Inner disk clearing around the Herbig Ae star HD\,139614: Evidence for a planet-induced gap ?

Spatially resolving the inner dust cavity of the transitional disks is a key to understanding the connection between planetary formation and disk dispersal. The disk around the Herbig star HD 139614 is of particular interest since it presents a pretransitional nature with an au-sized gap, in the dust, that was spatially resolved by mid-IR interferometry. Using new NIR interferometric observations, we aim to characterize the 0.1-10~au region of the HD~139614 disk further and identify viable mechanisms for the inner disk clearing. We report the first multiwavelength radiative transfer modeling of the interferometric data acquired on HD~139614 with PIONIER, AMBER, and MIDI, complemented by Herschel/PACS photometries. We confirm a gap structure in the um-sized dust, extending from about 2.5 au to 6 au, and constrained the properties of the inner dust component: e.g., a radially increasing surface density profile, and a depletion of 10^3 relative to the outer disk. Since self-shadowing and photoevaporation appears unlikely to be responsible for the au-sized gap of HD~139614, we thus tested if dynamical clearing could be a viable mechanism using hydrodynamical simulations to predict the gaseous disk structure. Indeed, a narrow au-sized gap is expected when a single giant planet interacts with the disk. Assuming that small dust grains are well coupled to the gas, we found that a ~ 3~Mjup planet located at 4.5 au from the star could, in less than 1 Myr, reproduce most of the aspects of the dust surface density profile, while no significant depletion in gas occurred in the inner disk, in contrast to the dust. However, the dust-depleted inner disk could be explained by the expected dust filtration by the gap and the efficient dust growth/fragmentation in the inner disk regions. Our results support the hypothesis of a giant planet opening a gap and shaping the inner region of the HD~139614 disk.Comment: Version accepted in A&A, with typos corrections in the tex

Carbonate sedimentation and effects of eutrophication observed at the Kališta subaquatic springs in Lake Ohrid (Macedonia)

To date, little is known about the role of spring waters with respect to authigenic carbonate precipitation in a shallow lacustrine setting. Lake Ohrid, located in Southeastern Europe, is a large lake fed to over 50% by karstic springs of which half enter subaquatically and influence significantly its ecology and species distribution. In order to evaluate how sedimentological processes are influenced by such shallow-water springs, the Kališta subaquatic spring area in the north west of Lake Ohrid was investigated by a sidescan sonar survey and with sediment traps and three transects of gravity short cores. Results indicate that sedimentation in the spring area is dominated by authigenic carbonate precipitation. High sedimentation rates and evidences for bio-induced precipitation processes were observed in the water column and in the sediments. Two distinct stratigraphic units characterize the shallow subsurface, both composed of carbonate silts with high carbonate contents of up to 96%, but differing in color, carbonate content and diatom content. A chronological correlation of the cores by radiocarbon dates and <sup>137</sup>Cs activities places the transition between the two stratigraphic units after ~1955 AD. At that time, coastal sedimentation changed drastically to significantly darker sediments with higher contents of organic matter and more abundant diatoms. This change coincides with the recent human impact of littoral eutrophication

Enterocolic phlebitis: a rare cause of bowel ischemia and review of the literature.

Enterocolic phlebitis (EP) is a rare cause of bowel ischemia due to isolated venulitis of the bowel wall and mesentery without arterial involvement. EP is often misdiagnosed as inflammatory bowel disease, carcinoma, or diverticulitis due to non-specific symptoms as well as non-specific clinical and radiological findings. While unresponsive to pharmacotherapy, surgical resection of the affected bowel appears to be the only successful therapy with a very low recurrence rate. Etiology of EP remains unknown. We report a case of EP with rare presentation in the left hemicolon and unusual histological findings emphasizing the heterogeneity of this cause of enterocolic ischemia. The review and comparison of the three entities-EP, mesenteric inflammatory veno-occlusive disease (MIVOD), and idiopathic myointimal hyperplasia of mesenteric veins (IMHMV), all describing patterns of bowel ischemia due to isolated pathology of mesenteric veins-reveal that the current terminology is unclear. EP and MIVOD are very similar and may be considered the same disease. IMHMV, though, differs in localization, symptom duration, and histological findings but also shares features with EP and MIVOD. Further studies and harmonized terminology are inevitable for better understanding of the disease, prevention of unnecessary pharmacotherapy, and reduction in time to diagnosis

Targeting the mTOR pathway in hepatocellular carcinoma: Current state and future trends

SummaryMechanistic target of rapamycin (mTOR) regulates cell growth, metabolism and aging in response to nutrients, cellular energy stage and growth factors. mTOR is frequently up-regulated in cancer including hepatocellular carcinoma (HCC) and is associated with bad prognosis, poorly differentiated tumors, and earlier recurrence. Blocking mTOR with rapamycin and first generation mTOR inhibitors, called rapalogs, has shown promising reduction of HCC tumor growth in preclinical models. Currently, rapamycin/rapalogs are used in several clinical trials for the treatment of advanced HCC, and as adjuvant therapy in HCC patients after liver transplantation and TACE. A second generation of mTOR pathway inhibitors has been developed recently and is being tested in various clinical trials of solid cancers, and has been used in preclinical HCC models. The results of series of clinical trials using mTOR inhibitors in HCC treatment will emerge in the near future

Guide to Leveraging Conducting Polymers and Hydrogels for Direct Current Stimulation

The tunable electrical properties of conducting polymers (CPs), their biocompatibility, fabrication versatility, and cost-efficiency make them an ideal coating material for stimulation electrodes in biomedical applications. Several biological processes like wound healing, neuronal regrowth, and cancer metastasis, which rely on constant electric fields, demand electrodes capable of delivering direct current stimulation (DCs) for long times without developing toxic electrochemical reactions. Recently, CPs such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) have demonstrated outstanding capability for delivering DCs without damaging cells in culture while not requiring intermediate buffers, contrary to the current research setups relying on noble-metals and buffering bridges. However, clear understanding of how electrode design and CP synthesis influence DCs properties of these materials has not been provided until now. This study demonstrates that various PEDOT-based CP coatings and hydrogels on rough electrodes can deliver DCs without substantial changes to the electrode and the noticeable development of chemical by-products depending on the electrode area and polymer thickness. A comprehensive analysis of the tested coatings is provided according to the desired application and available resources, alongside a proposed explanation for the observed electrochemical behavior. The CPs tested herein can pave the way toward the widespread implementation of DCs as a therapeutic stimulation paradigm

Addition of cetuximab to first-line chemotherapy in patients with advanced non-small-cell lung cancer: a cost-utility analysis

Background: Adding cetuximab to standard chemotherapy results in a moderate increase of overall survival in patients with advanced non-small-cell lung cancer (NSCLC), but the cost-effectiveness is unknown. Materials and methods: A Markov model was constructed based on the results of the First-Line ErbituX in lung cancer randomized trial, adding cetuximab to cisplatin-vinorelbine first-line chemotherapy in patients with advanced NSCLC. The primary outcome was the incremental cost-effectiveness ratio (ICER) of adding cetuximab, expressed as cost per quality-adjusted life year (QALY) gained, and relative to a willingness-to-pay threshold of €60 000/QALY. The impact of cetuximab intermittent dosing schedules on the ICER was also evaluated. Results: Adding cetuximab to standard chemotherapy leads to a gain of 0.07 QALYs per patient at an additional cost of €26 088. The ICER for adding cetuximab to chemotherapy was €376 205 per QALY gained. Intermittent cetuximab dosing schedules resulted in ICERs per QALY gained between €31 300 and €83 100, under the assumption of equal efficacy. Conclusions: From a health economic perspective, the addition of cetuximab to standard first-line chemotherapy in patients with epidermal growth factor receptor-expressing advanced NSCLC cannot be recommended to date, due to a high ICER compared with other health care interventions. Treatment schedules resulting in more favorable cost-utility ratios should be evaluate

Valinomycin Biosynthetic Gene Cluster in Streptomyces: Conservation, Ecology and Evolution

Many Streptomyces strains are known to produce valinomycin (VLM) antibiotic and the VLM biosynthetic gene cluster (vlm) has been characterized in two independent isolates. Here we report the phylogenetic relationships of these strains using both parsimony and likelihood methods, and discuss whether the vlm gene cluster shows evidence of horizontal transmission common in natural product biosynthetic genes. Eight Streptomyces strains from around the world were obtained and sequenced for three regions of the two large nonribosomal peptide synthetase genes (vlm1 and vlm2) involved in VLM biosynthesis. The DNA sequences representing the vlm gene cluster are highly conserved among all eight environmental strains. The geographic distribution pattern of these strains and the strict congruence between the trees of the two vlm genes and the housekeeping genes, 16S rDNA and trpB, suggest vertical transmission of the vlm gene cluster in Streptomyces with no evidence of horizontal gene transfer. We also explored the relationship of the sequence of vlm genes to that of the cereulide biosynthetic genes (ces) found in Bacillus cereus and found them highly divergent from each other at DNA level (genetic distance values≥95.6%). It is possible that the vlm gene cluster and the ces gene cluster may share a relatively distant common ancestor but these two gene clusters have since evolved independently

Sigurðar saga fóts (The Saga of Sigurðr Foot): A Translation

This is the first English translation of the short Icelandic romance Sigurðar saga fóts, with an introduction presenting the evidence for its dating and immediate literary context. Like most Icelandic romances, Sigurðar saga is a bridal-quest story; the support of a foster-brother is key to the hero winning the bride; and the foster-brothers start out as opponents before recognising their mutual excellence and swearing foster-brotherhood. Uniquely, however, the men who become foster-brothers begin by competing for the same bride (Signý): the eponymous Sigurðr fótr wins Signý only because Ásmundr gives her to him in exchange for foster-brotherhood. Ásmundr’s decision can be read as demonstrating with unusual starkness the superior importance in much Icelandic romance of homosocial relationships over heterosexual ones, giving the saga a certain paradigmatic status. Translating the saga in an open-access forum and reconstructing its literary context will, we hope, encourage further analyses

Trastuzumab beyond progression: a cost-utility analysis

Background: The continuation of trastuzumab beyond progression in combination with capecitabine as secondary chemotherapy for HER2-positive metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase in toxicity. Patients and methods: A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Information on response rates and major adverse effects was derived, and transition probabilities were estimated, based on the results of the Breast International Group 03-05 clinical trial. Direct costs were assessed from the perspective of the Swiss health care system. Results: The addition of trastuzumab to capecitabine is estimated to cost on average an additional of €33 980 and to yield a gain of 0.35 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of €98 329/QALYs gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of €60 000/QALY was reached in 12% of cases. Conclusion: The addition of trastuzumab to capecitabine in MBC patients is more expensive than what is typically regarded as cost-effective but falls within the value ranges found for established regimens in the treatment of MB

MarvelD3 regulates the c-Jun N-terminal kinase pathway during eye development in Xenopus.

Ocular morphogenesis requires several signalling pathways controlling the expression of transcription factors and cell-cycle regulators. However, despite a well-known mechanism, the dialogue between those signals and factors remains to be unveiled. Here, we identify a requirement for MarvelD3, a tight junction transmembrane protein, in eye morphogenesis in Xenopus MarvelD3 depletion led to an abnormally pigmented eye or even an eye-less phenotype, which was rescued by ectopic MarvelD3 expression. Altering MarvelD3 expression led to deregulated expression of cell-cycle regulators and transcription factors required for eye development. The eye phenotype was rescued by increased c-Jun terminal Kinase activation. Thus, MarvelD3 links tight junctions and modulation of the JNK pathway to eye morphogenesis