gebhart/patrepeval huggingface dataset:
Supervising the fold: functional principles of molecular chaperones (1996)

Molecular chaperones are a set of conserved protein families that share the remarkable ability to recognize and selectively bind nonnative proteins under physiological and stress conditions. Thus, they prevent irreversible aggregation reactions and keep proteins on the productive folding pathway. Evidence suggests that the cell has developed several functionally distinct chaperone families to support protein folding. The importance of molecular chaperones under stress conditions is highlighted by the finding that all the major heat shock protein families (Hsp104, Hsp90, Hsp70, Hsp60/GroEL, and small Hsps) suppress irreversible unfolding reactions. Under heat shock, only the increased expression of a repertoire of different chaperones seems to convey thermotolerance and guarantee survival. The molecular mechanism by which chaperones in general influence protein folding processes is still far from clear. However, significant progress has been achieved in understanding some of the partial reactions of the chaperone folding cycles and in functionally differentiating between the different chaperone families.
Characterization of the Acetate Binding Pocket in theMethanosarcina thermophilaAcetate Kinase (2005)

Acetate kinase catalyzes the reversible magnesium-dependent synthesis of acetyl phosphate by transfer of the ATP gamma-phosphoryl group to acetate. Inspection of the crystal structure of the Methanosarcina thermophila enzyme containing only ADP revealed a solvent-accessible hydrophobic pocket formed by residues Val(93), Leu(122), Phe(179), and Pro(232) in the active site cleft, which identified a potential acetate binding site. The hypothesis that this was a binding site was further supported by alignment of all acetate kinase sequences available from databases, which showed strict conservation of all four residues, and the recent crystal structure of the M. thermophila enzyme with acetate bound in this pocket. Replacement of each residue in the pocket produced variants with K(m) values for acetate that were 7- to 26-fold greater than that of the wild type, and perturbations of this binding pocket also altered the specificity for longer-chain carboxylic acids and acetyl phosphate. The kinetic analyses of variants combined with structural modeling indicated that the pocket has roles in binding the methyl group of acetate, influencing substrate specificity, and orienting the carboxyl group. The kinetic analyses also indicated that binding of acetyl phosphate is more dependent on interactions of the phosphate group with an unidentified residue than on interactions between the methyl group and the hydrophobic pocket. The analyses also indicated that Phe(179) is essential for catalysis, possibly for domain closure. Alignments of acetate kinase, propionate kinase, and butyrate kinase sequences obtained from databases suggested that these enzymes have similar catalytic mechanisms and carboxylic acid substrate binding sites.
Liposomes as adjuvants with immunopurified tetanus toxoid: influence of liposomal characteristics. (1987)

The effect of various manipulations of liposomes composed of equimolar phospholipid and cholesterol on immune responses to the incorporated immunopurified tetanus toxoid was investigated in BALB/c mice. In studies designed to establish proper dosage for immunization and to reveal the roles of the liposomal phospholipid to toxoid mass ratio, gel-liquid crystalline transition temperatures (Tc) of the liposomal phospholipids and mode of antigen incorporation into liposomes on immune responses, animals were injected intramuscularly with various amounts of the toxoid, free, entrapped in multilamellar dehydration-rehydration vesicles (DRV) or covalently linked to the surface of multilamellar vesicles (MLV) prepared by the classical procedure. Two identical injections separated by 4 weeks were given and IgG1 and IgG2b antibodies specific for the toxoid assayed in sera by an enzyme-linked immunosorbent assay. Results suggest that the adjuvant effect of liposomes is improved considerably when liposomal phospholipid to toxoid mass ratios are as high as 2049:1; however, adjuvanticity is reduced to reach very low levels for much higher ratios (e.g. 90,361:1); antibody responses are similar for liposomes (phospholipid to toxoid mass ratios: 14.3-33.1) made of a variety of phospholipids with Tcs ranging from -32 degrees to 41.5 degrees but are low or non-existent when liposomes are made of distearoyl phosphatidylcholine (Tc, 54 degrees) (however, see Discussion); there are no differences in antibody responses between liposomes with entrapped and surface-linked toxoid.
A computational framework for optimal masking in the synthesis of oligonucleotide microarrays (2002)

High-throughput genomic technologies are revolutionizing modern biology. In particular, DNA microarrays have become one of the most powerful tools for profiling global mRNA expression in different tissues and environmental conditions, and for detecting single nucleotide polymorphisms. The broad applicability of gene expression profiling to the biological and medical realms has generated expanding demand for mass production of microarrays, which in turn has created considerable interest in improving the cost effectiveness of microarray fabrication techniques. We have developed the computational framework for an optimal synthesis strategy for oligonucleotide microarrays. The problem was introduced by Hubbell et al. Here, we formalize the problem, obtain precise bounds on its complexity and devise several computational solutions.
Both membrane‐bound and soluble forms of CD14 bind to Gram‐negative bacteria (1995)

Tissue macrophages and their precursors-the blood monocytes-respond rapidly to a bacterial infection with the release of inflammatory mediators. These mediators are involved in the recruitment of phagocytic cells, principally neutrophils, from the blood to the site of infection. To initiate this process macrophages and monocytes must be able to detect the presence of bacteria in a reliable, but nevertheless nonspecific, fashion. It is thought that this is achieved by means of receptors on the cell surface which recognize structures common to many different bacteria. One candidate for such a "pattern recognition element" is the cell surface glycoprotein CD14. CD14 has been shown to bind components of the Gram-positive cell wall and it also binds soluble lipopolysaccharide released from Gram-negative bacteria. In both cases the interaction with CD14 leads to an activation of the cell. Here we show that human peripheral blood monocytes can, in addition, bind intact Gram-negative bacteria in the presence of serum and this process involves CD14. When CD14 expression is induced on the myelomonocytic cell line U937 by treatment with vitamin D3 the cells concomittently acquire the capacity to bind bacteria. Furthermore, a non-monocytic cell line which does not bind bacteria acquires the capacity to do so when transfected with either the human or mouse CD14 gene. This binding can be inhibited by blocking the CD14 receptor with anti-CD14 antibody or by blocking the ligand on the bacteria with soluble CD14. Finally we demonstrate binding of sCD14 to Escherichia coli. We conclude that in the presence of serum both membrane-bound and soluble forms of CD14 can bind to Gram-negative bacteria. This suggests that CD14 may play a role in the detection and elimination of intact bacteria in vivo.
The New Europeans (1991)

Fifty years after Jean Monnet penned in 1943 his ideas for a united states of Europe the Single Market will formally, if not in every detail, have been completed. Many British managers and sales executives, however, will be 'newcomers' to the Single Market and the wider European marketplace, having lived apart from Europe in body and in spirit all their lives. Others may have travelled to and from the Continent several times, though without absorbing much of the business atmosphere. There are those, too, who do not even think about European unity, and doubt that it will have any noticeable bearing on their lives. Recent political developments in Europe, however, have been of epic dimensions and must have convinced at least some of the sceptics of the reality of European unity. The sheer force of events has compelled everyone to look beyond British shores to witness the political map of Europe being redrawn. The dismantling of the Berlin wall, the re-unification of the two Germanies, the disintegration of the Warsaw Pact, and the Russian-German co-operation pact of 1990 were events of monumental importance, resulting from a new mood of conciliation which had swept through Europe, taking millions of citizens by surprise. These events have clarified modern aims and values which the peoples of Europe are, in the main, determined to share. The reluctant British, it seems, and the newly liberated East Europeans, are also ready to become members of the international business community.KeywordsEuropean UnityMonetary UnionEuropean Monetary UnionEuropean Economic CommunityEuropean Monetary SystemThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
30% external quantum efficiency from surface textured, thin-film light-emitting diodes (1993)

There is a significant gap between the internal efficiency of light-emitting diodes (LEDs) and their external efficiency. The reason for this shortfall is the narrow escape cone for light in high refractive index semiconductors. We have found that by separating thin-film LEDs from their substrates (by epitaxial lift-off, for example), it is much easier for light to escape from the LED structure and thereby avoid absorption. Moreover, by nanotexturing the thin-film surface using ‘‘natural lithography,’’ the light ray dynamics becomes chaotic, and the optical phase-space distribution becomes ‘‘ergodic,’’ allowing even more of the light to find the escape cone. We have demonstrated 30% external efficiency in GaAs LEDs employing these principles.
Layer Transfer of FDSOI CMOS to 150mm InP Substrates for Mixed-Material Integration (2006)

A low-temperature wafer bonding process has been developed to extend a silicon 3D circuit integration process to mixed-material systems. As part of this effort a functional FDSOI CMOS layer was transferred to a 150 mm diameter InP wafer without significantly affecting circuit operation. InGaAs and InGaAsP layers grown in a commercial OMVPE reactor had excellent characteristics for both 150 mm and 50 mm diameter substrates. These results suggest that it is feasible to build a near-IR imager with a tight pixel pitch by transferring a readout layer fabricated in SOI to an InGaAs/InP detector wafer
In Vitro Translation (1998)

The two most frequently used systems for in vitro translation are the rabbit reticulocyte system and the wheat germ extract. These systems are useful for mRNAs isolated from cells, tissues, and capped or uncapped mRNA produced in vitro by transcription of cDNA. In a combined system, mRNA can be transcribed and translated in a single reaction. In addition these systems can be used for translation reactions with biotinylated amino acids; this allows capture of the newly synthesized protein using streptavidin immobilized on agarose.
Design and in vivo testing of 17 beta-estradiol-HP beta CD sublingual tablets. (1996)

17 beta-Estradiol is almost insoluble in water. The effect of various cyclodextrins and two different polymers, polyvinylpyrrolidone (PVP) and carboxymethylcellulose (CMC), on the aqueous solubility of 17 beta-estradiol was investigated. 17 beta-Estradiol was dissolved in aqueous 50% w/v 2-hydroxypropyl-beta- cyclodextrin (HP beta CD) solution containing 0.25% (w/v) CMC and the dry 17 beta-estradiol-HP beta CD complex formed by lyophilisation of the solution. Sublingual tablets from the dry complex were produced by direct compression. The dissolution of 17 beta-estradiol from tablets containing the drug in a lyophilised HP beta CD complex was determined. For reference the dissolution of 17 beta-estradiol was determined from tablets containing physical mixture of 17 beta-estradiol and HP beta CD or tablets containing 17 beta-estradiol without HP beta CD. Sublingual tablets containing 17 beta-estradiol-HP beta CD in the lyophilised complex demonstrated the fastest dissolution profile and those tablets were selected for further studies in humans. Six postmenopausal women received a sublingual tablet containing 17 beta-estradiol-HP beta CD complex equivalent to 100 micrograms 17 beta-estradiol. Blood samples were collected over a 12 h period and the 17 beta-estradiol plasma concentration was determined. 17 beta-Estradiol was rapidly absorbed from the sublingual tablets, resulting in a peak 17 beta-estradiol plasma concentration of 568 +/- 97 pmol/l 15 min after administration of the tablets, followed by a biphasic elimination.
Novel surface plasmon waveguide for high integration (2005)

A novel surface plasmon waveguide structure is proposed for highly integrated planar lightwave circuits. By etching a small trench through a metallic thin film on a silica substrate, a guided mode with highly confined light fields is realized. The mode properties of the proposed structure are studied. The necessity of using a polymer upper-cladding is discussed. The coupling between two closely positioned waveguides and a 90o bending are also studied numerically. Sharp bending and high integration can be realized with the present surface plasmon waveguide. The proposed structure is easy to fabricate as compared with some other types of surface plasmon waveguides for high integration.
Treatment of asthmatic bronchoconstriction by percutaneous low voltage vagal nerve stimulation: case report. (2009)

Background: A 34 year old Hispanic male patient presented himself in the emergency room with recurring severe asthma that was unresponsive to b-adrenergic and steroid therapy. Spirometry demonstrated significant airflow obstruction. Objective: We sought to test the ability of low voltage vagus nerve stimulation to induce bronchodilation and improve airflow.Method: A percutaneous electrode was inserted into the patient’s neck and positioned to lie in the vicinity of the carotid sheath. Following placement, stimulation was administered and the signal amplitude slowly increased until muscle twitching or discomfort was reported by the patient then reduced to a comfortable level. Results: Within minutes of stimulation, the patient reported reduced dyspnea that was confirmed by spirometry fifteen minutes later (FEV1 increased from 2.70 L to 3.18 L). The FEV1 remained elevated during the 180min treatment (3.29 ± 0.04 L) and at 30min post stimulation (3.36 L). The FEV1 then decreased to 2.84 L 60min after stimulation ended. Conclusion: This finding indicates that low voltage vagus nerve stimulation could be a useful critical care treatment to alleviate smooth muscle bronchoconstriction and offer a new therapeutic approach to the treatment of acute asthma.
Mutational analysis of the interaction between staphylococcal protein A and human IgG1 (1993)

The interactions have been studied between an IgG-binding domain derivative based on domain B of staphylococcal protein A (designated Z) and human immunoglobulin G class 1 (IgG1) and its Fc fragment (Fc1) respectively. Five single amino acid substituted mutant forms of Z were constructed at the gene level, produced intracellularly in Escherichia coli, purified to homogeneity and characterized. Four of these Z variants, designated Z(L17D), Z(N28A), Z(I31A) and Z(K35A), were mutated in residues suggested to be involved in binding, based on the three-dimensional structure of the complex between a one domain protein A molecule and Fc1 [Deisenhofer, J. (1981) Biochemistry, 20, 2361-2370]. The fifth mutant protein, Z(F30A), had a mutation in a phenylalanine residue which was not expected to be involved in the interaction. Analysis by far UV circular dichroism spectroscopy suggests that all Z mutant proteins have similar folds. Their respective binding to human monoclonal IgG1 and to human recombinant Fc1 were studied in a competitive binding assay using radioactively labeled Z as a tracer, demonstrating that the mutant proteins with a substitution in the postulated binding surface showed a weakened binding to both the full-length antibody and the recombinant Fc1. The affinity constants of the interactions as well as relative binding free energies from the parent Z molecule were calculated. These values were similar for each Z variant to both IgG1 and Fc1, suggesting that Fc and not Fab binding was measured also for IgG1. However, the binding strengths differ significantly, and these binding properties were used to compare the contribution of each mutated amino acid residue in the Fc interaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Optically inscribed surface relief diffraction gratings on azobenzene-containing polymers for coupling light into slab waveguides (1996)

Surface relief diffraction gratings inscribed on azobenzene-containing polymers are designed to act as light couplers into slab waveguides. The gratings are inscribed both directly in poly{4-[2-(methacryloyloxy)ethyl]azobenzene} (pMEA) waveguide material, and in an azopolymer cladding layer applied to polyimide, silicon nitride, and silicon oxynitride films. Input and output coupling of both 633 and 830 nm light is observed in the waveguides.
评《纪律和社会(社会哲学方面)》一书 (1985)

本专著对纪律问题进行社会哲学分析,考察纪律的国家形式和社会形式。本书除导言和结束语外,共有九章。书中分析了现代社会哲学著作中说明得不够的一些纪律问题,例如,纪律和民主的社会形式;纪律的各种形式的分类;组织性;纪律、法纪和法制的相互关系以及违反纪律的原因;保证纪律的主要方向和方式;劳动集体在巩固国家纪律和社会纪律中的作用等等。作者把纪律作为社会哲学范畴来加以研究,同时指出了许多法学界的代表人物观念的局限性,这些人把纪律看作是纯上层建筑的现象。作者考察了苏联的一些经济学、伦理学、社会心理学和哲学研究等著作对纪律
Contact sensitizers modulate mechanisms of receptor‐mediated endocytosis but not fluid‐phase endocytosis in murine epidermal Langerhans cells (1995)

In order to define the influence of contact allergens on the fluid-phase endocytosis (FPE) of soluble molecules of murine epidermal Langerhans cells (LC), we studied the internalization of FITC-labeled bovine serum albumin (FITC-BSA), TRITC-labeled dextrane (TRITC-DEX) as well as horseradish peroxidase by LC. A 3-parameter flow-cytometric technique was performed for quantification of internalized FITC-BSA in LC using quantum red-labeled reagents for detection of Ia-antigen expression by LC and propidium iodide for exclusion of dead cells from analysis. A temperature-dependent rapid accumulation of FITC-BSA was noticed in time-course studies reaching a plateau between 1 and 2 h of in vitro culture at 37 degrees C. The quantity of FPE under stimulation with phorbol 12-myristate 13-acetate (PMA), concanavalin A (Con A), staphylococcal enterotoxin B (SEB) and contact sensitizers (DNFB, Kathon CG, K2Cr2O7) as well as the irritant SLS was determined. Treatment of LC with PMA and Con A resulted in a significant increase of total FITC-BSA uptake. The contact sensitizers as well as SEB and SLS failed to mediate augmented fluid-phase endocytosis. By use of the pH-insensitive soluble marker, TRITC-DEX and a microscope photometer for evaluation these findings could be confirmed. This excluded any artificial influence of differences in pH values in endocytotic compartments which might have influenced the fluorescence intensity of the pH-sensitive fluorochrome FITC. For qualitative analysis of FPE, the intracellular distribution of internalized horseradish peroxidase in LC was studied. An aggregated pattern became apparent in untreated LC and did not change under stimulation with any of the substances used.(ABSTRACT TRUNCATED AT 250 WORDS)
Critical impact velocity for ice fragmentation (2011)

The fragmentation process is a main concern in many engineering applications such as preventing flameouts of aircraft engines. The authors of this article are interested in measuring the critical impact velocity for ice fragmentation. Precisely, a dropweight technique was applied to study the ice ball impacts on glass plates. The influence of ice ball temperature, diameter and impact angle is also investigated. The after-impact ice ball state was found to be classified into two cases: an altered state and a non-altered state. The critical impact velocity is defined as the minimum impact velocity for which the ice ball is altered after impact or the maximum impact velocity for which the ice ball is not altered after impact. The experimental results are analysed by a model, assuming that the alteration regime is observed as soon as the ice ball normal kinetic energy is higher than a critical value of its deformation energy. This model depends on one parameter which is determined in this study. This last result is the major achievement of this article as there is almost no measurement of this parameter in the literature.
Galactose oxidase of Dactylium dendroides. Gene cloning and sequence analysis. (1992)

The gaoA gene, encoding the secreted copper-containing enzyme galactose oxidase, has been isolated from the Deuteromycete fungus Dactylium dendroides. Degenerate oligonucleotide primers were designed from amino acid sequence data for use in the polymerase chain reaction. A 1.4-kilobase DNA fragment amplified from genomic DNA was used to screen a genomic library constructed in ZAP. A strongly hybridizing clone was rescued as a pBluescript derivative, pGAO9, by in vivo excision. The sequence of 3466 nucleotides of pGAO9 insert DNA was determined by progressively designing sequencing primers. The translation product of the single long open reading frame matches the available galactose oxidase peptide sequence data, which represents 42% of the residues in the protein. The mature enzyme has 639 residues, which have been assigned to a 1.7-A electron density map (Ito, N., Phillips, S. E. V., Stevens, C., Ogel, Z. B., McPherson, M. J., Keen, J. N., Yadav, K. D. S., and Knowles, P. F. (1991) Nature 350, 87-90). The gene lacks introns and encodes an mRNA of approximately 2.5 kilobases with three transcription initiation start points at least 324 nucleotides upstream of the translation start site. Multiple ATG codons are present between the transcription initiation region and the start of the mature protein; two in-frame ATGs could encode the initiating Met residue to give proteins with 89 or 41 residue N-terminal leader peptides. The shorter potential leader has N-terminal features characteristic of a secretion signal sequence and may also contain a pro-sequence processed by an enzyme specific for a monobasic (arginine) cleavage site, as proposed for other fungal genes. The codon bias of gaoA is characteristic of other filamentous fungal genes. No significant homologies exist between galactose oxidase and other protein sequences available in data bases.