Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel (Rp)-cAMPS Analogs as Tools for Inhibition of cAMP-kinase in Cell Culture

Novel (Rp)-cAMPS analogs differed widely in ability to antagonize cAMP activation of pure cAMP-dependent protein kinase I and II and to antagonize actions of cAMP on gene expression, shape change, apoptosis, DNA replication, and protein phosphorylation in intact cells. These differences were related to different abilities of the analogs to stabilize the holoenzyme form relative to the dissociated form of cAMP kinase type I and II. (Rp)-8-Br-cAMPS and (Rp)-8-Cl-cAMPS were the most potent cAMP antagonists for isolated type I kinase and for cells expressing mostly type I kinase, like IPC-81 leukemia cells, fibroblasts transfected with type I regulatory subunit (RI), and primary hepatocytes. It is proposed that (Rp)-8-Br-cAMPS or (Rp)-8-Cl-cAMPS should replace (Rp)-cAMPS as the first line cAMP antagonist, particularly for studies in cells expressing predominantly type I kinase. The phosphorylation of endogenous hepatocyte proteins was affected oppositely by (Rp)-8-Br-cAMPS and increased cAMP, indicating that (Rp)-8-Br-cAMPS inhibited basal cAMP-kinase activity. The inhibition of basal kinase activity was accompanied by enhanced DNA replication, an effect which could be reproduced by microinjected mutant cAMP-subresponsive RI. It is concluded that the basal cAMP-kinase activity exerts a tonic inhibition of hepatocyte replication. (Rp)-8-Br-cAMPS and microinjected RI also desensitized hepatocytes toward inhibition of DNA synthesis by interleukin-1β. This indicates that basal cAMP-kinase activity can have a permissive role for the action of another (interleukin-1β) signaling pathway.
Modulation of bone morphogenic protein signaling in T-cells for cancer immunotherapy

Abstract Immunotherapy is becoming an increasingly attractive therapeutic alternative for conventional cancer therapy. In recent years Foxp3+ regulatory T-cells (TR) were identified as the major obstacle to effective cancer immunotherapy. The abundance of these cells in peripheral blood is increased in patients with multiple types of cancer and their prevalence among tumor-infiltrating lymphocytes correlated with poor clinical prognosis. In contrast, removal or inactivation of TR cells led to enhanced anti-tumor immune response and better efficacy of cancer vaccines. This study reports that Bone Morphogenic Protein Receptor 1α (BMPR1α, Alk-3) is expressed by activated effector CD4+ and TR cells and modulates functions of both cell types. Bone Morphogenic Proteins (BMPs) belong to the transforming growth factor (TGF)-β family of cytokines that also include TGFβ and activins. BMPs play crucial roles in embryonic development, tissue differentiation and homeostasis, and development of cancer. It was demonstrated that BMPs and activins synergize with TGFβ to regulate thymic T-cell development, maintain TR cells, and control peripheral tolerance. Inactivation of BMPR1α in T-cells results in impaired thymic and peripheral generation of TR cells. BMPR1α-deficient activated T-cells produced a higher level of interferon (IFN)-γ than BMPR1α-sufficient T-cells. Moreover, transplanted B16 melanoma tumors grew smaller in mice lacking expression of BMPR1α in T-cells and tumors had few infiltrating TR cells and a higher proportion of CD8+ T-cells than wild-type mice.
Prostaglandin E1‐containing nanoparticles improve walking activity in an experimental rat model of intermittent claudication

Due to the low stability of lipid emulsions, a lipid emulsion of prostaglandin E1 (Lipo‐PGE1) necessitates daily intravenous drip infusions. To overcome this issue, we developed nanoparticles containing PGE1 (Nano‐PGE1). Nano‐PGE1 showed a good sustained‐release profile of PGE1 from the nanoparticles in vitro, which may permit a longer‐lasting therapeutic effect to be achieved. We here examined the pharmacological activity of Nano‐PGE1 in a rat experimental model of intermittent claudication induced by femoral artery ligation.
Dietary intake and the dynamics of stress, hypertension and obesity in a peri-urban community in Accra.

OBJECTIVES This study intends to investigate the association between dietary intake, stress and prevalence of chronic diseases. DESIGN AND SETTING The study was a cross-sectional design conducted in two poor peri-urban communities in Accra. PARTICIPANTS AND OUTCOME MEASURES A total of 90 households each with a male and female between the ages of 18 and 45 years were sampled, and their socio-demographic status, anthropometric measurement and fasting blood sugar were assessed. Blood pressure was measured and chronic stress/anxiety was determined using the trait and state inventory (T-stai) questionnaire. Three days repeated 24-hour dietary recall was also done. Analysis of variance and linear regression analysis were used in data analysis. RESULTS About 28% of the subjects were hypertensive and 55.5% had high chronic stress. Hypertension was higher in males (32.2%) than females (24.4%) (p=.023) whiles stress was higher in females (60.9%) than males (50.0%) (p=.017). Hypertensive subjects recorded higher stress (51.02%) and hypertension was more prevalent in subjects with high stress (32.89%) especially in females (57.14%, p=.036). Hypertension increased with mean age whiles stress decreased with mean age. Hypertensive subjects recorded a significantly higher BMI and sodium intake whiles high stress individuals recorded a lower animal protein but a higher cereal protein intake (p<.05). Chronic stress was associated with intake of low animal protein and high cereal protein. Increased dietary diversity score was associated with decreased obesity prevalence (p<.05). CONCLUSION Hypertension, chronic stress, and obesity were linked, and affected by dietary sodium, animal protein, and dietary diversity of subjects respectively.
Herpes simplex virus type 1-induced ribonucleotide reductase activity is dispensable for virus growth and DNA synthesis: isolation and characterization of an ICP6 lacZ insertion mutant

Herpes simplex virus (HSV) encodes a ribonucleotide reductase consisting of two subunits (140 and 38 kilodaltons) whose genes map to coordinates 0.56 to 0.60 on the viral genome. Host cell lines containing the HpaI F fragment which includes the reductase subunit genes of HSV type 1 strain KOS (coordinates 0.535 to 0.620) were generated. Transfection of these cells with a plasmid containing the immediate-early ICP0 gene resulted in the expression of ICP6; interestingly, ICP4 plasmids failed to induce expression, indicating an unusual pattern of ICP6 regulation. One such cell line (D14) was used to isolate a mutant with the structural gene of lacZ inserted into the ICP6 gene such that the lacZ gene is read in frame with the N-terminal region of ICP6. This mutant generated a protein containing 434 amino acids (38%) of the N terminus of ICP6 fused to beta-galactosidase under control of the endogenous ICP6 promoter. Screening for virus recombinants was greatly facilitated by staining virus plaques with 5-bromo-4-chloro-3-indoyl-beta-D-galactoside (X-gal). Enzyme assays of infected BHK cells indicated that the mutant is incapable of inducing viral ribonucleotide reductase activity. Surprisingly, although plaque size was greatly reduced, mutant virus yield was reduced only four- to fivefold compared with that of the wild type grown in exponentially growing Vero cells. Mutant virus plaque size, yields, and ability to synthesize viral DNA were more severely compromised in serum-starved cells as compared with the wild type grown under the same condition. Although our evidence suggests that the HSV type 1 ribonucleotide reductase is not required for virus growth and DNA replication in dividing cells, it may be required for growth in nondividing cells.
A Randomized Double‐Blind, Placebo Controlled Trial of Steroid Withdrawal after Pediatric Renal Transplantation

In an effort to reduce rejection, extend allograft survival and minimize complications, we hypothesized that robust immunosuppression during the first 6 months after transplantation would allow for the safe withdrawal of steroids. A total of 274 pediatric subjects were enrolled and received an anti‐CD25 antibody, sirolimus, calcineurin inhibitor and steroids. At 6 months after transplantation, subjects were randomized to steroid withdrawal (n = 73) versus continued low‐dose steroids (n = 59). This study was stopped prior to target enrollment because of the incidence of post‐transplant lymphoproliferative disorder. At the time of study termination, 132 subjects had been randomized and were available for analysis. At 18 months after transplantation, there was no difference in the standardized height z score; however, the standardized height velocity was greater in the steroid withdrawal group compared to the control group (p = 0.033). There were no differences in acute rejection episodes between treatment groups. The 3‐year allograft survival rate was 84.5% in the control group and 98.6% in the steroid withdrawal group (p = 0.002). The immunosuppressive protocol utilized in this study allowed for the withdrawal of steroids without an increased risk of rejection or allograft loss. However, the complications associated with the use of this immunosuppressive protocol were too high to recommend its routine use in pediatric patients.
Hygromycin B resistance mediates elimination of Leishmania virus from persistently infected parasites

A series of pX63-HYG derivatives encoding Leishmania RNA virus 1-4 (LRV1-4) sequences were electroporated into cells of Leishmania strain M4147, a virus-infected strain of L. guyanensis. After 6 weeks of drug selection (hygromycin B), transfected parasites lacked detectable quantities of viral genomic double-stranded RNA, viral capsid protein, and RNA-dependent RNA polymerase (RDRP) activity. Evidence of viral infection was not recovered upon removal of the drug. While viral RNA transcripts were produced from electroporated expression vectors, as determined by reverse transcription-PCR, viral antigens were not detected, suggesting that the antiviral effects of hygromycin B are mediated through translation inhibition. A short-term selection study suggests that the LRV1-4 elimination may not only be a function of hygromycin B as a protein synthesis inhibitor but also possibly related to the mechanism of hygromycin B resistance in Leishmania strains.
Document image denoising and binarization using Curvelet transform for OCR applications

Practically document images may have complex background in form of non-uniform illumination (shading) or an image in background. Such complex backgrounds result poor binarization causing character recognition errors. If such images are transmitted over a noisy analog channel, they are also corrupted by white Gaussian noise that makes binarization even worse. In this paper, a denoising and binarization scheme of document images to make them suitable for OCR using discrete Curvelet transform is presented. The proposed Curvelet based method is able to remove complex image background as well as white Gaussian noise and results in a better binarized document image as compared to other conventional methods. The ability of sparse representation and edge preservation of Curvelet transform helps better in text shape preservation even in the presence of noise. The proposed method is able to remove low frequency complex backgrounds and high frequency Gaussian noise and their combinations from document images and shows better performance in such noise combination cases when compared to commercial OCR packages.
ACI-1 from Acidaminococcus fermentans: Characterization of the First β-Lactamase in Anaerobic Cocci

ABSTRACT Acidaminococcus fermentans belongs to the group of strictly anaerobic gram-negative cocci. All previously describedAcidaminococcus strains are susceptible to β-lactam antibiotics. An A. fermentans strain (RYC-MR95) resistant to penicillin and expanded-spectrum cephalosporin (amoxicillin and cefotaxime MICs, 64 μg/ml) was isolated from a human perianal abscess. A fragment encoding a β-lactamase from genomic DNA was cloned in Escherichia coli K-12 strain HB101, and the recombinant strain expressed resistance to amoxicillin (MIC, 1,024 μg/ml) and cefotaxime (MIC, 4 μg/ml). Clavulanic acid decreased the MICs to 8 and 0.03 μg/ml, respectively. Analysis of the nucleotide sequence revealed a new class A β-lactamase, ACI-1. In accordance with its biochemical properties, we propose to assign ACI-1 to functional group 2be. The ACI-1 enzyme (estimated pI 4.3) had <50% amino acid identity with any other class A β-lactamases, the closest being ROB-1 from Haemophilus influenzae (44%). ACI-1 was closer to class A β-lactamases from some gram-positive organisms (41 to 44% amino acid identity withBacillus β-lactamases) than to most class A enzymes from gram-negative organisms (TEM-1, 24.6%). The aci1 gene had a G+C content of 42.1%, in contrast with 56% G+C content for genomic DNA from A. fermentans, thus suggesting that aci1 may have been obtained by horizontal gene transfer.
Artificial neural network and PID based control system for DC motor drives

This paper presents the design and implementation of a control system for permanent magnet motors using PID and artificial neural network controllers. The system consists of two major components: a PC application and a hardware component controlled by an FPGA device. The role of the system implemented in the FPGA device is to acquire and process data related to the DC motor's operation, to control the motor's voltage and to exchange data with the PC application. The PC application provides to the user an interface for visualizing information related to the motor's operation and for interacting with the system. It implements speed and position controllers based on PID algorithm and artificial neural networks, and provides multiple auto-tuning methods for automatic evaluation of the PID controllers parameters and also training sets for the neural network controller. The main advantage of the system is that it allows to automatically determine the control parameters for different DC motors without any prior knowledge regarding the motor parameters, and to easily verify the performances of the controllers.
Multi-level barriers analysis to promote guideline based nursing care: a leadership strategy from home health care.

BACKGROUND Understanding the types of barriers that exist when implementing change can assist healthcare managers to tailor implementation strategies for optimal patient outcomes. AIM The aim of this paper is to present an organising framework, the Barriers Assessment Taxonomy, for understanding barriers to nurses' use of clinical practice guideline recommendations. Barriers to recommendations are illustrated using the Barriers Assessment Taxonomy and insights discussed. METHOD As part of a pilot implementation study, semi-structured interviews (n = 26) were conducted to understand barriers to nurses' use of nine guideline recommendations for diabetic foot ulcers. Content analysis of verbatim transcripts included thematic coding and categorising barriers using the Barriers Assessment Taxonomy. RESULTS Nineteen barriers were associated with nine recommendations, crossing five levels of the health care delivery system. The Barriers Assessment Taxonomy revealed that all recommendations had individual and organisational level barriers, with one recommendation having barriers at all levels. Individual level barriers were most frequent and lack of knowledge and skills was the only barrier that crossed all recommendations. IMPLICATIONS FOR NURSING MANAGEMENT The Barriers Assessment Taxonomy provides a framework for nursing managers to understand the complexity of barriers that exist, and can assist in choosing intervention strategies to support improved quality care and patient outcomes.
Jagged1 Ablation Results in Cerebellar Granule Cell Migration Defects and Depletion of Bergmann Glia

Jagged1 is a ligand for members of the Notch family of receptors. Mutations in the human JAG1 gene are the major cause of Alagille syndrome, an autosomal dominant disorder affecting the liver, heart, eye, skeleton, kidneys, and craniofacial structures. Although expressed throughout mammalian embryonic development and in the adult, the function of Jagged1 in the central nervous system is not clear. Jagged1 is broadly expressed in the cerebellum suggesting an important role in Notch signaling. In order to address the function of Jagged1 in the mouse central nervous system, we have inactivated the Jag1 gene in the cerebellar primordium at mid-embryogenesis. Loss of Jagged1 results in aberrant granule cell migration and ectopic differentiation in the external germinal layer and molecular layer of the early postnatal cerebellum. We show that Bergmann glia in the cerebellum lose contact to the pial surface and have stunted processes. In vitro analysis revealed a depletion of Bergmann glia in the Jagged1 mutant mice. Our findings suggest that Jagged1 plays a role in cell fate specification and survival in the cerebellum.
Predictive factors of the long‐term outcome in reflux esophagitis in a low‐prevalence gastroesophageal reflux disease region

Background: There are no data concerning the long‐term outcome of patients with reflux esophagitis in Taiwan. In this study the outcome and the specific prognostic indicators associated with outcome in patients were assessed retrospectively, 7 years after diagnosis of esophagitis. Methods: The study comprised a total of 128 patients with endoscopic esophagitis, diagnosed between January and June 1995, at Taichung Veterans' General Hospital. The outcome at 7 years after diagnosis was assessed by outpatient or telephone interview. Factors associated with requiring long‐term acid suppression therapy were analyzed. Results: In all, 105 patients were eligible for analysis; 61 patients (58.1%) with LA (Los Angeles classification) grade A, 29 patients (27.6%) with grade B, 11 patients (10.5%) with grade C and 4 patients (3.5%) with grade D esophagitis. Seven years after diagnosis, there were 52 patients (49.5%) with no or occasional reflux symptoms, 8 patients (7.6%) with occasional symptoms requiring treatment with histamine‐2 receptor antagonists (H 2 RAs), 12 patients (11.4%) with occasional symptoms requiring treatment with proton pump inhibitors (PPIs), as needed, and 33 patients (31.3%) with sustained symptoms needing daily maintenance with PPIs. Conclusion: Nearly 50% of patients in Taiwan with endoscopic esophagitis still required treatment 7 years after diagnosis. Approximately 31% of patients still required daily acid suppression therapy. Presence of hiatal hernia and the severity of esophagitis at initial endoscopy independently were predictive of those who would require long‐term acid suppression therapy.
Regrowth of transected retinal ganglion cell axons despite persistent astrogliosis in the lizard (Gallotia galloti)

We analysed the astroglia response that is concurrent with spontaneous axonal regrowth after optic nerve (ON) transection in the lizard Gallotia galloti. At different post‐lesional time points (0.5, 1, 3, 6, 9 and 12 months) we used conventional electron microscopy and specific markers for astrocytes [glial fibrillary acidic protein (GFAP), vimentin (Vim), sex‐determining region Y‐box‐9 (Sox9), paired box‐2 (Pax2)¸ cluster differentiation‐44 (CD44)] and for proliferating cells (PCNA). The experimental retina showed a limited glial response since the increase of gliofilaments was not significant when compared with controls, and proliferating cells were undetectable. Conversely, PCNA+ cells populated the regenerating ON, optic tract (OTr) and ventricular wall of both the hypothalamus and optic tectum (OT). Subpopulations of these PCNA+ cells were identified as GFAP+ and Vim+ reactive astrocytes and radial glia. Reactive astrocytes up‐regulated Vim at 1 month post‐lesion, and both Vim and GFAP at 12 months post‐lesion in the ON‐OTr, indicating long‐term astrogliosis. They also expressed Pax2, Sox9 and CD44 in the ON, and Sox9 in the OTr. Concomitantly, persistent tissue cavities and disorganised regrowing fibre bundles reaching the OT were observed. Our ultrastructural data confirm abundant gliofilaments in reactive astrocytes joined by desmosomes. Remarkably, they also accumulated myelin debris and lipid droplets until late stages, indicating their participation in myelin removal. These data suggest that persistent mammalian‐like astrogliosis in the adult lizard ON contributes to a permissive structural scaffold for long‐term axonal regeneration and provides a useful model to study the molecular mechanisms involved in these beneficial neuron–glia interactions.
A Low‐Km 5′‐Nucleotidase from Rat Brain Cytosolic Fraction: Purification, Kinetic Properties, and Description of Regulation by a Novel Factor that Increases Sensitivity to Inhibition by ATP and ADP

Abstract: A readily soluble 5′‐nucleotidase was purified 1,800‐fold from rat brain 105,000‐g supernatant. The enzyme showed similarity to the 5′‐nucleotidase ectoenzyme of plasma membranes. It exhibited a low Km for AMP, which was preferred over IMP as substrate. It was inhibited by free ATP and ADP and by α,β‐methylene ADP. The enzyme appeared to be a glycoprotein on the basis of its interaction with concanavalin A. It contained a phosphatidylinositol moiety because treatment with phosphatidylinositol‐specific phospholipase C increased its hydrophilicity. A single subunit of Mr = 54,300 ± 800 was observed, which is appreciably smaller than published values for the 5′‐nucleotidase ectoenzyme or for other low‐Km“soluble” 5′‐nucleotidases. The soluble 5′‐nucleotidase showed an elution profile on AMP‐Sepharose affinity chromatography or on Mono Q ion‐exchange chromatography different from that of the brain ectoenzyme. Forty‐two percent of the soluble 5′‐nucleotidase in brain 105,000‐g supernatant did not bind to a Mono Q ion‐exchange column because of its interaction with a soluble factor. This factor could be removed by chromatography on concanavalin A‐Sepharose. The factor had the novel property of increasing the sensitivity of the purified soluble 5′‐nucleotidase toward the inhibitor ATP by 20‐fold. This factor was also able to increase the inhibition of brain 5′‐nucleotidase ectoenzyme by ATP.
WST 50.9 088 corr

Due to the hydrophobic nature of the polyaromatic hydrocarbons (PAHs) they are mostly bound to the sludge and escape aerobic treatment in a wastewater treatment plant. They therefore proceed directly to the anaerobic post treatment, terminate in the sludge, and can be released to the environment if land spreading is used. PAH degradation in anaerobic methanogenic systems has only recently been shown to occur. In this study we have assessed several factors of anaerobic PAH degradation by evaluating thermodynamic feasibility of degradation, assessing degradation at different temperatures, and investigating the enriched cultures using fluorescent in-situ hybridization (FISH). Thermodynamic calculations indicated that PAH degradation was possible under methanogenic conditions, in the presence of hydrogen utilizing methanogens. Removal of naphthalene and 1-methyl naphthalene depended both on temperature and the initial inoculum. Inocula sourced from contaminated land sites were the most effective. The enrichments were all a mixture of Bacteria, and Archaea, and the Archaea were generally identified as Methanobacteriales, using an order-specific probe. The bacteria were not specifically identified. The results indicate a syntrophic culture, with the bacteria oxidizing the naphthalene, and the Archaea converting the hydrogen produced by oxidation, to methane.