterologous expression. Receptor-receptor interactions strongly influence surface trafficking of other GPCRs, and we examined whether a similar mechanism might be involved in OR surface expression. Olfactory neurons are known to express beta-adrenergic receptors (ARs), and we found that coexpression with beta(2)-ARs, but not any other AR subtypes, dramatically increased mouse 71 (M71) OR surface expression in human embryonic kidney 293 cells. A persistent physical interaction between M71 ORs and beta(2)-ARs was shown by coimmunoprecipitation and by cointernalization of the two receptors in response to their specific ligands. Also, coexpression of wild-type M71 ORs with beta(2)-ARs resulted in cAMP responses to the M71 ligand acetophenone. Finally, in situ hybridization studies showed extensive colocalization of M71 OR and beta(2)-AR expression in mouse olfactory epithelium. These data demonstrate the successful heterologous surface expression of a functional wild-type OR and reveal that persistent physical association with other GPCRs can control OR surface expression.
lnterleukin‐2 mediated regulation of mitogen‐activated T cell reactivity from different lymphoid sources in patients with squamous cell carcinoma of the oral cavity (1989)

Peripheral blood lymphocytes (PBL) from patients with oral cancer (treated and untreated), oral leukoplakia and healthy donors; lymphocytes from metastatic and non-metastatic lymph nodes (met LNL and non-met LNL); and tumor infiltrating lymphocytes (TIL) were tested for proliferative response to mitogen PHA (phytohemagglutinin) and its augmentation by recombinant Interleukin-2 (rIL-2), for expression of Tac antigen (CD25) and for production of IL-2. Depressed PHA responses were found in PBL of treated and untreated patients, and in TIL. Addition of IL-2 could bring about 16% to 31% augmentation in lymphocyte response to PHA from all the three sources. PBL from 50% of healthy donors, 45% of patients with leukoplakia, 25% untreated oral cancer patients and 35% treated oral cancer patients showed IL-2 mediated augmentation of PHA response. While, 40% non-met LNL samples, 70% met LNL samples and only 23% TIL samples showed increased mitogen induced proliferation by IL-2. The augmented levels of PHA response of PBL from treated and untreated patients, and of TIL, were still below those of normal PBL. PBL from patients with leukoplakia, treated oral cancer patients and TIL showed depressed CD25 antigen expression. Depressed IL-2 production was observed only in PBL of leukoplakia patients. Thus the IL-2 mediated events of T cell activation from different lymphoid sources in patients with oral cancer did not correlate with their proliferative responses.
The physiology and the pathophysiology of the gastric accommodation reflex in man. (2000)

Summarizing the previous sections, we have demonstrated that the gastric accommodation reflex in man involves the release of serotonin and the activation of a nitrergic motor neuron. We observed that almost half of the patients with functional dyspepsia have an impaired accommodation reflex, and this is associated with early satiety and weight loss. Drug-induced inhibition of the accommodation reflex is able to induce early satiety in healthy subjects. Administration of the anti-migraine drug sumatriptan, an agonist at 5-HT1P receptors on gastric myenteric neurons, causes a relaxation of the proximal stomach in man through a nitrergic pathway. Pretreatment with sumatriptan is able to restore impaired accommodation and to improve early satiety in patients with functional dyspepsia. We conclude from these data that fundus-relaxing drugs may have a therapeutic potential in functional dyspepsia, and we hypothesize that fundus-contracting drugs may have therapeutic potential in the treatment of obesity.