Immune and Anticancer Responses Elicited by Fully Synthetic Aberrantly Glycosylated MUC1 Tripartite Vaccines Modified by a TLR2 or TLR9 Agonist

The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O‐linked saccharides. Although tumor‐associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T‐lymphocytes (CTLs) and ADCC‐mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous T_helper peptide, and a TLR2 (Pam₃CysSK₄) or TLR9 (CpG‐ODN 1826) agonist. It was found that the Pam₃CysSK₄‐containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor‐associated glycopeptide. The unique adjuvant properties of Pam₃CysSK₄, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor‐specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1 .     

Trees and wood: working with natural river processes

A history of land clearance and riparian tree and wood management has resulted in limited riparian woodland and wood along British rivers. However, river management approaches are now being promoted that ‘work with natural processes’ to reduce flood risk through measures intended to restore, protect and emulate the natural function of catchments, rivers, estuaries and coasts. Wood has started to be reintroduced into river channels during river restoration and natural flood management activities, but this needs to be undertaken using appropriate quantities, locations and designs that mimic natural tree‐wood features. This paper reviews the knowledge that is needed to support wood reintroduction activities including (i) the characteristics of the riparian tree species and wood that are present; (ii) the importance of river size relative to that of trees and wood pieces; and (iii) the way trees, wood and geomorphic processes interact across rivers and floodplains of different energy and style.     

Housing subsidies and income distribution

While housing subsidy programmes directed through government budgets have become more highly focused on those in need, indirect subsidies operating through the taxation and financial systems have become greater during the inflationary period, and have generally been directed towards those with higher incomes. The Housing Subsidies Study identified several hundred housing assistance programmes in Australia, and after aggregating these to manageable proportions, estimated income distributions for the recipients of each programme.     

Characteristics of Bi-metallic Interfaces Formed During Direct Energy Deposition Additive Manufacturing Processing

Metallurgical and Materials Transactions B - Various additive manufacturing processes are being evaluated to reduce the time and cost for fabrication of low volume, complex, and multifunctional...     

Welding of Very Dissimilar Materials (Fe-Al)

Designers of transportation vehicles (air, land, or sea) continually seek ways to reduce vehicle weight in response to increasing fuel economy mandates, mission requirements, or other competitive pressures. One way to do this is by the selection of material types and their properties based on functional and structural requirements. While these material changes can help meet performance mandates, their implementation in a production environment relies on retaining economic competitiveness. This article traces the history of the various joining processes relevant to the current challenge in joining the very dissimilar families of steel (Fe) and aluminum (Al) alloys.     

Stackable nonvolatile memory with ultra thin polysilicon film and low-leakage (Ti, Dy)xOy for low processing temperature and low operating voltages

We report the fabrication process as well as material and electrical characterization of ultra thin body (UTB) thin film transistors (TFTs) for stackable nonvolatile memories by using in situ phosphorous doped low-temperature polysilicon followed by the chemical mechanical polishing (CMP) process. The resulting polysilicon film is about 13 nm thick with approximately 10¹⁹ cm⁻³ doping. Root mean square surface roughness below 1 nm is achieved. Metal nanocrystals and high-k dielectric are selected for storage nodes and tunneling barriers to achieve low operating voltages. The number density and average diameter of nanocrystals embedded in the gate stack are 7.5 × 10¹¹ cm⁻² and 5.8 nm, respectively. Furthermore, scanning transmission electron microscopy (STEM), convergent beam electron diffraction (CBED) and electron energy loss spectroscopy (EELS) are performed for material characterization. The dielectric constant of the (Ti, Dy)_xO_y film is 35, and the off-state leakage current at −1 V bias and 2.8 nm equivalent oxide thickness is 5 × 10⁻⁷ A/cm². We obtain a memory window of about 0.95 V with ±6 V program/erase voltages. Our results show that UTB TFT is a promising candidate for the three-dimensional integration in high-density nonvolatile memory applications.     

A continual improvement framework with integration of CMMI and six‐sigma model for auto industry

During the recent years, the major driving forces of customer preference, vehicle safety, environmental protection, and flat demand for new cars led to a proliferation of car models and associated price reduction in the auto supply chain. To react to the complex and competitive environment, auto suppliers are urgent to conduct continual improvement (CI) in an effective and systematic way. Thus, this paper presents a framework for CI. The Integrated Development System is proposed to integrate both capability maturity model integration and six‐sigma approach. By implementing the framework, an automaker can establish a solid process‐based management system, identify critical processes, and optimize these processes. For demonstrating the application of this framework, a case study is presented and the result shows that all expected processes' performance targets are achieved, which has dramatically improved by 70% compared with the past records. Apparently, the proposed framework would act as a useful reference to improve an organization's process maturity. Copyright © 2008 John Wiley & Sons, Ltd.     

A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals.

Objective: To evaluate cognitive-behavioral therapy to enhance medication adherence and reduce depression (CBT-AD) in individuals with HIV. Design: A two arm, randomized, controlled, cross-over trial comparing CBT-AD to enhanced treatment as usual only (ETAU). ETAU, which both groups received, included a single-session intervention for adherence and a letter to the patient's provider documenting her or his continued depression. The intervention group also received 10 to 12 sessions of CBT-AD. Main Outcome Measures: Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems (MEMs) and depression as assessed by blinded structured evaluation. Results: At the acute outcome assessment (3-months), those who received CBT-AD evidenced significantly greater improvements in medication adherence and depression relative to the comparison group. Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes. Treatment gains for those in the intervention group were generally maintained at 6- and 12-month follow-up assessments. By the end of the follow-up period, those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations, though these differences did not emerge before the cross-over, and hence there were not between-groups differences. Conclusions: CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence. Replication and extension in larger efficacy trials are needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Choosing Confrontation or Consensus in the Inner City: Lessons from a Community-University Partnership

This article describes the experiences of a Los Angeles inner-city neighbourhood in its attempt for revitalization. The authors headed a Community-University Partnership and worked with graduate students to offer technical support to a neighbourhood-based coalition. The students, local residents, merchants and neighbourhood institutions attempted to follow an asset-based consensus building approach to community development. The article describes the different components of their strategy for physical, economic, cultural and social revitalization, and analyzes the lessons learned from the successes and setbacks of this effort. Finally, the authors discuss some apparent limitations of the asset-based consensus approach.