A window to quantum gravity phenomena in the emergence of the seeds of cosmic structure

Inflationary cosmology has, in the last few years,received a strong dose of support from observations. The fact that the fluctuation spectrum can be extracted from the inflationary scenario through an analysis that involves quantum field theory in curved space-time, and that it coincides with the observational data has lead to a certain complacency in the community, which prevents the critical analysis of the obscure spots in the derivation. We argue here briefly, as we have discussed in more detail elsewhere, that there is something important missing in our understanding of the origin of the seeds of Cosmic Structure, as is evidenced by the fact that in the standard accounts the inhomogeneity and anisotropy of our universe seems to emerge from an exactly homogeneous andisotropic initial state through processes that do not break those symmetries. This article gives a very brief recount of the problems faced by the arguments based on established physics. The conclusion is that we need some new physics to be able to fully address the problem. The article then exposes one avenue that has been used to address the central issue and elaborates on the degree to which, the new approach makes different predictions from the standard analyses. The approach is inspired on Penrose's proposals that Quantum Gravity might lead to a real, dynamical collapse of the wave function, a process that we argued has the properties needed to extract us from the theoretical impasse described above.Comment: 13 pages, 3 figures. To appear in DICE 2008 conference proceeding

Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery

<p>Abstract</p> <p>Background</p> <p>Adenoviral vectors have provided effective methods for <it>in vivo </it>gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector re-application. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes.</p> <p>Methods</p> <p><it>In vitro</it>, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. <it>In vivo</it>, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector.</p> <p>Results</p> <p>The results show an acute induction of type-I-interferon after <it>in vitro </it>transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response <it>in vivo</it>.</p> <p>Conclusion</p> <p>The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin.</p

Discussing Depression with Vietnamese American Patients

Background Asian patients preferentially seek mental health care from their primary care providers but are unlikely to receive it. Primary care providers need culturally-informed strategies for addressing stigmatizing illnesses. Methods 11 Vietnamese American community members participated in semi-structured interviews. Interviews were audio-taped and transcribed. The grounded theory approach was used for qualitative coding and thematic analysis. Results Vietnamese community members describe experiences with depression under four themes: (1) Stigma and face; (2) Social functioning and the role of the family; (3) Traditional healing and beliefs about medications; and (4) Language and culture. Based on this data, we offer suggestions for improving culturally-informed care for Vietnamese Americans. Disucssion Our study adds to the research aimed at improving communication and health care relationships between physicians and Vietnamese American patients. Physicians should learn to tailor their interviewing style to the increasingly diverse patient population

Comparing the Epidermal Growth Factor Interaction with Four Different Cell Lines: Intriguing Effects Imply Strong Dependency of Cellular Context

The interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of 125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®

Integrated Insulation System for Automotive Cryogenic Storage Tanks

No abstract availabl

Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML

Expression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML.In this study, we investigated the potential roles of dileucine and tyrosine-based motifs within the cytoplasmic domain of the G-CSFR in modulating ligand/receptor internalization. Using standard binding assays with radiolabeled ligand and COS-7 cells, substitutions in the dileucine motif or deletion of tyrosine residues in the G-CSFR did not alter internalization. Attachment of the transferrin receptor YTRF internalization motif to a truncated G-CSFR form from a patient with SCN/AML corrected defective internalization, but not receptor degradation suggesting that receptor internalization and degradation occur independently via distinct domains and/or processes.Our data suggest that distinct domains within the G-CSFR mediate separate processes for receptor internalization and degradation. Our findings using standard binding assays differ from recently published data utilizing flow cytometry

Human RAD18 Interacts with Ubiquitylated Chromatin Components and Facilitates RAD9 Recruitment to DNA Double Strand Breaks

RAD18 is an ubiquitin ligase involved in replicative damage bypass and DNA double-strand break (DSB) repair processes. We found that RPA is required for the dynamic pattern of RAD18 localization during the cell cycle, and for accumulation of RAD18 at sites of γ-irradiation-induced DNA damage. In addition, RAD18 colocalizes with chromatin-associated conjugated ubiquitin and ubiquitylated H2A throughout the cell cycle and following irradiation. This localization pattern depends on the presence of an intact, ubiquitin-binding Zinc finger domain. Using a biochemical approach, we show that RAD18 directly binds to ubiquitylated H2A and several other unknown ubiquitylated chromatin components. This interaction also depends on the RAD18 Zinc finger, and increases upon the induction of DSBs by γ-irradiation. Intriguingly, RAD18 does not always colocalize with regions that show enhanced H2A ubiquitylation. In human female primary fibroblasts, where one of the two X chromosomes is inactivated to equalize X-chromosomal gene expression between male (XY) and female (XX) cells, this inactive X is enriched for ubiquitylated H2A, but only rarely accumulates RAD18. This indicates that the binding of RAD18 to ubiquitylated H2A is context-dependent. Regarding the functional relevance of RAD18 localization at DSBs, we found that RAD18 is required for recruitment of RAD9, one of the components of the 9-1-1 checkpoint complex, to these sites. Recruitment of RAD9 requires the functions of the RING and Zinc finger domains of RAD18. Together, our data indicate that association of RAD18 with DSBs through ubiquitylated H2A and other ubiquitylated chromatin components allows recruitment of RAD9, which may function directly in DSB repair, independent of downstream activation of the checkpoint kinases CHK1 and CHK2

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on Dietary Reference Values for energy

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived dietary reference values for energy, which are provided as average requirements (ARs) of specified age and sex groups. For children and adults, total energy expenditure (TEE) was determined factorially from estimates of resting energy expenditure (REE) plus the energy needed for various levels of physical activity (PAL) associated with sustainable lifestyles in healthy individuals. To account for uncertainties inherent in the prediction of energy expenditure, ranges of the AR for energy were calculated with several equations for predicting REE in children (1-17 years) and adults. For practical reasons, only the REE estimated by the equations of Henry (2005) was used in the setting of the AR and multiplied with PAL values of 1.4, 1.6, 1.8 and 2.0, which approximately reflect low active (sedentary), moderately active, active and very active lifestyles. For estimating REE in adults, body heights measured in representative national surveys in 13 EU Member States and body masses calculated from heights assuming a body mass index of 22 kg/m2 were used. For children, median body masses and heights from the WHO Growth Standards or from harmonised growth curves of children in the EU were used. Energy expenditure for growth was accounted for by a 1 % increase of PAL values for each age group. For infants (7-11 months), the AR was derived from TEE estimated by regression equation based on doubly labelled water (DLW) data, plus the energy needs for growth. For pregnant and lactating women, the additional energy for the deposition of newly formed tissue, and for milk output, was derived from data obtained by the DLW method and from factorial estimates, respectively. The proposed ARs for energy may need to be adapted depending on specific objectives and target populations