Thermochemical scanning probe lithography of protein gradients at the nanoscale

Patterning nanoscale protein gradients is crucial for studying a variety of cellular processes in vitro. Despite the recent development in nano-fabrication technology, combining nanometric resolution and fine control of protein concentrations is still an open challenge. Here, we demonstrate the use of thermochemical scanning probe lithography (tc-SPL) for defining micro- and nano-sized patterns with precisely controlled protein concentration. First, tc-SPL is performed by scanning a heatable atomic force microscopy tip on a polymeric substrate, for locally exposing reactive amino groups on the surface, then the substrate is functionalized with streptavidin and laminin proteins. We show, by fluorescence microscopy on the patterned gradients, that it is possible to precisely tune the concentration of the immobilized proteins by varying the patterning parameters during tc-SPL. This paves the way to the use of tc-SPL for defining protein gradients at the nanoscale, to be used as chemical cues e.g. for studying and regulating cellular processes in vitro

Human-Agent Teamwork in Cyber Operations: Supporting Co-evolution of Tasks and Artifacts with Luna

Abstract. In this article, we outline the general concept of coactive emergence, an iterative process whereby joint sensemaking and decision-making activities are undertaken by analysts and software agents. Then we explain our rationale for the development of the Luna software agent framework. In particular, we focus on how we use capabilities for comprehensive policy-based governance to ensure that key requirements for security, declarative specification of task-work, and built-in support for joint activity within mixed teams of humans and agents are satisfied

Cosmic Acceleration in Brans-Dicke Cosmology

We consider Brans-Dicke theory with a self-interacting potential in Einstein conformal frame. We show that an accelerating expansion is possible in a spatially flat universe for large values of the Brans-Dicke parameter consistent with local gravity experiments.Comment: 10 Pages, 3 figures, To appear in General Relativity and Gravitatio

Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary.

The female ovary contains a finite number of oocytes, and their release at ovulation becomes sporadic and dis-ordered with aging and with obesity, leading to loss of fertility. Understanding the molecular defects underpinning this pathology is essential as age of childbearing and obesity rates increase globally. We identify that fibrosis within the ovarian stromal compartment is an underlying mechanism responsible for impaired oocyte release, which is initiated by mitochondrial dysfunction leading to diminished bioenergetics, oxidative damage, inflam-mation, and collagen deposition. Furthermore, antifibrosis drugs (pirfenidone and BGP-15) eliminate fibrotic collagen and restore ovulation in reproductively old and obese mice, in association with dampened M2 macro-phage polarization and up-regulated MMP13 protease. This is the first evidence that ovarian fibrosis is reversible and indicates that drugs targeting mitochondrial metabolism may be a viable therapeutic strategy for women with metabolic disorders or advancing age to maintain ovarian function and extend fertility.Takashi Umehara, Yasmyn E. Winstanley, Eryk Andreas, Atsushi Morimoto, Elisha J. Williams, Kirsten M. Smith, John Carroll, Mark A. Febbraio, Masayuki Shimada, Darryl L. Russell, Rebecca L. Robke

Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n= 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend< 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited

Interstellar MHD Turbulence and Star Formation

This chapter reviews the nature of turbulence in the Galactic interstellar medium (ISM) and its connections to the star formation (SF) process. The ISM is turbulent, magnetized, self-gravitating, and is subject to heating and cooling processes that control its thermodynamic behavior. The turbulence in the warm and hot ionized components of the ISM appears to be trans- or subsonic, and thus to behave nearly incompressibly. However, the neutral warm and cold components are highly compressible, as a consequence of both thermal instability in the atomic gas and of moderately-to-strongly supersonic motions in the roughly isothermal cold atomic and molecular components. Within this context, we discuss: i) the production and statistical distribution of turbulent density fluctuations in both isothermal and polytropic media; ii) the nature of the clumps produced by thermal instability, noting that, contrary to classical ideas, they in general accrete mass from their environment; iii) the density-magnetic field correlation (or lack thereof) in turbulent density fluctuations, as a consequence of the superposition of the different wave modes in the turbulent flow; iv) the evolution of the mass-to-magnetic flux ratio (MFR) in density fluctuations as they are built up by dynamic compressions; v) the formation of cold, dense clouds aided by thermal instability; vi) the expectation that star-forming molecular clouds are likely to be undergoing global gravitational contraction, rather than being near equilibrium, and vii) the regulation of the star formation rate (SFR) in such gravitationally contracting clouds by stellar feedback which, rather than keeping the clouds from collapsing, evaporates and diperses them while they collapse.Comment: 43 pages. Invited chapter for the book "Magnetic Fields in Diffuse Media", edited by Elisabete de Gouveia dal Pino and Alex Lazarian. Revised as per referee's recommendation

Effect of a whey protein and rapeseed oil gel feed supplement on milk fatty acid composition of Holstein cows

Isoenergetic replacement of dietary saturated fatty acids (SFA) with cis-monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) can reduce cardiovascular disease (CVD) risk. Supplementing dairy cow diets with plant oils lowers milk fat SFA concentrations. However, this feeding strategy can also increase milk fat trans FA (TFA), and negatively impact rumen fermentation. Protection of oil supplements from the rumen environment is therefore needed. In the present study a whey protein gel (WPG) of rapeseed oil (RO) was produced for feeding to dairy cows, in two experiments. In Experiment 1 four multiparous Holstein-Friesian cows in mid-lactation were used in a change-over experiment, with 8-d treatment periods separated by a 5-day washout period. Total mixed ration diets containing 420 g RO or WPG providing 420 g of RO were fed and the effects on milk production, composition and FA concentration were measured. Experiment 2 involved four multiparous mid-lactation Holstein-Friesian cows in a 4 x 4 Latin square design experiment, with 28-d periods, to investigate the effect of incremental dietary inclusion (0, 271, 617 and 814 g/d supplemental oil) of WPG on milk production, composition and FA concentration in the last week of each period. There were minimal effects of WPG on milk FA profile in experiment 1, but trans-18:1 and total trans-MUFA were higher after 8 days of supplementation with RO than with WPG. Incremental diet inclusion of WPG in experiment 2 resulted in linear increases in milk yield, cis- and trans-MUFA and PUFA, and linear decreases in SFA (from 73 to 58 g/100 g FA), and milk fat concentration. The WPG supplement was effective at decreasing milk SFA concentration by replacement with MUFA and PUFA in experiment 2, but the increase in TFA suggested that protection was incomplete

Field Measurements of Terrestrial and Martian Dust Devils

Surface-based measurements of terrestrial and martian dust devils/convective vortices provided from mobile and stationary platforms are discussed. Imaging of terrestrial dust devils has quantified their rotational and vertical wind speeds, translation speeds, dimensions, dust load, and frequency of occurrence. Imaging of martian dust devils has provided translation speeds and constraints on dimensions, but only limited constraints on vertical motion within a vortex. The longer mission durations on Mars afforded by long operating robotic landers and rovers have provided statistical quantification of vortex occurrence (time-of-sol, and recently seasonal) that has until recently not been a primary outcome of more temporally limited terrestrial dust devil measurement campaigns. Terrestrial measurement campaigns have included a more extensive range of measured vortex parameters (pressure, wind, morphology, etc.) than have martian opportunities, with electric field and direct measure of dust abundance not yet obtained on Mars. No martian robotic mission has yet provided contemporaneous high frequency wind and pressure measurements. Comparison of measured terrestrial and martian dust devil characteristics suggests that martian dust devils are larger and possess faster maximum rotational wind speeds, that the absolute magnitude of the pressure deficit within a terrestrial dust devil is an order of magnitude greater than a martian dust devil, and that the time-of-day variation in vortex frequency is similar. Recent terrestrial investigations have demonstrated the presence of diagnostic dust devil signals within seismic and infrasound measurements; an upcoming Mars robotic mission will obtain similar measurement types

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Materiality, health informatics and the limits of knowledge production

© IFIP International Federation for Information Processing 2014 Contemporary societies increasingly rely on complex and sophisticated information systems for a wide variety of tasks and, ultimately, knowledge about the world in which we live. Those systems are central to the kinds of problems our systems and sub-systems face such as health and medical diagnosis, treatment and care. While health information systems represent a continuously expanding field of knowledge production, we suggest that they carry forward significant limitations, particularly in their claims to represent human beings as living creatures and in their capacity to critically reflect on the social, cultural and political origins of many forms of data ‘representation’. In this paper we take these ideas and explore them in relation to the way we see healthcare information systems currently functioning. We offer some examples from our own experience in healthcare settings to illustrate how unexamined ideas about individuals, groups and social categories of people continue to influence health information systems and practices as well as their resulting knowledge production. We suggest some ideas for better understanding how and why this still happens and look to a future where the reflexivity of healthcare administration, the healthcare professions and the information sciences might better engage with these issues. There is no denying the role of health informatics in contemporary healthcare systems but their capacity to represent people in those datascapes has a long way to go if the categories they use to describe and analyse human beings are to produce meaningful knowledge about the social world and not simply to replicate past ideologies of those same categories