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Critical Determinant (critical + determinant)
Selected AbstractsThe Lateral Ala's Volume and Position Are Critical Determinants of Aesthetically Successful Nasal Reconstruction: A Photographic Case SeriesDERMATOLOGIC SURGERY, Issue 4 2009JONATHAN L. COOK MD First page of article [source] Critical determinants of the interactions of capsule-expressing Neisseria meningitidis with host cells: the role of receptor density in increased cellular targeting via the outer membrane Opa proteinsCELLULAR MICROBIOLOGY, Issue 10 2005Christopher J. Bradley Summary Neisseria meningitidis capsule is an important virulence determinant required for survival in the blood but is reportedly involved in inhibiting cellular interactions mediated by meningococcal outer membrane adhesins. However, evidence from our previous studies suggested that target receptor density on host cells may determine whether or not capsulate bacteria can adhere via outer membrane proteins such as Opa. To confirm this and evaluate the impact of capsulation on bacterial interactions, we used Opa+ and Opa, derivatives of capsulate and acapsulate meningococcal isolates and transfected cell lines expressing CEACAM1, a receptor targeted by Opa proteins. To assess the extent and rate of cell association, subpopulations of stably transfected Chinese hamster ovary cells with different receptor levels were derived. A quantitative correlation of CEACAM1 levels and Opa-dependent binding of both capsulate and acapsulate bacteria was demonstrated, which was accelerated at high receptor densities. However, it appears that invasion by Opa+ capsulate bacteria only occurs when a threshold level of CEACAM density has been reached. Target cells expressing high levels of CEACAM1 (MFI c. 400) bound threefold more, but internalized 20-fold more Opa+ capsulate bacteria than those with intermediate expression (MFI c. 100). No overall selection of acapsulate phenotype was observed in the internalized population. These observations confirm that capsule may not be an adequate barrier for cellular interactions and demonstrate the role of a host factor that may determine capsulate bacterial invasion potential. Upregulation of CEACAMs, which can occur in response to inflammatory cytokines, could lead to translocation of a small number of fully capsulate bacteria across mucosal epithelium into the bloodstream sufficient to cause a rapid onset of disseminated disease. Thus the data also suggest a novel rationale for the epidemiological observations that individuals with prior infectious/inflammatory conditions carry a high risk of invasive meningococcal disease. [source] "I Am Not Alone": The Feasibility and Acceptability of Interactive Voice Response-Facilitated Telephone Peer Support Among Older Adults With Heart FailureCONGESTIVE HEART FAILURE, Issue 3 2007Michele Heisler MD Patient self-management is a critical determinant of heart failure (HF) outcomes, yet patients with HF are often frail and socially isolated, factors that may limit their ability to manage self-care and access clinic-based services. Mobilizing peer support among HF patients is a promising strategy to improve self-management support. In this pilot, the authors evaluated the feasibility and acceptability of an interactive voice response (IVR)-based platform to facilitate telephone peer support among older adults with HF. Participants completed a baseline survey, were offered a 3-hour training session in peer communication skills, and were paired with another patient who had HF. Participants were asked to contact their partner weekly using a toll-free IVR phone system that protected their anonymity and provided automated reminders if contacts were not made. Times and duration of participants' telephone contacts were monitored and recorded. After the 7-week intervention, participants completed surveys and brief face-to-face interviews. The authors found high levels of use and satisfaction and improvements in depressive symptoms among the 20 pilot study participants. An IVR peer-support intervention is feasible, is acceptable to patients, and may have positive effects on patients' HF social support and health outcomes, in conjunction with structured health system support, that warrant more rigorous evaluation in a randomized trial. [source] Optical tweezers for measuring red blood cell elasticity: application to the study of drug response in sickle cell diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003M. M. Brandão Abstract: The deformability of erythrocytes is a critical determinant of blood flow in microcirculation. By capturing red blood cells (RBC) with optical tweezers and dragging them through a viscous fluid we were able to measure their overall elasticity. We measured, and compared, the RBC deformability of 15 homozygous patients (HbSS) including five patients taking hydroxyurea (HU) for at least 6 months (HbSS/HU), 10 subjects with sickle cell trait (HbAS) and 35 normal controls. Our results showed that the RBC deformability was significantly lower in haemoglobin S (HbS) subjects (HbSS and HbAS), except for HbSS/HU cells, whose deformability was similar to the normal controls. Our data showed that the laser optical tweezers technique is able to detect differences in HbS RBC from subjects taking HU, and to differentiate RBC from normal controls and HbAS, indicating that this is a very sensitive method and can be applied for detection of drug-response in sickle cell disease. [source] Efficient help for autoreactive B-cell activation requires CD4+ T-cell recognition of an agonist peptide at the effector stageEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2009Brian D. Hondowicz Abstract T-cell recognition of peptide/MHC complexes is flexible and can lead to differential activation, but how interactions with agonist (full activation) or partial agonist (suboptimal activation) peptides can shape immune responses in vivo is not well characterized. We investigated the effect of stimulation by agonist or partial agonist ligands during initial CD4+ T-cell priming, and subsequent T-B-cell cognate interactions, on antibody production by anti-chromatin B cells. We found that autoantibody production required TCR recognition of an agonist peptide at the effector stage of B-cell activation. However, interaction with a weak agonist ligand at this effector stage failed to promote efficient autoantibody production, even if the CD4+ T cells were fully primed by an agonist peptide. These studies suggest that the reactivity of the TCR for a target self-peptide during CD4+ T-B-cell interaction can be a critical determinant in restraining anti-chromatin autoantibody production. [source] The Vps4 C-terminal helix is a critical determinant for assembly and ATPase activity and has elements conserved in other members of the meiotic clade of AAA ATPasesFEBS JOURNAL, Issue 7 2008Parimala R. Vajjhala Sorting of membrane proteins into intralumenal endosomal vesicles, multivesicular body (MVB) sorting, is critical for receptor down regulation, antigen presentation and enveloped virus budding. Vps4 is an AAA ATPase that functions in MVB sorting. Although AAA ATPases are oligomeric, mechanisms that govern Vps4 oligomerization and activity remain elusive. Vps4 has an N-terminal microtubule interacting and trafficking domain required for endosome recruitment, an AAA domain containing the ATPase catalytic site and a , domain, and a C-terminal , helix positioned close to the catalytic site in the 3D structure. Previous attempts to identify the role of the C-terminal helix have been unsuccessful. Here, we show that the C-terminal helix is important for Vps4 assembly and ATPase activity in vitro and function in vivo, but not endosome recruitment or interactions with Vta1 or ESCRT-III. Unlike the , domain, which is also important for Vps4 assembly, the C-terminal helix is not required in vivo for Vps4 homotypic interaction or dominant-negative effects of Vps4,E233Q, carrying a mutation in the ATP hydrolysis site. Vta1 promotes assembly of hybrid complexes comprising Vps4,E233Q and Vps4 lacking an intact C-terminal helix in vitro. Formation of catalytically active hybrid complexes demonstrates an intersubunit catalytic mechanism for Vps4. One end of the C-terminal helix lies in close proximity to the second region of homology (SRH), which is important for assembly and intersubunit catalysis in AAA ATPases. We propose that Vps4 SRH function requires an intact C-terminal helix. Co-evolution of a distinct Vps4 SRH and C-terminal helix in meiotic clade AAA ATPases supports this possibility. [source] Order of genetic events is critical determinant of aberrations in chromosome count and structureGENES, CHROMOSOMES AND CANCER, Issue 4 2004Christine Fauth A sequential acquisition of genetic events is critical in tumorigenesis. A key step is the attainment of infinite proliferative potential. Acquisition of this immortalization requires the activation of telomerase in addition to other activities, including inactivation of TP53 and the retinoblastoma family of tumor-suppressor proteins. However, the importance of the order in which these genetic events occur has not been established. To address this question, we used a panel of normal mammary fibroblasts and endothelial cultures that were immortalized after transduction with the catalytic subunit of telomerase (hTERT) and a temperature-sensitive mutant of the SV40 large-tumor (tsLT) oncoprotein in different orders in early- and late-passage stocks. These lines were maintained in continuous culture for up to 90 passages, equivalent to >300 population doublings (PDs) post-explantation during 3 years of continuous propagation. We karyotyped the cultures at different passages. Cultures that received hTERT first followed by tsLT maintained a near-diploid karyotype for more than 150 PDs. However, in late-passage stocks (>200 PDs), metaphase cells were mostly aneuploid. In contrast, the reverse order of gene transduction resulted in a marked early aneuploidy and chromosomal instability, already visible after 50 PDs. These results suggest that the order of genetic mutations is a critical determinant of chromosome count and structural aberration events. © 2004 Wiley-Liss, Inc. [source] Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: Interaction with IL-10 gene polymorphismsHEPATOLOGY, Issue 3 2007Koko Bate Aborsangaya The host immune response is a critical determinant in viral infection outcome. Epidemiological studies indicate that North American indigenous peoples are more resistant to chronic HCV infection than other populations. Due to the prominence of IL-10 in chronic HCV infection, we investigated the genetic tendency to produce IL-10 in Caucasian (CA) and First Nation (FN) populations. Peripheral blood mononuclear cells (PBMCs) from CA subjects had a greater tendency to produce IL-10 defined by allelic polymorphisms, as well as genotypes and haplotypes, at the -1082, -819, and -592 positions of the IL-10 promoter. More importantly, we directly evaluated the influence of ethnicity on the ability of HCV core protein to induce IL-10 synthesis and found significantly higher IL-10 production by PBMCs isolated from healthy CA subjects compared with FN subjects. Further examination of the underlying relationship between core-induced IL-10 with the high, intermediate, and low phenotypes at the -1082, -819, and -592 position revealed that spontaneous and core-induced IL-10 synthesis tended to interact negatively with defined polymorphisms. This was particularly evident for the FN cohort, in which the relationship was strengthened by a stronger interaction of core with the low,IL-10,producing phenotypes. As with previous studies, concanavalin A induced IL-10 synthesis from the CA cohort positively associated with defined genetic phenotypes. Conclusion: Cells from FN subjects had a reduced capacity to produce IL-10 in response to HCV core protein, suggesting that reduced susceptibility of FN immunity to virally induced IL-10 synthesis might contribute to epidemiological observations of enhanced HCV clearance. (HEPATOLOGY 2007;45:623,630.) [source] Application of devices for safe laparoscopic hepatectomyHPB, Issue 4 2008H. KANEKO Abstract The continuing evolution of a variety of laparoscopic instrument and device has been gradually applied to the laparoscopic hepatectomy in many countries. Recent experience has persuaded us that there are great potential benefits derived from laparoscopic hepatectomy and much has been learned about patient selection, the grade of surgical difficulty with respect to tumor location, and the required instrumentation. Among these efforts, various ways of hepatic parenchymal transection with mechanical devices have been attempted and continuing to innovate to perform safe laparoscopic hepatectomy Important technologic developments and improved endoscopic procedures are being established equipment modifications. For safe laparoscopic hepatectomy, it is important to have all necessary equipment. The intraoperative laparoscopic ultrasonography, microwave coagulators, ultrasonic dissection, argon beam coagulators, laparoscopic coagulation shears, endolinear staplers and TissueLink monopolar sealer are essential. This procedure is in need that well experienced endoscopic surgeon and well-experienced liver surgeon should be collaborated in laparoscopic hepatectomy and the indications are strictly followed based upon the location and size of tumors. Finally critical determinant for success and safe laparoscopic hepatectomy is through familiarity with the relevant laparoscopic instruments and equipments. Laparoscopic hepatectomy is expected to develop further in the future as a new surgical instrument, equipment and method, which improves patients' quality of life. [source] Hilar cholangiocarcinoma: diagnosis and stagingHPB, Issue 4 2005William Jarnagin Cancer arising from the proximal biliary tree, or hilar cholangiocarcinoma, remains a difficult clinical problem. Significant experience with these uncommon tumors has been limited to a small number of centers, which has greatly hindered progress. Complete resection of hilar cholangiocarcinoma is the most effective and only potentially curative therapy, and it now clear that concomitant hepatic resection is required in most cases. Simply stated, long-term survival is generally possible only with an en bloc resection of the liver with the extrahepatic biliary apparatus, leaving behind a well perfused liver remnant with adequate biliary-enteric drainage. Preoperative imaging studies should aim to assess this possibility and must evaluate a number of tumor-related factors that influence resectability. Advances in imaging technology have improved patient selection, but a large proportion of patients are found to have unresectable disease only at the time of exploration. Staging laparoscopy and 13fluoro-deoxyglucose positron emission tomography (FDG-PET) may help to identify some patients with advanced disease; however, local tumor extent, an equally critical determinant of resectability, may be underestimated on preoperative studies. This paper reviews issues pertaining to diagnosis and preoperative evaluation of patients with hilar biliary obstruction. Knowledge of the imaging features of hilar tumors, particularly as they pertain to resectability, is of obvious importance for clinicians managing these patients. [source] ,-Arrestin 2 regulates toll-like receptor 4-mediated apoptotic signalling through glycogen synthase kinase-3,IMMUNOLOGY, Issue 4 2010Hui Li Summary Toll-like receptor 4 (TLR4), a key member of the TLR family, has been well characterized by its function in the induction of inflammatory products of innate immunity. However, the involvement of TLR4 in a variety of apoptotic events by an unknown mechanism has been the focus of great interest. Our investigation found that TLR4 promoted apoptotic signalling by affecting the glycogen synthase kinase-3, (GSK-3,) pathway in a serum-deprivation-induced apoptotic paradigm. Serum deprivation induces GSK-3, activation in a pathway that leads to subsequent cell apoptosis. Intriguingly, this apoptotic cascade is amplified in presence of TLR4 but greatly attenuated by ,-arrestin 2, another critical molecule implicated in TLR4-mediated immune responses. Our data suggest that the association of ,-arrestin 2 with GSK-3, contributes to the stabilization of phospho-GSK-3,, an inactive form of GSK-3,. It becomes a critical determinant for the attenuation of TLR4-initiated apoptosis by ,-arrestin 2. Taken together, we demonstrate that the TLR4 possesses the capability of accelerating GSK-3, activation thereby deteriorating serum-deprivation-induced apoptosis; ,-arrestin 2 represents an inhibitory effect on the TLR4-mediated apoptotic cascade, through controlling the homeostasis of activation and inactivation of GSK-3,. [source] The p38 mitogen-activated protein kinase regulates interleukin-1,-induced IL-8 expression via an effect on the IL-8 promoter in intestinal epithelial cellsIMMUNOLOGY, Issue 4 2003Kuljit Parhar Summary Several lines of evidence implicate the p38 mitogen-activated protein kinase (p38 MAPK) in the proinflammatory response to bacterial agents and cytokines. Equally, the transcription factor, nuclear factor (NF)-,B, is recognized to be a critical determinant of the inflammatory response in intestinal epithelial cells (IECs). However, the precise inter-relationship between the activation of p38 MAPK and activation of the transcription factor NF-,B in the intestinal epithelial cell (IEC) system, remains unknown. Here we show that interleukin (IL)-1, activates all three MAPKs in Caco-2 cells. The production of IL-8 and monocyte chemotactic protein 1 (MCP-1) was attenuated by 50% when these cells were preincubated with the p38 MAPK inhibitor, SB 203580. Further investigation of the NF-,B signalling system revealed that the inhibitory effect was independent of the phosphorylation and degradation of I,B,, the binding partner of NF-,B. This effect was also independent of the DNA binding of the p65 Rel A subunit, as well as transactivation, determined by an NF-,B luciferase construct, using both SB 203580 and dominant,negative p38 MAPK. Evaluation of IL-8 and MCP-1 RNA messages by reverse transcription,polymerase chain reaction (RT,PCR) revealed that the inhibitory effect of SB 203580 was associated with a reduction in this parameter. Using an IL-8,luciferase promoter construct, an effect of p38 upon its activation by both pharmacological and dominant,negative p38 construct co-transfection was demonstrated. It is concluded that p38 MAPK influences the expression of chemokines in intestinal epithelial cells, through an effect upon the activation of the chemokine promoter, and does not directly involve the activation of the transcription factor NF-,B. [source] Telomere Higher-Order Structure and Genomic InstabilityIUBMB LIFE, Issue 8 2003Terace Fletcher Abstract Telomeres, nucleoprotein complexes at the end of eukaryotic chromosomes, have vital roles in chromosome integrity. Telomere chromatin structure is both intricate and dynamic allowing for a variety of responses to several stimuli. A critical determinant in telomere structure is the G-strand overhang. Facilitated by telomeric proteins, the G-strand overhang stabilizes telomere higher-order assemblies most likely by adopting unusual DNA structures. These structures influence activities that occur at the chromosome end. Dysfunctional telomeres induce signals resulting in cell growth arrest or death. To overcome telomere dysfunction, cancer cells activate the DNA polymerase, telomerase. The presence of telomerase at the telomere may establish a particular telomeric state. If the chromosome ends of cancer and normal cells exist in different states, cancer-specific telomere structures would offer a unique chemotherapeutic target. IUBMB Life, 55: 443-449, 2003 [source] Perspective: Quantifying Osteoblast and Osteocyte Apoptosis: Challenges and Rewards,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007Robert L Jilka Abstract Since the initial demonstration of the phenomenon in murine and human bone sections ,10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass. The detection of apoptotic osteoblasts in bone sections remains challenging because apoptosis represents only a tiny fraction of the life span of osteoblasts, not unlike a 6-mo -long terminal illness in the life of a 75-yr -old human. Importantly, the phenomenon is 50 times less common in human bone biopsies because human osteoblasts live longer and are fewer in number. Be that as it may, well-controlled assays of apoptosis can yield accurate and reproducible estimates of the prevalence of the event, particularly in rodents where there is an abundance of osteoblasts for inspection. In this perspective, we focus on the biological significance of the phenomenon for understanding basic bone biology and the pathogenesis and treatment of metabolic bone diseases and discuss limitations of existing techniques for quantifying osteoblast apoptosis in human biopsies and their methodologic pitfalls. [source] Quantity and Quality of Trabecular Bone in the Femur Are Enhanced by a Strongly Anabolic, Noninvasive Mechanical InterventionJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2002Clinton Rubin Ph.D. Abstract The skeleton's sensitivity to mechanical stimuli represents a critical determinant of bone mass and morphology. We have proposed that the extremely low level (<10 microstrain), high frequency (20-50 Hz) mechanical strains, continually present during even subtle activities such as standing are as important to defining the skeleton as the larger strains typically associated with vigorous activity (>2000 microstrain). If these low-level strains are indeed anabolic, then this sensitivity could serve as the basis for a biomechanically based intervention for osteoporosis. To evaluate this hypothesis, the hindlimbs of adult female sheep were stimulated for 20 minutes/day using a noninvasive 0.3g vertical oscillation sufficient to induce approximately 5 microstrain on the cortex of the tibia. After 1 year of stimulation, the physical properties of 10-mm cubes of trabecular bone from the distal femoral condyle of experimental animals (n = 8) were compared with controls (n = 9), as evaluated using microcomputed tomography (,CT) scanning and materials testing. Bone mineral content (BMC) was 10.6% greater (p < 0.05), and the trabecular number (Tb.N) was 8.3% higher in the experimental animals (p < 0.01), and trabecular spacing decreased by 11.3% (p < 0.01), indicating that bone quantity was increased both by the creation of new trabeculae and the thickening of existing trabeculae. The trabecular bone pattern factor (TBPf) decreased 24.2% (p < 0.03), indicating trabecular morphology adapting from rod shape to plate shape. Significant increases in stiffness and strength were observed in the longitudinal direction (12.1% and 26.7%, respectively; both, p < 0.05), indicating that the adaptation occurred primarily in the plane of weightbearing. These results show that extremely low level mechanical stimuli improve both the quantity and the quality of trabecular bone. That these deformations are several orders of magnitude below those peak strains which arise during vigorous activity indicates that this biomechanically based signal may serve as an effective intervention for osteoporosis. [source] PR-39 coordinates changes in vascular smooth muscle cell adhesive strength and locomotion by modulating cell surface heparan sulfate,matrix interactionsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2001John H. Chon PR-39 is proline-rich peptide produced at sites of tissue injury. While the functional properties of this peptide have not been fully defined, PR-39 may be an important regulator of processes related to cell-matrix adhesion since it reportedly upregulates syndecan-4, which is a critical determinant of focal adhesion formation. The ability of PR-39 to modulate the adhesion and chemokinetic migration behavior of arterial smooth muscle cells (SMCs) in a fashion coordinated with syndecan-4 expression was investigated. Treatment of SMCs with PR-39 did not alter syndecan-1 mRNA, but did induce a two-fold increase in syndecan-4 mRNA (P,<,0.0001) and significantly enhanced cell surface expression of both syndecan-4 (P,<,0.01) and heparan sulfate (HS) (P,<,0.05). These observations were consistent with an observed increase in cell-matrix adhesive strength (P,<,0.05) and a reduction in cell speed (P,<,0.01) on fibronectin-coated substrates. Incubation of PR-39 treated cells with a soluble fibronectin derived heparin-binding peptide, as a competitive inhibitor of heparan sulfate/matrix interactions, abolished these effects. These data suggest that PR-39 mediated alterations of cell adhesion and motility may be related, in part, to the increased expression of heparan sulfate glycosaminoglycans (GAGs) that accompany the upregulation of cell surface syndecan-4. Futhermore, this investigation supports the notion that factors which control syndecan-4 expression may play an important role in regulating adhesion related cell processes. © 2001 Wiley-Liss, Inc. [source] Pharmacokinetic aspects of biotechnology productsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2004Lisa Tang Abstract In recent years, biotechnologically derived peptide and protein-based drugs have developed into mainstream therapeutic agents. Peptide and protein drugs now constitute a substantial portion of the compounds under preclinical and clinical development in the global pharmaceutical industry. Pharmacokinetic and exposure/response evaluations for peptide and protein therapeutics are frequently complicated by their similarity to endogenous peptides and proteins as well as protein nutrients. The first challenge frequently comes from a lack of sophistication in various analytical techniques for the quantification of peptide and protein drugs in biological matrices. However, advancements in bioassays and immunoassays,along with a newer generation of mass spectrometry-based techniques,can often provide capabilities for both efficient and reliable detection. Selection of the most appropriate route of administration for biotech drugs requires comprehensive knowledge of their absorption characteristics beyond physicochemical properties, including chemical and metabolic stability at the absorption site, immunoreactivity, passage through biomembranes, and active uptake and exsorption processes. Various distribution properties dictate whether peptide and protein therapeutics can reach optimum target site exposure to exert the intended pharmacological response. This poses a potential problem, especially for large protein drugs, with their typically limited distribution space. Binding phenomena and receptor-mediated cellular uptake may further complicate this issue. Elimination processes,a critical determinant for the drug's systemic exposure,may follow a combination of numerous pathways, including renal and hepatic metabolism routes as well as generalized proteolysis and receptor-mediated endocytosis. Pharmacokinetic/pharmacodynamic (PK/PD) correlations for peptide and protein-based drugs are frequently convoluted by their close interaction with endogenous substances and physiologic regulatory feedback mechanisms. Extensive use of pharmacokinetic and exposure/response concepts in all phases of drug development has in the past been identified as a crucial factor for the success of a scientifically driven, evidence-based, and thus accelerated drug development process. Thus, PK/PD concepts are likely to continue and expand their role as a fundamental factor in the successful development of biotechnologically derived drug products in the future. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2184,2204, 2004 [source] Emergent Negotiations: Stability and Shifts in Negotiation DynamicsNEGOTIATION AND CONFLICT MANAGEMENT RESEARCH, Issue 2 2008Mara Olekalns Abstract Negotiation is a dynamic process in which negotiators change their strategies in response to each other. We believe mutual adaptation is best conceptualized as an emergent process and is a critical determinant of negotiators' abilities to identify mutually beneficial solutions. We argue that three factors drive the process of negotiation and influence the quality of agreements: alignment of negotiators' strategies across individuals (strategy sequences), alignment of negotiators' strategies with the negotiation-wide dynamic (phases), and congruence of negotiators' goals. [source] Relationships across multiple settings: An overviewNEW DIRECTIONS FOR YOUTH DEVELOPMENT, Issue 103 2004Gil G. Noam The quality and perception of the relationship between patient and therapist, student and teacher, mentee and mentor, and youth and youth worker is the most critical determinant of success in a myriad of fields. [source] Predicting invertebrate diversity from disturbance regimes in forest streamsOIKOS, Issue 1 2002Russell G. Death The link between substrate disturbance and stream invertebrate species richness is often complicated by the fact that substrate disturbance removes both invertebrates and periphyton (a potential food source). It is never clear whether disturbance acts directly on species diversity by removing animals or indirectly by reducing one of their food sources. To examine this relationship invertebrate diversity patterns were examined in 25 forest streams in Urewera National Park, New Zealand, where light attenuation from the forest canopy was postulated to limit periphyton biomass and remove the confounding influence of periphyton on the link between substrate disturbance and invertebrate diversity. Invertebrate species richness declined linearly with increasing substrate disturbance. Although periphyton biomass was comparatively low, species richness was more strongly related to periphyton biomass than to any disturbance measure. The highly mobile nature and terrestrial reproductive stage of many lotic invertebrates suggest that colonisation dynamics may have a more important influence on diversity patterns than monopolisation of resources for population growth. Although both the intermediate disturbance hypothesis and the dynamic equilibrium model encompass colonisation as a critical determinant of diversity both models also require a trade-off between the colonising and competitive ability of individual species; a phenomenon which does not appear to occur widely in lotic communities. Rather, it is postulated that resource levels will set an upper limit to the species richness of a benthic community that can be achieved through colonisation of taxa in the absence of disturbance, while disturbance removes taxa and resets the colonisation process. [source] On-line waiting: The role of download time and other important predictors on attitude toward e-retailersPSYCHOLOGY & MARKETING, Issue 2 2005Gregory M. Rose Across both marketing and management-information-system disciplines, download time has been identified as an important factor for on-line business success. This research is intended to clarify counterintuitive findings generated from previous research and Web-based experimentation. Here the roles of several factors, including download time, on the overall evaluation of an e-retailer are explored. With an experimental design, the article explores the impact of 5-, 30-, and 45-second download delays on attitude toward an e-retailer. Consistent with prior works, findings from both a main study and replication study indicate that objective download delay is not a critical determinant of attitude toward an e-retailer. However, findings show there are other direct and indirect delay effects, including those resulting from perceived retailer control of delay, that impact Web-system success. © 2005 Wiley Periodicals, Inc. [source] Tax Reform and ProgressivityTHE ECONOMIC JOURNAL, Issue 460 2000Michael Keen The established theory of tax progressivity cannot handle basic tax reform questions, such as whether an increase in personal allowances makes the tax system more progressive, because the core results assume that tax liability is never zero. This paper generalises the core theory to allow for zero tax payments, and applies the new framework to the analysis of allowances, income-related deductions and tax credits. Log concavity of the tax schedule,a property quite distinct from any existing notion of progressivity,emerges as the critical determinant of whether the distribution of the tax burden becomes more progressive as allowances are increased. [source] REVIEW ARTICLE: HIV Infection in the Female Genital Tract: Discrete Influence of the Local Mucosal MicroenvironmentAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Charu Kaushic Citation Kaushic C, Ferreira VH, Kafka JK, Nazli A. HIV infection in the female genital tract: discrete influence of the local mucosal microenvironment. Am J Reprod Immunol 2010 Women acquire HIV infections predominantly at the genital mucosa through heterosexual transmission. Therefore, the immune milieu at female genital surfaces is a critical determinant of HIV susceptibility. In this review, we recapitulate the evidence suggesting that several distinctive innate immune mechanisms in the female genital tract (FGT) serve to significantly deter or facilitate HIV-1 infection. Epithelial cells lining the FGT play a key role in forming a primary barrier to HIV entry. These cells express Toll-like receptors and other receptors that recognize and respond directly to pathogens, including HIV-1. In addition, innate biological factors produced by epithelial and other cells in the FGT have anti-HIV activity. Female sex hormones, co-infection with other pathogens and components in semen may also exacerbate or down-modulate HIV transmission. A combination of innate and adaptive immune factors and their interactions with the local microenvironment determine the outcome of HIV transmission. Improving our understanding of the female genital microenvironment will be useful in developing treatments that augment and sustain protective immune responses in the genital mucosa, such as microbicides and vaccines, and will provide greater insight into viral pathogenesis in the FGT. [source] Correlation of Local Interleukin-1beta Levels with Specific IgA Response Against Gardnerella vaginalis Cytolysin in Women with Bacterial VaginosisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2002SABINA CAUCI PROBLEM:,Mucosal immune system activation may represent a critical determinant of adverse sequelae correlated with bacterial vaginosis, as HIV sexual transmission, upper genital tract infections, cervicitis, endometritis, postsurgical infections, and adverse pregnancy outcomes as preterm delivery (PTD), low birth weight (LBW). METHOD OF STUDY:,Levels of interleukin-1beta (IL-1beta), anti- Gardnerella vaginalis hemolysin (Gvh) IgA, pH, Nugent score, and number of leukocytes were measured in vaginal fluids of 60 fertile women with bacterial vaginosis and of 64 healthy controls. RESULTS:,Vaginal IL-1beta levels were nearly 13-fold higher in women with bacterial vaginosis (BV) and were associated with anti-Gvh IgA response. IL-1beta was positively correlated with leukocyte counts in the smear both in healthy and bacterial vaginosis positive women. CONCLUSIONS:,Induction of the proinflammatory cytokine IL-1beta may be a necessary event to elicit an innate immune response to control anaerobic genital tract infections. High levels of vaginal IL-1beta are associated with mounting of an antigen-specific mucosal immune response in women with bacterial vaginosis. Parallel induction of innate and adaptive immune response may be associated with protection from ascent of micro-organisms to the upper genital tract, and from acquiring viral infection through the vaginal tract. [source] Human Islet Isolation for Autologous Transplantation: Comparison of Yield and Function Using SERVA/Nordmark Versus Roche EnzymesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009T. Anazawa Islet autotransplantation (IAT) is used to preserve as much insulin-secretory capacity as possible in patients undergoing total pancreatectomy for painful chronic pancreatitis. The enzyme used to dissociate the pancreas is a critical determinant of islet yield, which is correlated with posttransplant function. Here, we present our experience with IAT procedures to compare islet product data using the new enzyme SERVA/Nordmark (SN group; n = 46) with the standard enzyme Liberase-HI (LH group; n = 40). Total islet yields (mean ± standard deviation; 216 417 ± 79 278 islet equivalent [IEQ] in the LH group; 227 958 ± 58 544 IEQ in the SN group; p = 0.67) were similar. However, the percentage of embedded islets is higher in the SN group compared to the LH group. Significant differences were found in pancreas digestion time, dilution time, and digested pancreas weight between the two groups. Multivariate linear regression analysis showed the two groups differed in portal venous pressure changes. The incidence of graft function and insulin independence was not different between the two groups. The SN and LH enzymes are associated with similar outcomes for IAT. Further optimization of the collagenase/neutral protease ratio is necessary to reduce the number of embedded islets obtained when using the SN enzyme. [source] Reassessing the Impact of Donor HLA-C Genotype on Long-Term Liver Transplant SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009T. H. Tran HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIRs) that are expressed on natural killer (NK) cells. Based on their KIR specificity, HLA-C alleles can be divided into two groups, termed HLA-C1 and HLA-C2. Donor HLA-C group has recently been identified by Hanvesakul et al. (Am J Transplant 2008) as a critical determinant of clinical outcome following liver transplantation: Possession of at least one HLA-C group 2 allele by the donor was associated with significantly improved long-term graft and patient survival, presumably due to an inhibition of host NK cell function. To verify this study, we performed genotyping of 913 deceased liver donors for the relevant KIR epitopes of HLA-C and correlated the presence or absence of donor HLA-C2 genotype with graft and patient survival. In our study, donor HLA-C2 genotype had no impact on 10-year graft or patient survival. We cannot confirm a major role of donor HLA-C2 genotype on long-term allograft survival after liver transplantation. [source] The role of importance/consequentiality appraisal in flashbulb memory formation: the case of the death of Pope John Paul IIAPPLIED COGNITIVE PSYCHOLOGY, Issue 2 2009Carla Tinti This study investigates how flashbulb memories (FBMs) relative to the death of Pope John Paul II vary according to the persons' evaluation of the event's importance and consequences. In particular, FBMs were investigated in persons who were expected to attribute different degrees of importance/consequentiality to the event as a function of two factors: (1) religious involvement, (2) nationality (Polish, Italian, Swiss). The comparison was made with respect to the following hypothesized determinants of FBMs: surprise, emotional reaction, rehearsal, event memory and especially the attitudes towards the Pope and the appraisal of the importance and the consequences of his death. Structural equation modelling indicates that importance/consequentiality is a fundamental determinant of FBM and is influenced by antecedent personal and social characteristics reflected in the person's attitudes. Moreover, memory consistency seems to be both directly influenced by emotional intensity and indirectly through rehearsal, whereas surprise seems not a critical determinant of FBM. Copyright © 2008 John Wiley & Sons, Ltd. [source] Dihydrosphingosine 1-phosphate has a potent antifibrotic effect in scleroderma fibroblasts via normalization of phosphatase and tensin homolog levelsARTHRITIS & RHEUMATISM, Issue 7 2010Shizhong Bu Objective Previous studies have revealed a phosphatase and tensin homolog (PTEN),dependent interaction between the sphingolipid agonist dihydrosphingosine 1-phosphate (dhS1P) and the transforming growth factor ,/Smad3 signaling pathway. This study was undertaken to examine responses of systemic sclerosis (SSc) fibroblasts to sphingosine 1-phosphate (S1P) and dhS1P and to gain further insight into the regulation of the S1P/dhS1P/PTEN pathway in SSc fibrosis. Methods Fibroblast cultures were established from skin biopsy samples obtained from patients with SSc and matched healthy controls. Western blotting and quantitative polymerase chain reaction were used to measure protein and messenger RNA levels, respectively. PTEN protein was examined in skin biopsy samples by immunohistochemistry. Results PTEN protein levels were low in SSc fibroblasts and correlated with elevated levels of collagen and phospho-Smad3 and reduced levels of matrix metalloproteinase 1 (MMP-1). Treatment with dhS1P restored PTEN levels and normalized collagen and MMP-1 expression, as well as Smad3 phosphorylation status in SSc fibroblasts. S1P was strongly profibrotic in SSc and control fibroblasts. Distribution of S1P receptor isoforms was altered in SSc fibroblasts, which had reduced levels of S1P receptor 1 and S1P receptor 2 and elevated levels of S1P receptor 3. Only depletion of S1P receptor 1 abrogated the effects of dhS1P and S1P in control dermal fibroblasts. In contrast, depletion of either S1P receptor 1 or S1P receptor 2 prevented the effects of S1P and dhS1P in SSc fibroblasts. Conclusion Our findings demonstrate that PTEN deficiency is a critical determinant of the profibrotic phenotype of SSc fibroblasts. The antifibrotic effect of dhS1P is mediated through normalization of PTEN expression, suggesting that dhS1P or its derivatives may be effective as therapeutic antifibrotic agents. The distribution and function of S1P receptors differ in SSc and healthy fibroblasts, suggesting that alteration in the sphingolipid signaling pathway may contribute to SSc fibrosis. [source] Experimental manipulation reveals the importance of refuge habitat temperature selected by lizardsAUSTRAL ECOLOGY, Issue 3 2010MICHA ANDERSSON Abstract Refuges provide shelter from predators, and protection from exposure to the elements, as well as other fitness benefits to animals that use them. In ectotherms, thermal benefits may be a critical aspect of refuges. We investigated microhabitat characteristics of refuges selected by a heliothermic scincid lizard, Carlia rubrigularis, which uses rainforest edges as habitat. We approached lizards in the field, simulating a predator attack, and quantified the refuge type used, and effect of environmental temperatures (air temperature, substrate temperature and refuge substrate temperature) on the amount of time skinks remained in refuges after hiding (emergence time). In respone to our approach, lizards were most likely to flee into leaf litter, rather than into rocks or woody debris, and emergence time was dependent on refuge substrate temperature, and on refuge substrate temperature relative to substrate temperature outside the refuge. Lizards remained for longer periods in warmer refuges, and in refuges that were similar in temperature to outside. We examined lizard refuge choice in response to temperature and substrate type in large, semi-natural outdoor enclosures. We experimentally manipulated refuge habitat temperature available to lizards, and offered them equal areas of leaf litter, woody debris and rocks. When refuge habitat temperature was unmanipulated, lizards (85%) preferred leaf litter, as they did in the field. However, when we experimentally manipulated the temperature of the leaf litter by shading, most skinks (75%) changed their preferred refuge habitat from leaf litter to woody debris or rocks. These results suggest that temperature is a critical determinant of refuge habitat choice for these diurnal ectotherms, both when fleeing from predators and when selecting daytime retreats. [source] A comparison of international occupational therapy competencies: Implications for Australian standards in the new millenniumAUSTRALIAN OCCUPATIONAL THERAPY JOURNAL, Issue 6 2009Sylvia Rodger Background/aim:, A timely evaluation of the Australian Competency Standards for Entry-Level Occupational Therapists© (1994) was conducted. This thorough investigation comprised a literature review exploring the concept of competence and the applications of competency standards; systematic benchmarking of the Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) against other national and international competency standards and other affiliated documents, from occupational therapy and other cognate disciplines; and extensive nationwide consultation with the professional community. This paper explores and examines the similarities and disparities between occupational therapy competency standards documents available in English from Australia and other countries. Methods:, An online search for national occupational therapy competency standards located 10 documents, including the Australian competencies. Results:, Four ,frameworks' were created to categorise the documents according to their conceptual underpinnings: Technical-Prescriptive, Enabling, Educational and Meta-Cognitive. Other characteristics that appeared to impact the design, content and implementation of competency standards, including definitions of key concepts, authorship, national and cultural priorities, scope of services, intended use and review mechanisms, were revealed. Conclusion:, The proposed ,frameworks' and identification of influential characteristics provided a ,lens' through which to understand and evaluate competency standards. While consistent application of and attention to some of these characteristics appear to consolidate and affirm the authority of competency standards, it is suggested that the national context should be a critical determinant of the design and content of the final document. The Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) are critiqued accordingly, and preliminary recommendations for revision are proposed. [source] | ||||||||||||||||||||||||||||||||||