gebhart/patrepeval huggingface dataset:
Duality of polynucleotide substrates for Phi29 DNA polymerase: 3′→5′ RNase activity of the enzyme (2008)

Phi29 DNA polymerase is a small DNA-dependent DNA polymerase that belongs to eukaryotic B-type DNA polymerases. Despite the small size, the polymerase is a multifunctional proofreading-proficient enzyme. It catalyzes two synthetic reactions (polymerization and deoxynucleotidylation of Phi29 terminal protein) and possesses two degradative activities (pyrophosphorolytic and 3'-->5' DNA exonucleolytic activities). Here we report that Phi29 DNA polymerase exonucleolyticaly degrades ssRNA. The RNase activity acts in a 3' to 5' polarity. Alanine replacements in conserved exonucleolytic site (D12A/D66A) inactivated RNase activity of the enzyme, suggesting that a single active site is responsible for cleavage of both substrates: DNA and RNA. However, the efficiency of RNA hydrolysis is approximately 10-fold lower than for DNA. Phi29 DNA polymerase is widely used in rolling circle amplification (RCA) experiments. We demonstrate that exoribonuclease activity of the enzyme can be used for the target RNA conversion into a primer for RCA, thus expanding application potential of this multifunctional enzyme and opening new opportunities for RNA detection.
Spectral-domain optical coherence tomography on a silicon chip (2012)

Optical coherence tomography (OCT) is a non-invasive optical technique for high-resolution cross-sectional imaging of specimens, with many applications in clinical medicine and industry (e.g. materials testing, quality assurance, and process control). Current state-of-the-art OCT systems operate in the frequency domain, using either a broad-band light source and a spectrometer, known as ‘spectral-domain OCT’ (SD-OCT), or a rapidly tunable laser, known as ‘swept-source OCT’ (SS-OCT). Both systems contain a multitude of fiber and free-space optical components which make these instruments costly and bulky. The size and cost of an OCT system can be decreased significantly by the use of integrated optics. A suitable fabrication technology and optimum design may allow one to fabricate extremely compact, low-cost, and rugged OCT systems. The main goal of this PhD project is miniaturization of an SD-OCT system by integrating its spectrometer and interferometer parts on a silicon chip. For this purpose and arrayed-waveguide grating (AWG) spectrometer and a Michelson interferometer (MI) comprising wavelength-insensitive 3-dB couplers were designed, fabricated, and characterized. Although integration of a spectrometer on a chip is challenging, AWGs present a well-established way towards miniaturization. Besides their extensive usage in telecommunication for (de)multiplexing, AWGs are also ideally suited for applications such as OCT and spectroscopy, with their high spectral resolution, small form factor, large bandwidth, and low insertion loss. In addition to their advantages listed above, AWGs are cost-effective, which makes them favorable for integration with SD-OCT systems. Wavelength-insensitive 3-dB couplers can be realized by either cascading two conventional couplers in a Mach-Zehnder configuration with a relative phase shift of 2?/3 introduced between them (i.e. balanced coupler) or using two adiabatically tapered asynchronous waveguides (i.e. non-uniform adiabatic coupler). Such couplers can be designed to yield a maximally flat response with respect to deviations in wavelength, polarization, or uniform fabrication over a broad spectral range, with no excess loss. Therefore, these couplers are very good candidates for application in MIs. In the first chapter of this thesis an overview is given of OCT systems. In chapter 2, the background, design, fabrication, and characterization of AWG spectrometers and their application in OCT imaging are discussed. In chapter 3, integrated MIs and wavelength-insensitive 3-dB couplers are presented; here, two different coupler designs (non-uniform adiabatic and balanced couplers) are analyzed in detail. The OCT measurements at 800 nm and 1300 nm are presented in chapter 4. Results of depth-range enhancement and polarization effect on signal roll-off are presented in chapter 5. In addition, an integrated field-flattening lens design and its characterization are discussed as a part of chapter 5 as well. In chapter 6, conclusions and outlook, based on the results presented in this thesis, are given.
Reducing complexity for converged voice/data networks and services architecture (2002)

The telecommunications industry today is facing an increasing degree of complexity due to the proliferation of available technologies and separate implementations of voice and data networks and services. Recent trends in the industry toward a convergence of telephony/computer technologies, networks, and services create an opportunity for reducing complexity in the converged voice/data network. The converged telecommunications network will be packet based, providing integrated voice/data/video services with third-party programmability to any subscriber, anywhere, over any access media. This paper describes an architectural approach to meet these challenges. A set of guiding principles is formulated and used for developing the converged network and service architectures. These principles, which provide an overall framework for partitioning network and service functions into components, are illustrated using the planned 7R/E™ Packet Solutions system and service architectures to build component-based converged voice and data services with interfaces to operations, administration, maintenance, and provisioning (OAM&P) frameworks for industry-grade reliability, availability, and security.
Neuropsychological Results of Long-Term Therapy with Oxiracetam in Patients with Dementia of Alzheimer Type and Multi-Infarct Dementia in Comparison with a Control Group (1989)

The cognitive and behavioral effects of oxiracetam therapy during long-term treatment in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID) were studied in comparison with a historical control group. Twenty DAT/MID outpatients, aged 54-86 years, received oxiracetam (800 mg twice a day) for a period of 6 months. Another 20 DAT/MID outpatients, aged 67-85 years, were selected from our clinical records in order to obtain a control group of patients matched for age, sex, diagnosis, baseline Mini Mental State Examination (MMSE) score and follow-up duration. All the patients were diagnosed as having mild to moderate degrees of dementia as defined by a baseline MMSE score between 14 and 24. The patients of both groups underwent, both at baseline and after 6 months, the following neuropsychological tests: MMSE, Idiopathic Cerebral Dysfunction Scale, Babcock Test, Gibson Spiral, Toulouse-Pieron Test. Statistical analysis of experimental data demonstrated that at baseline the two groups were comparable. At the end of the study period the oxiracetam group scored significantly better on the majority of the tests evaluating memory, attention, orientation, concentration and psychomotricity than the control group, in which a worsening trend was seen on the whole. No side effects were seen during oxiracetam treatment. The present study, showing positive clinical findings after long-term oxiracetam therapy in controlled conditions, confirms that this drug can be a useful pharmacological treatment for mild to moderate degrees of dementia.
Highlights of the Eighteenth Annual Meeting of the American Society of Preventive Oncology (1995)

Introduction to molecular genetics: from the laboratory to prevention (special genetics workshop preceding the annual meeting)
A CMOS large-swing low-distortion three-stage class AB power amplifier (1990)

A CMOS power amplifier with a class AB rail-to-rail output stage is presented. By using a three-stage amplifier with double Miller compensation, the harmonic distortion of the output stage is suppressed by the internal feedback loops. This approach is thoroughly investigated, and it is shown that a three-stage amplifier has apparent advantages for DC gain, harmonic distortion, and power-supply rejection ratio (PSRR). A realized prototype for ISDN applications with a gain bandwidth (GBW) of 5 MHz and with -80-dB THD at 10 kHz for an output current of 20 mA in a load of 81 Omega is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Toll-Like Receptor 5 Stimulation Protects Mice from Acute Clostridium difficile Colitis (2011)

Clostridium difficile is a spore-forming bacterium that infects the lower intestinal tract of humans and is the most common known cause of diarrhea among hospitalized patients. Clostridium difficile colitis is mediated by toxins and develops during or following antibiotic administration. We have used a murine model of C. difficile infection, which reproduces the major features of the human disease, to study the effect of innate immune activation on resistance to C. difficile infection. We found that administration of purified Salmonella-derived flagellin, a Toll-like receptor 5 (TLR5) agonist, protects mice from C. difficile colitis by delaying C. difficile growth and toxin production in the colon and cecum. TLR5 stimulation significantly improves pathological changes in the cecum and colon of C. difficile-infected mice and reduces epithelial cell loss. Flagellin treatment reduces epithelial apoptosis in the large intestine, thereby protecting the integrity of the intestinal epithelial barrier during C. difficile infection. We demonstrate that restoring intestinal innate immune tone by TLR stimulation in antibiotic-treated mice ameliorates intestinal inflammation and prevents death from C. difficile colitis, potentially providing an approach to prevent C. difficile-induced pathology.
Inhibition of Hypoxia-inducible Factor (HIF) Hydroxylases by Citric Acid Cycle Intermediates (2006)

The stability and transcriptional activity of the hypoxia-inducible factors (HIFs) are regulated by two oxygen-dependent events that are catalyzed by three HIF prolyl 4-hydroxylases (HIF-P4Hs) and one HIF asparaginyl hydroxylase (FIH). We have studied possible links between metabolic pathways and HIF hydroxylases by analyzing the abilities of citric acid cycle intermediates to inhibit purified human HIF-P4Hs and FIH. Fumarate and succinate were identified as in vitro inhibitors of all three HIF-P4Hs, fumarate having K(i) values of 50-80 microM and succinate 350-460 microM, whereas neither inhibited FIH. Oxaloacetate was an additional inhibitor of all three HIF-P4Hs with K(i) values of 400-1000 microM and citrate of HIF-P4H-3, citrate being the most effective inhibitor of FIH with a K(i) of 110 microM. Culturing of cells with fumarate diethyl or dimethyl ester, or a high concentration of monoethyl ester, stabilized HIF-1alpha and increased production of vascular endothelial growth factor and erythropoietin. Similar, although much smaller, changes were found in cultured fibroblasts from a patient with fumarate hydratase (FH) deficiency and upon silencing FH using small interfering RNA. No such effects were seen upon culturing of cells with succinate diethyl or dimethyl ester. As FIH was not inhibited by fumarate, our data indicate that the transcriptional activity of HIF is quite high even when binding of the coactivator p300 is prevented. Our data also support recent suggestions that the increased fumarate and succinate levels present in the FH and succinate dehydrogenase-deficient tumors, respectively, can inhibit the HIF-P4Hs with consequent stabilization of HIF-alphas and effects on tumor pathology.
The effect of cicloxolone sodium on the replication in cultured cells of adenovirus type 5, reovirus type 3, poliovirus type 1, two bunyaviruses and Semliki Forest virus (1992)

The effect of cicloxolone sodium (CCX) on the replication of typical representatives of different virus families [adenovirus type 5 (Ad-5), reovirus type 3 (Reo-3), Bunyamwera and Germiston viruses, poliovirus type 1 (Polio-1) and Semliki Forest virus (SFV)] in tissue culture was investigated. The Golgi apparatus inhibitor monensin (Mon) and CCX were shown to have analogous effects on some aspects of virus replication. Although the Mon-like effect of CCX played no role in the antiviral activity against Ad-5, Reo-3 or Polio-1, it could entirely account for the antiviral activity against the Bunyamwera and Germiston viruses, for which inhibition of glycoprotein processing was responsible for the antiviral activity. In the case of SFV, the Mon-like activity of CCX caused cytoplasmic assembly of fully infectious SFV within vacuoles and thus impaired virus release without altering total infectious virus yield. Fewer Ad-5 and Reo-3 progeny were produced in the presence of the drug. CCX had a dose-dependent biphasic effect on the particle:p.f.u. ratio of the Reo-3 yield. At low CCX concentration (&lt;50 µm) the virus yield contained poor quality, non-infectious virus, but at higher CCX concentration (⩾ 100 µm) low quality virus could no longer be successfully assembled. We conclude that the antiviral effect can be manifested in three ways: (i) by a reduction in the virus particle yield produced; (ii) by a loss of quality (relative infectivity); (iii) by a virucidal effect of the drug. We have previously defined three CCX sensitivity classes. Mechanisms (i), (ii) and (iii) operate against viruses belonging to class CCXs-1 [herpes simplex virus (HSV) type 1, HSV-2 and vesicular stomatitis virus], but essentially only (i) and (ii) affect Reo-3 (CCXs-2), whereas (i) and possibly (iii) affect Ad-5 (CCXs-2). In the case of SFV (CCXs-3) none of these mechanisms operate, but relocation of assembled virus is found.
Systemic and Persistent Muscle Gene Expression in Rhesus Monkeys with a Liver De-Targeted Adeno-Associated Virus Vector (2017)

The liver is a major off-target organ in gene therapy approaches for cardiac and musculoskeletal disorders. Intravenous administration of most of the naturally occurring adeno-associated virus (AAV) strains invariably results in vector genome sequestration within the liver. In the current study, we compared the muscle tropism and transduction efficiency of a liver de-targeted AAV variant to AAV9 following systemic administration in newborn rhesus monkeys. In vivo bioluminescence imaging was performed to monitor transgene expression (firefly luciferase) post administration. Results indicated comparable and sustained levels of systemic firefly luciferase gene expression in skeletal muscle over a period of two years. Quantitation of vector biodistribution in harvested tissues post-administration revealed widespread recovery of vector genomes delivered by AAV9 but markedly decreased levels in major systemic organs from the AAV variant. These studies validate the translational potential and safety of liver de-targeted AAV strains for gene therapy of muscle-related diseases.
Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing (2012)

To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase-mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease.
Inhibition of Salmonella enterica Biofilm Formation Using Small-Molecule Adenosine Mimetics (2014)

ABSTRACT Biofilms have been widely implicated in chronic infections and environmental persistence of Salmonella enterica , facilitating enhanced colonization of surfaces and increasing the ability of the bacteria to be transmitted to new hosts. Salmonella enterica serovar Typhi biofilm formation on gallstones from humans and mice enhances gallbladder colonization and bacterial shedding, while Salmonella enterica serovar Typhimurium biofilms facilitate long-term persistence in a number of environments important to food, medical, and farming industries. Salmonella regulates expression of many virulence- and biofilm-related processes using kinase-driven pathways. Kinases play pivotal roles in phosphorylation and energy transfer in cellular processes and possess an ATP-binding pocket required for their functions. Many other cellular proteins also require ATP for their activity. Here we test the hypothesis that pharmacological interference with ATP-requiring enzymes utilizing adenosine mimetic compounds would decrease or inhibit bacterial biofilm formation. Through the screening of a 3,000-member ATP mimetic library, we identified a single compound (compound 7955004) capable of significantly reducing biofilm formation by S . Typhimurium and S . Typhi. The compound was not bactericidal or bacteriostatic toward S . Typhimurium or cytotoxic to mammalian cells. An ATP-Sepharose affinity matrix technique was used to discover potential protein-binding targets of the compound and identified GroEL and DeoD. Compound 7955004 was screened against other known biofilm-forming bacterial species and was found to potently inhibit biofilms of Acinetobacter baumannii as well. The identification of a lead compound with biofilm-inhibiting capabilities toward Salmonella provides a potential new avenue of therapeutic intervention against Salmonella biofilm formation, with applicability to biofilms of other bacterial pathogens.
Grafting of β‐cyclodextrin‐modified 2‐hydroxyethyl methacrylate onto polyurethane (1996)

2-Hydroxyethyl methacrylate (HEMA) and β-cyclodextrin are bridged using toluene-2,4-diisocyanate (TDI) by reacting the OH group of HEMA and one of the primary OH groups of β-cyclodextrin. The modified HEMA is grafted to polyurethane by γ-irradiation. The preliminary study showed that the membrane potential of conventional polymers like polyurethane could be enhanced considerably by this type of modification. © 1996 John Wiley & Sons, Inc.
Transcriptome Analysis Describing New Immunity and Defense Genes in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients (2009)

Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic interventions.
Stability of esmolol hydrochloride in 5% dextrose injection (1995)

Journal Article Stability of esmolol hydrochloride in 5% dextrose injection Get access Donald B. Wiest, Pharm.D., Donald B. Wiest, Pharm.D. Associate Professor of Clinical Pharmacy and Instructor in Pediatrics Colleges of Pharmacy and Medicine, Medical University of South Carolina (MUSC), Charleston Address reprint requests to Dr. Wiest at the College of Pharmacy, Medical University of South Carolina, QF 220, 171 Ashley Avenue, Charleston, SC 29425. Search for other works by this author on: Oxford Academic Google Scholar Sandra S. Garner, Pharm.D., Sandra S. Garner, Pharm.D. Assistant Professor of Clinical Pharmacy and Instructor in Pediatrics Colleges of Pharmacy and Medicine, Medical University of South Carolina (MUSC), Charleston Search for other works by this author on: Oxford Academic Google Scholar Leah M. Childress, Pharm.D. Leah M. Childress, Pharm.D. Pediatric Pharmacotherapy Resident The Children's Hospital, Denver, CO; at the time of this study she was a Pharm.D. degree candidate, MUSC Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 52, Issue 7, 1 April 1995, Pages 716–718, https://doi.org/10.1093/ajhp/52.7.716 Published: 01 April 1995
Model-based reasoning in biomedicine. (1992)

Significant advances have been achieved in model-based reasoning in the past decade, rendering it one of the most active branches of artificial intelligence. Research on model-based reasoning focuses on two major goals: being able to predict and explain device behavior, mostly using qualitative representations. Viewed from the same perspective, many research issues in biomedicine share the same outlook: being able to predict the behavior of a certain biological system, and being able to explain why the system behaves as it does (or will behave as it is predicted to). Qualitative modeling, with its wide margins for ambiguity, provides an excellent toolset for the simulation of biological systems which do not lend themselves easily to mathematical modeling. This article presents a review of recent advances in model-based reasoning in biomedicine.
An overview of superelastic stent design (2000)

The purpose of this paper is to contrast the performance of self-expanding and balloon-expandable stents. While both approaches to stenting have proven to be successful in treating a wide range of vascular disease, there are significant differences in the philosophy behind and properties of the two types of stents. Many of these differences, such as strength, stiffness (or compliance), recoil, dynamic scaffolding, vessel conformity and fatigue resistance will be highlighted by studying the mechanics of the stent alone, and then of a stent within a vessel. These differences can be summarised by observing that self-expanding stents provide more anatomically-correct scaffolding, while balloon-expandable stents provide rigid and uncompromising reinforcement. Other differences, such as corrosion resistance, placement accuracy and visibility, will also be briefly summarised.
Instant fabrication and selection of folded structures using drop impact (2011)

A drop impacting a target cutout in a thin polymer film is wrapped by the film in a dynamic sequence involving both capillary forces and inertia. Different 3D structures can be produced from a given target by slightly varying the impact parameters. A simplified model for a nonlinear dynamic Elastica coupled with a drop successfully explains this shape selection and yields detailed quantitative agreement with experiments. This first venture into the largely unexplored dynamics of elastocapillary assemblies opens up the perspective of mass production of 3D packages with individual shape selection.
Reference value standards and primary standards for pH measurements in organic solvents and water + organic solvent mixtures of moderate to high permittivities (1987)

Article Reference value standards and primary standards for pH measurements in organic solvents and water + organic solvent mixtures of moderate to high permittivities was published on January 1, 1987 in the journal Pure and Applied Chemistry (volume 59, issue 11).