gebhart/patrepeval huggingface dataset:
Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-Cycle Infectious Influenza Virus (2014)

The effector functions of specific CD8 T cells are crucial in mediating influenza heterologous protection. However, new approaches for influenza vaccines that can trigger effective CD8 T cell responses have not been extensively explored. We report here the generation of single-cycle infectious influenza virus that lacks a functional hemagglutinin (HA) gene on an X31 genetic background and demonstrate its potential for triggering protective CD8 T cell immunity against heterologous influenza virus challenge. In vitro, X31-sciIV can infect MDCK cells, but infectious virions are not produced unless HA is transcomplemented. In vivo, intranasal immunization with X31-sciIV does not cause any clinical symptoms in mice but generates influenza-specific CD8 T cells in lymphoid (mediastinal lymph nodes and spleen) and nonlymphoid tissues, including lung and bronchoalveolar lavage fluid, as measured by H2-Db NP366 and PA224 tetramer staining. In addition, a significant proportion of X31-sciIV-induced antigen-specific respiratory CD8 T cells expressed VLA-1, a marker that is associated with heterologous influenza protection. Further, these influenza-specific CD8 T cells produce antiviral cytokines when stimulated with NP366 and PA224 peptides, indicating that CD8 T cells triggered by X31-sciIV are functional. When challenged with a lethal dose of heterologous PR8 virus, X31-sciIV-primed mice were fully protected from death. However, when CD8 T cells were depleted after priming or before priming, mice could not effectively control virus replication or survive the lethal challenge, indicating that X31-sciIV-induced memory CD8 T cells mediate the heterologous protection. Thus, our results demonstrate the potential for sciIV as a CD8 T cell-inducing vaccine. Importance: One of the challenges for influenza prevention is the existence of multiple influenza virus subtypes and variants and the fact that new strains can emerge yearly. Numerous studies have indicated that the effector functions of specific CD8 T cells are crucial in mediating influenza heterologous protection. However, influenza vaccines that can trigger effective CD8 T cell responses for heterologous protection have not been developed. We report here the generation of an X31 (H3N2) virus-derived single-cycle infectious influenza virus, X31-sciIV. A one-dose immunization with X31-sciIV is capable of inducing functional influenza virus-specific CD8 T cells that can be recruited into respiratory tissues and provide protection against lethal heterologous challenge. Without these cells, protection against lethal challenge was essentially lost. Our data indicate that an influenza vaccine that primarily relies on CD8 T cells for protection could be developed.
MIXING TASTE ILLUSIONS: THE EFFECT OF MIRACULIN ON BINARY AND TRINARY MIXTURES (2011)

ABSTRACT Miraculin, the extract of miracle fruit ( Richadella dulcifica or Synsepalum dulcificum ), is a taste‐modifying protein, its effect consisting in a temporary and almost complete replacement of sour taste with sweet taste. Despite psychophysical investigations were carried out in the past, very little is known about the effect of this molecule on taste interactions. We investigated the changes induced by miraculin on the gustatory sensations evoked by isolated tastants (citric acid, caffeine, NaCl and sucrose) and by binary and trinary mixtures that included a sour tastant (citric acid). We confirmed the effects of miraculin on citric acid, both as a single tastant and in mixtures. In mixtures including a salty tastant, the “illusory sweetness” induced by miraculin significantly reduced saltiness. Variable effects were shown on the perception of bitterness, although mostly in the direction of bitterness suppression. Finally, contrary to previous results, miraculin added sweetness in mixtures that included a sweet tastant. PRATICAL APPLICATIONS The taste‐modifying protein miraculin has been known since long time due to its surprising property of transforming sourness into sweetness. Here, we put at test the properties of miraculin in mixtures, proving that its sweetness‐inducing effect has an impact also on saltiness and bitterness, provided that the mixture includes a sour tastant (citric acid). In all mixtures containing NaCl (sour‐salty, sour‐salty‐bitter and sour‐salty‐sweet), saltiness was significantly reduced, suggesting a suppressive interaction between miraculin‐induced sweetness and NaCl. Similarly, although less strongly, the bitterness (of caffeine) was suppressed in two mixtures out of three (sour‐bitter and sour‐bitter‐sweet).
Graphene Oxide: Intrinsic Peroxidase Catalytic Activity and Its Application to Glucose Detection (2010)

Carboxyl-modified graphene oxide (GO–COOH) possesses intrinsic peroxidase-like activity that can catalyze the reaction of peroxidase substrate 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue color reaction. A simple, cheap, and highly sensitive and selective colorimetric method for glucose detection has been developed and will facilitate the utilization of GOCOOH intrinsic peroxidase activity in medical diagnostics and biotechnology. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Multi-C/A code acquisition method (2007)

There are about 30 GPS satellites in space, but the number of satellite received by a conventional receiver is about 10 or 11 under the clear sky. When the users are in urban area or any difficult environment, the number of satellite in view will be significantly reduced. Thus, the acquisition method needs to be improved to identify more satellites. If the receiver extends the searching space or increases the coherent integration time and non-coherent stages, then it needs more time to identify all satellite. The proposed idea in this paper is to acquire the satellite with stronger power first, and it will then change the acquisition method to deal with the satellite with weak power. This new acquisition method will slightly change the conventional FFT method, and it can combine with the other acquisition methods for the weak signal process. The main algorithm of this new acquisition method is to process the convolution with the summation of multi-C/A codes, and we call that Multi-C/A code acquisition method. The new method can save the processing time to acquire strong power satellite first, and the saving in the processing time could be used to acquire weak power satellite with other acquisition methods.
Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes (2014)

Our results demonstrate that MRgFUS thalamotomy is a safe, effective and less-invasive surgical method for treating medication-refractory ET. However, several issues must be resolved before clinical application of MRgFUS, including optimal patient selection and management of patients during treatment.
Secure Web scripting (1998)

Current Web scripting languages lack an explicit security model. The model proposed in the article has been implemented for JavaScript in the Mozilla browser source code; it is realized by a "safe" interpreter and based on three basic building blocks: access control, to regulate what data a script can access on a user's machine and in what mode; independence of contexts, to ensure that two scripts executing in different contexts (for example, simultaneously in different browser windows or sequentially in the same browser window) cannot access each other's data at will; and trust management, to regulate how trust is established and terminated among scripts executing simultaneously in different contexts. We also advocate a clear separation between a security policy and an implementation. Different users require different degrees of privacy and security, which translate to different degrees of flexibility when interacting with a Web server; these differences can be expressed in different security policies. A sound implementation, however, should be universally applicable. These are principles that first appeared decades ago in work on secure operating systems.
The art of the obvious (1992)

In addition to normal reading, knowledge can be gained from a paper document by pattern recognition and encoding of characteristics of the information media. There are reasons to believe that this can be done automatically with very little attentional demand. The knowledge gained is accessible to consciousness and can be used for task components like orientation, navigation, detection of changes and as a complement to normal reading. When information is computerized, and is read from a screen instead of from a paper, the conditions for automaticity are often radically changed. In most cases the reader has to gain the corresponding knowledge by effortful cognitive processes. This means adding to the cognitive load leaving less attentional capacity for the main task at hand. This problem can be avoided by a careful analysis of a reading task into its automatic and non-automatic components, followed by a dedicated user interface design where information relevant for orientation, navigation, etc. is presented in a way that the reader can perceive rather than read.
Expression of cell-associated and secreted forms of herpes simplex virus type 1 glycoprotein gB in mammalian cells (1987)

The gene for glycoprotein gB1 of herpes simplex virus type 1 strain Patton was expressed in stable Chinese hamster ovary cell lines. Expression vectors containing the dihydrofolate reductase (dhfr) cDNA plus the complete gB1 gene or a truncated gene lacking the 194 carboxyl-terminal amino acids of gB1 were transfected into CHO DHFR-deficient cells. Radioimmunoprecipitation demonstrated that the complete gB1 protein expressed in CHO cell lines was cell associated, whereas the truncated protein was secreted from the cells due to deletion of the transmembrane and C-terminal domains of gB1. Cells expressing the truncated gB1 protein were subjected to stepwise methotrexate selection, and a cell line was isolated in which the gB1 gene copy number had been amplified 10-fold and the level of expression of gB1 had increased over 60-fold. The truncated gB1 protein was purified from medium conditioned by the amplified cell line. N-terminal amino acid sequence analysis of this purified protein identified the signal peptide cleavage site and predicted the cleavage of a 30-amino-acid signal sequence from the primary protein. The immunogenicity of the truncated gB1 protein was also tested in mice, and high levels of antibody and protection from virus challenge were observed.
Frequency Modulation Response of a Tunable Birefringent Mode Nematic Liquid Crystal Electrooptic Device Fabricated by Doping Nanoparticles of Pd Covered with Liquid-Crystal Molecules (2002)

We fabricated a tunable birefringent (TB) mode nematic liquid-crystal (NLC) electrooptic device using NLC-K15 (Merck) as a host NLC (called NLC-1), where the cell is doped with Pd nanoparticles covered with NLC (NLC-2) molecules, having a cyano group such as 5CB (Merck) with positive dielectric anisotropy (Δε>0) or CCN-47 (Merck) with negative Δε (Δε<0). The diameter of the core Pd particle is 2.5 nm and the concentration of nanoparticles is 1 wt%. The TB mode LCD cell fabricated in this way exhibits a remarkable frequency modulation response below 100 Hz of the driving voltage waveform. It is considered that the frequency modulation (FM) response of the TB-NLCD may be attributed to Maxwell-Wagner type interfacial polarization between the host NLC medium and doped nanoparticles.
Pharmacological brake-release of mRNA translation enhances cognitive memory (2013)

Phosphorylation of the α-subunit of initiation factor 2 (eIF2) controls protein synthesis by a conserved mechanism. In metazoa, distinct stress conditions activate different eIF2α kinases (PERK, PKR, GCN2, and HRI) that converge on phosphorylating a unique serine in eIF2α. This collection of signaling pathways is termed the 'integrated stress response' (ISR). eIF2α phosphorylation diminishes protein synthesis, while allowing preferential translation of some mRNAs. Starting with a cell-based screen for inhibitors of PERK signaling, we identified a small molecule, named ISRIB, that potently (IC50 = 5 nM) reverses the effects of eIF2α phosphorylation. ISRIB reduces the viability of cells subjected to PERK-activation by chronic endoplasmic reticulum stress. eIF2α phosphorylation is implicated in memory consolidation. Remarkably, ISRIB-treated mice display significant enhancement in spatial and fear-associated learning. Thus, memory consolidation is inherently limited by the ISR, and ISRIB releases this brake. As such, ISRIB promises to contribute to our understanding and treatment of cognitive disorders. DOI:http://dx.doi.org/10.7554/eLife.00498.001.
Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis (2010)

Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.
The Role of Medications in Causing Dry Eye (2012)

The purpose of this paper is to review the possible role of polypharmacy in causing dry eye disease (DED), reflecting the complex interactions and complications associated with the use of multiple systemic and topical ocular medications. The pharmacological, physiological, anatomical, and histological mechanisms causing dry mouth differ little from those causing dry eye. Oral polypharmacy is the most common cause of dry mouth, but has not been investigated as a cause of dry eye. Topical ocular polypharmacy has been shown to cause DED. Information on drugs that likely cause or aggravate DED and the controversial role of preservatives in topical ocular medications are examined. Systemic or topical ocular medications and preservatives used in topical ocular drugs may cause dry eye through the drug's therapeutic action, ocular surface effects, or preservatives, and the effects probably are additive. Long-term use of topical ocular medications, especially those containing preservatives such as BAK, may play an important role in DED and the role of polypharmacy needs further study. We review possible ways to decrease the risk of medication-related dry eye.
A Linear Peptide Containing Minimal T- and B-Cell Epitopes ofPlasmodium falciparumCircumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge (2006)

An effective malaria vaccine is needed to address the public health tragedy resulting from the high levels of morbidity and mortality caused by Plasmodium parasites. The first protective immune mechanism identified in the irradiated sporozoite vaccine, the "gold standard" for malaria preerythrocytic vaccines, was sporozoite-neutralizing antibody specific for the repeat region of the surface circumsporozoite (CS) protein. Previous phase I studies demonstrated that a branched peptide containing minimal T- and B-cell epitopes of Plasmodium falciparum CS protein elicited antirepeat antibody and CD4(+)-T-cell responses comparable to those observed in volunteers immunized with irradiated P. falciparum sporozoites. The current study compares the immunogenicity of linear versus tetrabranched peptides containing the same minimal T- and B-cell epitopes, T1BT*, comprised of a CS-derived universal Th epitope (T*) synthesized in tandem with the T1 and B repeats of P. falciparum CS protein. A simple 48-mer linear synthetic peptide was found to elicit antisporozoite antibody and gamma interferon-secreting T-cell responses comparable to the more complex tetrabranched peptides in inbred strains of mice. The linear peptide was also immunogenic in outbred nonhuman primates (Aotus nancymaae), eliciting antibody titers equivalent to those induced by tetrabranched peptides. Importantly, the 48-mer linear peptide administered in adjuvants suitable for human use elicited antibody-mediated protection against challenge with rodent malaria transgenic sporozoites expressing P. falciparum CS repeats. These findings support further evaluation of linear peptides as economical, safe, and readily produced malaria vaccines for the one-third of the world's population at risk of malaria infection.
SDA, A New Solution for Transceivers (1986)

SDA stands as a synonym for "Switchable Direction Amplifier". For such an amplifier the direction of amplification is controlled by the polarity of the applied DC voltages. The same principle may be extended to build active mixers of switchable direction (SDMs). Therefore it is possible to operate a complete receiver front-end, consisting of an RF-amplifier, mixer and IF-amplifier, as a transmitter by reversing the polarity of the supply voltage. The basics of such amplifiers and some experimental results are presented.
Toxicity and Mode of Action of Bacillus thuringiensis Cry Proteins in the Mediterranean Corn Borer, Sesamia nonagrioides (Lefebvre) (2006)

Sesamia nonagrioides is one of the most damaging pests of corn in Spain and other Mediterranean countries. Bt corn expressing the Bacillus thuringiensis Cry1Ab toxin is being grown on about 58,000 ha in Spain. Here we studied the mode of action of this Cry protein on S. nonagrioides (binding to specific receptors, stability of binding, and pore formation) and the modes of action of other Cry proteins that were found to be active in this work (Cry1Ac, Cry1Ca, and Cry1Fa). Binding assays were performed with (125)I- or biotin-labeled toxins and larval brush border membrane vesicles (BBMV). Competition experiments indicated that these toxins bind specifically and that Cry1Aa, Cry1Ab, and Cry1Ac share a binding site. Cry1Ca and Cry1Fa bind to different sites. In addition, Cry1Fa binds to Cry1A's binding site with very low affinity and vice versa. Binding of Cry1Ab and Cry1Ac was found to be stable over time, which indicates that the observed binding is irreversible. The pore-forming activity of Cry proteins on BBMV was determined using the voltage-sensitive fluorescent dye DiSC(3)(5). Membrane permeability increased in the presence of the active toxins Cry1Ab and Cry1Fa but not in the presence of the nonactive toxin Cry1Da. In terms of resistance management, based on our results and the fact that Cry1Ca is not toxic to Ostrinia nubilalis, we recommend pyramiding of Cry1Ab with Cry1Fa in the same Bt corn plant for better long-term control of corn borers.
Recombinant factor VIII and factor VIII-von Willebrand factor complex do not present danger signals for human dendritic cells (2006)

Several lines of evidence have shown that antibody responses to coagulation factor VIII (FVIII) in patients with hemophilia A depend on the help of activated CD4(+) T cells. The primary activation of CD4(+) T cells requires interaction with mature dendritic cells (DCs) that present antigenic peptides in the context of MHC class II and express costimulatory molecules. Maturation of DCs requires danger signals provided by exogenous or endogenous stimuli such as pathogen-derived products or inflammatory cytokines. We asked the question whether FVIII itself, FVIII complexed with von Willebrand factor (VWF) or thrombin-activated FVIII contain danger signals for human DCs that induce the upregulation of costimulatory molecules or the expression of proinflammatory cytokines necessary for effective activation of CD4(+) T cells. Human peripheral monocytes were differentiated into DCs. FVIII, thrombin-activated FVIII, VWF, VWF-FVIII, lipopolysaccharide (LPS), LPS + FVIII, LPS + VWF or LPS + FVIII-VWF were added either on day 0 or on day 5 of differentiation cultures. Differentiation markers, cytokines in cell culture supernatants and the capacity of DCs to stimulate autologous and allogeneic T cells were analysed after seven days of differentiation cultures. Our results indicate that neither FVIII, thrombin-activated FVIII, VWF nor a complex of FVIII and VWF modulate the maturation of human DCs or their capacity to stimulate autologous or allogeneic T cells. We conclude that neither of these proteins present danger signals to human DCs.
A polybasic domain allows nonprenylated Ras proteins to function in Saccharomyces cerevisiae. (1994)

Ras proteins undergo a series of posttranslational modifications prior to association with the cytoplasmic surface of the plasma membrane. The modification steps include farnesylation, proteolysis, methylesterification, and palmitoylation. A 4-amino acid residue motif known as the CaaX box (C is cysteine, a is generally aliphatic, and X is the carboxyl-terminal residue) is the sequence recognized by the prenyl transferase that initiates the modification pathway. As part of our studies to define the requirements for Ras membrane association, we directed mutagenesis to the yeast Ras2 protein CaaX box to assess the relative importance of prenylation, palmitoylation, and stretches of basic amino acids on the function of the protein. The wild type yeast Ras2 protein terminates in the sequence Cys-Cys-Ile-Ile-Ser. We have identified mutations that do not contain a CaaX box but still encode functional Ras proteins. These mutations replace the terminal serine of the CaaX box with the sequence -Lys-Leu-Ile-Lys-Arg-Lys. Three mutants have been analyzed in detail. Ras2(CCIIKLIKRK) functions at a level similar to wild type Ras2, whereas cells expressing only Ras2(SCIIKLIKRK) and Ras2(SSIIKLIKRK) forms of Ras2 protein grow more slowly at 30 degrees C. In addition, strains expressing only Ras2(SSIIKLIKRK) protein fail to grow at 37 degrees C. Replacement of the basic residues with neutral amino acids (Ras2(CCIISIIS)) completely abolishes their ability to support Ras-dependent growth. The extension mutants are not prenylated, but Ras2(CCIIKLIKRK) and Ras2(SCIIKLIKRK) are palmitoylated. These results demonstrate that a diverse set of carboxyl-terminal sequence motifs and posttranslational modifications lead to functional Ras proteins in yeast.
Von Willebrand factor in the vessel wall mediates platelet adherence (1985)

A monoclonal antibody directed against the von Willebrand factor moiety (vWF) of factor VIII-von Willebrand factor (FVIII-vWF), which blocks ristocetin-induced platelet aggregation as well as the binding of FVIII-vWF to platelets in the presence of ristocetin, inhibited platelet adherence to human artery subendothelium when present in normal flowing blood. This monoclonal antibody, CLB-RAg 35, inhibited platelet adherence as a function of the shear rate. At wall shear rates below 500 s-1, platelet adherence was not affected, but at higher shear rates platelet adherence was gradually inhibited, reaching an average of 11% of the normal value at 2,500 s-1. Indirect immunofluorescence established the reactivity of CLB-RAg 35 with vWF present in artery subendothelium. Pretreatment of normal vessel walls with this antibody inhibited adherence of platelets in blood from a patient with severe homozygous von Willebrand's disease and in blood from normal individuals. The inhibition was shear-rate dependent and significant at high shear rates (2,500 s-1). By adding increasing amounts of purified FVIII-vWF to normal blood, the inhibition was gradually overcome. These data indicate that vWF present in the vessel wall contributes appreciably to platelet adherence. At high wall shear rates, platelet adherence is mediated virtually completely by both plasma FVIII-vWF and vWF in the vessel wall. At low wall shear rates (below 500 s-1), platelet adherence occurs independent of FVIII-vWF in plasma and vWF in the vessel wall.