Adsorption of proteins to thin-films of PDMS and its effect on the adhesion of human endothelial cells

This paper describes a simple and inexpensive procedure to produce thin-films of poly(dimethylsiloxane). Such films were characterized by a variety of techniques (ellipsometry, nuclear magnetic resonance, atomic force microscopy, and goniometry) and used to investigate the adsorption kinetics of three model proteins (fibrinogen, collagen type-I, and bovine serum albumin) under different conditions. The information collected from the protein adsorption studies was then used to investigate the adhesion of human dermal microvascular endothelial cells. The results of these studies suggest that these films can be used to model the surface properties of microdevices fabricated with commercial PDMS. Moreover, the paper provides guidelines to efficiently attach cells in BioMEMS devices.Fil: Chumbimuni Torres, Karin Y.. The University of Texas at San Antonio; Estados UnidosFil: Coronado, Ramon E.. The University of Texas at San Antonio; Estados UnidosFil: Mfuh, Adelphe M.. The University of Texas at San Antonio; Estados UnidosFil: Castro Guerrero, Carlos. The University of Texas at San Antonio; Estados UnidosFil: Silva, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Negrete, George R.. The University of Texas at San Antonio; Estados UnidosFil: Bizios, Rena. The University of Texas at San Antonio; Estados UnidosFil: Garcia, Carlos D.. The University of Texas at San Antonio; Estados Unido

Evidence that GZ proteins couple to hypothalamic 5-HT1A receptors in vivo

This is the publisher's version, also available electronically from "http://www.jneurosci.org".Using in situ hybridization and immunoblot analysis, the present studies identified Gz mRNA and Gz-protein in the hypothalamic paraventricular nucleus. The role of Gz-proteins in hypothalamic 5-HT1Areceptor signaling was examined in vivo. Activation of 5-HT1A receptors increases the secretion of oxytocin and ACTH, but not prolactin. Intracerebroventricular infusion (3–4 d) of Gz antisense oligodeoxynucleotides, with different sequences and different phosphorothioate modification patterns, reduced the levels of Gz-protein in the hypothalamic paraventricular nucleus, whereas missense oligodeoxynucleotides had no effect. Neither antisense nor missense oligodeoxynucleotide treatment altered basal plasma levels of ACTH, oxytocin, or prolactin, when compared with untreated controls. An antisense-induced decrease in hypothalamic Gz-protein levels was paralleled by a significant decrease in the oxytocin and ACTH responses to the 5-HT1A agonist 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT). In contrast, the prolactin response to 8-OH-DPAT (which cannot be blocked by 5-HT1A antagonists) was not inhibited by Gz antisense oligodeoxynucleotides. Gz-proteins are the only members of the Gi/Go-protein family that are not inactivated by pertussis toxin. In a control experiment, pertussis toxin treatment (1μg/5 μl, i.c.v.; 48 hr before the 8-OH-DPAT challenge) did not inhibit the ACTH response, potentiated the oxytocin response, and eliminated the prolactin response to 8-OH-DPAT. Thus, pertussis toxin-sensitive Gi/Go-proteins do not mediate the 5-HT1A receptor-mediated increase in ACTH and oxytocin secretion. Combined, these studies provide the firstin vivo evidence for a key role of Gz-proteins in coupling hypothalamic 5-HT1Areceptors to effector mechanisms

Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation

This is the publisher's version, also available electronically from "www.jneurosci.org".Desensitization of 5-HT1A receptors could be involved in the long-term therapeutic effect of anxiolytic and antidepressant drugs. Pretreatment of rats with the 5-HT2A/2C agonist DOI induces an attenuation of hypothalamic 5-HT1Areceptor–Gz-protein signaling, measured as the ACTH and oxytocin responses to an injection of the 5-HT1A agonist 8-OH-DPAT. We characterized this functional heterologous desensitization of 5-HT1A receptors in rats and examined some of the mechanisms that are involved. A time course experiment revealed that DOI produces a delayed and reversible reduction of the ACTH and oxytocin responses to an 8-OH-DPAT challenge. The maximal desensitization occurred at 2 hr, and it disappeared 24 hr after DOI injection. The desensitization was dose-dependent, and it shifted the oxytocin and ACTH dose–response curves of 8-OH-DPAT to the right (increased ED50) with no change in their maximal responses (E max). The 5-HT2A receptor antagonist MDL 100,907 prevented the DOI-induced desensitization, indicating that 5-HT2Areceptors mediate the effect of DOI. Analysis of the components of the 5-HT1A receptor–Gz-protein signaling system showed that DOI did not alter the level of membrane-associated Gz-proteins in the hypothalamus. Additionally, DOI did not alter the binding of [3H]8-OH-DPAT or the inhibition by GTPγS of [3H]8-OH-DPAT binding in the hypothalamus. In conclusion, the activation of 5-HT2Areceptors induces a transient functional desensitization of 5-HT1A receptor signaling in the hypothalamus, which may occur distal to the 5-HT1A receptor–Gz-protein interface

The Nature of LINERs

We present $J$-band ($1.15-1.35 \mu$m) spectroscopy of a sample of nine galaxies showing some degree of LINER activity (classical LINERs, weak-[O {\sc i}] LINERs and transition objects), together with $H$-band spectroscopy for some of them. A careful subtraction of the stellar continuum allows us to obtain reliable [Fe {\sc ii}]$1.2567 \mu$m/Pa$\beta$ line ratios. We conclude that different types of LINERs (i.e., photoionized by a stellar continuum or by an AGN) cannot be easily distinguished based solely on the [Fe {\sc ii}]$1.2567 \mu$m/Pa$\beta$ line ratio. The emission line properties of many LINERs can be explained in terms of an aging starburst. The optical line ratios of these LINERs are reproduced by a model with a metal-rich H {\sc ii} region component photoionized with a single stellar temperature $T_* = 38,000$K, plus a supernova remnant (SNR) component. The [Fe {\sc ii}] line is predominantly excited by shocks produced by SNRs in starbursts and starburst-dominated LINERs, while Pa$\beta$ tracks H {\sc ii} regions ionized by massive young stars. The contribution from SNRs to the overall emission line spectrum is constrained by the [Fe {\sc ii}]$1.2567 \mu$m/Pa$\beta$ line ratio. Although our models for aging starbursts are constrained only by these infrared lines, they consistently explain the optical spectra of the galaxies also. The LINER-starburst connection is tested by predicting the time dependence of the ratio of the ionizing luminosity ($L_{\rm ion}$) to the supernova rate (SNr), $L_{\rm ion}$/(SNr). We predict the relative number of starbursts to starburst-dominated LINERs (aging starbursts) and show that it is in approximate agreement with survey findings for nearby galaxies.Comment: Accepted in ApJ (19 pages, 8 figures, uses emulateapj.sty

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

HV/HR-CMOS sensors for the ATLAS upgrade—concepts and test chip results

In order to extend its discovery potential, the Large Hadron Collider (LHC) will have a major upgrade (Phase II Upgrade) scheduled for 2022. The LHC after the upgrade, called High-Luminosity LHC (HL-LHC), will operate at a nominal leveled instantaneous luminosity of 5× 1034 cm−2 s−1, more than twice the expected Phase I . The new Inner Tracker needs to cope with this extremely high luminosity. Therefore it requires higher granularity, reduced material budget and increased radiation hardness of all components. A new pixel detector based on High Voltage CMOS (HVCMOS) technology targeting the upgraded ATLAS pixel detector is under study. The main advantages of the HVCMOS technology are its potential for low material budget, use of possible cheaper interconnection technologies, reduced pixel size and lower cost with respect to traditional hybrid pixel detector. Several first prototypes were produced and characterized within ATLAS upgrade R&D effort, to explore the performance and radiation hardness of this technology. In this paper, an overview of the HVCMOS sensor concepts is given. Laboratory tests and irradiation tests of two technologies, HVCMOS AMS and HVCMOS GF, are also given

Radiation-hard active pixel sensors for HL-LHC detector upgrades based on HV-CMOS technology

Luminosity upgrades are discussed for the LHC (HL-LHC) which would make updates to the detectors necessary, requiring in particular new, even more radiation-hard and granular, sensors for the inner detector region. A proposal for the next generation of inner detectors is based on HV-CMOS: a new family of silicon sensors based on commercial high-voltage CMOS technology, which enables the fabrication of part of the pixel electronics inside the silicon substrate itself. The main advantages of this technology with respect to the standard silicon sensor technology are: low material budget, fast charge collection time, high radiation tolerance, low cost and operation at room temperature. A traditional readout chip is still needed to receive and organize the data from the active sensor and to handle high-level functionality such as trigger management. HV-CMOS has been designed to be compatible with both pixel and strip readout. In this paper an overview of HV2FEI4, a HV-CMOS prototype in 180 nm AMS technology, will be given. Preliminary results after neutron and X-ray irradiation are shown

Hard X-ray spectral variability of the brightest Seyfert AGN in the Swift/BAT sample

Aims: We used data from the 58 month long, continuous Swift/Burst Alert Telescope (BAT) observations of the five brightest Seyfert galaxies at hard X-rays, to study their flux and spectral variability in the 20-100 keV energy band. The column density in these objects is less than 10^24 cm-2, which implies that the Swift/BAT data allow us to study the "true" variability of the central source. Results: All objects show significant variations, with an amplitude which is similar to the AGN variability amplitude at energies below 10 keV. We found evidence for an anti-correlation between variability amplitude and black hole mass. The light curves in both bands are well correlated, with no significant delays on time scales as short as 2 days. NGC 4151 and NGC 2110 do not show spectral variability, but we found a significant anti-correlation between hardness ratios and source flux in NGC 4388 (and NGC 4945, IC 4329, to a lesser extent). This "softer when brighter" behaviour is similar to what has been observed at energies below 10 keV, and cannot be explained if the continuum varies only in flux; the intrinsic shape should also steepen with increasing flux. Conclusions: The presence of significant flux variations indicate that the central source in these objects is intrinsically variable on time scales as short as 1-2 days. The intrinsic slope of the continuum varies with the flux (at least in NGC 4388). The positive "spectral slope-flux" correlation can be explained if the temperature of the hot corona decreases with increasing flux. The lack of spectral variations in two objects, could be due to the fact that they may operate in a different "state", as their accretion rate is less than 1% of the Eddington limit (significantly smaller than the rate of the other three objects in the sample).Comment: Accepted (29/10/11) for publication in A&A (12 pages, containing 14 figures and 2 tables). (Abstract shortened --see link for the complete one

Component analysis of errors in satellite-based precipitation estimates

Satellite-based precipitation estimates have great potential for a wide range of critical applications, but their error characteristics need to be examined and understood. In this study, six (6) high-resolution, satellite-based precipitation data sets are evaluated over the contiguous United States against a gauge-based product. An error decomposition scheme is devised to separate the errors into three independent components, hit bias, missed precipitation, and false precipitation, to better track the error sources associated with the satellite retrieval processes. Our analysis reveals the following. (1) The three components for each product are all substantial, with large spatial and temporal variations. (2) The amplitude of individual components sometimes is larger than that of the total errors. In such cases, the smaller total errors are resulting from the three components canceling one another. (3) All the products detected strong precipitation (\u3e40 mm/d) well, but with various biases. They tend to overestimate in summer and underestimate in winter, by as much as 50% in either season, and they all miss a significant amount of light precipitation (\u3c10 mm/d), up to 40%. (4) Hit bias and missed precipitation are the two leading error sources. In summer, positive hit bias, up to 50%, dominates the total errors for most products. (5) In winter, missed precipitation over mountainous regions and the northeast, presumably snowfall, poses a common challenge to all the data sets. On the basis of the findings, we recommend that future efforts focus on reducing hit bias, adding snowfall retrievals, and improving methods for combining gauge and satellite data. Strategies for future studies to establish better links between the errors in the end products and the upstream data sources are also proposed