gebhart/patrepeval huggingface dataset:
Analysis of Interacting Nucleic Acids in Dilute Solutions (2007)

Motivated by the growing demand for analysis tools for diverse natural and engineered DNA and RNA systems, we develop a general theory and set of computational algorithms to perform thermodynamic analysis of dilute reactive solutions and then apply these techniques to interacting nucleic acids. The theory correctly accounts for the effects of indistinguishability in partition function calculations for complexes of interacting strands. With partition functions in hand, the unique complex concentrations corresponding to thermodynamic equilibrium are obtained by solving a convex programming problem. Partition function and concentration information can then be used to calculate equilibrium base-pairing observables corresponding to experimentally measurable properties. The underlying physics and mathematical formulation of these problems lead to an interesting blend of approaches, including ideas from graph theory, group theory, dynamic programming, combinatorics, convex optimization, and Lagrange duality. To make these analysis tools available to researchers worldwide, we present NUPACK, a web-based software suite for thermodynamic analysis of nucleic acids. Its efficacy is demonstrated in example calculations and the results are shown to be in agreement with experiment. Finally, the thermodynamic properties of a DNA-based triggered self-assembly device [1] are analyzed using NUPACK and extensions of its tools. The computational results complement experimental studies, exposing novel properties about the system and dictating further research.
AlGaN/GaN current aperture vertical electron transistors with regrown channels (2004)

AlGaN/GaN current aperture vertical electron transistors with regrown aperture and source regions have been fabricated and tested. A 2 μm thick GaN:Si drain region followed by a 0.4 μm GaN:Mg current-blocking layer were grown by metalorganic chemical vapor deposition on a c-plane sapphire substrate. Channel apertures were etched, and a maskless regrowth was performed to grow unintentionally doped GaN inside the aperture as well as above the insulating layer, and to add an AlGaN cap layer. Cl2 reactive ion etching was used to pattern the device mesa, and source, drain, and gate metals were then deposited. Devices were achieved with a maximum source-drain current of 750 mA/mm, an extrinsic transconductance of 120 mS/mm, and a 2-terminal gate breakdown of 65 V while exhibiting almost no DC-RF dispersion for 80 μs pulsed I–V curves. The suppression of DC-RF dispersion was shown to result from the absence of the large electric fields at the surface on the drain-side edge of the gate that are present in high electron mobility transistors. Parasitic leakage currents, which were present in all devices, have been studied in detail. Three leakage paths have been identified, and methods to eliminate them are discussed.
GCR1 , the putative Arabidopsis G protein-coupled receptor gene is cell cycle-regulated, and its overexpression abolishes seed dormancy and shortens time to flowering (2002)

Although signaling through heterotrimeric G proteins has been extensively studied in eukaryotes, there is little information about this important signaling pathway in plants. We observed that expression of GCR1, the gene encoding the only known (but still putative) G protein-coupled receptor of Arabidopsis thaliana, is modulated during the cell cycle and during plant development. Overexpression of GCR1 in tobacco (Nicotiana tabacum) BY-2 cells caused an increase in thymidine incorporation and in the mitotic index of aphidicolin synchronized cells. Overexpression of GCR1 in Arabidopsis caused two remarkable phenotypes: seed dormancy was abolished and time to flowering was reduced. Molecular markers of these two developmental processes (phosphatase PP2A and MYB65 in germination; LFY during flowering) were up-regulated in GCR1 overexpressors. These data are consistent with the hypothesis that GCR1 may be a regulator of the cell cycle and that this regulation underlies the developmental changes observed in the GCR1 transformants.
Does near-to-patient testing contribute to the diagnosis of streptococcal pharyngitis in adults? (1994)

Near-to-patient testing, except the erythrocyte sedimentation rate, may, in addition to the clinical evaluation, contribute to the differential diagnosis of streptococcal pharyngitis in adults.
Properties of six pesticide degradation plasmids isolated from Alcaligenes paradoxus and Alcaligenes eutrophus (1981)

Biophysical and genetic properties of six independently isolated plasmids encoding the degradation of the herbicides 2,4-dichlorophenoxyacetic acid and 4-chloro-2-methylphenoxyacetic acid are described. Four of the plasmids, pJP3, pJP4, pJP5, and pJP7, had molecular masses of 51 megadaltons, belonged to the IncP1 incompatibility group, and transferred freely to strains of Escherichia coli, Rhodopseudomonas sphaeroides, Rhizobium sp., Agrobacterium tumefaciens, Pseudomonas putida, Pseudomonas fluorescens, and Acinetobacter calcoaceticus. In addition, these four plasmids conferred resistance to merbromin, phenylmercury acetate, and mercuric ions, had almost identical restriction endonuclease cleavage patterns, and encoded degradation of m-chlorobenzoate. The two other plasmids, pJP2 and pJP9, did not belong to the IncP1 incompatibility group, had molecular masses of 37 megadaltons, encoded the degradation of phenoxyacetic acid, and possessed identical restriction endonuclease cleavage patterns.
An Asymmetric Polymer Nanopore for Single Molecule Detection (2004)

We describe a sensor capable of detecting single DNA molecules. The sensor is based on a single nanopore prepared in a polymer film by a latent ion track-etching technique. For this purpose, a polymer foil was penetrated by a single heavy ion of total kinetic energy of 2.2 GeV, followed by preferential etching of the ion track. DNA molecules were detected as they blocked current flow during translocation through the nanopore, driven by an electric field. The nanopores are highly stable and their dimensions are adjustable by controlling etching conditions. For detecting DNA, conical nanopores with opening diameters of 2 μm and 4 nm were used. The nanopore sensor was able to discriminate between DNA fragments of different lengths.
An Aminoglycoside Microarray Platform for Directly Monitoring and Studying Antibiotic Resistance (2007)

Antibiotic resistance is a major threat to human health. Since resistance to the aminoglycoside class of antibiotics is most commonly caused by enzymatic modification, we developed a high-throughput microarray platform for directly assaying resistance enzyme activity on aminoglycosides. After modification, the array can be hybridized with the therapeutic target, a bacterial rRNA A-site mimic, to study the effect that modification has on binding. Such studies will help identify important factors that contribute to high-affinity recognition of therapeutic targets and low-affinity recognition of and modification by resistance enzymes. This platform may also be useful for screening chemical libraries to discover new antibiotics that evade resistance.
Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter (1993)

We show here that the immediate upstream region (from position -12 to -270) of the murine interleukin 4 (Il-4) gene harbors a strong cell-type specific transcriptional enhancer. In T lymphoma cells, the activity of the Il-4 promoter/enhancer is stimulated by phorbol esters, Ca++ ionophores and agonists of protein kinase A and inhibited by low doses of the immunosuppressant cyclosporin A. The Il-4 promoter/enhancer is transcriptionally inactive in B lymphoma cells and HeLa cells. DNase I footprint protection experiments revealed six sites of the Il-4 promoter/enhancer to be bound by nuclear proteins from lymphoid and myeloid cells. Among them are four purine boxes which have been described to be important sequence motifs of the Il-2 promoter. They contain the motif GGAAA and are recognized by the inducible and cyclosporin A-sensitive transcription factor NFAT-1. Three of the Il-4 NFAT-1 sites are closely linked to weak binding sites of Octamer factors. Several purine boxes and an AT-rich protein-binding site of the Il-4 promoter are also recognized by the high mobility group protein HMG I(Y). Whereas the binding of NFAT-1 and Octamer factors enhance the activity of the Il-4 promoter, the binding of HMG I(Y) suppresses its activity and, therefore, appears to be involved in the suppression of Il-4 transcription in resting T lymphocytes.
The metastatic niche and stromal progression (2012)

The tumor stroma is comprised of extracellular matrix, non-malignant cells, and the signaling molecules they produce. It is an integral and vital component of primary tumors that together with the underlying genetic defects in the tumor cells determines the growth characteristics, morphology, and invasiveness of the tumor. In parallel to continuing genetic changes in the tumor cells themselves, the tumor stroma progressively evolves during primary tumor development. Cancer cells that disseminate from primary tumors are dependent on this stromal microenvironment, and therefore the microenvironment they encounter at secondary sites determines their fate. For those cells that survive at these sites, stromal progression can serve to re-establish a supportive tumor stroma, fostering the outgrowth of the cells as metastases. Formation of a metastatic niche that supports the survival and growth of disseminated tumor cells is a key feature of this stromal progression. The endogenous organ microenvironment can provide components of the metastatic niche. In addition, microenvironmental changes in organs prior to receipt of disseminated tumor cells can be induced by factors secreted systemically by primary tumors, causing the formation of pre-metastatic niches. Further maturation of metastatic niches can be responsible for the re-activation of dormant disseminated tumor cells many years after removal of the primary tumor. The concept of the metastatic niche and stromal progression has profound consequences for our understanding of metastatic disease, and promises to open up new strategies for the diagnosis, prognostic evaluation, and therapy of cancer.
Substituted 2-iminothiolanes: reagents for the preparation of disulfide cross-linked conjugates with increased stability (1990)

Much attention has been focused recently on the stability of immunotoxin (antibody-toxin) conjugates linked by a disulfide bridge. Conflicting reports have appeared regarding the in vivo stability of such conjugates prepared with the two most commonly used cross-linking reagents, SPDP and 2-iminothiolane. We have developed (i) a series of reagents based on 2-iminothiolane substituted at the 4- and/or 5-positions (X2ITs) which, based on model studies with simple amines, should show enhanced disulfide stability when conjugated with antibodies or other proteins and (ii) a real-time method for monitoring the rate and extent of conjugation of these reagents with amino groups. Depending upon the substituent, the stability of model-activated disulfides relative to unsubstituted 2-iminothiolane was increased from 5- to 4000-fold as measured by glutathione-induced release of thionitrobenzoic acid. This family of cross-linking reagents should allow the construction of disulfide cross-linked toxin, drug, or enzyme conjugates with enhanced stability in vivo.
Sh3rf2/POSHER Protein Promotes Cell Survival by Ring-mediated Proteasomal Degradation of the c-Jun N-terminal Kinase Scaffold POSH (Plenty of SH3s) Protein (2011)

We report that Sh3rf2, a homologue of the pro-apoptotic scaffold POSH (Plenty of SH3s), acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway. siRNA-mediated knockdown of Sh3rf2 promotes apoptosis of neuronal PC12 cells, cultured cortical neurons, and C6 glioma cells. This death appears to result from activation of JNK signaling. Loss of Sh3rf2 triggers activation of JNK and its target c-Jun. Also, apoptosis promoted by Sh3rf2 knockdown is inhibited by dominant-negative c-Jun as well as by a JNK inhibitor. Investigation of the mechanism by which Sh3rf2 regulates cell survival implicates POSH, a scaffold required for activation of pro-apoptotic JNK/c-Jun signaling. In cells lacking POSH, Sh3rf2 knockdown is unable to activate JNK. We further find that Sh3rf2 binds POSH to reduce its levels by a mechanism that requires the RING domains of both proteins and that appears to involve proteasomal POSH degradation. Conversely, knockdown of Sh3rf2 promotes the stabilization of POSH protein and activation of JNK signaling. Finally, we show that endogenous Sh3rf2 protein rapidly decreases following several different apoptotic stimuli and that knockdown of Sh3rf2 activates the pro-apoptotic JNK pathway in neuronal cells. These findings support a model in which Sh3rf2 promotes proteasomal degradation of pro-apoptotic POSH in healthy cells and in which apoptotic stimuli lead to rapid loss of Sh3rf2 expression, and consequently to stabilization of POSH and JNK activation and cell death. On the basis of these observations, we propose the alternative name POSHER (POSH-eliminating RING protein) for the Sh3rf2 protein.
Characterization of rifampin-resistance in pathogenic mycobacteria (1994)

The emergence of rifampin-resistant strains of pathogenic mycobacteria has threatened the usefulness of this drug in treating mycobacterial diseases. Critical to the treatment of individuals infected with resistant strains is the rapid identification of these strains directly from clinical specimens. It has been shown that resistance to rifampin in Mycobacterium tuberculosis and Mycobacterium leprae apparently involves mutations in the rpoB gene encoding the beta-subunit of the RNA polymerases of these species. DNA sequences were obtained from a 305-bp fragment of the rpoB gene from 110 rifampin-resistant and 10 rifampin-susceptible strains of M. tuberculosis from diverse geographical regions throughout the world. In 102 of 110 rifampin-resistant strains 16 mutations affecting 13 amino acids were observed. No mutations were observed in rifampin-susceptible strains. No association was found between particular mutations in the rpoB gene and drug susceptibility patterns of multidrug-resistant M. tuberculosis strains. Drug-resistant M. tuberculosis strains from the same outbreak and exhibiting the same IS6110 DNA fingerprint and drug susceptibility pattern contained the same mutation in the rpoB gene. However, mutations are not correlated with IS6110 profiling outside of epidemics. The evolution of rifampin resistance as a consequence of mutations in the rpoB gene was documented in a patient who developed rifampin resistance during the course of treatment. Rifampin-resistant strains of M. leprae, Mycobacterium avium, and Mycobacterium africanum contained mutations in the rpoB gene similar to that documented for M. tuberculosis. This information served as the basis for developing a rapid DNA diagnostic assay (PCR-heteroduplex formation) for the detection of rifampin susceptibility of M. tuberculosis.
Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How? (2014)

Proteins and genes of therapeutic interests in conjunction with different delivery systems are growing towards new heights. "Next generation delivery systems" may provide more efficient platform for delivery of proteins and genes. In the present review, snapshots about the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next generation delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with their detailed explanation.
Redirecting Lentiviral Vectors Pseudotyped with Sindbis Virus-Derived Envelope Proteins to DC-SIGN by Modification of N-Linked Glycans of Envelope Proteins (2010)

Redirecting the tropism of viral vectors enables specific transduction of selected cells by direct administration of vectors. We previously developed targeting lentiviral vectors by pseudotyping with modified Sindbis virus envelope proteins. These modified Sindbis virus envelope proteins have mutations in their original receptor-binding regions to eliminate their natural tropisms, and they are conjugated with targeting proteins, including antibodies and peptides, to confer their tropisms on target cells. We investigated whether our targeting vectors interact with DC-SIGN, which traps many types of viruses and gene therapy vectors by binding to the N-glycans of their envelope proteins. We found that these vectors do not interact with DC-SIGN. When these vectors were produced in the presence of deoxymannojirimycin, which alters the structures of N-glycans from complex to high mannose, these vectors used DC-SIGN as their receptor. Genetic analysis demonstrated that the N-glycans at E2 amino acid (aa) 196 and E1 aa 139 mediate binding to DC-SIGN, which supports the results of a previous report of cryoelectron microscopy analysis. In addition, we investigated whether modification of the N-glycan structures could activate serum complement activity, possibly by the lectin pathway of complement activation. DC-SIGN-targeted transduction occurs in the presence of human serum complement, demonstrating that high-mannose structure N-glycans of the envelope proteins do not activate human serum complement. These results indicate that the strategy of redirecting viral vectors according to alterations of their N-glycan structures would enable the vectors to target specific cells types expressing particular types of lectins.
A synthetic luxCDABE gene cluster optimized for expression in high-GC bacteria (2007)

The luxCDABE operon of the bioluminescent bacterium Photorhabdus luminescens has proven to be a superb transcriptional reporter. It encodes a luciferase (LuxA and LuxB) and the enzymes that produce its substrate (LuxC, LuxD and LuxE) so cells that express the cluster emit the 490-nm light spontaneously. The sequence of these genes is AT-rich (>69%) and for this and other reasons, they are not expressed efficiently in high-GC bacteria like Streptomyces coelicolor. We therefore constructed a synthetic luxCDABE operon encoding the P. luminescens Lux proteins optimized for expression in high-GC bacteria. We tested the genes using transcriptional fusions to S. coelicolor promoters having well-established expression profiles during this organism's life cycle. The hrdB gene encodes a housekeeping sigma factor; while ramC is important for the formation of the spore-forming cells called aerial hyphae and whiE is required for the production of a grey, spore-associated pigment that is deposited in the walls of developing spores. Using these fusions we demonstrated that our synthetic lux genes are functional in S. coelicolor and that they accurately report complex developmental gene expression patterns. We suggest that this lux operon and our procedure for generating synthetic high-GC genes will be widely useful for research on high-GC bacteria.
Acetylhomoserine (1967)

The acetyl ester of homoserine was found to be an intermediate in methionine biosynthesis in fungi, where it plays the role that O-succinylhomoserine does in bacteria. The latter is formed from succinyl coenzyme A and homoserine, and is decomposed by the replacement of succinate by cysteine to yield cystathionine. When grown in the presence of labeled homoserine, Neurospora accumulated labeled O-acetylhomoserine as well as larger amounts of the α-hydroxy analogue. A methionine-requiring mutant, me-5, which could grow when given acetylhomoserine in place of methionine, failed to accumulate it or to form labeled cystathionine when grown with labeled homoserine. A sensitive assay for hydroxyamino acid-acylating enzymes was devised, utilizing the observation that these enzymes catalyze exchange between alcohol and ester. Extracts of yeast and Neurospora were shown to catalyze homoserine exchange only with acetylhomoserine; extracts of Salmonella, only with succinylhomoserine. Homoserine acetylase was purified 60-fold from Neurospora. Acetyl-CoA could not be replaced by acetyl derivatives of phosphate, carnitine, or acyl carrier protein. The exchange rate was not affected by end product methionine. Although not leaky nutritionally, the me-5 mutant appears to produce a modified enzyme able to catalyze net acetylation but not exchange. Extracts of both fungi and bacteria can utilize either the succinyl or the acetyl ester of homoserine for cystathionine synthesis. In Salmonella this is due to the low specificity of the cystathionine γ-synthetase, but cystathionine synthesis from succinylhomoserine in Neurospora appears to be catalyzed by γ-cystathionase.
Leukocyte subset-derived genomewide expression profiles in pediatric septic shock* (2009)

These data demonstrate that genome-level repression of adaptive immunity gene programs early in the course of pediatric septic shock remained evident when analyses were conducted using leukocyte subset-specific RNA.
Highly Efficient, Organocatalytic Aerobic Alcohol Oxidation (2011)

5-Fluoro-2-azaadamantane N-oxyl (5-F-AZADO) realizes a simple, organocatalytic aerobic alcohol oxidation system that has a wide scope under mild conditions at ambient pressure and temperature and is weakly acidic and halogen- and transition-metal-free. The oxoammonium nitrate (5-F-AZADO(+)NO(3)(-)) works as a bifunctional catalyst of 5-F-AZADO and NO(x) that enables the catalytic aerobic oxidation of alcohols by itself (a metal-salt-free system).
On second order statistics and linear estimation of cepstral coefficients (2002)

Explicit expressions for the second order statistics of cepstral components representing clean and noisy signal waveforms are derived. The noise is assumed additive to the signal, and the spectral components of each process are assumed statistically independent complex Gaussian random variables. The key result developed here is an explicit expression for the cross-covariance between the log-spectra of the clean and noisy signals. In the absence of noise, this expression is used to show that the covariance matrix of cepstral components representing a vector of N signal samples, approaches a fixed, signal independent, diagonal matrix at a rate of 1/N/sup 2/. In addition, the cross-covariance expression is used to develop an explicit linear minimum mean square error estimator for the clean cepstral components given noisy cepstral components. Recognition results on the ten English digits using the fixed covariance and linear estimator are presented.