The LabMatrix system

The LabMatrix^™ is a prototyping system designed to give the user a practical and versatile platform for testing microfluidic applications in the fields of health care and life sciences. The LabMatrix^™ system consists of a microfluidic breadboard and cover that align and secure a series of specially designed LabMatrix^™ microfluidic chips. Chips are easily arranged and rearranged into a user-defined fluidic network. The LabMatrix^™ system is designed with maximum flexibility in mind, providing the user with a means to prototype a wide range of microfluidic applications in a short period.     

Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.     

Multi‐Material Tissue Engineering Scaffold with Hierarchical Pore Architecture

Multi‐material polymer scaffolds with multiscale pore architectures are characterized and tested with vascular and heart cells as part of a platform for replacing damaged heart muscle. Vascular and muscle scaffolds are constructed from a new material, poly(limonene thioether) (PLT32i), which meets the design criteria of slow biodegradability, elastomeric mechanical properties, and facile processing. The vascular–parenchymal interface is a poly(glycerol sebacate) (PGS) porous membrane that meets different criteria of rapid biodegradability, high oxygen permeance, and high porosity. A hierarchical architecture of primary (macroscale) and secondary (microscale) pores is created by casting the PLT32i prepolymer onto sintered spheres of poly(methyl methacrylate) (PMMA) within precisely patterned molds followed by photocuring, de‐molding, and leaching out the PMMA. Prefabricated polymer templates are cellularized, assembled, and perfused in order to engineer spatially organized, contractile heart tissue. Structural and functional analyses show that the primary pores guide heart cell alignment and enable robust perfusion while the secondary pores increase heart cell retention and reduce polymer volume fraction.     

Cryptographic Hash Functions from Expander Graphs

We propose constructing provable collision resistant hash functions from expander graphs in which finding cycles is hard. As examples, we investigate two specific families of optimal expander graphs for provable collision resistant hash function constructions: the families of Ramanujan graphs constructed by Lubotzky-Phillips-Sarnak and Pizer respectively. When the hash function is constructed from one of Pizer’s Ramanujan graphs, (the set of supersingular elliptic curves over with ℓ-isogenies, ℓ a prime different from p), then collision resistance follows from hardness of computing isogenies between supersingular elliptic curves. For the LPS graphs, the underlying hard problem is a representation problem in group theory. Constructing our hash functions from optimal expander graphs implies that the outputs closely approximate the uniform distribution. This property is useful for arguing that the output is indistinguishable from random sequences of bits. We estimate the cost per bit to compute these hash functions, and we implement our hash function for several members of the Pizer and LPS graph families and give actual timings.     

Processing aspects in the low-frequency noise of nMOSFETs on strained-silicon substrates

The impact of different processing factors on the low-frequency (LF) noise of nMOSFETs fabricated in strained-silicon (SSi) substrates will be described. It is shown that the use of an SSi substrate can yield improved LF noise performance compared with standard Czochralski silicon material. This is demonstrated for both full-wafer and selective epitaxial SSi material. The lower 1/f noise points to an improved gate oxide quality, i.e., with a lower interface and bulk defect density, and is correlated with the low-field mobility or transconductance of the transistors. At the same time, it will be demonstrated that there exist defect-related LF noise mechanisms, which generally give rise to excess generation-recombination (GR) noise. Associated with this GR noise, a degradation of either the OFF-state leakage current or the mobility (transconductance) of the devices is observed. It is clear that noise is a sensitive parameter to local defectiveness and may be a useful tool for both materials' characterization and the analysis of processing-related device degradation mechanisms.     

Not so black and white: Memory for ambiguous group members.

Exponential increases in multiracial identities, expected over the next century, create a conundrum for perceivers accustomed to classifying people as their own- or other-race. The current research examines how perceivers resolve this dilemma with regard to the own-race bias. The authors hypothesized that perceivers are not motivated to include ambiguous-race individuals in the in-group and therefore have some difficulty remembering these individuals. Both racially ambiguous and other-race faces were misremembered more often than own-race faces (Study 1), though memory for ambiguous faces was improved among perceivers motivated to include biracial individuals in the in-group (Study 2). Racial labels assigned to racially ambiguous faces determined memory for these faces, suggesting that uncertainty provides the motivational context for discounting ambiguous faces in memory (Study 3). Finally, an inclusion motivation fostered cognitive associations between racially ambiguous faces and the in-group. Moreover, the extent to which perceivers associated racially ambiguous faces with the in-group predicted memory for ambiguous faces and accounted for the impact of motivation on memory (Study 4). Thus, memory for biracial individuals seems to involve a flexible person construal process shaped by motivational factors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Underage drinking among young adolescent girls: The role of family processes.

Guided by family interaction theory, this study examined the influences of psychological, peer, and familial processes on alcohol use among young adolescent girls and assessed the contributions of familial factors. An ethnically diverse sample of 1,187 pairs of girls (M age = 12.83 years), and their mothers completed surveys online. Questionnaires assessed girls’ lifetime and recent alcohol use, as well as girls’ demographic, psychological, peer, and family characteristics. Hierarchical logistic regression models showed that although girls’ drinking was associated with a number of psychological and peer factors, the contributions of family domain variables to girls’ drinking were above and beyond that of psychological and peer factors. The interaction analyses further highlighted that having family rules, high family involvement, and greater family communication may offset risks in psychological and peer domains. Study findings underscore the multifaceted etiology of drinking among young adolescent girls and assert the crucial roles of familial processes. Prevention programs should be integrative, target processes at multiple domains, and include work with parents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cx43 Promotes Endothelial Cell Migration and Angiogenesis via the Tyrosine Phosphatase SHP-2

The gap junction protein connexin 43 (Cx43) is associated with increased cell migration and to related changes of the actin cytoskeleton, which is mediated via its C-terminal cytoplasmic tail and is independent of its channel function. Cx43 has been shown to possess an angiogenic potential, however, the role of Cx43 in endothelial cell migration has not yet been investigated. Here, we found that the knock-down of Cx43 by siRNA in human microvascular endothelial cells (HMEC) reduces migration, as assessed by a wound assay in vitro and impaired aortic vessel sprouting ex vivo. Immunoprecipitation of Cx43 revealed an interaction with the tyrosine phosphatase SHP-2, which enhanced its phosphatase activity, as observed in Cx43 expressing HeLa cells compared to cells treated with an empty vector. Interestingly, the expression of a dominant negative substrate trapping mutant SHP-2 (CS) in HMEC, via lentiviral transduction, also impaired endothelial migration to a similar extent as Cx43 siRNA compared to SHP-2 WT. Moreover, the reduction in endothelial migration upon Cx43 siRNA could not be rescued by the introduction of a constitutively active SHP-2 construct (EA). Our data demonstrate that Cx43 and SHP-2 mediate endothelial cell migration, revealing a novel interaction between Cx43 and SHP-2, which is essential for this process.     

Synergism of Toughening Mechanisms in Whisker-Reinforced Ceramic-Matrix Composites

The improved fracture resistance of whisker-reinforced ceramic-matrix composites involves more than one energy-absorbing mechanism. The possible mechanisms are reviewed and a micromechanical model evaluating the relative contributions to the overall toughness is presented. The mechanisms involve microcracking, load transfer, bridging, and crack deflection. The synergism of these mechanisms is examined using an energy release rate balance equation. The basic assumption of the proposed model is that the load transfer between the matrix and the whiskers is due to Coulomb friction. The model has been applied to an Al₂O₃/SiC whisker composite and shows reasonable agreement with reported experimental results. The role of the thermal residual stresses is also examined in light of the frictional load transfer assumption.     

Novel Type II Fatty Acid Biosynthesis (FAS II) Inhibitors as Multistage Antimalarial Agents

Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood‐ and pre‐erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver‐stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood‐stage parasite growth with IC₅₀ values of 1.7 and 3.0 μM and lead to a more prominent developmental attenuation of liver‐stage parasites than the gold‐standard drug, primaquine.