Knudsen Diffusion in Silicon Nanochannels

Measurements on helium and argon gas flow through an array of parallel, linear channels of 12 nm diameter and 200 micrometer length in a single crystalline silicon membrane reveal a Knudsen diffusion type transport from 10^2 to 10^7 in Knudsen number Kn. The classic scaling prediction for the transport diffusion coefficient on temperature and mass of diffusing species,D_He ~ sqrt(T), is confirmed over a T range from 40 K to 300 K for He and for the ratio of D_He/D_Ar ~ sqrt(m_Ar/m_He). Deviations of the channels from a cylindrical form, resolved with transmission electron microscopy down to subnanometer scales, quantitatively account for a reduced diffusivity as compared to Knudsen diffusion in ideal tubular channels. The membrane permeation experiments are described over 10 orders of magnitude in Kn, encompassing the transition flow regime, by the unified flow model of Beskok and Karniadakis.Comment: 4 pages, 3 figure

Realizing the Future State of K-12 Public Education: Data Exchange and Functional Integration with Local Government

It is no news that K-12 school districts can more effectively provide instruction and support services by leveraging current and emerging information technologies. Nor is it news that when districts fail to adopt up-to-date IT-based systems, endemic underfunding gets the blame. In fact, however, districts can leverage existing funding sources and ROI from early projects to support later projects and sustain services over the long term. What is required is a thorough understanding of functions and dependencies in the local school, school district, and community; structured planning and functional alignment in the district and its IT organization; and ongoing commitment by all stakeholders. A central technology goal is establishment of secure, properly controlled electronic data exchange. Implemented within the district and between the district and municipal government and services agencies, it enables all partners to eliminate redundancies, enhance quality of service, and reduce costs

Gz, a guanine nucleotide-binding protein with unique biochemical properties

Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it during purification from bovine brain. Additionally, expression of the cDNA in Escherichia coli has resulted in the production and purification of the recombinant protein. Purification of Gz from bovine brain is tedious, and only small quantities of protein have been obtained. The protein copurifies with the beta gamma subunit complex common to other G proteins; another 26- kDa GTP-binding protein is also present in these preparations. The purified protein could not serve as a substrate for NAD-dependent ADP- ribosylation catalyzed by either pertussis toxin or cholera toxin. Purification of recombinant Gz alpha (rGz alpha) from E. coli is simple, and quantities of homogeneous protein sufficient for biochemical analysis are obtained. Purified rGz alpha has several properties that distinguish it from other G protein alpha subunit polypeptides. These include a very slow rate of guanine nucleotide exchange (k = 0.02 min^-1), which is reduced greater than 20-fold in the presence of mM concentrations of Mg2+. In addition, the rate of the intrinsic GTPase activity of Gz alpha is extremely slow. The hydrolysis rate (kcat) for rGz alpha at 30 degrees C is 0.05 min^-1, or 200-fold slower than that determined for other G protein alpha subunits. rGz alpha can interact with bovine brain beta gamma but does not serve as a substrate for ADP-ribosylation catalyzed by either pertussis toxin or cholera toxin. These studies suggest that Gz may play a role in signal transduction pathways that are mechanistically distinct from those controlled by the other members of the G protein family

The covariance of cosmic shear correlation functions and cosmological parameter estimates using redshift information

Cosmological weak lensing by the large scale structure of the Universe, cosmic shear, is coming of age as a powerful probe of the parameters describing the cosmological model and matter power spectrum. It complements CMB studies, by breaking degeneracies and providing a cross-check. An important measure of the cosmic shear signal are the shear correlation functions; these can be directly calculated from data, and compared with theoretical expectations for different cosmological models and matter power spectra. We present a Monte Carlo method to quickly simulate mock cosmic shear surveys. One application of this method is in the determination of the full covariance matrix for the correlation functions; this includes redshift binning and is applicable to arbitrary survey geometries. Terms arising from shot noise and cosmic variance (dominant on small and large scales respectively) are accounted for naturally. As an illustration of the use of such covariance matrices, we consider to what degree confidence regions on parameters are tightened when redshift binning is employed. The parameters considered are those commonly discussed in cosmic shear analyses - the matter density parameter, dark energy density parameter (classical cosmological constant), power spectrum normalisation and shape parameter. We incorporate our covariance matrices into a likelihood treatment, and also use the Fisher formalism to explore a larger region of parameter space (abridged).Comment: 14 pages, 8 figures, accepted by A&A corrected typos, some changes in the discussion, shortened sections 2.1, 2.2 and 6.2.

Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNβ3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours

Dissecting interferon-induced transcriptional programs in human peripheral blood cells

Interferons are key modulators of the immune system, and are central to the control of many diseases. The response of immune cells to stimuli in complex populations is the product of direct and indirect effects, and of homotypic and heterotypic cell interactions. Dissecting the global transcriptional profiles of immune cell populations may provide insights into this regulatory interplay. The host transcriptional response may also be useful in discriminating between disease states, and in understanding pathophysiology. The transcriptional programs of cell populations in health therefore provide a paradigm for deconvoluting disease-associated gene expression profiles.We used human cDNA microarrays to (1) compare the gene expression programs in human peripheral blood mononuclear cells (PBMCs) elicited by 6 major mediators of the immune response: interferons alpha, beta, omega and gamma, IL12 and TNFalpha; and (2) characterize the transcriptional responses of purified immune cell populations (CD4+ and CD8+ T cells, B cells, NK cells and monocytes) to IFNgamma stimulation. We defined a highly stereotyped response to type I interferons, while responses to IFNgamma and IL12 were largely restricted to a subset of type I interferon-inducible genes. TNFalpha stimulation resulted in a distinct pattern of gene expression. Cell type-specific transcriptional programs were identified, highlighting the pronounced response of monocytes to IFNgamma, and emergent properties associated with IFN-mediated activation of mixed cell populations. This information provides a detailed view of cellular activation by immune mediators, and contributes an interpretive framework for the definition of host immune responses in a variety of disease settings

The influence of host genetics on erythrocytes and malaria infection: is there therapeutic potential?

As parasites, Plasmodium species depend upon their host for survival. During the blood stage of their life-cycle parasites invade and reside within erythrocytes, commandeering host proteins and resources towards their own ends, and dramatically transforming the host cell. Parasites aptly avoid immune detection by minimizing the exposure of parasite proteins and removing themselves from circulation through cytoadherence. Erythrocytic disorders brought on by host genetic mutations can interfere with one or more of these processes, thereby providing a measure of protection against malaria to the host. This review summarizes recent findings regarding the mechanistic aspects of this protection, as mediated through the parasites interaction with abnormal erythrocytes. These novel findings include the reliance of the parasite on the host enzyme ferrochelatase, and the discovery of basigin and CD55 as obligate erythrocyte receptors for parasite invasion. The elucidation of these naturally occurring malaria resistance mechanisms is increasing the understanding of the host-parasite interaction, and as discussed below, is providing new insights into the development of therapies to prevent this disease.We acknowledge funding support from the National Health and Medical Research Council (Grant APP605524, 490037 and 1047082), the Australian Research Council (Grant DP12010061), the National Collaborative Research Infrastructure Strategy of Australia and the Education investment fund from the Department of Innovation, Industry, Science and Research. PML is a recipient of an Australian Postgraduate award