Analysis of the topography of microchannels with different sizes

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.The longterm aim in the design of modern evaporators is to find a heat transfer calculation method based on the phenomena of growing and departing vapour bubbles on the heated surface. New developments in computer calculation and in measurement technique support the local analysis of the heat transfer, bubble formation and the microstructure of the heated surface. All three kinds of data originate from the same equipment and from experiments performed with equal detail and precision. The influence of different rough and structured surfaces on the heat transfer coefficient will be investigated by a joint research project of Brunel and Hannover Universities with refrigerants boiling in single microchannels of different inner diameter. The microchannels are capillary tubes and they are manufactured by industrial processes. The samples of the microchannels have to be prepared by special methods, because the surfaces inside the microchannels cannot be measured in the same way as used for the heat transfer measurements. The microstructure of the surfaces of three microchannels (D = 0.4, 0.5 and 0.8mm) is measured by a contact stylus instrument. The paper will focus on the detailed description of the profiles and the topographies of the samples. The roughness parameter in accordance with standard practice are calculated for ca 1000 runs (profiles). The roughness parameters of the smaller microchannels are twofold higher than those of the largest microchannel investigated. The scattering of the roughness of the largest microchannel (D = 0.8 mm) is less and the cavities are smaller than those of the other ones (D = 0.4 and 0.5 mm). All surfaces investigated demonstrate a deterministic microstructure as for emery ground surfaces on smooth tubes in the literature

Tuning the Properties of Active Microtubule Networks by Depletion Forces

Suspensions of microtubules and nonadsorbing particles form thick and long bundles due to depletion forces. Such interactions act at the nanometer scale and define the structural and dynamical properties of the resulting networks. In this study, we analyze the depletion forces exerted by two types of nonadsorbing particles, namely, the polymer, poly(ethylene glycol) (PEG), and the block copolymer, Pluronic. We characterize their effects both in passive and active networks by adding motor proteins to the suspensions. By exploiting its bundling effect via entropic forces, we observed that PEG generates a network with thick structures showing a nematic order and larger mesh size. On the other hand, Pluronic builds up a much denser gel-like network without a recognizable mesh structure. This difference is also reflected in the network activity. PEG networks show moderate contraction in lateral directions while Pluronic networks exhibit faster and isotropic contraction. Interestingly, by mixing the two nonadsorbing polymers in different ratios, we observed that the system showed a behavior that exhibited properties of both agents, leading to a robust and fast responsive structure compared to the single-depletant networks. In conclusion, we show how passive osmotic compression modifies the distribution of biopolymers. Its combination with active motors results in a new active material with potential for nanotechnological applications.I.G. acknowledges support from the MaxSynBio Consortium, which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society. V.N. and I.G. acknowledge the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement MAMI No. 766007. A.V. acknowledges support from the Slovenian Research Agency (grant no. P1-0099

One-pot multicomponent synthesis of 2,3-dihydropyrans: new access to furanose–pyranose 1,3-C–C-linked-disaccharides

An efficient synthesis of 2,3-dihydropyrans starting from different terminal alkynes was developed. The 2,3-dihydropyrans were obtained in a few minutes through a microwave-assisted multicomponent enyne cross-metathesis/hetero-Diels–Alder reaction. Starting from C-ethynyl-ribofuranose, a new multicomponent approach to furanose–pyranose 1,3-C–C-linked disaccharides was also developed

Intracellular calcium strongly potentiates agonist-activated TRPC5 channels

TRPC5 is a calcium (Ca2+)-permeable nonselective cation channel expressed in several brain regions, including the hippocampus, cerebellum, and amygdala. Although TRPC5 is activated by receptors coupled to phospholipase C, the precise signaling pathway and modulatory signals remain poorly defined. We find that during continuous agonist activation, heterologously expressed TRPC5 currents are potentiated in a voltage-dependent manner (∼5-fold at positive potentials and ∼25-fold at negative potentials). The reversal potential, doubly rectifying current–voltage relation, and permeability to large cations such as N-methyl-d-glucamine remain unchanged during this potentiation. The TRPC5 current potentiation depends on extracellular Ca2+: replacement by Ba2+ or Mg2+ abolishes it, whereas the addition of 10 mM Ca2+ accelerates it. The site of action for Ca2+ is intracellular, as simultaneous fura-2 imaging and patch clamp recordings indicate that potentiation is triggered at ∼1 µM [Ca2+]. This potentiation is prevented when intracellular Ca2+ is tightly buffered, but it is promoted when recording with internal solutions containing elevated [Ca2+]. In cell-attached and excised inside-out single-channel recordings, increases in internal [Ca2+] led to an ∼10–20-fold increase in channel open probability, whereas single-channel conductance was unchanged. Ca2+-dependent potentiation should result in TRPC5 channel activation preferentially during periods of repetitive firing or coincident neurotransmitter receptor activation

Data mining of high density genomic variant data for prediction of Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>The discovery of genetic associations is an important factor in the understanding of human illness to derive disease pathways. Identifying multiple interacting genetic mutations associated with disease remains challenging in studying the etiology of complex diseases. And although recently new single nucleotide polymorphisms (SNPs) at genes implicated in immune response, cholesterol/lipid metabolism, and cell membrane processes have been confirmed by genome-wide association studies (GWAS) to be associated with late-onset Alzheimer's disease (LOAD), a percentage of AD heritability continues to be unexplained. We try to find other genetic variants that may influence LOAD risk utilizing data mining methods.</p> <p>Methods</p> <p>Two different approaches were devised to select SNPs associated with LOAD in a publicly available GWAS data set consisting of three cohorts. In both approaches, single-locus analysis (logistic regression) was conducted to filter the data with a less conservative p-value than the Bonferroni threshold; this resulted in a subset of SNPs used next in multi-locus analysis (random forest (RF)). In the second approach, we took into account prior biological knowledge, and performed sample stratification and linkage disequilibrium (LD) in addition to logistic regression analysis to preselect loci to input into the RF classifier construction step.</p> <p>Results</p> <p>The first approach gave 199 SNPs mostly associated with genes in calcium signaling, cell adhesion, endocytosis, immune response, and synaptic function. These SNPs together with <it>APOE and GAB2 </it>SNPs formed a predictive subset for LOAD status with an average error of 9.8% using 10-fold cross validation (CV) in RF modeling. Nineteen variants in LD with <it>ST5, TRPC1, ATG10, ANO3, NDUFA12, and NISCH </it>respectively, genes linked directly or indirectly with neurobiology, were identified with the second approach. These variants were part of a model that included <it>APOE </it>and <it>GAB2 </it>SNPs to predict LOAD risk which produced a 10-fold CV average error of 17.5% in the classification modeling.</p> <p>Conclusions</p> <p>With the two proposed approaches, we identified a large subset of SNPs in genes mostly clustered around specific pathways/functions and a smaller set of SNPs, within or in proximity to five genes not previously reported, that may be relevant for the prediction/understanding of AD.</p

Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics

Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca²+ entry because of the critical roles played by Ca²+ in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (−)-englerin A. We conclude that further research is both justified and necessary before these proteins can be considered as strong targets for anti-cancer cell drug discovery programmes. It is nevertheless already apparent that inhibitors of the channels would be unlikely to cause significant adverse effects, but, rather, have other effects which may be beneficial in the context of cancer and chemotherapy, potentially including suppression of innate fear, visceral pain and pathological cardiac remodelling

Transient receptor potential channels in Alzheimer's disease

AbstractCognitive impairment and emotional disturbances in Alzheimer's disease (AD) result from the degeneration of synapses and neuronal death in the limbic system and associated regions of the cerebral cortex. An alteration in the proteolytic processing of the amyloid precursor protein (APP) results in increased production and accumulation of amyloid β-peptide (Aβ) in the brain. Aβ can render neurons vulnerable to excitotoxicity and apoptosis by disruption of cellular Ca2+ homeostasis and neurotoxic factors including reactive oxygen species (ROS), nitric oxide (NO), and cytokines. Many lines of evidence have suggested that transient receptor potential (TRP) channels consisting of six main subfamilies termed the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin) are involved in Ca2+ homeostasis disruption. Thus, emerging evidence of the pathophysiological role of TRP channels has yielded promising candidates for molecular entities mediating Ca2+ homeostasis disruption in AD. In this review, we focus on the TRP channels in AD and highlight some TRP “suspects” for which a role in AD can be anticipated. An understanding of the involvement of TRP channels in AD may lead to the development of new target therapies

Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia

Retinoic acid (RA) is essential for the generation of GABAergic inhibitory neurons in the mouse forebrain, and RA treatment of embryonic stem cells induces the production of GABAergic neurons

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed