gebhart/patrepeval huggingface dataset:
Multiple Colorectal Adenomas, Classic Adenomatous Polyposis, and Germ-Line Mutations inMYH (2003)

Germ-line MYH mutations predispose persons to a recessive phenotype, multiple adenomas, or polyposis coli. For patients with about 15 or more colorectal adenomas--especially if no germ-line APC mutation has been identified and the family history is compatible with recessive inheritance--genetic testing of MYH is indicated for diagnosis and calculation of the level of risk in relatives. Clinical care of patients with biallelic MYH mutations should be similar to that of patients with classic or attenuated familial adenomatous polyposis.
Expanding range of pulsed range sensors with active projection from spatial light modulators (2006)

LIDAR-based systems measure the time-of-flight of a laser source onto the scene and back to the sensor, building a wide field of view 3D raster image, but as a scanning process, there are problems associated with motion inside the scene over the duration of the scan. By illuminating the entire scene simultaneously using a broad laser pulse, a 2D camera equipped with a high speed shutter can measure the time-of-flight over the entire field of view (FOV), thereby, recording an instantaneous snap-shot of the entire scene. However, spreading the laser reduces the range. So what is required is a programmable system that can track multiple regions of interest by varying the field of regard to (1) a single direction, (2) the entire FOV, or (3) intermediate views of interest as required by the evolving scene environment. In this project, the investigators intend to add this variable illumination capability to existing instantaneous ranging hardware by using a liquid crystal spatial light modulator (SLM) beam steering system that adaptively varies the (single or multi) beam intensity profiles and pointing directions. For autonomous satellite rendezvous, docking, and inspection, the system can perform long-range sensing with a narrow FOV while being able to expand the FOV as the target object approaches the sensor. To this end in a previous paper, we analyzed the performance of a commercially available TOF sensor (3DVSystems' Zmini) in terms of the depth sensitivity versus target range and albedo. In this paper, we will analyze the laser system specifications versus range of field-of-view when beam steering is performed by means of a Boulder Nonlinear Systems' phase-only liquid crystal SLM. Experimental results show that the adjustable laser beam FOV extensively compensate the reflected image grayscale from objects at long range, and prove the feasibility of expanding range with the projection from the SLM.
Development of a Zika vaccine using a novel MVA-VLP platform (2016)

Purpose: Zika is a rapidly spreading, emerging infectious disease linked to infant microcephaly, Guillain Barre Syndrome, and other neurological disorders putting half of the world's population at risk of infection. No approved preventive or therapeutic products are currently available. To rapidly develop a Zika vaccine, GeoVax is leveraging its 4th generation MVA-VLP technology, improved for transgene stability and designed to produce VLPs in vaccinated individuals, for the construction of a Zika virus (ZIKV) vaccine. Methods & Materials: Two MVA-VLP vaccine candidates have been developed from ZIKV strain Suriname 2015 sequences: one expressing pre-Membrane and Envelope (prME) genes, and the other expressing prME + Non-Structural protein 1 (NS1) genes. These antigens were chosen based on documented evidence that flavivirus prME and NS1 proteins are sufficient to elicit protective immune responses. Results: The production of ZIKV prME VLPs was demonstrated by EM in after infections of DF1 cells with MVA-PrME virus. VLP were produced at high concentrations in production cell lines. ZIKV-specific antibodies detected both E (54 kD) and NS1 (40 kD) proteins in cell lysate and supernatant (only E) of infected cells. Research stocks were made from sucrose gradient purified MVA-VLP viruses at titeres of >10e8 TCID50/ml and being used for immunizations of various strians of mice at our collaborators’ laboratories at CDC and University of Georgia. Conclusion: This is the first report that a viral vector (replication competent or replication deficient) has produced a vaccine candidate for Zika that forms VLPs in vivo. Induction of VLPs in the host cells of the vaccine recipients not only eliminates the need for VLP purifications during manufacturing, but also generates a potent single dose vaccine (as shown with our MVA-VLP Ebola vaccine) that induces strong humoral and cellular immune responses similar to that of a natural Zika virus. Being tested safely in more than 120,000 subjects, including immunodeficient individuals, MVA based vaccines will be appropriate to be used in women of child bearing age, elderly or infant population. A potential single dose MVA-VLP Zika vaccine can be used for stockpiling by governments as well as for an immediate response to an ongoing epidemic.
SARS in Newborns and Children (2004)

The severe acute respiratory syndrome (SARS) is a highly contagious infection caused by a newly discovered strain of coronavirus (SARS-CoV). Infants born to pregnant women with SARS did not appear to acquire the infection through vertical transmission. Some newborn infants, however, developed severe intrauterine growth retardation and life-threatening gastrointestinal complications. It is now known that the clinical course and prognosis are different between paediatric and adult SARS patients. Young children (< 12 years), in general, run a less aggressive clinical course than do teenage and adult patients. Thus far, no fatalities have been reported in the paediatric age group (< or =18 years). This review describes the current understanding of the clinical manifestations, diagnostic tests, immunological profiles, patient management and outcomes of SARS-CoV infection in the paediatric population.
Posture and policymaking in Canada‐US relations: The first two Mulroney and Chrétien years (1998)

Roy Norton provides a broad review of the policy “rhetoric” of consecutive Mulroney and Chrétien governments, comparing the treatment of major issues in Canada‐US relations over the first two years of each tenure. Analysis begins with an identification of key rhetorical statements of each government, and provides a detailed review of their records around major foreign policy issues. For the PCs these include acid rain, arctic sovereignty, the Strategic Defence Initiative/Anti‐Ballistic Missile Treaty, Central America; and for the Liberals, NAFTA, national unity/summitry, cruise missile testing, NAAD, the environment, Cuba, and military cooperation in Bosnia and Haiti. The author concludes that the Conservatives sometimes adopted policies at odds with their pro‐US rhetoric, while the Liberals tended to have more bark than bite when it came to relations with the US. Norton describes several variables that should be considered in case comparisons: the personal relationship between leaders, intangible aspects, and the ethereal nature of independence.
Multiple Sources Initiating Atrial Fibrillation from a Single Pulmonary Vein Identified by a Circumferential Catheter (2000)

The pulmonary veins are the predominant source of ectopic activity initiating AF. The reproducibility of intrapulmonary vein activation during ectopic activity and/or initiation of multiple AF episodes was examined. Eighty-nine pulmonary veins (PVs) among 29 patients undergoing radiofrequency ablation of AF were studied with a 15- to 20-mm diameter, circumferential PV catheter equipped with ten electrodes and a deflectable shaft. Local electrograms were recorded simultaneously during sinus rhythm, ectopic activity, or AF onset, spontaneously or induced via the catheter left in a stable position. Fifty-four arrhythmogenic veins were identified, 39 showing isolated ectopy, and 8 displayed repetitive ectopy (in salvos). The earliest site of activation and the sequence of intra-PV activation during isolated ectopy was identical to that observed during consecutive ectopic complexes in 77% and variable in 23% during isolated ectopy. The earliest activity was sometimes limited to a single bipole. During repetitive ectopy and AF initiation, multiple sources and/or variable activation patterns were noted in 53% of instances, indicating the presence of multiple arrhythmogenic foci within the same PV. Simultaneous electrogram recordings with a circumferential PV catheter identified the presence of multiple arrhythmogenic foci within a single PV.
Gd(III)-Labeled Peptide Nanofibers for Reporting on Biomaterial Localization in Vivo (2014)

Bioactive supramolecular nanostructures are of great importance in regenerative medicine and the development of novel targeted therapies. In order to use supramolecular chemistry to design such nanostructures, it is extremely important to track their fate in vivo through the use of molecular imaging strategies. Peptide amphiphiles (PAs) are known to generate a wide array of supramolecular nanostructures, and there is extensive literature on their use in areas such as tissue regeneration and therapies for disease. We report here on a series of PA molecules based on the well-established β-sheet amino acid sequence V3A3 conjugated to macrocyclic Gd(III) labels for magnetic resonance imaging (MRI). These conjugates were shown to form cylindrical supramolecular assemblies using cryogenic transmission electron microscopy and small-angle X-ray scattering. Using nuclear magnetic relaxation dispersion analysis, we observed that thermal annealing of the nanostructures led to a decrease in water exchange lifetime (τm) of hundreds of nanoseconds only for molecules that self-assemble into nanofibers of high aspect ratio. We interpret this decrease to indicate more solvent exposure to the paramagnetic moiety on annealing, resulting in faster water exchange within angstroms of the macrocycle. We hypothesize that faster water exchange in the nanofiber-forming PAs arises from the dehydration and increase in packing density on annealing. Two of the self-assembling conjugates were selected for imaging PAs after intramuscular injections of the PA C16V3A3E3-NH2 in the tibialis anterior muscle of a murine model. Needle tracts were clearly discernible with MRI at 4 days postinjection. This work establishes Gd(III) macrocycle-conjugated peptide amphiphiles as effective tracking agents for peptide amphiphile materials in vivo over the timescale of days.
A fully monolithic 4-18 GHz digital vector modulator (2002)

A fully monolithic vector modulator covering the entire 4-18 GHz band and featuring independent direct digital control of amplitude and phase is presented. The modulator output amplitude can be varied over a 25-dB range with 32 steps of resolution and the phase can be independently varied over 360 degrees with 32 steps. The vector modulator chip set consists of a miniaturized 5-b MMIC (monolithic microwave integrated circuit) phase shifter and a 5-b MMIC segmented dual-gate distributed variable-gain amplifier-attenuator. The chips are assembled on a carrier measuring less than 0.4 in *0.5 in and require no supporting RF-hybrid hybrid or DAC (digital-to-analog converter) circuitry. The vector modulator demonstrates state-of-the-art performance with ultrawide (instantaneous) bandwidth, high uncorrected accuracy and resolution, and direct digital control with a potential transition time of a few nanoseconds. In addition, the individual MMIC chip performance is the best reported to date for ultrawide bandwidth phase and amplitude control functions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hydrogenation Pathway of Quinolines over Raney Nickel and Ru/C (1990)

Abstract Quinoline, 2-methylquinoline, and 8-methylquinoline were hydrogenated over Raney nickel (R-Ni) under 10 atm hydrogen pressure at about 200°C and over ruthenium on carbon (Ru/C) under 100 atm hydrogen pressure at 150°C. All the substrates were commonly hydrogenated into the initial products, 1,2,3,4-tetrahydroquinolines. The initial products were competitively converted over R-Ni to the final products, decahydroquinolines, directly or via 5,6,7,8-tetrahydroquinolines which were mainly formed from the initial products by isomerization. Ru/C promoted exclusively the direct hydrogenation of 1,2,3,4-tetrahydro derivatives to the final products. The hydrogenation and isomerization of 1,2,3,4-tetrahydroquinoline was completely inhibited in the competitive hydrogenation of quinoline and isoquinoline over R-Ni. Such features of these substrates are explained by the strong basicity of 1,2,3,4-tetrahydroisoquinoline. Roles of 1,2,3,4-tetrahydroisoquinoline are much moderate on Ru/C, where the π-coordination may be important. The effects of methyl substituent and different reactivities of quinoline and isoquinoline are discussed in terms of the steric hindrance on adsorption, heats of hydrogenation, basicities, and electronic properties of the related compound, which are calculated according to the MNDO-PM3 method.
High-speed electro-optic analog-to-digital converter (1978)

The periodic dependence of the output of an electro-optic intensity modulator on applied voltage can be utilized to perform A/D conversion. The feasibility of the concept has been demonstrated by such a modulator in a threshold circuit to simulate one bit channel of an A/D converter. The optical approach offers several potential improvements over present technique: faster conversion rates, fewer comparators, lower electrical power dissipation, and the opportunity to record the output on photographic film. Further work in modulator fabrication, mode-locked injection laser development, laser-to-modulator coupling techniques, and threshold optical detection techniques will be needed before the full potential of this device can be realized. Application areas include digital signal processors for wideband radar and electronic warfare systems. (Author)
Expression of a Gene Encoding the Major Antigenic Protein 2 Homolog ofEhrlichia chaffeensisand Potential Application for Serodiagnosis (2000)

The major antigenic protein 2 (MAP2) homolog of Ehrlichia chaffeensis was cloned and expressed. The recombinant protein was characterized and tested in an enzyme-linked immunosorbent assay (ELISA) format for potential application in the serodiagnosis of human monocytic ehrlichiosis. The recombinant protein, which contained a C-terminal polyhistidine tag, had a molecular mass of approximately 26 kDa. The antigen was clearly identified by Western immunoblotting using antihistidine antibody. However, immune sera failed to react with the recombinant on immunoblots when the antigen was denatured by heat or reduced using beta-mercaptoethanol. The recombinant MAP2 (rMAP2) was used in an ELISA format with 60 blinded serum samples. Twenty of the serum samples were previously demonstrated to contain antibodies reactive with E. chaffeensis by indirect immunofluorescence assays (IFAs). The remaining 40 samples were seronegative. All samples negative by IFA were also found to be negative for antibodies against the rMAP2 of E. chaffeensis by using the ELISA. Only 1 of 20 IFA-positive samples tested negative in the rMAP2 ELISA. There was 100% agreement using IFA-negative samples and 95% agreement using IFA-positive samples, resulting in a 97.5% overall agreement between the two assays. These data suggest that the rMAP2 homolog of E. chaffeensis may have potential as a test antigen for the serodiagnosis of human monocytic ehrlichiosis. To our knowledge, this recombinant is unique because it is thus far the only E. chaffeensis recombinant antigen that has been shown to work in an ELISA format.
Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance. (1999)

This short review describes the localization of somatostatin receptors with in vitro receptor autoradiography techniques in several non-classical, normal human somatostatin target tissues as well as in selected human tumors. In addition to brain, gut and neuroendocrine localizations, somatostatin receptors are expressed in most lymphatic tissues, including gut-associated lymphatic tissue, spleen and thymus; in the cortical and medullary area of the kidney; in the stroma of the prostate and in the epithelial cells of the thyroid. Among human tumors, the extremely high density of somatostatin receptors in medulloblastomas should be stressed as well as the favorable prognostic role of the presence of somatostatin receptors in neuroblastomas. Moreover, several types of mesenchymal tumors have somatostatin receptors as well. The receptor subtypes expressed by distinct tumors may vary: Whereas medulloblastomas and neuroblastomas predominantly express sst2, prostate cancers express sst1 rather than sst2. A further emerging somatostatin target is represented by the peritumoral veins, also known to express sst2 receptors. The multiple somatostatin targets in normal and pathological human tissues represents the basis for potential diagnostic and clinical applications of somatostatin analogs.
CA3-Driven Hippocampal-Entorhinal Loop Controls Rather than SustainsIn VitroLimbic Seizures (1997)

Continuous application of 4-aminopyridine (4-AP, 50 microM) to combined slices of hippocampus-entorhinal cortex obtained from adult mice induces (1) interictal discharges that initiate in the CA3 area and propagate via the hippocampal regions CA1 and subiculum to the entorhinal cortex and return to the hippocampus through the dentate gyrus; and (2) ictal discharges that originate in the entorhinal cortex and propagate via the dentate gyrus to the hippocampus proper. Ictal discharges disappear over time, whereas synchronous interictal discharges continue to occur throughout the experiment. Lesioning the Schaffer collaterals abolishes interictal discharges in CA1, entorhinal cortex, and dentate gyrus and discloses entorhinal ictal discharges that propagate, via the dentate gyrus, to the CA3 subfield. Interictal discharges originating in CA3 also prevent the occurrence of ictal events generated in the entorhinal cortex during application of Mg2+-free medium. In both models, ictal discharge generation recorded in the entorhinal cortex after Schaffer collateral cut is prevented by mimicking CA3 neuronal activity through rhythmic electrical stimulation (0.25-1.5 Hz) of the CA1 hippocampal output region. Our findings demonstrate that interictal discharges of hippocampal origin control the expression of ictal epileptiform activity in the entorhinal cortex. Sectioning the Schaffer collaterals may model the chronic epileptic condition in which cell damage in the CA3 subfield results in loss of CA3 control over the entorhinal cortex. Hence, we propose that the functional integrity of hippocampal output neurons may represent a critical control point in temporal lobe epileptogenesis.
The multivariate skew-normal distribution (1996)

The paper extends earlier work on the so-called skew-normal distribution, a family of distributions including the normal, but with an extra parameter to regulate skewness. The present work introduces a multivariate parametric family such that the marginal densities are scalar skew-normal, and studies its properties, with special emphasis on the bivariate case.
Studies on natural product derivatives : HIV therapies incorporating marine natural products. (2001)

CV-N is an 11 kDa, anti-HIV protein that binds strongly to the envelope glycoprotein, gp120, expressed on the outer surface of the free virion and also on HIV-infected cells. As such, it represents an important lead for development of anti-HIV therapeutics. Marine toxins such as the halichondrins have potent in vivo cytotoxicities and are lethal to cells. The combination of this potency of the marine toxins with the unique targeting capability of CV-N has been harnessed to produce conjugates that have the potential to selectively target and eliminate HIV-infected cells. Three forms of the protein were developed; the native protein itself, a derivative recombinantly produced in E. coli with an extra cysteine at the C-terminal (CV-N-Cys) and CV-N with the lysine side chain amines converted into thiols (thiolated-CV-N). To facilitate release of the toxin within infected cells an enzymatically-cleavable pHdependent biolinker was incorporated separating the toxin from the protein. The chemistry required for incorporation of protein, biolinker, and toxin, was established through synthesis of fluorescently labelled conjugates capable of reaction with CV-N. Biological testing of these derivatives showed no interference with the anti-HIV activity of the CV-N when conjugated in these model compounds. Synthetic strategies were developed to produce two derivatives of norhomohalichondrin B amine, both containing the cleavable biolinker, but with activation from succinimidyl esters and maleimido groups respectively. Native CV-N was reacted with the succinimidyl ester derived toxin construct to produce a CV-N-biolinker-toxin conjugate. The maleimido derivative toxin construct was reacted with both CV-N-Cys and thiolated-CV -N to produce closely related CV-N-toxin conjugates. Investigations into the binding properties and cell toxicities of these conjugates is currently underway.
Computational design of a pH-sensitive IgG binding protein (2013)

Computational design provides the opportunity to program protein-protein interactions for desired applications. We used de novo protein interface design to generate a pH-dependent Fc domain binding protein that buries immunoglobulin G (IgG) His-433. Using next-generation sequencing of naïve and selected pools of a library of design variants, we generated a molecular footprint of the designed binding surface, confirming the binding mode and guiding further optimization of the balance between affinity and pH sensitivity. In biolayer interferometry experiments, the optimized design binds IgG with a Kd of ∼ 4 nM at pH 8.2, and approximately 500-fold more weakly at pH 5.5. The protein is extremely stable, heat-resistant and highly expressed in bacteria, and allows pH-based control of binding for IgG affinity purification and diagnostic devices.