Molecular-beam epitaxy of monolayer and bilayer WSe2: a scanning tunneling microscopy/spectroscopy study and deduction of exciton binding energy

Interest in two-dimensional (2D) transition-metal dichalcogenides (TMDs) has prompted some recent efforts to grow ultrathin layers of these materials epitaxially using molecular-beam epitaxy (MBE). However, growths of monolayer (ML) and bilayer (BL) WSe2—an important member of the TMD family—by the MBE method remain uncharted, probably because of the difficulty in generating tungsten fluxes from the elemental source. In this work, we present a scanning tunneling microscopy and spectroscopy (STM/S) study of MBE-grown WSe2 ML and BL, showing atomically flat epifilm with no domain boundary (DB) defect. This contrasts epitaxial MoSe2 films grown by the same method, where a dense network of the DB defects is present. The STS measurements of ML and BL WSe2 domains of the same sample reveal not only the bandgap narrowing upon increasing the film thickness from ML to BL, but also a band-bending effect across the boundary (step) between ML and BL domains. This band-bending appears to be dictated by the edge states at steps of the BL islands. Finally, comparison is made between the STS-measured electronic bandgaps with the exciton emission energies measured by photoluminescence, and the exciton binding energies in ML and BL WSe2 (and MoSe2) are thus estimated.postprin

Imaging and Dynamics of Light Atoms and Molecules on Graphene

Observing the individual building blocks of matter is one of the primary goals of microscopy. The invention of the scanning tunneling microscope [1] revolutionized experimental surface science in that atomic-scale features on a solid-state surface could finally be readily imaged. However, scanning tunneling microscopy has limited applicability due to restrictions, for example, in sample conductivity, cleanliness, and data aquisition rate. An older microscopy technique, that of transmission electron microscopy (TEM) [2, 3] has benefited tremendously in recent years from subtle instrumentation advances, and individual heavy (high atomic number) atoms can now be detected by TEM [4 - 7] even when embedded within a semiconductor material [8, 9]. However, detecting an individual low atomic number atom, for example carbon or even hydrogen, is still extremely challenging, if not impossible, via conventional TEM due to the very low contrast of light elements [2, 3, 10 - 12]. Here we demonstrate a means to observe, by conventional transmision electron microscopy, even the smallest atoms and molecules: On a clean single-layer graphene membrane, adsorbates such as atomic hydrogen and carbon can be seen as if they were suspended in free space. We directly image such individual adatoms, along with carbon chains and vacancies, and investigate their dynamics in real time. These techniques open a way to reveal dynamics of more complex chemical reactions or identify the atomic-scale structure of unknown adsorbates. In addition, the study of atomic scale defects in graphene may provide insights for nanoelectronic applications of this interesting material.Comment: 9 pages manuscript and figures, 9 pages supplementary informatio

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Green tea polyphenols supplementation and Tai Chi exercise for postmenopausal osteopenic women: safety and quality of life report

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that both green tea polyphenols (GTP) and Tai Chi (TC) exercise may benefit bone health in osteopenic women. However, their safety in this population has never been systematically investigated. In particular, there have been hepatotoxicity concerns related to green tea extract. This study was to evaluate the safety of 24 weeks of GTP supplementation combined with TC exercise in postmenopausal osteopenic women, along with effects on quality of life in this population.</p> <p>Methods</p> <p>171 postmenopausal women with osteopenia were randomly assigned to 4 treatment arms for 24 weeks: (1) Placebo (500 mg starch/day), (2) GTP (500 mg GTP/day), (3) Placebo + TC (placebo plus TC training at 60 min/session, 3 sessions/week), and (4) GTP + TC (GTP plus TC training). Safety was examined by assessing liver enzymes (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, and total bilirubin at baseline and every 4 weeks. Kidney function (urea nitrogen and creatinine), calcium, and inorganic phosphorus were also assessed at the same times. Qualify of life using SF-36 questionnaire was evaluated at baseline, 12, and 24 weeks. A mixed model of repeated measures ANOVA was applied for analysis.</p> <p>Results</p> <p>150 subjects completed the study (12% attrition rate). The compliance rates for study agents and TC exercise were 89% and 83%, respectively. Neither GTP supplementation nor TC exercise affected liver or kidney function parameters throughout the study. No adverse event due to study treatment was reported by the participants. TC exercise significantly improved the scores for role-emotional and mental health of subjects, while no effect on quality of life was observed due to GTP supplementation.</p> <p>Conclusions</p> <p>GTP at a dose of 500 mg/day and/or TC exercise at 3 hr/week for 24 weeks appear to be safe in postmenopausal osteopenic women, particularly in terms of liver and kidney functions. TC exercise for 24 weeks (3 hr/wk) significantly improved quality of life in terms of role-emotional and mental health in these subjects. ClinicalTrials.gov identifier: NCT00625391.</p

Uneven splitting-ratio 1x2 multimode interference splitters based on silicon wire waveguides

Two types of 1x2 multi-mode interference (MMI) splitters with splitting ratios of 85:15 and 72:28 are designed. On the basis of a numerical simulation, an optimal length of the MMI section is obtained. Subsequently, the devices are fabricated and tested. The footprints of the rectangular MMI regions are only 3x18.2 and 3x14.3 (mu m). The minimum excess losses are 1.4 and 1.1 dB. The results of the test on the splitting ratios are consistent with designed values. The devices can be applied in ultra-compact photonic integrated circuits to realize the &quot;tap&quot; function

Quality of reporting according to the CONSORT, STROBE and Timmer instrument at the American Burn Association (ABA) annual meetings 2000 and 2008

<p>Abstract</p> <p>Background</p> <p>The quality of oral and poster conference presentations differ. We hypothesized that the quality of reporting is better in oral abstracts than in poster abstracts at the American Burn Association (ABA) conference meeting.</p> <p>Methods</p> <p>All 511 abstracts (2000: N = 259, 2008: N = 252) from the ABA annual meetings in year 2000 and 2008 were screened. RCT's and obervational studies were analyzed by two independent examiners regarding study design and quality of reporting for randomized-controlled trials (RCT) by CONSORT criteria, observational studies by the STROBE criteria and additionally the Timmer instrument.</p> <p>Results</p> <p>Overall, 13 RCT's in 2000 and 9 in 2008, 77 observational studies in 2000 and 98 in 2008 were identified. Of the presented abstracts, 5% (oral; 7%(n = 9) vs. poster; 3%(n = 4)) in 2000 and 4% ((oral; 5%(n = 7) vs. poster; 2%(n = 2)) in 2008 were randomized controlled trials. The amount of observational studies as well as experimental studies accepted for presentation was not significantly different between oral and poster in both years. Reporting quality of RCT was for oral vs. poster abstracts in 2000 (CONSORT; 7.2 ± 0.8 vs. 7 ± 0, p = 0.615, CI -0.72 to 1.16, Timmer; 7.8 ± 0.7 vs. 7.5 ± 0.6,) and 2008 (CONSORT; 7.2 ± 1.4 vs. 6.5 ± 1, Timmer; 9.7 ± 1.1 vs. 9.5 ± 0.7). While in 2000, oral and poster abstracts of observational studies were not significantly different for reporting quality according to STROBE (STROBE; 8.3 ± 1.7 vs. 8.9 ± 1.6, p = 0.977, CI -37.3 to 36.3, Timmer; 8.6 ± 1.5 vs. 8.5 ± 1.4, p = 0.712, CI -0.44 to 0.64), in 2008 oral observational abstracts were significantly better than posters (STROBE score; 9.4 ± 1.9 vs. 8.5 ± 2, p = 0.005, CI 0.28 to 1.54, Timmer; 9.4 ± 1.4 vs. 8.6 ± 1.7, p = 0.013, CI 0.32 to 1.28).</p> <p>Conclusions</p> <p>Poster abstract reporting quality at the American Burn Association annual meetings in 2000 and 2008 is not necessarily inferior to oral abstracts as far as study design and reporting quality of clinical trials are concerned. The primary hypothesis has to be rejected. However, endorsement for the comprehensive use of the CONSORT and STROBE criteria might further increase the quality of reporting ABA conference abstracts in the future.</p

Topological Photonics

Topology is revolutionizing photonics, bringing with it new theoretical discoveries and a wealth of potential applications. This field was inspired by the discovery of topological insulators, in which interfacial electrons transport without dissipation even in the presence of impurities. Similarly, new optical mirrors of different wave-vector space topologies have been constructed to support new states of light propagating at their interfaces. These novel waveguides allow light to flow around large imperfections without back-reflection. The present review explains the underlying principles and highlights the major findings in photonic crystals, coupled resonators, metamaterials and quasicrystals.Comment: progress and review of an emerging field, 12 pages, 6 figures and 1 tabl