gebhart/patrepeval huggingface dataset:
Structural proteins and DNA characteristics of 14 Listeria typing bacteriophages (1994)

The major structural proteins of 13 temperate and one virulent Listeria typing bacteriophages were analysed and compared using isoelectric focusing in immobilized pH gradients (IPG), ultrathin-layer two-dimensional electrophoresis, amino acid analysis and N-terminal amino acid sequences of selected proteins. Isoelectric points for major capsid and tail proteins of the 12 members of the siphoviridae family included in this study ranged from 4.70 to 5.92, whereas one of the two myoviridae investigated (B054) showed structural proteins in the 6.1 to 6.3 range. In comparison to protein profiles from one-dimensional SDS gels, the IPG technique gave better resolution and improved discrimination of phage proteins. Combination of this technique and SDS gel electrophoresis made it possible to correlate M(r) and isoelectric points of major structural proteins. Tail polypeptides of all siphoviridae are smaller and, with one exception, more acidic than their corresponding capsid counterparts. We also determined the amino acid composition of capsid and tail proteins. When compared with an average protein, they were found to be fairly rich in acidic and short-chain hydrophobic amino acids, as well as in lysine. In addition, the N-terminal amino acid sequences of major capsid and tail proteins of four representative listeriaphages were compared. The base composition of listeriaphage DNAs was between 37% and 39% G + C, reflecting that of their bacterial hosts. Each phage had a distinct restriction endonuclease pattern, and genome sizes ranged from 35 to 116 kb. DNA-DNA hybridization permitted the identification of five DNA homology groups. The two myoviruses studied (A511 and B054) showed no DNA homology to other phages, confirming their unique nature. The 12 siphoviruses were classified into three DNA homology groups with little cross-homology. Furthermore, phage A006 was found to share little DNA homology with the other investigated members of species 2671. Therefore, a new species (A006) is proposed. With respect to phage classification and taxonomy, a good correlation between the various approaches was observed, mostly corresponding to particle morphology.
NetMHCpan-4.0: Improved Peptide–MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data (2017)

Cytotoxic T cells are of central importance in the immune system's response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules. Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway. Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention. In the past, predictors of peptide-MHC interactions have primarily been trained on binding affinity data. Recently, an increasing number of MHC-presented peptides identified by mass spectrometry have been reported containing information about peptide-processing steps in the presentation pathway and the length distribution of naturally presented peptides. In this article, we present NetMHCpan-4.0, a method trained on binding affinity and eluted ligand data leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an increase in predictive performance compared with state-of-the-art methods when it comes to identification of naturally processed ligands, cancer neoantigens, and T cell epitopes.
Binding of Symmetrical Cyanine Dyes into the DNA Minor Groove (2000)

Optical methods, such as fluorescence, circular dichroism and linear flow dichroism, were used to study the binding to DNA of four symmetrical cyanine dyes, each consisting of two identical quinoline, benzthiazole, indole, or benzoxazole fragments connected by a trimethine bridge. The ligands were shown to form a monomer type complex into the DNA minor groove. The complex of quinoline-containing ligand with calf thymus DNA appeared to be the most resistant to ionic strength, and it did not dissociate completely even in 1 M NaCl. Binding of cyanine dyes to DNA could also be characterized by possibility to form ligand dimers into the DNA minor groove, by slight preference of binding to AT pairs, as well as by possible intercalation between base pairs of poly(dG)-poly(dC). The correlation found between the binding constants to DNA and the extent of cyanine dyes hydrophobicity estimated as the n-octanol/water partition coefficient is indicative of a significant role of hydrophobic interactions for the ligand binding into the DNA minor groove.
A recursive feature vector normalization approach for robust speech recognition in noise (2002)

The acoustic mismatch between testing and training conditions is known to severely degrade the performance of speech recognition systems. Segmental feature vector normalization was found to improve the noise robustness of mel-frequency cepstral coefficients (MFCC) feature vectors and to outperform other state-of-the-art noise compensation techniques in speaker-dependent recognition. The objective of feature vector normalization is to provide environment-independent parameter statistics in all noise conditions. We propose a more efficient implementation approach for feature vector normalization where the normalization coefficients are computed in a recursive way. Speaker-dependent recognition experiments show that the recursive normalization approach obtains over 60%, the segmental method approximately 50%, and parallel model combination a 14% overall error rate reduction, respectively. Moreover, in the recursive case, this performance gain is obtained with the smallest implementation costs. Also in speaker-independent connected digit recognition, over a 16% error rate reduction is obtained with the proposed feature vector normalization approach.
Control and Applications of Immiscible Liquids in Microchannels (2002)

Photolithography was used in combination with photocleavable self-assembled monolayers to pattern surface free energies inside microchannels enabling the control of the boundary between immiscible liquids. While aqueous solutions are confined to the hydrophilic pathways by surface forces alone, organic liquids are confined to the hydrophobic region only if the aqueous liquid first occupies the hydrophilic region. In this way, stable liquid boundaries between immiscible liquids are possible as long as the pressures are maintained below critical values. The maximum pressures are determined by the interfacial tension of the aqueous solution and organic liquid, channel depth, and advancing contact angle (theta;(a)). Experimental results on maximum pressures are in good agreement with the analytical values. The ability to confine and position the boundary between immiscible liquids inside microchannels leads to a broad range of applications in microfluidic systems, which is exemplified by fabrication of a semipermeable membrane in a surface-patterned channel via interfacial polymerization.
Small-Molecule Prodigiosin Restores p53 Tumor Suppressor Activity in Chemoresistant Colorectal Cancer Stem Cells via c-Jun-Mediated ΔNp73 Inhibition and p73 Activation (2016)

Tumor suppressor p53 is frequently mutated or inactivated in colorectal cancer. In contrast, p53 family member p73 is rarely mutated in colorectal cancer and p73 activation elicits p53-like tumor suppression. Colorectal cancer stem cells (CRCSC) comprise a rare self-renewing subpopulation that contributes to tumor maintenance and chemoresistance. p53 restoration is known to target CRCSCs, but p73 restoration in CRCSCs has not been examined. In this study, we investigated the effects of the small-molecule prodigiosin, which restores the p53 pathway in tumor cells via p73 activation, on CRCSCs in vitro and in vivo Prodigiosin prevented colonosphere formation independent of p53 status and reduced the viability of self-renewing, 5-fluorouracil-resistant Aldefluor positive [Aldefluor(+)] CRCSCs in vitro Furthermore, prodigiosin inhibited the growth of xenograft tumors initiated with Aldefluor+ cells without toxic effects and limited the tumorigenic potential of these cells. Consistently, prodigiosin induced activation of a p53-responsive luciferase reporter in colonospheres, Aldefluor(+) cells, and tumor xenografts. Mechanistic studies revealed that prodigiosin increased the levels of p73 and reduced levels of the oncogenic N-terminally truncated isoform ΔNp73 in Aldefluor(+) cells. Accordingly, p73 knockdown or ΔNp73 overexpression suppressed prodigiosin-mediated inhibition of colonosphere formation. Moreover, prodigiosin increased levels of the transcription factor c-Jun, a regulator of p73 and ΔNp73, in both the cytoplasm and nucleus. c-Jun knockdown attenuated prodigiosin-mediated p53-reporter activation, ΔNp73 downregulation, p73 activation, and cell death. Collectively, our findings highlight the previously uncharacterized use of p73-activating therapeutics to target CRCSCs. Cancer Res; 76(7); 1989-99. ©2016 AACR.
Hydrophobically Modified Oligoethylenimines as Highly Efficient Transfection Agents for siRNA Delivery (2009)

RNA interference is a promising therapeutic strategy for treatment of diseases, in particular, cancer. Despite a huge number of targets identified for different cancer types, there are no effective delivery strategies available so far. Polymeric delivery vehicles are often based on large macromolecules. Such approaches often lead to accumulation of toxicity and narrow therapeutic windows. In the current paper, an alternative approach is presented. Low molecular weight oligoethylenimine (OEI) 800 Da was hydrophobically modified through the Michael addition of different alkyl acrylates. An optimal structure containing ten hexyl acrylate residues per one OEI chain (OEI-HA-10) was found to be a promising candidate for siRNA delivery. Hydrophobic modification stabilized the siRNA polyplex structure, increased the colloidal stability of the nanoparticles, and provided lytic properties to OEI required for crossing cellular membranes in the delivery process. In addition, the acrylate ester bond enables fast degradation of OEI-HA-10 into far less toxic components. Further improvement of biological properties of the OEI-HA-10 polyplexes by different formulation strategies was demonstrated. In particular, a remarkable increase of biocompatibility without loss of efficiency could be achieved by coformulation of OEI-HA-10 with lauryl acrylate modified OEI-LA-5.
Magnetic resonance imaging of vulnerable atherosclerotic plaques: Current imaging strategies and molecular imaging probes (2007)

The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of vulnerable plaque and may allow for monitoring the efficacy of antiatherosclerotic therapies. In this review we focus on MR imaging strategies for the detection and evaluation of atherosclerotic plaques and their composition. We highlight recent advancements in the development of MR pulse sequences, computer image analysis, and the use of commercially available MR contrast agents, such as gadopentic acid (Gd-DTPA), for plaque characterization. We also discuss molecular imaging strategies that are currently being used to design specific imaging probes targeted to biochemical and cellular markers of atherosclerotic plaque vulnerability.
Conditional likelihood maximisation: a unifying framework for information theoretic feature selection (2012)

We present a unifying framework for information theoretic feature selection, bringing almost two decades of research on heuristic filter criteria under a single theoretical interpretation. This is in response to the question: “what are the implicit statistical assumptions of feature selection criteria based on mutual information?”. To answer this, we adopt a different strategy than is usual in the feature selection literature—instead of trying to define a criterion, we derive one, directly from a clearly specified objective function: the conditional likelihood of the training labels. While many hand-designed heuristic criteria try to optimize a definition of feature ‘relevancy ’ and ‘redundancy’, our approach leads to a probabilistic framework which naturally incorporates these concepts. As a result we can unify the numerous criteria published over the last two decades, and show them to be low-order approximations to the exact (but intractable) optimisation problem. The primary contribution is to show that common heuristics for information based feature selection (including Markov Blanket algorithms as a special case) are approximate iterative maximisers of the conditional likelihood. A large empirical study provides strong evidence to favour certain classes of criteria, in particular those that balance the relative size of the relevancy/redundancy terms. Overall we conclude that the JMI criterion (Yang and Moody, 1999; Meyer et al., 2008) provides the best tradeoff in terms of accuracy, stability, and flexibility with small data samples.
Structural Studies on the Zinc-endopeptidase Light Chain of Tetanus Neurotoxin (1995)

Tetanus neurotoxin (TeNT) blocks neuroexocytosis via a zinc-endopeptidase activity highly specific for vescicle-associated membrane protein(VAMP)/synaptobrevin. TeNT is the prototype of clostridial neurotoxins, a new family of metalloproteinases. They consist of three domains and the proteolytic activity is displayed by the 50-kDa light chain (L chain). The L chain was isolated here in the native state from bacterial filtrates of Clostridium tetani and its structure was studied via circular dichroism (CD) and fluorescence spectroscopy. The secondary structure content (27% alpha-helix and 43% beta-sheet), estimated by far-ultraviolet CD measurements, was in reasonable agreement with that obtained by standard predictive methods (25% alpha-helix and 49% beta-sheet). Moreover, the hypothetical zinc-binding motif, encompassing residues His-Glu-Leu-Ile-His, was correctly predicted to be in alpha-helical conformation, as also expected on the basis of the geometrical requirements for a correct coordination of the zinc ion. Both near-ultraviolet CD and fluorescence data strongly suggest that the single Trp43 residue is buried and constrained in a hydrophobic environment, likely distant from the zinc ion located in the active-site cleft. The contribution of the bound zinc ion to the overall conformation of TeNT L chain was investigated by different and complementary techniques, including spectroscopic (far- and near-ultraviolet CD, fluorescence, second derivative absorption spectroscopy) as well as proteolytic probes. The results indicate that the zinc ion plays little, if any, role in determining the structural properties of the L chain molecule. Similarly, the metal-free apo-enzyme and the holo-protein share common stability features evaluated in respect to different physico-chemical parameters (pH, temperature and urea concentration). These results parallel those obtained on thermolysin, a zinc-dependent neutral endoprotease from Bacillus thermoproteolyticus, where both conformational and stability properties are unchanged upon zinc removal.
Induction of oxyradicals by arsenic: Implication for mechanism of genotoxicity (2001)

Although arsenic is a well-established human carcinogen, the mechanisms by which it induces cancer remain poorly understood. We previously showed arsenite to be a potent mutagen in human-hamster hybrid (A(L)) cells, and that it induces predominantly multilocus deletions. We show here by confocal scanning microscopy with the fluorescent probe 5',6'-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate that arsenite induces, within 5 min after treatment, a dose-dependent increase of up to 3-fold in intracellular oxyradical production. Concurrent treatment of cells with arsenite and the radical scavenger DMSO reduced the fluorescent intensity to control levels. ESR spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-1-hydroxypiperidine (TEMPOL-H) as a probe in conjunction with superoxide dismutase and catalase to quench superoxide anions and hydrogen peroxide, respectively, indicates that arsenite increases the levels of superoxide-driven hydroxyl radicals in these cells. Furthermore, reducing the intracellular levels of nonprotein sulfhydryls (mainly glutathione) in A(L) cells with buthionine S-R-sulfoximine increases the mutagenic potential of arsenite by more than 5-fold. The data are consistent with our previous results with the radical scavenger DMSO, which reduced the mutagenicity of arsenic in these cells, and provide convincing evidence that reactive oxygen species, particularly hydroxyl radicals, play an important causal role in the genotoxicity of arsenical compounds in mammalian cells.
Adaptation of an Orthogonal Archaeal Leucyl-tRNA and Synthetase Pair for Four-base, Amber, and Opal Suppression (2003)

Recently, it has been shown that an amber suppressor tRNA/aminoacyl-tRNA synthetase pair derived from the tyrosyl-tRNA synthetase of Methanococcus jannaschii can be used to genetically encode unnatural amino acids in response to the amber nonsense codon, TAG. However, we have been unable to modify this pair to decode either the opal nonsense codon, TGA, or the four-base codon, AGGA, limiting us to a 21 amino acid code. To overcome this limitation, we have adapted a leucyl-tRNA synthetase from Methanobacterium thermoautotrophicum and leucyl tRNA derived from Halobacterium sp. NRC-1 as an orthogonal tRNA-synthetase pair in Escherichia coli to decode amber (TAG), opal (TGA), and four-base (AGGA) codons. To improve the efficiency and selectivity of the suppressor tRNA, extensive mutagenesis was performed on the anticodon loop and acceptor stem. The two most significant criteria required for an efficient amber orthogonal suppressor tRNA are a CU(X)XXXAA anticodon loop and the lack of noncanonical or mismatched base pairs in the stem regions. These changes afford only weak suppression of TGA and AGGA. However, this information together with an analysis of sequence similarity of multiple native archaeal tRNA sequences led to efficient, orthogonal suppressors of opal codons and the four-base codon, AGGA. Ultimately, it should be possible to use these additional orthogonal pairs to genetically incorporate multiple unnatural amino acids into proteins.
Monitoring and analysis strategies for digital networks (1988)

The telecommunications networks managed by the divested Bell operating companies (BOCs/IDCs) are rapidly evolving into digital networks. The authors discuss the major driving forces and characteristics that are shaping operations transition plans and formulate an operations strategy that is designed to position BOCs/IDCs to manage these digital networks. They describe a Bellcore prototype operations system, referred to as the network monitoring and analysis (NMA) system, that has been tested in one of the BOCs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Tenofovir Disoproxil Fumarate Therapy for Chronic Hepatitis B in Human Immunodeficiency Virus/Hepatitis B Virus–Coinfected Individuals for Whom Interferon‐α and Lamivudine Therapy Have Failed (2002)

A significant proportion of human immunodeficiency virus (HIV) infected patients are coinfected with hepatitis B virus (HBV). Currently available treatments for chronic hepatitis B (interferon [IFN]-alpha and lamivudine [3TC]) have limited long-term utility because of side effects or of the development of resistance. Tenofovir disoproxil fumarate (TDF) is a nucleotide analog with excellent activity in vitro against HBV, which is also active against 3TC-resistant HBV variants. In this 24-week pilot study, the anti-HBV activity of TDF was prospectively evaluated in a cohort of 6 HIV coinfected subjects for whom 3TC and IFN therapy had previously failed. At baseline, all patients were taking 3TC or FTC and were hepatitis B surface antigen and hepatitis B e antigen positive; 4 had cirrhosis. Baseline HBV load was 7.95 log(10) copies/mL. By weeks 12 and 24, HBV load had decreased by 3.1 log(10) copies/mL and 4.3 log(10) copies/mL, respectively. There was a transient increase of transaminases after the initiation of treatment. No patient developed HBe antibodies. TDF is a very promising drug for the treatment of chronic hepatitis B in HIV-infected individuals.
Stabilization of double-stranded oligonucleotides using backbone-linked disulfide bridges (1995)

A convenient, practical route to the synthesis of disulfide-bridged oligonucleotides has been developed. Aliphatic linkers with terminal thiol groups have been attached to the phosphodiester backbones of partially or fully complementary oligonucleotide sequences and oxidized to yield covalently closed oligonucleotides with disulfide bridges. This procedure has been used to prepare a duplex with disulfide bridges at both ends and stem-loop sequences with single disulfide bridges. Oxidation of a self-complementary duplex possessing terminal thiol groups produced both hairpin and duplex structures with disulfide bridges, the relative proportions of each being dependent upon the reaction conditions. These bridged hairpin and duplex structures were shown to be interconvertible by reduction and re-oxidation. The melting profiles of disulfide-bridged oligonucleotides were compared with the same sequences without bridges and with sequences possessing triethylene glycol bridges, and in all cases the introduction of disulfide bridges resulted in a considerable increase in thermal stability. EcoRI endonuclease was capable of cleaving a disulfide-bridged duplex possessing a recognition site for this enzyme, thus supporting a lack of distortion of the recognition site. The disulfide bridges could be cleaved using a large excess of DTT to regenerate the corresponding sulfhydryl compounds. A study of the serum stabilities of disulfide-bridged oligonucleotides showed that the bridged duplexes were much more stable than their unmodified counterparts, whereas the rate of degradation of the stem-loop structures was more dependent upon the size of the loop than the presence or absence of the disulfide bridge. In summary, we have described a novel methodology, employing commercially available reagents, for the stabilization of oligonucleotide duplexes or stem-loop structures by disulfide bridge formation.
Metagenomic Analysis of Microbial Symbionts in a Gutless Worm (2016)

Symbioses between bacteria and eukaryotes are ubiquitous, yet our understanding of the interactions driving these associations is hampered by our inability to cultivate most host-associated microbes. Here we use a metagenomic approach to describe four co-occurring symbionts from the marine oligochaete Olavius algarvensis, a worm lacking a mouth, gut and nephridia. Shotgun sequencing and metabolic pathway reconstruction revealed that the symbionts are sulphur-oxidizing and sulphate-reducing bacteria, all of which are capable of carbon fixation, thus providing the host with multiple sources of nutrition. Molecular evidence for the uptake and recycling of worm waste products by the symbionts suggests how the worm could eliminate its excretory system, an adaptation unique among annelid worms. We propose a model that describes how the versatile metabolism within this symbiotic consortium provides the host with an optimal energy supply as it shuttles between the upper oxic and lower anoxic coastal sediments that it inhabits.