Work stressors, role-based performance, and the moderating influence of organizational support.

As a test of the 2-dimensional model of work stressors, the present study proposed differential relationships between challenge stressors and hindrance stressors and role-based performance, which were expected to be moderated by organizational support. In a sample of 215 employees across 61 offices of a state agency, the authors obtained a positive relationship between challenge stressors and role-based performance and a negative relationship between hindrance stressors and role-based performance. In addition, organizational support moderated the relationship between challenge stressors and role-based performance but did not moderate the relationship between hindrance stressors and role-based performance. This suggests that organizations would benefit from increasing challenges in the workplace as long as they are supportive of employees and removing hindrances. Further implications for organizational theory and practice are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers

Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies.     

A component-based parallel infrastructure for the simulation of fluid–structure interaction

The Uintah computational framework is a component-based infrastructure, designed for highly parallel simulations of complex fluid–structure interaction problems. Uintah utilizes an abstract representation of parallel computation and communication to express data dependencies between multiple physics components. These features allow parallelism to be integrated between multiple components while maintaining overall scalability. Uintah provides mechanisms for load-balancing, data communication, data I/O, and checkpoint/restart. The underlying infrastructure is designed to accommodate a range of PDE solution methods. The primary techniques described here, are the material point method (MPM) for structural mechanics and a multi-material fluid mechanics capability. MPM employs a particle-based representation of solid materials that interact through a semi-structured background grid. We describe a scalable infrastructure for problems with large deformation, high strain rates, and complex material behavior. Uintah is a product of the University of Utah Center for Accidental Fires and Explosions (C-SAFE), a DOE-funded Center of Excellence. This approach has been used to simulate numerous complex problems, including the response of energetic devices subject to harsh environments such as hydrocarbon pool fires. This scenario involves a wide range of length and time scales including a relatively slow heating phase punctuated by pressurization and rupture of the device.     

Involvement of heme components in sterol metabolism ofSaccharomyces cerevisiae

There is an intimate association between sterol biosynthesis in yeast and aerobicity. Besides the requirement for molecular oxygen for the epoxidation of squalene, cytochrome hemoproteins are involved in demethylation and desaturation steps. Regulatory effects of hemes on sterol formation have been demonstrated using specifically defective mutants of yeast. Heme competency participates in a mechanism whereby wild-type cells are prevented from taking exogenous sterols from the growth media. The multiple interactions of hemes and sterols appear to be associated with the variously defined functions for sterols in the yeast cells. Based on a paper presented at the Symposium on Plant and Fungal Sterols: Biosynthesis, Metabolism and Function, held at the AOCS Annual Meeting, Baltimore, MD, April 1990.     

Adenoma characteristics at first colonoscopy as predictors of adenoma recurrence and characteristics at follow-up. The Polyp Prevention Study Group

In Bacillus transformation, sexual isolation is known to be an exponential function of the sequence divergence between donor and recipient. Here, we have investigated the mechanism under which sequence divergence results in sexual isolation. We tested the effect of mismatch repair by comparing a wild-type strain and an isogenic mismatch-repair mutant for the relationship between sexual isolation and sequence divergence. Mismatch repair was shown to contribute to sexual isolation but was responsible for only a small fraction of the sexual isolation observed. Another possible mechanism of sexual isolation is that more divergent recipient and donor DNA strands have greater difficulty forming a heteroduplex because a region of perfect identity between donor and recipient is required for initiation of the heteroduplex. A mathematical model showed that this heteroduplex-resistance mechanism yields an exponential relationship between sexual isolation and sequence divergence. Moreover, this model yields an estimate of the size of the region of perfect identity that is comparable to independent estimates for Escherichia coli. For these reasons, and because all other mechanisms of sexual isolation may be ruled out, we conclude that resistance to heteroduplex formation is predominantly responsible for the exponential relationship between sexual isolation and sequence divergence in Bacillus transformation.     

Long-term expression and secretion of human glucocerebrosidase by primary murine and human myoblasts and differentiated myotubes

The majority of studies dealing with DNA analyses are made on fixed cells. In this context, the efficiency as fixatives of ethanol, methanol, acetone, Carnoy, Boehm-Sprenger and aldehydes was determined using two different DNA fluorescent probes, Hoechst 33342 and propidium iodide. The purpose of our study was to find the fixative that would provide the best results with respect to the following parameters: aggregates, cell size and granularity, and DNA staining analysis. Using murine fibroblasts, we found that 68% ethanol, 85% methanol and aldehydes did not increase aggregate formation, whereas Carnoy, acetone or Boehm-Sprenger fixatives did. The results show that aldehydes seem to alter cell size least. All fixatives induce an increase in cell granularity, which is very pronounced with alcohols, but aldehydes alter morphology less than alcohols. We observed that the fixatives giving the best resolution with Hoechst 33342 staining lead to a lower measurement variability than with propidium iodide staining. This study leads us to conclude that 68% ethanol and 85% methanol can be considered as appropriate fixatives for flow cytometry studies of DNA content.     

Single-chain immunotoxins targeted to CD40 for the treatment of human B-lineage hematologic malignancies

Immunotoxins, in chemical conjugate form, have shown limited efficacy in clinical trials in patients with hematologic malignancies. Single-chain immunotoxins (SCIT) provide for enhanced therapeutic efficacy over chemical conjugate forms without additional toxicity and thus may result in improved antitumor activity. We have evaluated two SCITs targeted to CD40, a receptor expressed on most B-lineage hematologic malignancies, for the treatment of non-Hodgkin's lymphoma and multiple myeloma. Both SCITs, G28-5 sFv-PE40 and BD1-G28-5 sFv, were highly potent and specifically cytotoxic against non-Hodgkin's lymphoma and multiple myeloma cell lines. G28-5 sFv-PE40 has proven to be efficacious in SCID mice bearing human non-Hodgkin's lymphoma and multiple myeloma xenografts. Antitumor activity has also been noted in preliminary studies using BD1-G28-5 sFv in non-Hodgkin's lymphoma models. The data presented here indicate that these agents should be considered for use in clinical trials in patients with refractive non-Hodgkin's lymphoma, multiple myeloma and other CD40-expressing hematologic malignancies.     

Lens transmission by fluorophotometry after brachytherapy and thermotherapy of choroidal melanoma

We studied the effect of transpupillary thermotherapy (TTT) by a diode laser at 810 nm combined with episcleral ruthenium-106 plaque treatment (106Ru) on lens transparency in patients with choroidal melanoma. Lens transmission of blue-green light was measured by fluorophotometry in 17 patients treated with 106Ru treatment and TTT (measured 0.36 years after treatment), 12 patients treated with 106Ru alone (measured 19 years after treatment) and 25 age-matched healthy controls. Differences in lens transmission were not significant between treated and untreated fellow eyes (p > 0.15) nor between patient and control eyes (p > 0.25). TTT of choroidal melanoma combined with 106Ru plaque irradiation did not have a significant effect on the lens transparency up to 6 years after treatment.     

Molecular and immunophenotypical characterization of a feline immunodeficiency virus (FIV)-associated lymphoma: a direct role for FIV in B-lymphocyte transformation?

We describe the histopathological, immunohistochemical, and molecular characterization of a lymphoma arising in a 7-year-old cat following experimental infection with feline immunodeficiency virus (FIV). The tumor was high grade and of B-cell lineage. The transformed cell had an immature phenotype (CD79a+, CD79b-, CD21-, immunoglobulin heavy and light chain negative), confirmed by antigen receptor gene analysis, which showed germ line configuration. Single-copy, clonally integrated FIV provirus was detected in tumor genomic DNA. FIV p24 antigen was not detected in tumor cells by immunostaining. This study provides the first evidence that the feline lentivirus may play a direct role in cell transformation under certain circumstances.