Rigidized inflatable solar energy concentrators, 1 august 1963 - 25 december 1964

Processes for fabrication in space environment of five-foot diameter inflatable rigidized solar energy concentrator

Structural analysis of Salmonella enterica effector protein SopD

Salmonella outer protein D (SopD) is a type III secreted virulence effector protein from Salmonella enterica. Full-length SopD and SopD lacking 16 amino acids at the N-terminus (SopDDeltaN) have been expressed as fusions with GST in Escherichia coli, purified with a typical yield of 20-30 mg per litre of cell culture and crystallized. Biophysical characterization has been carried out mainly on SopDDeltaN. Analytical size exclusion chromatography shows that SopDDeltaN is monomeric and probably globular in aqueous solution. The secondary structure composition, calculated from the CD spectrum, is mixed (38% alpha-helix and 26% beta-strand). Sequence analysis indicates that SopD contains a coiled coil motif, as found in numerous other type III secretion system-associated proteins. This suggests that SopD has the potential for one or more heterotypic protein-protein interactions. Limited trypsin digestion of SopDDeltaN, monitored by both one-dimensional proton NMR spectroscopy and SDS-PAGE, shows that the protein has a large, protease-resistant core domain of 286 amino acid residues. This single-domain architecture suggests that SopD lacks a cognate chaperone. In crystallization trials, SopDDeltaN produced better crystals than either full-length SopD or trypsin-digested SopDDeltaN. Diffraction to 3.0 Angstrom resolution has so far been obtained from crystals of SopDDeltaN

Drug delivery to the lymphatic system: importance in future cancer diagnosis and therapies

This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Delivery on 2009-08, available online: http://www.tandfonline.com/10.1517/17425240903085128.Cancer is the second leading cause of death in the US. Currently, protocols for cancer treatment include surgery to remove diseased and suspect tissues, focused radiation, systemic chemotherapy, immunotherapy and their combinations. With conventional chemotherapy, it is almost impossible to deliver anticancer drugs specifically to the tumor cells without damaging healthy organs or tissues. Over the past several decades, efforts have been made to improve drug delivery technologies that target anticancer drugs specifically to tumor cells. It has been known for over four decades that the lymphatics are the first site of metastasis for most solid cancers; however, few efforts have been made to localize chemotherapies to lymphatic tissues. Trials of several systemic targeted drug delivery systems based on nanoparticles containing chemotherapeutic agents (e.g., liposomal doxorubicin) have shown similar antitumor activity but better patient tolerance compared with conventional formulations. Animal studies have demonstrated that nanoparticles made of natural or synthetic polymers and liposomal carriers have higher accumulation in the lymph nodes and surrounding lymphatics compared to conventional intravenous therapies. This combination has the potential to both reduce nonspecific organ toxicities and increase the chemotherapeutic dose to the most likely sites of locoregional cancer metastasis

Cognitive change in cognitive-behavioural therapy

BACKGROUND: Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model. METHODS: The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models. RESULTS: Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant. CONCLUSIONS: The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change

The role of outcome expectancy in therapeutic change across psychotherapy versus pharmacotherapy for depression.

BACKGROUND: Patient outcome expectancy - the belief that treatment will lead to an improvement in symptoms - is linked to favourable therapeutic outcomes in major depressive disorder (MDD). The present study extends this literature by investigating the temporal dynamics of expectancy, and by exploring whether expectancy during treatment is linked to differential outcomes across treatment modalities, for both optimistic versus pessimistic expectancy. METHODS: A total of 104 patients with MDD were randomized to receive either cognitive behavioral therapy (CBT) or pharmacotherapy for 16 weeks. Outcome expectancy was measured throughout treatment using the Depression Change Expectancy Scale (DCES). Depression severity was measured using both the Hamilton Depression Rating Scale and Beck Depression Inventory-II. RESULTS: Latent growth curve models supported improvement in expectancy across both treatments. Cross-lagged panel models revealed that both higher optimistic and lower pessimistic expectancy at mid-treatment predicted greater treatment response in pharmacotherapy. For CBT, the associative patterns between expectancy and depression differed as a function of expectancy type; higher optimistic expectancy at pre-treatment and lower pessimistic expectancy at mid-treatment predicted greater treatment response. LIMITATIONS: The sample size limited statistical power and the complexity of models that could be explored. CONCLUSIONS: Results suggest that outcome expectancy improved during treatment for depression. Whether outcome expectancy represents a specific mechanism for the reduction of depression warrants further investigation