Adsorption and desorption of deuterium on partially oxidized Si(100) surfaces

Adsorption and desorption of deuterium are studied on the partially oxidized Si(100) surfaces. The partial oxygen coverage causes a decrease in the initial adsorption probability of D atoms. The observed D2 temperature-programmed-desorption (TPD) spectra comprise of multiple components depending on the oxygen coverage (θO). For θO=0.1ML the D2 TPD spectrum is deconvoluted into four components, each of which has a peak in the temperature region higher than the D2 TPD peaking at 780 K on the oxygen free surface. The highest TPD component with a peak around 1040 K is attributed to D adatoms on Si dimers backbonded by an oxygen atom. The other components are attributed to D adatoms on the nearest or second nearest sites of the O-backbonded Si dimers. D adatoms on the partially oxidized Si surfaces are abstracted by gaseous H atoms along two different abstraction pathways: one is the pathway along direct abstraction (ABS) to form HD molecules and the other is the pathway along indirect abstraction via collision-induced-desorption (CID) of D adatoms to form D2 molecules. The ABS pathway is less seriously affected by oxygen adatoms. On the other hand, the CID pathway receives a strong influence of oxygen adatoms since the range of surface temperature effective for CID is found to considerably shift to higher surface temperatures with increasing θO. Gradual substitution of D adatoms with H atoms during H exposure results in HD desorption along the CID pathway in addition to the ABS one. By employing a modulated beam technique the CID-related HD desorption is directly distinguished from the ABS-related one

Structural variation in the incoming Philippine Sea plate along the Nankai Trough

The next large-thrust earthquake along the Nankai Trough, southwest Japan is concerned to occur within this century. Nonvolcanic deep low-frequency tremors and earthquakes are observed around the down-dip limit of the coseismic rupture zone of the last Tonankai and Nankai earthquakes [Obara, 2002]. One of the causes of these low-frequency seismic phenomena is considered to be fluid generated by dehydration processes from the subducting slab. It is important to investigate structural variation in the incoming Philippine Sea plate, including its fluid content to understand the generation of the low-frequency seismic phenomena as well as large-thrust earthquakes. In 2014, we conducted the seismic refraction and reflection survey in the northern margin of the Shikoku Basin, where the Philippine Sea plate is subducting beneath the Eurasia plate at the Nankai Trough. We conducted a 360km long seismic profile about 50-60km seaward of the deformation front along the Nankai Trough. 35 OBSs were deployed along the profile with the interval of 10km. A tuned airgun array shot with a total volume of 7800 cu. in. every 200m for OBSs, and 380 cu. in. every 37.5m for a 192-channel, 1.2km-long hydrophone streamer. In the time-migrated reflection section, variation in the sedimentary layer and basement reflection can be recognized off Shikoku, which may correspond with the boundary of the plate age proposed by magnetic lineation [Okino et al., 1999]. In the southwestern part of the profile, the basement reflection is not always clear, and shows smooth structure. Comparatively in the northeastern part, basement changes in depth drastically with prominent reflection signals. In the wide-angle OBS data, PS converted waves are clearly observed over along the seismic profile. In particular, PS converted waves refracted from the uppermost mantle can be remarkably recognized in the northeastern half of the profile. We will show the structural variation of the oceanic crust of the incoming plate, which may be related to the formation of the Shikoku Basin as well as the generation of the various seismic activities including the low-frequency events, by using OBS data. This study is part of ‘Research project for compound disaster mitigation on the great earthquakes and tsunamis around the Nankai Trough region’ funded by MEXT, Japan.Poster abstract T51A-4578 presented at 2014 Fall Meeting, AGU, San Francisco, Calif., 15-19 Dec.http://www.godac.jamstec.go.jp/darwin/cruise/kairei/kr14-05/ehttp://www.godac.jamstec.go.jp/darwin/cruise/kaiyo/ky14-07/

Vacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans

Peer reviewedPreprin

Structural variation in the incoming Philippine Sea plate along the southwestern Nankai Trough

B32-08発表要旨, 日本地震学会2014年度秋季大会（2014年11月24日～26日, 新潟県新潟市）http://www.godac.jamstec.go.jp/darwin/cruise/kairei/kr14-05/ehttp://www.godac.jamstec.go.jp/darwin/cruise/kaiyo/ky14-07/

STAT3 the oncogene - still eluding therapy?

The STAT family of transcription factors (signal transducers and activators of transcription) transduce signals from cytokine receptors to the nucleus, where STAT dimers bind to DNA and regulate transcription. STAT3 is the most ubiquitous of the STATs, being activated by a wide variety of cytokines and growth factors. STAT3 has many roles in physiological processes such as inflammatory signalling, aerobic glycolysis and immune suppression, and was also the first family member shown to be aberrantly activated in a wide range of both solid and liquid tumours. STAT3 promotes tumorigenesis by regulating the expression of various target genes, including cell-cycle regulators, angiogenic factors and anti-apoptosis genes. Paradoxically, in some circumstances, STAT3 signalling induces cell death. The best known example is the involuting mammary gland, where STAT3 is essential for induction of a lysosomal pathway of cell death. Nevertheless, direct silencing or inhibition of STAT3 diminishes tumour growth and survival in both animal and human studies. This suggests that abolishing STAT3 activity may be an effective cancer therapeutic strategy. However, despite this potential as a therapeutic target, and the extensive attempts by many laboratories and pharmaceutical companies to develop an effective STAT3 inhibitor for use in the clinic, no direct STAT3 inhibitor has been approved for clinical use. In this review, we focus on the role of STAT3 in tumorigenesis, and discuss its potential as a therapeutic target for cancer treatment.M.S.W. is supported by a UK Biotechnology and Biological Sciences Research Council CASE PhD studentship in collaboration with GlaxoSmithKline.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/febs.1328

LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Persistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation. Originally published in British Journal of Cancer 2009 Vol. 110, No.

Precipitation Behavior of Wrought Fe-Ni-Based Alloy HR6W

Age-hardening behavior of Fe-Ni-based alloy HR6W was investigated at the temperature range between 973 K and 1073 K. Two-step increase in hardness is detected for the alloy at each temperature; the first increase in hardness results from the precipitation of M23C6 phase and the second one corresponds to that of Laves phase. The TTP (time-temperature precipitation) diagram for the alloy is established based on the results of hardness measurement and microstructure observation, where the precipitation of Laves phase is slower than that of M23C6 phase by three orders of magnitude and the nose temperature of Laves phase is above 1073 K. The M23C6 phase precipitates with plate-like morphology along grain-boundaries at the early stage of aging, followed by the precipitation of Laves phase with granular morphology with increasing aging time. It is found that the M23C6 and Laves phases are aligned under stress condition, due to their precipitation on the dislocations introduced during creep deformation

Chemical proteomics approaches for identifying the cellular targets of natural products.

Covering: 2010 up to 2016. Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied "in situ" - in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide-alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss 'competitive mode' approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

Atypical bovine spongiform encephalopathy (BSE) has recently been identified in Europe, North America, and Japan. It is classified as H-type and L-type BSE according to the molecular mass of the disease-associated prion protein (PrPSc). To investigate the topographical distribution and deposition patterns of immunolabeled PrPSc, H-type BSE isolate was inoculated intracerebrally into cattle. H-type BSE was successfully transmitted to 3 calves, with incubation periods between 500 and 600 days. Moderate to severe spongiform changes were detected in the cerebral and cerebellar cortices, basal ganglia, thalamus, and brainstem. H-type BSE was characterized by the presence of PrP-immunopositive amyloid plaques in the white matter of the cerebrum, basal ganglia, and thalamus. Moreover, intraglial-type immunolabeled PrPSc was prominent throughout the brain. Stellate-type immunolabeled PrPSc was conspicuous in the gray matter of the cerebral cortex, basal ganglia, and thalamus, but not in the brainstem. In addition, PrPSc accumulation was detected in the peripheral nervous tissues, such as trigeminal ganglia, dorsal root ganglia, optic nerve, retina, and neurohypophysis. Cattle are susceptible to H-type BSE with a shorter incubation period, showing distinct and distinguishable phenotypes of PrPSc accumulation