gebhart/patrepeval huggingface dataset:
Flash photography enhancement via intrinsic relighting (2004)

We enhance photographs shot in dark environments by combining a picture taken with the available light and one taken with the flash. We preserve the ambiance of the original lighting and insert the sharpness from the flash image. We use the bilateral filter to decompose the images into detail and large scale. We reconstruct the image using the large scale of the available lighting and the detail of the flash. We detect and correct flash shadows. This combines the advantages of available illumination and flash photography.
Differential Gene Regulation by PPARγ Agonist and Constitutively Active PPARγ2 (2002)

The PPARgamma is a key adipogenic determination factor. Ligands for PPARgamma such as antidiabetic thiazolidinedione (TZD) compounds are adipogenic, and many adipocyte genes that are activated by TZDs contain binding sites for PPARgamma. Like ligands for other nuclear receptors, TZDs can regulate genes positively or negatively. Here, we sought to understand the importance of positive regulation of gene expression by PPARgamma in adipogenesis. Fusion of the potent viral transcriptional activator VP16 to PPARgamma2 (VP16-PPARgamma) created a transcription factor that constitutively and dramatically activated transcription of PPARgamma-responsive genes in the absence of ligand. Forced expression of VP16-PPARgamma in 3T3-L1 preadipocytes using retroviral vectors led to adipogenesis in the absence of standard differentiating medium or any exogenous PPARgamma ligand. Gene microarray analysis revealed that VP16-PPARgamma induced many of the genes associated with adipogenesis and adipocyte function. Thus, direct up-regulation of gene expression by PPARgamma is sufficient for adipogenesis. TZD-induced adipogenesis up-regulated many of the same genes, although some were divergently regulated, including resistin, whose gene expression was reduced inVP16-PPARgamma adipocytes treated with TZDs. These results show that, although activation of PPARgamma by a heterologous activation domain is sufficient for adipogenesis, it is not equivalent to TZD treatment. This conclusion has important implications for understanding biological effects of the TZDs on adipogenesis and insulin sensitization.
A Synthetic Lectin for O‐Linked β‐N‐Acetylglucosamine (2008)

Changing employment: Receptor 1 binds beta-N-acetylglucosaminyl (beta-GlcNAc) up to 100 times more strongly than it does glucose. This synthetic lectin shows affinities similar to wheat germ agglutinin (WGA), a natural lectin used to bind GlcNAc. Remarkably, 1 is more selective than WGA. It favors especially the glycoside unit in glycopeptide 2, a model of the serine-O-GlcNAc posttranslational protein modification.
Long-Term Histopathological Changes Observed in Rats Subjected to Augmentation Cystoplasty (1994)

Possible development of proliferative lesions in bladders subjected to augmentation cystoplasty is a matter of concern for many clinicians. We have previously reported on the development of bladder papillomas in 5 of 15 rats approximately 18 months after gastrocystoplasty. We now report a followup study designed to investigate histopathological changes occurring in rat bladders approximately 2 years after augmentation cystoplasty using various gastrointestinal segments. Prepubescent Long-Evans female rats were randomly divided into 4 groups and underwent either gastrocystoplasty, ileocystoplasty, colocystoplasty or a sham operation (controls). Animals were sacrificed 14 to 27 months (average 21.5) postoperatively and bladders were examined histologically. Metaplastic and/or hyperplastic changes were observed in the gastrointestinal patches or surrounding urothelium in all bladders having undergone augmentation cystoplasty. Tumors occurred on or adjacent to the lumenal surface of the augmented segment in 4 of 10, 3 of 11 and 2 of 11 rats that underwent gastrocystoplasty, ileocystoplasty or colocystoplasty, respectively. None of the tumors was observed to invade blood vessels, lymphatics or the underlying muscle layers. However, histological features of malignancy characterized by varying degrees of cellular pleomorphism occurred in some tumors. Control rats (10) had only minor changes related to reapposition of tissues and remnants of suture. Possible etiologies and the potential significance of these augmentation cystoplasty related proliferative lesions are discussed.
A 0.5 V Receiver in 90 nm CMOS for 2.4 GHz Applications (2007)

We report an ultra-low voltage RF receiver for applications in the 2.4 GHz band, designed in a 90 nm CMOS technology. The sliding-IF receiver prototype includes an LNA, an image-reject LC filter with single-ended to differential conversion, an RF mixer, an LC IF filter, a quadrature IF mixer, RF and IF LO buffers, and an I/Q baseband section with a VGA and a low-pass channel-select filter in each path, all integrated on-chip. It has a programmable overall gain of 30 dB, noise figure of 18 dB, out-of-channel IIP3 of -22 dBm, and 26 dB of on-chip image rejection. The 3.4 mm2 chip consumes 8.5 mW from a 0.5 V supply.
Identification of tumor‐associated antigens by screening phage‐displayed human cDNA libraries with sera from tumor patients (2003)

Screening cDNA libraries from solid human tumors with sera of autologous patients (SEREX) has proven to be a powerful approach to identifying tumor antigens recognized by the humoral arm of the immune system. In many cases, application of this methodology has led to the discovery of novel tumor antigens as unknown gene products. We tried to improve the potency of the SEREX approach by combining it with phage-display technology. We designed a new lambda vector to express protein fragments as N-terminal fusions to the D capsid protein and generated high-complexity cDNA libraries from human breast carcinoma cell lines and solid tumors. Screening these phage-displayed libraries required limited amounts of sera from patients and efficiently identified several tumor antigens specifically reacting with sera from breast cancer patients.
Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo (1990)

1. Three analogues of L-arginine were characterized as inhibitors of endothelial nitric oxide (NO) synthase by measuring their effect on the endothelial NO synthase from porcine aortae, on the vascular tone of rings of rat aorta and on the blood pressure of the anaesthetized rat. 2. NG-monomethyl-L-arginine (L-NMMA), N-iminoethyl-L-ornithine (L-NIO) and NG-nitro-L-arginine methyl ester (L-NAME; all at 0.1-100 microM) caused concentration-dependent inhibition of the Ca2(+)-dependent endothelial NO synthase from porcine aortae. 3. L-NMMA, L-NIO and L-NAME caused an endothelium-dependent contraction and an inhibition of the endothelium-dependent relaxation induced by acetylcholine (ACh) in aortic rings. 4. L-NMMA, L-NIO and L-NAME (0.03-300 mg kg-1, i.v.) induced a dose-dependent increase in mean systemic arterial blood pressure accompanied by bradycardia. 5. L-NMMA, L-NIO and L-NAME (100 mg kg-1, i.v.) inhibited significantly the hypotensive responses to ACh and bradykinin. 6. The increase in blood pressure and bradycardia produced by these compounds were reversed by L-arginine (30-100 mg kg-1, i.v.) in a dose-dependent manner. 7. All of these effects were enantiomer specific. 8. These results indicate that L-NMMA, L-NIO and L-NAME are inhibitors of NO synthase in the vascular endothelium and confirm the important role of NO synthesis in the maintenance of vascular tone and blood pressure.
The MAP kinase Fus3 associates with and phosphorylates the upstream signaling component Ste5. (1994)

Activation of the Saccharomyces cerevisiae MAP kinase Fus3 is thought to occur via a linear pathway involving the sequential action of three proteins: Ste5, a protein of unknown function, Ste11, a MAPKK kinase homolog, and Ste7, a MAPK kinase homolog which phosphorylates and activates Fus3. In this report, we present evidence for a novel mechanism of Fus3 activation that involves a direct association with Ste5, a protein not predicted to interact with Fus3. First, overexpression of Ste5 suppresses fus3 point mutations in an allele-specific manner and increases Fus3 kinase activity in vitro. Second, Ste5 associates with Fus3 in vivo as demonstrated by the two-hybrid system and by two methods of copurification. Third, Ste5 and Fus3 associate prior to pheromone stimulation even when Fus3 is inactive, and in strains lacking Ste7 and Ste11. Fourth Ste5 is phosphorylated by Fus3 in purified complexes and copurifies with an additional protein kinase(s). These observations suggest the possibility that Ste5 promotes signal transduction by tethering Fus3 to its activating protein kinase(s).
A Novel Minimal-Size Vector (MIDGE) Improves Transgene Expression in Colon Carcinoma Cells and Avoids Transfection of Undesired DNA (2001)

Viral and plasmid vectors may cause unwanted immunological side effects resulting from the expression of nontherapeutic genes contained in their sequence. Furthermore, replication-defective viral vectors carry the potential risk of recombination with wild-type viruses or activation of oncogenes. A new vector type for minimalistic, immunologically defined gene expression (MIDGE) may overcome these problems. MIDGE is a minimal-size gene transfer unit containing the expression cassette, including promoter, gene, and RNA-stabilizing sequence, flanked by two short hairpin oligonucleotide sequences. The resulting vector is a small, linear, covalently closed, dumbbell-shaped molecule. DNA not encoding the desired gene is reduced to a minimum. Here, we transfected colon carcinoma cell lines using cationic lipid, cationic polymer, and electroporation with several MIDGE vectors and corresponding plasmids containing transgenes encoding enhanced green fluorescent protein (eGFP) and human interleukin-2 (hIL-2). Transfection efficiency as measured qualitatively and quantitatively with eGFP was found to be comparable for both vector types. However, hIL-2 secretion and eGFP expression were approximately two- to fourfold higher in most cells transfected with these transgenes using MIDGE vectors compared to the plasmid control. This report demonstrates the advantages of this new vector type and its prospects for ex vivo gene therapy studies.
Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain (2006)

Selective activation of the peripheral cannabinoid receptor 1 (CB1R) has been shown to suppress neuropathic pain symptoms in rodents. However, relatively little is known about changes in CB1R and its endogenous ligands during development or maintenance of neuropathic pain. Using immunohistochemistry, Western blot, real-time reverse transcription polymerase chain reaction, as well as liquid chromatography/mass spectrometry, we studied the changes in CB1Rs and endocannabinoids N-arachidonoylethanolamine/anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat lumbar (L4 and L5) dorsal root ganglia (DRG) after neuropathic pain induction (L5 spinal nerve ligation: SNL). Immunohistochemistry revealed that in control rats, CB1R is expressed in the majority (76-83%) of nociceptive neurons as indicated by co-labeling with isolectin B4 (IB4) or antibodies recognizing transient receptor potential vanilloid (TRPV1), calcitonin gene related peptide (CGRP), and the NR2C/2D subunits of the N-methyl-D-aspartate receptor. After L5 SNL, CB1R mRNA and protein increases in the ipsilateral uninjured L4 DRG whereas the percentages of CB1R immunoreactive (CB1R-ir) neurons remain unchanged in L4 and L5 DRG. However, for these CB1R-ir neurons, we observe significant increases in percentage of TRPV1-ir cells in ipsilateral L4 DRG, and decreases in percentage of IB4- and CGRP-co-labeled cells in ipsilateral L5 DRG. Levels of both AEA and 2-AG increase significantly only in the ipsilateral L5 DRG. These results are consistent with the preserved analgesic effects of cannabinoids in neuropathic pain and provide a rational framework for the development of peripherally acting endocannabinoid-based therapeutic interventions for neuropathic pain.
Genetic and Pharmacological Inhibition of Galectin-3 Prevents Cardiac Remodeling by Interfering With Myocardial Fibrogenesis (2012)

Genetic disruption and pharmacological inhibition of galectin-3 attenuates cardiac fibrosis, LV dysfunction, and subsequent heart failure development. Drugs binding to galectin-3 may be potential therapeutic candidates for the prevention or reversal of heart failure with extensive fibrosis.
TheO-Carbamoyl-Transferase Alb15 Is Responsible for the Modification of Albicidin (2016)

Albicidin is a potent antibiotic and phytotoxin produced by Xanthomonas albilineans which targets the plant and bacterial DNA gyrase. We now report on a new albicidin derivative which is carbamoylated at the N-terminal coumaric acid by the action of the ATP-dependent O-carbamoyltransferase Alb15, present in the albicidin (alb) gene cluster. Carbamoyl-albicidin was characterized by tandem mass spectrometry from cultures of a Xanthomonas overproducer strain and the gene function confirmed by gene inactivation of alb15 in X. albilineans. Expression of alb15 in Escherichia coli and in vitro reconstitution of the carbamoyltransferase activity confirmed albicidin as the substrate. The chemical synthesis of carbamoyl-albicidin finally enabled us to assess its bioactivity by means of in vitro gyrase inhibition and antibacterial assays. Compared to albicidin, carbamoyl-albicidin showed a significantly higher inhibitory efficiency against bacterial gyrase (∼8 vs 49 nM), which identifies the carbamoyl group as an important structural feature of albicidin maturation.
The lysine residue in the membrane-spanning domain of the beta chain is necessary for cell surface expression of the T cell antigen receptor. (1988)

The TCR is a complex receptor composed of seven polypeptide chains consisting of a ligand-binding subunit, Ti, and a putative signal-transducing subunit, CD3. Phylogenetically conserved charged amino acid residues within the membrane-spanning domains present in all seven chains of the TCR have been proposed to be important in the association between Ti and CD3. Using a Ti beta chain-deficient mutant of the cell line Jurkat, site-directed mutagenesis and transfection of Ti beta chain cDNA was performed to assess the importance of the lysine residue at position 290 within the membrane-spanning domain of the Ti beta chain to expression of the TCR complex. These studies demonstrated that the lysine residue, and not simply conservation of either basic charge or secondary structure, is important at this position.
Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literature (2005)

Varma M & Jasani B (2005) Histopathology47, 1-16 Diagnostic utility of immunohistochemistry in morphologically difficult prostate cancer: review of current literatureImmunohistochemistry is widely used to distinguish prostate cancer from benign mimics and to establish the prostatic origin of poorly differentiated carcinoma. We critically review the recent advances in prostate cancer immunohistochemistry, including the introduction of newer basal cell markers such as p63 and the discovery of the overexpression of alpha-methylacyl coenzyme A racemase (AMACR) in prostate cancer. The description of newer urothelial markers to aid the distinction of prostate cancer from urothelial carcinoma is also presented together with refinements in the quality control of PSA and PSAP immunostaining. Although AMACR is a useful immunohistochemical marker for prostate cancer, it has significant limitations. These limitations are discussed and the need for interpreting AMACR immunoreactivity in the appropriate morphological context and in conjunction with basal call markers is emphasized. We also describe the utility of an immunohistochemical panel composed of PSA, PSAP and high molecular weight cytokeratin for distinguishing poorly differentiated prostate cancer from high-grade urothelial carcinoma. A morphological differential diagnosis based selection of immunohistochemical markers is highlighted as a novel approach in the diagnosis of prostate cancer in routine surgical pathology practice.
X‐ray crystallographic and kinetic correlation of a clinically observed human fumarase mutation (2002)

Fumarase catalyzes the reversible conversion of fumarate to S- malate during the operation of the ubiquitous Kreb's cycle. Previous studies have shown that the active site includes side chains from three of the four subunits within the tetrameric enzyme. We used a clinically observed human mutation to narrow our search for potential catalytic groups within the fumarase active site. Offspring homozygous for the missense mutation, a G-955-C transversion in the fumarase gene, results in the substitution of a glutamine at amino acid 319 for the normal glutamic acid. To more fully understand the implications of this mutation, a single-step site-directed mutagenesis method was used to generate the homologous substitution at position 315 within fumarase C from Escherichia coli. Subsequent kinetic and X-ray crystal structure analyses show changes in the turnover number and the cocrystal structure with bound citrate.
Experimental demonstration of a robust and scalable flux qubit (2010)

A rf--superconducting quantum interference device (SQUID) flux qubit that is robust against fabrication variations in Josephson-junction critical currents and device inductance has been implemented. Measurements of the persistent current and of the tunneling energy between the two lowest-lying states, both in the coherent and incoherent regimes, are presented. These experimental results are shown to be in agreement with predictions of a quantum-mechanical Hamiltonian whose parameters were independently calibrated, thus justifying the identification of this device as a flux qubit. In addition, measurements of the flux and critical current noise spectral densities are presented that indicate that these devices with Nb wiring are comparable to the best Al wiring rf SQUIDs reported in the literature thus far, with a $1/f$ flux noise spectral density at 1 Hz of ${1.3}_{\ensuremath{-}0.5}^{+0.7}\text{ }\ensuremath{\mu}{\ensuremath{\Phi}}_{0}/\sqrt{\text{Hz}}$. An explicit formula for converting the observed flux noise spectral density into a free-induction-decay time for a flux qubit biased to its optimal point and operated in the energy eigenbasis is presented.
A real‐time PCR assay to identify and discriminate among wild‐type and vaccine strains of varicella‐zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses (2009)

A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human beta-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results.
Screening of Type I and II Drug Binding to Human Cytochrome P450-3A4 in Nanodiscs by Localized Surface Plasmon Resonance Spectroscopy (2009)

A prototype nanoparticle biosensor based on localized surface plasmon resonance (LSPR) spectroscopy was developed to detect drug binding to human membrane-bound cytochrome P450 3A4 (CYP3A4). CYP3A4 is one of the most important enzymes in drug and xenobiotic metabolism in the human body. Because of the inherent propensity of CYP3A4 to aggregate, it is difficult to study drug binding to this protein in solution and on surfaces. In this paper, we use a soluble nanometer scale membrane bilayer disk (Nanodisk) to functionally stabilize monomeric CYP3A4 on Ag nanoparticle surfaces fabricated by nanosphere lithography. CYP3A4-Nanodiscs have absorption bands in the visible wavelength region, which upon binding certain drugs shift to either shorter (type I) or longer wavelengths (type II). On the basis of the coupling between the LSPR of the Ag nanoparticles and the electronic resonances of the heme chromophore in CYP3A4-Nanodiscs, LSPR spectroscopy is used to detect drug binding with high sensitivity. This paper combines LSPR and Nanodisc techniques to optically sense drug binding to a functionally stable membrane protein, with the goal of integrating this with microfluidics and expanding it into a multiarray format, enabling high-throughput screening.
Graded Otx2 activities demonstrate dose-sensitive eye and retina phenotypes (2013)

In the human, mutations of OTX2 (Orthodenticle homeobox 2 transcription factor) translate into eye malformations of variable expressivity (even between the two eyes of the same individual) and incomplete penetrance, suggesting the existence of subtle thresholds in OTX2 activity. We have addressed this issue by analyzing retinal structure and function in six mutant mice with graded Otx2 activity: Otx2(+/+), Otx2(+/AA), Otx2(+/GFP), Otx2(AA/AA), Otx2(AA/GFP) and Otx2(GFP/GFP). Null mice (Otx2(GFP/GFP)) fail to develop the head and are embryonic lethal, and compound heterozygous Otx2(AA/GFP) mice show a truncated head and die at birth. All other genotypes develop until adulthood. We analyzed eye structure and visual physiology in the genotypes that develop until adulthood and report that phenotype severity parallels Otx2 activity. Otx2(+/AA) are only mildly affected whereas Otx2(+/GFP) are more affected than Otx2(+/AA) but less than Otx2(AA/AA) mice. Otx2(AA/AA) mice later manifest the most severe defects, with variable expressivity. Electrophysiological and histological analyses of the mouse retina revealed progressive death of bipolar cells and cone photoreceptors that is both Otx2 activity- and age-dependent with the same ranking of phenotypic severity. This study demonstrates the importance of gene dosage in the development of age-dependent pathologies and underscores the fact that small gene dosage differences can cause significant pathological states.