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Direct Correlation (direct + correlation)
Kinds of Direct Correlation Terms modified by Direct Correlation Selected AbstractsDirect Correlation of Organic Semiconductor Film Structure to Field-Effect Mobility,ADVANCED MATERIALS, Issue 19 2005M. DeLongchamp Near-edge X-ray fine structure spectroscopy is used to measure simultaneous chemical conversion, molecular ordering, and defect formation in soluble oligothiophene precursor films. Film structure is correlated to OFET performance. Molecular orientation is determined by evaluating antibonding orbital overlap with the polarized electric field vector of incident soft X-rays (see Figure and cover). Upon conversion, the molecules become vertically oriented, allowing , overlap in the plane of hole transport. [source] Role of two arginine residues in domain II, loop 2 of Cry1Ab and Cry1Ac Bacillus thuringiensis,-endotoxin in toxicity and binding to Manduca sexta and Lymantria dispar aminopeptidase NMOLECULAR MICROBIOLOGY, Issue 2 2000Mi Kyong Lee Two arginine residues (368,369) of Cry1Ab and Cry1Ac were mutated to alanine, glutamic acid and lysine by site-directed mutagenesis. Insecticidal activities of the mutant toxins on Manduca sexta and Lymantria dispar larvae were examined. Cry1Ac mutant toxins (c)RR-AA and (c)RR-EE and Cry1Ab mutant toxins (b)RR-AA and (b)RR-EE showed great reductions in toxicity against both insects. In contrast, conservatively changed (c)RR-KK and (b)RR-KK mutants did not alter toxicity to either insect. Binding assays with brush border membrane vesicles (BBMVs) prepared from L. dispar midguts demonstrated that (c)RR-AA, (c)RR-EE, (b)RR-AA and (b)RR-EE bound with lower affinities compared with their respective wild-type toxins. To M. sexta BBMVs, (c)RR-AA and (c)RR-EE showed great reductions in BBMV binding. However, (b)RR-AA and (b)RR-EE did not alter BBMV competition patterns, despite their reduced toxicity. Further binding assays were performed with aminopeptidase N (APN) purified from L. dispar and M. sexta BBMVs using surface plasmon resonance (BIAcore). Direct correlation between toxicity and APN binding was observed for the mutant toxins using this technique. The inconsistency between BBMV and APN binding data with Cry1Ab to M. sexta suggests the possibility of a different Cry1Ab toxin-binding mechanism or the importance of another receptor in M. sexta. [source] Spontaneous apoptosis in chronic lymphocytic leukemia and its relationship to clinical and cell kinetic parametersCYTOMETRY, Issue 6 2001Gislaine B. Oliveira Abstract Chronic lymphocytic leukemia (CLL) presents considerable variability in clinical presentation as well as in its evolution. In contrast to the inhibition of apoptosis in vivo, spontaneous apoptosis after short-term culture occurs. We studied the degree of this apoptosis in vitro, and its interactions with several clinical and laboratory parameters. Apoptosis was measured by the annexin V technique. Proliferation rate was evaluated by the AgNOR (nucleolar organizer regions) technique. There were inverse correlations between the percentage of annexin V-positive cells and peripheral lymphocyte count (r = - 0.49), Rai stage (r = - 0.40), Binet stage (r = - 0.50), TTM (total tumor mass score; r = - 0.51), and percentage of cells with one AgNOR cluster (r = - 0.45). Direct correlations were found with hemoglobin values ( r = 0.34) and platelet counts (r = 0.52). The number of CD8-positive cells showed a correlation with peripheral lymphocyte count (r = 0.49). When this variable was held constant, a correlation was detected between CD8-positive cells and staging (r = -0.47), TTM (r = - 0.42), and platelet count (r = 0.67). CD4-positive lymphocytes presented a correlation only with CD8-positive lymphocytes. In a cluster analysis, it was possible to create three groups of patients with different apoptosis rates using the TTM and AgNOR values. We conclude that, with the progression of the disease, together with the increase of tumor mass and proliferation rate, there is a decrease in the suceptibility to apoptosis. Cytometry (Comm. Clin. Cytometry) 46:329,335, 2001. © 2001 Wiley-Liss, Inc. [source] Intraoperative evaluation of sentinel lymph nodes in breast carcinoma by imprint cytology, frozen section and rapid immunohistochemistryDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2009Sharma Upender M.D. Abstract Sentinel lymph nodes (SLN) isolated in 40 patients of breast carcinoma (stage T1/T2) were evaluated intraoperatively by imprint cytology and frozen section. Rapid immunohistochemistry (IHC) was done in cases where both imprint smears and frozen sections were negative for any metastatic tumor deposits. The results of these different techniques were compared with postoperative paraffin sections taken as "Gold Standard." Nottingham modification of Bloom Richardson scoring system was used for grading the tumors. Further, the correlation of the SLN status with tumor size, grade, and lymphovascular invasion was studied. The sensitivity, specificity, and overall accuracy of imprint cytology were 91.7, 100, and 95% respectively, and those of the frozen section were 95.8, 100, and 97.5% respectively. Examination of multiple serial sections improved the sensitivity and overall accuracy of frozen section. Results of intraoperative rapid IHC were equivalent to final paraffin sections. Histological grade and lymphovascular invasion were in direct correlation with SLN metastasis (P < 0.05). The risk of lymphovascular invasion increased from 22.2% in grade I tumors to 85.7% in grade III tumors. SLN biopsy is a reliable method to evaluate the status of the axillary lymph nodes. Imprint cytology can be used reliably where the facility of frozen section is not available. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Association of mast cells with tumor angiogenesis in esophageal squamous cell carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2001M. Tomita The association of mast cells with tumor angiogenesis was investigated in patients with esophageal squamous cell carcinoma. Surgical specimens from 48 patients with esophageal squamous cell carcinoma were studied. Mast cells in tumor sections were stained with Alcian blue and safranin O. The number of mast cells was counted under light microscopy and the average count recorded. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. Microvessel density was also counted. We found a significant correlation between mast cell count and microvessel density in patients with esophageal squamous cell carcinoma. Double staining of the microvessels revealed highly angiogenic areas densely populated with mast cells. There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with esophageal squamous cell carcinoma. [source] Transcription dynamics of the functional tfdA gene during MCPA herbicide degradation by Cupriavidus necator AEO106 (pRO101) in agricultural soilENVIRONMENTAL MICROBIOLOGY, Issue 3 2008Mette Haubjerg Nicolaisen Summary A modified protocol for simultaneous extraction of RNA and DNA, followed by real-time polymerase chain reaction quantification, was used to investigate tfdA gene expression during in situ degradation of the herbicide MCPA (4-chloro-2-methylphenoxy-acetic acid) in soil. tfdA encodes an ,-ketoglutarate-dependent dioxygenase catalysing the first step in the degradation pathway of MCPA and 2,4-D (2,4-dichlorophenoxy-acetic acid). A linear recovery of tfdA mRNA over three orders of magnitude was shown, and the tfdA mRNA level was normalized using the tfdA mRNA/DNA ratio. The density of active cells required for tfdA mRNA detection was 105 cells g,1 soil. Natural soil microcosms inoculated with Cupriavidus necator (formerly Ralstonia eutropha) AEO106 (pRO101) cells were amended with four different MCPA concentrations (2, 20, 50 and 150 mg kg,1). Mineralization rates were estimated by quantification of 14CO2 emission from degradation of 14C-MCPA. tfdA mRNA was detected 1 h after amendment at all four concentrations. In soils amended with 2 and 20 mg kg,1, the mRNA/DNA ratio for tfdA demonstrated a sharp transient maximum of tfdA expression from no to full expression within 3 and 6 h respectively, followed by a decline and complete loss of expression after 19 and 43 h. A more complex pattern of tfdA expression was observed for the higher 50 and 150 mg kg,1 amendments; this coincided with growth of C. necator AEO106 (pRO101) in the system. Repeated amendment with MCPA after 2 weeks in the 20 mg kg,1 scenario revealed a sharp increase of tfdA mRNA, and absence of a mineralization lag phase. For all amendments, tfdA mRNA was detectable only during active mineralization, and thus revealed a direct correlation between tfdA mRNA presence and microbial degrader activity. The present study demonstrates that direct analysis of functional gene expression dynamics by quantification of mRNA can indeed be made in natural soil. [source] Hydrogen ,leakage' during methanogenesis from methanol and methylamine: implications for anaerobic carbon degradation pathways in aquatic sedimentsENVIRONMENTAL MICROBIOLOGY, Issue 4 2007Niko Finke Summary The effect of variations in H2 concentrations on methanogenesis from the non-competitive substrates methanol and methylamine (used by methanogens but not by sulfate reducers) was investigated in methanogenic marine sediments. Imposed variations in sulfate concentration and temperature were used to drive systematic variations in pore water H2 concentrations. Specifically, increasing sulfate concentrations and decreasing temperatures both resulted in decreasing H2 concentrations. The ratio of CO2 and CH4 produced from 14C-labelled methylamine and methanol showed a direct correlation with the H2 concentration, independent of the treatment, with lower H2 concentrations resulting in a shift towards CO2. We conclude that this correlation is driven by production of H2 by methylotrophic methanogens, followed by loss to the environment with a magnitude dependent on the extracellular H2 concentrations maintained by hydrogenotrophic methanogens (in the case of the temperature experiment) or sulfate reducers (in the case of the sulfate experiment). Under sulfate-free conditions, the loss of reducing power as H2 flux out of the cell represents a loss of energy for the methylotrophic methanogens while, in the presence of sulfate, it results in a favourable free energy yield. Thus, hydrogen leakage might conceivably be beneficial for methanogens in marine sediments dominated by sulfate reduction. In low-sulfate systems such as methanogenic marine or freshwater sediments it is clearly detrimental , an adverse consequence of possessing a hydrogenase that is subject to externally imposed control by pore water H2 concentrations. H2 leakage in methanogens may explain the apparent exclusion of acetoclastic methanogenesis in sediments dominated by sulfate reduction. [source] Activation of gelatinolytic/collagenolytic activity in dentin by self-etching adhesivesEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2006Yoshihiro Nishitani Mild acids are known to activate dentin matrix metalloproteinase (MMPs). All self-etching dental adhesives are acidic (pH 1.5,2.7) and may activate dentin MMPs. The purpose of this study was to compare the ability of several all-in-one adhesives to activate gelatinolytic and collagenolytic activities in powdered mineralized dentin. Powdered dentin made from human teeth was mixed with all-in-one adhesives (Clearfil Tri-S Bond, G-Bond, Adper Prompt L-Pop) or a self-etching primer (Clearfil SE Bond primer) for varying times and then the reaction was stopped by extracting the adhesives using acetone. Fresh untreated mineralized dentin powder had a gelatinolytic activity of 3.31 ± 0.39 relative fluorescent units (RFU) per mg dry weight (24 h) that increased, over storage time, to 87.5 RFU mg,1 (24 h) after 6,8 wk. When fresh powder was treated with acidic Tri-S Bond, the gelatinolytic activity increased from 3.24 ± 0.70 RFU mg,1 to >,112.5 RFU mg,1 (24 h) after 20 min and then remained unchanged. Monomers with lower pH values produced less activity. There was a significant, direct correlation between gelatinolytic activity and pH, with Tri-S giving the highest activity. Coating dentin powder with Tri-S resin prevented fluorescent substrates from gaining access to the enzyme, even though it activated the enzyme. In conclusion, self-etch adhesives may activate latent MMP and increase the activity to near-maximum levels and contribute to the degradation of resin,dentin bonds over time. [source] The evolution of the stress,strain fields near a fatigue crack tip and plasticity-induced crack closure revisitedFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 1 2004L. G. ZHAO ABSTRACT The evolution of the stress,strain fields near a stationary crack tip under cyclic loading at selected R -ratios has been studied in a detailed elastic,plastic finite element analysis. The material behaviour was described by a full constitutive model of cyclic plasticity with both kinematic and isotropic hardening variables. Whilst the stress/strain range remains mostly constant during the cyclic loading and scales with the external load range, progressive accumulation of tensile strain occurs, particularly at high R -ratios. These results may be of significance for the characterization of crack growth, particularly near the fatigue threshold. Elastic,plastic finite element simulations of advancing fatigue cracks were carried out under plane-stress, plane-strain and generalized plane-strain conditions in a compact tension specimen. Physical contact of the crack flanks was observed in plane stress but not in the plane-strain and generalized plane-strain conditions. The lack of crack closure in plane strain was found to be independent of the material studied. Significant crack closure was observed under plane-stress conditions, where a displacement method was used to obtain the actual stress intensity variation during a loading cycle in the presence of crack closure. The results reveal no direct correlation between the attenuation in the stress intensity factor range estimated by the conventional compliance method and that determined by the displacement method. This finding seems to cast some doubts on the validity of the current practice in crack-closure measurement, and indeed on the role of plasticity-induced crack closure in the reduction of the applied stress intensity factor range. [source] Construction of hybrid peptide synthetases for the production of ,- l -aspartyl- l -phenylalanine, a precursor for the high-intensity sweetener aspartameFEBS JOURNAL, Issue 22 2003Thomas Duerfahrt Microorganisms produce a large number of pharmacologically and biotechnologically important peptides by using nonribosomal peptide synthetases (NRPSs). Due to their modular arrangement and their domain organization NRPSs are particularly suitable for engineering recombinant proteins for the production of novel peptides with interesting properties. In order to compare different strategies of domain assembling and module fusions we focused on the selective construction of a set of peptide synthetases that catalyze the formation of the dipeptide ,- l -aspartyl- l -phenylalanine (Asp-Phe), the precursor of the high-intensity sweetener ,- l -aspartyl- l -phenylalanine methyl ester (aspartame). The de novo design of six different Asp-Phe synthetases was achieved by fusion of Asp and Phe activating modules comprising adenylation, peptidyl carrier protein and condensation domains. Product release was ensured by a C-terminally fused thioesterase domains and quantified by HPLC/MS analysis. Significant differences of enzyme activity caused by the fusion strategies were observed. Two forms of the Asp-Phe dipeptide were detected, the expected ,-Asp-Phe and the by-product ,-Asp-Phe. Dependent on the turnover rates ranging from 0.01,0.7 min,1, the amount of ,-Asp-Phe was between 75 and 100% of overall product, indicating a direct correlation between the turnover numbers and the ratios of ,-Asp-Phe to ,-Asp-Phe. Taken together these results provide useful guidelines for the rational construction of hybrid peptide synthetases. [source] Hierarchical Zeolite Catalysts: Zeolite Catalysts with Tunable Hierarchy Factor by Pore-Growth Moderators (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 24 2009Mater. On page 3972, Pérez-Ramírez et al. introduce the hierarchy factor as a valuable descriptor to categorize hierarchical zeolites and to optimize their design for catalytic applications. They demonstrate a direct correlation between the catalytic performance of ZSM-5 in benzene alkylation and the hierarchy factor. Maximization of the hierarchy factor is achieved by enhancing the mesopore surface area without reducing the micropore volume. For this purpose, a novel desilication variant involving NaOH treatment in the presence of pore growth moderators (quaternary ammonium cations) is presented. [source] Stage-specific alterations of the genome, transcriptome, and proteome during colorectal carcinogenesis,GENES, CHROMOSOMES AND CANCER, Issue 1 2007Jens K. Habermann To identify sequential alterations of the genome, transcriptome, and proteome during colorectal cancer progression, we have analyzed tissue samples from 36 patients, including the complete mucosa-adenoma-carcinoma sequence from 8 patients. Comparative genomic hybridization (CGH) revealed patterns of stage specific, recurrent genomic imbalances. Gene expression analysis on 9K cDNA arrays identified 58 genes differentially expressed between normal mucosa and adenoma, 116 genes between adenoma and carcinoma, and 158 genes between primary carcinoma and liver metastasis (P < 0.001). Parallel analysis of our samples by CGH and expression profiling revealed a direct correlation of chromosomal copy number changes with chromosome-specific average gene expression levels. Protein expression was analyzed by two-dimensional gel electrophoresis and subsequent mass spectrometry. Although there was no direct match of differentially expressed proteins and genes, the majority of them belonged to identical pathways or networks. In conclusion, increasing genomic instability and a recurrent pattern of chromosomal imbalances as well as specific gene and protein expression changes correlate with distinct stages of colorectal cancer progression. Chromosomal aneuploidies directly affect average resident gene expression levels, thereby contributing to a massive deregulation of the cellular transcriptome. The identification of novel genes and proteins might deliver molecular targets for diagnostic and therapeutic interventions. © Wiley-Liss, Inc. [source] Structural and Room-Temperature Transport Properties of Zinc Blende and Wurtzite InAs NanowiresADVANCED FUNCTIONAL MATERIALS, Issue 13 2009Shadi A. Dayeh Abstract Here, direct correlation between the microstructure of InAs nanowires (NWs) and their electronic transport behavior at room temperature is reported. Pure zinc blende (ZB) InAs NWs grown on SiO2/Si substrates are characterized by a rotational twin along their growth-direction axis while wurtzite (WZ) InAs NWs grown on InAs (111)B substrates have numerous stacking faults perpendicular to their growth-direction axis with small ZB segments. In transport measurements on back-gate field-effect transistors (FETs) fabricated from both types of NWs, significantly distinct subthreshold characteristics are observed (Ion/Ioff,,,2 for ZB NWs and ,104 for WZ NWs) despite only a slight difference in their transport coefficients. This difference is attributed to spontaneous polarization charges at the WZ/ZB interfaces, which suppress carrier accumulation at the NW surface, thus enabling full depletion of the WZ NW FET channel. 2D Silvaco-Atlas simulations are used for ZB and WZ channels to analyze subthreshold current flow, and it is found that a polarization charge density of ,1013,cm,2 leads to good agreement with experimentally observed subthreshold characteristics for a WZ InAs NW given surface-state densities in the 5,×,1011,5,×,1012,cm,2 range. [source] Scintigraphic evaluation of intrapulmonary shunt in normoxemic cirrhotic patients and effects of terlipressinHEPATOLOGY RESEARCH, Issue 10 2010George Kalambokis Aim:, The magnitude of intrapulmonary shunt (IPS) in cirrhotic patients without hypoxemia remains undefined. We evaluated the severity and clinical correlations of IPS in normoxemic cirrhotics, and possible IPS alterations after terlipressin treatment. Methods:, Fifteen patients with alcoholic cirrhosis without hypoxemia were studied at baseline and after the administration of 2 mg of terlipressin. The IPS fraction was evaluated by lung perfusion scan after the i.v. injection of technetium-99m -labeled macroaggregated albumin (99mTc-MAA) and calculation of brain uptake (positive value ,6%). Cardiac output (CO), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were evaluated by Doppler echocardiography. Mean arterial pressure (MAP) was measured and the ratio MAP/CO was calculated as an index of systemic vascular resistance (SVR). Portal vein velocity (PVV) and portal venous flow (PVF) were also assessed by Doppler ultrasonography. Results:, Three patients (20%) had an IPS fraction of more than 6%. A significant inverse correlation with platelet count (P = 0.001) and a direct correlation with Child,Pugh score (P = 0.06), PVV (P = 0.07) and PVF (P = 0.07) were noted. IPS fractions decreased significantly after terlipressin administration (P = 0.00001); the IPS fraction fell below 6% in all three patients with positive baseline values. Terlipressin treatment induced a significant decrease in CO (P = 0.003) and significant increases in MAP (P = 0.0003), SVR (P = 0.0003), SPAP (P = 0.001) and PVR (P = 0.01). Conclusion:, IPS fractions detected by 99mTc-MAA lung scan were inversely correlated with platelet count and directly with liver disease severity, and found abnormal in 20% of normoxemic cirrhotic patients. Terlipressin reduced significantly the magnitude of the shunt. [source] Perceived Risk and Efficacy Beliefs as Motivators of ChangeHUMAN COMMUNICATION RESEARCH, Issue 3 2003Use of the Risk Perception Attitude (RPA) Framework to Understand Health Behaviors Evidence of a direct correlation between risk perception and self-protective behavior is ambiguous at best. Witte's (1992, 1994) extended parallel process model (EPPM) explains many contradictory findings by pointing out the moderating role played by efficacy beliefs. Working from the EPPM, this article introduces the risk perception attitude (RPA) framework that categorizes individuals into one of four attitudinal groups: responsive (high risk, high efficacy), avoidance (high risk, low efficacy), proactive (low risk, high efficacy), and indifference (low risk, low efficacy). We conducted two studies to test our hypotheses that these groups differ in their self-protective motivation, intention to seek information, behavioral intention, knowledge acquisition, and time spent seeking information. Results, though not entirely consistent, suggest that, when risk and efficacy are made salient (Study 1), people's risk perception guides most of their subsequent actions, but in a natural context (Study 2), risk and efficacy jointly affect subsequent action. [source] Human natural killer cell receptors and co-receptorsIMMUNOLOGICAL REVIEWS, Issue 1 2001Roberto Biassoni Summary: In the absence of sufficient signaling by their HLA class I-specific inhibitory receptors, human natural killer (NK) cells become activated and display potent cytotoxicity against cells that are either HLA class I negative or deficient. This indicates that the NK receptors responsible for the induction of cytotoxicity recognize ligands on target cells different from HLA class I molecules. On this basis, the process of NK-cell triggering can be considered as a mainly non-MHC-restricted mechanism. The recent identification of a group of NK-specific triggering surface molecules has allowed a first series of pioneering studies on the functional/molecular characteristics of such receptors. The first three members of a receptor family that has been termed natural cytotoxicity receptors (NCR) are represented by NKp46, NKp44 and NKp30. These receptors are strictly confined to NK cells, and their engagement induces a strong activation of NK-mediated cytolysis. A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various target cells. Importantly, mAb-mediated blocking of these receptors has been shown to suppress cytotoxicity against most NK-susceptible target cells. However, the process of NK-cell triggering during target cell lysis may also depend on the concerted action of NCR and other triggering receptors, such as NKG2D, or surface molecules, including 2B4 and NKp80, that appear to function as co-receptors rather than as true receptors. Notably, a dysfunction of 2B4 has been associated with a severe form of immunodeficiency termed X-linked lymphoproliferative disease. Future studies will clarify whether also the altered expression and/or function of other NK-triggering molecules may represent a possible cause of immunological disorders. This work was supported by grants awarded by Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.), Istituto Superiore di Sanità (I.S.S.), Ministero della Sanità, and Ministero dell'Università e della Ricerca Scientifica e Tecnologica (M.U.R.S.T.) and Consiglio Nazionale delle Ricerche, Progetto Finalizzato Biotecnologie. The financial support of Telethon-Italy (grant no. E.0892) is gratefully acknowledged. [source] Suppressor of cytokine signalling-3 at pathological levels does not regulate lipopolysaccharide or interleukin-10 control of tumour necrosis factor-, production by human monocytesIMMUNOLOGY, Issue 1 2006Cecilia M. Prêle Summary Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that suppresses the production of tumour necrosis factor-, (TNF-,) by monocytes and macrophages. Suppressor of cytokine signalling-3 (SOCS3), a negative regulator of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, is induced following IL-10 exposure but recent studies in mice suggest that SOCS3 only targets gp-130-dependent signal transduction pathways. Understanding the signalling pathways responsible for IL-10-mediated effects in primary human monocytes is relevant to human inflammatory disease and necessary for the identification of potential therapeutic targets. An adenoviral transfection system was used to express different levels of SOCS3 (quantified experimentally with its tag green fluorescent protein (GFP)) with the aim of investigating the role of SOCS3 in LPS-induced and IL-10-mediated suppression of TNF-, production by non-transformed human monocytes. SOCS3 over-expression had no effect on TNF-, mRNA levels induced by LPS or LPS plus IL-10, or on IL-10 phosphorylation of STAT3, STAT1 and ERK1/2. When data from all donors were combined, adenoviral overexpression of SOCS3 significantly reversed the suppressive effects of IL-10 on LPS-induced TNF-, production after 2 hr. However, there was a direct correlation between mean GFP intensity (extent of viral infection) and extent of reversal of IL-10's inhibitory effects. Physiological levels of SOCS3 detected in IL-10-exposed human monocytes had no effect on LPS-induced TNF-, production. Although overexpression of SOCS3 to supraphysiological levels transiently antagonized the regulatory properties of IL-10 by a post-transcriptional mechanism, these findings suggest that under pathological conditions SOCS3 does not control LPS-activation or the anti-inflammatory properties of IL-10 in primary human monocytes. [source] Molecular mechanics in the context of the finite element methodINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 7 2009Jens Wackerfuß Abstract In molecular mechanics, the formalism of the finite element method can be exploited in order to analyze the behavior of atomic structures in a computationally efficient way. Based on the atom-related consideration of the atomic interactions, a direct correlation between the type of the underlying interatomic potential and the design of the related finite element is established. Each type of potential is represented by a specific finite element. A general formulation that unifies the various finite elements is proposed. Arbitrary diagonal- and cross-terms dependent on bond length, valence angle, dihedral angle, improper dihedral angle and inversion angle can also be considered. The finite elements are formulated in a geometrically exact setting; the related formulas are stated in detail. The mesh generation can be performed using well-known procedures typically used in molecular dynamics. Although adjacent elements overlap, a double counting of the element contributions (as a result of the assembly process) cannot occur a priori. As a consequence, the assembly process can be performed efficiently line by line. The presented formulation can easily be implemented in standard finite element codes; thus, already existing features (e.g. equation solver, visualization of the numerical results) can be employed. The formulation is applied to various interatomic potentials that are frequently used to describe the mechanical behavior of carbon nanotubes. The effectiveness and robustness of this method are demonstrated by means of several numerical examples. Copyright © 2008 John Wiley & Sons, Ltd. [source] Mast cells and transforming growth factor-, expression: a possible relationship in the development of porphyria cutanea tarda skin lesionsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2008Glalcyara Lançoni MD Background, Porphyria cutanea tarda (PCT) is a metabolic disease characterized by vesicles and blisters in sun-exposed areas and scleroderma-like lesions in sun-exposed and non-sun-exposed areas. Mast cells participate in the pathogenesis of bullous diseases and diseases that show sclerosis, including PCT. Moreover, transforming growth factor-, (TGF-,) is the main cytokine in the development of tissue sclerosis. The correlation of mast cells and TGF-, with the lesions of PCT has not been examined, however. The possible role of mast cells and TGF-, (and the relationship between them) in the development of PCT lesions is discussed. Methods, To quantify mast cells and cells expressing TGF-, in skin samples from patients with PCT and controls, immunohistochemical studies were performed in tissue sections allied to morphometric analyses. Results, The numbers of mast cells and cells expressing TGF-, per square millimiter were increased in the PCT group relative to controls, and there was a direct and significant correlation between the mast cell number and cells expressing TGF-, in PCT. Conclusions, The results suggest that the increased number of mast cells and of cells expressing TGF-,, as well as their direct correlation, may contribute to the pathogenesis of the skin lesions in PCT. [source] Evidence that thalidomide modifies the immune response of patients suffering from actinic prurigoINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2004Iris Estrada-G PhD Background, Actinic prurigo (AP) is a photodermatosis with a restricted ethnic distribution, mainly affecting Mestizo women (mixed Indian and European). The lesions are polymorphic and include macules, papules, crusts, hyperpigmentation and lichenification. Thalidomide, an effective immunomodulatory drug, was first used successfully to treat AP in 1973. In this work we describe the effect that thalidomide had on TNF-, sera levels and on IL-4- and IFN gamma (IFN,)-producing lymphocytes of actinic prurigo (AP) patients. Methods, Actinic prurigo patients were analyzed before and after thalidomide treatment. The percentage of IL-4+ or IFN,+ CD3+ lymphocytes was analyzed in eight of them by flow cytometry. TNF, in sera was measured by ELISA in 11 patients. Results, A direct correlation was observed between resolution of AP lesions and an increase in IFN,+ CD3+ peripheral blood mononuclear cells (P , 0.001) and a decrease in TNF, serum levels (no statistical difference). No IL-4+ CD3+ cells were detected. Conclusions, Our findings confirm that AP is a disease that has an immunological component and that thalidomide clinical efficacy is exerted not only through inhibition of TNF, synthesis, but also through modulation of INF,-producing CD3+ cells. These cells could be used as clinical markers for recovery. [source] The role of early neural activity in the maturation of turtle retinal functionJOURNAL OF ANATOMY, Issue 4 2001EVELYNE SERNAGOR In the developing vertebrate retina, ganglion cells fire spontaneous bursts of action potentials long before the eye becomes exposed to sensory experience at birth. These early bursts are synchronised between neighbouring retinal ganglion cells (RGCs), yielding unique spatiotemporal patterns: ,waves' of activity sweep across large retinal areas every few minutes. Both at retinal and extraretinal levels, these embryonic retinal waves are believed to guide the wiring of the visual system using hebbian mechanisms of synaptic strengthening. In the first part of this review, we recapitulate the evidence for a role of these embryonic spontaneous bursts of activity in shaping developing complex receptive field properties of RGCs in the turtle embryonic retina. We also discuss the role of visual experience in establishing RGC visual functions, and how spontaneous activity and visual experience interact to bring developing receptive fields to maturation. We have hypothesised that the physiological changes associated with development reflect modifications in the dendritic arbours of RGCs, the anatomical substrate of their receptive fields. We demonstrate that there is a temporal correlation between the period of receptive field expansion and that of dendritic growth. Moreover, the immature spontaneous activity contributes to dendritic growth in developing RGCs. Intracellular staining of RGCs reveals, however, that immature receptive fields only rarely show direct correlation with the layout of the corresponding dendritic tree. To investigate the possibility that not only the presence of the spontaneous activity, but even the precise spatiotemporal patterns encoded in retinal waves might contribute to the refinement of retinal neural circuitry, first we must clarify the mechanisms mediating the generation and propagation of these waves across development. In the second part of this review, we present evidence that turtle retinal waves, visualised using calcium imaging, exhibit profound changes in their spatiotemporal patterns during development. From fast waves sweeping across large retinal areas and recruiting many cells on their trajectory at early stages, waves become slower and eventually stop propagating towards hatching, when they become stationary patches of neighbouring coactive RGCs. A developmental switch from excitatory to inhibitory GABAA responses appears to mediate the modification in spontaneous activity patterns while the retina develops. Future chronic studies using specific spatiotemporal alterations of the waves will shed a new light on how the wave dynamics help in sculpting retinal receptive fields. [source] Topoisomerase inhibitor induced dephosphorylation of H1 and H3 histones as a consequence of cell cycle arrestJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2005Nicole Happel Abstract Posttranslational modifications of histones have an integral function in the structural and functional organization of chromatin. Several changes in the modification state of histones could be observed after induction of apoptosis with topoisomerase inhibitors and other inducers. Most of these studies include the analysis of the state of phosphorylation of histones, and the results are to some extent controversial, depending on cell lines and agents used. In the present study we compared the kinetics of the dephosphorylation of H1 and H3 histones with apoptosis markers after treatment of leukemic cell lines with topoisomerase inhibitors. In parallel, we determined cell cycle parameters in detail. Dephosphorylation of both histone classes started within 1 h of induction, and no direct correlation with timing and intensity of the investigated apoptotic features could be observed. In contrast, we show that the effect of topoisomerase inhibitors on the state of H1 and H3 phosphorylation is not directly related to apoptosis, but reflects the changes in the cell cycle distribution of cells treated with these inducers. © 2005 Wiley-Liss, Inc. [source] Reduced oxidative stress in parallel to improved cardiac performance one year after selective removal of anti-beta 1-adrenoreceptor autoantibodies in patients with idiopathic dilated cardiomyopathy: data of a preliminary study,JOURNAL OF CLINICAL APHERESIS, Issue 3 2005Ingolf Schimke Abstract Patients with idiopathic dilated cardiomyopathy (IDC) were treated with selective immunoadsorption to remove anti-beta 1-adrenoreceptor autoantibodies (anti-beta1A-AB). After one year, the effect on cardiac performance and oxidative stress was tested. Extracorporeal immunoadsorption of the whole IgG class in IDC patients for the removal of anti-beta1A-AB reduced oxidative stress in parallel to an improvement of cardiac performance. However, the non-specificity of IgG adsorption means that these beneficial effects cannot be attributed exclusively to anti-beta1A-AB removal. In an open clinical pilot study enrolling 8 patients with IDC prior to and one year after selective immunoadsorption of anti-beta1A-AB, plasma markers for oxidative stress,thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO) and anti-oxidized low-density lipoprotein autoantibodies (anti-oxLDL-AB),were measured in parallel to evaluation of the left ventricular function using conventional echocardiography and wall motion analysis by tissue Doppler imaging. After one year, TBARS (Wilcoxon test with bootstrapping simulation for paired data: 95% confidence interval of the P value 0.020 to 0.029) and anti-oxLDL-AB (P = 0.025 to 0.035) were decreased in parallel to an improvement of the peak systolic wall motion velocity (P = 0.006 to 0.01) and left ventricular ejection fraction (P = 0.002 to 0.02). For changes over the study period, a direct correlation with borderline significance (P = 0.076) was calculated for TBARS to the left ventricular diameter in the diastole. One year after selective immunoadsorption for anti-beta1A-AB removal, patients with ICD show a reduction in oxidative stress and a parallel improvement in cardiac performance. J. Clin. Apheresis © 2005 Wiley-Liss, Inc. [source] Hospital discharge planning for frail older people and their family.JOURNAL OF CLINICAL NURSING, Issue 18 2009Are we delivering best practice? Aims and objectives., This paper examined the available evidence concerning hospital discharge practices for frail older people and their family caregivers and what practices were most beneficial for this group. Background., Hospital discharge practices are placing an increasing burden of care on the family caregiver. Discharge planning and execution is significant for older patients where inadequate practices can be linked to adverse outcomes and an increased risk of readmission. Design., Literature review. Methods., A review of English language literature published after 1995 on hospital discharge of frail older people and family carer's experiences. Results., Numerous factors impact on the hospital discharge planning of the frail older person and their family carer's that when categorised focus on the role that discharge planning plays in bridging the gap between the care provided in hospital and the care needed in the community, its potential to reduce the length of hospital stay, the impact of the discharge process on family carer's and the need for a coordinated health professional approach that includes dissemination of information, clear communication and active support. Conclusion., The current evidence indicates that hospital discharge planning for frail older people can be improved if interventions address family inclusion and education, communication between health care workers and family, interdisciplinary communication and ongoing support after discharge. Interventions should commence well before discharge. Relevance to clinical practice., An awareness of how the execution of the hospital discharge plan is perceived by the principal family carer of a frail older person, will allow nurses and others involved with the discharge process to better reconcile the family caregivers' needs and expectations with the discharge process offered by their facility. The research shows there is a direct correlation between the quality of discharge planning and readmission to hospital. [source] Transvaginal sonographic appearance of thrombosed uterine arteries after uterine artery embolization: the "White Snake" signJOURNAL OF CLINICAL ULTRASOUND, Issue 8 2003Iftikhar Ahmad MD Abstract Purpose The aim of this prospective study was to describe the appearance of thrombosed uterine arteries on transvaginal sonography performed after uterine artery embolization (UAE) and to assess the prognostic value of the "white snake" sign with regard to symptomatic outcome at 12 months. Methods Patients who underwent UAE from January 1, 1999, to July 31, 2000, for the treatment of symptomatic leiomyomas were included in the study. Transvaginal sonography was performed before and at 3, 6, and 12 months after UAE. Patients graded the severity of their symptoms on a scale from 1 to 5, with 1 being the least and 5 the most severe, before and at 12 months after the procedure. The Wilcoxon rank-sum test was used to determine correlations between severity of symptoms and presence of the white snake sign; a p value of less than 0.05 was considered significant. Results During the study period, UAE was performed in 19 patients with a mean age of 41 years (range, 32,48 years). UAE was technically successful in all patients. Eighteen patients (95%) reported symptomatic improvement at 12 months: 8 patients (42%) by 4 severity-scale points, 5(26%) by 3 points, and 5 (26%) by 2 points. The 1 patient who did not experience improvement had undergone a hysterectomy at 4 months after the UAE. At the 3-month follow-up, transvaginal sonography demonstrated a tortuous echogenic structure in the adnexa (the white snake sign) in all patients; the finding was still apparent in 10 patients at 6 months but in only 2 patients at 12 months. A direct correlation was found between persistence of the white snake sign and the degree of symptomatic improvement at 6 months (p = 0.04) but not at 12 months (p = 0.08). Conclusions After UAE, a thrombosed uterine artery appears on transvaginal sonography as an echogenic tortuous structure in the adnexa. Persistence of this white snake sign at 6 months after UAE may suggest a more favorable symptomatic outcome. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:401,406, 2003 [source] Des-,-carboxyprothrombin, ,-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2008Francisco A Durazo Abstract Background and Aim:, Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis. Detection of HCC at an early stage is critical for a favorable clinical outcome. The study aim was to: (i) compare the levels of des-,-carboxyprothrombin (DCP), ,-fetoprotein (AFP) and AFP-L3 in HCC patients and in chronic viral hepatitis patients without HCC; (ii) define the level of each tumor marker with the best sensitivity and specificity for HCC diagnosis; and (iii) to correlate the levels of these markers with respect to size and tumor burden. Methods:, Two hundred and forty patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were studied. These included 144 with HCC, 47 with chronic hepatitis (fibrosis stage I,III on liver biopsy) and 49 with cirrhosis. Results:, Levels of DCP, AFP and AFP L-3 were significantly higher in patients with HCC than in those without HCC (P , 0.0001). Receiver,operating curves (ROC) indicated that the cut-off value with the best sensitivity and specificity for each test was ,84 mAU/mL for DCP, ,25 ng/mL for AFP and ,10% for AFP-L3. The sensitivity, specificity and positive predictive value (PPV) for DCP was 87%, 85% and 86.8%, for AFP 69%, 87% and 69.8%, and for AFP-L3 56%, 90% and 56.1%, respectively. DCP levels were below the ROC cut-off in all patients without HCC. In patients with single lesions, there was a direct correlation of DCP to tumor size. High levels of AFP correlated with diffuse type of HCC. All three markers were significantly elevated in the presence of metastatic HCC. No advantage was observed by combining two or three markers for HCC diagnosis. Conclusion:, DCP had the highest sensitivity and PPV for HCC diagnosis, had a direct correlation with tumor size, and was not elevated in any patients without HCC. DCP should be used as the main serum test for HCC detection. [source] Time course of hepatitis A viremia and viral load in the blood of human hepatitis A patientsJOURNAL OF MEDICAL VIROLOGY, Issue 1 2004Andrea Normann Abstract The hepatitis A virus (HAV) is the most common etiological cause of acute hepatitis infections in humans in industrialized countries. Investigations into the viral load during HAV viremia, however, are rare. Therefore, correlation studies between viral load, biochemical, and specific serological markers have been undertaken. The group of sera comprised a series of multiple consecutive blood samples drawn from 11 patients at different times after onset of the disease. During the period up to 70 days after the onset of icterus, the individual range was at 1×103 to 3×104 HAV genome equivalents/ml. From day 75 until 120 after onset of the disease, the levels traced were at 103. In one case, it was possible to trace 1.25×104 genome equivalents/ml up to 180 days after onset of icterus and in two cases even up to 408 and 490 days viral load levels of 5×103 and 4×104 were detected, respectively. The same sera were used to measure IgM class antibodies to hepatitis A virus and the total anti-HAV. The results demonstrate that a direct correlation to peak levels of viral load exists with peak serum transaminase levels, but neither with peak anti-HAV IgM levels nor with total anti-HAV. Decreasing amounts of anti-HAV IgM tend to occur with decreasing amounts of HAV genome equivalents; and, vice versa, increasing amounts of total anti-HAV are accompanied by decreasing amounts of HAV genome equivalents. The longest duration of viremia was found in patients infected with HAV genotype IA. J. Med. Virol. 72:10,16, 2004. © 2004 Wiley-Liss, Inc. [source] Basal replication of hepatitis C virus in nude mice harboring human tumorJOURNAL OF MEDICAL VIROLOGY, Issue 3 2002Patrick Labonté Abstract Hepatitis C virus (HCV) can infect and propagate in humans and chimpanzees. Whereas the chimpanzee has been used as an animal model for infection, ethical considerations, conservation, and the prohibitively high cost preclude progress for experimental research on the biology of the virus. The development of a small animal model for HCV infection is thus desirable to facilitate studies on the infectious cycle of the virus and for the evaluation of drugs for the treatment of HCV infections in humans. As an alternative to the chimpanzee model, we have established a model based on ex vivo infection of orthotopically-implanted human hepatocellular carcinoma cells (HCC) in athymic nude mice. The results show that up to 42 days post-infection, HCV RNA was present in the tumor cells as well as in the liver and serum of infected mice. Furthermore, a direct correlation between size of the tumor and the presence of HCV RNA in the liver was observed, which is concordant with the finding that HCV RNA was detectable only in mice harboring human tumor. Immunohistochemistry analysis of infected liver specimens showed cells expressing the HCV encoded NS5B protein. A few mice developed a humoral response against the nonstructural viral proteins, providing further evidence for expression of these proteins during viral infection. In summary, these results suggest that mice harboring orthotopic tumors support a basal level of HCV replication in vivo. J. Med. Virol. 66:312-319, 2002. © 2002 Wiley-Liss, Inc. [source] Multinuclear NMR characterisation and dermal delivery of fluorinated drugs in soybean-microemulsion systemsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2009Sonja Hoeller Abstract The present study evaluated the effect of different commercially available soybean lecithins in microemulsion systems in terms of microstructure transformation, physicochemical properties and transport of selected entrapped fluorinated drugs through skin. Physicochemical characterisations by particle size and polydispersity index (PDI) measurements were performed and a direct correlation with NMR self-diffusion coefficients of the individual components was found. An increase of lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) in the phospholipid mixtures increased the mean particle sizes and PDI. Bicontinous microemulsion structures were proven by 1H and 31P NMR in the placebo microemulsions. Reasonable permeation of the lipophilic drugs of all microemulsions systems was confirmed in standard diffusion studies using porcine skin. This could be due to the incorporation of the drugs in the surfactant structure of the lecithin based bicontinous micro textures, as proven by 19F NMR self-diffusion studies. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2686,2695, 2009 [source] Comparative DFT study on the role of conformers in the ruthenium alkylidene-catalyzed ROMP of norborn-2-eneJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2008Sergej Naumov Abstract Comparative quantum chemical calculations on the reaction pathways for the formation of ruthena(IV)cyclobutanes from both 1st - and 2nd -generation Grubbs catalysts of the general formula RuX2(L)(L,)(CH2) (L,=,PCy3 or 1,3-dimesityl-4,5-dihydroimidazolin-2-ylidene, L,,=,PCy3) and norborn-2-ene (NBE) were carried out on the B3LYP/LACVP** level in dependence on the ligand X,=,I, Br, Cl, and F. The mechanism proposed by Straub for the formation of (one) active and (three) inactive NBE,Ru,carbene complexes for non-cyclic alkenes was applied to the cyclic alkene NBE. In RuX2(PCy3)2(CH2), the inactive NBE,Ru,carbene complex is energetically more stable than the active one; however, in RuX2(IMesH2)(PCy3)(CH2), the active NBE,Ru,carbene complex is more stable than the inactive one. In due consequence, the possible rate limiting barrier for the conversion of the NBE,Ru,carbene complex into the corresponding metallocyclobutane (MCB) is systematically larger in the case of 1st -generation Grubbs catalysts than of 2nd -generation Grubbs catalysts due to an additional re-arrangement for the formation of an active , -complex from the more stable (inactive) conformer. This correlates with the observed reactivity of both types of initiators. There is a strong influence of the ligands L and X on the conformational properties and relative stabilities of the 14-electron intermediates, which has a direct effect on the distribution of the inactive and active conformations of the corresponding Ru,carbene,NBE complexes. A direct correlation between the conformational properties of the 14-electron intermediates and the relative stabilities of the active Ru,carbene,NBE complexes was observed. Copyright © 2008 John Wiley & Sons, Ltd. [source] |