gebhart/patrepeval huggingface dataset:
Induction of the proto-oncogene fos by nerve growth factor. (1985)

Nerve growth factor (NGF) causes the differentiation of PC12 cells to sympathetic neuron-like cells and also induces a rapid but transient expression of fos mRNA and protein. fos mRNA transcripts can be detected 5 min after the addition of NGF, are maximally abundant after 30 min, and then their levels decrease. fos protein synthesis parallels the expression of fos mRNA, and the induced fos proteins are located in the nucleus. cAMP, epidermal growth factor, the phorbol ester phorbol 12-myristate 13-acetate, and K+ depolarization also induce the fos gene. Growth of PC12 cells in the presence of dexamethasone, which induces differentiation into chromaffin-like cells, is not accompanied by fos expression. We propose that while fos gene induction is associated with the differentiation of PC12 cells to sympathetic nerve, its enhanced expression is primarily involved in the anabolic responses induced by NGF and many growth factors.
Cloning and expression of a human ATP‐citrate lyase cDNA (1992)

A full-length cDNA clone of 4.3 kb encoding the human ATP-citrate lyase enzyme has been isolated by screening a human cDNA library with the recently isolated rat ATP-citrate lyase cDNA clone [Elshourbagy et al. (1990) J. Biol. Chem. 265, 1430]. Nucleic-acid sequence data indicate that the cDNA contains the complete coding region for the enzyme, which is 1105 amino acids in length with a calculated molecular mass of 121,419 Da. Comparison of the human and rat ATP-citrate lyase cDNA sequences reveals 96.3% amino acid identity throughout the entire sequence. Further sequence analysis identified the His765 catalytic phosphorylation site, the ATP-binding site, as well as the CoA binding site. The human ATP-citrate lyase cDNA clone was subcloned into a mammalian expression vector for expression in African green monkey kidney cells (COS) and Chinese hamster ovary cells (CHO) cells. Transfected COS cells expressed detectable levels of an enzymatically active recombinant ATP-citrate lyase enzyme. Stable, amplified expression of ATP-citrate lyase in CHO cells as achieved by using coamplification with dihydrofolate reductase. Resistant cells expressed high levels of enzymatically active ATP-citrate lyase (3 pg/cell/d). Site-specific mutagenesis of His765----Ala diminishes the catalytic activity of the expressed ATP-citrate lyase protein. Since catalysis of ATP-citrate lyase is postulated to involve the formation of phosphohistidine, these results are consistent with the pattern of earlier observations of the significance of the histidine residue in catalysis of the human ATP-citrate lyase.
A new concept of porous thermoelectric module using a reciprocating flow for cooling/heating system (2002)

This paper presents the conceptual design of a novel thermoelectric cooler and/or heater utilizing the heat transfer effect due to forced convection. A porous thermoelectric converter combined with a reciprocating flow system in which the flow direction of air passing through the element is reversed after regular intervals is proposed. This flow system in effect makes the thermal conductivity insignificant and contributes toward the achievement of a high efficient cooler and/or heater. For the first phase, a one-dimensional numerical analysis is performed to examine the detailed characteristics of the device by systematically varying the relevant thermo-fluid parameters. In particular, the flow velocity and the porosity of the thermoelectric elements are the most important parameters which directly affect the system performance. For example in a porous thermoelectric cooler, the lowest temperature of air is approximately -20/spl deg/C for an ambient temperature of 27/spl deg/C, which is attained with a flow velocity u=0.35 m/s, a material porosity /spl epsiv/=0.5, and 2.5 cm thick thermoelectric elements. As a notable feature, the temperature of the cooling section of the system varies considerably with the velocity, and it attains a minimum at u=0.35 m/s. Subsequently, on the basis of the proposed cooling system, an extended concept aimed to realize commercial coolers and/or heaters is briefly discussed.
Abstract 20407: Restoration of p21-Activated Kinase (Pak1) Activity Attenuates Arrhythmic Activity in a Dog Model of Atrial Fibrillation (2014)

Introduction: The mechanisms underlying the genesis of atrial fibrillation (AF) are not fully understood. Activation of the small GTPase Rac1 through production of reactive oxygen species (ROS) is believed to contribute to the development of an AF substrate. We identified Pak1 as an endogenous negative regulator of Rac1 and hypothesized that stimulation of Pak1 activity attenuates atrial arrhythmia by antagonizing ROS induced changes in Ca handling. Method: Tissue and isolated myocytes (left superior pulmonary vein, LSPV) were obtained from dogs with persistent AF (atrial tachypacing, 600bpm, 3 weeks) or sinus rhythm (SR) and changes in Pak1 expression were quantified by western blotting. Changes in [Ca] i (fluo-4/AM) or ROS (fluorescent29,79-dichlorofluorescein, DCF) were monitored by confocal microscopy in isolated atrial myocytes (AMs). AMs from WT and Pak1 -/- mice were used to determine the mechanism by which a decrease in Pak1 enhances arrhythmic activity. Results: For the first time we demonstrate that Pak1 is down regulated in the atria of the canine AF model (adjusted density: SR: 85.6±7.2 % vs. AF 50±8.1%, n=3; p -/- mice and an increased number of delayed after depolarizations during Ctrl and AngII stimulation in isolated Pak1 -/- AMs. On a cellular level Rac1 stimulation by AngII (1microM) induced exaggerated ROS production in Pak1 -/- AMs (DCF(au): WT AngII : 4572±487, n=20 vs. Pak1 -/- AngII : 11231±838, n=16, p i (F/F 0 : WT AngII : 3.4±0.4 n=6 vs. Pak1 -/- AngII : 4.1±0.4 n=9, p AF s prevented the AngII induced increase in DADs that was based on spontaneous Ca release. Conclusion: In AF ROS production is enhanced by down-regulation of Pak1, an endogenous negative regulator of Rac1. Restoring Pak1 activity could be a therapeutic strategy to attenuate ROS induced arrhythmia and remodeling.
Application of Cognitive Changes Markers for Diagnostics’ Purposes and in Neurofeedback Therapy (2019)

Thanks to the automation of diagnostic processes based on the EEG signal and the creation of classifications of various attention disorders based on the analysis of the EEG signals (as diagnostic markers) - it may be possible to refer patients to appropriate specialists and provide them with appropriate neurofeedback-based treatment. The marker method proposed by the authors of the hereof paper is based on analysis of the EEG, which signal can be widely use in screening diagnostics. The proposed solution in this work may be used for neurofeedback or Brain Computer Interfaces (BCI). In this paper the authors presented implementation of markers for the purpose of analysis of some memory disorders and short-time attention disorder. The study is still in progress. Presented results have initial-study character.
Differential Regulation of Leptin Transport by the Choroid Plexus and Blood-Brain Barrier and High Affinity Transport Systems for Entry into Hypothalamus and Across the Blood-Cerebrospinal Fluid Barrier* (2000)

Leptin is a circulating hormone that controls food intake and energy homeostasis. Little is known about leptin entry into the central nervous system (CNS). The blood-cerebrospinal fluid (CSF) barrier at the choroid plexus and the blood-brain barrier (BBB) at the cerebral endothelium are two major controlling sites for entry of circulating proteins into the brain. In the present study, we characterized leptin transport across the blood-CSF barrier and the BBB by using a brain perfusion model in lean rats. Rapid, high-affinity transport systems mediated leptin uptake by the hypothalamus (KM = 0.2 ng/ml) and across the blood-CSF barrier (KM = 1.1 ng/ml). High affinity in vivo binding of leptin was also detected in the choroid plexus (KD = 2.6 ng/ml). In contrast, low affinity carriers for leptin (KM = 88 to 345 ng/ml) were found at the BBB in the CNS regions outside the hypothalamus (e.g. cerebral cortex, caudate nucleus, hippocampus). Our findings suggest a key role of high affinity leptin transporters in the hypothalamus and choroid plexus in regulating leptin entry into the CNS and CSF under physiological conditions. Low affinity transporters at the BBB outside the hypothalamus could potentially contribute to overall neuropharmacological effects of exogenous leptin.
The performance and utility of rapid diagnostic assays for Plasmodium falciparum malaria in a field setting in the Lao People's Democratic Republic (2001)

Rapid diagnostic assays for malaria have the potential to improve the management and control of the disease in developing countries. The objectives of the present study were to evaluate, in a field setting, the performance of several such assays for Plasmodium falciparum infection and to examine the usefulness of these assays in identifying subjects for treatment trials in rural field sites. Residents of 12 villages in Laos who presented with fever were eligible for inclusion. Blood was collected by fingerprick for a dipstick assay, developed by the Program for Appropriate Technology in Health (PATH), performed and interpreted in the field by local healthcare workers. Compared with 'blinded' reference microscopy (N =196), the sensitivity and specificity of the PATH assay were 96.2% and 93.0%, respectively. Two rapid diagnostic assays (PATH and OptiMAL) were also performed on the subset of subjects eligible to participate in an in-vivo treatment trial (N = 97), and the results again compared with those of 'blinded' reference microscopy. In this subset, a subject was considered a 'true positive' if found positive by microscopy or the alternate rapid assay. Using this modified reference standard, the sensitivity and specificity of the PATH assay were 96.7% and 94.4%, and those of the OptiMAL assay were 91.8% and 100%, respectively. Both of the rapid assays tested therefore appear suitable for use in rural field settings by local healthcare providers and can accurately identify participants for treatment trials.
Aldose dehydrogenase-modified carbon paste electrodes as amperometric aldose sensors (1993)

A biosensor using pyrroloquinoline quinone-dependent aldose dehydrogenase (ALDH) as a biological component was developed and used for the measurement of the aldose sugars xylose and glucose. Different immobilization methods for ALDH in carbon paste were studied. The best electrode performance was obtained when ALDH was adsorbed on the surface of a carbon paste electrode. Several mediator compounds were mixed into the carbon paste. The lowest working potential and highest catalytic current were obtained with dimethylferrocene as a mediator. Both storage and operational stability of the ALDH electrodes could be improved by the application of a membrane consisting of a poly(ester-sulfonic acid) cation-exchanger, Eastman AQ-29D. Application of the membrane reduced the non-specific oxidation of fermentation samples on the electrode surface.
Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance (2014)

The Nek2 and Plk4 kinases serve as crucial regulators of mitotic processes such as the centrosome duplication cycle and spindle assembly. Deregulation of these processes can trigger chromosome instability and aneuploidy, which are hallmarks of many solid tumors, including breast cancer. Emerging data from the literature illustrated various functions of Nek2 in breast cancer models, with compelling evidence of its prognostic value in breast tumors. The two kinases control distinct steps in the centrosome-centriole cycle and their dysregulation lead to centrosome amplification, marked by the presence of more than two centrosomes within the cell. We found single or composite overexpression of these kinases in breast tumor samples, regardless of subtype, which strongly associated with poor prognosis. Interestingly, in a panel of established cell lines, both kinases are highly expressed in Her2-positive breast cancer cells exhibiting centrosome amplification and trastuzumab resistance. In summary, it appears that Nek2 and Plk4 might synergize to promote breast tumorigenesis and may also be involved in tamoxifen and trastuzumab resistance.
Analytical Solutions for Determining Vertical Air Permeability in Unsaturated Soils (1995)

The study of flow and transport in unsaturated soils requires a good knowledge of the soil properties. When advective gas phase transport is of interest, air permeability is the key parameter of soil characterization. Although an air permeability test can easily be done in a laboratory, the reported values are frequently found to be not very representative of the air permeability in situ. Air permeability determined by a field test is useful both in the study of gas flow through unsaturated soils and in the prediction of the saturated hydraulic conductivity. This paper presents analytical solutions for determining the vertical air permeability of unsaturated soils using observed air pressure data at the land surface and at depth in the vadose zone. One solution is developed for a single‐layer soil, and the other is developed for layered soils. Example calculations using field data have demonstrated the significant potential of the solution applications in field tests.
Effect of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil on Epstein-Barr virus antigen expression in P3HR-1 cells: comparison with acyclovir. (1987)

The effect of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) in comparison to 9-(2-hydroxyethoxymethyl)guanine (ACV) on the proliferation of human lymphoblastoid P3HR-1 cells in culture and on the expression of Epstein-Barr virus capsid antigen (VCA) in the same cells was evaluated. After 7 days of cell growth, at 100 mumol/l the total number of new generations in drug-treated cultures was similar or 5 and 10% below that in drug-free control cultures, for VaraU, ACV, and BrVaraU, respectively. During the same time the percentage of VCA-expressing cells decreased from 6.3% in drug-free cultures to 1.3, 1.5, and 2.0% in cultures treated with VaraU, ACV and BrVaraU, respectively. In VaraU-treated cultures a further decrease in the percentage of VCA-positive cells down to 0.5% was revealed 7 days after drug removal. VaraU was also effective in reducing the proportion of VCA-expressing cells at 10 and 1 mumol/l. At 14 days after drug removal, the inhibitory effect of ACV was nearly reversed, whereas BrVaraU showed a prolonged VCA- suppressing effect.
Reduced representation model of protein structure prediction: Statistical potential and genetic algorithms (1993)

A reduced representation model, which has been described in previous reports, was used to predict the folded structures of proteins from their primary sequences and random starting conformations. The molecular structure of each protein has been reduced to its backbone atoms (with ideal fixed bond lengths and valence angles) and each side chain approximated by a single virtual united-atom. The coordinate variables were the backbone dihedral angles phi and psi. A statistical potential function, which included local and nonlocal interactions and was computed from known protein structures, was used in the structure minimization. A novel approach, employing the concepts of genetic algorithms, has been developed to simultaneously optimize a population of conformations. With the information of primary sequence and the radius of gyration of the crystal structure only, and starting from randomly generated initial conformations, I have been able to fold melittin, a protein of 26 residues, with high computational convergence. The computed structures have a root mean square error of 1.66 A (distance matrix error = 0.99 A) on average to the crystal structure. Similar results for avian pancreatic polypeptide inhibitor, a protein of 36 residues, are obtained. Application of the method to apamin, an 18-residue polypeptide with two disulfide bonds, shows that it folds apamin to native-like conformations with the correct disulfide bonds formed.
Faculty Opinions recommendation of Rapamycin prevents and breaks the anti-CD3-induced tolerance in NOD mice. (2009)

OBJECTIVE: Non-Fc-binding anti-CD3-specific antibodies represent a promising therapy for preserving C-peptide production in subjects with recent-onset type 1 diabetes. However, the mechanisms by which anti-CD3 exerts its beneficial effect are still poorly understood, and it is questionable whether this therapeutic approach will prove durable with regard to its ability to impart metabolic preservation without additional actions designed to maintain immunological tolerance. We used the NOD mouse model to test whether rapamycin, a compound well-known for its immunomodulatory activity in mice and humans, could increase the therapeutic effectiveness of anti-CD3 treatment in type 1 diabetes.RESEARCH DESIGN AND METHODS: Rapamycin was administered to diabetic NOD mice simultaneously with anti-CD3 or to NOD mice cured by anti-CD3 therapy. The ability of this combined therapy to revert type 1 diabetes and maintain a state of long-term tolerance was monitored and compared with that of anti-CD3 therapy alone.RESULTS: Rapamycin inhibited the ability of anti-CD3 to revert disease without affecting the frequency/phenotype of T-cells. Rapamycin also reinstated diabetes in mice whose disease was previously reversed by anti-CD3. Withdrawal of rapamycin in these latter animals promptly restored a normoglycemic state.CONCLUSIONS: Our findings indicate that, when combined with anti-CD3, rapamycin exerts a detrimental effect on the disease outcome in NOD mice for as long as it is administered. These results suggest strong caution with regard to combining these treatments in type 1 diabetic patients. PMID: 19151201 Funding information This work was supported by: Telethon, Italy Grant ID: GJT04014
3D mapping of blood vessel networks and cells in COPD and non-COPD lung tissue samples using micro-computed tomography and immunofluorescence (2020)

Micro-computed tomography (µCT) is a non-destructive 3D imaging technique used to map tissue microstructure at typical resolutions of 1-10 µm. Correlated with 2D immunofluorescence (IF) microscopy pathophysiologically relevant cells can be identified in 3D. We aimed to investigate 3D networks of small blood vessels (&lt;2mm) and the distribution of immune cells in mild-moderate COPD patients. FFPE peripheral lung samples from 5 non-COPD and 5 COPD patients were scanned using µCT. IF staining for smooth muscle actin, airway epithelium, mast cells and macrophages was digitised, and co-registered with 3D µCT scans. Blood vessels, airways and infiltrating cells were identified semi-automatically by IF in the µCT volume (Fig 1). Quantitative estimates of blood vessel thickness were made,&nbsp;initial modal thickness values were lower in non-COPD (12-25µm) compared to COPD samples (40-60µm).&nbsp;Thousands of macrophages (2100-7200) and mast cells (1700-9000)&nbsp;were localised by IF per tissue section with fewer mast cells (&lt;1500) detected in COPD tissue sections. Combined with the 3D vasculature network the distribution of macrophages and mast cells were found to be similar in both COPD and non-COPD with 70-80% of cells within 2mm of a blood vessel. In summary, we demonstrate an approach to identify, localise and analyse lung networks in 3D and relevant infiltrating cells in human lung disease.
Filter plane resolution requirements for coherent optical correlators (1977)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text David Casasent and Alan Furman, "Filter plane resolution requirements for coherent optical correlators," Appl. Opt. 16, 285_1-286 (1977) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Alpha/sub 1/ receptor coupling events initiated by methoxy-substituted tolazoline partial agonists (1986)

A series of mono- and dimethyoxy substituted tolazoline derivatives, known to be partial agonists at the alpha/sub 1/ receptor, were compared with the ..cap alpha../sub 1/ selective full agonist phenylephrine (PE) on isolated strips of rabbit aorta Agonist activity was evaluated in contraction, /sup 45/Ca influx, /sup 45/Ca efflux, and /sup 32/P-Phospholipid labelling studies. Maximum contractile responses for the 2-, 3-, and 3, 5- methoxy substituted tolazoline derivatives (10/sup -5/M) were 53.8, 67.6 and 99.7% of the PE (10/sup -5/M) response respectively. These same partial agonists caused a stimulation of /sup 45/Ca influx to the extent of 64, 86, and 95% of the PE response respectively. In /sup 45/Ca efflux studies, (a measure of the intracellular Ca/sup +2/ release) the tolazolines caused: 30%, 63%, and 78% of the PE stimulated level. /sup 32/P-Phosphatidic acid (PA) labelling was measured as an index of PI turnover after ..cap alpha../sub 1/ receptor stimulation. Compared to PE, the 2-, 3-, and 3,5- methoxy substituted tolazoline derivatives caused 22, 46, and 72% PA labelling. The above values are all in reasonable accord with the rank order or agonist activity shown in maximum contractile responses. The results of this investigation suggest that partial agonists stimulate ..capmore » alpha.. receptor coupling events at a level which is quantitatively comparable to their potencies in causing contraction of arterial smooth muscle.« less
Record Low Loss, Record High FOM Optical Fiber with Manufacturable Process (2013)

Record-low loss of 0.149dB/km at 1550nm is realized by pure-silica-core fiber having optimally enlarged Aeff, which indicates record-high figure-of-merit for digital coherent system. Mass-productivity is verified with 7,000km long fabrication whose averaged loss of 0.154dB/km.
Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay (2004)

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOS). Elevated ADMA plasma levels have been reported in connection with diseases associated with an impaired endothelial L-arginine-NO pathway and endothelial dysfunction, such as atherosclerosis, hypercholesterolemia, chronic heart failure, diabetes mellitus, and hypertension. NO production by NOS is decreased due to elevated ADMA levels. In fact, there is increasing interest in determination of ADMA levels in samples of various origins. The aim of this work was to develop a precise and easy immunoassay in contrast to the existing methods, such as HPLC, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS. We determined cross-reactivity in our immunoassay of 1.2% for symmetric dimethylarginine and <0.02% for L-arginine. The limit of quantitation was 0.05 micromol/l. We found good correlation of the values measured when we compared our assay with LC-tandem MS (n = 29; r = 0.984; p < 0.0001). We determined ADMA levels in human serum and plasma, mouse and rat plasma, and cell culture supernatant. For human plasma we found a mean of 0.65 micromol/l in healthy subjects. In the plasma of mice and rats we found mean concentrations of 1.05 and 1.09 micromol/l, respectively.
Hypoxia Changes the Expression of the Epidermal Growth Factor (EGF) System in Human Hearts and Cultured Cardiomyocytes (2012)

Hypoxia in the human heart alters the expression of the EGF system. Mimicking the HER2 down-regulation seen in the human heart in cultured cardiomyocytes inhibited their proliferation under hypoxic conditions. Interestingly, HB-EGF is induced in the hypoxic human hearts, and rescues hypoxic cardiomyocytes from the effect of HER2 inhibition in the in vitro model. The results have implications for future treatment strategies of patients with ischemic heart disease.