gebhart/patrepeval huggingface dataset:
Methylation pharmacogenetics: Thiopurine methyltransferase as a model system (1992)

1. Methyl conjugation is an important pathway in the biotransformation of many drugs and xenobiotic compounds. 'Pharmacogenetic' variation exists in the activities of many methyltransferase enzymes, and experiments with the drug-metabolizing enzyme thiopurine methyltransferase (TPMT) offer a model for one approach that has proven useful in the study of methyltransferase pharmacogenetics. 2. TPMT catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. This enzyme activity is present in the human red blood cell (RBC), and RBC TPMT activity is controlled by a common genetic polymorphism that regulates also the enzyme activity in all other human tissues that have been studied. 3. Subjects with inherited low levels of TPMT activity are at increased risk for thiopurine drug-induced myelotoxicity, while patients with high TPMT activities may be 'undertreated' with these drugs. 4. TPMT activity in tissue from selected strains of inbred mice also is regulated by a genetic polymorphism. These mice provide an animal model for use in the study of pharmacological or toxicological consequences of inherited differences in TPMT activity. 4. Other methyltransferase enzymes including thiol methyltransferase, catechol O-methyltransferase, and histamine N-methyltransferase also are present in the human RBC, are regulated by inheritance, and are responsible for individual variation in drug metabolism. Enhanced understanding of the pharmacogenetics of methylation may make it possible to understand and predict individual variation in the biotransformation, toxicity and therapeutic effect of compounds that undergo methyl conjugation.
Ring-opening polymerization of 6-hydroxynon-8-enoic acid lactone: Novel biodegradable copolymers containing allyl pendent groups (2000)

This article reports the synthesis and copolymerization of 6-hydroxynon-8-enoic acid lactone. The ring-opening polymerization of this lactone-type monomer bearing a pendant allyl group led to new homopolymers and random copolymers with ε-caprolactone and L,L-lactide. The copolymerizations were carried out at 110 °C with Sn(Oct)2 as a catalyst. The introduction of unsaturations into the aliphatic polyester permitted us to carry out different chemical transformations on this family of polymers. For example, this article reports the bromination, epoxidation, and hydrosylilation of the allyl group in the new polyester copolymers. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 870–875, 2000
Oxidative coupling of methane in dense ceramic membrane reactor with high yields (2002)

Abstract Oxidative coupling of methane (OCM) was studied with dense tubular Bi 1.5 Y 0.3 Sm 0.2 O 3 (BYS) membranes at various temperatures (870–930°C). BYS powders were synthesized by a citrate method. Tubular‐shaped dense membranes of BYS in the fluorite‐type FCC phase structure were fabricated by cold isostatic pressing with green machining. The best one‐pass C 2 (C 2 H 4 + C 2 H 6 ) yield achieved for OCM in the BYS dead‐end membrane reactor was 35% at a C 2 selectivity of 54% at 900°C. At the same C 2 yield, the membrane reactor mode gives C 2 selectivity of over 200% higher than the cofeed mode in the same membrane reactor under similar conditions. The oxygen permeation fluxes through tubular BYS membrane reactors under OCM reaction conditions are approximately 1.5 to 3.5 times higher than those under oxygen permeation conditions with He as the purge. After 6 days of OCM, BYS membrane remained in good integrity with minor phase segregation observed at the reaction side of the membrane.
Identification and characterization of B-cell epitopes of IpaC, an invasion-associated protein of Shigella flexneri (1992)

Invasion plasmid antigen C (IpaC) is a 43-kDa plasmid-encoded protein associated with the ability of shigellae to invade epithelial cells. This protein is consistently strongly recognized by sera from convalescent patients and monkeys experimentally infected with shigellae. The strong immunogenicity of IpaC in the course of natural infection makes it a good candidate as a potentially protective antigen. To map the B-cell epitopes of this protein, the gene encoding IpaC was cloned and expressed at a high level in Escherichia coli. The partially purified recombinant protein was used to raise rabbit polyclonal antisera and murine monoclonal antibodies. A lambda gt11 ipaC gene library was screened with the antisera and antibodies. Recombinant DNA clones producing specific antigenic determinants were isolated, and the sequence of their DNA inserts was determined. The amino acid sequence of each determinant was deduced from the minimal overlap of DNA inserts of multiple antibody-positive DNA clones. Two distinct epitopes, located between amino acid residues 25 and 33 and 90 and 97, were identified. Two additional B-cell epitopes which were located between residues 297 and 349, near the carboxy-terminal end of the protein, were characterized. Each of these epitopes was also recognized by sera from convalescent humans and monkeys. Therefore, it seems likely that these epitopes are relevant to the humoral response against IpaC during natural infection.
Observation of Coherent Surface Optical Phonon Oscillations by Time-Resolved Surface Second-Harmonic Generation (1997)

We demonstrate a new time-domain surface phonon spectroscopy. We excite coherent surface optical phonons with an ultrashort laser pulse and probe the free-induction decay with time-resolved surface second-harmonic generation. For both clean GaAs (110) and (100) surfaces, the signals are remarkably large due to the highly localized electron-phonon interaction at the surface and the intrinsic surface sensitivity of second-harmonic generation. This work suggests that coherent oscillations of surface optical phonons may be used as probes of electron-phonon interactions at surfaces and to control or drive nonthermal surface chemical reactions.
Improved waveguide structures derived from new rapid optimization techniques (2003)

We present structures obtained with numerical optimization techniques capable of efficiently channeling light at a fraction of the length of a conventional taper. These results could open the way to novel designs in ultra-short light injection devices. We also consider the rather different problem of how to optimise the transmission through a photonic crystal bend. We show how, using a deterministic global optimisation algorithm, novel optimal geometries can be obtained leading to considerable performance improvements.
Environmental and typewriter control systems for high-level quadriplegic patients: evaluation and prescription. (1979)

A formal 44-month clinical evaluation was conducted to determine the suitability of selected electronic equipment for use in high-level quadriplegia. A total of 52 traumatic high-level quadriplegic patients (C-2 to C-5,6) participated in the testing of 13 commercial electronic assistive devices including 8 environmental control units, 1 self-contained telephone, and 4 typewriter systems. Most devices were pneumatically ("breath") controlled. Devices were tested in an occupational therapy laboratory, bedside, and homes. Testing yielded data on device reliability, suitability, and acceptance by patients.
Fractional Quantum Energy Levels of Hydrogen (1995)

Report is made of the detection of atomic hydrogen in fractional quantum energy levels below the traditional “ground” state — hydrinos — by X-ray photoelectron spectroscopy and by a reinterpretation of soft X-ray emissions from the interstellar medium, Hydrino formation occurs with the release of energy on nickel cathodes during the electrolysis of aqueous potassium carbonate. The detection of a new molecular species—the diatomic hydrino molecule — by high-resolution mass spectroscopy is also reported.
Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality. (2005)

Clinicians now have five oral antifungal therapeutic agents to choose from when assessing the risk-benefits associated with a particular treatment for onychomycosis (OM): griseofulvin, itraconazole, terbinafine, ketoconazole, and fluconazole. Only the first three are approved by the FDA for this indication. Griseofulvin is fungistatic and inhibits nucleic acid synthesis, arresting cell division at metaphase, and impairing fungal wall synthesis. Due to its low cure rates and high relapse, it is rarely used for treatment of onychomycosis. Itraconazole is a broad spectrum drug and is effective against dermatophytes, candida, and some nondermatophytic molds. Itraconazole works by inhibiting ergosterol synthesis via cytochrome P-450 (CYP450)-dependent demethylation step. This azole antifungal agent is metabolized in the liver by cytochrome P-450 3A4 (CYP3A4), and therefore has the potential to interact with drugs metabolized through this pathway. Terbinafine, an allylamine, is fungicidal and remains at therapeutic levels in keratinized tissues, but with a short plasma half-life of 36 hours. Terbinafine has the advantage in that it does not inhibit CYP3A4 isoenzyme during its metabolism where some 50% of all commonly prescribed drugs are metabolized. The only potentially significant drug interaction with terbinafine is with the cytochrome P-450 2D6 (CYP2D6) isoenzyme. The lack of widely reported or published clinically relevant drug interactions, and extensive experience from a large prospective, surveillance study conducted in "real world" setting with no patient exclusions, suggest that this is not a major issue. The high cure rates of terbinafine against dermatophytes, as shown in many studies since its launch in the 1990s, together with lack of clinically significant drug interactions and well established safety record, indicate the use of continuous oral terbinafine as the top choice for the treatment of onychomycosis in most patients.
Optimal transversal filter bank for 3D real-time acoustical imaging (2003)

An optimal transversal filter bank for parallel processing of echo data in 3-D real-time acoustical imaging is proposed. It is based on discretized linear time-domain formation of the imaging equation for systems that use either coded-aperture transducers or transmitter arrays with coded-excitation. The two approaches are mathematically equivalent and result in an imaging system architecture which is based on parallel processing of a sampled vector of echo data with a bank of transversal filters. The filter coefficients are obtained through a pseudoinverse operator which is designed to decouple echoes received from different image lines.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Large fragments of human serum albumin (1977)

Large fragments of human serum albumin were produced by treatment of the native protein with pepsin at pH3.5. Published sequences of human albumin [Behrens, Spiekerman & Brown (1975) Fed. Proc. Fed. Am. Soc. Exp. Biol. 34, 591; Meloun, Moravek & Kostka (1975) FEBSLett.58, 134-137]were used to locate the fragments in the primary structure. The fragments support both the sequence and proposed disulphide-linkage pattern (Behrens et al., 1975). As the pH of a solution of albumin is lowered from pH4 to pH3.5, the protein undergoes a reversible conformational change known as the N-F transition. The distribution of large fragments of human albumin digested with pepsin in the above pH region was critically dependent on pH. It appeared that this distribution was dependent on the conformation of the protein at low pH, rather than the activity of pepsin. The yields of the large fragments produced by peptic digestion at different values of pH suggested that the C-terminal region of albumin unfolds or separates from the rest of the molecule during the N-F transition. The similarity of peptic fragments of human and bovine albumin produced under identical conditions supports the proposed similar tertiary structure of these molecules.
Resting EEG is affected by exposure to a pulsed ELF magnetic field (2004)

An increasing number of reports have demonstrated a significant effect of extremely low frequency magnetic fields (ELF MFs) on aspects of animal and human behavior. Recent studies suggest that exposure to ELF MFs affects human brain electrical activity as measured by electroencephalography (EEG), specifically within the alpha frequency (8-13 Hz). Here we report that exposure to a pulsed ELF MF with most power at frequencies between 0 and 500 Hz, known to affect aspects of analgesia and standing balance, also affects the human EEG. Twenty subjects (10 males; 10 females) received both a magnetic field (MF) and a sham session in a counterbalanced design for 15 min. Analysis of variance (ANOVA) revealed that alpha activity was significantly higher over the occipital electrodes (O1, Oz, O2) [F(1,16) = 6.858; P =.019, eta2 = 0.30] and marginally higher over the parietal electrodes (P3, Pz, P4) [F(1,16) = 4.251; P =.056, eta2 = 0.21] post MF exposure. This enhancement of alpha activity was transient, as it marginally decreased over occipital [F(1,16) = 4.417; P =.052; eta2 = 0.216] and parietal electrodes [F(1,16) = 4.244; P =.056; eta2 = 0.21] approximately 7 min after MF exposure compared to the sham exposure. Significantly higher occipital alpha activity is consistent with other experiments examining EEG responses to ELF MFs and ELF modulated radiofrequency fields associated with mobile phones. Hence, we suggest that this result may be a nonspecific physiological response to the pulsed MFs.
AmpG, a signal transducer in chromosomal β‐lactamase induction (1993)

The chromosomal ampC beta-lactamase in Citrobacter freundii and Enterobacter cloacae is inducible by beta-lactam antibiotics. When an inducible ampC gene is introduced on a plasmid into Escherichia coli together with its transcriptional regulator ampR, the plasmid-borne beta-lactamase is still inducible. We have isolated mutants, containing alterations in a novel E. coli gene, ampG, in which a cloned C. freundii ampC gene is unable to respond to beta-lactam inducers. The ampG gene was cloned, sequenced and mapped to minute 9.6 on the E. coli chromosome. The deduced amino acid sequence predicted AmpG to be a 53 kDa, transmembrane protein, which we propose acts as a signal transducer or permease in the beta-lactamase induction system. Immediately upstream of ampG there is another 579-base-pair-long open reading frame (ORF) encoding a putative lipoprotein shown to be non-essential for beta-lactamase induction. We have found that ampG and this ORF form an operon, whose promoter is located in front of the ORF. Located closely upstream of the putative promoter is the morphogene bolA, which is transcribed in the opposite orientation. However, using transcription fusions, we have found that the ampG transcription is not regulated by bolA. In addition, we show that transcription is probably not regulated by either the starvation specific sigma factor RpoS, which controls bolA, or by AmpD the negative regulator for ampC transcription.
Making the Business Case for Health and Productivity Management (2004)

Health and productivity management (HPM) is an important innovation for businesses concerned with rising health care costs. Like any innovation, however, it will not be adopted rapidly unless it is tailored to the needs of employers. For the last 6 years the Institute for Health and Productivity Management has studied the needs of American employers and sponsored employer driven case studies of health care and productivity. From these studies and the work of academic experts we have fashioned a set of programs to effectively communicate the advantages of health and productivity measurement and management. To make the business case for health and productivity management, researchers need to (1) demonstrate the relative advantage of HPM, (2) keep the evidence simple, (3) show that HPM is compatible with employer practices, and (4) communicate the results within and across corporate departments.
MKK6 Activates Myocardial Cell NF-κB and Inhibits Apoptosis in a p38 Mitogen-activated Protein Kinase-dependent Manner (1998)

In cardiac myocytes the stimulation of p38 mitogen-activated protein kinase activates a hypertrophic growth program and the induction of the cardiac-specific genes associated with this program. This study focused on determining whether these novel growth-promoting effects are accompanied by the p38-mediated inhibition of apoptosis, and if so, what signaling pathways might be responsible. Primary neonatal rat ventricular myocytes were driven into apoptosis by treatments known to induce apoptosis in other cell types, e.g. incubation with anisomycin or overexpression constitutively active MEKK-1 (MEKK-1COOH), a protein that strongly activates extracellular signal-regulated kinase and N-terminal c-Jun kinase, but not p38. Overexpression of constitutively active MKK6, MKK6 (Glu), which selectively activates p38 in cardiac myocytes, protected cells from either anisomycin- or MEKK-1COOH-induced apoptosis. This protection was blocked by SB 203580, a selective p38 inhibitor. MKK6 (Glu) also activated transcription mediated by NF-kappaB, a factor which protects other cell types from apoptosis. The activation of NF-kappaB and the protection from apoptosis mediated by MKK6 (Glu) were both blocked by SB 203580. Interestingly, overexpression of a mutant form of I-kappaBalpha, which inhibits nuclear translocation of NF-kappaB, completely blocked MKK6 (Glu)-activated NF-kappaB but had little effect on MKK6s anti-apoptotic effects. These findings suggest that, in part, the overexpression of MKK6 (Glu) may foster growth and survival of cardiac myocytes by protecting them from apoptosis in a p38-dependent manner. Additionally, while NF-kappaB is activated in myocardial cells by p38, this does not appear to be the major mechanism by which MKK6 (Glu) exerts its anti-apoptotic effects in this cell type, suggesting a novel pathway for p38-mediated protection from apoptosis.
A lamin-independent pathway for nuclear envelope assembly. (1990)

The nuclear envelope is composed of membranes, nuclear pores, and a nuclear lamina. Using a cell-free nuclear assembly extract derived from Xenopus eggs, we have investigated how these three components interact during nuclear assembly. We find that the Xenopus embryonic lamin protein LIII cannot bind directly to chromatin or membranes when each is present alone, but is readily incorporated into nuclei when both of the components are present together in an assembly extract. We find that depleting lamin LIII from an extract does not prevent formation of an envelope consisting of membranes and nuclear pores. However, these lamin-depleted envelopes are extremely fragile and fail to grow beyond a limited extent. This suggests that lamin assembly is not required during the initial steps of nuclear envelope formation, but is required for later growth and for maintaining the structural integrity of the envelope. We also present results showing that lamins may only be incorporated into nuclei after DNA has been encapsulated within an envelope and nuclear transport has been activated. With respect to nuclear function, our results show that the presence of a nuclear lamina is required for DNA synthesis to occur within assembled nuclei.
Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks (2001)

The genome of Borrelia burgdorferi encodes a large number of lipoproteins, many of which are expressed only at certain stages of the spirochete's life cycle. In the current study we describe the B. burgdorferi population structure with respect to the production of two lipoproteins [outer surface protein A (OspA) and outer surface protein C (OspC)] during transmission from the tick vector to the mammalian host. Before the blood meal, the bacteria in the tick were a homogeneous population that mainly produced OspA only. During the blood meal, the population became more heterogeneous; many bacteria produced both OspA and OspC, whereas others produced only a single Osp and a few produced neither Osp. From the heterogeneous spirochetal population in the gut, a subset depleted of OspA entered the salivary glands and stably infected the host at time points >53 hr into the blood meal. We also examined genetic heterogeneity at the B. burgdorferi vlsE locus before and during the blood meal. In unfed ticks, the vlsE locus was stable and one predominant and two minor alleles were detected. During the blood meal, multiple vlsE alleles were observed in the tick. Tick feeding may increase recombination at the vlsE locus or selectively amplify rare vlsE alleles present in unfed ticks. On the basis of our data we propose a model, which is different from the established model for B. burgdorferi transmission. Implicit in our model is the concept that tick transmission converts a homogeneous spirochete population into a heterogeneous population that is poised to infect the mammalian host.
A fast single-chip implementation of 8192 complex point FFT (1995)

Large-scale single-frequency networks are now being considered in Europe as very promising network topologies to achieve drastic savings in spectrum usage for digital terrestrial television transmission. Such networks are possible using the COFDM system, with large guard intervals (more than 200 /spl mu/s) to absorb long echoes. In order to limit the spectral efficiency loss to about 20%, very long size fast Fourier transforms (up to 8 K complex points) have to be performed in real time for the demodulation of every COFDM symbol (every 1 ms). This paper presents the first VLSI single chip dedicated to the computation of direct or inverse fast Fourier transforms of up to 8192 complex points. Due to its pipelined architecture, it can perform an 8 K FFT every 400 /spl mu/s and a 1 K FFT every 50 /spl mu/s. All the storage is onchip, so that no external memories are required. A new internal result scaling technique, called convergent block floating point, has been introduced in order to minimize the required storage for a given quantization noise, The chip, 1 cm/sup 2/ large with 1.5 million transistors, has been designed in a 3.3 V-0.5 /spl mu/m triple-level metal CMOS process and is fully functional. The 8 K complex FFT function could therefore be introduced in the coming years in digital terrestrial TV receivers at low cost.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SGDR: Stochastic Gradient Descent with Warm Restarts (2016)

Restart techniques are common in gradient-free optimization to deal with multimodal functions. Partial warm restarts are also gaining popularity in gradient-based optimization to improve the rate of convergence in accelerated gradient schemes to deal with ill-conditioned functions. In this paper, we propose a simple warm restart technique for stochastic gradient descent to improve its anytime performance when training deep neural networks. We empirically study its performance on the CIFAR-10 and CIFAR-100 datasets, where we demonstrate new state-of-the-art results at 3.14% and 16.21%, respectively. We also demonstrate its advantages on a dataset of EEG recordings and on a downsampled version of the ImageNet dataset. Our source code is available at https://github.com/loshchil/SGDR
Nanowire nanosensors (2005)

The detection of biological and chemical species is central to many areas of healthcare and the life sciences, ranging from uncovering and diagnosing disease to the discovery and screening of new drug molecules. Hence, the development of new devices that enable direct, sensitive, and rapid analysis of these species could impact humankind in significant ways. Devices based on nanowires are emerging as a powerful and general class of ultrasensitive, electrical sensors for the direct detection of biological and chemical species.