Expected Sensitivity to Galactic/Solar Axions and Bosonic Super-WIMPs based on the Axio-electric Effect in Liquid Xenon Dark Matter Detectors

We present systematic case studies to investigate the sensitivity of axion searches by liquid xenon detectors, using the axio-electric effect (analogue of the photoelectric effect) on xenon atoms. Liquid xenon is widely considered to be one of the best target media for detection of WIMPs (Weakly Interacting Massive Particles which may form the galactic dark matter) using nuclear recoils. Since these detectors also provide an extremely low radioactivity environment for electron recoils, very weakly-interacting low-mass particles (< 100 keV/c^2), such as the hypothetical axion, could be detected as well - in this case using the axio-electric effect. Future ton-scale liquid Xe detectors will be limited in sensitivity only by irreducible neutrino background (pp-chain solar neutrino and the double beta decay of 136Xe) in the mass range between 1 and 100 keV/c^2. Assuming one ton-year of exposure, galactic axions (as non-relativistic dark matter) could be detected if the axio-electric coupling g_Ae is greater than 10^-14 at 1 keV/c^2 (or $10^-13 at 100 keV/c^2). Below a few keV/c^2, and independent of the mass, a solar axion search would be sensitive to a coupling g_Ae ~ 10^-12. This limit will set a stringent upper bound on axion mass for the DFSV and KSVZ models for the mass ranges m_A < 0.1 eV/c^2 and < 10 eV/c^2, respectively. Vector-boson dark matter could also be detected for a coupling constant alpha'/alpha > 10^-33 (for mass 1 keV/c^2) or > 10^-27 (for mass 100 keV/c^2).Comment: 17 pages, 10 figure

Unexpected positive intraoperative cultures (UPIC) at index osseointegration do not lead to increased postoperative infectious events

Introduction: The most common complication following transcutaneous osseointegration for amputees is infection. Although an obvious source of contamination is the permanent stoma, operative site contamination at the time of implantation may be an additional source. This study investigates the impact of unexpected positive intraoperative cultures (UPIC) on postoperative infection. Methods: Charts were reviewed for 8 patients with UPIC and 22 patients with negative intraoperative cultures (NIC) who had at least 1 year of post-osseointegration follow-up. All patients had 24 h of routine postoperative antibiotic prophylaxis, with UPIC receiving additional antibiotics guided by culture results. The main outcome measure was postoperative infection intervention, which was graded as (0) none, (1) antibiotics unrelated to the initial surgery, (2) operative debridement with implant retention, or (3) implant removal. Results: The UPIC vs. NIC rate of infection management was as follows: Grade 0, 6/8 = 75 % vs. 14/22 = 64 %, p = 0.682; Grade 1, 2/8 = 25 % vs. 8/22 = 36.4 % (Fisher's p = 0.682); Grade 2, 1/8 = 12.5 % vs. 0/22 = 0 % (Fisher's p = 0.267); Grade 3, 0/8 = 0 % vs. 1/22 = 4.5 % (Fisher's p = 1.000). No differences were statistically significant. Conclusions: UPIC at index osseointegration, managed with directed postoperative antibiotics, does not appear to increase the risk of additional infection management. The therapeutic benefit of providing additional directed antibiotics versus no additional antibiotics following UPIC is unknown and did not appear to increase the risk of other adverse outcomes in our cohort.</p

Wigner's Dynamical Transition State Theory in Phase Space: Classical and Quantum

A quantum version of transition state theory based on a quantum normal form (QNF) expansion about a saddle-centre-...-centre equilibrium point is presented. A general algorithm is provided which allows one to explictly compute QNF to any desired order. This leads to an efficient procedure to compute quantum reaction rates and the associated Gamov-Siegert resonances. In the classical limit the QNF reduces to the classical normal form which leads to the recently developed phase space realisation of Wigner's transition state theory. It is shown that the phase space structures that govern the classical reaction d ynamicsform a skeleton for the quantum scattering and resonance wavefunctions which can also be computed from the QNF. Several examples are worked out explicitly to illustrate the efficiency of the procedure presented.Comment: 132 pages, 31 figures, corrected version, Nonlinearity, 21 (2008) R1-R11

The role of mechanotransduction versus hypoxia during simulated orthodontic compressive strain—an in vitro study of human periodontal ligament fibroblasts

During orthodontic tooth movement (OTM) mechanical forces trigger pseudo-inflammatory, osteoclastogenic and remodelling processes in the periodontal ligament (PDL) that are mediated by PDL fibroblasts via the expression of various signalling molecules. Thus far, it is unknown whether these processes are mainly induced by mechanical cellular deformation (mechanotransduction) or by concomitant hypoxic conditions via the compression of periodontal blood vessels. Human primary PDL fibroblasts were randomly seeded in conventional six-well cell culture plates with O-2-impermeable polystyrene membranes and in special plates with gas-permeable membranes (Lumox (R), Sarstedt), enabling the experimental separation of mechanotransducive and hypoxic effects that occur concomitantly during OTM. To simulate physiological orthodontic compressive forces, PDL fibroblasts were stimulated mechanically at 2 g.cm(-2) for 48 h after 24 h of pre-incubation. We quantified the cell viability by MTT assay, gene expression by quantitative real-time polymerase chain reaction (RT-qPCR) and protein expression by western blot/enzyme-linked immunosorbent assays (ELISA). In addition, PDL-fibroblast-mediated osteoclastogenesis (TRAP(+) cells) was measured in a 72-h coculture with RAW264.7 cells. The expression of HIF-1 alpha, COX-2, PGE2, VEGF, COL1A2, collagen and ALPL, and the RANKL/OPG ratios at the mRNA/protein levels during PDL-fibroblast-mediated osteoclastogenesis were significantly elevated by mechanical loading irrespective of the oxygen supply, whereas hypoxic conditions had no significant additional effects. The cellular-molecular mediation of OTM by PDL fibroblasts via the expression of various signalling molecules is expected to be predominantly controlled by the application of force (mechanotransduction), whereas hypoxic effects seem to play only a minor role. In the context of OTM, the hypoxic marker HIF-1 alpha does not appear to be primarily stabilized by a reduced O-2 supply but is rather stabilised mechanically

Selective cyclooxygenase-2 silencing mediated by engineered E. coli and RNA interference induces anti-tumour effects in human colon cancer cells

Colorectal cancer (CRC) has an elevated incidence worldwide and represents one of the most aggressive human tumours. Many experimental data provide the evidence of a strong association between cyclooxygenase-2 (COX-2) enzyme overexpression and colon tumorigenesis. Furthermore, it has been demonstrated that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs, a class of COX-2 inhibitors), partially protects patients from CRC development and progression. Unfortunately, NSAIDs have been shown to induce severe side effects in chronically treated patients and, therefore, new strategies for selective COX-2 blockade are needed. In this paper we present an innovative COX-2 silencing approach mediated by RNA Interference (RNAi) which is a mechanism we have already described as a powerful tool to knockdown COX-2 protein in CRC cells. In particular, we developed an improved method to gain a highly selective COX-2 silencing in CRC cells by a tumour-dependent expression of anti-COX-2 short hairpin RNA (shCOX-2). Moreover, we efficiently delivered shCOX-2 expressing vectors in CRC cells, in vitro and ex vivo, by using engineered Escherichia coli strains, capable of infecting and invading human tumour cells (InvColi). Combining the highly selective shCOX-2 expression and the delivery of COX-2 silencers mediated by InvColi strains, we obtained a strong reduction of both proliferative and invasive behaviour of tumour cells and we also confirmed the pivotal role of COX-2 overexpression for the survival of CRC cells. Finally, ex vivo data showed a global anti-inflammatory and anti-tumour effect elicited by COX-2 silencing

Targeted Sister Chromatid Cohesion by Sir2

The protein complex known as cohesin binds pericentric regions and other sites of eukaryotic genomes to mediate cohesion of sister chromatids. In budding yeast Saccharomyces cerevisiae, cohesin also binds silent chromatin, a repressive chromatin structure that functionally resembles heterochromatin of higher eukaryotes. We developed a protein-targeting assay to investigate the mechanistic basis for cohesion of silent chromatin domains. Individual silencing factors were tethered to sites where pairing of sister chromatids could be evaluated by fluorescence microscopy. We report that the evolutionarily conserved Sir2 histone deacetylase, an essential silent chromatin component, was both necessary and sufficient for cohesion. The cohesin genes were required, but the Sir2 deacetylase activity and other silencing factors were not. Binding of cohesin to silent chromatin was achieved with a small carboxyl terminal fragment of Sir2. Taken together, these data define a unique role for Sir2 in cohesion of silent chromatin that is distinct from the enzyme's role as a histone deacetylase

Female Sex Worker Social Networks and STI/HIV Prevention in South China

Reducing harm associated with selling and purchasing sex is an important public health priority in China, yet there are few examples of sustainable, successful programs to promote sexual health among female sex workers. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female sex workers to collectively organize, advocate for their rights, and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female sex workers in South China to determine their potential for sexual health promotion.Semi-structured interviews with 34 low-income female sex workers and 28 health outreach members were used to examine how social relationships affected condom use and negotiation, STI/HIV testing and health-seeking behaviors, and dealing with violent clients. These data suggested that sex worker's laoxiang (hometown social connections) were more powerful than relationships between women selling sex at the same venue in establishing the terms and risk of commercial sex. Female sex workers from the same hometown often migrated to the city with their laoxiang and these social connections fulfilled many of the functions of nongovernmental organizations, including collective mobilization, condom promotion, violence mitigation, and promotion of health-seeking behaviors. Outreach members observed that sex workers accompanied by their laoxiang were often more willing to accept STI/HIV testing and trust local sexual health services.Organizing STI/HIV prevention services around an explicitly defined laoxiang social network may provide a strong foundation for sex worker health programs. Further research on dyadic interpersonal relationships between female sex workers, group dynamics and norm establishment, and the social network characteristics are needed

Gene regulatory network reveals oxidative stress as the underlying molecular mechanism of type 2 diabetes and hypertension

<p>Abstract</p> <p>Background</p> <p>The prevalence of diabetes is increasing worldwide. It has been long known that increased rates of inflammatory diseases, such as obesity (OBS), hypertension (HT) and cardiovascular diseases (CVD) are highly associated with type 2 diabetes (T2D). T2D and/or OBS can develop independently, due to genetic, behavioral or lifestyle-related variables but both lead to oxidative stress generation. The underlying mechanisms by which theses complications arise and manifest together remain poorly understood. Protein-protein interactions regulate nearly every living process. Availability of high-throughput genomic data has enabled unprecedented views of gene and protein co-expression, co-regulations and interactions in cellular systems.</p> <p>Methods</p> <p>The present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D. The genes differentially regulated through T2D were 'mined' and their 'wirings' were studied to get a more complete understanding of the overall gene network topology and their role in disease progression.</p> <p>Results</p> <p>By analyzing the genes related to T2D, HT and OBS, a highly regulated gene-disease integrated network model has been developed that provides useful functional linkages among groups of genes and thus addressing how different inflammatory diseases are connected and propagated at genetic level. Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed. The results from this study revealed that the oxidative stress mediated regulation cascade is the common mechanistic link among the pathogenesis of T2D, HT and other inflammatory diseases such as OBS.</p> <p>Conclusion</p> <p>The findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.</p

Tumour–stroma interactions in colorectal cancer: converging on β-catenin activation and cancer stemness

Sporadic cases of colorectal cancer are primarily initiated by gene mutations in members of the canonical Wnt pathway, ultimately resulting in β-catenin stabilisation. Nevertheless, cells displaying nuclear β-catenin accumulation are nonrandomly distributed throughout the tumour mass and preferentially localise along the invasive front where parenchymal cells are in direct contact with the stromal microenvironment. Here, we discuss the putative role played by stromal cell types in regulating β-catenin intracellular accumulation in a paracrine fashion. As such, the tumour microenvironment is likely to maintain the cancer stem cell phenotype in a subset of cells, thus mediating invasion and metastasis