gebhart/patrepeval huggingface dataset:
Coordinated reset has sustained aftereffects in Parkinsonian monkeys (2012)

Coordinated reset neuromodulation consists of the application of consecutive brief high-frequency pulse trains through the different contacts of the stimulation electrode. In theoretical studies, by achieving unlearning of abnormal connectivity between neurons, coordinated reset neuromodulation reduces pathological synchronization, a hallmark feature of Parkinson's disease pathophysiology. Here we show that coordinated reset neuromodulation of the subthalamic nucleus has both acute and sustained long-lasting aftereffects on motor function in parkinsonian nonhuman primates. Long-lasting aftereffects were not observed with classical deep brain stimulation. These observations encourage further development of coordinated reset neuromodulation for treating motor symptoms in Parkinson disease patients.
Scenario-based and model-driven information development with XML DITA (2003)

In this paper, I describe how I followed an end-to-end development process in the development of the user's guide and help information for XML DITA, using scenarios to define my information needs and maps to describe my information model. By using technology driven by maps and scenarios, I was able to keep the information focused on user goals and requirements from its inception through to its final form. The paper will also look at how an integrated end-to-end process can help keep information on track through staged delivery of content to ensure early and ongoing feedback, and will look at some future opportunities for further integration in the stages of the information development process.
S9, a Novel Anticancer Agent, Exerts Its Anti-Proliferative Activity by Interfering with Both PI3K-Akt-mTOR Signaling and Microtubule Cytoskeleton (2009)

Taken together, S9 targets both PI3K-Akt-mTOR signaling and microtubule cytoskeleton, which combinatorially contributes its antitumor activity and provides new clues for anticancer drug design and development.
Heterogeneity of plasma low-density lipoproteins and atherosclerosis risk (1994)

Increased levels of IDL and small, dense LDL are associated with the risk of coronary artery disease. Possible mechanisms include increased susceptibility of small, dense LDL to oxidation, and to other pathologic effects, such as increased retention in the arterial wall. Beneficial effects of a low-fat diet and certain lipid-lowering therapies on the levels and properties of small, dense LDL or their precursors may contribute substantially to the reductions in coronary atherosclerosis observed in several Iipid-lowermg trials.
Urea Cycle Disorders (2007)

The urea cycle was first described in 1932 by Krebs and Henseleit [1] (Figure 36.1). The urea cycle disorders (UCD) result from defects in the metabolism of the extra nitrogen produced by the breakdown of protein and other nitrogen-containing molecules. The incidence of these disorders in the United States is estimated to be at least 1 in 25,000 births, but partial defects may make this number much higher. In a comprehensive Japanese study covering several years the incidence was 1 in 46,000. Severe deficiency or total absence of activity of any of the first four enzymes (CPSI, OTC, ASS, and ASL) in the urea cycle or the cofactor producer (NAGS) results in the accumulation of ammonia and other precursor metabolites during the first few days of life. In milder (or partial) urea cycle enzyme deficiencies, ammonia accumulation may be triggered by illness or stress at almost any time of life, resulting in multiple mild elevations of plasma ammonia concentration. The hyperammonemia is less severe and the symptoms more subtle. The mainstays of treatment are (1) reducing plasma ammonia concentration, (2) pharmacologic management to allow alternative pathway excretion of excess nitrogen, (3) reducing the amount of nitrogen in the diet, (4) reducing catabolism through the introduction of calories supplied by carbohydrates and fat, and (5) taking measures to reduce the risk of neurologic damage. Defects in the fifth enzyme in the pathway, arginase, result in a more subtle disease involving neurologic symptoms.
Purification of the fusion protein of Sendai virus: analysis of the NH2-terminal sequence generated during precursor activation. (1978)

The two glycoproteins of Sendai virus, the hemagglutinin-neuraminidase and the fusion protein (F), were separated and purified by affinity chromatography on a Lens culinaris lectin-Sepharose column. F was shown to consist of two disulfide-bonded glycopolypeptide chains, F1 and F2, of molecular weights 51,000 and 11,000, each of which contained 15% carbohydrate by weight. Amino-terminal sequence analysis showed that F2 was blocked and that the hydrophobic sequence NH2-Phe-Phe-Gly-Ala-Val-Ile-Gly-Ile-Ile-Ala-Leu-Gly-Pro-Ala-Thr- was at the amino terminus of F1. This sequence shows identity at six positions with the hydrophobic amino-terminal sequence of the smaller glycopolypeptide chain, HA2, of the hemagglutinin of influenza virus. Both F1 and HA2 are formed by proteolytic cleavage of precursor glycoproteins (Fo, Sendai virus; HAo, influenza virus). Since these cleavages confer infectivity upon both Sendai and influenza viruses and the ability to induce cell-to-cell fusion upon Sendai virus, the hydrophobic NH2-terminal sequences on F1 and HA2 may play a role in fusion of viral and host-cell membranes.
EGENES and BASCO - National beef evaluations in the UK (2007)

Performance recording and genetic evaluations for dairy and beef cattle and sheep in the UK have undergone significant changes in the last few years. This has resulted in consolidation of recording agencies (and thus data sources) and concentration of previously dispersed genetic evaluations into one site. This paper describes those changes and how the separate agencies are working together to bring added benefits to UK producers.
Proliferation of Human Smooth Muscle Cells Promoted by Lipoprotein(a) (1993)

Elevated blood concentrations of lipoprotein(a) [Lp(a)] and its constituent, apolipoprotein(a) [apo(a)], constitute a major risk factor for atherosclerosis, but their physiological activities remain obscure. Lp(a) and purified apo(a) stimulated the growth of human smooth muscle cells in culture. This effect resulted from inhibition of plasminogen activation, and consequently the activation by plasmin of latent transforming growth factor-beta, which is an inhibitor of smooth muscle cell growth. Because smooth muscle proliferation is one of the hallmarks of atherosclerotic lesions, these results point to a plausible mechanism for the atherogenic activity of Lp(a).
Posttherapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs (1994)

Imiquimod, an immunomodulator with no direct in vitro antiviral activity, has in vivo anti-herpesvirus activity by inducing interferon and enhancing other only partially defined immune responses. Imiquimod treatment of primary genital herpes simplex virus (HSV) infection in guinea pigs reduces the level of genital disease by 90%. We further investigated its utility as suppressive therapy of recurrent disease in animals that had recently recovered from primary genital HSV-2 disease. Imiquimod administered intravaginally once per day for 5 days reduced the number of recurrences only during treatment, while a 21-day regimen reduced the number of recurrences for 8 weeks. For the entire 10 weeks of observation, overall numbers of recurrences were reduced 67% by the 21-day imiquimod treatment (P < 0.0001). Latent HSV in ganglia was not affected by either regimen. Increased circulating alpha interferon activity was observed during therapy with both regimens. Interferon levels rapidly returned to baseline with cessation of treatment. Posttreatment, 5-day imiquimod treatment did not provide clinical benefit or enhancement of cell-mediated or cytokine responses. Twenty-one-day imiquimod treatment reduced both the number of clinical recurrences and levels of HSV antibody for 5 to 6 weeks posttreatment compared with the placebo. Additionally, 21-day imiquimod treatment enhanced HSV antigen-specific interleukin 2 production and proliferative responses by mononuclear cells (P < 0.001) for 4 weeks after treatment. Twenty-one-day imiquimod therapy suppressed recurrent HSV genital disease during and for weeks after therapy, enhanced memory-dependent cytokine and T-cell responses, and reduced the level of antibody responses.
Mg2+-Dependent Conformational Changes in the Hammerhead Ribozyme (1996)

Conformational changes of the hammerhead ribozyme were examined by fluorescence changes of 2-aminopurine riboside incorporated either in the substrate or in the ribozyme. Fluorescence changes could be observed for both the substituted substrate and ribozyme upon complex formation, indicating a different environment for the 2-aminopurine in the complex. Ribozyme-substrate constructs for ciscleavage containing 2-aminopurine at various sites were used for the determination of binding constants of Mg2+ and Ca2+. Depending upon the site of 2-aminopurine substitutions, the fluorescence intensity upon addition of Mg2+ or Ca2+ was reduced by 0-50%. The measurements were performed in high ionic strength buffers such that base pairing in the helical regions is expected to be complete. With three of the ribozymes, the dependence of the fluorescence emission as a function of Mg2+ concentration could be fitted by single binding processes, whereas for the two remaining ribozymes a second binding process needed to be included. The binding constants range from 7600 M-1 down to 12 M-1 in 75 mM Tris-HCl (pH 7.5) and indicate the presence of multiple binding sites in the ribozymes with varying degrees of affinity toward the metal ions. Mg2+ binding constants determined in the same buffer from the Mg2+ dependence of the cleavage rate are of the order of 100 M-1; thus, Mg2+ sites directly involved in catalysis are of intermediate affinity. The ribozyme containing 2-aminopurine in loop III demonstrated the highest binding constant whereas the ribozyme with a 2-aminopurine next to a 2'-deoxy-2'-aminocytosine at the cleavage site exhibited only low metal ion affinity. The data obtained for Ca2+ are very similar to those found for Mg2+. This approach provides a first set of data describing a Mg2+ binding topography to hammerhead RNA molecules and should be useful for the analysis of other RNA molecules.
Purification and Concentration of DNA from Aqueous Solutions (2002)

This unit presents basic procedures for manipulating solutions of single- or double-stranded DNA through purification and concentration steps. These techniques are useful when proteins or solute molecules need to be removed from aqueous solutions, or when DNA solutions need to be concentrated. The , using phenol extraction and ethanol (or isopropanol) precipitation, is appropriate for purification of DNA from small volumes (<0.4 ml) at concentrations lower than 1 mg/ml. Three support protocols outline methods to buffer the phenol used in extractions, concentrate DNA using butanol, and extract residual organic solvents with ether. An alternative to these methods is nucleic acid purification using glass beads and this is also presented. These protocols may also be used for purifying RNA. The final two alternate protocols are used for concentrating RNA and extracting and precipitating DNA from larger volumes and from dilute solutions, and for removing low-molecular-weight oligonucleotides and triphosphates.
Sustained correction of bleeding disorder in hemophilia B mice by gene therapy (1999)

Mice generated by disrupting the clotting factor IX gene exhibit severe bleeding disorder and closely resemble the phenotype seen in hemophilia B patients. Here we demonstrate that a single intraportal injection of a recombinant adeno-associated virus (AAV) vector encoding canine factor IX cDNA under the control of a liver-specific enhancer/promoter leads to a long-term and complete correction of the bleeding disorder. High level expression of up to 15-20 microgram/ml of canine factor IX was detected in the plasma of mice injected with 5.6 x 10(11) particles of an AAV vector for >5 months. The activated partial thromboplastin time of the treated mice was fully corrected to higher than normal levels. Liver-specific expression of canine factor IX was confirmed by immunofluorescence staining, and secreted factor IX protein was identified in the mouse plasma by Western blotting. All treated mice survived the tail clip test without difficulty. Thus, a single intraportal injection of a recombinant adeno-associated virus vector expressing factor IX successfully cured the bleeding disorder of hemophilia B mice, proving the feasibility of using AAV-based vectors for liver-targeted gene therapy of genetic diseases.
Study of genotoxic effects of antidiarrheal medicinal herbs on human cells in vitro. (1995)

The use of medicinal herbs has been a common practice in Asia but their genotoxic properties are little known. In the present study, genotoxic effects of three antidiarrheal herbs, guava leaf, mangosteen peel and pomegranate peel, were examined using established human cell lines, Raji and P3HR-1. Cells were treated with boiled-water extract of the herbs at various concentrations for 24 and 48 hours in vitro. Cell growth and viability were dose dependently reduced. No apparent chromosomal aberrations were induced by the treatment. Administration of pomegranate extract induced apoptotic DNA fragmentation. This genotoxicity test system is simple and convenient for the primary screening.
Elastic scattering of evanescent electromagnetic waves (1979)

Analytic and numerical results are given for the elastic scattering of evanescent electromagnetic waves by dielectric spheres. Some polarization and symmetry effects not found in Lorenz-Mie scattering are noted. The possibility of experimental studies is also discussed.
Palladiumkatalysierte Kupplungen von Arylchloriden (2002)

Palladiumkatalysierte Kupplungen gehören zu den leistungsfähigsten und vielseitigsten Reaktionen, die dem organischen Chemiker für die Synthese zur Verfügung stehen. Ihre große Beliebtheit rührt teilweise daher, dass sie bei den Umsetzungen gewöhnlich viele funktionelle Gruppen tolerieren, was ihre breite Verwendung in vielen Bereichen ermöglicht. Allerdings unterlagen die palladiumkatalysierten Kupplungen jahrelang großen Einschränkungen durch die geringe Reaktivität der Arylchloride; diese Verbindungen sind in Bezug auf Kosten und Verfügbarkeit attraktivere Substrate als die entsprechenden Bromide, Iodide und Triflate. Herkömmliche Palladium/Triarylphosphan-Katalysatoren setzten nur bestimmte aktivierte Arylchloride um (z. B. Heteroarylchloride und Substrate mit elektronenanziehenden Gruppen), nicht aber Arylchloride generell. Seit 1998 haben mehrere Forschungsgruppen bedeutende Fortschritte hinsichtlich dieser Herausforderung beschrieben; Katalysatoren mit voluminösen, elektronenreichen Phosphanen und Carbenen erwiesen sich als sehr vielseitig und ermöglichen besonders milde Reaktionsbedingungen. Dieser Aufsatz fasst die frühen, wegweisenden Arbeiten und die spannenden neuartigen Entwicklungen auf dem Gebiet der palladiumkatalysierten Kupplungen von Arylchloriden zusammen.
Dynamic in Vivo Response Characteristics of Three Oximeters: Hewlett-Packard 47201A, Biox III, and Nellcor N-100 (1987)

Pulse oximeters (Biox III, Nellcor N-100) and a transmittance oximeter [Hewlett-Packard 47201A (HP)] were compared for SaO2 measurement and responsiveness during dynamic changes in arterial oxygen saturation and heart rate. Five sleep apnea syndrome patients were studied because they had large oscillations in SaO2 and heart rate in sleep. During sleep, each patient exhibited a series of rapid (18.0 +/- 8.3 s, mean +/- SD) oscillations in oxygen saturation (92.1 +/- 2.6% to 74.2 +/- 7.7%). Oxygen saturation measurements were sampled simultaneously from each oximeter by computer (at 2 Hz). Accuracy was assessed by comparing pulse and transmittance oxygen saturation measurements at the peak and trough of each apnea-related oscillation. Oximeter response was defined in terms of the "delay" or absolute time difference between the pulse oximeters and the transmittance oximeter for the determination of the peak and trough saturations. Linear regression analysis was used to establish accuracy and response relationships between pulse oximeter sensors (reusable ear, reusable digit, disposable digit, and disposable nasal sensors) and the transmittance oximeter sensor (reusable ear sensor). Pulse oximeter response delay was highly correlated with heart rate. Pulse oximeter SaO2 measurement and response characteristics varied considerably with sensor type (disposable, reusable) and sensor location (ear, nose, and digit). One must be aware of these differences in clinical and research application.
Intrinsic Raman spectroscopy for quantitative biological spectroscopy Part II: Experimental applications (2008)

We demonstrate the effectiveness of intrinsic Raman spectroscopy (IRS) at reducing errors caused by absorption and scattering. Physical tissue models, solutions of varying absorption and scattering coefficients with known concentrations of Raman scatterers, are studied. We show significant improvement in prediction error by implementing IRS to predict concentrations of Raman scatterers using both ordinary least squares regression (OLS) and partial least squares regression (PLS). In particular, we show that IRS provides a robust calibration model that does not increase in error when applied to samples with optical properties outside the range of calibration.
Loss of PTEN Expression as a Prognostic Marker for Tongue Cancer (2001)

Although genetic alterations of the PTEN gene are rare in head and neck squamous cell carcinoma, loss of PTEN is not an uncommon event in squamous cell carcinoma of the tongue. Lack of PTEN expression may be an independent prognostic indicator for clinical outcome in patients with this tumor type.
Image and video based painterly animation (2004)

We present techniques for transforming images and videos into painterly animations depicting different artistic styles. Our techniques rely on image and video analysis to compute appearance and motion properties. We also determine and apply motion information from different (user-specified) sources to static and moving images. These properties that encode spatio-temporal variations are then used to render (or paint) effects of selected styles to generate images and videos with a painted look. Painterly animations are generated using a mesh of brush stroke objects with dynamic spatio-temporal properties. Styles govern the behavior of these brush strokes as well as their rendering to a virtual canvas. We present methods for modifying the properties of these brush strokes according to the input images, videos, or motions. Brush stroke color, length, orientation, opacity, and motion are determined and the brush strokes are regenerated to fill the canvas as the video changes. All brush stroke properties are temporally constrained to guarantee temporally coherent non-photorealistic animations.
A single silent substitution in the genome of Apple stem grooving virus causes symptom attenuation (2003)

Among randomly mutagenized clones derived from an infectious cDNA copy of genomic RNA of Apple stem grooving virus (ASGV), we previously identified a clone, pRM21, whose in vitro transcript (ASGV-RM21) does not induce any symptoms characteristic of the original (wild-type) cDNA clone (ASGV-wt) in several host plants. Interestingly, ASGV-RM21 has only a single, translationally silent nucleotide substitution, U to C, at nucleotide 4646 of the viral genome within open reading frame (ORF) 1. Here, we characterize and verify this unprecedented silent-mutation-induced attenuation of symptoms in infected plants. Northern and Western blot analyses showed that less ASGV-RM21 accumulates in host plants than ASGV-wt. In addition, two more silent substitutions, U to A and U to G, constructed by site-directed mutagenesis at the same nucleotide (4646), also induced attenuated symptoms. This is the first report that a single silent substitution attenuates virus-infection symptoms and implicates a novel determinant of disease symptom severity.
Control of Erythropoietin Delivery by Doxycycline in Mice After Intramuscular Injection of Adeno-Associated Vector (1998)

We reported previously that controlled expression of a foreign gene in response to tetracycline derivative can be accomplished in mice by the autologous transplantation of retrovirus-modified muscle cells. Although regulated systemic delivery of therapeutic proteins from engineered tissues has potential clinical application, the transplantation of muscle cells is not currently feasible in humans. Several studies have shown that a single injection of adeno-associated virus (AAV) vectors into mouse muscle results in long-term expression of reporter genes as well as sustained delivery of proteins into the serum. Because this method is potentially applicable clinically, we constructed an AAV vector in which the expression of the mouse erythropoietin (Epo) cDNA is modulated in response to doxycycline. The vector was injected intramuscularly in normal mice. We observed that hematocrit and serum Epo concentrations could be modulated over a 29-week period in response to the presence or absence of doxycycline in the drinking water of these animals. Thus, a regulated gene expression cassette can be incorporated into a single AAV vector, such that intramuscular injection of the vector allows sustained and regulated expression of a desired gene.
NADH‐dependent dehydrogenase activity estimation by flow cytometric analysis of 3‐(4,5‐dimethylthiazolyl‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction (1992)

MTT reduction is usually analysed by colorimetric assay to study mitochondrial dehydrogenase activity as a test of cytotoxicity. This enzymatic reaction produces dark-blue granules of formazan, which increase cell refringency. In this work, we define the conditions for MTT use in quantitative flow cytometric analysis. MTT reduction provides a non-fluorescent dye usable by this technique to study an intracellular NADH-dependent dehydrogenase activity in vital cells. We observe that formazan production increases asymptotically with cell concentration and that this temperature-dependent Michaelis enzymatic reduction is produced essentially by mitochondrial dehydrogenases. In isolated mitochondria from rat hepatocytes and in whole L1210 murine leukemia cells, the Michaelis constants (KM) observed in the presence of respiratory substrates were, respectively, 10 microM and 500 microM. The inhibition of mitochondrial protein synthesis by chloramphenicol, which induces a rise of MTT reduction due to the correlative stimulation of glycolysis (Pasteur effect), is a limit of the MTT assay as a cytotoxicity test.
Mammalian RNAi: a Practical Guide (2005)

Silencing of gene expression by RNA interference (RNAi) has become a powerful tool for the functional annotation of the Caenorhabditis elegans and Drosophila melanogaster genomes. Recent advances in the design and delivery of targeting molecules now permit efficient and highly specific gene silencing in mammalian systems as well. RNAi offers a simple, fast, and cost-effective alternative to existing gene targeting technologies both in cell-based and in vivo settings. Synthetic small interfering RNA (siRNA) and retroviral short hairpin RNA (shRNA) libraries targeting thousands of human and mouse genes are publicly available for high-throughput genetic screens, and knockdown animals can be rapidly generated by lentivirus-mediated transgenesis. RNAi also holds great promise as a novel therapeutic approach. This review provides insight into the current gene silencing techniques in mammalian systems.