gebhart/patrepeval huggingface dataset:
Purification, Characterization, and Potential Bacterial Wax Production Role of an NADPH-Dependent Fatty Aldehyde Reductase from Marinobacter aquaeolei VT8 (2009)

Wax esters, ester-linked fatty acids and long-chain alcohols, are important energy storage compounds in select bacteria. The synthesis of wax esters from fatty acids is proposed to require the action of a four-enzyme pathway. An essential step in the pathway is the reduction of a fatty aldehyde to the corresponding fatty alcohol, although the enzyme responsible for catalyzing this reaction has yet to be identified in bacteria. We report here the purification and characterization of an enzyme from the wax ester-accumulating bacterium Marinobacter aquaeolei VT8, which is a proposed fatty aldehyde reductase in this pathway. The enzyme, a 57-kDa monomer, was expressed in Escherichia coli as a fusion protein with the maltose binding protein on the N terminus and was purified to near homogeneity by using amylose affinity chromatography. The purified enzyme was found to reduce a number of long-chain aldehydes to the corresponding alcohols coupled to the oxidation of NADPH. The highest specific activity was observed for the reduction of decanal (85 nmol decanal reduced/min/mg). Short-chain and aromatic aldehydes were not substrates. The enzyme showed no detectable catalysis of the reverse reaction, the oxidation of decanol by NADP(+). The mechanism of the enzyme was probed with several site-specific chemical probes. The possible uses of this enzyme in the production of wax esters are discussed.
A physiological study on acetylcholine receptor expressed in Xenopus oocytes from cloned cDNAs. (1985)

Nicotinic ACh receptor was expressed in Xenopus oocytes by injecting mRNAs produced from cloned cDNAs encoding the four subunits of ACh receptor of Torpedo californica. ACh responses recorded from oocytes 3 days after injection of the mRNAs were reversibly blocked by d-tubocurarine (1-2 microM), indicating that the newly synthesized receptor is of nicotinic type. The reversal potential of ACh response was found at around -1 - -5 mV. The reversal potential was not changed by removal of extracellular C1-, suggesting that the ionic channel of the newly expressed ACh receptor is permeable only to cations. Repetitive applications of ACh caused desensitization of the receptor. The rate of the desensitization was greater when the membrane potential was more negative. Subunit deletion studies showed that all four subunits are required for the formation of ACh receptors with normal ACh sensitivity. However, ACh receptors without delta subunit responded to ACh with low sensitivity. Studies on ACh receptor mutants with -subunits altered by site directed mutagenesis of the cDNA suggest that the anphipathic segment is involved in the channel function of the receptor as well as the four hydrophobic segments since partial deletion of amino acids in these segments essentially abolished ACh sensitivity with relatively little change in 125I-alpha-bungarotoxin binding activity.
Regression Analysis of Multivariate Incomplete Failure Time Data by Modeling Marginal Distributions (1989)

Abstract Many survival studies record the times to two or more distinct failures on each subject. The failures may be events of different natures or may be repetitions of the same kind of event. In this article, we consider the regression analysis of such multivariate failure time observations. Each marginal distribution of the failure times is formulated by a Cox proportional hazards model. No specific structure of dependence among the distinct failure times on each subject is imposed. The regression parameters in the Cox models are estimated by maximizing the failure-specific partial likelihoods. The resulting estimators are shown to be asymptotically jointly normal with a covariance matrix that can be consistently estimated. Simultaneous inferential procedures are then proposed. Extensive Monte Carlo studies indicate that the normal approximation is adequate for practical use. The new methods allow time-dependent covariates, missing observations, and arbitrary patterns of censorship. They are illustrated with two real-life examples. For recurrent failure time data, various regression methods have been proposed in the literature. These methods, however, generally assume stringent structures of dependence among the recurrences of each subject. Moreover, as shown in the present article, they are rather sensitive to model misspecification.
Preoptic/anterior hypothalamic neurons: thermosensitivity in rapid eye movement sleep (1995)

The thermosensitivity of 15 warm-sensitive neurons (WSNs) and 19 cold-sensitive neurons (CSNs) from the medial preoptic/anterior hypothalamus (POAH) was tested during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by local POAH warming and cooling in freely moving cats. Thermosensitivity was quantified by three criteria, Q10, impulses per second per degree Celsius, and percent change per degree Celsius. Irrespective of the criterion used, WSNs did not exhibit a significant change in thermosensitivity during REM sleep compared with wakefulness and NREM sleep. In contrast, CSNs exhibited decreased mean thermosensitivity during REM sleep compared with wakefulness. CSNs as a group did not retain significant thermosensitivity in REM sleep. These findings are consistent with evidence that thermoeffector responses to cooling are lost in REM sleep, whereas some responses to warming are preserved.
Mouse strain differences in autonomic responses to stress (2005)

In humans, anxiety disorders are often accompanied by an overactive autonomic nervous system, reflected in increased body temperature (BT) and heart rate (HR). In rodents, comparable effects are found after exposure to stress. These autonomic parameters can give important information on stress and anxiety responses in mice. In the present experiments, stress reactivity of three frequently used mouse strains [129 Sv/Ev, Swiss Webster (SW) and C57 BL/6] was assessed using their autonomic stress responses. BT, HR and activity were telemetrically measured. Undisturbed circadian rhythms already showed clear differences between the mouse strains. Hereafter, autonomic responses to stressors with increasing intensity were measured. Strain differences were found in magnitude and duration of the stress responses, especially after high-intensity stressors. Generally, C57BL/6 mice showed the largest autonomic response, SW the lowest and the 129Sv/Ev the intermediate response. Interestingly, the observed ranking in autonomic stress response does not match the behavioral stress responsivity of these strains. Finally, sensitivity to the anxiolytic diazepam (0, 1, 2, 4 and 8 mg/kg) was tested using the stress-induced hyperthermia paradigm. Pharmacological sensitivity to diazepam differed between the strains with the 129Sv/Ev being most sensitive. These studies show that simultaneous measurement of behavioral and autonomic parameters under stressful conditions contributes considerably to a better interpretation of anxiety and stress levels in mice.
A CMOS integrated three-axis accelerometer fabricated with commercial submicrometer CMOS technology and bulk-micromachining (2001)

In this paper, a bulk-micromachined three-axis accelerometer fabricated with commercial submicrometer CMOS wafers has been developed for low-cost realization of smart accelerometers and improvement of device performance. The signal processing circuits for three-axis detection were formed using a commercial 0.8-/spl mu/m CMOS technology. After that, micromachining processes were performed to the complete CMOS wafers to form accelerometer structures. The important technologies to separate micromachining processes from the CMOS process are wafer thickness control after CMOS fabrication and backside polishing with chemical spin etching. Accelerometers with 3/spl times/3 mm/sup 2/ and 6/spl times/6 mm/sup 2/ die size were fabricated with the developed fabrication technology. As a result of device evaluation, 2.0 mg/sub rms/ resolution of Z-axis acceleration, and 10.8 mg/sub rms/ resolution of X and Y-axis acceleration were obtained by the accelerometers with 6/spl times/6 mm/sup 2/ die size. Comparing for the same die area, the 6/spl times/6 mm/sup 2/ size accelerometer showed about 21.3 times higher resolution of Z-axis acceleration and 37.8 times higher resolution of X, Y-axis acceleration as compared to our previous three-axis accelerometer fabricated with 5.0-/spl mu/m CMOS technology. Temperature dependence and reliability for repetitive vibration loads were also evaluated. Through these evaluations, basic performance of the CMOS integrated three-axis accelerometer has been confirmed.
Ligands for Glutamate Receptors:  Design and Therapeutic Prospects (2000)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTLigands for Glutamate Receptors: Design and Therapeutic ProspectsHans Bräuner-Osborne, Jan Egebjerg, Elsebet Ø. Nielsen, Ulf Madsen, and Povl Krogsgaard-LarsenView Author Information NeuroScience PharmaBiotec Research Center, Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, DK-2100 Copenhagen, Denmark, Department for Molecular and Structural Biology, University of Aarhus, DK-8000 Aarhus, Denmark, and Department of Neurochemistry, NeuroSearch A/S, DK-2750 Ballerup, Denmark Cite this: J. Med. Chem. 2000, 43, 14, 2609–2645Publication Date (Web):July 13, 2000Publication History Received5 January 2000Published online13 July 2000Published inissue 1 July 2000https://pubs.acs.org/doi/10.1021/jm000007rhttps://doi.org/10.1021/jm000007rreview-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views2557Altmetric-Citations469LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Agonists,Antagonists,Monomers,Peptides and proteins,Receptors Get e-Alerts
Analysis of the signal for attachment of a glycophospholipid membrane anchor. (1989)

The COOH terminus of decay accelerating factor (DAF) contains a signal that directs attachment of a glycophospholipid (GPI) membrane anchor. To define this signal we deleted portions of the DAF COOH terminus and expressed the mutant cDNAs it CV1 origin-deficient SV-40 cells. Our results show that the COOH-terminal hydrophobic domain (17 residues) is absolutely required for GPI anchor attachment. However, when fused to the COOH terminus of a secreted protein this hydrophobic domain is insufficient to direct attachment of a GPI anchor. Additional specific information located within the adjacent 20 residues appears to be necessary. We speculate that by analogy with signal sequences for membrane translocation, GPI anchor attachment requires both a COOH-terminal hydrophobic domain (the GPI signal) as well as a suitable cleavage/attachment site located NH2 terminal to the signal.
Simple and Versatile Methods To Integrate Directed Self-Assembly with Optical Lithography Using a Polarity-Switched Photoresist (2010)

We report novel strategies to integrate block copolymer self-assembly with 193 nm water immersion lithography. These strategies employ commercially available positive tone chemically amplified photoresists to spatially encode directing information into precise topographical or chemical prepatterns for the directed self-assembly of block copolymers. Each of these methods exploits the advantageous solubility and thermal properties of polarity-switched positive tone photoresist materials. Precisely registered, sublithographic self-assembled structures are fabricated using these versatile integration schemes which are fully compatible with current optical lithography patterning materials, processes, and tooling.
Transcriptional Activators of Human Genes with Programmable DNA-Specificity (2011)

TAL (transcription activator-like) effectors are translocated by Xanthomonas bacteria into plant cells where they activate transcription of target genes. DNA target sequence recognition occurs in a unique mode involving a central domain of tandem repeats. Each repeat recognizes a single base pair in a contiguous DNA sequence and a pair of adjacent hypervariable amino acid residues per repeat specifies which base is bound. Rearranging the repeats allows the design of novel TAL proteins with predictable DNA-recognition specificities. TAL protein-based transcriptional activation in plant cells is mediated by a C-terminal activation domain (AD). Here, we created synthetic TAL proteins with designed repeat compositions using a novel modular cloning strategy termed "Golden TAL Technology". Newly programmed TAL proteins were not only functional in plant cells, but also in human cells and activated targeted expression of exogenous as well as endogenous genes. Transcriptional activation in different human cell lines was markedly improved by replacing the TAL-AD with the VP16-AD of herpes simplex virus. The creation of TAL proteins with potentially any desired DNA-recognition specificity allows their versatile use in biotechnology.
Nutrient Processing Capacity of a Constructed Wetland in Western Ireland (2002)

ABSTRACT In Ireland, constructed wetland systems are increasingly being used to perform tertiary treatment on municipal waste effluent from small towns and villages located in areas whose receiving waters are deemed sensitive. The bedrock formation in the west of Ireland is primarily karst limestone and where the overburden–soil cover is very shallow, such waters are highly sensitive to pollution sources, as little or no natural attenuation and/or treatment will occur. Constructed wetland technology has been seen to offer a relatively low‐cost alternative to the more conventional tertiary treatment technologies, particularly when dealing with low population numbers in small rural communities. This paper examines the waste treatment performance, in terms of nutrient (P and N) reduction, of a recently constructed surface‐flow wetland system at Williamstown, County Galway, Ireland. Performance evaluation is based on more than two years of water quality and hydrological monitoring data. The N and P mass balances for the wetland indicate that the average percentage reduction over the two‐year study period is 51% for total N and 13% for total P. The primary treatment process in the wetland system for suspended solids (between 84 and 90% reduction), biological oxygen demand (BOD) (on average, 49% reduction), N, and P is the physical settlement of the particulates. However, the formation of algal bloom during the growing season reduces the efficiency of the total P removal.
Rational Design and Evaluation of New Lead Compound Structures for Selective βARK1 Inhibitors (2002)

Beta-adrenergic receptor kinase 1 (betaARK1) and cyclic adenosine 5'-monophosphate-dependent protein kinase A (PKA) have structurally similar adenine-binding pockets but have different physiologic functions. To obtain specific betaARK1 inhibitors, a two step rational drug design process was used. First, a search was conducted on three-dimensional models of commercially available compounds to find compounds that fit the adenine-binding pocket of betaARK1. Second, a comparative docking study that focused on the differences between the adenine-binding pockets of the two enzymes was used to evaluate the binding specificity of each compound that inhibited betaARK1 activity. The results of these analyses yielded three betaARK1-selective inhibitor leads from 11 candidates, a hit rate for selectivity of 27%. Although the IC50 values of these compounds for betaARK1 ranged from only 1.3 x 10(-4) M to 5.6 x 10(-4) M, the compounds did not inhibit PKA at concentrations up to 1.0 x 10(-3) M. Thus, the present study shows the usefulness of a rational drug design strategy in finding specific kinase inhibitors for proteins with similar drug target binding sites.
Recognition of all four Watson-Crick base pairs in the minor groove of DNA by synthetic ligands (2006)

The design of synthetic ligands that read the information stored in the DNA double helix has been a long standing goal at the interface of chemistry and biology. Cell-permeable small molecules which target predetermined DNA sequences offer a potential approach for the regulation of gene-expression. Oligodeoxynucleotides that recognize the major groove of double-helical DNA via triple-helix formation bind to a broad range of sequences with high affinity and specificity. Although oligonucleotides and their analogs have been shown to interfere with gene expression, the triple helix approach is limited to purine tracks and suffers from poor cellular uptake. The subsequent development of pairing rules for minor groove binding polyamides containing pyrrole (Py) and imidazole (Im) amino acids offers a second code to control sequence specificity. An Im/Py pair distinguishes G•C from C•G and both of these from A•T/T•A base pairs. A Py/Py pair specifies A,T from G,C but does not distinguish A•T from T•A. In order to break this degeneracy, a new aromatic amino acid, 3-hydroxypyrrole (Hp), has been added to the repertoire to test for pairings which discriminate A•T from T•A. We find that replacement of a single hydrogen atom with a hydroxy group in a Hp/Py pairing regulates affinity and specificity by an order of magnitude. By incorporation of a third amino acid, hydroxypyrrole-imidazole-pyrrole polyamides form four ring-pairings (Im/Py, Py/Im, Hp/Py, and Py/Hp) which distinguish all four Watson-Crick base pairs in the minor groove of DNA.
Serializability for eventual consistency: criterion, analysis, and applications (2016)

Developing and reasoning about systems using eventually consistent data stores is a difficult challenge due to the presence of unexpected behaviors that do not occur under sequential consistency. A fundamental problem in this setting is to identify a correctness criterion that precisely captures intended application behaviors yet is generic enough to be applicable to a wide range of applications.
Converting thread-level parallelism to instruction-level parallelism via simultaneous multithreading (1997)

To achieve high performance, contemporary computer systems rely on two forms of parallelism: instruction-level parallelism (ILP) and thread-level parallelism (TLP). Wide-issue super-scalar processors exploit ILP by executing multiple instructions from a single program in a single cycle. Multiprocessors (MP) exploit TLP by executing different threads in parallel on different processors. Unfortunately, both parallel processing styles statically partition processor resources, thus preventing them from adapting to dynamically changing levels of ILP and TLP in a program. With insufficient TLP, processors in an MP will be idle; with insufficient ILP, multiple-issue hardware on a superscalar is wasted. This article explores parallel processing on an alternative architecture, simultaneous multithreading (SMT), which allows multiple threads to complete for and share all of the processor's resources every cycle. The most compelling reason for running parallel applications on an SMT processor is its ability to use thread-level parallelism and instruction-level parallelism interchangeably. By permitting multiple threads to share the processor's functional units simultaneously, the processor can use both ILP and TLP to accommodate variations in parallelism. When a program has only a single thread, all of the SMT processor's resources can be dedicated to that thread; when more TLP exists, this parallelism can compensate for a lack of per-thread ILP. We examine two alternative on-chip parallel architectures for the next generation of processors. We compare SMT and small-scale, on-chip multiprocessors in their ability to exploit both ILP and TLP. First, we identify the hardware bottlenecks that prevent multiprocessors from effectively exploiting ILP. Then, we show that because of its dynamic resource sharing, SMT avoids these inefficiencies and benefits from being able to run more threads on a single processor. The use of TLP is especially advantageous when per-thread ILP is limited. The ease of adding additional thread contexts on an SMT (relative to adding additional processors on an MP) allows simultaneous multithreading to expose more parallelism, further increasing functional unit utilization and attaining a 52% average speedup (versus a four-processor, single-chip multiprocessor with comparable execution resources). This study also addresses an often-cited concern regarding the use of thread-level parallelism or multithreading: interference in the memory system and branch prediction hardware. We find the multiple threads cause interthread interference in the caches and place greater demands on the memory system, thus increasing average memory latencies. By exploiting threading-level parallelism, however, SMT hides these additional latencies, so that they only have a small impact on total program performance. We also find that for parallel applications, the additional threads have minimal effects on branch prediction.
Structure of KW‐2228, a tailored human granulocyte colony‐ stimulating factor with enhanced biological activity and stability (1997)

KW-2228 is a tailored human granulocyte colony-stimulating factor (hG-CSF) which has more potent granulopoietic activity and is more stable than wild-type hG-CSF. Analysis of the 2.3 A resolution crystal structure of KW-2228 unambiguously revealed a four-alpha-helix bundle motif with up-up-down-down connectivity. The structures of long overhand loops connecting the helices and the N-terminus have been definitively determined. The present analysis has clearly revealed that substituted residues play important roles in fastening a long overhand loop to the N- and C-termini to fix the conformation. This conformation should be responsible for a substantial enhancement of the biological activity and stability.
Implications of lowering threshold of plasma troponin concentration in diagnosis of myocardial infarction: cohort study (2012)

Lowering the diagnostic threshold to the 99th centile and accepting greater assay imprecision would identify more patients with acute coronary syndrome at risk of recurrent myocardial infarction and death but would increase the diagnosis of myocardial infarction by 47%. It remains to be established whether reclassification of these patients and treatment for myocardial infarction would improve outcome.
PET/CT in Clinical Practice (2008)

PET/CT has an ability that has revolutionized the detection and staging of various tumors: the ability to accurately identify the anatomic location of abnormal metabolic activity. This new technology has also had a significant impact on cardiology and neurology.

This small handbook of 10 chapters
Using geometric hashing to repair CAD objects (1997)

Problems in CAD software sometimes cause defects in the boundaries of polyhedral objects-small gaps bounded by edges incident to one polyhedron face. Using geometric hashing, algorithms can resolve this problem, which has vexed layered manufacturing. Similar techniques hold promise for solving problems in such areas as computer vision, medical imaging, and molecular biology.