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.     

Dietary Alcohol and Fat Differentially Affect Plasma Cholesteryl Ester Transfer Activity and Triglycerides in Normo- and Hypertriglyceridemic Subjects

Moderate alcohol consumption is associated with increased plasma high-density lipoprotein (HDL)-cholesterol concentrations and reduced risk for cardiovascular disease. Plasma cholesteryl ester transfer activity (CETA) mediates the exchange of HDL-cholesteryl ester (CE) for the triacylglycerol (TAG) of very-low-density lipoproteins. We compared the effects of oral challenges of Alcohol, saturated fat (SAT), and (Alcohol + SAT) on plasma CETA, cholesterol, nonesterified fatty acids (NEFA), and TAG among normo-triglyceridemic (NTG) and mildly hypertriglyceridemic (HTG) volunteers having a range of plasma TAG concentrations. The major changes were (1) CETA increased more after ingestion of SAT and (Alcohol + SAT) in the HTG group versus the NTG group; (2) after all three challenges, elevation of plasma TAG concentration persisted longer in the HTG versus NTG group. Plasma cholesterol was not affected by the three dietary challenges, while Alcohol increased NEFA more in the HTG group than the NTG group. Plasma TAG best predicted plasma CETA, suggesting that intestinally derived lipoproteins are acceptors of HDL-CE. Unexpectedly, ingestion of (Alcohol + SAT) reduced the strength of the correlation between plasma TAG and CETA, that is the effects of (SAT and Alcohol) on plasma CETA are not synergistic nor additive but rather mutually suppressive. The alcohol-mediated inhibition of CE-transfer to chylomicrons maintains a higher plasma HDL-cholesterol concentration, which is athero-protective, although the suppressive metabolite underlying this correlation could be acetate, the terminal alcohol metabolite, other factors, including CETA inhibitors, are also likely important.     

Elevated temperature impact on performance of Low Temperature Co-fired Ceramic dielectrics

The need for electronics to operate at temperatures of 200°C and above continues to grow. These applications include avionics, aerospace, automotive, downhole drilling, mining, and many others. To satisfy this demand, a significant amount of research and development has been conducted. Despite the efforts, the number of new electronic components designed specifically for high-temperature operation is still relatively limited. In Low Temperature Co-fired Ceramic (LTCC) packages, LTCC materials are generally used as the host media for a number of pre-fabricated semiconductor components. As a result, reliability of the entire LTCC package largely depends on the performance of the least robust component. Ferro A6M-E and Ferro L8 are the two well-established and recognized LTCC dielectrics widely used for mid and high frequency LTCC applications, including several high reliability aerospace and defense applications that require demanding Mil-Spec qualifications. This study is our first attempt to characterize and understand basic high-temperature dielectric properties of these two commercial LTCC materials. The secondary objective is to initiate a dialogue in attempt to establish reliability requirements for LTCC packages dedicated for high-temperature operation.     

Rheological behavior of neat and carbon fiber-reinforced poly(ether ketone ketone) for extrusion deposition additive manufacturing

To develop new materials for extrusion additive manufacturing (AM) systems, a fundamental understanding of rheological properties is essential to correlate the effect of processing on material structure and its properties. In this work, the rheological properties of five different grades of neat and carbon fiber (CF)-reinforced poly(ether ketone ketone) are reported. Rheological properties are essential to understand the effect of reinforcing fibers and AM process parameters such as time, temperature, environment, and shear rate on flow behavior during processing. Small-amplitude oscillatory shear tests and steady shear tests indicated neat grades to exhibit less increase in viscosity over time when processed in air than the CF-filled grades. The filled grades showed greater shear thinning and lower sensitivity to temperature. Overall, this rheological analysis provides a broad framework for determining appropriate processing conditions for extrusion deposition AM of such high-temperature polymer systems.     

Preschool Competency in Context: An Investigation of the Unique Contribution of Child Competencies to Early Academic Success.

The present concurrent study combined developmental and ecological considerations to examine the unique contribution of multiple preschool competencies to an indicator of early academic success. Participants included 195 Head Start children from 32 classrooms representative of a large, urban Head Start program. Dimensional (variable-centered) analyses revealed 3 distinct classroom competency dimensions (i.e., General Classroom Competencies, Specific Approaches to Learning, and Interpersonal Classroom Behavioral Problems). The first 2 of these dimensions were found to be uniquely associated with early academic success. Findings from typological (person-centered) analyses supported the dimensional findings. Typological analyses revealed 7 profiles of classroom competency distinguished by high scores on the dimensions of General Competencies and Approaches to Learning, and these profiles were found to relate differentially to the indicator of early academic success. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biological evaluation of two anomeric glucose analogues iodinated in position 6

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.     

PARTNERS IN EXCELLENCE Metrics and Productivity Programs

For many companies, productivity improvements are the watchwords of the 1990s. IS organizations are having to demonstrate increased productivity on an annual basis. For the end-user computing (EUC) department, this requirement often comes in addition to the request to quantify the services it provides, presenting the EUC manager with the proverbial nightmare of juggling two number-one priorities. Which should receive the highest attention? The savvy manager recognizes that the correct answer is both.