gebhart/patrepeval huggingface dataset:
A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients. (2001)

Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has been no consensus on their usefulness. We report an analysis of six ligands and two receptors of which a subset correlate to tumor stage and survival. Biopsies from bladder cancer tumors were obtained from 73 patients followed for a median of 28 months. The mRNA content for six ligands [EGF, transforming growth factor alpha (TGF-alpha), amphiregulin (AR), betacellulin (betaCL), heparin-binding EGF-like growth factor (HB-EGF), epiregulin (EPI)] and two receptors [EGF receptor I Human EGF Receptor (HER1) and 2 (HER2)] was examined by a newly developed quantitative reverse transcription-PCR method. Five ligands and two receptors (HER1 and HER2) were present in median concentrations of (10(-21) mol/microg RNA) 0.39 (AR), 11 (betaCL), 2.4 (EPI), 40 (HB-EGF), 1.4 (TGF-alpha), 75 (HER1), and 39,000 (HER2). EGF was barely detectable. A significantly higher expression of EPI (P < 0.001), HB-EGF (P < 0.001), and TGF-alpha (P < 0.05) were observed in T2-T4 tumors as compared with Ta tumors. Especially the expression of EPI mRNA correlated strongly to survival (P < 0.0005), but increased expression of TGF-alpha (P < 0.005), AR, and HB-EGF (P < 0.02) was also associated with a reduced life span. For the first time, mRNA expression of six ligands and two receptors of the EGF family have been examined in bladder cancer tumors. Our data emphasize that members of the EGF family, especially EPI, may be potential bladder tumor markers.
Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration (1999)

The objective of the present investigation was to examine the functional reestablishment of polarity in freshly isolated hepatocytes cultured between 2 layers of gelled collagen (sandwich configuration). Immunoblot analysis demonstrated that the canalicular multispecific organic anion transport protein (multidrug resistance-associated protein, Mrp2) was partially maintained in day 5 hepatocytes cultured in a sandwich configuration. Fluorescein-labeled taurocholate and carboxydichlorofluorescein were excreted into and concentrated in the bile canalicular lumen of day 5 sandwich-cultured hepatocytes, resulting in formation of fluorescent networks in standard buffer (intact bile canaliculi). Confocal microscopy studies demonstrated that 1) carboxydichlorofluorescein that had concentrated in the canalicular lumen was released into the incubation buffer in the presence of Ca(2+)-free buffer (disrupted bile canaliculi), and 2) rhodamine-dextran, an extracellular space marker, was only able to diffuse into the canalicular lumen in the presence of Ca(2+)-free buffer. The cumulative uptake of [(3)H]taurocholate in day 5 sandwich-cultured hepatocytes was significantly higher in standard buffer compared with Ca(2+)-free buffer, due to accumulation of taurocholate in canalicular spaces. When [(3)H]taurocholate was preloaded in the day 5 sandwich-cultured hepatocytes, taurocholate efflux was greater in Ca(2+)-free compared with standard buffer. The biliary excretion index of taurocholate, equivalent to the percentage of retained taurocholate in the canalicular networks, increased from approximately 8% at day 0 to approximately 60% at day 5 in sandwich-cultured hepatocytes. In summary, hepatocytes cultured in a collagen-sandwich configuration for up to 5 days establish intact canalicular networks, maintain Mrp2, reestablish polarized excretion of organic anions and bile acids, and represent a useful in vitro model system to investigate the hepatobiliary disposition of substrates.
MOLECULAR BASIS OF FERTILIZATION (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
The severe cardiorenal syndrome: ‘Guyton revisited’ (2004)

The incidence of cardiac failure and chronic renal failure is increasing and it has now become clear that the co-existence of the two problems has an extremely bad prognosis. We propose the severe cardiorenal syndrome (SCRS), a pathophysiological condition in which combined cardiac and renal dysfunction amplifies progression of failure of the individual organ, so that cardiovascular morbidity and mortality in this patient group is at least an order of magnitude higher than in the general population. Guyton has provided an excellent framework describing the physiological relationships between cardiac output, extracellular fluid volume control, and blood pressure. While this model is also sufficient to understand systemic haemodynamics in combined cardiac and renal failure, not all aspects of the observed accelerated atherosclerosis, structural myocardial changes, and further decline of renal function can be explained. Since increased activity of the renin-angiotensin system, oxidative stress, inflammation, and increased activity of the sympathetic nervous system seem to be cornerstones of the pathophysiology in combined chronic renal disease and heart failure, we have explored the potential interactions between these cardiorenal connectors. As such, the cardiorenal connection is an interactive network with positive feedback loops, which, in our view, forms the basis for the SCRS.
High‐level accumulation of a recombinant antibody fragment in the periplasm of Escherichia coli requires a triple‐mutant (degP prc spr) host strain (2004)

During production of a humanized antibody fragment secreted into the periplasm of Escherichia coli, proteolytic degradation of the light chain was observed. In order to determine which protease(s) were responsible for this degradation, we compared expression of the F(ab')(2) antibody fragment in several E. coli strains carrying mutations in genes encoding periplasmic proteases. Analysis of strains cultured in high cell density fermentations showed that the combination of mutations in degP prc spr was necessary for the cells to produce high levels of the desired recombinant antibody fragment. In order to eliminate the possible effects of mutations in other genes, we constructed E. coli strains with protease mutations in isogenic backgrounds and repeated the studies in high cell density fermentations. Extensive light chain proteolysis persisted in degP strains. However, light chain proteolysis was substantially decreased in prc and prc spr strains, and was further decreased with the introduction of a degP mutation in prc and prc spr mutant strains. These results show that the periplasmic protease Prc (Tsp) is primarily responsible for proteolytic degradation of the light chain during expression of a recombinant antibody fragment in E. coli, and that DegP (HtrA) makes a minor contribution to this degradation as well. The results also show that spr, a suppressor of growth defects in prc strains, is required for a prc mutant to survive throughout high cell density fermentations.
The reverse transcriptase of HIV‐1: from enzymology to therapeutic intervention (1994)

The human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS. Replication of this virus requires the activity of a retrovirus encoded RNA-dependent DNA polymerase, or reverse transcriptase (RT). HIV-1 RT is required for the synthesis of the double-stranded proviral DNA from the single-stranded retroviral RNA genome. HIV-1 RT has two subunits of 66 kDa and 51 kDa. The 66-kDa subunit contains the DNA polymerase and RNase H domains whereas the 51-kDa subunit, obtained by proteolytic maturation of the former subunit, has only the DNA synthetic activity. Two recently reported crystal structures of HIV-1 RT have revealed the very asymmetric structure of this molecule. In addition to providing information concerning the mechanism of nucleic acid polymerization, biochemical and biophysical studies of this enzyme are providing key insights for the design of selective antiviral agents. The multiple activities displayed by reverse transcriptase in the replication of the retroviral genome ensure that this enzyme will remain at the forefront of antiviral strategies in the fight against AIDS and other retrovirus-related pathologies.
Weak electromagnetic fields attenuate tremor in multiple sclerosis (1994)

It has been estimated that about 75% of patients diagnosed with multiple sclerosis (MS) have tremor which can be exceedingly disabling. The most common tremor observed in patients with MS is a cerebellar intention tremor ('kinetic tremor') although postural tremor ('static tremor') is also common and often extremely incapacitating. Currently there is no effective medical treatment for the tremor of MS which, in some severe cases, may be abolished by stereotactic thalamotomy. It was reported recently that extracranial application of brief AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range produced improvement in motor and cognitive functions in patients with MS. The present communication concerns three MS patients with a chronic progressive course of the disease (mean age: 39.3 +/- 8.3 years; mean duration of illness: 11.3 +/- 3.2 years) in whom brief external applications of pulsed EMFs of 7.5 pT intensity reduced intention and postural tremors resulting in significant functional improvement. The report suggests that these extremely low intensity EMFs are beneficial also in the treatment of tremors in MS and that this treatment may serve as an alternative method to stereotactic thalamotomy in the management of tremor in MS. The mechanisms by which EMFs attenuate the tremors of MS are complex and are thought to involve augmentation of GABA and serotonin (5-HT) neurotransmission in the cerebellum and its outflow tracts.
Cloudlets Activation Scheme for Scalable Mobile Edge Computing with Transmission Power Control and Virtual Machine Migration (2018)

Mobile devices have several restrictions due to design choices that guarantee their mobility. A way of surpassing such limitations is to utilize cloud servers called cloudlets on the edge of the network through Mobile Edge Computing. However, as the number of clients and devices grows, the service must also increase its scalability in order to guarantee a latency limit and quality threshold. This can be achieved by deploying and activating more cloudlets, but this solution is expensive due to the cost of the physical servers. The best choice is to optimize the resources of the cloudlets through an intelligent choice of configuration that lowers delay and raises scalability. Thus, in this paper we propose an algorithm that utilizes Virtual Machine Migration and Transmission Power Control, together with a mathematical model of delay in Mobile Edge Computing and a heuristic algorithm called Particle Swarm Optimization, to balance the workload between cloudlets and consequently maximize cost-effectiveness. Our proposal is the first to consider simultaneously communication, computation, and migration in our assumed scale and, due to that, manages to outperform other conventional methods in terms of number of serviced users.
Uptake of poly(D,L‐lactic‐co‐glycolic acid) microspheres by antigen‐presenting cells in vivo (2002)

Abstract Dendritic cells are the most potent antigen‐presenting cells (APC) and the most effective stimulators of primary T cell responses. Based on the strong influence of the APC on the immune response, we investigated cellular uptake of a biodegradable antigen delivery system, poly( D,L ‐lactic‐ co ‐glycolic acid) (PLGA) microspheres, at two sites of injection: intraperitoneal and intradermal. We hypothesized that a fluorescent probe, tetramethylrhodamine labeled dextran, loaded in PLGA microspheres would be taken up by APCs and thereby provide a means for studying cellular uptake of PLGA microspheres in vivo . Phagocytic load and cell phenotype were determined using flow cytometry and confocal laser scanning microscopy. The results revealed cellular uptake of tetramethylrhodamine dextran loaded PLGA microspheres at both injection sites. After intraperitoneal immunization, the predominant cell phagocytosing PLGA microspheres in the peritoneal cavity was the macrophage whereas the intradermal immunization resulted in uptake of PLGA microspheres by dendritic cells. Hence, these results suggest that the profile for cellular uptake varies with the site of injection. More importantly, this study provides direct and conclusive evidence of uptake of PLGA microspheres by the most potent APC, the dendritic cell. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 480–486, 2002; DOI 10.1002/jbm.10019
Identification of a transcription factor, encoded by two vaccinia virus early genes, that regulates the intermediate stage of viral gene expression (1999)

Vaccinia virus early, intermediate, and late stage genes are sequentially transcribed by the viral RNA polymerase within the cytoplasm of infected cells. We found that the 34- and 45-kDa polypeptides encoded by vaccinia virus ORFs A8R and A23R, respectively, were necessary to reconstitute transcription of a template with an intermediate stage promoter. Coexpression of the A8R and A23R genes in Escherichia coli was required for in vitro activity. In addition, the two polypeptides copurified, indicating their association as protein subunits of a vaccinia virus intermediate transcription factor. This factor, which we named VITF-3, complemented three viral proteins-namely, the RNA polymerase, capping enzyme, and a 30-kDa protein called VITF-1 that is also a subunit of the RNA polymerase-and an unidentified cell factor called VITF-2. Expression of the A8R and A23R genes occurred between 1 and 5 h after vaccinia virus infection and was not prevented by an inhibitor of DNA replication, consistent with a role for VITF-3 in specifically regulating intermediate transcription in vivo. The vaccinia virus A8R and A23R genes are highly conserved among vertebrate poxviruses, but no other viral or cellular homologs were identified.
[Actions of dehydroepiandrosterone: possible links with aging]. (1996)

Dehydroepiandrosterone (DHEA) and its sulfo-conjugated derivative (SDHEA), secreted by the adrenal glands, are the most abundant circulating steroids in the human organism. The well-established fact that levels decrease progressively with age suggests a role in the aging process. They could also play a preventive role via an antitumoral action, stimulation of the immune system, an antiosteoporotic effect, a neuropsychologic action and cardiovascular protection. Nevertheless, it is not certain that evidence obtained from animal models can be transposed to man due to the specific nature of adrenal secretion of steroids in the human species. Epidemiological studies have often provided conflicting results. There have been few trials of administration in man, mostly aimed at studying the metabolic effects of DHEA. There is no evidence of secondary effects. Inversely, high-doses lead to transformation into active androgens with deleterious metabolic effects. Consequently, the current trend is to use low doses. Body weight, body composition, and sensitivity to insulin are not modified although variable effects on the lipid profile have been observed. Finally one study has produced much debate: a randomized trial demonstrating an improvement in wellbeing... Confirmation of this effect is certainly needed. In the absence of a satisfactory animal model, randomized prospective studies versus placebo are required to study the effect of substitution therapy in elderly subjects.
INS/GPS/LiDAR Integrated Navigation System for Urban and Indoor Environments Using Hybrid Scan Matching Algorithm (2015)

This paper takes advantage of the complementary characteristics of Global Positioning System (GPS) and Light Detection and Ranging (LiDAR) to provide periodic corrections to Inertial Navigation System (INS) alternatively in different environmental conditions. In open sky, where GPS signals are available and LiDAR measurements are sparse, GPS is integrated with INS. Meanwhile, in confined outdoor environments and indoors, where GPS is unreliable or unavailable and LiDAR measurements are rich, LiDAR replaces GPS to integrate with INS. This paper also proposes an innovative hybrid scan matching algorithm that combines the feature-based scan matching method and Iterative Closest Point (ICP) based scan matching method. The algorithm can work and transit between two modes depending on the number of matched line features over two scans, thus achieving efficiency and robustness concurrently. Two integration schemes of INS and LiDAR with hybrid scan matching algorithm are implemented and compared. Real experiments are performed on an Unmanned Ground Vehicle (UGV) for both outdoor and indoor environments. Experimental results show that the multi-sensor integrated system can remain sub-meter navigation accuracy during the whole trajectory.
Mutagenesis Reveals a Role for Epidermal Growth Factor Receptor Extracellular Subdomain IV in Ligand Binding (1999)

The extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) comprises four subdomains (I-IV) and mediates binding of several different polypeptide ligands, including EGF, transforming growth factor-alpha, and heparin-binding EGF. Previous studies have predominantly implicated subdomain III in ligand binding. To investigate a possible role for sequences in subdomain IV, we constructed several mutant EGFRs in which clusters of charged or aromatic amino acids were replaced with alanine. Analysis of stably transfected Chinese hamster ovary cells expressing mutant EGFRs confirmed that they were present on the cell surface at levels approaching that of the wild-type receptor. Although tyrosine phosphorylation of most mutants was markedly induced by EGF, a cluster mutation (mt25) containing four alanine substitutions in the span of residues 521-527 failed to respond. EGF-induced tyrosine phosphorylation of an alternative mutant (DeltaEN) with amino acids 518-589 deleted was also greatly diminished. Larger doses of EGF or heparin-binding EGF induced only weak tyrosine phosphorylation of mt25, whereas the response to transforming growth factor-alpha was undetectable. These results suggest that mt25 might be defective with respect to either ligand binding or receptor dimerization. Quantitative analyses showed that binding of (125)I-EGF to mt25 and DeltaEN was reduced to near background levels, whereas binding of EGF to other cluster mutants was reduced 60-70% compared with wild-type levels. Among the mutants, only mt25 and DeltaEN failed to form homodimers or to transphosphorylate HER2/Neu in response to EGF treatment. Collectively, our results are the first to provide direct evidence that discrete subdomain IV residues are required for normal binding of EGF family ligands. Significantly, they were obtained with the full-length receptor in vivo, rather than a soluble truncated receptor, which has been frequently used for structure/function studies of the EGFR extracellular region.
Iso- and anteiso-fatty acids in bacteria: biosynthesis, function, and taxonomic significance. (1991)

Branched-chain fatty acids of the iso and anteiso series occur in many bacteria as the major acyl constituents of membrane lipids. In addition, omega-cyclohexyl and omega-cycloheptyl fatty acids are present in several bacterial species. These two types of fatty acids are synthesized by the repeated condensation of malonyl coenzyme A with one of the branched-chain and cyclic primers by the same enzyme system. The pathway of de novo branched-chain fatty acid synthesis differs only in initial steps of synthesis from that of the common straight-chain fatty acid (palmitic acid) present in most organisms. The cell membranes composed largely of iso-, anteiso-, and omega-alicyclic acids support growth of bacteria, which inhabit normal as well as extreme environments. The occurrence of these types of fatty acids as major cellular fatty acids is an important criterion used to aid identification and classification of bacteria.
Effects of EGF, BFGF, NGF and PDGF(bb) on cell proliferative, migratory and invasive capacities of human brain‐tumour biopsies In Vitro (1993)

Spheroids initiated directly from human primary gliomas were used to investigate the effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferation, migration and invasion into foetal rat brain tissue. EGF increased tumour spheroid volume in 10 of 13 glioblastomas studied, whereas 5 of 11 tumours responded to bFGF. NGF increased the spheroid volume in 2 of 5 tumours. In 8 tumours, PDGF(bb) had no effect on tumour spheroid volume. An increase in BUdR-labelling indices confirmed that cell proliferation was responsible for the volume increase observed in stimulated spheroids. EGF stimulated cell migration in 5 and bFGF in 3 of 8 tumours studied. NGF stimulated cell migration in 1 of 5 glioblastomas, whereas 1 of 3 glioblastomas responded to PDGF(bb). The effects of growth factors on the invasion of spheroids prepared from the glioblastoma biopsy specimens were also studied in vitro using foetal rat brain aggregates as target tissue. EGF stimulated invasion in 7 of 8 glioblastomas studied, whereas bFGF stimulated invasion in 2 of these tumours. NGF or PDGF(bb) did not increase the invasiveness of the glioblastoma tissue. Our results represent the net effect of the growth factors on a complex tumour-cell population. We conclude that exogenously administered growth factors, EGF in particular, increase the cell proliferation as well as migratory and invasive capacities of cultured primary brain tumour biopsies in vitro.
17 alpha-hydroxyprogesterone caproate (17P) usage in a Medicaid managed care plan and reduction in neonatal intensive care unit days. (2005)

Offering 17P as a benefit to pregnant women enrollees with a history of preterm delivery can decrease NICU days significantly for a Medicaid managed care plan.
A biochemical framework for RNA silencing in plants (2003)

RNA silencing phenomena were first discovered in plants, yet only the RNA interference pathway in animals has been subject to biochemical analysis. Here, we extend biochemical analysis to plant RNA silencing. We find that standard wheat germ extract contains Dicer-like enzymes that convert double-stranded RNA (dsRNA) into two classes of small interfering RNAs, as well as an RNA-dependent RNA polymerase activity that can convert exogenous single-stranded RNA into dsRNA. In this plant embryo extract, an endogenous microRNA (miRNA) that lacks perfect complementarity to its RNA targets nonetheless acts as a small interfering RNA. The miRNA guides an endonuclease to cleave efficiently wild-type Arabidopsis PHAVOLUTA mRNA, but not a dominant mutant previously shown to perturb leaf development. This finding supports the view that plant miRNAs direct RNAi and that miRNA-specified mRNA destruction is important for proper plant development. Thus, endonuclease complexes guided by small RNAs are a common feature of RNA silencing in both animals and plants.
Selective, Efficient and Functional Group‐Tolerant CuOAc‐Mediated N‐Arylation of 1H‐Indoles and 9H‐Carbazole with Aryl Iodides Under Base‐Free and Ligandless Conditions (2007)

Abstract CuOAc‐Mediated N ‐arylation of 1 H ‐indole derivatives and 1 H ‐carbazole with aryl iodides under base‐free and ligandless conditions provides the required N ‐arylazoles with complete N ‐selectivity and in moderate to good yields. The experimental conditions for this new version of the Ullmann reaction allow an unprecedented tolerance of functional groups and facilitate the workup of the reaction mixtures and isolation of the required chemically pure reaction products. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)