gebhart/patrepeval huggingface dataset:
Culturability and In Situ Abundance of Pelagic Bacteria from the North Sea (2000)

The culturability of abundant members of the domain Bacteria in North Sea bacterioplankton was investigated by a combination of various cultivation strategies and cultivation-independent 16S rRNA-based techniques. We retrieved 16S rRNA gene (rDNA) clones from environmental DNAs and determined the in situ abundance of different groups and genera by fluorescence in situ hybridization (FISH). A culture collection of 145 strains was established by plating on oligotrophic medium. Isolates were screened by FISH, amplified ribosomal DNA restriction analysis (ARDRA), and sequencing of representative 16S rDNAs. The majority of isolates were members of the genera Pseudoalteromonas, Alteromonas, and Vibrio. Despite being readily culturable, they constituted only a minor fraction of the bacterioplankton community. They were not detected in the 16S rDNA library, and FISH indicated rare (<1% of total cell counts) occurrence as large, rRNA-rich, particle-associated bacteria. Conversely, abundant members of the Cytophaga-Flavobacteria and gamma proteobacterial SAR86 clusters, identified by FISH as 17 to 30% and up to 10% of total cells in the North Sea bacterioplankton, respectively, were cultured rarely or not at all. Whereas SAR86-affiliated clones dominated the 16S rDNA library (44 of 53 clones), no clone affiliated to the Cytophaga-Flavobacterum cluster was retrieved. The only readily culturable abundant group of marine bacteria was related to the genus Roseobacter. The group made up 10% of the total cells in the summer, and the corresponding sequences were also present in our clone library. Rarefaction analysis of the ARDRA patterns of all of the isolates suggested that the total culturable diversity by our method was high and still not covered by the numbers of isolated strains but was almost saturated for the gamma proteobacteria. This predicts a limit to the isolation of unculturable marine bacteria, particularly the gamma-proteobacterial SAR86 cluster, as long as no new techniques for isolation are available and thus contrasts with more optimistic accounts of the culturability of marine bacterioplankton.
Association of Tyrosine Phosphatases SHP-1 and SHP-2, Inositol 5-Phosphatase SHIP with gp49B1, and Chromosomal Assignment of the Gene (1998)

We have analyzed the molecules participating in the inhibitory function of gp49B1, a murine type I transmembrane glycoprotein expressed on mast cells and natural killer cells, as well as the chromosomal location of its gene. As assessed by SDS-polyacrylamide gel electrophoresis and immunoblot analysis, tyrosine-phosphorylated, but not nonphosphorylated, synthetic peptides matching each of the two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences found in the cytoplasmic portion of gp49B1 associated with the approximately 65-kDa tyrosine phosphatase SHP-1 and approximately 70-kDa SHP-2 derived from RBL-2H3 cells. In addition, the phosphotyrosyl peptide matching the second ITIM-like sequence also bound the approximately 145-kDa inositol polyphosphate 5-phosphatase SHIP. Thus, it has been strongly suggested that the inhibitory nature of gp49B involves the recruitment of SHP-1, SHP-2, and SHIP for the delivery of inhibitory signal to the cell interior upon phosphorylation of tyrosine residues in their ITIMs. The gp49B gene has been found to be in the juxtaposition of its cognate gene, gp49A. The gene pair was shown to locate in the B4 band of mouse chromosome 10. In this region, no conserved linkage homology to human chromosome 19, where the genes for killer cell inhibitory receptors are found, has been identified.
Semantic Replaceability of eScience Web Services (2007)

Once tried-and-tested, scientific workflows can be, just like web services, stored in public repositories to be shared and reused by other scientists. In practice, however, the reuse of an existing workflow is frequently hampered by the volatility of its constituent service operations. To deal with this issue, we propose a method for locating service operations that can substitute the unavailable operations in a workflow based on a set of replaceability criteria that we formally define. The proposed method has been implemented as part of a tool for the automatic discovery of substitutes for unavailable service operations, and the evaluation of the proposed method against real world scientific workflows developed under the aegis of e- Science projects demonstrated its practical applicability.
Translation of nondopaminergic treatments for levodopa‐induced dyskinesia from MPTP‐lesioned nonhuman primates to phase IIa clinical studies: Keys to success and roads to failure (2006)

Abstract Studies in MPTP‐lesioned nonhuman primates have demonstrated the potential of nondopaminergic drugs in reducing the problems of levodopa‐induced dyskinesia (LID). Here we review the process of translating findings from the monkey to man. Agents targeting glutamate, adensosine, noradrenaline, 5‐hydroxytryptamine, cannabinoid, and opioid transmitter systems have been assessed for antidyskinetic potential in human studies. Eleven nondopaminergic drugs with antidyskinetic efficacy in the MPTP primate have been advanced to proof‐of‐concept phase IIa trials in PD patients (amantadine, istradefylline, idazoxan, fipamezole, sarizotan, quetiapine, clozapine, nabilone, rimonabant, naloxone, and naltrexone). For all six nondopaminergic transmitter systems reviewed, the MPTP‐lesioned primate correctly predicted phase II efficacy of at least one drug. Of the 11 specific molecules tested in both monkeys and humans, 8 showed clear antidyskinetic properties in both human and monkey. In the instances where the primate studies did not, or did not consistently, predict the outcome of the human studies, the discrepancy may reflect limitations in the validity of the model or limitations in the design of either the clinical or the preclinical studies. We find that the major determinant of success in predicting efficacy is to ensure that primate studies are conducted in a statistically rigorous way and incorporate designs and outcome measures with clinical applicability. On the other hand, phase IIa trials should strive to replicate the preclinical study, especially in terms of protocol, drug dose equivalence, and outcome measure, so as to test the same hypothesis. Failure to meet these criteria carries the risk of false negative conclusions in phase IIa trials. © 2006 Movement Disorder Society
Group A streptococcal vaccines: facts versus fantasy (2009)

Several vaccine candidates against GAS infection are in varying stages of preclinical and clinical development. Although there is great hope that one of these vaccine candidates will reach licensure in the next decade, only one, the multivalent N-terminal vaccine, has entered clinical trials in the last 30 years. Although strong advocacy for GAS vaccine development is important, there remains an urgent need to institute available public health control measures against GAS diseases globally, particularly in developing countries.
A Rapid Blood Test To Determine the Active Status and Duration of Acute Viral Infection (2017)

The ability to rapidly detect and diagnose acute viral infections is crucial for infectious disease control and management. Serology testing for the presence of virus-elicited antibodies in blood is one of the methods used commonly for clinical diagnosis of viral infections. However, standard serology-based tests have a significant limitation: they cannot easily distinguish active from past, historical infections. As a result, it is difficult to determine whether a patient is currently infected with a virus or not, and on an optimal course of action, based off of positive serology testing responses. Here, we report a nanoparticle-enabled blood test that can help overcome this major challenge. The new test is based on the analysis of virus-elicited immunoglobulin G (IgG) antibody present in the protein corona of a gold nanoparticle surface upon mixing the gold nanoparticles with blood sera. Studies conducted on mouse models of influenza A virus infection show that the test gives positive responses only in the presence of a recent acute viral infection, approximately between day 14 and day 21 following the infection, and becomes negative thereafter. When used together with the traditional serology testing, the nanoparticle test can determine clearly whether a positive serology response is due to a recent or historical viral infection. This new blood test can provide critical clinical information needed to optimize further treatment and/or to determine if further quarantining should be continued.
A survey of design issues in spatial input (1994)

We present a survey of design issues for developing effective free-space three-dimensional (3D) user interfaces. Our survey is based upon previous work in 3D interaction, our experience in developing free-space interfaces, and our informal observations of test users. We illustrate our design issues using examples drawn from instances of 3D interfaces.For example, our first issue suggests that users have difficulty understanding three-dimensional space. We offer a set of strategies which may help users to better perceive a 3D virtual environment, including the use of spatial references, relative gesture, two-handed interaction, multisensory feedback, physical constraints, and head tracking. We describe interfaces which employ these strategies.Our major contribution is the synthesis of many scattered results, observations, and examples into a common framework. This framework should serve as a guide to researchers or systems builders who may not be familiar with design issues in spatial input. Where appropriate, we also try to identify areas in free-space 3D interaction which we see as likely candidates for additional research.An extended and annotated version of the references list for this paper is available on-line through mosaic at address http://uvacs.cs.virginia.edu/~kph2q/.
Molecular and Biologic Markers of Premalignant Lesions of Human Breast (2002)

There is currently great interest in the detection and characterization of putative precursor breast cancer lesions because of the possibility of chemoprevention. Knowledge of the biologic features of premalignant lesions, although limited, is rapidly evolving. Premalignant breast lesions have been examined for the presence of genetic alterations and for the expression of biomarkers such as the estrogen receptor (ER), Ki67, p53, and HER2/neu. Data obtained from genetic studies of precursor breast lesions clearly support the contention that genetic alterations begin quite early in selected subsets of histologically benign lesions. Although the results of biomarker expression profiles have been contradictory, most studies agree that precursor lesions significantly overexpress ER and that progressive alterations in ER expression accompany the transition of normal cells to hyperplastic lesions and carcinoma in situ. So far, the collected evidence indicates that precursor lesions in the breast demonstrate biomarker expression profiles and genetic abnormalities that are distinct from those of terminal ductal lobular units but share some of these features with invasive tumors. Future research in this field is urgently needed to identify specific biomarkers of prognostic and predictive value, which can help not only in the selection of patients for chemopreventive therapy but in monitoring the progression of high-risk lesions.
Compact planar 980/1550-nm wavelength multi/demultiplexer based on multimode interference (1995)

A compact integrated 980/1550-nm wavelength multi/demultiplexing coupler based on multimode interference effects is demonstrated. The device is useful for integration with rare-earth doped waveguide amplifiers and lasers. It is shown that the device performance can be optimized with an appropriate choice of the coupler width. The coupler is fabricated in a SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -SiON deeply-etched rib waveguide system. Theoretical and experimental results for the demultiplexer configuration are presented. At an optimum coupler length of 458 μm, contrast of about 18 dB, and on-chip insertion loss of 0.5 dB at both wavelengths are achieved.
Exon‐skipping therapy for Duchenne muscular dystrophy (2009)

Duchenne muscular dystrophy (DMD) is a lethal muscle disorder caused by mutations in the DMD gene for which no mutation-targeted therapy has been available thus far. However, exon-skipping mediated by antisense oligonucleotides (AOs), which are short single-strand DNAs, has considerable potential for DMD therapy, and clinical trials in DMD patients are currently underway. This exon-skipping therapy changes an out-of-frame mutation into an in-frame mutation, aiming at conversion of a severe DMD phenotype into a mild phenotype by restoration of truncated dystrophin expression. Recently, stable and less-toxic AOs have been developed, and their higher efficacy was confirmed in mice and dog models of DMD. In this review, we briefly summarize the genetic basis of DMD and the potential and perspectives of exon skipping as a promising therapy for this disease.
Site-SpecificN-Glycosylation of Recombinant Pentameric and Hexameric Human IgM (2016)

Glycosylation is known to play an important role in IgG antibody structure and function. Polymeric IgM, the largest known antibody in humans, displays five potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a pentamer with a connecting singly N-glycosylated J-chain (with a total of 51 glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the N-glycosylation of recombinant pentameric and hexameric IgM produced by the same human cell type and culture conditions was site-specifically profiled by RP-LC-CID/ETD-MS/MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy of all putative N-glycosylation sites on the pentameric and hexameric IgM were able to be determined. Distinct glycosylation differences were observed between each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332, and Asn395 all had predominantly complex type glycans, differences in glycan branching and sialylation were observed between the sites. Asn563, a high mannose-rich glycosylation site that locates in the center of the IgM polymer, was only approximately 60% occupied in both the pentameric and hexameric IgM forms, with a difference in relative abundance of the glycan structures between the pentamer and hexamer. This study highlights the information obtained by characterization of the site-heterogeneity of a highly glycosylated protein of high molecular mass with quaternary structure, revealing differences that would not be seen by global glycan or deglycosylated peptide profiling. Graphical Abstract ᅟ.
Latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus-8) binds ATF4/CREB2 and inhibits its transcriptional activation activity (2000)

Latency-associated nuclear antigen (LANA), encoded by ORF 73 of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus-8), may play an important role in the persistence of the viral episome by tethering it to host chromosomes during mitosis. It also has been suggested from its amino acid sequence features that LANA may have transcription-regulatory activity. Here, it is reported that LANA interacts with activating transcription factor (ATF) 4/cAMP response element-binding protein (CREB) 2, a member of the ATF/CREB family of transcription factors, and represses the transcriptional activation activity of ATF4/CREB2. Repression by LANA is independent of the DNA-binding ability of ATF4/CREB2, since LANA also represses transactivation of ATF4/CREB2 fused to the GAL4 DNA-binding domain and does not affect the DNA-binding ability of ATF4/CREB2 in an electrophoretic mobility shift assay. The putative leucine zipper domain of LANA is required for binding to the relatively conserved basic region/leucine zipper domain (bZIP) of ATF4/CREB2, suggesting that the interaction may involve leucine zipper dimerization.
Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group (2004)

Physicians, hospitals, and other health care facilities will assume the responsibility for aiding individuals injured by a terrorist act involving radioactive material. Scenarios have been developed for such acts that include a range of exposures resulting in few to many casualties. This consensus document was developed by the Strategic National Stockpile Radiation Working Group to provide a framework for physicians in internal medicine and the medical subspecialties to evaluate and manage large-scale radiation injuries. Individual radiation dose is assessed by determining the time to onset and severity of nausea and vomiting, decline in absolute lymphocyte count over several hours or days after exposure, and appearance of chromosome aberrations (including dicentrics and ring forms) in peripheral blood lymphocytes. Documentation of clinical signs and symptoms (affecting the hematopoietic, gastrointestinal, cerebrovascular, and cutaneous systems) over time is essential for triage of victims, selection of therapy, and assignment of prognosis. Recommendations based on radiation dose and physiologic response are made for treatment of the hematopoietic syndrome. Therapy includes treatment with hematopoietic cytokines; blood transfusion; and, in selected cases, stem-cell transplantation. Additional medical management based on the evolution of clinical signs and symptoms includes the use of antimicrobial agents (quinolones, antiviral therapy, and antifungal agents), antiemetic agents, and analgesic agents. Because of the strong psychological impact of a possible radiation exposure, psychosocial support will be required for those exposed, regardless of the dose, as well as for family and friends. Treatment of pregnant women must account for risk to the fetus. For terrorist or accidental events involving exposure to radioiodines, prophylaxis against malignant disease of the thyroid is also recommended, particularly for children and adolescents.
DNA Methylation Is Involved in Maintenance of an Unusual Expression Pattern of an Introduced Gene (1992)

In one of 30 transgenic tobacco (Nicotiana tabacum) plants, the expression of an introduced beta-glucuronidase (GUS) gene driven by the cauliflower mosaic virus 35S promoter, was found to be repressed as the plant matured, whereas the endogenous GUS activity was unaffected. Plants grown from seeds or regenerated from leaf discs derived from this plant showed a similar temporal pattern of expression. Suspension-cultured cells established from nonexpressing leaves did not express the introduced gene. In these cells, the silent gene could be reactivated by treatment for 5 or 10 days with 5-azacytidine. Overall, demethylation of the genome preceded recovery of the enzyme activity. The increase in the fraction of reactivated cells progressed in two phases. Up to 8 weeks after starting the 5-azacytidine treatment, approximately 2 to 4% of the cells were expressing GUS, followed by a dramatic increase of GUS-expressing cells. Thirteen weeks after starting the 5-azacytidine treatment, the fraction of GUS-expressing cells amounted to 80%. At this time, the original overall level of DNA methylation was reestablished. The degree of DNA demethylation, as well as the magnitude of reactivation, was dependent on the duration of the 5-azacytidine treatment. These results demonstrate that DNA methylation appears to be involved in the regulation of the introduced GUS gene and that this development-dependent pattern of expression can be inherited.
Robust low-computation sensor-driven control for task-directed navigation (2002)

Reliable goal-directed navigation is demonstrated on a real robot in an unmodified office environment using crude sensors and minimal computation. The control system is based on reactive behaviors which fail cognizantly, that is, which can detect when something goes wrong. Cognizant failure allows unreliable behaviors to be combined by a reactive scheduler to produce an overall behavior which is more reliable than any of its components. Algorithms which fail cognizantly are much easier to produce than algorithms which never fail. Several such algorithms are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mechanism of Elevated Plasma Noradrenaline in the Course of Essential Hypertension (1986)

Increased sympathetic nervous system tone may be the initiating pathophysiologic event in some patients with essential hypertension. We estimated sympathetic nervous activity from radiotracer-derived measurements of noradrenaline release to plasma in 34 patients with essential hypertension and 23 subjects with normal blood pressure. The plasma concentration of noradrenaline (32% increased) and the rate of release of noradrenaline to plasma (38% increased) were elevated overall in patients with essential hypertension, largely due to higher noradrenaline release in hypertensive patients aged less than 40 years. Noradrenaline release from the kidneys and heart was elevated; renal noradrenaline spillover was 2.4 times normal in patients aged less than 40 years. Increased renal noradrenaline spillover accounted for 42% and increased cardiac noradrenaline spillover for 4% of the excess total noradrenaline spillover in essential hypertension, leaving 54% unexplained. Total noradrenaline spillover to plasma was normal in hypertensive patients aged 60 years and over. The plasma noradrenaline concentration was similar in younger and older hypertensive patients, despite lower noradrenaline release in the latter due to an age-dependent fall in noradrenaline plasma clearance in essential hypertension. Cardiorenal sympathetic nervous system tone appears to be increased in essential hypertension, particularly in younger patients. This contributes substantially to the higher plasma noradrenaline values found.
BeadArray ™ Technology: Enabling an Accurate, Cost-Effective Approach to High-Throughput Genotyping (2002)

The Human Genome Project has opened the door to personalized medicine, provided that human genetic diversity can be analyzed in a high-throughput and cost-effective way Illumina has developed a genotyping system that combines very high throughput and accuracy with low cost per SNP analysis. The system uses our BeadArray platform, a high level of multiplexing, and modular, scalable automation to meet the requirements for cost-effective, genome-wide linkage disequilibrium studies. As implemented in a high-throughput genotyping service facility at Illumina, the system has a current capacity of one million SNP assays per day and is easily expandable. Each SNP call is associated with a quality score that correlates with accuracy
Stabilization of a new antiulcer drug (Lansoprazole) in the solid dosage forms (1992)

In the previous study, we clarified that enteric granules were appropriate dosage forms of lansoprazole. The establishment of these formulations, however, was difficult because some of the excipients needed for these formulations are incompatible with the drug. We examined the effects of adding magnesium carbonate as an alkaline stabilizer and could get stable enteric granules. We also discuss the mechanism of stabilization.