gebhart/patrepeval huggingface dataset:
The antiviral drug ribavirin does not mimic the 7-methylguanosine moiety of the mRNA cap structure in vitro (2005)

The eukaryotic initiation factor eIF4E binds the mRNA 5' cap structure and has a central role during translational initiation. eIF4E and the mechanisms to control its activity have oncogenic properties and thus have become targets for anticancer drug development. A recent study (Kentsis et al. 2004) presented evidence that the antiviral nucleoside ribavirin and its phosphorylated derivatives were structural mimics of the mRNA cap, high-affinity ligands for eIF4E, and potent repressors of eIF4E-mediated cell transformation and tumor growth. Based on these findings, we tested ribavirin, ribavirin triphosphate (RTP), and the dinucleotide RpppG for their ability to inhibit translation in vitro. Surprisingly, the ribavirin-based compounds did not affect translation at concentrations where canonical cap analogs efficiently block cap-dependent translation. Using a set of reporter mRNAs that are translated via either cap-dependent or viral internal ribosome entry sites (IRES)-dependent initiation, we found that these ribavirin-containing compounds did inhibit translation at high (millimolar) concentrations, but there was no correlation of this inhibition with an eIF4E requirement for translation. The addition of a ribavirin-containing cap to mRNA did not stimulate translation. Fluorescence titration experiments with eIF4E and the nuclear cap-binding complex CBC indicated affinities for RTP and RpppG that were two to four orders of magnitude lower than those of m(7)GTP and m(7)GpppG. We conclude that, at least with respect to translation, ribavirin does not act in vitro as a functional mimic of the mRNA cap.
Guillain-Barré as an Autoimmune Disease (1996)

Guillain-Barré syndrome (GBS) entails a demyelinating process of the peripheral nervous system. The etiopathogenesis of the syndrome is still a matter of debate although considerable progress has been accomplished in the recent years. Abundant evidence has been put forward so as to support the role of the immune system in initiating and perpetuating the ongoing damage culminating in the emergence of the clinically overt syndrome. As such, data on the involvement of the humoral immune pathways add to the information already presented with regard to cell-mediated mechanisms participating in disruption of peripheral nerve. The following review will focus on the current knowledge of these complex mechanisms and the relative significance of each in the pathogenesis of GBS.
Black box variational inference for state space models (2015)

Latent variable time-series models are among the most heavily used tools from machine learning and applied statistics. These models have the advantage of learning latent structure both from noisy observations and from the temporal ordering in the data, where it is assumed that meaningful correlation structure exists across time. A few highly-structured models, such as the linear dynamical system with linear-Gaussian observations, have closed-form inference procedures (e.g. the Kalman Filter), but this case is an exception to the general rule that exact posterior inference in more complex generative models is intractable. Consequently, much work in time-series modeling focuses on approximate inference procedures for one particular class of models. Here, we extend recent developments in stochastic variational inference to develop a `black-box' approximate inference technique for latent variable models with latent dynamical structure. We propose a structured Gaussian variational approximate posterior that carries the same intuition as the standard Kalman filter-smoother but, importantly, permits us to use the same inference approach to approximate the posterior of much more general, nonlinear latent variable generative models. We show that our approach recovers accurate estimates in the case of basic models with closed-form posteriors, and more interestingly performs well in comparison to variational approaches that were designed in a bespoke fashion for specific non-conjugate models.
Evaluation of the meaningfulness of health‐related quality of life improvements as assessed by the SF‐36 and the EQ‐5D VAS in patients with active Crohn’s disease (2009)

For the first time, the MCID values provided interpretation guidelines for PRO results in CD. This research demonstrates that patients treated with certolizumab pegol benefit from meaningful and sustained HRQOL improvements.
A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities (1997)

The authors have informed us that, in the above paper, several polypeptide GalNAc transferases were listed as part of family 2, i.e. a family of inverting enzymes. However, these enzymes transfer GalNAc from UDP-GalNAc to Ser or Thr residues forming an linkage. They are therefore retaining enzymes and, on this basis, they should be removed from family 2 and grouped in a new family (family 27) of retaining nucleotide-diphosphosugar glycosyltransferases. It is important to point out that the sequences of family 27 members display limited similarities with those of enzymes from family 2. It is therefore possible that these two families share some structural similarities. The composition of family 27 is given in the table below.
Bifunctional Gold-Coated Magnetic Silica Spheres (2006)

A method for the development of bifunctional magnetic and optically tunable nanoparticles with a structural design involving a magnetic iron oxide core (Fe3O4/γ-Fe2O3) surrounded by a thick silica shell and further covered with an outer shell of gold is reported. These gold-coated magnetic silica spheres take advantage of the strong resonance absorption they show in the visible and near-infrared (NIR) range and can be controlled by using an external magnetic field, which makes them very promising in biomedical applications.
Palladium-catalyzed inter- and intramolecular cross-coupling reactions of B-alkyl-9-borabicyclo[3.3.1]nonane derivatives with 1-halo-1-alkenes or haloarenes. Syntheses of functionalized alkenes, arenes, and cycloalkenes via a hydroboration-coupling sequence (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPalladium-catalyzed inter- and intramolecular cross-coupling reactions of B-alkyl-9-borabicyclo[3.3.1]nonane derivatives with 1-halo-1-alkenes or haloarenes. Syntheses of functionalized alkenes, arenes, and cycloalkenes via a hydroboration-coupling sequenceNorio Miyaura, Tatsuo Ishiyama, Hirotomo Sasaki, Masako Ishikawa, Makoto Sato, and Akira SuzukiCite this: J. Am. Chem. Soc. 1989, 111, 1, 314–321Publication Date (Print):January 1, 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://pubs.acs.org/doi/10.1021/ja00183a048https://doi.org/10.1021/ja00183a048research-articleACS PublicationsRequest reuse permissionsArticle Views9458Altmetric-Citations496LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Evolutionary dynamics of an Arabidopsis insect resistance quantitative trait locus (2003)

Glucosinolate profiles differ among Arabidopsis thaliana ecotypes, caused by the composition of alleles at several glucosinolate biosynthetic loci. One of these, GS-Elong, harbors a family of methylthioalkylmalate synthase (MAM) genes that determine the side chain length of aliphatic glucosinolate structures. Fine mapping reveals that GS-Elong constitutes an insect resistance quantitative trait locus, caused by variation in glucosinolate profiles conferred by polymorphism of MAM alleles in this region. A sequence survey of randomly chosen ecotypes indicates that GS-Elong is highly variable among A. thaliana ecotypes: indel polymorphisms are frequent, as well as gene conversion events between gene copies arranged in tandem. Furthermore, statistical methods of molecular population genetics suggest that one of the genes, MAM2, is subject to balancing selection. This may be caused by ecological tradeoffs, i.e., by contrasting physiological effects of glucosinolates on generalist vs. specialist insects.
Flash-Photolysis of Fully Reduced and Mixed-Valence CO-Bound Rhodobacter sphaeroides Cytochrome c Oxidase:  Heme Spectral Shifts (2007)

Conformational changes, internal electron transfer, and CO rebinding processes in cytochrome c oxidase from Rhodobacter sphaeroides reduced to different degrees were investigated. The reactions were followed using a gated optical spectrometric multichannel analyzer. Light-induced difference spectra, recorded in the 350-700 nm region over the 100 ns to 1 s time interval, were analyzed by singular value decomposition and global exponential fitting. The photolyzed fully reduced enzyme showed two relaxations, approximately 1 and 190 mus, prior to the 20 ms CO rebinding process. Intramolecular electron transfer was monitored following photolysis of the mixed-valence CO-bound enzyme. The analysis revealed 1.1 micros, 2.4 micros, 31 micros, 68 ms, and 240 ms apparent lifetimes, the first three of which are attributed to electron transfer from heme a3 to heme a with contribution from a relaxation process at the heme a3 site. Spectral changes associated with the microsecond processes are consistent with 75% electron transfer from heme a3 to heme a. A comparison of the experimental spectra and model difference spectra for the intramolecular electron transfer indicated approximately 3 nm blue shift in the absolute spectra of both the oxidized heme a3 and reduced heme a generated in the process. The 68 and 240 ms lifetimes are due to CO recombination to heme a3 and are attributed to the presence of two conformers, the slower rate corresponding to the conformer in higher abundance. The dependency of the apparent rate of CO rebinding on the intensity of the probe beam in single-wavelength experiments is explained.
A scalable speech and audio coding scheme with continuous bitrate flexibility (2004)

Networks are getting more and more heterogeneous. Scalable codecs are especially suited for such a context as they permit the bitrate to be lowered in a simple way, at any point of the transmission, for adaptation to network conditions and to terminal capacities. Classically, scalable codecs are organised in layers and scalability is obtained by sending more or fewer layers to the decoder. The obtained granularity depends on the layer sizes, and the available bitrates are fixed and limited in number. The paper presents a novel scalable audio coding scheme where the bitrates vary continuously between a minimal and a maximal value, allowing free modification of the bitrate. With this novel approach, all bitrates are valid, sending even one more bit results in different output signal with statistically growing quality. Test results show that this method provides quality as good as or even better than that of a non-scalable version.
Functional Characterization of Human Cancer-Derived TRKB Mutations (2011)

Cancer originates from cells that have acquired mutations in genes critical for controlling cell proliferation, survival and differentiation. Often, tumors continue to depend on these so-called driver mutations, providing the rationale for targeted anticancer therapies. To date, large-scale sequencing analyses have revealed hundreds of mutations in human tumors. However, without their functional validation it remains unclear which mutations correspond to driver, or rather bystander, mutations and, therefore, whether the mutated gene represents a target for therapeutic intervention. In human colorectal tumors, the neurotrophic receptor TRKB has been found mutated on two different sites in its kinase domain (TRKB(T695I) and TRKB(D751N)). Another site, in the extracellular part of TRKB, is mutated in a human lung adenocarcinoma cell line (TRKB(L138F)). Lastly, our own analysis has identified one additional TRKB point mutation proximal to the kinase domain (TRKB(P507L)) in a human melanoma cell line. The functional consequences of all these point mutations, however, have so far remained elusive. Previously, we have shown that TRKB is a potent suppressor of anoikis and that TRKB-expressing cells form highly invasive and metastatic tumors in nude mice. To assess the functional consequences of these four TRKB mutations, we determined their potential to suppress anoikis and to form tumors in nude mice. Unexpectedly, both colon cancer-derived mutants, TRKB(T695I) and TRKB(D751N), displayed reduced activity compared to that of wild-type TRKB. Consistently, upon stimulation with the TRKB ligand BDNF, these mutants were impaired in activating TRKB and its downstream effectors AKT and ERK. The two mutants derived from human tumor cell lines (TRKB(L138F) and TRKB(P507L)) were functionally indistinguishable from wild-type TRKB in both in-vitro and in-vivo assays. In conclusion, we fail to detect any gain-of-function of four cancer-derived TRKB point mutations.
Specific High Affinity Interactions of Monomeric Endotoxin·Protein Complexes with Toll-like Receptor 4 Ectodomain (2006)

Potent Toll-like receptor 4 (TLR4) activation by endotoxin has been intensely studied, but the molecular requirements for endotoxin interaction with TLR4 are still incompletely defined. Ligand-receptor interactions involving endotoxin and TLR4 were characterized using monomeric endotoxin.protein complexes of high specific radioactivity. The binding of endotoxin.MD-2 to the TLR4 ectodomain (TLR4ECD) and transfer of endotoxin from CD14 to MD-2/TLR4ECD were demonstrated using HEK293T-conditioned medium containing TLR4ECD+/-MD-2. These interactions are specific, of high affinity (KD<300 pm), and consistent with the molecular requirements for potent cell activation by endotoxin. Both reactions result in the formation of a Mr approximately 190,000 complex composed of endotoxin, MD-2, and TLR4ECD. CD14 facilitates transfer of endotoxin to MD-2 (TLR4) but is not a stable component of the endotoxin.MD-2/TLR4 complex. The ability to assay specific high affinity interactions of monomeric endotoxin.protein complexes with TLR4ECD should allow better definition of the structural requirements for endotoxin-induced TLR4 activation.
Human Kallikrein 6: A New Potential Serum Biomarker for Uterine Serous Papillary Cancer (2005)

hK6 is highly expressed in USPC and is released in the plasma and serum of USPC patients. hK6 may represent a novel biomarker for USPC for monitoring early disease recurrence and response to therapy.
Interferometric measurement of the refractive-index distribution in plastic lenses by use of computed tomography (2002)

A nondestructive measurement method that makes possible the measurement of a three-dimensional refractive-index distribution of any shape plastic lens is presented. In this method, a Mach-Zehnder interferometer and shearing interferometer are combined into a single optical system and are used selectively. Interference fringes of a test object that is immersed in matching liquid are detected at various rotation angles. And transmitted wave fronts are calculated with these interference fringes. Finally, the refractive-index distribution is obtained by computed tomography analysis. In addition, accurate control of the matching liquid temperature makes it possible to measure the absolute refractive index of the test object. This system has good performance with a measurement accuracy of 10(-4) or better peak to valley.
A mitochondrial membrane protein defined by a novel monoclonal antibody is preferentially detected in apoptotic cells (1996)

Studies toward the biologic and molecular understanding of programmed cell death have been stimulated by the recent identification of genes and their products that regulate apoptosis. A panel of mAbs has been raised against dying cells in the present study by immunizing mice with apoptotic Jurkat cells. One of these Abs, anti-7A6, was found to react with apoptotic cells. Using ELISA or flow cytometry, little reactivity of anti-7A6 was observed in normal or digitonin-permeabilized human peripheral blood lymphocytes and a number of hemopoietic cell lines tested. The Ab, however, strongly reacted with these cells when they were induced to undergo apoptosis by irradiation or treatment with apoptosis-inducing agents. Cell sorting and DNA fragmentation experiments revealed that 7A6-positive cells, but not 7A6-negative cells, had apparent DNA fragments characteristic of cells undergoing apoptosis. By immunoblot, under reducing conditions, anti-7A6 detected a 38-kDa protein band in the cell lysates prepared from apoptotic cells. Immunoelectron microscopy showed the 7A6 Ag to be localized to the membrane of mitochondria in apoptotic Jurkat cells. These results indicate that anti-7A6 defines a novel epitope on the mitochondrial membrane protein that appears to be exposed on cells undergoing apoptosis, suggesting that the 7A6 molecule may be involved in the molecular cascade of apoptotic cell death.
Effect of dilution rate on lipopolysaccharide and serum resistance of Neisseria gonorrhoeae grown in continuous culture (1983)

Growth of Neisseria gonorrhoeae strain FA171 in continuous culture under glucose-limiting conditions resulted in a growth-rate-dependent change in the lipopolysaccharide (LPS). The evidence for this change is an alteration in the mobility of purified alkali-treated LPS on sodium dodecyl sulfate-polyacrylamide gels and a quantitative difference in the amount of the LPS serotype antigen. The LPS from cells grown at a low dilution rate (0.12 h-1) contained ca. eightfold less serotype antigen than the LPS from cells grown at a high dilution rate (0.56 h-1). The decrease in LPS serotype antigen was associated with an increase in sensitivity to the bactericidal activity of normal human serum and an increase in cell surface hydrophobicity. An increase in the amount of serotype antigen was associated with a reduction in the accessibility of a monoclonal antibody to a core LPS determinant, an increase in resistance to normal human serum, and a decrease in cell surface hydrophobicity. The microheterogeneity of gonococcal LPS with respect to the content of serotype antigen may result from an alteration in the metabolism of glucose.
Dissecting cytotoxic T cell responses towards the NY‐ESO‐1 protein by peptide/MHC‐specific antibody fragments (2004)

NY-ESO-1 is a germ cell antigen aberrantly expressed by different tumor types that elicits strong humoral and cellular immune responses, representing one of the most promising candidates for vaccination of cancer patients. A detailed analysis of CD8(+) T cells generated in vaccine trials using NY-ESO-1-derived peptides (157-165 and 157-167) revealed that the dominant immune response was directed against a cryptic epitope (159-167) diverting the immune response from tumor recognition. Only CTL reactivity to the NY-ESO-1(157-165) peptide appeared to be capable of lysing NY-ESO-1/HLA-A0201-expressing tumor cells. To study the process of NY-ESO-1 peptide presentation by tumor cells in more detail we generated a high-affinity (K(D)=60 nM) antibody fragment that specifically recognizes the NY-ESO-1(157-165) peptide/HLA-A0201 complex. Peptide variants such as the NY-ESO-1(157-167) peptide or the cryptic NY-ESO-1(159-167) peptide were not recognized. The antibody fragment blocked in a dose-dependent fashion the recognition of NY-ESO-1/HLA-A2-positive tumor cells by NY-ESO-1(157-165) peptide-specific CD8(+) T cells. This antibody fragment is a novel reagent that binds with TCR-like specificity to the NY-ESO-1(157-165)/HLA-A2 complex thus distinguishing between CTL responses against immunological meaningful or cryptic NY-ESO-1-derived peptides. It may therefore become a useful monitoring tool for the development of NY-ESO-1-based cancer vaccines.
High resolution optical A/D conversion using oversampling and interpolative coding (2002)

A novel approach to optical analog-to-digital (A/D) conversion based on oversampling and interpolative coding techniques is proposed. This approach incorporates the high resolution capabilities of classical oversampled A/D conversion with the high speed of optical processing technology to extend the resolution and conversion rates beyond those currently possible with other electronic or optical converters. The proposed optical converter uses optical threshold and arithmetic operators and fundamentally trades bandwidth for improving amplitude resolution. A non-interferometric realization using multiple quantum well electroabsorption modulators, photodetectors, and a novel approach for noninterferometric optical subtraction is described that can provide 8 bit resolution at a conversion rate of approximately 1 GHz.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum. (1985)

The complete primary structure of the 3.1S leucine-rich alpha 2-glycoprotein (LRG) present in human plasma has been determined. This protein (Mr approximately 45,000) consists of a single polypeptide chain with one galactosamine and four glucosamine oligosaccharides attached. The polypeptide has two intrachain disulfide bonds and contains 312 amino acid residues of which 66 are leucine. The amino acid sequence can be exactly divided into 13 segments of 24 residues each, eight of which exhibit a periodic pattern in the occurrence of leucine, proline, and asparagine. The consensus sequence for the repeating tetracosapeptide unit is Pro-Xaa-Xaa-Leu-Leu-Xaa-Xaa-Xaa-X aa-Xaa-Leu-Xaa-Xaa-Leu-Xaa-Leu-Xaa-Xaa-Asn-Xaa-Leu-Xaa-Xaa-Leu. This periodicity suggests that the unique structure of LRG arose from a series of unequal crossovers of a precursor oligonucleotide sequence that encoded a building block rich in leucine. Overall, the amino acid sequence of LRG is not significantly homologous to the continuous sequence of any protein in the current data base. However, the consensus tetracosapeptide sequence shows strong homology to segments of many mitochondrial proteins, viral envelope proteins, and oncogene proteins that have a high leucine content and transmembrane domains. Tandem repetition of similar segments also occurs in apolipoproteins that have amphipathic helical potential. Prediction of the secondary structure by the Chou-Fasman rules and calculation of the hydrophilic/hydrophobic profile by several methods confirm the tandem repetition of largely hydrophobic structural units; these begin with a beta-turn that leads into an organized structure with alpha-helical or beta-sheet potential. These structural characteristics and the homology to mitochondrial proteins and apolipoproteins suggest that LRG is a membrane-derived or membrane-associated protein containing a series of domains capable of bipolar surface orientation.