gebhart/patrepeval huggingface dataset:
Modulation of Intraocular Pressure by Adenosine Agonists (1994)

Adenosine receptors have been shown to modulate a variety of physiological functions; however, little is known about the role these receptors play in the modulation of ocular function. To investigate the potential role of adenosine receptors in modulating intraocular pressure (IOP), the A1 agonist N6-cyclopentyladenosine (CPA), the nonselective adenosine agonist 5'-N-ethylcarboxamideadenosine (NECA) and the A2 agonist 8-phenylaminoadenosine (CV-1808) were evaluated. Topical administration of NECA produced a dose-related reduction in IOP. However, an initial ocular hypertension of 1 to 2 hours was also observed in rabbits treated with NECA. The administration of CPA (165 micrograms) resulted only in a reduction in IOP, while the administration of CV-1808 produced only an initial ocular hypertension. As adenosine A1 receptors have been shown to be negatively coupled to adenylate cyclase in several systems, CPA was evaluated for its ability to suppress cAMP formation in the isolated iris/ciliary body. CPA produced a dose-related suppression of cAMP accumulation induced by 10(-6) M forskolin (EC50 = 3.2 nM). These results indicate that selected adenosine agonists can modulate IOP. The ocular hypotension induced by adenosine agonists is consistent with the activation of adenosine A1 receptors and may involve the modulation of cAMP levels in the iris/ciliary body.
ACTIVE, A PLATFORM FOR BUILDING INTELLIGENT OPERATING ROOMS (2007)

Today computers are part of the standard equipment of modern surgery rooms. They assist surgeons in performing complex procedures that would not be possible otherwise. However, despite the availability of more powerful and complex computer systems, their user interfaces have not been adapted to fully leverage their potential. A new type of software, behaving as an independent intelligent assistant, is needed to better assist surgeons and their staff. Building an intelligent assistant is a difficult task that requires expertise in many fields ranging from artificial intelligence to core software and hardware engineering. We believe that providing a unified tool and methodology to create intelligent software will bring many benefits to this area of research. Our solution, the Active framework, introduces the original concept of Active Ontologies to model and implement intelligent applications. Based on suggestions and constant evaluations from surgeons, an Active based assistant for endoscopic neurosurgery is under development. Using natural modalities such as speech recognition and hand gestures, it enables surgeons to interact with computer based equipments of the operating room as if they were full active members of the team. In a broader context, Active aims to ease the development of intelligent software by making required technologies more accessible. It will help foster research innovation, easier development cycle and deployment of this new type of applications.
Latent olefin metathesis catalysts (2009)

Olefin metathesis is a versatile synthetic tool for the redistribution of alkylidene fragments at carbon-carbon double bonds. This field, and more specifically the development of task-specific, latent catalysts, attracts emerging industrial and academic interest. This tutorial review aims to provide the reader with a concise overview of early breakthroughs and recent key developments in the endeavor to develop latent olefin metathesis catalysts, and to illustrate their use by prominent examples from the literature.
The Box-Percentile Plot (2003)

A variant of the boxplot is proposed in which the sides contain the information of a percentile plot (which is equivalent to the empirical cumulative distribution function). Unlike boxplots, there is no question about how long to draw the whiskers, nor is there loss of information due to grouping. Side-by-side comparisons of distributions are especially effective. In spite of including more detail, the impact on statistically-untrained readers remains similar to that of traditional boxplots.
Evaluation and Reduction of CRISPR Off-Target Cleavage Events (2019)

Introduction of CRISPR/Cas9 methods (clustered regularly interspaced short palindromic repeats, CRISPR-associated protein 9) have led to a huge surge in the use of precision genome editing for research applications. Translational medical efforts are likewise rapidly progressing, and Phase I clinical trials using these techniques have already started. As with any new technology that is applied to medical therapeutics, risks must be carefully defined and steps taken to mitigate side effects wherever possible. Effective methods are now available that permit identification of off-target cleavage events, a major class of potential side effects seen in mammalian genome editing. Off-target prediction algorithms are improving and have utility, but are insufficient to use alone. Empiric methods to define the off-target profile must also be used. Once defined, the frequency of off-target cleavage can be minimized using methods that limit the duration of exposure of the genome to the active genome editing complex, for example, using the ribonucleoprotein (RNP) approach. In addition, Cas9 mutants have been developed that markedly reduce the rate of off-target cleavage compared to the wild-type enzyme. Use of these new tools should become standard practice for medical applications.
C-C Chemokine Receptor 2 and Sarcoidosis (2003)

Abstract Sarcoidosis is thought to result from the interaction between an unknown environmental antigenic trigger and the host's genetic susceptibility. We hypothesized that sarcoidosis, or one of the disease subsets, could be associated with single nucleotide polymorphisms of C-C chemokine receptor 2 (CCR2) gene. Eight single-nucleotide polymorphisms in CCR2 were studied in a total of 304 Dutch individuals (90 non-Löfgren sarcoidosis, 47 Löfgren's syndrome, 167 control subjects). From the investigated CCR2 polymorphisms, nine haplotypes were deduced (haplotypes 1–9). In patients with Löfgren's syndrome, a strongly significant increase in the frequency of CCR2-haplotype 2, which includes four unique alleles (A at nucleotide position –6752, A at 3,000, T at 3,547, and T at 4,385), was observed compared with control subjects (74% vs. 38% respectively, p &amp;lt; 0.0001), whereas no difference was found between non-Löfgren sarcoidosis and control subjects (both 38%). The association between CCR2-haplotype 2 carriage frequency and Löfgren's syndrome (odds ratio, 4.4; p &amp;lt; 0.0001) remained significant after adjustment for human leukocyte antigen haplotype DRB1*0301-DQB1*0201 (odds ratio, 11.5; p &amp;lt; 0.0001) and female sex (odds ratio, 3.2; p = 0.003), two known risk factors for Löfgren's syndrome. In conclusion, this report describes a strong association between CCR2-haplotype 2 and Löfgren's syndrome. Further studies are needed to understand the molecular mechanisms underlying this association.
Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons (2004)

Approximately 14% of genetic mutations in patients with ataxia-telangiectsia (A-T) are single-nucleotide changes that result in primary premature termination codons (PTCs), either UAA, UAG, or UGA. The purpose of this study was to explore a potential therapeutic approach for this subset of patients by using aminoglycosides to induce PTC read-through, thereby restoring levels of full-length ATM (A-T mutated) protein. In experiments using a modified in vitro cDNA coupled transcription/translation protein truncation test, 13 A-T cell lines carrying PTC mutations in different contexts exhibited read-through expression of ATM fragments, with three of four aminoglycosides tested. In ex vivo experiments with lymphoblastoid cell lines, we used radiosensitivity, radioresistant DNA synthesis, and irradiation-induced autophosphorylation of ATM Ser-1981 to show that the aminoglycoside-induced full-length ATM protein was functional and corrected, to various extents, the phenotype of A-T cells. These results encourage further testing of other compounds in this class, as well as follow up animal studies. Because some A-T patients with 5-20% of normal levels of ATM protein show slower neurological progression, A-T may prove to be a good model for aminoglycoside-induced read-through therapy.
Structure of the Multidrug Resistance P-glycoprotein to 2.5 nm Resolution Determined by Electron Microscopy and Image Analysis (1997)

P-glycoprotein (P-gp) is a member of the ATP binding cassette superfamily of active transporters and can confer multidrug resistance on cells and tumors by pumping chemotherapeutic drugs from the cytoplasm. P-gp was purified from CHrB30 cells and retained the ability to bind substrates and hydrolyze ATP. Labeling of P-gp with lectin-gold particles suggested it is monomeric. An initial structure of purified P-gp was determined to 2.5 nm resolution by electron microscopy and single particle image analysis of both detergent-solubilized and lipid-reconstituted protein. The structure was further refined by three dimensional reconstructions from single particle images and by Fourier projection maps of small two-dimensional crystalline arrays (unit cell parameters: a, 14.2 nm; b, 18.5 nm; and gamma, 91.6 degrees ). When viewed from above the membrane plane the protein is toroidal, with 6-fold symmetry and a diameter of about 10 nm. There is a large central pore of about 5 nm in diameter, which is closed at the inner (cytoplasmic) face of the membrane, forming an aqueous chamber within the membrane. An opening from this chamber to the lipid phase is present. The projection of the protein perpendicular to the membrane is roughly rectangular with a maximum depth of 8 nm and two 3-nm lobes exposed at the cytoplasmic face of the membrane, likely to correspond to the nucleotide binding domains. This study provides the first experimental insight into the three-dimensional architecture of any ATP binding cassette transporter.
Erfahrungen mit der ersten schweizerischen Flockungsfiltrationsanlage auf der Kläranlage Hochdorf (1981)

In 1979 a contact filtration plant was installed at the wastewater treatment plant in Hochdorf. In a twelve months investigation, the Federal Institute for Water Resources and Water Pollution Control (EAWAG) optimized chemical conditions and filter configuration with respect to phosphorus and suspended solids removal and observed the performance of the process combination, consisting of mechanical-biological treatment with simultaneous precipitation preceding contact filtration. Operational parameters as filtration velocity, run time and backwash-water use were in the expected ranges. Consistent low phosphorus and suspended solids residuals confirm the high effluent quality under practical conditions.
Synthesis and evaluation of a new non-fluorescent quencher in fluorogenic oligonucleotide probes for real-time PCR (2005)

A non-fluorescent quencher, based on the diaminoanthraquinone Disperse Blue 3, has been incorporated into oligonucleotides at the 5'-end, the 3'-end and internally as a thymidine derivative. Fluorimetry and fluorogenic real-time PCR experiments demonstrate that the quencher is effective with a wide range of fluorescent dyes. The anthraquinone moiety increases the melting temperature of DNA duplexes, thus allowing shorter, more discriminatory probes to be used. The quencher has been used in Scorpion primers and TaqMan probes for human DNA sequence recognition and mutation detection.
Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non‐Hodgkin lymphoma (2009)

Marqibo is an active agent in patients with heavily pretreated aggressive NHL, and tolerated at approximately twice the dose intensity of standard vincristine. Its activity supports further investigation as a substitution for vincristine in combination treatment of lymphoid disorders.
Roles of HIV-1 Env Variable Regions in Viral Neutralization and Vaccine Development (2007)

A major focus of HIV-1 vaccine development has been directed towards a limited number of broadly conserved epitopes in the Envelope (Env) proteins that are sensitive neutralization targets in many primary isolates. However, evidence suggests that these epitopes are poorly immunogenic; similar antibodies are rarely produced by infected subjects, nor are they induced by various immunogens designed to express these epitopes. On the other hand, the major variable domains of Env are highly immunogenic; antibodies against these regions are common in sera of infected patients and easily generated upon immunization. Although these epitopes are extremely sensitive neutralization targets in some laboratory strains and primary isolates, the neutralization range of antibodies against these sites is limited. This review describes potent neutralization epitopes located in the variable regions of Env and discusses the bases for the limited neutralization breadth of antibodies against these targets. Strategies are discussed for using available information to design immunogens capable of exploiting the potential of these regions as vaccine targets.
Effects of glutamine on oxidative stress and nuclear factor-κB expression in the livers of rats with nonalcoholic fatty liver disease (2013)

The aim of this study was to investigate the effects of glutamine on the histomorphology of the liver, oxidative stress and nuclear factor-κB (NF-κB) expression in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD was induced in rats by a high-fat diet, and rats in the treatment group were subjected to oral administration of glutamine (1 g/kg/day). Rats from the treatment, model and normal control groups were assessed after 8 and 12 weeks (n=6 per group at each time-point). The levels of glutathione (GSH), malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in the liver, and the liver histopathology and NF-κB protein 65 (p65) expression in the liver were assessed. Compared with the control group under the same experimental period, the MDA and TNF-α levels in the liver, the hepatic steatosis and the hepatic expression of NF-κB p65 were significantly higher in the model and the treatment groups (P<0.05), while the GSH levels in the liver were significantly lower (P<0.05). These indices improved significantly in the treatment group compared with the model group (P<0.05). In conclusion, glutamine reduces the degree of oxidative stress in the liver, inhibits NF-κB p65 expression and improves hepatic steatosis. Glutamine has a certain protective effect in NAFLD.
[Virology of hepatitis C virus]. (2000)

Hepatitis C virus (HCV) along with hepatitis G virus are members of the hepacivirus genus of the flavi-viridae family to which the flavi- and pestis viruses also belong. The HCV genome has only one ORF which is flanked by a 5' and 3' noncoding region. The ORF encodes for a single polyprotein, which is stepwise cleaved into the 3 structural proteins, core (C), envelope 1 and 2 (E1,2) as well as into 7 non-structural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B). The proteolytic active NS3 plays a central role in this processing. Whereas expectations for development of an HCV vaccine are not very optimistic today, there is great hope in new therapeutic possibilities by inhibition of NS3 function. HCV is highly variable. In the liver and serum of a single patient, genetically slightly different virus particles (quasispecies) can be found. Worldwide, hepatitis C virus has been classified into genotypes and subtypes. This differentiation is not only important epidemiologically, but also has biological and therapeutical implications.
Cryogenic thermonuclear fuel implosions on the National Ignition Facility (2012)

The first inertial confinement fusion implosion experiments with equimolar deuterium-tritium thermonuclear fuel have been performed on the National Ignition Facility. These experiments use 0.17 mg of fuel with the potential for ignition and significant fusion yield conditions. The thermonuclear fuel has been fielded as a cryogenic layer on the inside of a spherical plastic capsule that is mounted in the center of a cylindrical gold hohlraum. Heating the hohlraum with 192 laser beams for a total laser energy of 1.6 MJ produces a soft x-ray field with 300 eV temperature. The ablation pressure produced by the radiation field compresses the initially 2.2-mm diameter capsule by a factor of 30 to a spherical dense fuel shell that surrounds a central hot-spot plasma of 50 μm diameter. While an extensive set of x-ray and neutron diagnostics has been applied to characterize hot spot formation from the x-ray emission and 14.1 MeV deuterium-tritium primary fusion neutrons, thermonuclear fuel assembly is studied by measuring the down-scattered neutrons with energies in the range of 10 to 12 MeV. X-ray and neutron imaging of the compressed core and fuel indicate a fuel thickness of (14 ± 3) μm, which combined with magnetic recoil spectrometer measurements of the fuel areal density of (1 ± 0.09) g cm–2 result in fuel densities approaching 600 g cm–3. The fuel surrounds a hot-spot plasma with average ion temperatures of (3.5 ± 0.1) keV that is measured with neutron time of flight spectra. The hot-spot plasma produces a total fusion neutron yield of 1015 that is measured with the magnetic recoil spectrometer and nuclear activation diagnostics that indicate a 14.1 MeV yield of (7.5±0.1)×1014 which is 70% to 75% of the total fusion yield due to the high areal density. Gamma ray measurements provide the duration of nuclear activity of (170 ± 30) ps. These indirect-drive implosions result in the highest areal densities and neutron yields achieved on laser facilities to date. This achievement is the result of the first hohlraum and capsule tuning experiments where the stagnation pressures have been systematically increased by more than a factor of 10 by fielding low-entropy implosions through the control of radiation symmetry, small hot electron production, and proper shock timing. The stagnation pressure is above 100 Gbars resulting in high Lawson-type confinement parameters of Pτ≃10 atm s. Comparisons with radiation-hydrodynamic simulations indicate that the pressure is within a factor of three required for reaching ignition and high yield. This will be the focus of future higher-velocity implosions that will employ additional optimizations of hohlraum, capsule and laser pulse shape conditions.
Vanilloid Receptor TRPV1 Antagonists as the Next Generation of Painkillers. Are We Putting the Cart before the Horse? (2004)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTVanilloid Receptor TRPV1 Antagonists as the Next Generation of Painkillers. Are We Putting the Cart before the Horse?Arpad Szallasi and Giovanni AppendinoView Author Information Department of Pathology and Laboratory Medicine, 6 Founders Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, and Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, 10131 Novara, Italy Cite this: J. Med. Chem. 2004, 47, 11, 2717–2723Publication Date (Web):April 3, 2004Publication History Received4 November 2003Published online3 April 2004Published inissue 1 May 2004https://pubs.acs.org/doi/10.1021/jm030560jhttps://doi.org/10.1021/jm030560jreview-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views1589Altmetric-Citations121LEARN 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 SUBJECTS:Agonists,Antagonists,Inflammation,Receptors,Rodent models Get e-Alerts
Herpes Simplex Virus Type 1 Infection via the Bloodstream with Apolipoprotein E Dependence in the Gonads Is Influenced by Gender (2005)

Herpes simplex virus type 1 (HSV-1) causes disease in humans and animals. Infection usually occurs via the neural route and possibly occurs via the hematogenous route. The latter, however, is the main route by which immunosuppressed individuals and neonates are infected. Gender-dependent differences in the incidence and severity of some viral infections have been reported. To detect differences between the sexes with respect to HSV-1 colonization and disease, the characteristics of both acute and latent infections in hematogenously infected male and female mice were compared. In acute infection, the female mice had a poorer outcome: HSV-1 colonization was more effective, especially in the gonads and brain. In the encephalon, the midbrain had the highest viral load. In latent infection, brain viral loads were not significantly different with respect to sex. Significant differences were seen, however, in the blood and trigeminal ganglia: HSV-1 seroprevalence was observed in females, with no virus detected in males. In brain dissections, only the cerebral cortex of the females had viral loads statistically higher than those observed in the males. The spread of the virus to several organs of interest during acute infection was examined immunohistochemically. Female mice showed greater viral immunostaining, especially in the adrenal cortex, gonads, and midbrain. In male mice, HSV-1 was detected predominantly in the adrenal cortex. It was also found that apolipoprotein E promotes virus colonization of the ovaries, the APOE gene dose being directly related to viral invasiveness.
VERBMOBIL: the use of prosody in the linguistic components of a speech understanding system (2000)

We show how prosody can be used in speech understanding systems. This is demonstrated with the VERBMOBIL speech to-speech translation system which, to our knowledge, is the first complete system which successfully uses prosodic information in the linguistic analysis. Prosody is used by computing probabilities for clause boundaries, accentuation, and different types, of sentence mood for each of the word hypotheses computed by the word recognizer. These probabilities guide the search of the linguistic analysis. Disambiguation is already achieved during the analysis and not by a prosodic verification of different linguistic hypotheses. So far, the most useful prosodic information is provided by clause boundaries. These are detected with a recognition rate of 94%. For the parsing of word hypotheses graphs, the use of clause boundary probabilities yields a speed-up of 92% and a 96% reduction of alternative readings.