gebhart/patrepeval huggingface dataset:
GENETIC ANALYSIS OF PROTEIN STABILITY AND FUNCTION (1989)

There is tremendous variability in the importance of individual amino acids in protein sequences. On the one hand, nonconservative residue substitutions can be tolerated with no loss of activity at many residue positions, especially those exposed on the protein surface. On the other hand, destabilizing mutations can occur at a large number of different sites in a protein, and for many proteins such mutations account for more than half of the randomly isolated missense mutations that confer a defective phenotype. At sites that are key determinants of stability or activity, even residue substitutions that are generally considered to be conservative (e.g., Glu in equilibrium Asp, Asn in equilibrium Asp, Ile in equilibrium Leu, Lys in equilibrium Arg and Ala in equilibrium Gly) can have severe phenotypic effects. Unfortunately, this means that there is no simple way to infer the likely effect of an amino acid substitution on the basis of sequence information alone. A nonconservative Gly----Arg substitution could be phenotypically silent at one position while a conservative Asn----Asp change could lead to complete loss of activity at another position. For proteins whose structures are known, it is often possible to predict whether particular residue substitutions will be destabilizing, as long as detailed estimates of the destabilization energy are not required. Substitutions that introduce polar groups, large cavities, or overly large side chains into the hydrophobic core are potentially the most destabilizing. Substitutions that disrupt hydrogen bonding or electrostatic interactions can also have significant effects, although the destabilization caused by these substitutions is smaller than that caused by severe core mutations. Destabilizing substitutions that involve replacing glycines in turns, or introducing prolines into alpha-helices and other disallowed positions are also reasonably common. Finally, most solvent exposed residues can apparently be freely substituted without serious effects on protein stability. Although exceptions may occur, these generalizations serve to summarize a large body of information and can be rationalized in physical and chemical terms. It is an especially encouraging result that proteins appear to tolerate most substitutions, even those that are destabilizing, without significant changes in the native structure. For proteins whose structures are known, this means that it is reasonable to interpret mutant phenotypes in terms of the wild-type structure. For proteins whose structures are not known, it is reasonable to infer that mutations that reduce activity without affecting stability are directly involved in function.(ABSTRACT TRUNCATED AT 400 WORDS)
Hardware-based ray casting for tetrahedral meshes (2004)

We present the first implementation of a volume ray casting algorithm for tetrahedral meshes running on off-the-shelf programmable graphics hardware. Our implementation avoids the memory transfer bottleneck of the graphics bus since the complete mesh data is stored in the local memory of the graphics adapter and all computations, in particular ray traversal and ray integration, are performed by the graphics processing unit. Analogously to other ray casting algorithms, our algorithm does not require an expensive cell sorting. Provided that the graphics adapter offers enough texture memory, our implementation performs comparable to the fastest published volume rendering algorithms for unstructured meshes. Our approach works with cyclic and/or non-convex meshes and supports early ray termination. Accurate ray integration is guaranteed by applying pre-integrated volume rendering. In order to achieve almost interactive modifications of transfer functions, we propose a new method for computing three-dimensional pre-integration tables.
ChemInform Abstract: The Direct Formation of Functionalized Alkyl(Aryl)zinc Halides by Oxidative Addition of Highly Reactive Zinc with Organic Halides and Their Reactions with Acid Chlorides, α,β‐Unsaturated Ketones, and Allylic, Aryl, and Vinyl Halides. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Two molecular forms of (Na+ + K+)-stimulated ATPase in brain. Separation, and difference in affinity for strophanthidin. (1979)

The brain contains two distinct molecular forms of the (Na,K)-ATPase (sodium and potassium ion-stimulated adenosine triphosphatase). They can be resolved by gel electrophoresis in sodium dodecyl sulfate, and can be identified by sodium-dependent, potassium-sensitive phosphorylation by [gamma-32P]ATP. They are present in the brain of every animal species examined, while only one molecular form is detected in the other organs examined. They are located in different kinds of cells within the brain, and can be physically separated while fully active by gentle tissue fractionation procedures. One is the only (Na,K)-ATPase of brain non-neuronal cells (astrocytes), while the other is the only (Na,K)-ATPase of axolemma (plasma membrane of myelinated axons). They differ in at least one kinetic parameter: the affinity for the specific inhibitor strophanthidin. They have similar one-dimensional peptide maps, but differ in their sensitivity to digestion by trypsin and in the number or reactivity of sulfhydryl groups. It is anticipated that they will be found to play functionally different roles in the complex ion transport mechanisms of the brain.
Documenting software architectures: views and beyond (2003)

This lecture maps the concepts and templates explored in this tutorial with well-known architectural prescriptions, including the 4+1 approach of the Rational Unified Process, the Siemens Four Views approach, and the ANSI/IEEE-1471-2000 recommended best practice for documenting architectures for software-intensive systems. The lecture concludes by re-capping the highlights of the tutorial, and asking for feedback.
POPLINE (1984)

POPLINE, previously POPINFORM, was initiated in 1973 and in 1980 became available through the National Library of Medicine's MEDLARS system. POPLINE covers the areas of research in human fertility, contraceptive methods, community-based services, program evaluation, demography, censuses, vital statistics, and related health, law, and policy issues. Search techniques using the controlled vocabulary from the POPLINE Thesaurus are presented. A comparison of sample searches done on POPLlNE and MEDLINE is also included.
.gamma.-Aminobutyric acid esters. 2. Synthesis, brain uptake, and pharmacological properties of lipid esters of .gamma.-aminobutyric acid (1985)

Two lipid esters of U-14C-labeled and unlabeled gamma-aminobutyric acid (GABA) were synthesized to test the possibility that natural lipid analogues, which resemble normal components of lipid bilayer membranes, can penetrate the blood-brain barrier and transport exogenous GABA to the brain. The uptake of 1-linolenoyl-2,3-bis(4-aminobutyryl)propane-1,2,3-triol and 1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol into mouse brain relative to liver was found to be, respectively, 75- and 127-fold greater than that of free GABA. The results indicate that there is little or no blood-brain barrier for the GABA ester molecules at doses up to 0.36 mmol/kg. Both ester compounds, but neither free GABA nor the lipid components delivered systemically, demonstrated central nervous system depressant properties by inhibiting the general motor activity of mice. Brain tissue has esterase activity which can release GABA from these compounds. This suggests that these compounds function as "prodrugs" to release GABA in the CNS.
Coupling coefficient modulation of waveguide grating using sampled grating (1994)

A new method of modulating the coupling coefficient along the waveguide is proposed. The effect of our method, which uses a nonperiodic sampled grating, is demonstrated both theoretically and experimentally. A Bragg filter is fabricated on an InGaAsP/InP wafer utilizing the method, and the sidelobe level is shown to improve by 7 dB compared with a conventional filter with a uniform coupling coefficient. The experimental results are found to be in good agreement with calculations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
<title>Modeling for optically interconnected packet switches</title> (2000)

This paper studies the performance of a large-scale free-space photonic packet switch based on the generalised knockout principle. Input and output channels are grouped into sectors to make the whole switch a Clos-like three-stage architecture. The input traffic is mainly IP data packets but compatible with ATM cells. Fan-in and fan-out stages are suitable to use free-space optical interconnections with Spatial Light Modulator (SLM) as the switching element. The switch performance was studied based on the switching simulation under different traffic conditions and routing schemes.
The Thermodynamics of DNA Structural Motifs (2004)

DNA secondary structure plays an important role in biology, genotyping diagnostics, a variety of molecular biology techniques, in vitro-selected DNA catalysts, nanotechnology, and DNA-based computing. Accurate prediction of DNA secondary structure and hybridization using dynamic programming algorithms requires a database of thermodynamic parameters for several motifs including Watson-Crick base pairs, internal mismatches, terminal mismatches, terminal dangling ends, hairpins, bulges, internal loops, and multibranched loops. To make the database useful for predictions under a variety of salt conditions, empirical equations for monovalent and magnesium dependence of thermodynamics have been developed. Bimolecular hybridization is often inhibited by competing unimolecular folding of a target or probe DNA. Powerful numerical methods have been developed to solve multistate-coupled equilibria in bimolecular and higher-order complexes. This review presents the current parameter set available for making accurate DNA structure predictions and also points to future directions for improvement.
Toward an Artificial Golgi: Redesigning the Biological Activities of Heparan Sulfate on a Digital Microfluidic Chip (2009)

Using digital microfluidics, recombinant enzyme technology, and magnetic nanoparticles, we have created a functional prototype of an artificial Golgi organelle. Analogous to the natural Golgi, which is responsible for the enzymatic modification of glycosaminoglycans immobilized on proteins, this artificial Golgi enzymatically modifies glycosaminoglycans, specifically heparan sulfate (HS) chains immobilized onto magnetic nanoparticles. Sulfo groups were transferred from adenosine 3'-phosphate 5'-phosphosulfate to the 3-hydroxyl group of the D-glucosamine residue in an immobilized HS chain using D-glucosaminyl 3-O-sulfotransferase. After modification, the nanoparticles with immobilized HS exhibited increased affinity for fluorescently labeled antithrombin III as detected by confocal microscopy. Since the biosynthesis of HS involves an array of specialized glycosyl transferases, epimerase, and sulfotransferases, this approach should mimic the synthesis of HS in vivo. Furthermore, our method demonstrates the feasibility of investigating the effects of multienzyme systems on the structure of final glycan products for HS-based glycomic studies.
Spectrum of clinical features in Muckle‐Wells syndrome and response to anakinra (2004)

The remarkable response of MWS to anakinra suggests that IL-1beta has a fundamental role in the pathogenesis of inflammation associated with mutations in the NALP3 gene, and supports study of IL-1 inhibition in patients with NOMID/CINCA syndrome or FCAS. The clinical features of the various syndromes associated with mutations in the NALP3 gene may overlap to a greater extent than has previously been recognized.
icaR Encodes a Transcriptional Repressor Involved in Environmental Regulation of ica Operon Expression and Biofilm Formation in Staphylococcus epidermidis (2002)

ABSTRACT Biofilm formation in Staphylococcus epidermidis is dependent upon the ica operon-encoded polysaccharide intercellular adhesin, which is subject to phase-variable and environmental regulation. The icaR gene, located adjacent to the ica operon, appears to be a member of the tetR family of transcriptional regulators. In the reference strain RP62A, reversible inactivation of the ica operon by IS 256 accounts for 25 to 33% of phase variants. In this study, icaA and icaR regulation were compared in RP62A and a biofilm-forming clinical isolate, CSF41498, in which IS 256 is absent. Predictably, ica operon expression was detected only in wild-type CSF41498 and RP62A but not in non-IS 256 -generated phase variants. In contrast, the icaR gene was not expressed in RP62A phase variants but was expressed in CSF41498 variants. An icaR ::Em r insertion mutation in CSF41498 resulted in an at least a 5.8-fold increase in ica operon expression but did not significantly alter regulation of the icaR gene itself. Activation of ica operon transcription by ethanol in CSF41498 was icaR dependent. In contrast, a small but significant induction of ica by NaCl and glucose (NaCl-glucose) was observed in the icaR ::Em r mutant. In addition, transcription of the icaR gene itself was not significantly affected by NaCl-glucose but was repressed by ethanol. Expression of the ica operon was induced by ethanol or NaCl-glucose in phase variants of CSF41498 ( icaR + ) but not in RP62A variants ( icaR deficient). These data indicate that icaR encodes a repressor of ica operon transcription required for ethanol but not NaCl-glucose activation of ica operon expression and biofilm formation.
Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer (2009)

Microarray-based readout of ER, PR, and HER2 shows a high concordance with immunohistochemistry/CISH and provides an additional, objective, and quantitative assessment of tumor receptor status in breast cancer.
Der Schauspieldirektor, K. 486 (1991)

Journal Article Der Schauspieldirektor, K. 486 Get access David E. Anderson David E. Anderson Search for other works by this author on: Oxford Academic Google Scholar The Opera Quarterly, Volume 8, Issue 3, Autumn 1991, Pages 179–180, https://doi.org/10.1093/oq/8.3.179 Published: 01 October 1991
Density scaling with gate-all-around silicon nanowire MOSFETs for the 10 nm node and beyond (2013)

We present results from gate-all-around (GAA) silicon nanowire (SiNW) MOSFETs fabricated using a process flow capable of achieving a nanowire pitch of 30 nm and a scaled gate pitch of 60 nm. We demonstrate for the first time that GAA SiNW devices can be integrated to density targets commensurate with CMOS scaling needs of the 10 nm node and beyond. In addition, this work achieves the highest performance for GAA SiNW NFETs at a gate pitch below 100 nm.
Synthesis of 4‐Substituted 1H‐Benzimidazole 2′‐Deoxyribonucleosides and Utility of the 4‐Nitro Compound as Universal Base (1996)

Abstract The stereoselective synthesis of 4‐substituted 1 H ‐benzimidazole 2′‐deoxyribonucleosides is described. Regioisomeric ( N 1 and N 3 ) β‐ D ‐deoxyribonucleosides 2a–c and 3a–c were formed. 13 C‐NMR Chemical shifts of the 1 H ‐benzimidazole 2′‐deoxy‐β‐ D ‐ribofuranosides were correlated with point charges of C‐atoms as well as with Hammett constants of the exocyclic substituents. Phosphonate and phosphoramidite building blocks of 4‐nitro‐1 H ‐benzimidazole 2′‐deoxyribofuranoside ( 2a ) were prepared (see 4a, b ). Oligonucleotides of the d(A 20 ) type were synthesized in which the two central dA bases were replaced by 4‐nitro‐1 H ‐benzimidazole residues. They were hybridized with oligomeric dT and related oligomers having the other conventional bases opposite to the 4‐nitro‐1 H ‐benzimidazole moieties. Within these duplexes ( 12·13, 12·14, 12·15 , and 12·16 ), the destabilization was almost independent of the mismatch which is required for a universal base. The thermodynamic data indicate that the 4‐nitro‐1 H ‐benzimidazole residues do not form H‐bonds with opposite bases but are stabilizing the duplex by stacking interactions and favorable entropic changes.
Thin film metal coated fiber optic hydrophone probe (2009)

Our purpose is to improve the performance sensitivity of a fiber sensor used as a fiber optic hydrophone probe (FOHP) by the addition of nanoscale thin film gold coating. The fiber is designed to provide a uniform and spatial averaging free response up to 100 MHz by etching down to an active diameter of approximately 9 mum. The performance sensitivity of straight cleaved (i.e., full size core and cladding) uncoated, tapered uncoated, and tapered thin film gold-coated fiber sensors was compared in the frequency range from 1.5 to 20 MHz in the presence of acoustic amplitude pressure levels as high as 6 MPa. An unprecedented voltage sensitivity of -245 dB relative to 1 V/muPa (560 mV/MPa) was measured for a thin film gold-coated FOHP by optimizing the gold coating thickness.
Insulin analog with additional disulfide bond has increased stability and preserved activity (2012)

Insulin is a key hormone controlling glucose homeostasis. All known vertebrate insulin analogs have a classical structure with three 100% conserved disulfide bonds that are essential for structural stability and thus the function of insulin. It might be hypothesized that an additional disulfide bond may enhance insulin structural stability which would be highly desirable in a pharmaceutical use. To address this hypothesis, we designed insulin with an additional interchain disulfide bond in positions A10/B4 based on Cα-Cα distances, solvent exposure, and side-chain orientation in human insulin (HI) structure. This insulin analog had increased affinity for the insulin receptor and apparently augmented glucodynamic potency in a normal rat model compared with HI. Addition of the disulfide bond also resulted in a 34.6°C increase in melting temperature and prevented insulin fibril formation under high physical stress even though the C-terminus of the B-chain thought to be directly involved in fibril formation was not modified. Importantly, this analog was capable of forming hexamer upon Zn addition as typical for wild-type insulin and its crystal structure showed only minor deviations from the classical insulin structure. Furthermore, the additional disulfide bond prevented this insulin analog from adopting the R-state conformation and thus showing that the R-state conformation is not a prerequisite for binding to insulin receptor as previously suggested. In summary, this is the first example of an insulin analog featuring a fourth disulfide bond with increased structural stability and retained function.
Chimeric hepatitis B virus core particles with parts or copies of the hepatitis C virus core protein (1993)

Either parts or multiple copies of the core gene of hepatitis C virus (HCV) were fused to the 3' terminus of the hepatitis B virus (HBV) core gene with 34 codons removed. As many as four copies of HCV core protein (720 amino acids) were fused to the carboxy terminus of truncated HBV core protein (149 amino acids) without preventing the assembly of HBV core particles. Chimeric core particles were sandwiched between monoclonal antibody to HBV core and that to HCV core, thereby indicating that antigenic determinants of both HBV and HCV cores were accessible on them. Proteolytic digestion deprived chimeric core particles of the antigenicity for the HCV core without affecting that of the HBV core, confirming the surface exposure of HCV core determinants. The density of HCV core determinants on chimeric core particles increased as copies of fused HCV core protein were increased. Hybrid core particles with multiple HCV core determinants would be instrumental as an antigen probe for detecting class-specific antibodies to the HCV core in patients with acute and chronic hepatitis C and for simultaneous detection of antibodies to HBV core and those to HCV core in donated blood.
Use of an LC filter to achieve a motor-friendly performance of the PWM voltage source inverter (1999)

By putting an LC filter between a PWM voltage source inverter and induction motor, standard industrial motors can also be utilized for adjustable speed drive applications. In this paper, the application of an LC filter to medium voltage motors fed by inverters with switching frequencies below 1000 Hz is described. For different filter topologies, rules for the electrical design are discussed as well as solutions for the stability problem. Also discussed are solutions against common mode voltage stress on the motor terminals. An example shows the implication of the filter on the minimum inverter power which has to be installed to feed a given motor.
Detection of a novel intracellular microbiome hosted in arbuscular mycorrhizal fungi (2013)

Arbuscular mycorrhizal fungi (AMF) are important members of the plant microbiome. They are obligate biotrophs that colonize the roots of most land plants and enhance host nutrient acquisition. Many AMF themselves harbor endobacteria in their hyphae and spores. Two types of endobacteria are known in Glomeromycota: rod-shaped Gram-negative Candidatus Glomeribacter gigasporarum, CaGg, limited in distribution to members of the Gigasporaceae family, and coccoid Mollicutes-related endobacteria, Mre, widely distributed across different lineages of AMF. The goal of the present study is to investigate the patterns of distribution and coexistence of the two endosymbionts, CaGg and Mre, in spore samples of several strains of Gigaspora margarita. Based on previous observations, we hypothesized that some AMF could host populations of both endobacteria. To test this hypothesis, we performed an extensive investigation of both endosymbionts in G. margarita spores sampled from Cameroonian soils as well as in the Japanese G. margarita MAFF520054 isolate using different approaches (molecular phylotyping, electron microscopy, fluorescence in situ hybridization and quantitative real-time PCR). We found that a single AMF host can harbour both types of endobacteria, with Mre population being more abundant, variable and prone to recombination than the CaGg one. Both endosymbionts seem to retain their genetic and lifestyle peculiarities regardless of whether they colonize the host alone or together. These findings show for the first time that fungi support an intracellular bacterial microbiome, in which distinct types of endobacteria coexist in a single cell.
Public Funding of Non-government Schools (2009)

Discusses the debate that is going on among the Humanists regarding the worth of funding non-government schools.