gebhart/patrepeval huggingface dataset:
The Pharmacokinetics and Pharmacodynamics of Levodopa in the Treatment of Parkinsons Disease (2007)

Levodopa, a prodrug of dopamine, remains to be one of the main drugs in the treatment of Parkinson's disease. All current levodopa products are formulated with aromatic amino acid decarboxylase inhibitors such as carbidopa or benserazide to prevent the metabolism of levodopa in the gastrointestinal tract and systemic circulation. Levodopa pharmacokinetic profiles remain unchanged after multiple doses, and are similar between healthy volunteers and patients and among patients at different stages of disease. Entacapone inhibits the metabolism of levodopa therefore increases the area under the plasma concentration-time profile of levodopa; however, it may decrease the initial absorption rate of levodopa in some patients probably due to competitive absorption. Food appears to affect the absorption of levodopa, but its effects vary with formulations. The results of positron emission tomography study suggest that a high protein diet may compete with the uptake of levodopa into the brain, therefore, may result in reduced levodopa effects. Since infusion studies demonstrated that it is beneficial to maintain stable plasma concentrations of levodopa, controlled-release formulations have been designed to provide prolonged absorption of levodopa. However, subsequent pharmacokinetic and pharmacodynamic studies demonstrated that a threshold concentration of levodopa appears to be necessary to switch patients "on". Once patients are turned "on", the duration of levodopa effects may be correlated with plasma concentration of levodopa. As such, more recent studies have demonstrated significant clinical benefits such as shorter time to "on" and longer duration of "on" when combining the immediate- and controlled-release levodopa products as compared to controlled-release levodopa products. Given these findings, it is important for physicians to understand the relationship between the pharmacokinetics and pharmacodynamics of levodopa in order to provide dosage regimens that meet patient needs. The pharmacokinetics and pharmacodynamics data of levodopa reported in the literature are reviewed here.
Effect of extraplanar ligands on the redox properties and the site of oxidation in iron, ruthenium, and osmium porphyrin complexes (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of extraplanar ligands on the redox properties and the site of oxidation in iron, ruthenium, and osmium porphyrin complexesGilbert M. Brown, Frederick R. Hopf, Thomas J. Meyer, and D. G. WhittenCite this: J. Am. Chem. Soc. 1975, 97, 19, 5385–5390Publication Date (Print):September 1, 1975Publication History Published online1 May 2002Published inissue 1 September 1975https://pubs.acs.org/doi/10.1021/ja00852a011https://doi.org/10.1021/ja00852a011research-articleACS PublicationsRequest reuse permissionsArticle Views467Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Applications of linear algebra in information retrieval and hypertext analysis (1999)

Article Applications of linear algebra in information retrieval and hypertext analysis Share on Authors: Jon Kleinberg Department of Computer Science, Cornell University, Ithaca, NY Department of Computer Science, Cornell University, Ithaca, NYView Profile , Andrew Tomkins IBM Almaden Research Center, San Jose, CA IBM Almaden Research Center, San Jose, CAView Profile Authors Info & Claims PODS '99: Proceedings of the eighteenth ACM SIGMOD-SIGACT-SIGART symposium on Principles of database systemsMay 1999 Pages 185–193https://doi.org/10.1145/303976.303995Online:01 May 1999Publication History 23citation1,039DownloadsMetricsTotal Citations23Total Downloads1,039Last 12 Months17Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Rabies Virus Expressing Dendritic Cell-Activating Molecules Enhances the Innate and Adaptive Immune Response to Vaccination (2010)

Our previous studies indicated that recruitment and/or activation of dendritic cells (DCs) is important in enhancing the protective immune responses against rabies virus (RABV) (L. Zhao, H. Toriumi, H. Wang, Y. Kuang, X. Guo, K. Morimoto, and Z. F. Fu, J. Virol. 84:9642-9648). To address the importance of DC activation for RABV vaccine efficacy, the genes for several DC recruitment and/or activation molecules, e.g., granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-derived chemokine (MDC), and macrophage inflammatory protein 1α (MIP-1α), were individually cloned into RABV. The ability of these recombinant viruses to activate DCs was determined in vitro and in vivo. Infection of mouse bone marrow-derived DCs with each of the recombinant viruses resulted in DC activation, as shown by increased surface expression of CD11c and CD86 as well as an increased level of alpha interferon (IFN-α) production compared to levels observed after infection with the parent virus. Intramuscular infection of mice with each of the viruses recruited and/or activated more DCs and B cells in the periphery than infection with the parent virus, leading to the production of higher levels of virus-neutralizing antibodies. Furthermore, a single immunization with recombinant RABV expressing GM-CSF or MDC protected significantly more mice against intracerebral challenge with virulent RABV than did immunization with the parental virus. Yet, these viruses did not show more virulence than the parent virus, since direct intracerebral inoculation with each virus at up to 1 × 10(7) fluorescent focus units each did not induce any overt clinic symptom, such as abnormal behavior, or any neurological signs. Together, these data indicate that recombinant RABVs expressing these molecules activate/recruit DCs and enhance protective immune responses.
Epidemiology of anxiety disorders: from surveys to nosology and back (2017)

On the basis of epidemiological survey findings, anxiety disorders are the most prevalent mental disorders around the world and are associated with significant comorbidity and morbidity. Such surveys rely on advances in psychiatric nosology and may also contribute usefully to revisions of the nosology. There are a number of questions at the intersection of psychiatric epidemiology and nosology. This review addresses the following: What is the prevalence of anxiety disorders and how do we best explain cross-national differences in prevalence estimates? What are the optimal diagnostic criteria for anxiety disorders, and how can epidemiological data shed light on this question? What are the comorbidities of anxiety disorders, and how do we best understand the high comorbidities seen in these conditions? What is the current treatment gap for anxiety disorders, and what are the implications of current understandings of psychiatric epidemiology and nosology for policy-making relevant to anxiety disorders? Here, we emphasize that anxiety disorders are the most prevalent of the psychiatric conditions, and that rather than merely contrasting cross-national prevalence in anxiety disorders, it is more productive to delineate cross-national themes that emerge about the epidemiology of these conditions. We discuss that optimizing diagnostic criteria for anxiety disorders is an iterative process to which epidemiological data can make a crucial contribution. Additionally, high comorbidity in anxiety disorders is not merely artefactual; it provides key opportunities to explore pathways to mental disorders and to intervene accordingly. Finally, work on the epidemiology and nosology of anxiety disorders has provided a number of important targets for mental health policy and for future integrative work to move between bench and bedside, as well as between clinic and community.
Dynamic management of scratchpad memory based on compiler driven approach (2010)

Scratchpad memory (SPM) is commonly used in embedded system because it is more efficient than cache in both performance and energy, and it can satisfy real time requirements as well. A compiler driven method is proposed in this paper to optimally mapping code segments to SPM at runtime. The algorithm uses compiler to identify hotspots in programs based on a greedy cost model, and utilizes DMA transfer instead of explicit load and store operations to fill SPM. Compared to cache method, experimental results show performance improvements by 27.3% and energy savings by 35.5%.
Ultrastructural relationships between noradrenergic nerve fibers and non-neuronal elements in the rat cerebral cortex (1996)

Pharmacological and biochemical data suggest that noradrenaline (NA)-containing fibers not only regulate the activity of cortical neurons but also influence the functional state of non-neuronal elements. In the present study, immunocytochemistry with an antiserum against NA, followed by silver-gold intensification of the immunoreaction end-product, was employed to examine the ultrastructural relationships between the NA fiber system and the intraparenchymal blood vessels, oligodendrocytes, and astrocytes in the rat visual cortex. Electron microscopy revealed a large number of fine varicose NA fibers to be in intimate contact with cortical capillaries. Examination of single thin sections showed that NA boutons were usually separated from the capillary wall by a fine astroglial sleeve. However, serial section analysis revealed that the continuity of the astrocytic end feet was interrupted at sites, resulting in direct apposition of the perivascular NA fibers to the capillary basal lamina. Noradrenergic fibers were found to contact both types of macroglial cells. Single or clustered oligodendrocytes in intimate contact with NA fibers were observed throughout the cortical depth. Individual contacts could be followed in more than six successive thin sections, and oligodendrocyte plasma membrane frequently exhibited a light thickening at the sites of the NA fiber apposition. NA fiber-astroglial relationships were largely encountered in supragranular layers. In these layers, astrocytic cell bodies were characteristically outlined by fine varicose NA fibers. However, no plasma membrane differentiations were observed at the sites of intimate NA fiber apposition. The present ultrastructural findings provide the anatomical substrate for the control exerted by the NA fiber system over cortical microvasculature and macroglia.
Ecological Planning With Virtual Landscapes: Three Examples From Switzerland (2000)

Abstract The instrument that links environmental protection and spatial planning is ecological planning, which can be either reactive or strategic. Ecological planning comprises components of natural science as well as of aesthetics. Having once been the driving force of nature protection, the visual quality of the landscape has been neglected for a long time. In the past few years digital 3D-visualization techniques have increasingly found a wider distribution. Based on examples from Switzerland, the potential of 3D-visualization techniques in ecological planning is illustrated in this article. These include a proposed hydroelectric project at the Bernina Pass, alternative development scenarios for the town of Brunnen on Lake Lucerne, and the modeling and visualization of functions and effects of landscape elements on the habitat of the Greater Mouse-Eared Bat.
Purification, gene cloning, amino acid sequence analysis, and expression of an extracellular lipase from an Aeromonas hydrophila human isolate (1993)

A structural gene which codes for an extracellular lipase (EC 3.1.1.3) in Aeromonas hydrophila H3, which was isolated from a female hospitalized patient, was cloned in Escherichia coli by using pBR322 as a vector. Lipase purified from both A. hydrophila culture supernatant and the periplasmic fluids of E. coli containing the lip determinant in the original clone (plasmid pLA2) showed an M(r) of 67,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which agrees with the M(r) determined by Sephacryl S-200 chromatography. Regarding substrate specificity, the optimum chain lengths for the acyl moiety were C6 for ester hydrolysis and C6 and C8 for triacylglycerol hydrolysis. Sequence analysis showed a major open reading frame of 2,052 bp, which predicts a polypeptide with an M(r) of 71,804. The polypeptide was found to contain an amino acid sequence (V-H-F-L-G-H-S-L-G-A) which is highly preserved among lipases.
Germ line transmission of an inactive N-myc allele generated by homologous recombination in mouse embryonic stem cells. (1990)

We have disrupted one allele of the N-myc locus in mouse embryonic stem (ES) cells by using homologous recombination techniques and have obtained germ line transmission of null N-myc ES cell lines with transmission of the null N-myc allele to the offspring. The creation of mice with a deficient N-myc allele will allow the generation of offspring bearing null N-myc alleles in both chromosomes and permit study of the role that this proto-oncogene plays in embryonic development.
Muscle morphogenetic protein induces myogenic gene expression in Swiss‐3T3 cells (1998)

Myogenesis is thought to be regulated by the MyoD family of regulatory genes, which includes MyoD, myogenin, MRF- 4/myf-6, and myf-5. In situ hybridization studies of vertebrate skeletal muscle development have shown the colocalization of the MyoD family of regulatory genes to specific stages of muscle development. Although many studies have analyzed the regulatory role of these genes during myogenesis, there have been few reports dealing with the activation of these myogenic regulatory genes by exogenous agents. We have previously shown that muscle morphogenetic protein induces myogenesis in clonal populations of avian pluripotent stem cells. The current study was designed to examine the ability of muscle morphogenetic protein to induce myogenesis in a clonal population derived from the established fibroblastic Swiss-3T3 cell line. Swiss-3T3 cells were cloned to generate separate cell populations, tested for pluripotency, propagated through 690 cell doublings, retested for pluripotency, treated with muscle morphogenetic protein, and examined for the induction of gene expression using probes for the transcription products of MyoD and myogenin. Muscle morphogenetic protein induced the expression of mRNAs for MyoD and myogenin, suggesting a role for this compound as an exogenous activator of myogenesis.
The relative importance of arterial remodeling compared with intimal hyperplasia in lumen renarrowing after balloon angioplasty. A study in the normal rabbit and the hypercholesterolemic Yucatan micropig. (1994)

In both the normal rabbit and the normal and atherosclerotic pig, restenosis after angioplasty results from both intimal hyperplasia and arterial remodeling. The exact etiology of arterial renarrowing after angioplasty has important implications on the design of antirestenosis drugs and new coronary devices.
Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. (1981)

During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.
Network Analysis Identifies an HSP90-Central Hub Susceptible in Ovarian Cancer (2013)

These results strongly support investigation of ganetespib, a single-targeted agent with effects on numerous proteins and pathways, in augmenting standard EOC therapies.
Phenotypes of rotavirus reassortants depend upon the recipient genetic background. (1989)

We have previously characterized the biological and immunological properties of a simian rotavirus SA11 variant (4F) with an altered genome segment 4. The SA11-4F variant formed large plaques in the presence of protease, formed small clear plaques in the absence of protease, and grew to high titer in the presence of protease when compared to our standard wild type (SA11 clone 3). To determine the genome segment of the rotavirus SA11 variant 4F that encoded the unique protease-associated phenotypes of the variant, reassortants were generated that segregated the outer capsid genes of 4F onto a genetic background derived from either the bovine rotavirus B223 or our standard SA11 wild type (clone 3), both of which have contrasting protease-associated phenotypes. The parental and reassortant viruses were examined to determine which genes from the 4F variant encoded the ability (i) to form large plaques in the presence of protease, (ii) to form small clear plaques in the absence of exogenous protease, and (iii) to grow to significantly higher titer in the presence of protease. These phenotypes could be transferred to a clone 3 genetic background by a single genome segment from the 4F variant segment 4. However, in the 4F/B223 reassortants a different and unexpected situation was found. On a B223 genetic background the same phenotypes segregated with a combination of a minimum of two 4F genome segments, segments 4 and 9. These results indicate that the recipient genetic background onto which the genes of a donor rotavirus are reassorted can affect the phenotypes conferred by the presence of the donor segments. Thus, the results of segregation mapping experiments using reassortant viruses should be interpreted with caution.
Inefficacy of infliximab in primary Sjögren's syndrome: Results of the randomized, controlled trial of remicade in primary Sjögren's syndrome (TRIPSS) (2004)

This randomized, double-blind, placebo-controlled study of an anti-TNF agent did not show any evidence of efficacy of infliximab in primary SS.
Large depth of focus dynamic micro integral imaging for optical see-through augmented reality display using a focus-tunable lens (2018)

We have developed a three-dimensional (3D) dynamic integral-imaging (InIm)-system-based optical see-through augmented reality display with enhanced depth range of a 3D augmented image. A focus-tunable lens is adopted in the 3D display unit to relay the elemental images with various positions to the micro lens array. Based on resolution priority integral imaging, multiple lenslet image planes are generated to enhance the depth range of the 3D image. The depth range is further increased by utilizing both the real and virtual 3D imaging fields. The 3D reconstructed image and the real-world scene are overlaid using an optical see-through display for augmented reality. The proposed system can significantly enhance the depth range of a 3D reconstructed image with high image quality in the micro InIm unit. This approach provides enhanced functionality for augmented information and adjusts the vergence-accommodation conflict of a traditional augmented reality display.
Anti-vascular endothelial growth factor therapy for neovascular ocular diseases other than age-related macular degeneration (2009)

The discovery of VEGF-A's role in the pathogenesis of neovascular ocular disease provided a strong rationale for the development of anti-VEGF-based therapies. There is now ample evidence that anti-VEGF therapies are viable treatment options for these diseases. Nevertheless, large, randomized controlled trials are still awaited to confirm early safety and efficacy findings from small, open-label prospective studies.
Multiplex sequencing of plant chloroplast genomes using Solexa sequencing-by-synthesis technology (2008)

Organellar DNA sequences are widely used in evolutionary and population genetic studies, however, the conservative nature of chloroplast gene and genome evolution often limits phylogenetic resolution and statistical power. To gain maximal access to the historical record contained within chloroplast genomes, we have adapted multiplex sequencing-by-synthesis (MSBS) to simultaneously sequence multiple genomes using the Illumina Genome Analyzer. We PCR-amplified approximately 120 kb plastomes from eight species (seven Pinus, one Picea) in 35 reactions. Pooled products were ligated to modified adapters that included 3 bp indexing tags and samples were multiplexed at four genomes per lane. Tagged microreads were assembled by de novo and reference-guided assembly methods, using previously published Pinus plastomes as surrogate references. Assemblies for these eight genomes are estimated at 88-94% complete, with an average sequence depth of 55x to 186x. Mononucleotide repeats interrupt contig assembly with increasing repeat length, and we estimate that the limit for their assembly is 16 bp. Comparisons to 37 kb of Sanger sequence show a validated error rate of 0.056%, and conspicuous errors are evident from the assembly process. This efficient sequencing approach yields high-quality draft genomes and should have immediate applicability to genomes with comparable complexity.