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.     

Mimicking the Brain Extracellular Matrix in Vitro: A Review of Current Methodologies and Challenges

The brain's extracellular matrix (ECM), a 3-dimensional macromolecular network that supports cell growth and viability, has crucial roles in homeostasis and disease. Accurate recapitulation of the chemical, structural, and mechanical properties of the ECM in brain cell cultures is essential for the development of translatable in vitro models; however, thus far, this task has proven highly challenging. This review provides an in-depth discussion of this challenge, including an overview of the properties of the ECM that in vitro models should endeavour to capture, a survey of ECM analogues that are currently used for this purpose, and a discussion of the main hindrances to developing more effective ECM-like coating materials.     

Polymorphic scenario-based specification models: semantics and applications

We present polymorphic scenarios, a generalization of a UML2-compliant variant of Damm and Harel??s live sequence charts (LSC) in the context of object-orientation. Polymorphic scenarios are visualized using (modal) sequence diagrams where lifelines may represent classes and interfaces rather than concrete objects. Their semantics takes advantage of inheritance and interface realization to allow the specification of most expressive, succinct, and reusable universal and existential inter-object scenarios for object-oriented system models. We motivate the use of polymorphic scenarios, formally define their trace-based semantics, and present their application for scenario-based testing and execution, as implemented in the S2A compiler developed at the Weizmann Institute of Science. We further discuss advanced semantic issues arising from the use of scenarios in a polymorphic setting, suggest possible extensions, present a UML profile to support polymorphic scenarios, consider the application of the polymorphic semantics to other variants of scenario-based specification languages, and position our work in the broader context of behavioral subtyping.     

Using aspects for testing of embedded software: experiences from two industrial case studies

Aspect-oriented software testing is emerging as an important alternative to conventional procedural and object-oriented testing techniques. This paper reports experiences from two case studies where aspects were used for the testing of embedded software in the context of an industrial application. In the first study, we used code-level aspects for testing non-functional properties. The methodology we used for deriving test aspect code was based on translating high-level requirements into test objectives, which were then implemented using test aspects in AspectC++. In the second study, we used high-level visual scenario-based models for the test specification, test generation, and aspect-based test execution. To specify scenario-based tests, we used a UML2-compliant variant of live sequence charts. To automatically generate test code from the models, a modified version of the S2A Compiler, outputting AspectC++ code, was used. Finally, to examine the results of the tests, we used the Tracer, a prototype tool for model-based trace visualization and exploration. The results of the two case studies show that aspects offer benefits over conventional techniques in the context of testing embedded software; these benefits are discussed in detail. Finally, towards the end of the paper, we also discuss the lessons learned, including the technological and other barriers to the future successful use of aspects in the testing of embedded software in industry.     

A novel, linear voltage variable MMIC attenuator

Voltage variable attenuators (VVAs) for microwave applications that are fabricated using present technology and design methods feature a nonlinear relationship between the attenuation measured in decibels and the control signal. A novel VVA that features a linear attenuation-control-voltage relationship without the need for external linearization is described. This is accomplished by connecting a number of FET segments in a unique fashion to form a composite FET. The channel resistance of the composite FET constitutes a prescribed function of its gate-source voltage. By careful design the resistance functions that are necessary for realization of linear attenuators are synthesized. The attenuator was fabricated using GaAs MMIC technology employing MESFETs as voltage variable resistors. It is completely passive and does not require a DC supply. The attenuation ranges from 2 to 15 dB over DC to 8 GHz while port impedance is kept close to 50 Ω. The deviation of the attenuation from a straight line is less than 0.2 dB     

Adult age differences in episodic memory: Further support for an associative-deficit hypothesis.

This study further tested an associative-deficit hypothesis (ADH; M. Naveh-Benjamin, 2000), which attributes a substantial part of older adults' deficient episodic memory performance to their difficulty in merging unrelated attributes-units of an episode into a cohesive unit. First, the results of 2 experiments replicate those observed by M. Naveh-Benjamin (2000) showing that older adults are particularly deficient in memory tests requiring associations. Second, the results extend the type of stimuli (pictures) under which older adults show this associative deficit. Third, the results support an ADH in that older adults show less of an associative deficit when the components of the episodes used are already connected in memory, thereby facilitating their encoding and retrieval. Finally, a group of younger adults who encoded the information under divided-attention conditions did not show this associative deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Application of the CALPHAD approach to Mg-alloys design

The CALPHAD method can be applied as a tool for both alloy development and process guideline determination. In this study, two Mg alloys were designed, their process parameters derived and, using the CALPHAD method, the final results simulated. These results were later confirmed using tangible experimental methods. It was found that γ$\gamma$- Mg₁₇Al₁₂ precipitates along the grain boundaries (GB), Mg₂Sn forms both along the GB and as fine precipitates in the α$\alpha$-Mg matrix and the addition of Ce mishmetal (MM) leads to the formation of elongated Al- rare earth (RE) precipitates along the GB. The microstructural stability at 200 ^°C is high, showing no decrease in microhardness for 32 days. It is shown that the CALPHAD method considerably reduces the effort of alloy design and that the reliability of the results is high.     

Organometallic Studies. XXXII. Iron π-Complexes of Some Polyunsaturated Terpenes

The reactions between iron carbonyls and the terpenes myrcene, alloocimene, and methyl levopimarate have been investigated. Nuclear magnetic resonance and mass spectra are reported for the newly prepared dieneiron tricarbonyl complexes.     

Transient charge accumulation in a capacitive self-assembled monolayer

Charge accumulation in an organosilane monolayer self-assembled on silicon is studied using electron-spectroscopy-based chemically resolved electrical measurements (CREM). By resolving the net electrical response of the organic layer, a significant capability of holding extra charge is indicated. Quantum size effects at a molecularly thin layer and the role of competing discharge mechanisms, including defect-assisted leakage currents, are discussed.