gebhart/patrepeval huggingface dataset:
Inhibition of Restriction Endonuclease Activity by DNA Binding Fluorochromes (1996)

Activity of type II restriction endonuclease is affected by many common factors including buffer composition and sequences flanking the recognition site (Brabec et al., Eur.J. Biochem. 216, 183, 1993). The successful development of Optical Mapping (Schwartz et al., Science, 262, 110, 1993; Meng et al., Nature Genet. 9, 432, 1995; Wang and Schwartz, PNAS, 1995 Cai et al., PNAS, 92, 5164, 1995) relied on optimization of light microscope-based imaging of fluorescently labeled DNA molecules during restriction endonuclease digestion. Little was known about the effects of commonly used DNA-fluorochromes on restriction endonuclease activity. Thus, we developed an enzyme activity assay using lambda bacteriophage DNA or adenovirus-2 DNA to evaluate the effects of five DNA binding fluorochromes (4'-6-daimidine-2-phenylindole (DAPI), ethidium bromide (EtdBr), ethidium bromide homodimer (EthD-1), bis-benzimide (H33258) and benzothiazolium-4-quinolinium dimer (TOTO-1)) on the enzymatic activities of eleven type II restriction endonucleases (Asc I, Csp I, Dra I, EcoR I, Hha I, Hind III, Not I, Rsr II, Sfi I, SgrA I and Sma I). We found that the minor groove binding fluorochrome, DAPI, did not measurably inhibit activity of this group, with the exception of Dra I. Similarly, another minor groove binding fluorochrome H33258 inhibited Dra I and Not I (slightly). The three intercalating fluorochromes EtdBr, EthD-1 and TOTO-1, however, variably inhibited the other enzymes. Since Beta-mercaptoethanol (Beta-ME) is used to discourage photodamage of stained DNA molecules, we also assessed its effect on restriction endonuclease activity. Interestingly, Dra I, Hind III, Sfi I and Sma I retained full activities at high concentration of Beta-ME (5%), but Asc I, Csp I, Not I, Rsr II and SgrA I showed varying sensitivities to the Beta-ME. Isoschizomers Csp I and Rsr II behaved differently to both fluorochromes and Beta-ME. The results presented here should provide a basis for further development of new Optical Mapping-based techniques requiring fluorescence labeling of other actively imaged enzymatic reactions.
An online algorithm for segmenting time series (2002)

In recent years, there has been an explosion of interest in mining time-series databases. As with most computer science problems, representation of the data is the key to efficient and effective solutions. One of the most commonly used representations is piecewise linear approximation. This representation has been used by various researchers to support clustering, classification, indexing and association rule mining of time-series data. A variety of algorithms have been proposed to obtain this representation, with several algorithms having been independently rediscovered several times. In this paper, we undertake the first extensive review and empirical comparison of all proposed techniques. We show that all these algorithms have fatal flaws from a data-mining perspective. We introduce a novel algorithm that we empirically show to be superior to all others in the literature.
Solid‐State Electrochemical Kinetics of Li‐Ion Intercalation into Li1 − x CoO2: Simultaneous Application of Electroanalytical Techniques SSCV, PITT, and EIS (1999)

The electroanalytical behavior of thin electrodes is elucidated by the simultaneous application of three electroanalytical techniques: slow‐scan‐rate cyclic voltammetry (SSCV), potentiostatic intermittent titration technique, and electrochemical impedance spectroscopy. The data were treated within the framework of a simple model expressed by a Frumkin‐type sorption isotherm. The experimental SSCV curves were well described by an equation combining such an isotherm with the Butler‐Volmer equation for slow interfacial Li‐ion transfer. The apparent attraction constant was −4.2, which is characteristic of a quasi‐equilibrium, first‐order phase transition. Impedance spectra reflected a process with the following steps: ion migration in solution, ion migration through surface films, strongly potential‐dependent charge‐transfer resistance, solid‐state diffusion, and accumulation of the intercalants into the host materials. An excellent fit was found between these spectra and an equivalent circuit, including a Voigt‐type analog ( migration through multilayer surface films and charge transfer) in series with a finite‐length Warburg‐type element ( solid‐state diffusion), and a capacitor (Li accumulation). In this paper, we compare the solid‐state diffusion time constants and the differential intercalation capacities obtained by the three electroanalytical techniques. © 1999 The Electrochemical Society. All rights reserved.
15 Investigation of IL-1 inhibition in patients presenting with non-ST elevation myocardial infarction acute coronary syndromes (the MRC ILA Heart Study) (2011)

<h3>Background</h3> Inflammatory mechanisms are involved in both coronary atherogenesis and its presentation as acute coronary syndromes (ACS). To date, drugs used at the time of ACS, or for primary and secondary prevention have not primarily targeted inflammatory mechanisms. Studies with aspirin and statin drugs indicate that anti-inflammatory properties of these compounds may contribute to their beneficial effects. Pre-clinical studies from our group have indicated that the pro-inflammatory cytokine IL-1 drives a number of vascular events relevant to coronary artery disease and ACS. IL-1 can be inhibited by IL-1 receptor antagonist (IL-1ra, Anakinra, Amgen) which is licensed for the treatment of rheumatoid arthritis. <h3>Aims</h3> To investigate the effects of interleukin-1 receptor antagonist (IL-1ra) on inflammatory biomarkers in patients with ACS &lt;48 h from symptom onset, and to evaluate the safety and tolerability of treatment. <h3>Design and methods</h3> The UK MRC ILA-HEART study is an investigator-initiated, non-industry sponsored, phase 2, multi-centre, placebo-controlled trial, comparing the IL-1ra (100 mg) with matching placebo given as a single, daily subcutaneous injection over 2 weeks. The primary outcome of the study was area under the curve (AUC) of high sensitivity CRP (hs-CRP) over the first 7 days of treatment, and the main secondary outcomes are AUC of troponin and safety and compliance of trial treatment. Patients were encouraged to self-administer trial treatment, and underwent daily assessment of hs-CRP, troponin, von Willebrand factor and other biomarkers up to 7 days, and again at 2 weeks and 30 days. Patients were followed up to 12 months for safety (Abstract 15 table 1). <h3>Results</h3> Five UK centres randomised 182 patients with non-ST elevation (NSTEMI) ACS to IL-1ra or placebo. Enrolment completed in March 2010. Mean age was 61 years, 32% female, 28% prior MI, 15% diabetes, 90% were receiving a statin at the time of randomisation and 64% had early PCI or CABG. Compliance was good with 85% of patients receiving daily injections during the first 7 days, and 70% of patients were able to self-administer the injections. Injection site reactions reported as adverse events occurred in 14% of patients. There was no significant difference in area under the curve for hsCRP between active and placebo groups. The MACE and serious adverse event rates are shown in Abstract 15 table 2. <h3>Discussion</h3> NSTEMI ACS treated with all the current evidenced-based therapies still has significant recurrent events. MRC ILA-HEART is the first study to evaluate the effects of the anti-inflammatory IL-1ra in ACS. The data indicates that despite encouraging pre-clinical evidence, the inflammatory driver for NSTEMI-ACS is not IL-1 mediated.
Chemistry and biochemistry of chinese drugs. VII. Cytostatic pheophytins from silkworm excreta, and derived photocytotoxic pheophorbides. (1981)

Four chlorophyll derivatives (pheophytins) were isolated from silkworm excreta by column and thin-layer chromatography and their structures were elucidated by spectroscopy. Among them, two substances, 132-hydroxy (132-R, S) pheophytin a and pheophytin b, have in vitro cytostatic activity against hepatoma tissue culture (HTC) cells. The methyl ester derivatives of pheophorbides showed cytotoxic effects towards the tumor cells under illumination. This can be explained by photodynamic destruction of HTC cells by singlet oxygen, as has already been shown in the case of hematoporphyrin. The observation that natural pheophytins have cytostatic effects even in the dark suggests that there is another biological mechanism for the action of these chlorophyll derivatives.
Oxygen Vacancy Enhanced Photocatalytic Activity of Pervoskite SrTiO3 (2014)

A facile and general method has been developed to fabricate oxygen vacancies on perovskite SrTiO3 (STO) nanocrystals through a controllable solid-state reaction of NaBH4 and SrTiO3 nanocrystals. STO samples with tunable color, oxygen vacancy concentration on nanocrystal surface have been synthesized. TEM results reveal that these STO samples have a crystalline core/amorphous shell structure (SrTiO3@SrTiO3–x). XPS and EPR results disclose that the oxygen vacancy concentration increases with the increase of reaction time and temperature. The concentration of oxygen vacancies calculated from TGA data, could reach 5.07% (atom) in this study. UV–vis spectra and photocatalytic results indicate that oxygen vacancies on STO surface play an important role in influencing the light absorption and photocatalytic performance. However, an excess amount of oxygen vacancies leads to a decrease of photocatalytic performance. The optimal photocatalytic activity for H2 production under UV–vis irradiation is up to 2.2 mmol h–1 g–1, which is about 2.3 times than the original SrTiO3, corresponding to 3.28% (atom) of oxygen vacancy concentration.
Nonparaxial elegant Laguerre-Gaussian beams (2008)

Closed-form nonparaxial expressions for optical beams are useful to calculate the fields produced by tightly focused laser beams. Such expressions for elegant Laguerre-Gaussian (eLG) beams that are exact solutions of the Helmholtz equation are introduced. These solutions are expressed as linear combinations of a finite number of analytic functions that involve spherical Bessel functions and associated Legendre functions of complex arguments. In the paraxial limit, the expressions proposed have the property to reduce to the well-known eLG beams.
Activation of Metabotropic Glutamate Receptor 5 Has Direct Excitatory Effects and Potentiates NMDA Receptor Currents in Neurons of the Subthalamic Nucleus (2000)

The subthalamic nucleus (STN) is a key nucleus in the basal ganglia motor circuit that provides the major glutamatergic excitatory input to the basal ganglia output nuclei. The STN plays an important role in normal motor function, as well as in pathological conditions such as Parkinson's disease (PD) and related disorders. Development of a complete understanding of the roles of the STN in motor control and the pathophysiological changes in STN that underlie PD will require a detailed understanding of the mechanisms involved in regulation of excitability of STN neurons. Here, we report that activation of group I metabotropic glutamate receptors (mGluRs) induces a direct excitation of STN neurons that is characterized by depolarization, increased firing frequency, and increased burst-firing activity. In addition, activation of group I mGluRs induces a selective potentiation of NMDA-evoked currents. Immunohistochemical studies at the light and electron microscopic levels indicate that both subtypes of group I mGluRs (mGluR1a and mGluR5) are localized postsynaptically in the dendrites of STN neurons. Interestingly, pharmacological studies suggest that each of the mGluR-mediated effects is attributable to activation of mGluR5, not mGluR1, despite the presence of both subtypes in STN neurons. These results suggest that mGluR5 may play an important role in the net excitatory drive to the STN from glutamatergic afferents. Furthermore, these studies raise the exciting possibility that selective ligands for mGluR5 may provide a novel approach for the treatment of a variety of movement disorders that involve changes in STN activity.
An Adaptive Quadrilateral Mesh in Curved Domains (2009)

An nonlinear elliptic system for generating adaptive quadrilateral meshes in curved domains is presented. The presented technique has been implemented in the C++ language with the help of the standard template library. The software package writes the converged meshes in the GMV and the Matlab formats. Grid generation is the first very important step for numerically solving partial differential equations. Thus, the presented C++ grid generator is extremely important to the computational science community.
Novel Mutations Detected in the TSC2 Hene From Both Sporadic and Familial TSC Patients (1996)

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by hamartomas in one or more organs, including the brain, skin, heart and kidneys. Linkage studies have shown locus heterogeneity with one TSC gene mapped to chromosome 9q34 and a second to 16p13.3. The gene on 16p13.3, TSC2, has been cloned and shown to encode a 5.5 kb transcript that is widely expressed. To facilitate the search for mutations in the TSC2 gene product, tuberin, we have designed an RT-PCR-based assay system to scan the expressed coding region of the TSC2 gene in lymphoblasts. Using 34 overlapping PCR assays we performed single-strand conformation polymorphism analysis of DNA from 26 apparently sporadic TSC cases, two TSC families non-informative for linkage analysis and two confirmed chromosome 16-linked TSC families. Of the 60 chromosomes scanned, 14 showed abnormal SSCP mobility shifts. Using direct PCR sequencing we have identified five missense mutations, one 3 bp in-frame deletion and one 2 bp frameshift deletion, one nonsense mutation, one 29 bp tandem duplication and five silent nucleotide changes that are likely to be polymorphisms. There is no apparent clustering of mutations within TSC2. The diversity of mutation types argues that TSC2 may not act in a classic tumor suppressor fashion. In addition, we saw no specific correlation between the different mutations and clinical severity or expression. These data confirm that TSC2 is indeed the relevant gene, and that a substantial number of sporadic cases arise from mutations in the TSC2 gene.
Bovine Parainfluenza Virus Type 3 (BPIV3) Fusion and Hemagglutinin-Neuraminidase Glycoproteins Make an Important Contribution to the Restricted Replication of BPIV3 in Primates (2000)

This study examines the contribution of the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein genes of bovine parainfluenza virus type 3 (BPIV3) to its restricted replication in the respiratory tract of nonhuman primates. A chimeric recombinant human parainfluenza type 3 virus (HPIV3) containing BPIV3 F and HN glycoprotein genes in place of its own and the reciprocal recombinant consisting of BPIV3 bearing the HPIV3 F and HN genes (rBPIV3-F(H)HN(H)) were generated to assess the effect of glycoprotein substitution on replication of HPIV3 and BPIV3 in the upper and lower respiratory tract of rhesus monkeys. The chimeric viruses were readily recovered and replicated in simian LLC-MK2 cells to a level comparable to that of their parental viruses, suggesting that the heterologous glycoproteins were compatible with the PIV3 internal proteins. HPIV3 bearing the BPIV3 F and HN genes was restricted in replication in rhesus monkeys to a level similar to that of its BPIV3 parent virus, indicating that the glycoprotein genes of BPIV3 are major determinants of its host range restriction of replication in rhesus monkeys. rBPIV3-F(H)HN(H) replicated in rhesus monkeys to a level intermediate between that of HPIV3 and BPIV3. This observation indicates that the F and HN genes make a significant contribution to the overall attenuation of BPIV3 for rhesus monkeys. Furthermore, it shows that BPIV3 sequences outside the F and HN region also contribute to the attenuation phenotype in primates, a finding consistent with the previous demonstration that the nucleoprotein coding sequence of BPIV3 is a determinant of its attenuation for primates. Despite its restricted replication in the respiratory tract of rhesus monkeys, rBPIV3-F(H)HN(H) conferred a level of protection against challenge with HPIV3 that was indistinguishable from that induced by previous infection with wild-type HPIV3. The usefulness of rBPIV3-F(H)HN(H) as a vaccine candidate against HPIV3 and as a vector for other viral antigens is discussed.
Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth. (1990)

Mechanisms involved in the development or the regression of myocardial hypertrophy cannot be fully explained as responses to blood pressure control alone. We had hypothesized that the development of hypertrophy is initiated by a signal (mechanical or humoral) to the myocardium, which in turn produces a soluble factor that triggers protein synthesis and initiates myocardial growth. Using the stimulation of protein synthesis in isolated cardiac myocytes obtained from normal rat hearts as an assay system, we have identified a soluble factor from the hypertrophied myocardium of spontaneously hypertensive rats. This factor, which has been purified to apparent homogeneity, is a protein of 12 kDa. The sequence of three internally liberated peptides containing 7-24 residues was determined. Based on the determined amino acid sequences of these peptides, this factor (designated myotrophin) appears to be a novel protein that shows no homology with any previously described growth factors. Myotrophin is present in human, dog, and rat hypertrophied hearts (28-35% stimulation of protein synthesis over control) and in small amounts in normal hearts (5-6% stimulation). Myotrophin causes two dose-dependent effects in neonatal cardiac myocytes: an increase in the surface area of the myocyte and the appearance of organized myofibrils, which become apparent within 48 h. Myotrophin may play an important role in the pathogenesis of cardiac hypertrophy as well as in the normal development of cardiac myocytes.
Orthostatic Hypotension Associated With Hypothyroidism (1984)

SummaryWe report the case of a 65-year-old woman with highly symptomatic orthostatic hypotension associated with primary hypothyroidism. This orthostatic hypotension was caused by an autonomic dysfunction with a loss of integrity of the baroreceptor reflex arc and proved to be quite reversible with thyroid hormone replacement. We are unaware of such a clinical feature of hypothyroid autonomic neuropathy and suggest that hypothyroidism should be considered as an additional cause of orthostatic hypotension.
Mechanical resonant immunospecific biological detector (2000)

We have demonstrated high-sensitivity detection of bacteria using an array of bulk micromachined resonant cantilevers. The biological sensor is a micromechanical oscillator that consists of an array of silicon-nitride cantilevers with an immobilized antibody layer on the surface of the resonator. Measured resonant frequency shift as a function of the additional cell loading was observed and correlated to the mass of the specifically bound Escherichia coli O157:H7 cells. Deposition and subsequent detection of E. coli cells was achieved under ambient conditions.
Synthesis and Application of Unprotected Cyclic Peptides as Building Blocks for Peptide Dendrimers (1997)

We describe an efficient regiospecific method for cyclization of unprotected peptide segments based on intramolecular transthioesterification of unprotected cysteinyl peptide thioesters under the control of ring−chain tautomeric equilibrium in aqueous buffered solutions at pH ranging from 5 to 7.5. The initial cyclization to form an intramolecular thioester under the ring−chain tautomeric equilibrium is reversible and could be performed in relatively high concentrations without observable oligomerization. This method overcomes the limitation of conventional cyclization methods that require high dilutions. The reaction becomes irreversible by a subsequent, spontaneous proximity-driven S- to N-acyl transfer to the adjacent Nα-amine of cysteine to form an end-to-end cyclic peptide. The cyclization is regioselective. No side reactions were observed with side-chain functionalities such as the Nε-amine of lysine, thiol of internal cysteine, or imidazole of histidine. Since a free thiol group was introduced to the product after cyclization, these cyclic peptides were exploited as building blocks for synthesizing peptides with unusual architectures such as bicyclic peptides containing end-to-end backbones and disulfide bridges as well as cascade branched peptide dendrimers.
No Grouping Left Behind: From Edges to Curve Fragments (2007)

We present a framework for extracting image contours based on geometric and structural consistency among edge element locations and orientations. The paper presents two contributions. First, we observe that while the traditional edge orientation operators are based on first-order derivatives, orientation as tangent of a localized curve requires third-order derivatives. We derive a numerically stable third-order edge operator and show that it outperforms current techniques. Second, we consider all discrete n-tuples of edges in a local neighborhood (7times7) and retain those that are geometrically consistent with a third-order local curve model. This results in a number of ordered discrete combinations of edges, each represented by a bundle of curves. The resulting curve bundle map is a representation of all possible local groupings from which longer contour fragments are constructed. We validate our results and show that our framework outperforms traditional approaches to contour extraction.
[Treatment with statins of the elderly]. (2004)

Previous studies of treatment with statins have included few subjects aged 70 years or above. While the absolute risk of cardiovascular disease in the elderly is very high, the benefits of treatment may be reduced by adverse events, polypharmacy and competing risks.A statistician and a clinician reviewed the Pravastatin in elderly individuals at risk of vascular disease (PROSPER) study and compared the results with subgroup analyses of previous studies.Subgroup analyses of previous studies showed that treatment with statins reduces cardiovascular events among patients with coronary heart disease aged > or = 65 years. The Heart Protection Study (HPS) included elderly with known atherosclerotic disease, while only 44% of subjects in the PROSPER study had such disease. Among subjects aged 70 or above the difference in events between the groups that received a statin or placebo was 6.1% in the HPS study and 2.1% in the PROSPER study (numbers needed to treat were 6 and 48, respectively). The studies gave conflicting results with regard to stroke and cancer.Elderly people with cardiovascular disease may benefit from treatment with statins. We do not have data that show that statins reduce total mortality among the elderly.
The prevalence of dust on the exoplanet HD 189733b from Hubble and Spitzer observations (2013)

The hot Jupiter HD 189733b is the most extensively observed exoplanet. Its atmosphere has been detected and characterized in transmission and eclipse spectroscopy, and its phase curve measured at several wavelengths. This paper brings together the results of our campaign to obtain the complete transmission spectrum of the atmosphere of this planet from UV to infrared with the Hubble Space Telescope, using the STIS, ACS and WFC3 instruments. We provide a new tabulation of the transmission spectrum across the entire visible and infrared range. The radius ratio in each wavelength band was re-derived, where necessary, to ensure a consistent treatment of the bulk transit parameters and stellar limb darkening. Special care was taken to correct for, and derive realistic estimates of the uncertainties due to, both occulted and unocculted star spots.