gebhart/patrepeval huggingface dataset:
Protein kinase C and the development of diabetic vascular complications (2001)

Hyperglycemic control in diabetes is key to preventing the development and progression of vascular complications such as retinopathy, nephropathy and neuropathy. Increased activation of the diacylglycerol (DAG)-protein kinase C (PKC) signal transduction pathway has been identified in vascular tissues from diabetic animals, and in vascular cells exposed to elevated glucose. Vascular abnormalities associated with glucose-induced PKC activation leading to increased synthesis of DAG include altered vascular blood flow, extracellular matrix deposition, basement membrane thickening, increased permeability and neovascularization. Preferential activation of the PKCbeta isoform by elevated glucose is reported to occur in a variety of vascular tissues. This has lead to the development of LY333531, a PKCbeta isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction. Additionally, the antioxidant vitamin E has been identified as an inhibitor of the DAG-PKC pathway, and shows promise in reducing vascular complications in animal models of diabetes. Given the overwhelming evidence indicating a role for PKC activation in contributing to the development of diabetic vascular complications, pharmacological therapies that can modulate this pathway, particularly with PKC isoform selectivity, show great promise for treatment of vascular complications, even in the presence of hyperglycemia.
Brain Iron Metabolism and Neurodegenerative Disorders (2002)

Iron, an essential element for central nervous system (CNS) function, has frequently been found to accumulate in brain regions that undergo degeneration in neurological diseases such as Alzheimer disease, Parkinson disease, Friedreich ataxia and other disorders. However, the precise role of iron in the cause of many neurodegenerative diseases is unclear. To assist in understanding the potential importance of iron in CNS disease, this review summarizes the present knowledge in the areas of CNS iron metabolism, homeostasis and disregulation of iron balance caused by mutations in genes encoding proteins involved in iron transport, storage and metabolism. This review encompasses neurodegenerative disorders associated with both iron overload and deficiency to highlight areas where iron misregulation is likely to be important in the pathophysiology of several human brain diseases.
Escherichia coli DnaK and GrpE heat shock proteins interact both in vivo and in vitro (1989)

Previous studies have demonstrated that the Escherichia coli dnaK and grpE genes code for heat shock proteins. Both the Dnak and GrpE proteins are necessary for bacteriophage lambda DNA replication and for E. coli growth at all temperatures. Through a series of genetic and biochemical experiments, we have shown that these heat shock proteins functionally interact both in vivo and in vitro. The genetic evidence is based on the isolation of mutations in the dnaK gene, such as dnaK9 and dnaK90, which suppress the Tr- phenotype of bacteria carrying the grpE280 mutation. Coimmunoprecipitation of DnaK+ and GrpE+ proteins from cell lysates with anti-DnaK antibodies demonstrated their interaction in vitro. In addition, the DnaK756 and GrpE280 mutant proteins did not coimmunoprecipitate efficiently with the GrpE+ and DnaK+ proteins, respectively, suggesting that interaction between the DnaK and GrpE proteins is necessary for E. coli growth, at least at temperatures above 43 degrees C. Using this assay, we found that one of the dnaK suppressor mutations, dnaK9, reinstated a protein-protein interaction between the suppressor DnaK9 and GrpE280 proteins.
Mechanisms of tumor-induced neutrophilia: constitutive production of colony-stimulating factors and their synergistic actions (1989)

Abstract Transplantation of a murine mammary carcinoma (CE maca) into mice induces marked granulocytosis and hypercalcemia secondary to excessive bone resorption. Such responses are not induced by another murine mammary carcinoma Bc66. In order to understand the mechanisms of these unique phenomena, we analyzed mRNA of tumor cells for expression of murine granulopoietic growth factors and studied interactions of tumor- derived factors using antiserum to a growth factor in vitro and in vivo. The Northern blot analysis of CE tumor clones revealed the expression of granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), but no other CSF genes, while the Bc66 clone expressed only M-CSF. The G-CSF and M-CSF gene expression in CE tumor clones was accompanied by secretion of these proteins in culture. The granulocyte stimulating activity of CE tumor- derived G-CSF or recombinant human G-CSF was markedly enhanced by purified M-CSF in vitro. Significant but variable neutrophilia was observed in mice inoculated with CE tumor clones. Anti-M-CSF treatment of CE tumor-bearing mice significantly reduced neutrophilia, but did not affect hypercalcemia. These studies document that G-CSF and M-CSF are produced constitutively from the CE maca, and G-CSF is likely responsible for granulocytosis induced by this tumor. G-CSF and M-CSF function synergistically in granulocyte stimulation in vitro and this synergism may also play a role in marked granulocytosis of tumor- bearing animals, providing further evidence of the effect of CSFs in vivo.
A Herpes Simplex Virus Recombinant That Exhibits a Single-Chain Antibody to HER2/neu Enters Cells through the Mammary Tumor Receptor, Independently of the gD Receptors (2006)

The human epidermal growth factor receptor 2/neuregulin (HER2/neu) receptor is overexpressed in highly malignant mammary and ovarian tumors and correlates with a poor prognosis. It is a target for therapy; humanized monoclonal antibodies to HER2 have led to increased survival of patients with HER2/neu-positive breast cancer. As a first step in the design of an oncolytic herpes simplex virus able to selectively infect HER2/neu-positive cells, we constructed two recombinants, R-LM11 and R-LM11L, that carry a single-chain antibody (scFv) against HER2 inserted at residue 24 of gD. The inserts were 247 or 256 amino acids long, and the size of the gD ectodomain was almost doubled by the insertion. We report the following. R-LM11 and R-LM11L infected derivatives of receptor-negative J or CHO cells that expressed HER2/neu as the sole receptor. Entry was dependent on HER2/neu, since it was inhibited in a dose-dependent manner by monoclonal antibodies to HER2/neu and by a soluble form of the receptor. The scFv insertion in gD disrupted the ability of the virus to enter cells through HVEM but maintained the ability to enter through nectin1. This report provides proof of principle that gD can tolerate fusion to a heterologous protein almost as large as the gD ectodomain itself without loss of profusion activity. Because the number of scFv's to a variety of receptors is continually increasing, this report makes possible the specific targeting of herpes simplex virus to a large collection of cell surface molecules for both oncolytic activity and visualization of tumor cells.
Microvesicles: mediators of extracellular communication during cancer progression (2010)

Microvesicles are generated by the outward budding and fission of membrane vesicles from the cell surface. Recent studies suggest that microvesicle shedding is a highly regulated process that occurs in a spectrum of cell types and, more frequently, in tumor cells. Microvesicles have been widely detected in various biological fluids including peripheral blood, urine and ascitic fluids, and their function and composition depend on the cells from which they originate. By facilitating the horizontal transfer of bioactive molecules such as proteins, RNAs and microRNAs, they are now thought to have vital roles in tumor invasion and metastases, inflammation, coagulation, and stem-cell renewal and expansion. This Commentary summarizes recent literature on the properties and biogenesis of microvesicles and their potential role in cancer progression.
Bactericidal effect of pulsed 1,064 nm Nd:YAG laser light on Staphylococcus epidermidis is of photothermal origin: An in vitro study (2000)

Background and Objective The aim was to investigate the bactericidal effect of the 1,064 nm Nd:YAG laser on Staphylococcus epidermidis. Material and Methods S. epidermidis was inoculated on agar plates and then exposed to pulsed laser light in three different modes: with an uninterrupted train of pulses, or with two different repeated cycles of fractionated trains of pulses. The agar temperature was measured directly after uninterrupted radiation. Results A bacterial growth inhibition area of 0.3 cm2 and maximum temperature of approximately 80°C was observed after uninterrupted radiation at 2,000 J cm−2. The corresponding figures after an exposure of 5,000 J cm−2 were 0.9 cm2 and 100°C, respectively. No bacterial inhibition was observed after exposure to repeated cycles of 20 seconds of radiation followed by 60 seconds of rest. Conclusion The antimicrobial effect of the 1,064 nm Nd:YAG laser light is caused by a photothermal rather than a photochemical effect. Lasers Surg. Med. 27:336–340, 2000. © 2000 Wiley-Liss, Inc.
Selective progesterone receptor modulators 3: use in oncology, endocrinology and psychiatry (2008)

In preliminary studies selective modulators of progesterone receptors had some activity on a number of neoplasias. Their antiglucocorticoid activity has been tested with some success in Cushing's syndrome, several psychiatric conditions (e.g., mood disorders and Alzheimer's disease) and acute renal failure. Finally they are being used in a gene regulator system.
Broad Repertoire of the CD4+ Th Cell Response in Spontaneously Controlled Hepatitis C Virus Infection Includes Dominant and Highly Promiscuous Epitopes (2005)

A vigorous hepatitis C virus (HCV)-specific Th cell response is regarded as essential to the immunological control of HCV viremia. The aim of this study was to comprehensively define the breadth and specificity of dominant HCV-specific CD4(+) T cell epitopes in large cohorts of subjects with chronic and spontaneously resolved HCV viremia. Following in vitro stimulation of PBMC, HCV-specific cell cultures from each subject were screened with an overlapping panel of synthetic 20-mer peptides spanning the entire HCV polyprotein. Of 22 subjects who spontaneously controlled HCV viremia, all recognized at least one of a group of six epitopes situated within the nonstructural (NS) proteins NS3, NS4, and NS5, each of which was detected by >30% of subjects, but most subjects recognized additional, more heterogeneous specificities. In contrast, none of the most frequently targeted epitopes was detected by >5% of persons with chronic infection. The most frequently recognized peptides showed promiscuous binding to multiple HLA-DR molecules in in vitro binding assays and were restricted by different HLA-DR molecules in functional assays in different persons. These data demonstrate that predominant CD4(+) T cell epitopes in persons with resolved HCV infection are preferentially located in the nonstructural proteins and are immunogenic in the context of multiple class II molecules. This comprehensive characterization of CD4(+) T cell epitopes in resolved HCV infection provides important information to facilitate studies of immunopathogenesis and HCV vaccine design and evaluation.
Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling (2012)

Human pluripotent stem cells (hPSCs) offer the potential to generate large numbers of functional cardiomyocytes from clonal and patient-specific cell sources. Here we show that temporal modulation of Wnt signaling is both essential and sufficient for efficient cardiac induction in hPSCs under defined, growth factor-free conditions. shRNA knockdown of β-catenin during the initial stage of hPSC differentiation fully blocked cardiomyocyte specification, whereas glycogen synthase kinase 3 inhibition at this point enhanced cardiomyocyte generation. Furthermore, sequential treatment of hPSCs with glycogen synthase kinase 3 inhibitors followed by inducible expression of β-catenin shRNA or chemical inhibitors of Wnt signaling produced a high yield of virtually (up to 98%) pure functional human cardiomyocytes from multiple hPSC lines. The robust ability to generate functional cardiomyocytes under defined, growth factor-free conditions solely by genetic or chemically mediated manipulation of a single developmental pathway should facilitate scalable production of cardiac cells suitable for research and regenerative applications.
Multi-Temporal Remote Sensing Image Registration Using Deep Convolutional Features (2018)

Registration of multi-temporal remote sensing images has been widely applied in military and civilian fields, such as ground target identification, urban development assessment, and geographic change assessment. Ground surface change challenges feature point detection in amount and quality, which is a common dilemma faced by feature-based registration algorithms. Under severe appearance variation, detected feature points may contain a large proportion of outliers, whereas inliers may be inadequate and unevenly distributed. This paper presents a convolutional neural network (CNN) feature-based multitemporal remote sensing image registration method with two key contributions: (i) we use a CNN to generate robust multi-scale feature descriptors and (ii) we design a gradually increasing selection of inliers to improve the robustness of feature point registration. Extensive experiments on feature matching and image registration are performed over a multi-temporal satellite image data set and a multi-temporal unmanned aerial vehicle image dataset. Our method outperforms four state-of-the-art methods in most scenarios.
Signal Detection for Cognitive Radios with Smashed Filtering (2009)

Compressed sensing and the related recently introduced smashed filter are novel signal processing methods, which allow for low-complexity parameter estimation by projecting the signal under analysis on a random subspace. In this paper the smashed filter of Davenport et al. is applied to a principal problem of digital communications: pilot-based time offset and frequency offset estimation. An application, motivated by current cognitive radio research, is wide-band detection of a narrowband signal, e.g. to synchronize terminals without prior channel or frequency allocation. Smashed filter estimation and maximum likelihood-based, uncompressed estimation for a signal corrupted by additive white Gaussian noise (matched filter estimation) are compared. Smashed Filtering adds a degree of freedom to signal detection and estimation problems, which effectively allows to trade signal-to-noise ratio against processing bandwidth for arbitrary signals.
Elastic protein-based polymers in soft tissue augmentation and generation (1998)

Five elastic protein-based polymers, designed as variations of polymer I, (GVGVP)251, elicited different responses when injected as subcutaneous implants in the guinea pig, a preclinical test used to evaluate materials for soft tissue augmentation and specifically for correction of urinary incontinence. All six polymers, prepared using recombinant DNA technology, expressed at good levels using transformed E. coli fermentation. These E. coli-produced polymers were purified for the first time to the exacting levels required for use as biomaterials where a large quantity could disperse into the tissues in a few days. Time periods of 2 and 4 weeks were used. Polymer I functioned as a bulking agent around which a fine fibrous capsule formed. Inclusion of (GVGVAP)8, a chemoattractant toward monocytes and elastin-synthesizing fibroblasts in the sequence of polymer I, resulted in an appropriate tissue response of invasion of macrophages. Inclusion of lysine residues, for lysyl oxidase cross-linking, suggested a possible remodeling of the implant toward fibers. Most promising however, when the cell attachment sequence, GRGDSP, was added to polymer I, the implant elicited tissue generation with a normal complement of collagen and elastic fibers, spindle-shaped histiocytes and angiogenesis. If this response is retained over time, the desired soft tissue augmentation and generation will have been achieved. Our working hypothesis is that on formation of elastin, with a half-life of the order of 70 years, a long lasting soft tissue augmentation would result rather than scar tissue as occurs with Contigen, the currently approved injectable implant for soft tissue augmentation.
Backward Compatible HDR Video Compression System (2016)

A new video compression scheme for High Dynamic Range (HDR) contents is presented. It is assumed that both Standard Dynamic Range (SDR) and HDR devices coexist in the ecosystem, and the scheme is constructed to ensure backward compatibility such that a single video stream carries both the original HDR video and an automatically generated SDR version of this video without noticeable overhead relatively to the distribution of the HDR video only. Compression performance are shown to be solidly improved compared to the conservative and non-backward-compatible approach using the HEVC Main10 codec and the Perceptual Quantizer (PQ) Electro-Optical Transfer Function (OETF) as non-linearity.
Transgenesis Techniques: Principles and Protocols (1993)

Over the past twenty years, the disciplines of cellular and molecular biology have generated a bounty of information pertaining to the understanding of the structure and function of eukaryotic cells . It is now recognized that individual cells regulate their activities in response to a multitude of external signals ; that external signals, a- ing through a limited number of second messenger systems, modulate the cell's pattern of gene expression; and that the cohort of genes available for regulation is dependent upon the developmental history of the cell. Extrapolating these truths to the whole organism is a challenge that has been met by an increasing number of investigators . The wealth of information that molecular and cell biology has provided us with is now being integrated into an understanding of whole t- sues, organs, and organisms. Without such an integration, the molecular information will be nothing more than a confusing catalog of sequences and structures. Central to this project will be the app- cation of the powerful new techniques described in Transgenesis Techniques: Principles and Protocols
Directed insertion of a selectable marker into a circular plasmid of Borrelia burgdorferi (1996)

Studies of the biology of Borrelia burgdorferi and the pathogenesis of Lyme disease are severely limited by the current lack of genetic tools. As an initial step toward facile genetic manipulation of this pathogenic spirochete, we have investigated gene inactivation by allelic exchange using a mutated borrelial gyrB gene that confers resistance to the antibiotic coumermycin A1 as a selectable marker. We have transformed B. burgdorferi by electroporation with a linear fragment of DNA in which this selectable marker was flanked by sequences from a native borrelial 26-kb circular plasmid. We have identified coumermycin A1-resistant transformants in which gyrB had interrupted the targeted site on the 26-kb plasmid via homologous recombination with the flanking sequences. Antibiotic resistance conferred by the mutated gyrB gene on the plasmid is dominant, and transformed spirochetes carrying this plasmid do not contain any unaltered copies of the plasmid. Coumermycin A1 resistance can be transferred to naive B. burgdorferi by transformation with borrelial plasmid DNA from the initial transformants. This work represents the first example of a directed mutation in B. burgdorferi whereby a large segment of heterologous DNA (gyrB) has been inserted via homologous recombination with flanking sequences, thus demonstrating the feasibility of specific gene inactivation by allelic exchange.
Interaction of cyclooxygenases with an apoptosis- and autoimmunity-associated protein. (1996)

Cyclooxygenases (COXs) 1 and 2 are 72-kDa, intralumenal residents of the endoplasmic reticulum (ER) and nuclear envelope, where they catalyze the rate-limiting steps in the conversion of arachidonate to the physiologically dynamic prostanoids. Recent studies, including the generation of knockout mice, show COX-1 and COX-2 to have biologically distinct roles within cells and organisms. Also apparent is that arachidonate substrate is selectably metabolized by COX-2 after mitogen stimulation in many cells that contain both isoforms. Because COX-1 and COX-2 are highly conserved in all residues needed for catalysis and in their purified forms have almost identical kinetic properties, we have searched for COX-interacting ER proteins that might mediate these unique isoenzymic properties. Using COXs as bait in the yeast two-hybrid system, we identified autoimmunity- and apoptosis-associated nucleobindin (Nuc) as a protein that specifically interacts with both isoenzymes. COX-Nuc binding was substantiated by immunoprecipitation experiments, which showed that COX-1 and, to a lesser extent, COX-2 form complexes with Nuc in vitro. When overexpressed in COS-1 cells, Nuc was found to be extracellularly released. However, when Nuc was co-overexpressed with COX-1 or COX-2, its release was reduced by >80%. This finding suggests that COX isoenzymes participate in the retention of Nuc within the lumen of the ER, where COX may regulate the release of Nuc from the cell. It also identifies Nuc as a potential regulator of COXs through this interaction.
Frameless stereotaxy of the brain. (2000)

Today's neurosurgical journals are replete with advertisements for systems designed to provide image guidance during surgery. These so-called "frameless" stereotactic systems provide the surgeon with navigational information, relating the location of instruments in the operative field to preoperative imaging data. Such information minimizes invasiveness by more accurately selecting the best trajectory to the lesion, ensures more precise identification of normal structures, and guides complete removal of a lesion. To achieve these goals, all of these systems utilize the stereotactic principle of co-registration of the patient with an imaging study. This review will trace the development of image-guided surgery from its origins in frame-based stereotaxy to its current use as a surgical navigation methodology. A review of the more prevalent techniques and available systems will be presented, along with examples of specific applications of surgical navigation. Finally, some of the future directions of frameless stereotaxy will be discussed.
An anti-parallel triple helix motif with oligodeoxynucleotidescontaining 2'-deoxyguanosine and 7-deaza-2'-deoxy xanthosine (1993)

Triple helix formation of oligodeoxynucleotides (ODNs) with a 15 base pair poly-purine DNA target in the HER2 promoter was examined by footprinting analysis. 7-deaza-2'-deoxyxanthosine (dzaX) was identified as a purine analogue of thymidine (T) which forms dzaX:A-T triplets. ODNs containing 2'-deoxyguanosine (G) and dzaX were found to form triple helices in an anti-parallel orientation, with respect to the poly-purine strand of the target DNA. In comparative studies under physiological K+ and Mg++ concentrations and at pH 7.2, the ODNs containing G and dzaX showed high affinity to the target sequence while the ODNs containing G and T were not able to bind. In the absence of added monovalent salts both ODNs showed high affinity to the target sequence. The substitution of 7-deaza-2'-deoxyguanosine for G substantially decreased the capacity of the ODNs to form triple helices under physiological conditions, indicating that dzaX may be unique in its ability to enhance triple helix formation in the anti-parallel motif.