gebhart/patrepeval huggingface dataset:
Natural and engineered nicking endonucleases--from cleavage mechanism to engineering of strand-specificity (2010)

Restriction endonucleases (REases) are highly specific DNA scissors that have facilitated the development of modern molecular biology. Intensive studies of double strand (ds) cleavage activity of Type IIP REases, which recognize 4-8 bp palindromic sequences, have revealed a variety of mechanisms of molecular recognition and catalysis. Less well-studied are REases which cleave only one of the strands of dsDNA, creating a nick instead of a ds break. Naturally occurring nicking endonucleases (NEases) range from frequent cutters such as Nt.CviPII (^CCD; ^ denotes the cleavage site) to rare-cutting homing endonucleases (HEases) such as I-HmuI. In addition to these bona fida NEases, individual subunits of some heterodimeric Type IIS REases have recently been shown to be natural NEases. The discovery and characterization of more REases that recognize asymmetric sequences, particularly Types IIS and IIA REases, has revealed recognition and cleavage mechanisms drastically different from the canonical Type IIP mechanisms, and has allowed researchers to engineer highly strand-specific NEases. Monomeric LAGLIDADG HEases use two separate catalytic sites for cleavage. Exploitation of this characteristic has also resulted in useful nicking HEases. This review aims at providing an overview of the cleavage mechanisms of Types IIS and IIA REases and LAGLIDADG HEases, the engineering of their nicking variants, and the applications of NEases and nicking HEases.
Inhibitors of acyl-CoA:cholesterol acyltransferase. 4. A novel series of urea ACAT inhibitors as potential hypocholesterolemic agents (1993)

We have synthesized a series of N-phenyl-N'-aralkyl and N-phenyl-N'-(1-phenylcycloalkyl)ureas as inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). This intracellular enzyme is thought to be responsible for the esterification of dietary cholesterol; hence inhibition of this enzyme could reduce diet-induced hypercholesterolemia. For this series of compounds, the in vitro ACAT inhibitory activity was improved by increasing the bulk of the 2,6-substituents on the phenyl ring. Additionally, we found that spacing of the aromatic rings was critical for ACAT inhibitory activity. A phenyl ring five atoms away from the requisite 2,6-diisopropylphenyl moiety was optimal for in vitro activity. Substitution alpha to the N'-phenyl moiety enhanced in vitro potency. In the case of phenylcycloalkyl ureas, ACAT inhibitory activity was independent of the size of the cycloalkyl ring. From this series of analogs, compound 25, which had excellent in vitro potency for inhibiting ACAT, was found to lower plasma cholesterol by 73% in vivo when administered in the diet at 50 mg/kg in an animal model of hypercholesterolemia. In this model, compound 25 lowered plasma cholesterol dose dependently and was as efficacious as the Lederle ACAT inhibitor CL 277082.
Polytetrafluoroethylene decomposition in air and nitrogen (2001)

Abstract The kinetics of the thermal decomposition of polytetrafluoroethylene (PTFE) have been studied using dynamic TG‐DTG at heating rates between 1 and 25°C/min at atmospheric pressure. Two different atmospheres were used: on the one hand, an inert atmosphere (N 2 )in order to study the pyrolysis of the material, and on the other hand an oxidative atmosphere (synthetic air) to study the combustion of the polymer. The same kinetic model has been applied simultaneously to runs performed at different heating rates and different atmospheres allowing a good correlation of the weight loss data. The kinetic model considers that the overall decomposition of the PTFE is done via two different parallel processes. Dynamic measurements were performed by combined thermogravimetry mass spectrometry (TG‐MS) in order to determine the decomposition products. The evolution of 2 F 4 , CF 4 , COF 2 , HF, hydrocarbons, benzene and some other compounds has been also analyzed.
Stereospecific presynaptic inhibitory effect of Δ<sup>9</sup>-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig (1978)

delta9-Tetrahydrocannabinol (THC) is very lipid soluble, as are many anesthetic agents. The action of anesthetics is nonspecific; isomers are equieffective. THC is optically active; therefore, the effects of its stereoisomers were studied on the electrically and chemically stimulated longitudinal muscle strip of guinea pig ileum. The results demonstrate that both isomers depress the response to electrical stimulation in a dose-related manner. The maximum effect is gradually reached in approximately 20 min. The (-) isomer is 24.6-fold more active than the (+) isomer (ED50 for (-) THC is 1.25 X 10(-7) M, for (+) THC, 3.08 X 10(-6) M) and the site of action appears to be presynaptic because responses to ACh are not significantly depressed. The depressant effects are relatively nonreversible. Membrane concentrations calculated at the ED50 values for the (-) isomer are of the order of 0.5 mM/kg dry membrane, well within the range for anesthesia. Thus THC may be regarded as a partial anesthetic since some of its actions are similar to those of the classical anesthetics, yet it possesses selective action at the neuronal membrane or tissue level.
Thermal conductivity of individual silicon nanowires (2003)

The thermal conductivities of individual single crystalline intrinsic Si nanowires with diameters of 22, 37, 56, and 115 nm were measured using a microfabricated suspended device over a temperature range of 20–320 K. Although the nanowires had well-defined crystalline order, the thermal conductivity observed was more than two orders of magnitude lower than the bulk value. The strong diameter dependence of thermal conductivity in nanowires was ascribed to the increased phonon-boundary scattering and possible phonon spectrum modification.
The GOES-R Advanced Baseline Imager and the Continuation of Current Sounder Products (2008)

Abstract The first of the next-generation series of Geostationary Operational Environmental Satellites (GOES-R) is scheduled for launch in the 2015 time frame. One of the primary instruments on GOES-R, the Advanced Baseline Imager (ABI), will offer more spectral bands, higher spatial resolution, and faster imaging than does the current GOES Imager. Measurements from the ABI will be used for a wide range of qualitative and quantitative weather, land, ocean, cryosphere, environmental, and climate applications. However, the first and, likely, the second of the new series of GOES will not carry an infrared sounder dedicated to acquiring high-vertical-resolution atmospheric temperature and humidity profiles that are key to mesoscale and regional severe-weather forecasting. The ABI will provide some continuity of the current sounder products to bridge the gap until the advent of the GOES advanced infrared sounder. Both theoretical analysis and retrieval simulations show that data from the ABI can be combined with temperature and moisture information from forecast models to produce derived products that will be adequate substitutes for the legacy products from the current GOES sounders. Products generated from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) measurements also demonstrate the utility of those legacy products for nowcasting applications. However, because of very coarse vertical resolution and limited accuracy in the legacy sounding products, placing a hyperspectral-resolution infrared sounder with high temporal resolution on future GOES is an essential step toward realizing substantial improvements in mesoscale and severe-weather forecasting required by the user communities.
Physics of Friction (2003)

Recent progress in the physical research of friction is reviewed. We discuss some mechanisms proposal for Amonton and Coulomb's law that is applied well in various systems. The energy dissipation process associated with dynamical friction is also discussed. New experimental techniques that aim to observe the sliding interfaces between solid surfaces and lubricants are introduced.
Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis (2010)

Heparanase enhances shedding of syndecan-1 (CD138), and high levels of heparanase and shed syndecan-1 in the tumor microenvironment are associated with elevated angiogenesis and poor prognosis in myeloma and other cancers. To explore how the heparanase/syndecan-1 axis regulates angiogenesis, we used myeloma cells expressing either high or low levels of heparanase and examined their impact on endothelial cell invasion and angiogenesis. Medium conditioned by heparanase-high cells significantly stimulated endothelial invasion in vitro compared with medium from heparanase-low cells. The stimulatory activity was traced to elevated levels of vascular endothelial growth factor (VEGF) and syndecan-1 in the medium. We discovered that the heparan sulfate chains of syndecan-1 captured VEGF and also attached the syndecan-1/VEGF complex to the extracellular matrix where it then stimulated endothelial invasion. In addition to its heparan sulfate chains, the core protein of syndecan-1 was also required because endothelial invasion was blocked by addition of synstatin, a peptide mimic of the integrin activating region present on the syndecan-1 core protein. These results reveal a novel mechanistic pathway driven by heparanase expression in myeloma cells whereby elevated levels of VEGF and shed syndecan-1 form matrix-anchored complexes that together activate integrin and VEGF receptors on adjacent endothelial cells thereby stimulating tumor angiogenesis.
Highly selective water and fat imaging applying multislice sequences without sensitivity to <i>B</i><sub>1</sub> field inhomogeneities (1997)

Improved selectivity to one chemical shift component was obtained using simultaneous slice-selective and chemical shift-selective excitation in sequences with usual spin-echo refocusing. The new type of sequences can be applied on modern whole-body units and permits multislice operation. Spatial-spectral excitation is based on prior research in this field, but the proposed improved version provides off-center slice excitation by the usual processing of the RF pulse envelopes. In addition, no irregular gradient shapes are necessary. The required B0 homogeneity of the new method is similar to conventional "fat-sat" techniques. In contrast to fat-sat methods, selectivity to water is not reduced by unavoidable misadjustments of the transmitter or B1 field inhomogeneities in the newly developed approach. Thus, the reported method has the potential to replace standard frequency selective fat-sat sequences for most applications.
Evidence for damage-dependent hygienic behaviour towards <i>Varroa destructor</i>-parasitised brood in the western honey bee, <i>Apis mellifera</i> (2011)

The ectoparasitic mite Varroa destructor and honey bee pathogenic viruses have been implicated in the recent demise of honey bee colonies. Several studies have shown that the combination of V. destructor and deformed wing virus (DWV) poses an especially serious threat to honey bee health. Mites transmitting virulent forms of DWV may cause fatal DWV infections in the developing bee, while pupae parasitised by mites not inducing or activating overt DWV infections may develop normally. Adult bees respond to brood diseases by removing affected brood. This hygienic behaviour is an essential part of the bees' immune response repertoire and is also shown towards mite-parasitised brood. However, it is still unclear whether the bees react towards the mite in the brood cell or rather towards the damage done to the brood. We hypothesised that the extent of mite-associated damage rather than the mere presence of parasitising mites triggers hygienic behaviour. Hygienic behaviour assays performed with mites differing in their potential to transmit overt DWV infections revealed that brood parasitised by 'virulent' mites (i.e. mites with a high potential to induce fatal DWV infections in parasitised pupae) were removed significantly more often than brood parasitised by 'less virulent' mites (i.e. mites with a very low potential to induce overt DWV infections) or non-parasitised brood. Chemical analyses of brood odour profiles suggested that the bees recognise severely affected brood by olfactory cues. Our results suggest that bees show selective, damage-dependent hygienic behaviour, which may be an economic way for colonies to cope with mite infestation.
[Myoclonic encephalopathy caused by bismuth salts. Efficacy of treatment with dimercaprol]. (1989)

Three patients with myoclonic encephalopathy caused by bismuth salts are reported, one with the severe and another with the mild form; dimercaprol was effective for the rapid improvement of the symptoms in both. In one of the patients in whom the clearance of bismuth was calculated it was found to be increased after dimercaprol therapy. We think that dimercaprol is an effective drug for the therapy of myoclonic encephalopathy caused by bismuth salts.
Classification of human senile cataractous changes by the American Cooperative Cataract Research Group (CCRG) method. I. Instrumentation and technique. (1983)

The American Cooperative Cataract Research Group (CCRG) has adopted a system of classifying human cataractous changes that is based on separate and independent photographic documentation of opacification and nuclear color. This system has been extremely useful to the laboratory scientist who wishes to know the significance of associations between laboratory data and the extent or type of cataractous change. It has been applied to the analysis of nearly 2500 cataracts since 1976. This study presents the details of the instrumentation and technique of this new system and the results of classifying 2231 intracapsularly-extracted cataracts.
Prediction of lung cancer using volatile biomarkers in breath1 (2007)

A two-minute breath test predicted lung cancer with accuracy comparable to screening CT of chest. The accuracy of the test was not affected by TNM stage of disease or tobacco smoking. Alterations in breath VOCs in lung cancer were consistent with a non-linear pathophysiologic process, such as an off-on switch controlling high-risk cytochrome p450 activity. Further research is needed to determine if detection of lung cancer with this test will reduce mortality.
Microarchitectural simulation and control of di/dt-induced power supply voltage variation (2004)

As the power consumption of modern high-performance microprocessors increases beyond 100 W, power becomes an increasingly important design consideration. This paper presents a novel technique to simulate power supply voltage variation as a result of varying activity levels within the microprocessor when executing typical software. The voltage simulation capability may be added to existing microarchitecture simulators that determine the activities of each functional block on a clock-by-clock basis. We then discuss how the same technique can be implemented in logic on the microprocessor die to enable real-time computation of current consumption and power supply voltage. When used in a feedback loop, this logic makes it possible to control the microprocessor's activities to reduce demands on the power delivery system. With on-die voltage computation and di/dt control, we show that a significant reduction in power supply voltage variation may be achieved with little performance loss or average power increase.
Elevated Frequency of Diabetes Mellitus in Hospitalized Manic-Depressive Patients (1999)

The frequency of diabetes mellitus in hospitalized patients diagnosed with bipolar disorder is higher than in the general population. Manic-depressive patients with diabetes mellitus have a more severe course of illness, as indicated by a greater number of psychiatric hospitalizations. Possible reasons for this increased comorbidity include a genetic relationship between the disorders, a causal relationship in which hypercortisolemia induces diabetes or diabetic vascular lesions contribute to mania, an overlapping functional disturbance affecting similar regions of the brain, or the effect of psychotropic medications.
A variational eigenvalue solver on a photonic quantum processor (2014)

Quantum computers promise to efficiently solve important problems that are intractable on a conventional computer. For quantum systems, where the physical dimension grows exponentially, finding the eigenvalues of certain operators is one such intractable problem and remains a fundamental challenge. The quantum phase estimation algorithm efficiently finds the eigenvalue of a given eigenvector but requires fully coherent evolution. Here we present an alternative approach that greatly reduces the requirements for coherent evolution and combine this method with a new approach to state preparation based on ansätze and classical optimization. We implement the algorithm by combining a highly reconfigurable photonic quantum processor with a conventional computer. We experimentally demonstrate the feasibility of this approach with an example from quantum chemistry--calculating the ground-state molecular energy for He-H(+). The proposed approach drastically reduces the coherence time requirements, enhancing the potential of quantum resources available today and in the near future.
Sequencing the unsequenceable: Expanded CGG-repeat alleles of the fragile X gene (2012)

The human fragile X mental retardation 1 (FMR1) gene contains a (CGG)(n) trinucleotide repeat in its 5' untranslated region (5'UTR). Expansions of this repeat result in a number of clinical disorders with distinct molecular pathologies, including fragile X syndrome (FXS; full mutation range, greater than 200 CGG repeats) and fragile X-associated tremor/ataxia syndrome (FXTAS; premutation range, 55-200 repeats). Study of these diseases has been limited by an inability to sequence expanded CGG repeats, particularly in the full mutation range, with existing DNA sequencing technologies. Single-molecule, real-time (SMRT) sequencing provides an approach to sequencing that is fundamentally different from other "next-generation" sequencing platforms, and is well suited for long, repetitive DNA sequences. We report the first sequence data for expanded CGG-repeat FMR1 alleles in the full mutation range that reveal the confounding effects of CGG-repeat tracts on both cloning and PCR. A unique feature of SMRT sequencing is its ability to yield real-time information on the rates of nucleoside addition by the tethered DNA polymerase; for the CGG-repeat alleles, we find a strand-specific effect of CGG-repeat DNA on the interpulse distance. This kinetic signature reveals a novel aspect of the repeat element; namely, that the particular G bias within the CGG/CCG-repeat element influences polymerase activity in a manner that extends beyond simple nearest-neighbor effects. These observations provide a baseline for future kinetic studies of repeat elements, as well as for studies of epigenetic and other chemical modifications thereof.
A three-dimensional mesh multiprocessor system using board-to-board free-space optical interconnects: COSINE-III (2002)

A prototype multiprocessor system using board-to-board free-space optical interconnects distributed over the processor boards is constructed for the first time. The system consists of 64 processing units interconnected in a three-dimensional (3D) mesh network with the help of bi-directional free-space optical interconnects. Theoretical analysis of signal delay and wiring congestion characteristics in the 3-D mesh network using free-space optical interconnects concludes that the network is superior to that using a conventional backplane interconnects. In the prototype system, signal transmission of all 96 free-space optical interconnects is stable even after repeated extraction and insertion of the processor boards, and system operation without error for 100 h is performed. The system is also shown to be easy to extend to a larger and more flexible system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Individual Fragrance and Flavor Materials (2006)

This chapter contains sections titled: Aliphatic Compounds Hydrocarbons Alcohols Aldehydes and Acetals Ketones Acids and Esters Miscellaneous Compounds Acyclic Terpenes Hydrocarbons Alcohols Aldehydes and Acetals Ketones Acids and Esters Miscellaneous Compounds Cyclic Terpenes Hydrocarbons Alcohols and Ethers Aldehydes and Ketones Esters Miscellaneous Compounds Other Cycloaliphatic Compounds Alcohols and Ethers Aldehydes Ketones Esters Miscellaneous Compounds Aromatic Compounds Hydrocarbons Alcohols and Ethers Aldehydes and Acetals Ketones Esters of Araliphatic Alcohols and Aliphatic Acids Aromatic Acids Esters Derived from Aromatic and Araliphatic Acids Miscellaneous Compounds Phenols and Phenol Derivatives Phenols, Phenyl Esters, and Phenyl Ethers Phenol Alcohols and their Esters Phenol Aldehydes Phenol Ketones Phenolcarboxylates O-, O,S- and S,S-Heterocycles Cyclic Ethers Lactones Glycidates Miscellaneous Compounds N- and N,S-Heterocycles
Epidermal growth factor labeled .beta.-amanitin-poly-L-ornithine: preparation and evidence for specific cytotoxicity (1990)

Poly-L-ornithine with an average molecular weight of 32K was reacted with beta-amanitin hydroxysuccinimide ester to form an amide-linked toxin conjugate. Loading of the polymeric chain with amanitin was high, corresponding to up to 35% of the total weight. To this amatoxin vehicle we attached a targeting molecule, human recombinant leucine-21 epidermal growth factor (hrEGFL), via a disulfide-containing linker moiety. A typical average stoichiometry of the hrEGFL labeled toxin conjugate was (L-Orn)164(beta-amanitin)19(COC2H4SSC2H4CO-hrEGFL)2. The affinity for EGF receptors of hrEGFL bound in this conjugate was tested by using A 431 cells. The affinity was eight times lower than that of unsubstituted hrEGFL but regarded as high enough for studying specific toxicity effects with cells bearing EGF receptors. We found that beta-amanitin in the labeled conjugate was able to inhibit the growth of A 431 cells at a concentration of 28 nM, 80 times lower than for native beta-amanitin and 20 times lower than for poly-L-ornithine-bound beta-amanitin without the hrEGFL label. The approximately 20-fold enhancement of cytotoxicity suggests a specific internalization of the toxin conjugate mediated by the hormone label. This idea is supported by the fact that also in another transformed fibroblast cell line, with an increased though smaller number of EGF receptors than A 431 cells, the corresponding enhancement of cytotoxicity was demonstrable but less pronounced (7-fold). The hormone-mediated increase in cytotoxicity of EGF labeled poly-L-ornithine-beta-amanitin conjugates, combined with their moderate toxicity in the mouse, encourages further examination of such compounds in tumor model systems in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Secondary electrospray ionization (SESI) of ambient vapors for explosive detection at concentrations below parts per trillion (2008)

We determine the sensitivity of several commercial atmospheric pressure ionization mass spectrometers towards ambient vapors, ionized by contact with an electrospray of acidified or ammoniated solvent, a technique often referred to as secondary electrospray ionization (SESI). Although a record limit of detection of 0.2 x 10(-12) atmospheres (0.2 ppt) is found for explosives such as PETN and 0.4 ppt for TNT (without preconcentration), this still implies the need for some 10(8)-10(9) vapor molecules/s for positive identification of explosives. This extremely inefficient use of sample is partly due to low charging probability ( approximately 10(-4)), finite ion transmission, and counting probability in the mass spectrometer (1/10 in quadrupoles), and a variable combination of duty cycle and background noise responsible typically for a 10(3) factor loss of useful signal.