gebhart/patrepeval huggingface dataset:
Direct evidence for multiple endothelin receptors (1991)

Competition binding experiments and peptide mapping techniques were employed in order to directly address the possible existence of endothelin (ET) receptor subtypes in the atria. Competition binding assays for 125I-labeled ET-1 or 125I-labeled ET-3 to bovine atrial membrane preparations suggest the existence of two ET receptor subtypes, one of which binds ET-1 and ET-3 with a similar affinity while the other shows preference for ET-3. However, cross-linking experiments of both peptides to this tissue resulted in the identification of a single 50-kDa protein. To identify directly the existence of multiple ET receptors, peptide mapping of cross-linked 125I-labeled ET-1 or 125I-labeled ET-3 receptors was conducted. Different peptide maps were obtained only under conditions that preferentially label one receptor subtype. These results indicate, for the first time, the existence of two ET receptor subtypes in the atria which differ from each other in both their binding characteristics and primary structure.
Characterization of LrpC DNA-Binding Properties and Regulation of Bacillus subtilis lrpC Gene Expression (2000)

The lrpC gene was identified during the Bacillus subtilis genome sequencing project. Previous experiments suggested that LrpC has a role in sporulation and in the regulation of amino acid metabolism and that it shares features with Escherichia coli Lrp, a transcription regulator (C. Beloin, S. Ayora, R. Exley, L. Hirschbein, N. Ogasawara, Y. Kasahara, J. C. Alonso, and F. Le Hégarat, Mol. Gen. Genet. 256:63-71, 1997). To characterize the interactions of LrpC with DNA, the protein was overproduced and purified. We show that LrpC binds to multiple sites in the upstream region of its own gene with a stronger affinity for a region encompassing P1, one of the putative promoters identified (P1 and P2). By analyzing lrpC-lacZ transcriptional fusions, we demonstrated that P1 is the major in vivo promoter and that, unlike many members of the lrp/asnC family, lrpC is not negatively autoregulated but rather slightly positively autoregulated. Production of LrpC in vivo is low in both rich and minimal media (50 to 300 LrpC molecules per cell). In rich medium, the cellular LrpC content is six- to sevenfold lower during the exponentional phase than during the stationary growth phase. Possible determinants and the biological significance of the regulation of lrpC expression are discussed.
365. Human Embryonic Stem Cells: Genetic Conversion to the Fanconi Anemia Phenotype (2006)

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by the progressive bone marrow failure, developmental anomalies and cancer susceptibility. Twelve distinct FA complementation groups have been identified (A–C, D1, D2, E–G, I, J, L, M) and 11 cDNAs cloned. A current working model proposes that eight FA proteins (A, B, C, E, F, G, L and M) assemble to form a multi-protein nuclear complex, involved the repair of damaged DNA. The FA complex facilitates the monoubiquitination of the FANCD2 protein following exposure to DNA damaging agents. Ubiquinated FANCD2 co-localizes with the key DNA repair proteins RAD51, BRCA2 (know as FANCD1), BRCA1, and FANCJ (BACH1) to promote homologous recombination. The hallmark of FA patients is marrow failure due to defective hematopoietic stem cells. The study of human FA stem cell biology is severely restricted due to the few CD34+ cells that can be isolated from FA patients compared with normal individuals. We set out to create a reusable source of human FA hematopoietic cells by introducing small double strand RNA species to ablate specific FA gene function in human embryonic stem cells (hESC). Human ES cells can then differentiate into human CD34+ cells to investigate human FA hematopoiesis. FANCD2-specific small hairpin RNAs (shRNAs) were designed and cloned into a self-inactivated lentiviral vector with a GFP cDNA. High titer virus (2×108 iu/ml) was used for transduction of the hESC line H1. FACS sorted hESC-FANCD2 clones were tested. FANCD2 protein expression was analyzed by Western blotting; FANCD2 shRNA targeted cells expressed 1–2% of the FANCD2 protein compared with control (mock transduced or scrambled shRNA) H1 cells. Functional assessment of the hESC-FANCD2 was performed by incubation with DNA cross-linking agent, mitomycin C (MMC). The hESC-FANCD2 cells were nearly 20 times more sensitive to MMC than untreated or scrambled shRNA ES cells. The effective dose 50 (ED50) of MMC required to induce apoptosis was only 5 ng/ml in hESC-FANCD2 cells compared with 80 ng/ml in mock- infected of scrambled shRNA controls. The expected cytogenetic aberrations were identified in hESC-FAND2 but not control cells confirming the FA phenotype. Differentiation of hESC-FANCD2 cells through a blastocyst intermediate produced a small but discrete number of CD34+/c-kit+ cells that form hematopoietic colonies in methylcellulose culture. In conclusion, we have successfully converted, using shRNAs, hESC H1 cells into cells exhibit the FA phenotype. Generation of hESC-FANCD2 cells provides a ready source of multipotent hematopoietic progenitors and a powerful tool for investigation of FA hematopoiesis. To our knowledge, this is the first description of the genetic conversion of hESCs into a disease phenotype.
Hierarchical decoder for MPEG compressed video data (1993)

An MPEG (Motion Picture Experts Group) hierarchical decoder structure capable of receiving an MPEG compressed bit stream decoding the bit stream, and providing outputs with different resolution pictures is described. In the structure of the decoder, full motion information can be used at low-resolution picture decoding. A smooth model is proposed for the compensation of block-based decimation. Simulation results show that the method with compensation outperforms the DCT-masked method with respect to PSNR (peak signal-to-noise ratio) and with the same memory requirements. The former needs more computation, but this can be alleviated by combined processing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Glycotyping of prostate specific antigen (2000)

Measurement of serum levels of the prostate specific antigen (PSA) is now widely used for the diagnosis of prostate cancer and benign prostate hyperplasia. This serum marker is of value since it is derived only from the tissue of interest, but increased levels of PSA in serum do not allow a completely clear cut diagnosis of benign versus malignant changes. Since PSA is a glycoprotein with one asparagine linked oligosaccharide, and since malignant transformation often leads to an increased branching of such oligosaccharides, we initially studied the asparagine linked structures on PSA made by a cell line derived from malignant metastatic prostate tissue. We observed that unlike normal PSA, which bears only biantennary oligosaccharides, PSA from the metastatic cell line has a mixture of biantennary and triantennary oligosaccharides. Further experiments will reveal carbohydrate differences derived from the PSA from sera or, prostate tissue of normal versus prostate cancer patients, and of the utility of such carbo-hydrate differences as a possible diagnostic marker for prostate cancer.
A preliminary study of the local treatment of preneoplastic and malignant skin lesions using methyl jasmonate. (2011)

Methyl jasmonate is a potentially promising novel topical treatment for prcancerous and cancerous skin lesions. Methyl jasmonate should be evaluated in a larger series of patients.
Cellular sources of IL‐17 in psoriasis: a paradigm shift? (2014)

Psoriasis is a common chronic inflammatory skin disease that results from interplay between the immune system and the epithelium. In the light of very successful anticytokine therapies for psoriasis, the focus has been directed towards the adaptive immune system. Expression studies, genetic studies and treatments specifically targeting players of the IL-23/IL-17 pathway, point at an important role for IL-17 in the pathogenesis of psoriasis. IL-17 stimulates the keratinocytes to produce psoriasis-associated molecules, eventually leading to chronic skin inflammation. The current opinion is that IL-17 is mainly produced by T cells, so-called T-helper 17 (Th17) cells, in psoriasis. However, evidence is accumulating that cells of the innate immune system, like neutrophils, mast cells, γδ T cells and innate lymphoid cells are the main source of IL-17 in psoriasis, rather than T cells. The paradigm in this field of research is shifting. With this viewpoint article, we will address this novel concept by critically summarizing the current literature on this subject. In psoriatic arthritis and atherosclerosis, important conditions related to psoriasis, it was also found that the majority of IL-17 is associated with cells of the innate immune system. This new concept changes our view of IL-17. Blocking IL-17 with targeted treatments might be more far-reaching than previously thought; not only IL-17 production by T cells but also by innate immune cells is blocked. Furthermore, therapies specifically targeting IL-17 may not only improve psoriasis, but also comorbidity that is associated with the IL-17 pathway, hereby preventing serious complications on the long term.
Innervation of Bladder and Bowel (2007)

The autonomic neuromuscular junction is described and neurotransmission, co-transmission and neuromodulation are defined, as well as the 'chemical coding' of sympathetic, parasympathetic, sensory-motor and intrinsic neurons in the wall of the bladder and bowel. A detailed description of the patterns of innervation of smooth muscle of the bowel, bladder and urethra and of the urethral and anal sphincters by intramural and extrinsic autonomic nerves is presented, and the functional and pharmacological features of this innervation are summarized. Finally, changes in the pattern of innervation and expression of co-transmitters and receptors in the bladder and bowel that occur during development and old age and following trauma, surgery and disease are discussed.
Experimental Anticancer Therapy with Vascular-disruptive Peptide and Liposome-entrapped Chemotherapeutic Agent (2010)

Vasculature is essential for the sustained growth of solid tumors and metastases. Tumor cells surviving vascular-disruptive therapeutic intervention (especially those present at the tumor rim) can contribute to tumor regrowth. The aim was to strengthen, by carrier-mediated delivery of a chemotherapeutic, the curative effects of a bifunctional anti-vascular oligopeptide capable of inducing vascular shutdown and tumor shrinkage. For the in vitro experiments and animal therapy, ACDCRGDCFC-GG-(D)(KLAKLAK)(2) peptide (900 microM in D-PBSA, i.e. Dulbecco's PBS without Ca(2+) and Mg(2+)) and size-calibrated, passively or actively targeted liposomes based on distearoylphosphatidylcholine, cholesterol, and N-carbamoyl-methoxypolyethyleneglycol coupled to distearoylphosphatidylethanolamine (PEG-DSPE) and containing gradient-entrapped doxorubicin were used. The KB (human nasopharyngeal carcinoma) cell line overexpressing folate receptors was used in the fluorescence studies of liposomal uptake. The B16-F10 melanoma cell line was used for confirming, by flow cytometry and confocal microscopy, doxorubicin intracellular transfer as well as to induce experimental tumors in C57BL/6 mice. Animal therapy was achieved with injections of vascular-disrupting peptide, doxorubicin-loaded liposomes, or alternating combined therapy. The results (tumor growth inhibition and survival) were compared using the Mann-Whitney U test and the log-rank test. Necrosis in H&E-stained tumor sections was assessed microscopically by pathologists. Treatment of C57BL/6 mice bearing B16-F10 experimental tumors with a combination of vascular-disruptive peptide and doxorubicin-carrying pegylated liposomes (either passively targeted liposomes (PTL) or folate receptor targeted) gave better therapeutic effects when tumor development was re-challenged with a second cycle of combined therapy. Marked inhibition of tumor growth and a statistically significant extension of the lifespan of the treated mice were observed when the re-challenge involved the use of folate receptor-targeted liposomes (FTL). Anticancer therapy involving vascular-disruptive peptide and doxorubicin delivered via pegylated folate receptor-targeted liposomes is more effective than either monotherapy, especially when tumor growth is re-challenged with the therapeutic combination.
Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat. (1991)

To determine whether supplemental dietary calcium and/or vitamin D deficiency are involved in modulating colon cancer induced by 1,2-dimethylhydrazine (DMH), Sprague-Dawley rats were fed diets containing either: (a) a normal content of calcium (0.87%) and phosphorus (0.60%) with 2.2 IU of vitamin D3 per g of feed (group A); (b) the same diet as group A, but with calcium and phosphorus increased to 1.80 and 0.80%, respectively (group B); or (c) a vitamin D-deficient diet with supplemental calcium (1.80%) and phosphorus (0.80%) (group C). After 6 weeks on their respective diets, one-half the animals in each group were given s.c. injections of either vehicle or DMH (20 mg/kg body weight/week) for 26 weeks. Animals were then sacrificed and the incidence of tumors as well as the number of tumors per tumor-bearing rat were determined. Colonic mucosal polyamine levels were measured after 15 weeks of exposure to vehicle or DMH, before development of histologically recognizable neoplasms. The results of these experiments demonstrated that neither calcium supplementation alone nor supplemental calcium in conjunction with vitamin D deficiency altered the incidence of colonic cancer induced by this carcinogen. Supplemental calcium, however, significantly decreased the number of rats with multiple tumors and reduced tumor size. Moreover, vitamin D deficiency abolished these protective effects of calcium on colon cancer in this experimental model. DMH treatment increased polyamine levels in the premalignant colonic mucosa in group A rats. This carcinogen-induced effect was blunted by high dietary calcium. Vitamin D-deficient, calcium-supplemented rats (group C) showed an increase in N1-acetylspermidine, but not the other polyamines, with DMH treatment.
The membrane repair response masks membrane disturbances caused by cell‐penetrating peptide uptake (2008)

Although cell-penetrating peptides are able to deliver cargo into cells, their uptake mechanism is still not fully understood and needs to be elucidated to improve their delivery efficiency. Herein, we present evidence of a new mechanism involved in uptake, the membrane repair response. Recent studies have suggested that there might be a direct penetration of peptides in parallel with different forms of endocytosis. The direct penetration of hydrophilic peptides through the hydrophobic plasma membrane, however, is highly controversial. Three proteins involved in target cell apoptosis--perforin, granulysin, and granzymes--share many features common in uptake of cell-penetrating peptides (e.g., they bind proteoglycans). During perforin uptake, the protein activates the membrane repair response, a resealing mechanism triggered in cells with injured plasma membrane, because of extracellular calcium influx. On activation of the membrane repair response, internal vesicles are mobilized to the site of the disrupted plasma membrane, resealing it within seconds. In this study, we have used flow cytometry, fluorescence, and electron microscopy, together with high-performance liquid chromatography and mass spectrometry, to present evidence that the membrane repair response is able to mask damages caused during cell-penetrating peptide uptake, thus preventing leakage of endogenous molecules out of the cell.
Multiplexed Assays for Detection of Mutations in PIK3CA (2008)

Multiplexed assays, which can easily be applied to clinical samples, have been developed for the detection of PIK3CA mutations.
Hybrid materials from organophosphorus coupling molecules (2005)

Organophosphorus acids and their derivatives (salts, esters) are quite complementary of organosilicon coupling molecules for the preparation of hybrid organic–inorganic materials, by sol–gel processing or surface modification. Organosilicon compounds are best suited for the anchoring of organic groups to silicon-containing inorganic matrices or supports, such as silica, silicates, silicon carbide, etc., whereas organophosphorus coupling molecules appear well adapted to matrices or supports based on metals or transition metals: oxides, hydroxides, as well as carbonates and phosphates. The different reactivity of organophosphorus coupling molecules leads to different structures and stabilities of the final hybrid materials and may provide decisive advantages in the sol–gel synthesis of homogeneous hybrids, the preparation of surface monolayers or the selective surface modification of nanopatterned supports.
Adenosine-provoked angina pectoris-like pain--time characteristics, influence of autonomic blockade and naloxone (1987)

In a study to characterize the time characteristics and the influence of blockade of beta, cholinergic and opioid receptors on the chest pain induced by adenosine, this agent was given as a bolus into a peripheral vein of six healthy volunteers (4 men) 24-45 years of age. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (1/3, 2/3, and a full maximum tolerable dose) and three doses of placebo were given as single blind doses in randomized order. Thereafter metoprolol (10 mg to males, 8 mg to females), followed by 1 mg atropine and then 0.4 mg naloxone were given intravenously. After each agent the test procedure was repeated. Heart rate and atrio-ventricular blocks were recorded by electrocardiography and respiration by dynamic spirometry. One minute after each dose of adenosine, the chest pain was scored. The maximum tolerable dose of adenosine was 8.0-15.9 mg. All subjects experienced angina pectoris-like pain. Following injection, onset of respiratory stimulation, AV-block and chest pain occurred after 14 +/- 4.0, 19 +/- 5.4 and 21 +/- 6.4 s, the differences being highly significant. Maximal respiratory stimulation occurred after 18 +/- 4.6, not statistically different from the onset of AV-block which in its turn occurred earlier (P less than 0.005) than the time for maximal central chest pain, 29 +/- 7.8 seconds. Metoprolol induced a 20% slowing of heart rate. After atropine there was a 30% faster heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Production of multilineage growth factors by hematopoietic stromal cells: an intercellular regulatory network involving mononuclear phagocytes and interleukin-1. (1987)

In the past 8 years, our group has carried out a series of in-vitro studies designed to characterize the role of mononuclear phagocytes as regulators of human hematopoiesis. The results of this program of investigation, some of which are reviewed below, led to the discovery that mononuclear phagocytes are more efficient recruitors of growth factor release by other cells than they are direct stimulators of progenitor cell growth. Specifically, mononuclear phagocytes release soluble factors (MRA) that stimulate other cells, including vascular endothelial cells, skin fibroblasts, and marrow fibroblasts, to release multilineage hematopoietic growth factors. Experiments designed to purify and characterize these monokines indicated unambiguously that the MRA that stimulates granulocyte/macrophage colony stimulating factor (GM-CSF) release is interleukin-1 (IL-1). Based on these observations and recent observations by other groups on the hematopoietic effects of other monokines including tumor necrosis factor alpha, we argue that mononuclear phagocytes serve as important regulators of hematopoiesis by producing monokines that, in turn, induce the expression of multiple hematopoietic growth factor genes in stromal cells of the hematopoietic microenvironment. Because IL-1 molecules and the mononuclear phagocytes producing them are evolutionarily conserved, and in view of the heterogeneous nonhematopoietic effects of these monokines, studies on their role in hematopoiesis may also provide new understanding of the molecular evolution of multicellular organisms.
Evaluating the feasibility to use microgrids as a resiliency resource (2016)

Summary form only given. Regulated electricity utilities are required to provide safe and reliable service to their customers at a reasonable cost. To balance the objectives of reliable service and reasonable cost, utilities build and operate their systems to operate under typical historic conditions. When abnormal events such as major storms or disasters occur, it is not uncommon to have extensive interruptions in service to the end-use customers. Society is becoming less tolerant of extensive interruption in services, and it is not cost effective to harden the existing electrical distribution architecture to ensure 100% reliable power; more utilities are examining the deployment of microgrids as a part of the a coordinated resiliency plan. This paper evaluates the feasibility of microgrids as a resiliency resource under three scenarios: as a local resource, a community resource, and as a black start resource. A method of nomograms is proposed, based on dynamic simulations and evaluations of an operational microgrid, to allow operators to quickly evaluate the feasibility of these difference scenarios in operational conditions.
Suppression of Herpes Simplex Virus Infection by Phosphonoacetic Acid (1973)

Disodium phosphonoacetate when administered orally or topically to mice experimentally infected with herpes simplex virus was able to significantly reduce the mortality associated with the agent. In addition, this compound was able to reduce herpesvirus lesions on the corneas of infected rabbits.
Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb (2006)

Neurogenesis in the subgranular zone of the hippocampal dentate gyrus and olfactory bulbs continues into adulthood and has been implicated in the cognitive function of the adult brain. The basal forebrain cholinergic system has been suggested to play a role in regulating neurogenesis as well as learning and memory in these regions. Herein, we report that highly polysialylated neural cell adhesion molecule (PSA-NCAM)-positive immature cells as well as neuronal nuclei (NeuN)-positive mature neurons in the dentate gyrus and olfactory bulb express multiple acetylcholine receptor subunits and make contact with cholinergic fibers. To examine the function of acetylcholine in neurogenesis, we used donepezil (Aricept), a potent and selective acetylcholinesterase inhibitor that improves cognitive impairment in Alzheimer's disease. Intraperitoneal administrations of donepezil significantly enhanced the survival of newborn neurons, but not proliferation of neural progenitor cells in the subgranular zone or the subventricular zone of normal mice. Moreover, donepezil treatment reversed the chronic stress-induced decrease in neurogenesis. Taken together, these results suggest that activation of the cholinergic system promotes survival of newborn neurons in the adult dentate gyrus and olfactory bulb under both normal and stressed conditions.