gebhart/patrepeval huggingface dataset:
New and improved AAVenues: current status of hemophilia B gene therapy (2015)

AAV mediated gene therapy for hemophilia B is safe and efficacious; however, to achieve gene therapy success on a global scale, improvements to large scale production and alternative AAV serotype approaches need to be designed. With the current means of AAV gene therapy treatment entering the market concomitantly with the advent of long half-life clotting factor products, the quality of life for hemophilia patients worldwide is likely to improve significantly.
Ringtail: Feature Selection For Easier Nowcasting. (2013)

In recent years, social media “nowcasting”—the use of online user activity to predict various ongoing real-world social phenomena—has become a popular research topic; yet, this popularity has not led to widespread actual practice. We believe a major obstacle to widespread adoption is the feature selection problem. Typical nowcasting systems require the user to choose a set of relevant social media objects, which is difficult, time-consuming, and can imply a statistical background that users may not have. We propose Ringtail, which helps the user choose relevant social media signals. It takes a single user input string (e.g., unemployment) and yields a number of relevant signals the user can use to build a nowcasting model. We evaluate Ringtail on six different topics using a corpus of almost 6 billion tweets, showing that features chosen by Ringtail in a wholly-automated way are better or as good as those from a human and substantially better if Ringtail receives some human assistance. In all cases, Ringtail reduces the burden on the user. 1.
Kinetic model for the biodistribution of an 111In-labeled monoclonal antibody in humans. (1987)

Using data from 12 patients, we have analyzed the pharmacokinetics of 111In-9.2.27, an antimelanoma monoclonal antibody, following i.v. infusion. Plasma data and scintillation camera images obtained from patients receiving either 1, 50, or 100 mg of monoclonal antibody indicated dose-dependent (i.e., saturable) kinetics. Based on these observations and known immunoglobulin kinetics, we developed a nonlinear compartmental model to describe the biodistribution of 111In-9.2.27 and the other coinjected 111In-associated compounds. The model included (a) three compartments representing intact 111In-9.2.27 ("plasma," "nonsaturable," and "saturable binding" compartments), (b) four compartments representing 111In-diethylenetriaminepentaacetic acid, and (c) one compartment representing 111In in an undetermined chemical form ("extravascular delay" compartment). Analysis of the rate of urinary excretion relative to plasma concentration indicated that the saturable binding compartment was a site for catabolism of monoclonal antibody. Further examination of the urinary data, together with previous studies of the site(s) of immunoglobulin catabolism, suggested that additional elimination took place from either the plasma or the nonsaturable compartment. The model indicated that to fill the saturable sites would require a dose of approximately 0.5 mg and suggested that greater than 3.5 mg would maintain saturation for 200 h. Computer integration of gamma camera counts over the spleen revealed a clear saturable component of uptake, whereas integration over the liver showed no such pattern. The proposed model was fitted to the liver and spleen imaging data by summing fractions of model simulations of each compartment. That analysis confirmed the suspected saturable uptake by the spleen (21% of the saturable binding compartment) and revealed a quantitatively important component of saturation in the liver (35% of the saturable binding compartment) that was not obvious from initial examination of the images. When the results were expressed on a concentration basis, the spleen accounted for 247% of the saturable compartment per kg, whereas the liver accounted for 25%/kg. The bone marrow also showed saturable uptake; hence, the saturable uptake may relate to the sinusoidal blood supply characteristic of liver, spleen, and marrow. The model predicts the dose levels required to overcome saturable background, suggests appropriate doses and schedules for cold loading strategies, and provides a format for explicit inclusion of tumor antigen.
Enabling the use of context in interactive applications (2000)

Context is an important, yet poorly understood and poorly utilized source of information in interactive computing. It will be of particular importance in the new millennium as users move away from their desktops and into settings where their contexts are changing rapidly. Context is difficult to use because, unlike other forms of user input, there is no common, reusable way to handle it. As a result, context-aware applications have been built in an ad hoc manner, making it difficult to build new applications or evolve existing ones. In this research, we are examining the requirements of context-aware applications, building a toolkit, which enables the use of context and fulfills these requirements, and testing the usability of this toolkit for application designers.
Rapid and simple isolation of the crystalline molybdenum-blue compounds with discrete and linked nanosized ring-shaped anions: Na-15[(Mo126Mo28O462H14)-Mo-VI-O-V(H2O)(70)](0.5) [(MO124MO28O457H14)-M-VI-O-V(H2O)(68)](0.5) center dot ca. 400 H2O and Na-22[(Mo118Mo28O442H14)-Mo-VI-O-V(H2O)(58)] center dot ca. 250 H2O (1999)

The blue mixed-crystal title compound Na-15[(MO126Mo28O462H14)-Mo-VI-O-V(H2O)(70)](0.5)[(Mo124Mo28O457H14)-Mo- VI-O-V.(H2O)(68)](0.5).ca.400H(2)O equivalent to Na-15[1a](0.5)[1b](0.5).ca. 400H(2)O 1, which crystallizes in the triclinic space group P (1) over bar (a=30.785(2), b=32.958(2), c=47.318(3)Angstrom, alpha=90.53(1), beta=89.86(1) gamma=96.85(1)degrees, V=47665(6) Angstrom(3), Z=2, D-calc=2.149 g cm(-3)), precipitates within one day when an acidic (pH approximate to 1) aqueous solution of sodium molybdate (because of the extremely high solubility of the reaction product used in relatively high concentration) is reduced by sodium dithionite. 1 contains hitherto unknown pure molybdenum-oxide based, nanosized, ring-shaped, crystallographically independent cluster anions of the type {Mo-154} la and {Mo-152} Ib, the lacunary-type analogue of la. Using the same reducing agent but in the presence of a reagent with a high affinity to the specific {Mo-2}-type building unit (also a leaving group) of la, such as formic acid, the compound Na-22[(Mo118Mo28O442H14)-Mo-VI-O-V(H2O)(58)].ca. 250H(2)O 2 (space group P (1) over bar, a=24.724(1), b=35.726(2), c=44.608(3)Angstrom, alpha=93.25(1), beta=93.51(1), gamma=106.72(1)degrees, V=37552(4)Angstrom(3), Z = 2, D-calc = 2.401g cm(-3)) is obtained in which the giant rings, having four missing {Mo-2} units compared to la, are linked to chains. Until now, similar chain-type compounds could only be obtained using a non-well-defined synthetic method.
Tumor‐associated macrophages stimulate the proliferation of murine tumor cells surviving treatment with the oncolytic cyclophosphamide analogue ASTA Z‐7557: In vivo implications (1984)

This report is concerned with the hypothesis that tumor-associated macrophages (TAM) present during cyclophosphamide (CY)-induced tumor regression stimulate proliferation of tumor stem cells that remain after the oncolytic after of CY has dissipated. In preliminary studies, plasma or serum from CY-injected mice was used as a source of CY metabolites. However, because of the relatively high background toxicity of normal mouse plasma/serum and the lack of a precise technique to quantify how much metabolite was present at any one time, this approach was abandoned. In place of the plasma metabolites, we used the Cy analogue, 4-(2-sulfonatoethylthio)-cyclophosphamide cyclohexylamine salt, Asta Z-7557. On solubilization in water, Asta Z-7557 yields phosphoramide mustard, one of the oncolytic metabolites of CY in vivo. This approach enabled us to quantitate the amount of drug used in vitro and to control the amount to which tumor cells and macrophages were exposed. It was demonstrated that when two different C57BL/6J tumor cell targets, the MCA/76-9 sarcoma and the EL4 lymphoma subline, E2G.2, were treated with defined quantities of Asta Z-7557, those cells surviving the toxic effects were stimulated to proliferate in the presence of TAM isolated from the MCA/76-9 sarcoma. Although pretreatment of the TAM with the drug slightly diminished the stimulatory effect, this was still significantly greater than the effect of culture medium alone. In no instance was there evidence that drug treatment rendered the macrophages cytotoxic towards the tumor cells. The data supported the notion that in vivo the presence of a high proportion of TAM during CY-induced temporary tumor regression may contribute directly to the resurgence of tumor growth.
Arousal, Increased respiratory efforts, blood pressure and obstructive sleep apnoea (1995)

The roles of hypoxaemia, of mechanical changes related to partial or complete airway obstruction and of arousals during sleep in the haemodynamic and heart rate changes seen in association with sleep-disordered breathing have been questioned. Several experiments have been performed by these authors to investigate the role of arousals and mechanical changes in the blood pressure changes associated with sleep disordered breathing. Investigation of the role of arousals. Two different populations were used in this study; one of normal, young volunteers without sleep-disordered breathing monitored at baseline (normal sleep) who were submitted to auditory stimulation during sleep, causing sleep fragmentation, and another of obstructive sleep apnoeic patients who were monitored at baseline and after nasal CPAP treatment. Before treatment and after one month of treatment while still being treated with nasal CPAP, these subjects were submitted to the same auditory stimulation and sleep fragmentation as normal controls. The studied variables were systolic and diastolic blood pressure and heart rate. In normal controls, auditory induced arousals lead to an increase in diastolic as well as systolic blood pressure. The increase was related to the type of arousal but was also noted with K complexes to a lesser degree. In OSAS patients under treatment with nasal CPAP, similar increases were noted with auditory stimulation. Compared to baseline hypoxaemia and hyperventilation periods, however, the haemodynamic increase was, at its highest, only one-third of the mean pressure monitored during the baseline, end-of-apnoea hyperventilation period with EEG arousals. Investigation of the role of nasal CPAP on blood pressure (BP) while patients had no hypoxaemia (SaO2>92%) but still showed increased respiratory efforts indicated a persistence of higher systolic and diastolic pressures than when nasal CPAP completely eliminated increased efforts. Possible long-term impact of arousals and mechanical changes. A last study was performed on patients with upper airway resistance syndrome (UARS). Out of 112 patients, 6 were identified using the World Health Organization (WHO) protocol and ambulatory monitoring as having borderline high BP (140-160//90-98). Subjects were calibrated with nasal CPAP and were asked to use their equipment on a nightly basis. The CPAP machines were equipped with counters that could accurately measure the number of hours that the device was used. Patients were their own controls and were re-monitored one month later. Four subjects used their nasal CPAP at least 6 nights per week and more than 5 hours per night. One patient used his CPAP approximately 3 nights per week and more than 4 hours per night. One patient used his CPAP a total of 3 nights in the whole month. Blood pressure was unchanged in the patient who failed to use his CPAP, but was normalized in the 5 others, as were nocturnal recordings.
Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model (2009)

Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury, but their role in chronic kidney diseases is still unknown. More specifically, it is not known whether MSCs halt fibrosis. The purpose of this work was to investigate the role of MSCs in fibrogenesis using a model of chronic renal failure. MSCs were obtained from the tibias and femurs of male Wistar-EPM rats. Female Wistar rats were subjected to the remnant model, and 2|x|10(5) MSCs were intravenously administrated to each rat every other week for 8 weeks or only once and followed for 12 weeks. SRY gene expression was observed in female rats treated with male MSCs, and immune localization of CD73(+)CD90(+) cells at 8 weeks was also assessed. Serum and urine analyses showed an amelioration of functional parameters in MSC-treated animals at 8 weeks, but not at 12 weeks. Masson's trichrome and Sirius red staining demonstrated reduced levels of fibrosis in MSC-treated animals. These results were corroborated by reduced vimentin, type I collagen, transforming growth factor beta, fibroblast specific protein 1 (FSP-1), monocyte chemoattractant protein 1, and Smad3 mRNA expression and alpha smooth muscle actin and FSP-1 protein expression. Renal interleukin (IL)-6 and tumor necrosis factor alpha mRNA expression levels were significantly decreased after MSC treatment, whereas IL-4 and IL-10 expression levels were increased. All serum cytokine expression levels were decreased in MSC-treated animals. Taken together, these results suggested that MSC therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal injury. The immunosuppressive and remodeling properties of MSCs may be involved in the decreased fibrosis in the kidney.
Synthetic Studies on Bacitracin. VII. Isomerization of Amino Acid Components of Thiazoline Peptides (1970)

Abstract Ethyl 2-(1-benzyloxycarbonylaminoethyl)-R-Δ2-thiazoline-4-carboxylate (III), ethyl 2-(1-benzyloxycarbonylamino-2-methyl-n-butyl)-R-Δ2-thiazoline-4-carboxylate (VI) and their acid amide derivatives (V, VII and VIII) were prepared by either the iminoether coupling method or the dehydration method. As a general character of thiazoline peptide, it was found that the amino acid residue connected to thiazoline ring at N-terminal side is completely racemized at the stage of thiazoline ring formation, and further epimerized, in the case of isoleucine, by treatment with the basic reagent.
Electrophysiologic Studies of Cervical Vagus Nerve Stimulation in Humans: II. Evoked Potentials (1992)

Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve not only can alter the EEG but evokes activity in specific brain areas. We report effects of electrical stimulation of the vagus nerve in 9 patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The left vagus nerve in the neck was stimulated with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus nerve evoked potential showed some unusual properties: a scalp negative component occurred with a latency of 12 ms, very high amplitude (< or = 60 microV), and widespread scalp distribution. Field distribution studies indicated that this potential was myogenic in origin and generated in the region of the stimulating electrodes in the neck area. Chemically induced muscle paralysis confirmed this observation. Bipolar scalp recording showed several small-amplitude topographically distinct potentials occurring in 30 ms. No effect, either acute or chronic, could be detected on pattern-reversal evoked potentials, auditory brainstem evoked potentials, auditory 40-Hz potentials, or cognitive evoked potentials.
Molecular Diagnostic Testing (1998)

Molecular diagnostic testing is a rapidly evolving field that currently includes analysis for single-gene disorders, multifactorial disorders, some forms of cancer, infectious disease, microbial epidemiology, and personal identification. The era of molecular medicine began in the late 1970s with the cloning of the β-globin gene and identification of the point mutation responsible for sickle-cell anemia. At the same time, population-based carrier testing, using other technologies, for common genetic diseases such as Tay-Sachs and sickle-cell disease and prenatal diagnosis for chromosomal abnormalities were becoming widely available. The diagnostic capability of molecular technology has expanded tremendously, and there are now tests available for more than 300 genetic diseases being performed in greater than 200 diagnostic laboratories, academic and commercial, throughout the country (information provided by Helix; Seattle, Washington). The completion of the Human Genome Project will facilitate the identification of all disease genes, making a greater number of molecular diagnostic tests possible. While improved technological tools are essential for molecular diagnostics to move forward, the basic strategies for designing and implementing testing, which we describe in this chapter, will be long-lasting. To illustrate these principles, we will focus on the application of molecular diagnostic testing for single-gene disorders using DNA technology.
Primary structure and functional expression of a glutaminyl cyclase. (1991)

A glutaminyl cyclase (QC) that is probably involved in the biosynthesis of pyroglutamyl peptides such as gonadotropin-releasing hormone and thyrotropin-releasing hormone has been purified to homogeneity from bovine anterior pituitary. On the basis of N-terminal sequence analysis, a 2088-base-pair cDNA clone was isolated from a bovine anterior pituitary library. From the nucleotide sequence of this clone, the primary structure of a 330-residue protein and a preceding 31-residue prepropeptide sequence was deduced. By transfection of COS-7 monkey cells with a QC cDNA/pCDM8 vector construct, QC activity was expressed. Hybridization with mRNAs of various bovine tissues revealed expression of QC mainly in brain tissue.
miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice (2011)

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.
Recent advances in the chemistry of dihydropyridines (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleRecent advances in the chemistry of dihydropyridinesDavid M. Stout and A. I. MeyersCite this: Chem. Rev. 1982, 82, 2, 223–243Publication Date (Print):April 1, 1982Publication History Published online1 May 2002Published inissue 1 April 1982https://pubs.acs.org/doi/10.1021/cr00048a004https://doi.org/10.1021/cr00048a004research-articleACS PublicationsRequest reuse permissionsArticle Views4180Altmetric-Citations834LEARN 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
Q-L/MRP: a buffer management mechanism for QoS support in a multimedia DBMS (2002)

Multimedia database systems (MMDBSs) have to be capable of efficiently handing time-dependent and time-independent data, and of supporting quality of service (QoS). To support continuous playout of time-dependent data, reservations of the resource-limited disk I/O bandwidth and network bandwidth have to be combined with appropriate buffer management. Based on the special requirements of the DEDICATION (DatabasE support for DIstance eduCATION) pre-study, i.e. building a cheap prototype system for asynchronous distance education, we have designed the buffer management mechanism Q-L/MRP (QoS-Least/Most Relevant for Presentation). Q-L/MRP is a buffer preloading and page replacement mechanism for multimedia applications with heterogeneous QoS requirements. Q-L/MRP extends L/MRP with two features: (1) it supports multiple concurrent users, and (2) it supports QoS with a dynamic prefetching daemon. This daemon is able to dynamically adapt to the changes in network and disk I/O load. Furthermore, QoS requirements from the users, such as the frame rate, are mapped into the buffer mechanism. A performance analysis shows that Q-L/MRP is very suitable for the special environment in DEDICATION and outperforms other buffer management mechanisms. Since we have implemented Q-L/MRP in software only, it is also suitable for other multimedia applications on other systems with different hardware configurations and workloads.
A New Rexinoid, NRX194204, Prevents Carcinogenesis in Both the Lung and Mammary Gland (2007)

The combined anti-inflammatory and anticarcinogenic actions of 4204 suggest that it is a promising new rexinoid that should be considered for future clinical trials.
Expression of the immunoglobulin VH gene 51p1 is proportional to its germline gene copy number. (1996)

51p1 is an immunoglobulin VH gene that is frequently expressed in B cell chronic lymphocytic leukemia and early in B cell ontogeny. The 51p1 gene locus is highly polymorphic, consisting of 13 alleles that can be classified as being either 51p1-related or hy1263-related, based on distinctive sequence motifs in the second complementarity determining region. Two of the 51p1-related genes usually occur as a linked pair on the same haopltype, resulting from gene duplication. Consequently, a person can have a total of zero to four copies of 51p1-related genes. These genes are detectable in genomic DNA by sequence-specific RFLP analysis using oligonucleotide probes. Ig encoded by nonmutated 51p1-related genes can be detected by G6, a murine antiidiotypic mAb. We have now studied lymphocytes from 35 human tonsils to examine the relation between the number of 51p1-related germlime gene copies and the proportion of IgD-bearing tonsillar B cells that react with G6. All subjects who had zero copies of 51p1-related genes lacked any G6-reactive B cells, whereas those with four copies of 51p1-related genes had the highest proportions of G6-positive IgD B cells, up to 11.4%. Subjects with intermediate gene doses had intermediate proportions of G6-reactive B cells. Over the entire data set, the percentage of IgD-bearing B cells that reacted with G6 was proportional to the 51p1-related gene copy number (r = 0.92, p < 0.001), with each copy accounting for 2.4-4.0% of the IgD-bearing B cells. We conclude that 51p1-related genes are expressed by a relatively large percentage of IgD+ tonsillar B cells and this percentage is proportional to the germline copy number of 51p1-related genes.