gebhart/patrepeval huggingface dataset:
Chapter 12 Regulation of Repressor Synthesis (1971)

Repressors of gene action in bacteria are assumed to be synthesized continuously, the genes under their control being expressed when the repressor is inactivated. This is known to be true for the lac repressor, which is reversibly inactivated by specific inducers (Gilbert and Muller-Hill, 1966). Such control seems reasonable in operons such as lac where it is advantageous to the bacterium to be able to respond as quickly as possible to environmental change. In temperate bacteriophages, however, induction of the prophage is usually irreversible, leading to productive growth of the phage and lysis of the bacteria. Thus one might expect that phage repressors need not be synthesized during all phases of the growth cycle. There is now evidence supporting the idea that repressor synthesis is regulated in λ . REGULATION OF GENE c I Only two genes are known to be expressed by the λ prophage: c I, the repressor gene, and rex, whose product prevents the growth of r II mutants of phage T4 (Howard, 1967). Conditions have been found in which the genes c I and rex stop functioning more or less permanently in lysogens. This can be seen in the behavior of cells lysogenic for the temperature-sensitive prophage λc 1857 containing mutations in gene N and in either gene O or P (Eisen et al., 1968a; and Calef and Neubauer, 1968). When such a lysogen is heated, immunity and, more slowly, rex function are abolished. When these lysogens are grown for prolonged periods at high temperature and are then allowed to grow at...
Dynamics of microtubules from erythrocyte marginal bands. (1993)

Microtubules can adjust their length by the mechanism of dynamic instability, that is by switching between phases of growth and shrinkage. Thus far this phenomenon has been studied with microtubules that contain several components, that is, a mixture of tubulin isoforms, with or without a mixture of microtubule-associated proteins (MAPs), which can act as regulators of dynamic instability. Here we concentrate on the influence of the tubulin component. We have studied MAP-free microtubules from the marginal band of avian erythrocytes and compared them with mammalian brain microtubules. The erythrocyte system was selected because it represents a naturally stable aggregate of microtubules; second, the tubulin is largely homogeneous, in contrast to brain tubulin. Qualitatively, erythrocyte microtubules show similar features as brain microtubules, but they were found to be much less dynamic. The critical concentration of elongation, and the rates of association and dissociation of tubulin are all lower than with brain microtubules. Catastrophes are rare, rescues frequent, and shrinkage slow. This means that dynamic instability can be controlled by the tubulin isotype, independently of MAPs. Moreover, the extent of dynamic behavior is highly dependent on buffer conditions. In particular, dynamic instability is strongly enhanced in phosphate buffer, both for erythrocyte marginal band and brain microtubules. The lower stability in phosphate buffer argues against the hypothesis that a cap of tubulin.GDP.Pi subunits stabilizes microtubules. The difference in dynamics between tubulin isotypes and between the two ends of microtubules is preserved in the different buffer systems.
Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors (2012)

Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regioselectivity in the condensation between a keto enamine and substituted hydrazines was observed when using toluene as the solvent, leading to selective formation of 1-substituted spiroindazoles. The 2-substituted spiroindazoles were formed selectively from alkyl hydrazones by ring closure with Vilsmeier reagent. The key step in the elaboration to the final products is the conversion of an intermediate olefin to the desired ketone through elimination of HBr from an O-methyl bromohydrin. This methodology enabled the synthesis of each desired regioisomer on 50-75 g scale with minimal purification. Acylation of the resultant spirocyclic amines provided potent ACC inhibitors.
Occluding junctions and cytoskeletal components in a cultured transporting epithelium (1980)

MDCK cells form uninterrupted monolayers and make occluding junctions similar to those of natural epithelia. This aricle explores the relationship between these junctions and the cytoskeleton by combining studies on the distribution of microfilaments and microtubules with the effect of drugs, such as colchicines and cytochalasin B, on the degree of tightness of the occluding junctions. To study the degree of tightness, monolayers were prepared by plating MDCK cells on mylon disks coated with collagen. Disks were mounted as flat sheets between two Lucite chambers, and the sealing capacity of the junctions was evaluated by measuring the electrical resistance across the monolayers. Equivalent monolayers on coverslips were used to study the distribution of microtubules and microfilaments by indirect immunofluorescence staining with antibodies against tubulin and actin. This was done both on complete cells and on cytoskeleton preparations in which the cell membranes had been solubilized before fixation. Staining with antiactin shows a reticular pattern of very fine filaments that spread radially toward the periphery where they form a continuous cortical ring underlying the plasma membrane. Staining with antitubulin depicts fibers that extend radially to form a network that occupies the cytoplasm up to the edges of the cell. Colchicine causes a profound disruption of microtubules but only a 27 percent decrease in the electrical resistance of the resting monolayers. Cytochalasin B, when present for prolonged periods, disrupts the cytoplasmic microfilaments and abolishes the electrical resistance. The cortical ring of filaments remains in place but appears fragmented with time. We find that removal of extracellular Ca(++), which causes the tight junctions to open, also causes the microfilaments and microtubules to retract toward the center of the cells. The process of junction opening and fiber retraction is reversed by the restoration of Ca(++). Colchicine has no effect on either the opening or reversal processes, but cytochalasin B inhibits the resealing of the junctions by disorganizing the filaments in the ring and at the apical border of the cells. These cytochalasin B effects are fully reversible. The correlation among cell shape, cytoskeletal patterns, and electrical resistance in the EGTA-opened and resealed monolayers suggests that microfilaments, through their association with plasma membrane components, play a role in positioning the junctional strands and influence the degree of sealing of the occluding junctions.
Dry colour dispensing : Automatic dispensing of granular stir-in-pigments eliminate solvents from point of sale colour matching (2005)

Point of sale (POS) tinting systems are gaining in popularity in the decorative coatings market, but the liquid tinters used show handling problems and may cause waterborne coatings to exceed future regulatory limits on VOC levels. An existing range of readily-dispersed dry granular tinters has been modified for use in POS tinting, and a novel automated dispenser has been developed to dose these dry colours accurately.
Effects of a new cystic fibrosis transmembrane conductance regulator inhibitor on Cl− conductance in human sweat ducts (2004)

Effective and specific inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel in epithelia has long been needed to better understand the role of anion movements in fluid and electrolyte transport. Until now, available inhibitors have required high concentrations, usually in the millimolar or high micromolar range, to effect even an incomplete block of channel conductance. These inhibitors, including 5-nitro-2(3-phenylpropyl-amino)benzoate (NPPB), bumetamide, glibenclamide and DIDS, are also relatively non-specific. Recently a new anion channel inhibitor, a thiazolidinone derivative, termed CFTRInh-172 has been synthesized and introduced with apparently improved inhibitory properties as shown by effects on anion conductance expressed in cell lines and on secretion in vivo. Here, we assay the effect of this inhibitor on a purely salt absorbing native epithelial tissue, the freshly isolated microperfused human sweat duct, known for its inherently high expression of CFTR. We found that the inhibitor at a maximum dose limited by its aqueous solubility of 5 microm partially blocked CFTR when applied to either surface of the membrane; however, it may be somewhat more effective from the cytosolic side (approximately 70% inhibition). It may also partially inhibit Na+ conductance. The inhibition was relatively slow, with a half time for maximum effect of about 3 min, and showed very slow reversibility. Results also suggest that CFTR Cl- conductance (GCl) was blocked in both apical and basal membranes. The inhibitor appears to exert some effect on Na+ transport as well.
Hypereosinophiles Syndrom: aktueller Stand der Diagnostik und Therapie (2007)

In case of eosinophilia persisting for more than 6 months a diagnosis of hypereosinophilic syndrome (HES) should be considered if secondary causes of eosinophilia ca be ruled out. Recent studies on the pathogenesis of HES revealed that the syndrome previously coined "idiopathic HES" is comprised of pathogenetically distinct subtypes which are defined by molecular, immunophenotypic or clinical markers. Eosinophilia in HES can be caused by increased production or survival of eosinophils due to cytokines such as interleukin-5 (IL-5) or clonal expansion due to mutations. Distinction of these pathogenetically different subtypes of HES is clinically relevant as new targeted treatment approaches are available for some of these subtypes, such as tyrosine kinase inhibitors for the FIP1L1-PDGFRA-positive myeloproliferativer subtype, immunomodulators such as interferon-alpha or monoclonal antibodies against IL-5 for FIP1L1-PDGFRA-negative patients.
Replication of Influenza A Viruses in a Green Monkey Kidney Continuous Cell Line (Vero) (1995)

A Vero cell line was investigated as a suitable host system for primary isolation and cultivation of influenza A viruses. The efficiency of primary isolation for currently circulating (H3N2) strains was similar in Vero and MDCK cells. Of 72 egg-adapted strains investigated, 90.3% were detectable hy hemagglutinin (HA) titration in Vero cells after the first passage and 51.4% after the second. The amino acid sequences of the HA1 region of influenza A viruses isolated and passaged in Vero cells were identical to those of their MDCK-grown counterparts. At low MOI, high yields of influenza virus were achieved in Vero cells by multiple additions of trypsin to the medium. After 20 passages of A/England/1/53 (H1N1) in Vero cells, the titer of infectious virus was 8.37 log10 TCID50/mL, and virus protein yields were as high as in MDCK cells.
Actuation of Self-Assembled Two-Component Rodlike Nanostructures (2008)

A model for predicting the effects of stimuli-induced contraction of the polypyrrole ends of two-segment gold-polypyrrole nanorods on their assembly into curved superstructures is presented. The model and experimental data presented here show that small changes (ca. 3%) in the diameter of the polypyrrole segment of each rod will induce dramatic changes (up to 20%) in the radii of the resulting superstructures, providing a convenient means for actuating their opening and closing. We show experimentally that this actuation can be affected via humidity, temperature, and light.
Synthesis of 15N-Enriched Pseudouridine Derivatives (2003)

[reaction: see text]. A procedure for the chemical synthesis of [3-15N]-labeled pseudouridine and a methylated derivative was developed. A suitably protected pseudouridine precursor was nitrated at N3 followed by treatment with 15NH4Cl to afford the 15N-labeled product in six steps with a 20% yield. This methodology will allow for the production of RNAs with [3-15N]pseudouridine and [3-15N-methyl]pseudouridine at specific locations.
Genotype Is Correlated with but Does Not Predict Virulence of Vibrio vulnificus Biotype 1 in Subcutaneously Inoculated, Iron Dextran-Treated Mice (2011)

Vibrio vulnificus is the leading cause of reported deaths from infections related to consumption of seafood in the United States. Affected predisposed individuals frequently die rapidly from sepsis. Otherwise healthy people can experience severe wound infection, which can lead to sepsis and death. A question is why, with so many people consuming contaminated raw oysters, the incidence of severe V. vulnificus disease is low. Molecular typing systems have shown associations of V. vulnificus genotypes and the environmental or clinical source of the strains, suggesting that different genotypes possess different virulence potentials. We examined 69 V. vulnificus biotype 1 strains that were genotyped by several methods and evaluated them for virulence in a subcutaneously inoculated iron dextran-treated mouse model. By examining the relationships between skin infection, systemic liver infection, and presumptive death (a decrease in body temperature), we determined that liver infection is predicated on severe skin infection and that death requires significant liver infection. Although most strains caused severe skin infection, not every strain caused systemic infection and death. Strains with polymorphisms at multiple loci (rrn, vcg, housekeeping genes, and repetitive DNA) designated profile 2 were more likely to cause lethal systemic infection with more severe indicators of virulence than were profile 1 strains with different polymorphisms at these loci. However, some profile 1 strains were lethal and some profile 2 strains did not cause systemic infection. Therefore, current genotyping schemes cannot strictly predict the virulence of V. vulnificus strains and further investigation is needed to identify virulence genes as markers of virulence.
Programmable photonic crystal nanobeam cavities (2010)

We present dynamically reconfigurable photonic crystal nanobeam cavities, operating at ~1550 nm, that can be continuously and reversibly tuned over a 9.5 nm wavelength range. The devices are formed by two coupled nanobeam cavities, and the tuning is achieved by varying the lateral gap between the nanobeams. An electrostatic force, obtained by applying bias voltages directly to the nanobeams, is used to control the spacing between the nanobeams, which in turn results in tuning of the cavity resonance. The observed tuning trends were confirmed through simulations that modeled the electrostatic actuation as well as the optical resonances in our reconfigurable geometries.
EnergyPlus: Energy simulation program (2000)

Various building energy simulation programs developed around the world are reaching maturity. Many use simulation methods (and even code) that originated in the 1960s. Without substantial redesign and restructuring of the programs, continuing to expand their capabilities has become difficult, time-consuming, and prohibitively expensive. However, phenomenal advances in analysis methods and computational power have increased the opportunity for significant improvements in the flexibility and comprehensiveness of these tools. The U.S. Department of Energy (DOE) began planning for a new generation of simulation tools in 1995 using a three-step process: � Create an inventory of existing DOE-sponsored tools � Sponsor workshops to get recommendations from users and developers about needs in energy simulation, and � Define new generation tools based on the recommendations from the workshops and experience in developing BLAST [BLA] and DOE-2 [WIN]. Three organizations formed the initial development team: Lawrence Berkeley National Laboratory (LBNL) — developers of DOE&amp;apos;s DOE-2 program (Winkelmann et al. 1993) — and U.S. Army Construction Engineering Laboratory (CERL) and the University of Illinois (UI) — developers of DOD&amp;apos;s BLAST program [BLA]. This article focuses on the structure, features, and capabilities of EnergyPlus. What is EnergyPlus? EnergyPlus is a new building performance simulation program that combines the best capabilities and features from BLAST and DOE-2 along with new capabilities. EnergyPlus comprises completely new code written in Fortran 90. It is primarily a simulation engine — there is no formal user interface. Both BLAST and DOE-2 have many user interfaces developed by independent third-party developers. We have invited these same developers to work on graphical user interfaces for EnergyPlus. Modular Code One of the main goals for EnergyPlus is to create a well-organized, modular structure that facilitates
Cleavage of a Recombinant Human Immunoglobulin A2 (IgA2)-IgA1 Hybrid Antibody by Certain Bacterial IgA1 Proteases (2000)

To understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed IgA2/A1 half hinge, a seven-amino-acid sequence corresponding to one half of the duplicated sequence making up the IgA1 hinge was incorporated into the equivalent site in IgA2. Insertion of the IgA1 half hinge into IgA2 did not affect antigen binding capacity or the functional activity of the hybrid molecule, as judged by its ability to bind to IgA Fcalpha receptors and trigger respiratory bursts in neutrophils. Although the IgA2/A1 hybrid contained only half of the IgA1 hinge, it was found to be cleaved by a variety of different bacterial IgA1 proteases, including representatives of those that cleave IgA1 in the different duplicated halves of the hinge, namely, those of Prevotella melaninogenica, Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage with S. oralis and some H. influenzae type 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition.
Directed evolution combined with rational design increases activity of GpdQ toward a non-physiological substrate and alters the oligomeric structure of the enzyme (2011)

Directed evolution was used to enhance the activity of the glycerophosphodiesterase enzyme from Enterobacter aerogenes, GpdQ, toward bis(para-nitrophenol) phosphate (BpNPP), a substrate that is frequently used to assay phosphodiesterases. Native GpdQ has a low level of activity toward BpNPP while the evolved enzymes exhibited k(cat) values that were well over 100 times better while improvements in k(cat)/K(m) of around 500 times were observed along with improved activity we observed a change in the oligomeric structure in the evolved enzymes. The native enzyme is a hexamer with tightly associated dimers related by a 3-fold axis. The stability of the dimer was attributed in part to the cap domain that forms a disulfide bond with its 2-fold-related subunit and in part due to the fact that dimerization results in burying 23.6% of the monomer's accessible surface area. The cap domain also forms the top of the active site and contributes an essential part of the interface between 3-fold-related molecules. The evolved proteins quickly lost one of the cysteine residues that formed the disulfide bond and other mutations that might stabilize the cap domain. The likely effect of these mutations was to open up the active site for the new substrate and to favor the formation of dimeric molecules. The breakdown of the oligomeric structure was accompanied by a reduction in the thermal stability of the protein-as monitored by the residual activity of the native and mutant proteins following pre-incubation at elevated temperatures. A discussion on the evolutionary implications of these studies is presented.
Improvements to Technology Mapping for LUT-Based FPGAs (2007)

This paper presents several orthogonal improvements to the state-of-the-art lookup table (LUT)-based field-programmable gate array (FPGA) technology mapping. The improvements target the delay and area of technology mapping as well as the runtime and memory requirements. 1) Improved cut enumeration computes all K-feasible cuts, without pruning, for up to seven inputs for the largest Microelectronics Center of North Carolina benchmarks. A new technique for on-the-fly cut dropping reduces, by orders of magnitude, the memory needed to represent cuts for large designs. 2) The notion of cut factorization is introduced, in which one computes a subset of cuts for a node and generates other cuts from that subset as needed. Two cut factorization schemes are presented, and a new algorithm that uses cut factorization for delay-oriented mapping for FPGAs with large LUTs is proposed. 3) Improved area recovery leads to mappings with the area, on average, 6% smaller than the previous best work while preserving the delay optimality when starting from the same optimized netlists. 4) Lossless synthesis accumulates alternative circuit structures seen during logic optimization. Extending the mapper to use structural choices reduces the delay, on average, by 6% and the area by 12%, compared with the previous work, while increasing the runtime 1.6 times. Performing five iterations of mapping with choices reduces the delay by 10% and the area by 19% while increasing the runtime eight times. These improvements, on top of the state-of-the-art methods for LUT mapping, are available in the package ABC