gebhart/patrepeval huggingface dataset:
Image restoration with Poisson–Gaussian mixed noise (2013)

This study focuses on the image denoising and deconvolution problem in case of mixed Gaussian–Poisson noise. By using a maximum a posteriori estimator, we derive a new variational formulation whose minimisation provides the desired restored image. The new functional is composed of the total variation (TV) regularisation term, the Kullback–Leibler divergence term for Poisson noise and the norm fidelity term for Gaussian noise. We consider a dual formulation for the TV term, thus changing the minimisation into a minimax problem. A fast iterative algorithm is derived by using the proximal point method to compute the saddle point of the minimax problem. We show the capability of our model both on synthetic examples and on real images of low-count fluorescence microscopy.
The regulation of nitrate and ammonium transport systems in plants (2002)

Inorganic nitrogen concentrations in soil solutions vary across several orders of magnitude among different soils and as a result of seasonal changes. In order to respond to this heterogeneity, plants have evolved mechanisms to regulate and influx. In addition, efflux analysis using (13)N has revealed that there is a co-ordinated regulation of all component fluxes within the root, including biochemical fluxes. Physiological studies have demonstrated the presence of two high-affinity transporter systems (HATS) for and one HATS for in roots of higher plants. By contrast, in Arabidopsis thaliana there exist seven members of the NRT2 family encoding putative HATS for and five members of the AMT1 family encoding putative HATS for. The induction of high-affinity transport and Nrt2.1 and Nrt2.2 expression occur in response to the provision of, while down-regulation of these genes appear to be due to the effects of glutamine. High-affinity transport and AMT1.1 expression also appear to be subject to down-regulation by glutamine. In addition, there is evidence that accumulated and may act post-transcriptionally on transporter function. The present challenge is to resolve the functions of all of these genes. In Aspergillus nidulans and Chlamydomonas reinhardtii there are but two high-affinity transporters and these appear to have undergone kinetic differentiation that permits a greater efficiency of absorption over the wide range of concentration normally found in nature. Such kinetic differentiation may also have occurred among higher plant transporters. The characterization of transporter function in higher plants is currently being inferred from patterns of gene expression in roots and shoots, as well as through studies of heterologous expression systems and knockout mutants.
The RsmA-Mutants ofErwinia carotovorasubsp.carotovoraStrain Ecc71 OverexpresshrpNECCand Elicit a Hypersensitive Reaction-like Response in Tobacco Leaves (1996)

Erwinia carotovora subsp. carotovora wild-type strain Ecc71 does not elicit the hypersensitive reaction (HR) in tobacco leaves. By mini-Tn5-Km and chemical mutagenesis we have isolated RsmA- mutants of Ecc71 that produce high basal levels of pectate lyases, polygalacturonase, cellulase, and protease; they also are hypervirulent. The RsmA- mutants, but not their parent strains, elicit an HR-like response in tobacco leaves. This reaction is characterized by the rapid appearance of water soaking followed by tissue collapse and necrosis. The affected areas remain limited to the region infiltrated with bacterial cells, and the symptoms closely resemble a typical HR, e.g., the reactions caused by Pseudomonas syringae pv. pisi. Moreover, low concentrations of cells of the mini-Tn5-Km insertion RsmA- mutant, AC5070, infiltrated into tobacco leaf tissue prevent elicitation of the rapid necrosis by AC5070 or by P. syringae pv. pisi. Elicitation of the HR-like response by the mutants is not affected by the deficiency of N-(3-oxohexanoyl)-L-homoserine lactone, the cell density (quorum) sensing signal. Cloning and sequence analysis have disclosed that E. carotovora subsp. carotovora strain Ecc71 possesses a homolog of E. chrysanthemi hrpN known to encode an elicitor of the HR; the corresponding Ecc71 gene is designated hrpNEcc. Northern (RNA) blot data show that the level of hrpNEcc mRNA is considerably higher in the RsmA- mutants than in the RsmA+ strains. Moreover, a low copy plasmid carrying the rsmA+ allele severely reduces the level of the hrpNEcc transcripts in the RsmA- mutants. These constructs, like the RsmA+ E. carotovora subsp. carotovora strains, do not elicit the HR-like response. These data taken along with the effects of rsmA on exoenzyme production and pathogenicity (A. Chatterjee et al., 1995, Appl. Environ. Microbiol. 61:1959-1967) demonstrate that this global regulator gene plays a critical role in plant interaction of E. carotovora subsp. carotovora.
Femtosecond experiments and absolute rate calculations on intervalence electron transfer of mixed-valence compounds (1993)

New experimental results and theoretical calculations are reported for the optical electron transfer (ET) and subsequent reverse radiationless ET for the molecules (NH3)5RuIIINCRuII(CN)−5 and (NH3)5FeIIINCRuII(CN)−5. A procedure is presented for extracting many of the key parameters in ET theory from a combined analysis of resonance Raman data and the optical absorption ET band shape. Using these parameters, ET rates have been calculated using contemporary ET models. The experimental and theoretical rates agree within the uncertainty of the theoretical predictions, which results from an uncertainty in some of the parameters. The results demonstrate that inertial solute/solvent interactions and intramolecular sources of fast energy fluctuations play an important role in ultrafast ET kinetics for these compounds.
Mitotic recombination among subtelomeric Y' repeats in Saccharomyces cerevisiae. (1990)

Y's are a dispersed family of repeats that vary in copy number, location and restriction fragment lengths between strains but exhibit within-strain homogeneity. We have studied mitotic recombination between members of the subtelomeric Y' repeated sequence family of Saccharomyces cerevisiae. Individual copies of Y's were marked with SUP11 and URA3 which allowed for the selection of duplications and losses of the marked Y's. Duplications occurred by ectopic recombinational interactions between Y's at different chromosome ends as well as by unequal sister chromatid exchange. Several of the ectopic duplications resulted in an originally Y'-less chromosome end acquiring a marked Y'. Among losses, most resulted from ectopic exchange or conversion in which only the marker sequence was lost. In some losses, the chromosome end became Y'-less. Although the two subsets of Y's, Y'-longs (6.7 kb) and Y'-shorts (5.2 kb), share extensive sequence homology, a marked Y' recombines highly preferentially within its own subset. These mitotic interactions can in part explain the maintenance of Y's and their subsets, the homogeneity among Y's within a strain, as well as diversity between strains.
Survival motor neuron protein facilitates assembly of stress granules (2004)

The survival motor neuron (SMN) protein forms cytoplasmic granules when overexpressed. We report here that SMN co-localizes with TIA-1/R and G3BP, protein assemblers of stress granules (SGs), and that SMN is co-immunoprecipitated with TIA-1/R, suggesting that SMN granules are SGs. Formation of SMN granules precedes accumulation of TIA-1/R, indicating that SMN serves as a facilitator of SG formation. However, the exon 7 skipping product, SMNDelta7, is largely retained in the nucleus and forms nuclear granules, indicating that exon 7 is critical for SG formation. Our findings reveal a novel SMN function and possible SG involvement in the pathogenesis of spinal muscular atrophy.
Modeling and Testing for Timing Faults in Synchronous Sequential Circuits (1984)

Even with proper design, integrated circuits and systems can have timing problems because of physical faults or variation of parameters. The authors introduce a fault model that takes into account timing related failures in both the combinational logic and the storage elements. Using their fault model and the system's requirements for proper operation, the authors propose ways to handle flipflop-to-flipflop delay, path selection, initialization, error propagation, race-around, and anomalous behavior. They discuss the advantages of scan designs like LSSD and the effectiveness of random delay testing.
Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo (2006)

Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology. Using prostate cancer as a model, we report docetaxel (Dtxl)-encapsulated nanoparticles formulated with biocompatible and biodegradable poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) copolymer and surface functionalized with the A10 2'-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen (PSMA), a well characterized antigen expressed on the surface of prostate cancer cells. These Dtxl-encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-Apt) bind to the PSMA protein expressed on the surface of LNCaP prostate epithelial cells and get taken up by these cells resulting in significantly enhanced in vitro cellular toxicity as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP) (P < 0.0004). The Dtxl-NP-Apt bioconjugates also exhibit remarkable efficacy and reduced toxicity as measured by mean body weight loss (BWL) in vivo [body weight loss of 7.7 +/- 4% vs. 18 +/- 5% for Dtxl-NP-Apt vs. Dtxl-NP at nadir, respectively (mean +/- SD); n = 7]. After a single intratumoral injection of Dtxl-NP-Apt bioconjugates, complete tumor reduction was observed in five of seven LNCaP xenograft nude mice (initial tumor volume of approximately 300 mm3), and 100% of these animals survived our 109-day study. In contrast, two of seven mice in the Dtxl-NP group had complete tumor reduction with 109-day survivability of only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles without drug were similarly nonefficacious. This report demonstrates the potential utility of nanoparticle-aptamer bioconjugates for a therapeutic application.
Selection, expression, and nucleotide sequencing of the glutamate dehydrogenase gene of Peptostreptococcus asaccharolyticus (1991)

The gene for the catabolic NAD-linked glutamate dehydrogenase of Peptostreptococcus asaccharolyticus was cloned by selection of Escherichia coli for complementation of a biosynthetic defect. Cloned fragments containing the gene and the P. asaccharolyticus transcription and translation signals are very highly expressed in E. coli. The nucleotide sequence of the cloned gene was determined. It codes for a polypeptide of 421 amino acids, the sequence of which is similar to those of the NADP-accepting glutamate dehydrogenases. The sequence similarity of this protein to the mammalian glutamate dehydrogenases, which accept both NADP and NAD, is greater than its similarity to the bacterial NADP-specific dehydrogenases, suggesting that this NAD-specific bacterial glutamate dehydrogenase and the NADP-specific bacterial dehydrogenases diverged separately from the line leading to the dual-specificity mammalian glutamate dehydrogenases.
Isolation and sequence of the cDNAs encoding the subunits of the isozyme form of wheat protein synthesis initiation factor 4F (1992)

The nucleotide sequences of the cDNAs for the two subunits, p82 and p28, of the isozyme form of wheat germ eukaryotic initiation factor 4F (eIF-(iso)4F) were determined. The cDNA for the p82 subunit encodes a polypeptide of 86,514 Da. The deduced amino acid sequence of p82 contains possible motifs for ATP binding, metal binding, and phosphorylation. The cDNA sequence for the small subunit, p28, which is a m7G cap-binding protein, encodes a polypeptide of 23,524 Da. The deduced amino acid sequence of p28 is similar (approximately 38%) to cap-binding proteins from yeast and mammals. The p28 of wheat eIF-(iso)4F does not contain a serine or threonine in the vicinity of the serine (Ser53) of mammalian cap-binding protein which is phosphorylated and shown to affect activity in mammalian cells.
Erythropoietin and erythropoietin receptors in the peripheral nervous system: changes after nerve injury (2001)

ABSTRACT Erythropoietin (Epo) is a hematopoietic factor that has recently been shown to function in the central nervous system. The presence or function of Epo or the erythropoietin receptor (EpoR) in the peripheral nervous system is unknown. Our results demonstrate the presence of both Epo and EpoR in the rat sciatic nerve. Epo was present in axons and was up‐regulated in Schwann cells after chronic constriction injury (CCI). EpoR was present in endothelial cells, cell bodies of the dorsal root ganglia (DRG), axons, and Schwann cells; it was not changed after injury. Using two different models of nerve injury, CCI and crush injury adjacent to the DRG, we demonstrated TUNEL labeling in DRG cell bodies after adjacent nerve crush, but not after CCI. TUNEL labeling in crush injury correlated with a significant reduction of EpoR in DRG as determined by morphometry and Western blotting. Immunoblotting of uninjured DRG homogenates revealed an immunoreactive band at 90 kDa and 70 kDa. After crush injury, both 70 kDa and 90 kDa proteins were reduced and the 90 kDa protein showed enhanced tyrosine phosphorylation, whereas the 70 kDa showed less. EpoR colocalized with NF200 in normal DRG, but not after crush injury to the adjacent axon. These findings demonstrate Epo and EpoR in the peripheral nervous system and their regulation after painful nerve injury.
Mechanisms of Cancer Cachexia (2009)

Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the alpha-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NFkappaB. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-alpha, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment.
Design, Synthesis, and Pharmacological Characterization of Indol-3-ylacetamides, Indol-3-yloxoacetamides, and Indol-3-ylcarboxamides: Potent and Selective CB2 Cannabinoid Receptor Inverse Agonists (2012)

In our search for new cannabinoid receptor modulators, we describe herein the design and synthesis of three sets of indole-based ligands characterized by an acetamide, oxalylamide, or carboxamide chain, respectively. Most of the compounds showed affinity for CB2 receptors in the nanomolar range, with K(i) values spanning 3 orders of magnitude (377-0.37 nM), and moderate to good selectivity over CB1 receptors. Their in vitro functional activity as inverse agonists was confirmed in vivo in the formalin test of acute peripheral and inflammatory pain in mice, in which compounds 10a and 11e proved to be able to reverse the effect of the CB2 selective agonist COR167.
The structure of polymyxin T1. Studies on antibiotics from the genus Bacillus. XXII. (1977)

Amino acid analysis of the acid hydrolyzate of polymyxin T1 revealed the amino acid composition. Isolation of the constituent amino acids and measurement of their optical activities clarified their chiralities. These were 2,4-diaminobutyric acid (6L), Thr(1L), Leu(2L) and Phe(1D). The constituent fatty acid was identified as anteisononanoic acid by gas chromatography and mass spectrometry. Deacylation with polymyxin acylase afforded deacyl polymyxin T. Successive EDMAN degradation on deacyl polymyxin T revealed most of its amino acid sequence. The chemical cleavage reaction for fragmentation of threonyl peptide amino acid sequence. The chemical cleavage reaction for fragmentation of threonyl peptide on penta(DNP)-polymyxin T1 cleaved it at the C-terminal side of the Thr residue to afford a DNP-octapeptide, whose sequence was clarified by EDMAN degradation. Thus, the structure of polymyxin T1 was determined.
Trop‐1 are conserved growth stimulatory molecules that mark early stages of tumor progression (2007)

The findings identify Trop-1 as a novel determinant of cell growth at early stages of tumor development and as a marker of early stages of development in normal tissues and in cancer, making this molecule a candidate for novel diagnostic and therapeutic procedures.
Store-Operated Ca2+ Entry through ORAI1 Is Critical for T Cell-Mediated Autoimmunity and Allograft Rejection (2010)

ORAI1 is the pore-forming subunit of the Ca(2+) release-activated Ca(2+) (CRAC) channel, which is responsible for store-operated Ca(2+) entry in lymphocytes. A role for ORAI1 in T cell function in vivo has been inferred from in vitro studies of T cells from human immunodeficient patients with mutations in ORAI1 and Orai1(-/-) mice, but a detailed analysis of T cell-mediated immune responses in vivo in mice lacking functional ORAI1 has been missing. We therefore generated Orai1 knock-in mice (Orai1(KI/KI)) expressing a nonfunctional ORAI1-R93W protein. Homozygosity for the equivalent ORAI1-R91W mutation abolishes CRAC channel function in human T cells resulting in severe immunodeficiency. Homozygous Orai1(KI/KI) mice die neonatally, but Orai1(KI/KI) fetal liver chimeric mice are viable and show normal lymphocyte development. T and B cells from Orai1(KI/KI) mice display severely impaired store-operated Ca(2+) entry and CRAC channel function resulting in a strongly reduced expression of several key cytokines including IL-2, IL-4, IL-17, IFN-γ, and TNF-α in CD4(+) and CD8(+) T cells. Cell-mediated immune responses in vivo that depend on Th1, Th2, and Th17 cell function were severely attenuated in ORAI1-deficient mice. Orai1(KI/KI) mice lacked detectable contact hypersensitivity responses and tolerated skin allografts significantly longer than wild-type mice. In addition, T cells from Orai1(KI/KI) mice failed to induce colitis in an adoptive transfer model of inflammatory bowel disease. These findings reaffirm the critical role of ORAI1 for T cell function and provide important insights into the in vivo functions of CRAC channels for T cell-mediated immunity.
p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. (1994)

Cell-cell contact and TGF-beta can arrest the cell cycle in G1. Mv1Lu mink epithelial cells arrested by either mechanism are incapable of assembling active complexes containing the G1 cyclin, cyclin E, and its catalytic subunit, Cdk2. These growth inhibitory signals block Cdk2 activation by raising the threshold level of cyclin E necessary to activate Cdk2. In arrested cells the threshold is set higher than physiological cyclin E levels and is determined by an inhibitor that binds to cyclin E-Cdk2 complexes. A 27-kD protein that binds to and prevents the activation of cyclin E-Cdk2 complexes can be purified from arrested cells but not from proliferating cells, using cyclin E-Cdk2 affinity chromatography. p27 is present in proliferating cells, but it is sequestered and unavailable to interact with cyclin E-Cdk2 complexes. Cyclin D2-Cdk4 complexes bind competitively to and down-regulate the activity of p27 and may thereby act in a pathway that reverses Cdk2 inhibition and enables G1 progression.
Reactions of Oxidatively Activated Arylamines with Thiols: Reaction Mechanisms and Biologic Implications. An Overview (1994)

Peter Eyer, Reactions of Oxidatively Activated Arylamines with Thiols: Reaction Mechanisms and Biologic Implications. An Overview, Environmental Health Perspectives, Vol. 102, Supplement 6: Carcinogenic and Mutagenic N-Substituted Aryl Compounds (Oct., 1994), pp. 123-132
The role of radiopharmacological imaging in streamlining the drug development process. (1997)

Radioimaging techniques have found a place in clinical diagnosis, but there has been a hesitancy to use this approach in drug development. This reluctance may have been due to the availability of ligands, the time and cost of synthesis and the number of centres and, although these perceived problems have been largely overcome, for many the benefits are not evident. The use in drug development is potentially large since tomography can measure drug levels, specific binding, blood flow and activity within the human body. In drug discovery, combinational chemistry and high throughput screening, the synthesis of candidate drugs with specific binding properties are dependent on understanding the disease and using appropriate in vitro or animal models. Using small animal tomographs, these can be validated using radioimaging. Pharmacokinetics and metabolic problems, such as the distribution of inhaled gases, drug targeting into tumours of the brain or specific gastrointestinal absorption sites can be investigated within the human rather than relying on animals. The high specific activity allows low doses to be administered to man with limited safety studies, permitting kinetic and metabolic studies to be undertaken early in development. Safety studies and ensuing toxicological endpoints in animals rely on histopathology for gross degenerative in physiological function. Where concern exists, radioimaging could detect early in situ changes in humans, for example hepatic toxicity, before they become hazardous. In clinical studies, the action of drugs can be measured directly at the effector site prior to undertaking longer studies, which is important for many diseases, but particularly for those such as Alzheimer's disease, where improvements may be slow or subtle.
Cell-Free Immunity in Insects (1987)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More