gebhart/patrepeval huggingface dataset:
Biomarkers and Parkinson's disease (2004)

Biomarkers are characteristics that can be measured as an indicator of a normal biological process, and they have special relevance in Parkinson's disease. Parkinson's disease is a chronic neurodegenerative disorder that is difficult to study, given the site of pathology and because the resultant clinical phenotype fluctuates over time. We currently have no definitive diagnostic test, and thus for the clinician there is hope that biomarkers will help diagnose symptomatic and presymptomatic disease or provide surrogate end-points to demonstrate clinical efficacy of new treatments, such as neuroprotective therapies, and help stratify this heterogeneous disease. No biomarker is likely to fulfil all these functions, so we need to know how each has been validated in order to understand their uses and limitations, and be aware of potential pitfalls. In this review we discuss the current potential biomarkers for Parkinson's disease, highlight the problems with their use, and conclude with a discussion of future alternatives.
CLEARANCE AND DISTRIBUTION OF CIPROFLOXACIN AFTER INTRAVITREAL INJECTION (1993)

This study was designed to determine the drug concentration and clearance after intravitreal injection of ciprofloxacin. Ciprofloxacin (100 micrograms/0.1 cc) was injected into the vitreous of normal eyes and into eyes that had undergone lensectomy and vitrectomy. Drug concentration was determined using high-pressure liquid chromatography analysis 0.5, 2, 4, and 12 hours after injection. In normal eyes, the elimination half life was 2.2 hours with a distribution volume of 1.2 ml. In aphakic vitrectomized eyes, the half life was 1 hour and the distribution volume was 1.4 ml. The majority of the drug appears to leave via a transretinal route, but clearance was not inhibited by probenecid. Because of the relatively short half life, intravitreal administration of ciprofloxacin for the treatment of endophthalmitis would provide only short-term therapy and would need to be supplemented by other forms of treatment.
Non-stoquastic Hamiltonians in quantum annealing via geometric phases (2017)

Abstract We argue that a complete description of quantum annealing implemented with continuous variables must take into account the non-adiabatic Aharonov-Anandan geometric phase that arises when the system Hamiltonian changes during the anneal. We show that this geometric effect leads to the appearance of non-stoquasticity in the effective quantum Ising Hamiltonians that are typically used to describe quantum annealing with flux qubits. We explicitly demonstrate the effect of this geometric non-stoquasticity when quantum annealing is performed with a system of one and two coupled flux qubits. The realization of non-stoquastic Hamiltonians has important implications from a computational complexity perspective, since it is believed that in many cases quantum annealing with stoquastic Hamiltonians can be efficiently simulated via classical algorithms such as Quantum Monte Carlo. It is well known that the direct implementation of non-stoquastic Hamiltonians with flux qubits is particularly challenging. Our results suggest an alternative path for the implementation of non-stoquasticity via geometric phases that can be exploited for computational purposes.
Carrier transport in PbS nanocrystal conducting polymer composites (2005)

In this letter we report the carrier mobilities in an inorganic nanocrystal: conducting polymer composite. The composite material in question (lead sulphide nanocrystals in the conducting polymer poly [2-methoxy-5-(2′-ethyl-hexyloxy)-p-phenylene vinylene] (MEH-PPV) was made using a single-pot, surfactant-free synthesis. Mobilties were measured using time of flight techniques. We have found that the inclusion of PbS nanocrystals in MEH-PPV both balances and markedly increases the hole and electron mobilities—the hole mobility is increased by a factor of ∼105 and the electron mobility increased by ∼107 under an applied bias of 5kVcm−1. These results explain why dramatic improvements in electrical conductivity and photovoltaic performance are seen in devices fabricated from these composites.
Targeting gene expression to the vascular wall in transgenic mice using the murine preproendothelin-1 promoter. (1995)

To develop a system for overexpressing genes in the vascular wall, we created transgenic mice using the reporter gene luciferase and the murine preproendothelin-1 promoter. In vitro analysis suggested that the murine 5'-flanking region contained endothelial-specific elements in a 5.9-kb fragment. Five transgenic mice colonies established from independent founders all exhibited the highest level of luciferase activity in the aorta with up to 8,540 light units per microgram of protein. Immunohistochemistry with anti-luciferase antisera revealed high levels of expression in the endothelial cells of both large and small arteries and lower levels of expression in veins and capillaries. Significant expression was also seen in arterial smooth muscle cells and in select epithelial surfaces which is consistent with the known distribution of endothelin-1 in mammals. The further demonstrate the targeting capability of this system, we overexpressed the lipid-peroxidating enzyme, human 15-lipoxygenase, in the vessel wall of transgenic mice. As with luciferase, expression of active enzyme and immunohistochemical localization in vascular cells were documented in transgenic animals. Hence, this new system can be used to direct expression of molecules to the vascular wall for the purpose of examining the biological significance of either overexpression or inhibition of select proteins.
Function of negative charge in the "address domain" of deltorphins (1991)

Deltorphins A, B, and C exhibit high delta-affinities (Ki = 0.12-0.31 nM) and very high delta-receptor binding selectivities (Ki mu/Ki delta = 1800-4100). A study of the delta-receptor binding properties of 15 deltorphin analogues focused primarily on the influence of the anionic group in the C-terminal tetrapeptide. Amidation of the beta-carboxyl groups of [Asp7], [Glu4], or [Asp4] in deltorphins A, B, and C, respectively, yielded peptides with enhanced mu-receptor affinities and minor changes in delta-affinities (Ki delta = 0.20-0.65 nM), but 5-8-fold diminished delta-selectivities. A free C-terminal carboxyl group markedly reduced delta-affinities and decreased delta-selectivities 6-11-fold; thus, the C-terminal amide group critically facilitates delta-affinity. Modifications in the anionic charged group or hydrophobic residues in the C-terminal tetrapeptide address domain of deltorphin A altered spatial distributions critical for delta-affinity and selectivity; e.g., [Nle6]deltorphin A enhanced mu-affinity and lowered delta-selectivity by two-thirds; the progressive, step-wise repositioning of Asp in deltorphin C (from position 4 to 7) was accompanied by linear decreases in delta-affinities and -selectivities, and increased mu-affinities of these peptides; enhancement of the charge density to -2, in [Asp6, Asp-OH7]deltorphin A, decreased delta-affinity and -selectivity, while [Asp4,5,His7]deltorphin A bound to neither mu- nor delta-sites. These results demonstrate that while an anionic group may occasionally facilitate high delta-receptor affinity, it represents an absolute requirement for the high delta-binding selectivity of these peptides. The locations of the charged groups relative to hydrophobic residues in the address domain of the peptide are also critical determinants for both delta-affinity and -selectivity.
Virtual reality and disability: emergence and challenge (2002)

(2002). Virtual reality and disability: emergence and challenge. Disability and Rehabilitation: Vol. 24, No. 11-12, pp. 567-569.
Ensembl 2006 (2005)

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased from 4 to 19, with the addition of the mammalian genomes of Rhesus macaque and Opossum, the chordate genome of Ciona intestinalis and the import and integration of the yeast genome. The year has also seen extensive improvements to both data analysis and presentation, with the introduction of a redesigned website, the addition of RNA gene and regulatory annotation and substantial improvements to the integration of human genome variation data.
Prognostic information provided during family meetings in the intensive care unit* (2007)

Critical Care Medicine: February 2007 - Volume 35 - Issue 2 - p 646-647 doi: 10.1097/01.CCM.0000255163.16683.14
Effects of nerve growth factor and acetyl‐l‐carnitine arginyl amide on the human neuronal line HCN‐1A (1992)

The HCN-1A clonal cell line, derived from the cortical tissue of a patient with unilateral megencephaly, was shown to differentiate into a mature neuronal-like state in the presence of the nerve growth factor, dibutyryl cyclic adenosine, 3',5'-monophosphate and either 1-isobutyl-3-methylxanthine or forskolin. Differentiation was assessed by measuring the percentage of cells that displayed branched, varicose processes that stained for synaptophysin. Treatment of cultures with a cocktail containing forskolin increased immunocytochemical staining for gamma aminobutyric (GABA), neurofilament protein and the nerve growth factor receptor species p75NGFR. Treatment with acetyl-L-carnitine alone had some effects on the cell morphology while acetyl-L-carnitine arginyl amide and nerve growth factor together increased the GABA content. Positive staining levels for the neurotransmitters gamma aminobutyric acid, glutamate, somatostatin, cholecystokinin and vasoactive intestinal polypeptide were measured quantitatively for HCN-1A under basal conditions.
Application of Digital Image Analysis and Flow Cytometry To Enumerate Marine Viruses Stained with SYBR Gold (2001)

A novel nucleic acid stain, SYBR Gold, was used to stain marine viral particles in various types of samples. Viral particles stained with SYBR Gold yielded bright and stable fluorescent signals that could be detected by a cooled charge-coupled device camera or by flow cytometry. The fluorescent signal strength of SYBR Gold-stained viruses was about twice that of SYBR Green I-stained viruses. Digital images of SYBR Gold-stained viral particles were processed to enumerate the concentration of viral particles by using digital image analysis software. Estimates of viral concentration based on digitized images were 1.3 times higher than those based on direct counting by epifluorescence microscopy. Direct epifluorescence counts of SYBR Gold-stained viral particles were in turn about 1.34 times higher than those estimated by the transmission electron microscope method. Bacteriophage lysates stained with SYBR Gold formed a distinct population in flow cytometric signatures. Flow cytometric analysis revealed at least four viral subpopulations for a Lake Erie sample and two subpopulations for a Georgia coastal sample. Flow cytometry-based viral counts for various types of samples averaged 1.1 times higher than direct epifluorescence microscopic counts. The potential application of digital image analysis and flow cytometry for rapid and accurate measurement of viral abundance in aquatic environments is discussed.
Head-to-Head Comparison of Second-Generation Nucleic Acid Amplification Tests for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae on Urine Samples from Female Subjects and Self-Collected Vaginal Swabs (2014)

In a comparison of 4 second-generation nucleic acid amplification tests performed with self-collected vaginal swab (SCVS) and first-void urine (FVU) specimens from 575 women, SCVS specimens indicated more infections than did FVU specimens in all assays. The prevalence rates were 9% (53/575 patients) for Chlamydia trachomatis and 2% (11/575 patients) for Neisseria gonorrhoeae. The clinical sensitivities for testing SCVS specimens for C. trachomatis were 98.1% on a Tigris system and 96.2% on a Panther system for the Aptima Combo 2 assay (Hologic Gen-Probe), 98.0% for the RealTime CT/NG assay on an m2000 instrument (Abbott), 90.6% for the ProbeTec CT/GC Q(x) assay on the Viper system (Becton Dickinson), and 84.6% for the cobas CT/NG assay on the cobas 4800 platform (Roche). Clinical sensitivities for C. trachomatis in FVU specimens were 88.7% (Tigris) and 88.0% (Panther) for the Aptima Combo 2 assay, 76.9% for the RealTime CT/NG assay, 75.5% for the ProbeTec CT/GC Q(x) assay, and 81.1% for the cobas CT/NG assay. Clinical sensitivities of the assays for N. gonorrhoeae, with limited positive results, ranged from 63.6% to 100%. Specificities for both infections ranged from 98.4 to 100%. Differences in analytical sensitivities and levels of molecular targets in clinical samples but not inhibitors of amplification may explain the differences in clinical sensitivities.
The sweet life (2014)

Jeffry Burden, BJ ’82, of Richmond, Va., received the 2007 development volunteer of the year award from the Arthritis Foundation’s national office. He serves on the foundation’s national income development committee and is a partner at the Virginia Estate Plans PLC and Virginia Fiduciary PLC law firms in Richmond. KLee Schaefer, BA ’82, of Belleville, Ill., received the workers’ compensation distinguished lawyer award from the Bar Association of Metropolitan St. Louis and Kids’ Chance Inc. She is an assistant attorney general and director of the Division of Labor in the office of Missouri Attorney General Jay Nixon. Michael Pritchett, BJ ’83, of Overland Park, Kan., wrote The Melancholy Fate of Capt. Lewis: A Novel of Lewis and Clark (Unbridled Books, 2007). Greg Michalson, MA ’78, of Columbia, edited the book. David Wright, BS Ag ’83, of Blue Springs, Mo., was elected to the board of directors of the Missouri State School Board Association. He has served on the Blue Springs R-4 Board of Education for the past seven years and is chief of financial operations for the USDA’s Risk Management Agency in Kansas City, Mo. KMichael Kodas, BJ, BJ ’84, of Hartford, Conn., wrote High Crimes: The Fate of Everest in an Age of Greed (Hyperion, 2008). An avid climber, he is a reporter and photographer for the Hartford Courant, and his work has also appeared in the Los Angeles Times, Washington Post, Boston Globe, Chicago Tribune and Newsweek. KKen Flottman, BA ’85, of Nairobi, Kenya, is resident director of the East Africa office of the International Republican Institute, a nonprofit organization that promotes the development of democracy. KLaura Pickard Meyer, BA ’85, BS Ed ’86, of Glenview, Ill., is past president of the Illinois Podiatric Medical Association. She was featured in the Spring 2007 newsletter of the American Association for Women Podiatrists. John J. Diehl Jr., BA ’87, of Ballwin, Mo., joined Armstrong Teasdale LLP as a partner. Tanja Ingeborg Heinen, BJ ’88, and husband David of Fairway, Kan., announce the birth of Mirabelle Gisela Sept. 16, 2007. Laura Stewart Knowles, A&S ’89, and husband T.K. Knowles of Pacific Palisades, Calif., announce the birth of Tiger Stephen Stewart The sweet life
Genome-Wide Prediction and Validation of Peptides That Bind Human Prosurvival Bcl-2 Proteins (2014)

Programmed cell death is regulated by interactions between pro-apoptotic and prosurvival members of the Bcl-2 family. Pro-apoptotic family members contain a weakly conserved BH3 motif that can adopt an alpha-helical structure and bind to a groove on prosurvival partners Bcl-xL, Bcl-w, Bcl-2, Mcl-1 and Bfl-1. Peptides corresponding to roughly 13 reported BH3 motifs have been verified to bind in this manner. Due to their short lengths and low sequence conservation, BH3 motifs are not detected using standard sequence-based bioinformatics approaches. Thus, it is possible that many additional proteins harbor BH3-like sequences that can mediate interactions with the Bcl-2 family. In this work, we used structure-based and data-based Bcl-2 interaction models to find new BH3-like peptides in the human proteome. We used peptide SPOT arrays to test candidate peptides for interaction with one or more of the prosurvival proteins Bcl-xL, Bcl-w, Bcl-2, Mcl-1 and Bfl-1. For the 36 most promising array candidates, we quantified binding to all five human receptors using direct and competition binding assays in solution. All 36 peptides showed evidence of interaction with at least one prosurvival protein, and 22 peptides bound at least one prosurvival protein with a dissociation constant between 1 and 500 nM; many peptides had specificity profiles not previously observed. We also screened the full-length parent proteins of a subset of array-tested peptides for binding to Bcl-xL and Mcl-1. Finally, we used the peptide binding data, in conjunction with previously reported interactions, to assess the affinity and specificity prediction performance of different models.
Peri-operative platelet function testing: The potential for reducing ischaemic and bleeding risks (2011)

The pivotal role of platelet activation and reactivity during atherothrombotic event occurrence associated with acute coronary syndromes (ACS) or percutaneous coronary interventions (PCI) is well established. Numerous translational research studies have established a threshold level of platelet reactivity during dual antiplatelet therapy above which a higher risk for ischaemic event occurrence has been observed. The clinical validity of these threshold values in reducing ischemic event occurrence with modified P2Y12 receptor therapy is currently under investigation in large-scale clinical trials. The association between on-treatment platelet reactivity measured by an ex vivo assay and the occurrence of bleeding events is less established. Currently, there is limited evidence of an association between platelet inhibition and coronary artery bypass grafting (CABG)- related bleeding in patients on clopidogrel therapy indicating that preoperative platelet function monitoring may guide both the timing of elective CABG and the administration of blood products in patients needing surgery. However, in the absence of a large-scale prospective clinical trial, routine platelet function monitoring and modification of timing of surgery based on platelet function monitoring are currently not recommended.
Molecular Pathogenesis of Neuromyelitis Optica (2012)

Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.
Inhibition of ribosomal and RNA polymerase functions by rubradirin and its aglycone. (1979)

The antibiotic rubradirin is structurally related to the ansamycin family of antibiotics. Most members of this group act as specific inhibitors of bacterial RNAP. Rubradirin and its aglycone possess diverging modes of action. Rubradirin inhibits ribosomal functions related to the peptide chain initiation process. It does not inhibit RNAP. By contrast the aglycone of rubradirin retains moderate inhibitory activity towards ribosomal functions but acts essentially as an extremely potent inhibitor of RNAP.
Clostridium scindens sp. nov., a Human Intestinal Bacterium with Desmolytic Activity on Corticoids (1985)

Clostridium scindens sp. nov., an obligate anaerobe with desmolytic activity, was isolated from human fecal flora. The desmolase, not associated previously with any specific intestinal microorganism, cleaves the carbon-carbon bond of 17-hydroxylated corticoids at C17-C20, thereby converting them to androstans (C19 steroids). In primary cultures on sheep blood agar plates, C. scindens forms minute, nonhemolytic colonies. The gram-positive rods (0.5 to 0.7 by 1 to 2.5 μm) are slightly curved. The rare oval terminal spores (0.8 to 2.0 μm in diameter) are extremely difficult to demonstrate in Gram-stained smears. More than 40% of the cells are fimbriated. Neither a capsule nor flagella are present. d-Fructose, d-glucose, lactose, d-mannose, d-ribose, and d-xylose are fermented. The major fermentation products are acetic acid, ethanol, and hydrogen. The type strain is ATCC 35704 (Bokkenheuser strain 19).
Evans blue dye adjuvant enhances delayed hypersensitivity while blocking immunity to Mycobacterium tuberculosis in mice (1981)

Evans blue dye functions as an adjuvant with protein antigens in saline to induce cell-mediated immunological responses in mice. But when used to help induce cell-mediated tuberculoimmunity, it decreased mouse resistance to tuberculosis instead of helping induce immunity. This paradox was investigated. As could be expected from previous work with other antigens, the dye did promote induction of delayed hypersensitivity in mice to tuberculoprotein when injected in saline with killed tubercle bacilli. Peritoneal macrophages from mice injected with the dye responded normally to migration inhibition factor. Morphologically, these cells were moderately "activated" compared with similar cells taken from untreated mice. However, such cells incubated with tuberculosis growth inhibition lymphokine in an in vitro test for tuberculoimmunity did not express tuberculoimmunity, whereas macrophages from untreated mice did. Therefore, Evans blue dye did promote induction of cell-mediated immunological responses and tuberculoimmunity in lymphocytes, but under the conditions used in these experiments, it also blocked expression of tuberculoimmunity by macrophages.
Dynamic Maintenance of Wavelet-Based Histograms (2000)

In this paper, we introduce an efficient method for the dynamic maintenance of wavelet-based histograms (and other transform-based histograms). Previous work has shown that wavelet-based histograms provide more accurate selectivity estimation than traditional histograms, such as equi-depth histograms. But since wavelet-based histograms are built by a nontrivial mathematical procedure, namely, wavelet transform decomposition, it is hard to maintain the accuracy of the histogram when the underlying data distribution changes over time. In particular, simple techniques, such as split and merge, which works well for equi-depth histograms, and updating a fixed set of wavelet coefficients, are not suitable here. We propose a novel approach based upon probabilistic counting and sampling to maintain waveletbased histograms with very little online time and space costs. The accuracy of our method is robust to changing data distributions, and we get a considerable improvement o...