gebhart/patrepeval huggingface dataset:
Chemically Modified Hammerhead Ribozymes with Improved Catalytic Rates (1996)

A site-specific chemical modification strategy has been employed to elucidate structure-function relationships at the only phylogenetically nonconserved position within the core of the hammerhead ribozyme (N7). Four different base substitutions at position 7 resulted in increased catalytic rates. A pyridin-4-one base substitution increased the rate of the chemical step up to 12-fold. These results are the first examples of chemical modifications within a catalytic RNA that enhance the rate of the chemical step. Four base substitutions resulted in decreased catalytic rates. The results do not correlate with proposed hydrogen bond interactions (Pley et al., 1994; Scott et al., 1995). This study demonstrates the utility of using unnatural nucleotide analogs-rather than mutagenesis with the four standard nucleotides alone-to elucidate structure-function relationships of small RNAs.
Imporved biological activity of antisense oligonucleotides conjugated to a fusogenic peptide (1994)

Recently several groups reported a dramatic improvement of reporter gene transfection efficiency using a fusogenic peptide, derived from the Influenza hemagglutinin envelop protein. This peptide changes conformation at acidic pH and destabilizes the endosomal membranes thus resulting in an increased cytoplasmic gene delivery. We describe the use of a similar fusogenic peptide in order to improve the antiviral potency of antisense oligodeoxynucleotides (anti TAT) and oligophosphorothioates (S-dC28) on de novo HIV infected CEM-SS lymphocytes in serum-free medium. We observed as 5 to 10 fold improvement of the anti HIV activities of the phosphodiester antisense oligonucleotides after chemical coupling to the peptide in a one to one ratio by a disulfide or thioether bond. No toxicities were observed at the effective doses (0.1-1 microM). No sequence specificity was obtained and the fusogenic peptide possessed some antiviral activities on its own (IC50: 6 microM). A S-dC28-peptide disulfide linked conjugate and a streptavidin-peptide-biotinylated S-dC28 adduct showed similar activities as the free S-dC28 oligonucleotide (IC50: 0.1-1 nM). As expected, all the compounds were less potent in the presence of serum but the relative contribution of peptide coupling was maintained.
Learning to rank with ties (2008)

Designing effective ranking functions is a core problem for information retrieval and Web search since the ranking functions directly impact the relevance of the search results. The problem has been the focus of much of the research at the intersection of Web search and machine learning, and learning ranking functions from preference data in particular has recently attracted much interest. The objective of this paper is to empirically examine several objective functions that can be used for learning ranking functions from preference data. Specifically, we investigate the roles of ties in the learning process. By ties, we mean preference judgments that two documents have equal degree of relevance with respect to a query. This type of data has largely been ignored or not properly modeled in the past. In this paper, we analyze the properties of ties and develop novel learning frameworks which combine ties and preference data using statistical paired comparison models to improve the performance of learned ranking functions. The resulting optimization problems explicitly incorporating ties and preference data are solved using gradient boosting methods. Experimental studies are conducted using three publicly available data sets which demonstrate the effectiveness of the proposed new methods.
Some factors affecting cerebral tissue saturation during obstructive sleep apnoea (2002)

Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA) may provide additional information to conventional peripheral oxygen saturation. Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7±27.9) were monitored using full polysomnography and monitoring of near-infrared cerebral tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen saturation ( S a,O 2 ) dip, minimum S a,O 2 , TOI dip and minimum TOI. Cerebral TOI is a measure of cerebral tissue saturation of haemoglobin with oxygen, calculated using near-infrared spatially resolved spectroscopy, which has been shown to have a high specificity for intracranial changes. Decreases in cerebral oxygenation were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1–73.0% and mean apnoea/hypopnoea related TOI dips ranged from 1.43–6.85%. Mean S a,O 2 dips varied from 3.8–21.7%. In regression analysis, factors significantly predicting the magnitude of the TOI dip were S a,O 2 dip, minimum S a,O 2 , apnoea duration and rapid eye movement sleep stage. The effect of apnoea duration and sleep stage remained significant after S a,O 2 was included in the regression equation. Near-infrared spectroscopy provides a noninvasive technique for monitoring cerebral tissue saturation during obstructive sleep apnoea.
High Resolution Mapping of the Binding Site on Human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and Design of IgG1 Variants with Improved Binding to the FcγR (2001)

Immunoglobulin G (IgG) Fc receptors play a critical role in linking IgG antibody-mediated immune responses with cellular effector functions. A high resolution map of the binding site on human IgG1 for human Fc gamma RI, Fc gamma RIIA, Fc gamma RIIB, Fc gamma RIIIA, and FcRn receptors has been determined. A common set of IgG1 residues is involved in binding to all Fc gamma R; Fc gamma RII and Fc gamma RIII also utilize residues outside this common set. In addition to residues which, when altered, abrogated binding to one or more of the receptors, several residues were found that improved binding only to specific receptors or simultaneously improved binding to one type of receptor and reduced binding to another type. Select IgG1 variants with improved binding to Fc gamma RIIIA exhibited up to 100% enhancement in antibody-dependent cell cytotoxicity using human effector cells; these variants included changes at residues not found at the binding interface in the IgG/Fc gamma RIIIA co-crystal structure (Sondermann, P., Huber, R., Oosthuizen, V., and Jacob, U. (2000) Nature 406, 267-273). These engineered antibodies may have important implications for improving antibody therapeutic efficacy.
Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 (2013)

The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.
Depleted-Heterojunction Colloidal Quantum Dot Solar Cells (2010)

Colloidal quantum dot (CQD) photovoltaics combine low-cost solution processability with quantum size-effect tunability to match absorption with the solar spectrum. Rapid recent advances in CQD photovoltaics have led to impressive 3.6% AM1.5 solar power conversion efficiencies. Two distinct device architectures and operating mechanisms have been advanced. The first-the Schottky device-was optimized and explained in terms of a depletion region driving electron-hole pair separation on the semiconductor side of a junction between an opaque low-work-function metal and a p-type CQD film. The second-the excitonic device-employed a CQD layer atop a transparent conductive oxide (TCO) and was explained in terms of diffusive exciton transport via energy transfer followed by exciton separation at the type-II heterointerface between the CQD film and the TCO. Here we fabricate CQD photovoltaic devices on TCOs and show that our devices rely on the establishment of a depletion region for field-driven charge transport and separation, and that they also exploit the large bandgap of the TCO to improve rectification and block undesired hole extraction. The resultant depleted-heterojunction solar cells provide a 5.1% AM1.5 power conversion efficiency. The devices employ infrared-bandgap size-effect-tuned PbS CQDs, enabling broadband harvesting of the solar spectrum. We report the highest open-circuit voltages observed in solid-state CQD solar cells to date, as well as fill factors approaching 60%, through the combination of efficient hole blocking (heterojunction) and very small minority carrier density (depletion) in the large-bandgap moiety.
Influence of Human CD8 on Antigen Recognition by T-Cell Receptor–Transduced Cells (2006)

The CD8 coreceptor on T cells has two functions. Namely, CD8 acts to stabilize the binding of the T-cell receptor (TCR) to the peptide-MHC complex while localizing p56(lck) (lck) to the TCR/CD3 complex to facilitate early signaling events. Although both functions may be critical for efficient activation of a CTL, little is known about how the structural versus signaling roles of CD8, together with the relative strength of the TCR, influences T-cell function. We have addressed these issues by introducing full-length and truncated versions of the CD8alpha and CD8beta chains into CD8(-) Jurkat cell clones expressing cloned TCRs with known antigen specificity and relative affinities. Using a combination of antigen recognition and tetramer-binding assays, we find that the intracellular lck-binding domain of CD8 is critical for enhanced T-cell activation regardless of the relative strength of the TCR. In contrast, the extracellular domain of CD8 seems to be critical for TCRs with lower affinity but not those with higher affinity. Based on our results, we conclude that there are different requirements for CD8 to enhance T-cell function depending on the strength of its TCR.
Population Structure and Breeding Patterns of 145 U.S. Rice Cultivars Based on SSR Marker Analysis (2005)

This study was undertaken to investigate the population structure of U.S. rice ( Oryza sativa L.). A total of 115 U.S. rice cultivars and 30 ancestral accessions introduced from Asia were genotyped by means of 169 simple sequence repeat (SSR) markers that are well distributed throughout the rice genome. SSR‐based clustering analysis identified three groups of U.S. rice cultivars that were recognizable as temperate japonica with short to medium grains, tropical japonica with medium grains, and tropical japonica with long grains. Indica cultivars were represented among ancestral accessions, but always clustered independently. Indica germplasm has been used for cultivar improvement, but never directly in U.S. rice production. Cluster analysis of cultivars based on four time periods representing their first release date or introduction (1900–1929, 1930–1959, 1960–1979, and 1980–2000) resulted in the identification of the same three groups. This suggests that the population structure in U.S. rice was established before 1930 and remains essentially intact today, despite a large amount of controlled crossing and artificial selection as a part of the breeding process. Fifty‐seven percent of U.S. rice cultivars were developed from intragroup crosses, indicating the availability of substantial genetic variability within each group. Similar results were obtained using genetic distance‐based and model‐based clustering methods. Information about population structure and associated phenotypic characteristics recognized by geneticists and breeders paves the way for coordinated association mapping studies in the future.
Exact image theory for the Sommerfeld half-space problem, part I: Vertical magnetic dipole (1984)

Applying the Laplace transform, the exact distributed image current function is obtained for the classical Sommerfeld half-space problem with vertical magnetic current source. The resulting field integral is well behaved when the image current is situated in complex space. Unlike previous approximate images, the present theory is valid for any distance, height of the source, frequency, and half-space parameters. It is demonstrated that the present image theory reduces to the well-known dipole image at complex depth for large dielectric parameters of the half-space. Also, the reflection-coefficient method is obtained as a farfield approximation. Calculation of fields through exact image integration is seen to be simple and accurate and require modest computer capacity and time. In an appendix, some properties of the multivalued Green's function arising from a dipole source in complex space are also studied.
Intramyocardial injection of naked DNA encoding HIF-1 /VP16 hybrid to enhance angiogenesis in an acute myocardial infarction model in the rat (2002)

The HIF-1alpha/VP16 hybrid transcription factor is able to reduce infarct size and enhance neovascularization in an acute ischemic myocardium. The potency of VEGF and HIF-1alpha/VP16 hybrid as therapeutic angiogenic factors in acute hypoxic myocardium is similar.
Identification and Characterization of Che a 1 Allergen from <i>Chenopodium album</i> Pollen (2002)

Che a 1, a relevant allergen from chenopod pollen, is structurally related to the Ole e 1-like protein family, but exhibits significant differences on its polypeptide sequence that could explain its different antigenic behavior and limited cross-reactivity.
Quantitative determination by real-time PCR of four vaginal Lactobacillus species, Gardnerella vaginalis and Atopobium vaginae indicates an inverse relationship between L. gasseri and L. iners (2007)

In our study we found a clear negative association between L. iners and L. gasseri and between A. vaginae and L. gasseri. Our results do not provide support for the generally held proposition that grade II is an intermediate stage between grades I and III, because L. gasseri, abundant in grade II is not predominant in grade III, whereas L. iners, abundant in grade III is present only in low numbers in grade II samples.
Eltoprazine in aggressive mentally handicapped patients (1994)

The efficacy of eltoprazine, a mixed 5-HT1 agonist, in treating aggressive behaviour in mentally handicapped patients was evaluated in a double-blind, placebo- and baseline-controlled study. In the total sample of 160 patients who entered the 8 week double-blind treatment phase, efficacy was not demonstrated. Also in a 28 week double-blind follow-up study, efficacy could not be demonstrated. Post-hoc exploratory analyses suggested eltoprazine was significantly better than placebo in reducing aggression scores of a subgroup of severely aggressive patients. There was no evident relationship between the plasma level of eltoprazine and therapeutic effect or safety and tolerance. The overall safety and tolerance of chronic eltoprazine treatment was good. In the discussion, several issues and pitfalls of aggression research are dealt with.
fipB and fipC: two bacterial loci required for morphogenesis of the filamentous bacteriophage f1 (1985)

We describe the identification of two mutations in bacterial genes, designated as fipB and fipC, which resulted in temperature-sensitive morphogenesis of bacteriophage f1. These mutations mapped at separate loci but had to be present simultaneously to block f1 production at 41.5 degrees C. One mutation defined the locus fipB at 85.3 min on the Escherichia coli linkage map; the other defined the locus fipC, which mapped very close to rpsL at 73 min. Since these mutations did not appear to affect phage DNA replication, gene expression, or protein localization, they probably interfered with the its life cycle at the level of assembly. fipB mutants were partially deficient in adsorption of bacteriophage lambda, and fipB and fipC mutants leaked beta-lactamase into the medium, suggesting that the mutations affect outer-membrane structure or function.
Dose dependency of aflatoxin B1 binding on human high molecular weight DNA in the activation of proto-oncogene. (1985)

The binding of aflatoxin B1, AFB1, a potent hepatocarcinogen, to various high molecular weight (HMW) DNAs from human normal liver and two liver cancer cell lines, Alexander primary liver carcinoma (PLC) and Mahlavu hepatocellular carcinoma (hHC) and from NIH/3T3 cell have been investigated. The kinetics of AFB1 binding to these DNAs showed similar initial rates but the extents of binding to the PLC and hHC DNAs seemed to be slightly higher. Preferential AFB1 bindings were identified in both PLC and hHC DNAs compared to normal liver DNA when analyzed by restriction endonuclease digestions and agarose gel electrophoresis. A critical AFB1 binding dosage, ranging 100 to 460 fmole/microgram DNA, was found to activate the carcinogenic effect of the Mahlavu hHC HMW DNA, but not normal liver HMW DNA, rendering it capable of inducing focal transformation in NIH/3T3 cell. Excessive AFB1 binding on the hHC and PLC HMW DNAs resulted in an "over-kill" of both cell transformation capability and templating activity of the DNA.
Polymethylated DOTA Ligands. 2. Synthesis of Rigidified Lanthanide Chelates and Studies on the Effect of Alkyl Substitution on Conformational Mobility and Relaxivity (2002)

M4DOTA, [(2S,5S,8S,11S)-4,7,10-tris-carboxymethyl-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid (2e), and M4DOTMA, (R)-2-[(2S,5S,8S,11S)-4,7,10-tris-((R)-1-carboxyethyl)-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]propionic acid (3e), are derivatives of ligand DOTA (1e) that form sterically crowded lanthanide chelates. M4DOTMA forms highly symmetric and totally rigid single Y(3+) and Yb(3+) species in which the ring substituents occupy corner positions in a square antiprismatic arrangement as shown by molecular mechanics calculations and by a quantitative interpretation of the relative magnitudes of the paramagnetic (1)H NMR shifts of dipolar origin. The NMR spectrum of YbM4DOTMA(-) displays two intense methyl peaks outside the 0-10 ppm range whose shift difference is strongly temperature dependent. YbM4DOTMA(-) (3d) could be a useful probe in magnetic resonance thermometric imaging. With only four methyl substituents on the tetraaza ring, M4DOTA forms three Yb(3+) species in solution. The methyl substituents prevent the inversion of configuration of the ethylenic groups but not of the acetate arms. Although the methyl groups are likely to preferably occupy ring corner positions, the dipolar equations do not allow one to distinguish with certainty between the two available corner (equatorial) orientations. Reliably applying the dipolar equations is less obvious than usually assumed. A single methyl substituent as in ligand MDOTA (5e) suffices to rigidify the tetraaza cycle but not the acetate arms. Racemic YbMDOTA(-) (5d) is present in solution as four totally asymmetric topomers with the methyl groups occupying either one of the two equatorial positions. A complete assignment of the solution structures on the basis of the dipolar equations is again uncertain. The nuclear magnetic relaxation dispersion curves of the Gd(3+) chelates of all the methylated DOTA ligands including DOTMA, (R)-2-[4,7,10-tris-((R)-carboxyethyl)- 1,4,7,10- tetraazacyclododecan-1-yl]propionic acid, are very similar, and intermolecular conformational processes appear to have no influence on the relaxivity of these small complexes for which the relaxation T(1) is mainly determined by the rotational correlation time (tau(r)). The hydration number of the Tb(3+) chelates measured by fluorescence decreases from DOTMA to M4DOTMA presumably because steric crowding leads to an increase of the metal-water distance.
Biochemical, Morphological, and Functional Analyses of a Cyclic Peptide, Phospholipid, and DNA Ternary Complex used for Gene Delivery (1998)

AbstractGene delivery and expression in mammalian cells can be facilitated by a complex composed of the cyclic amphipathic peptides, gramicidin S or tyro-cidine, dioleoylphosphatidylethanolamine (Dope) and DNA. We have characterized physical features of complexes formed from various peptide/Dope/ DNA ratios using dynamic light scattering, sedimentation, electrophoretic mobility and DNA accessibility to ethidium intercalation and correlated these with transfection. The addition of Dope dispersions to the peptide-DNA pair produces negatively-charged particles with zeta potentials between -27.5 mV and -55 mV at pH 8.5 and diameters as measured by dynamic light scattering, between 100 nm to 400 nm. The diameter of the complex depends upon the ratio of the components. The cyclic peptides, gramicidin S and tyrocidine, mediated similar transfection levels at a 1:1 peptide/ DNA charge ratio, however, tyrocidine could displace ethidium bromide from plasmid DNA at a lower peptide: DNA charge ratio than gramicidin S suggesting subtle differences in the manner these cyclic peptides interact with DNA. Fractionation of the complexes by sedimentation on sucrose gradients separated a major fraction with a density of about 1.10 g/cm3. This fraction was enriched in peptide and Dope and had a more negative zeta potential than the initial complex. It also had the highest transfection activity and the lowest toxicity. Electron microscopic examination of negatively stained peptide—DNA complexes revealed the cyclic peptides formed a compacted cylindrical tube-like structure when bound to DNA as compared to the toroidal structure obtained with polylysine. Upon addition of Dope dispersions to the peptide—DNA pair, the compacted tubes were replaced in the negative stain by spherical structures with diameters in the 200 nm to 400 nm range. The spherical structures are correlated with high transfection levels. Thus in contrast to polylysine-based systems, the cyclic peptide-Dope-DNA complex has a negative charge and the DNA is not completely compacted yet is capable of mediating high levels of transfection in cultured cells.Keywords:: compactionelectron microscopygramicidin Sphosphatidylethanolamine