gebhart/patrepeval huggingface dataset:
B cell epitope mapping of the bacterial superantigen staphylococcal enterotoxin B: the dominant epitope region recognized by intravenous IgG (1997)

We showed that i.v. IgG contains Abs against a major group of bacterial superantigens, and that they can inhibit superantigen-elicited T cell activation. The B cell epitope region of the superantigen and the inhibitory mechanism have remained unknown. To analyze the dominant B cell epitopes on the bacterial superantigen SEB (staphylococcal enterotoxin B), we constructed fusion proteins of SEB deletion mutants, and the reactivities of these recombinant proteins to i.v. IgG and healthy human sera were evaluated by means of immunoblotting. Intravenous IgG and healthy human sera mostly recognized the C-terminal fragment (amino acid (aa) 133-239). The C-terminally truncated protein (aa 1-228) and the truncated mutant delta 225-234 lost reactivity, while the truncated protein (aa 1-234) did not, suggesting that the region (aa 225-234) is the dominant B cell epitope. The mutant, in which residues 226-229 of SEB were exchanged for residues 209-212 of streptococcal pyrogenic exotoxin A, reduced the reactivity with the C-terminal region-specific IgG purified by affinity chromatography. The C-terminal region-specific IgG inhibited SEB-elicited T cell activation, suggesting that this Ab that recognizes the epitope functions as the humoral defensive factor against SEB in humans. Furthermore, the assumed epitope region was homology to the residues (aa 32-41) of human thymopoietin, containing the biologic active site.
Epigenetic modulation in the treatment of atherosclerotic disease (2014)

Cardiovascular disease is the single largest cause of death in the western world and its incidence is on the rise globally. Atherosclerosis, characterized by the development of atheromatus plaque, can trigger luminal narrowing and upon rupture result in myocardial infarction or ischemic stroke. Epigenetic phenomena are a focus of considerable research interest due to the role they play in gene regulation. Epigenetic mechanisms such as DNA methylation and histone acetylation have been identified as potential drug targets in the treatment of cardiovascular disease. miRNAs are known to play a role in gene silencing, which has been widely investigated in cancer. In comparison, the role they play in cardiovascular disease and plaque rupture is not well understood. Nutritional epigenetic modifiers from dietary components, for instance sulforaphane found in broccoli, have been shown to suppress the pro-inflammatory response through transcription factor activation. This review will discuss current and potential epigenetic therapeutics for the treatment of cardiovascular disease, focusing on the use of miRNAs and dietary supplements such as sulforaphane and protocatechuic aldehyde.
Binding and Antigen Presentation of Ceramide-Containing Glycolipids by Soluble Mouse and Human Cd1d Molecules (1999)

We have purified soluble mouse and human CD1d molecules to assess the structural requirements for lipid antigen presentation by CD1. Plate-bound CD1d molecules from either species can present the glycolipid alpha-galactosyl ceramide (alpha-GalCer) to mouse natural killer T cells, formally demonstrating both the in vitro formation of antigenic complexes, and the presentation of alpha-GalCer by these two CD1d molecules. Using surface plasmon resonance, we show that at neutral pH, mouse CD1 and human CD1d bind to immobilized alpha-GalCer, unlike human CD1b, which requires acidic pH for lipid antigen binding. The CD1d molecules can also bind both to the nonantigenic beta-GalCer and to phosphatidylethanolamine, indicating that diverse lipids can bind to CD1d. These studies provide the first quantitative analysis of monomeric lipid antigen-CD1 interactions, and they demonstrate that the orientation of the galactose, or even the nature of the polar head group, are likely to be more important for T cell receptor contact than CD1d binding.
An ion-controlled four-color fluorescent telomeric switch on DNA origami structures (2016)

The folding of single-stranded telomeric DNA into guanine (G) quadruplexes is a conformational change that plays a major role in sensing and drug targeting. The telomeric DNA can be placed on DNA origami nanostructures to make the folding process extremely selective for K(+) ions even in the presence of high Na(+) concentrations. Here, we demonstrate that the K(+)-selective G-quadruplex formation is reversible when using a cryptand to remove K(+) from the G-quadruplex. We present a full characterization of the reversible switching between single-stranded telomeric DNA and G-quadruplex structures using Förster resonance energy transfer (FRET) between the dyes fluorescein (FAM) and cyanine3 (Cy3). When attached to the DNA origami platform, the G-quadruplex switch can be incorporated into more complex photonic networks, which is demonstrated for a three-color and a four-color FRET cascade from FAM over Cy3 and Cy5 to IRDye700 with G-quadruplex-Cy3 acting as a switchable transmitter.
Kinesin family in murine central nervous system. (1992)

In neuronal axons, various kinds of membranous components are transported along microtubules bidirectionally. However, only two kinds of mechanochemical motor proteins, kinesin and brain dynein, had been identified as transporters of membranous organelles in mammalian neurons. Recently, a series of genes that encode proteins closely related to kinesin heavy chain were identified in several organisms including Schizosaccharomyces pombe, Aspergillus niddulans, Saccharomyces cerevisiae, Caenorhabditus elegans, and Drosophila. Most of these members of the kinesin family are implicated in mechanisms of mitosis or meiosis. To address the mechanism of intracellular organelle transport at a molecular level, we have cloned and characterized five different members (KIF1-5), that encode the microtubule-associated motor domain homologous to kinesin heavy chain, in murine brain tissue. Homology analysis of amino acid sequence indicated that KIF1 and KIF5 are murine counterparts of unc104 and kinesin heavy chain, respectively, while KIF2, KIF3, and KIF4 are as yet unidentified new species. Complete amino acid sequence of KIF3 revealed that KIF3 consists of NH2-terminal motor domain, central alpha-helical rod domain, and COOH-terminal globular domain. Complete amino acid sequence of KIF2 revealed that KIF2 consists of NH2-terminal globular domain, central motor domain, and COOH-terminal alpha-helical rod domain. This is the first identification of the kinesin-related protein which has its motor domain at the central part in its primary structure. Northern blot analysis revealed that KIF1, KIF3, and KIF5 are expressed almost exclusively in murine brain, whereas KIF2 and KIF4 are expressed in brain as well as in other tissues. All these members of the kinesin family are expressed in the same type of neurons, and thus each one of them may transport its specific organelle in the murine central nervous system.
Rapid, high fidelity analysis of simple sequence repeats on an electronically active DNA microchip (2000)

We describe a method for the discrimination of short tandem repeat (STR) alleles based on active microarray hybridization. An essential factor in this method is electronic hybridization of the target DNA, at high stringency, in <5 min. High stringency is critical to avoid slippage of hybrids along repeat tracts at allele-specific test sites in the array. These conditions are attainable only with hybridization kinetics realized by electronic concentration of DNA. A sandwich hybrid is assembled, in which proper base stacking of juxtaposed terminal nucleotides results in a thermodynamically favored complex. The increased stability of this complex relative to non-stacked termini and/or base pair mismatches is used to determine the identification of STR alleles. This method is capable of simultaneous and precise identification of alleles containing different numbers of repeats, as well as mutations within these repeats. Given the throughput capabilities of microarrays our system has the potential to enhance the use of microsatellites in forensic criminology, diagnostics and genetic mapping.
A neural network for 3D gaze recording with binocular eye trackers (2005)

Using eye tracking for the investigation of visual attention has become increasingly popular during the last few decades. Nevertheless, only a small number of eye tracking studies have employed 3D displays, although such displays would closely resemble our natural visual environment. Besides higher cost and effort for the experimental setup, the main reason for the avoidance of 3D displays is the problem of computing a subject's current 3D gaze position based on the measured binocular gaze angles. The geometrical approaches to this problem that have been studied so far involved substantial error in the measurement of 3D gaze trajectories. In order to tackle this problem, we developed an anaglyph-based 3D calibration procedure and used a well-suited type of artificial neural network—a parametrized self-organizing map (PSOM)—to estimate the 3D gaze point from a subject's binocular eye-position data. We report an experiment in which the accuracy of the PSOM gaze-point estimation is compared to a geometrical solution. The results show that the neural network approach produces more accurate results than the geometrical method, especially for the depth axis and for distant stimuli.
Preparation and physical characteristics of a hemoglobin solution modified by coupling to 2‐nor‐2‐formylpyridoxal 5‘‐phosphate (1987)

Stroma‐free hemoglobin (Hb) solutions were prepared on a 20‐I scale. In 3‐I batches, the beta chains of hemoglobin were crosslinked with 2‐nor‐ 2‐formylpyridoxal 5′‐phosphate (NFPLP) that was synthesized on a gram scale. The coupling efficiency was 60 to 80 percent. The oxygen dissociation curve of these Hb/HbNFPLP mixtures was shifted to the right with P50 (PO2 for 50% saturation with oxygen) values of 26 to 38 torr versus values of 12 to 16 torr for the nonmodified hemoglobin solutions. Both the H+ Bohr factor and the Hill coefficient were lower for the Hb/HbNFPLP mixture than for the original hemoglobin solution. The oxygen‐binding coefficient β was the same for both types of Hb solutions. The viscosity and the colloid osmotic pressure of both solutions were also the same. During storage at 4 ° C for 18 months, no precipitation or denaturation of hemoglobin was detectable in either solution. There was also no conversion of the modified hemoglobin molecules, HbNFPLP, to the native hemoglobin tetramers, dimers, or monomers. The percentage of methemoglobin remained at 5 percent for about 6 months; it increased to 26 percent over the next 12 months. The results indicate that intramolecular coupling of hemoglobin with NFPLP yields a stable product with physiologic oxygen‐carrying properties.
Vaccines containing purified GM2ganglioside elicit GM2 antibodies inmelanoma patients (1987)

ABSTRACT GM2, GD2, and GD3 gangliosides are ex-pressedonthesurfaceofhumanmelanomacells andrepresentpotential targets for immunological control of melanomagrowth by monoclonal antibodies and active immunization.TheimmunogenicityofGM2wasinvestigatedbyanalyzingthehumoralimmuneresponseofmelanomapatientstovaccinationwith cell lines selected for high GM2 expression and with vaccinescontainingpurified GM2.Thewhole-cell vaccineand vaccines containing purified GM2 and bacillus Calmette-Guerin (BCG) elicited GM2 antibody in a high proportion of patients, particularly in GM2/BCG-vaccinated patientspretreated with cyclophosphamide and given a GM2/BCG boosterimmunization. Vaccines containing purified GM2andSalmonella minnesota R595asthe adjuvant werealso effective, but only in patients pretreated with cyclophosphamide. GM2antibodies in vaccinated patients were of the IgM class andwere cytotoxic for GM2-positive targets in the presence of humancomplement.Gangliosides are prominentcell-surface constituents of
The Inside Out of Lentiviral Vectors (2011)

Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them.
RNA-Independent DNA Cleavage Activities of Cas9 and Cas12a (2017)

CRISPR-Cas systems provide bacteria and archaea with sequence-specific protection against invading mobile genetic elements. In the presence of divalent metal ions, Cas9 and Cas12a (formerly Cpf1) proteins target and cleave DNA that is complementary to a cognate guide RNA. The recognition of a protospacer adjacent motif (PAM) sequence in the target DNA by Cas9 and Cas12a is essential for cleavage. This RNA-guided DNA targeting is widely used for gene-editing methods. Here, we show that Francisella tularensis novicida (Fno) Cas12a, FnoCas9, and Streptococcus pyogenes Cas9 (SpyCas9) cleave DNA without a guide RNA in the presence of Mn<sup>2+</sup> ions. Substrate requirements for the RNA-independent activity vary. FnoCas9 preferentially nicks double-stranded plasmid, SpyCas9 degrades single-stranded plasmid, and FnoCas12a cleaves both substrates. These observations suggest that the identities and levels of intracellular metals, along with the Cas9/Cas12a ortholog employed, could have significant impacts in genome editing applications.
Comparison between low and high read bias in FB-RAM on UTBOX FDSOI devices (2012)

This paper investigates the drain read bias impact on the FB-BRAM performance of Ultra Thin Buried Oxide (UTBOX) Fully Depleted Silicon On Insulator (FDSOI) devices. Both simulations and experimental results are used. Two read regimes are clearly observed. In the read regime at higher drain voltage, impact ionization is occurring and this result in a higher sense margin and a lower retention time compared to the low drain voltage read regime.
The cue‐responsivity phenomenon in dependent drinkers: ‘personality’ vulnerability and anxiety as intervening variables (1991)

The cue-responsivity phenomenon to alcohol-associated stimuli in dependent drinkers was examined. In accordance with previous research, significant differences on both physiological and subjective cue-responsivity variables, between dependent and non-dependent drinkers were found. The unique contribution of this paper is two-fold. Firstly, evidence is presented which suggests that the Eysenckian personality traits of introversion and neuroticism are more predictive of cue-responsivity variance in the dependent drinkers than either severity of dependence or number of years' drinking. Secondly, within this dependent group, the relationship between cue-responsivity and 'craving' was seen to be less straightforward than traditionally thought. Specifically, it suggested that it was the extent to which autonomic cue-responsivity elicited increases in self-reported anxiety, which predicted most of the variance on the 'craving' variable. Taken together, these results raise the interesting possibility that a personality disposition akin to trait anxiety, and the degree to which cue exposure elicits state anxiety, mediated the relationship between cue-responsivity and 'craving' in dependent drinkers.
Molecular cloning and characterization of a proline iminopeptidase gene from Neisseria gonorrhoeae (1993)

Proline iminopeptidase (Pip) is a hydrolase elaborated by virtually all strains of Neisseria gonorrhoeae that selectively removes N-terminal proline residues from peptides. Escherichia coli clones expressing the gonococcal gene coding for Pip were identified in a genomic cosmid library using a synthetic colorimetric substrate. Nucleotide sequence determination and analyses of polypeptides detected by coupled in vitro transcription/translation reactions revealed that Pip is a 311-amino-acid polypeptide with a M(r) of 35 kDa and a pI of 5.4. Southern hybridization showed that the pip gene is present in a single copy on the chromosome of N. gonorrhoeae strain MS11 which maps immediately upstream of the previously identified opaA locus. The transcriptional start site of pip in E. coli, determined by primer extension analysis, was characteristic of an NtrA or sigma-54-dependent promotor. Complementation of an E. coli mutant deficient in both proline biosynthesis and dipeptide uptake confirmed that Pip is capable of releasing biologically active proline from peptides. Pip expression was found to be non-essential for in vitro growth of N. gonorrhoeae, based on the viability of a Pip- gonococcal mutant.
Phase 1 Single‐ and Multiple‐Ascending‐Dose Randomized Studies of the Safety, Pharmacokinetics, and Pharmacodynamics of AG‐348, a First‐in‐Class Allosteric Activator of Pyruvate Kinase R, in Healthy Volunteers (2018)

Pyruvate kinase deficiency is a chronic hemolytic anemia caused by mutations in PK-R, a key glycolytic enzyme in erythrocytes. These 2 phase 1 randomized, placebo-controlled, double-blind healthy-volunteer studies assessed the safety, tolerability, and pharmacokinetics/pharmacodynamics of AG-348, a first-in-class allosteric PK-R activator. Twelve sequential cohorts were randomized 2:6 to receive oral placebo or AG-348, respectively, as a single dose (30-2500 mg) in the single-ascending-dose (SAD) study (ClinicalTrials.gov: NCT02108106) or 15-700 mg every 12 hours or 120 mg every 24 hours, for 14 days in the multiple-ascending-dose (MAD) study (ClinicalTrials.gov: NCT02149966). All 48 subjects completed the fasted SAD part; 44 of 48 completed the MAD (2 discontinued because of adverse events [AEs], 2 withdrew consent). The most common treatment-related AEs in AG-348-treated subjects were headache (16.7% [SAD] and 13.9% [MAD]) and nausea (13.9%, both studies). AE frequency increased at AG-348 doses ≥ 700 mg (SAD) and at 700 mg every 12 hours (MAD); 1 grade ≥ 3 AE occurred in the latter cohort. Pharmacokinetics were favorable with low variability. Dose-dependent changes in blood glycolytic intermediates consistent with glycolytic pathway activation were observed at all MAD doses, supporting future trials investigating the potential of AG-348 for treating PK deficiency or other anemias.
Video Compression With Rate-Distortion Autoencoders (2019)

In this paper we present a deep generative model for lossy video compression. We employ a model that consists of a 3D autoencoder with a discrete latent space and an autoregressive prior used for entropy coding. Both autoencoder and prior are trained jointly to minimize a ratedistortion loss, which is closely related to the ELBO used in variational autoencoders. Despite its simplicity, we find that our method outperforms the state-of-the-art learned video compression networks based on motion compensation or interpolation. We systematically evaluate various design choices, such as the use offrame-based or spatio-temporal autoencoders, and the type of autoregressive prior. In addition, we present three extensions of the basic method that demonstrate the benefits over classical approaches to compression. First, we introduce semantic compression, where the model is trained to allocate more bits to objects of interest. Second, we study adaptive compression, where the model is adapted to a domain with limited variability, e.g. videos taken from an autonomous car, to achieve superior compression on that domain. Finally, we introduce multimodal compression, where we demonstrate the effectiveness of our model in joint compression of multiple modalities captured by non-standard imaging sensors, such as quad cameras. We believe that this opens up novel video compression applications, which have not been feasible with classical codecs.
Protein Insertion into the Membrane of the Endoplasmic Reticulum: The Architecture of the Translocation Site (1995)

In mammalian cells, most membrane proteins are inserted cotranslationally into the membrane of the endoplasmic reticulum (ER), and secretory proteins are translocated across this membrane (for review, see Rapoport 1992). These processes are initiated in the cytoplasm by binding of the signal sequence of the nascent polypeptide chain to the signal recognition particle (SRP) (Walter and Blobel 1981). The resulting ribosome nascent chain SRP complex is then targeted to the ER membrane by an interaction with the membrane-bound SRP receptor (docking protein) (Gilmore et al. 1982; Meyer et al. 1982). At the membrane, the signal sequence is released from SRP in a GTP-requiring step, and the nascent polypeptide is transferred into the ER translocation site (Connolly and Gilmore 1989).
Identification and Analysis of the Polyhydroxyalkanoate-Specific β-Ketothiolase and Acetoacetyl Coenzyme A Reductase Genes in the Cyanobacterium Synechocystis sp. Strain PCC6803 (2000)

Synechocystis sp. strain PCC6803 possesses a polyhydroxyalkanoate (PHA)-specific beta-ketothiolase encoded by phaA(Syn) and an acetoacetyl-coenzyme A (CoA) reductase encoded by phaB(Syn). A similarity search of the entire Synechocystis genome sequence identified a cluster of two putative open reading frames (ORFs) for these genes, slr1993 and slr1994. Sequence analysis showed that the ORFs encode proteins having 409 and 240 amino acids, respectively. The two ORFs are colinear and most probably coexpressed, as revealed by sequence analysis of the promoter regions. Heterologous transformation of Escherichia coli with the two genes and the PHA synthase of Synechocystis resulted in accumulation of PHAs that accounted for up to 12.3% of the cell dry weight under high-glucose growth conditions. Targeted disruption of the above gene cluster in Synechocystis eliminated the accumulation of PHAs. ORFs slr1993 and slr1994 thus encode the PHA-specific beta-ketothiolase and acetoacetyl-CoA reductase of Synechocystis and, together with the recently characterized PHA synthase genes in this organism (S. Hein, H. Tran, and A. Steinbüchel, Arch. Microbiol. 170:162-170, 1998), form the first complete PHA biosynthesis pathway known in cyanobacteria. Sequence alignment of all known short-chain-length PHA-specific acetoacetyl-CoA reductases also suggests an extended signature sequence, VTGXXXGIG, for this group of proteins. Phylogenetic analysis further places the origin of phaA(Syn) and phaB(Syn) in the gamma subdivision of the division Proteobacteria.