Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.     

Protecting local access telecommunications networks: Toward a minimum-cost solution

The problem of designing fibre-optic networks for local-access telecommunications generates (at least) three non-trivial subproblems. In the first of these subproblems one must determine how many fibre-optic cables (fibres) are required at either end of a street. In the next subproblem a minimum-cost network must be designed to support the fibres. The network must also provide distinct paths from either end of the street to the central exchange(s). Finally, the fibre-optic cables must be placed in protective covers. These covers are available in a number of different sizes, allowing some flexibility when covering each section of the network. In this paper we describe a dynamic programming (DP) formulation for finding a minimum-cost (protective) covering for the network (the third of the subproblems). This problem is a generalised set covering problem with side constraints and is further complicated by the introduction of fixed and variable welding costs. The DP formulation selects covers along each arc (in the network), but cannot exactly model the fixed costs and so does not guarantee optimality. We also describe an integer programming (IP) formulation for assessing the quality of the DP solutions. The cost of the networks constructed by the IP model is less than those designed using the DP model, but the saving is not significant for the problems examined (less than 0.1%). This indicates that the DP model will generally give very good solutions. Furthermore, as the problem dimensions grow, DP gives significantly better solution times than IP.     

Life is pleasant--and memory helps to keep it that way!

People's recollections of the past are often positively biased. This bias has 2 causes. The 1st cause lies in people's perceptions of events. The authors review the results of several studies and present several new comparative analyses of these studies, all of which indicate that people perceive events in their lives to more often be pleasant than unpleasant. A 2nd cause is the fading affect bias: The affect associated with unpleasant events fades faster than the affect associated with pleasant events. The authors review the results of several studies documenting this bias and present evidence indicating that dysphoria (mild depression) disrupts such bias. Taken together, this evidence suggests that autobiographical memory represents an important exception to the theoretical claim that bad is stronger than good. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Large deflection dynamics and control for planar continuum robots

This paper focuses on a class of robot manipulators termed "continuum" robots - robots that exhibit behavior similar to tentacles, trunks, and snakes. In previous work, we studied details of the mechanical design, kinematics, path-planning and small-deflection dynamics for continuum robots such as the Clemson "tentacle manipulator". In this paper, we discuss the dynamics of a planar continuum backbone section, incorporating a large-deflection dynamic model. Based on these dynamics, we formulate a vibration-damping setpoint controller, and include experimental results to illustrate the efficacy of the proposed controller.     

Analysis of volatiles evolved during high-temperature treatment of thermally stable polymers. I. Nitrogen-containing acetylene-terminated resin

Cured samples of a nitrogen-containing acetylene-terminated resin, N,N′-(1,3-phenylene-dimethylidene)bis(3-ethynylaniline), have been heated at 10°C/min up to 900°C in a pyroprobe attached to a gas chromatograph/mass spectrometer (GC/MS). Analysis of the volatiles evolved during heating identified both gases and higher boiling compounds. The major higher boiling compounds are benzene, toluene, xylene, aniline, benzonitrile, m-methylaniline, and m-methylbenzonitrile; the gases include ammonia, methane, and traces of carbon dioxide. Correlations between sample temperature and the evolution of each of these compounds have been made. The onset of all volatile formation occurs between 450 and 500°C. The higher boiling volatiles peak, then end by approximately 700°C, while the gases peak then fall off but are still being evolved at 900°C. Average weight loss measurements of 13.6% at 700°C and 15.7% at 900°C agree with previously published thermogravimetric analysis (TGA) data. © 1993 John Wiley & Sons, Inc.     

Should industrial/organizational psychologists be licensed?

A historical review of licensing among industrial/organizational (I/O) psychologists demonstrates that the American Psychological Association (APA) policy on such licensing is inconsistent. Arguments for and against licensure for this group are presented. Job analysis and APA data are drawn upon to show that few I/O activities may pose the personal risk that would seem to require the protection of a license. Alternatives are discussed for changes in present APA policy and state licensing requirements. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)