Rapid planetesimal formation in turbulent circumstellar discs

The initial stages of planet formation in circumstellar gas discs proceed via dust grains that collide and build up larger and larger bodies (Safronov 1969). How this process continues from metre-sized boulders to kilometre-scale planetesimals is a major unsolved problem (Dominik et al. 2007): boulders stick together poorly (Benz 2000), and spiral into the protostar in a few hundred orbits due to a head wind from the slower rotating gas (Weidenschilling 1977). Gravitational collapse of the solid component has been suggested to overcome this barrier (Safronov 1969, Goldreich & Ward 1973, Youdin & Shu 2002). Even low levels of turbulence, however, inhibit sedimentation of solids to a sufficiently dense midplane layer (Weidenschilling & Cuzzi 1993, Dominik et al. 2007), but turbulence must be present to explain observed gas accretion in protostellar discs (Hartmann 1998). Here we report the discovery of efficient gravitational collapse of boulders in locally overdense regions in the midplane. The boulders concentrate initially in transient high pressures in the turbulent gas (Johansen, Klahr, & Henning 2006), and these concentrations are augmented a further order of magnitude by a streaming instability (Youdin & Goodman 2005, Johansen, Henning, & Klahr 2006, Johansen & Youdin 2007) driven by the relative flow of gas and solids. We find that gravitationally bound clusters form with masses comparable to dwarf planets and containing a distribution of boulder sizes. Gravitational collapse happens much faster than radial drift, offering a possible path to planetesimal formation in accreting circumstellar discs.Comment: To appear in Nature (30 August 2007 issue). 18 pages (in referee mode), 3 figures. Supplementary Information can be found at 0708.389

An extrasolar planetary system with three Neptune-mass planets

Over the past two years, the search for low-mass extrasolar planets has led to the detection of seven so-called 'hot Neptunes' or 'super-Earths' around Sun-like stars. These planets have masses 5-20 times larger than the Earth and are mainly found on close-in orbits with periods of 2-15 days. Here we report a system of three Neptune-mass planets with periods of 8.67, 31.6 and 197 days, orbiting the nearby star HD 69830. This star was already known to show an infrared excess possibly caused by an asteroid belt within 1 AU (the Sun-Earth distance). Simulations show that the system is in a dynamically stable configuration. Theoretical calculations favour a mainly rocky composition for both inner planets, while the outer planet probably has a significant gaseous envelope surrounding its rocky/icy core; the outer planet orbits within the habitable zone of this star.Comment: 17 pages, 3 figures, preprint of the paper published in Nature on May 18, 200

Tracking Optical Welding through Groove Modes in Plasmonic Nanocavities.

We report the light-induced formation of conductive links across nanometer-wide insulating gaps. These are realized by incorporating spacers of molecules or 2D monolayers inside a gold plasmonic nanoparticle-on-mirror (NPoM) geometry. Laser irradiation of individual NPoMs controllably reshapes and tunes the plasmonic system, in some cases forming conductive bridges between particle and substrate, which shorts the nanometer-wide plasmonic gaps geometrically and electronically. Dark-field spectroscopy monitors the bridge formation in situ, revealing strong plasmonic mode mixing dominated by clear anticrossings. Finite difference time domain simulations confirm this spectral evolution, which gives insights into the metal filament formation. A simple analytic cavity model describes the observed plasmonic mode hybridization between tightly confined plasmonic cavity modes and a radiative antenna mode sustained in the NPoM. Our results show how optics can reveal the properties of electrical transport across well-defined metallic nanogaps to study and develop technologies such as resistive memory devices (memristors).Engineering and Physical Sciences Research Council (Grant IDs: EP/ G060649/1, EP/L027151/1, EP/G037221/1, EPSRC NanoDTC EP/L015978/1), European Research Council (Grant ID: LINASS 320503), Winton Programme of the Physics of Sustainability, Project FIS2013- 41184-P from MINECO and IT756-13 from the Basque Government consolidated groupsThis is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.nanolett.6b0216

Prescriptions of Traditional Chinese Medicine Are Specific to Cancer Types and Adjustable to Temperature Changes

Targeted cancer therapies, with specific molecular targets, ameliorate the side effect issue of radiation and chemotherapy and also point to the development of personalized medicine. Combination of drugs targeting multiple pathways of carcinogenesis is potentially more fruitful. Traditional Chinese medicine (TCM) has been tailoring herbal mixtures for individualized healthcare for two thousand years. A systematic study of the patterns of TCM formulas and herbs prescribed to cancers is valuable. We analysed a total of 187,230 TCM prescriptions to 30 types of cancer in Taiwan in 2007, a year's worth of collection from the National Health Insurance reimbursement database (Taiwan). We found that a TCM cancer prescription consists on average of two formulas and four herbs. We show that the percentage weights of TCM formulas and herbs in a TCM prescription follow Zipf's law with an exponent around 0.6. TCM prescriptions to benign neoplasms have a larger Zipf's exponent than those to malignant cancers. Furthermore, we show that TCM prescriptions, via weighted combination of formulas and herbs, are specific to not only the malignancy of neoplasms but also the sites of origins of malignant cancers. From the effects of formulas and natures of herbs that were heavily prescribed to cancers, that cancers are a ‘warm and stagnant’ syndrome in TCM can be proposed, suggesting anti-inflammatory regimens for better prevention and treatment of cancers. We show that TCM incorporated relevant formulas to the prescriptions to cancer patients with a secondary morbidity. We compared TCM prescriptions made in different seasons and identified temperatures as the environmental factor that correlates with changes in TCM prescriptions in Taiwan. Lung cancer patients were among the patients whose prescriptions were adjusted when temperatures drop. The findings of our study provide insight to TCM cancer treatment, helping dialogue between modern western medicine and TCM for better cancer care

Treatment of two postoperative endophthalmitis cases due to Aspergillus flavus and Scopulariopsis spp. with local and systemic antifungal therapy

<p>Abstract</p> <p>Background</p> <p>Endophthalmitis is the inflammatory response to invasion of the eye with bacteria or fungi. The incidence of endophthalmitis after cataract surgery varies between 0.072–0.13 percent. Treatment of endophthalmitis with fungal etiology is difficult.</p> <p>Case Presentation</p> <p><b>Case 1: </b>A 71-year old male diabetic patient developed postoperative endophthalmitis due to <it>Aspergillus flavus</it>. The patient was treated with topical amphotericin B ophthalmic solution, intravenous (IV) liposomal amphotericin-B and caspofungin following vitrectomy.</p> <p><b>Case 2: </b>A 72-year old male cachectic patient developed postoperative endophthalmitis due to <it>Scopulariopsis </it>spp. The patient was treated with topical and IV voriconazole and caspofungin.</p> <p>Conclusion</p> <p><it>Aspergillus </it>spp. are responsible of postoperative fungal endophthalmitis. Endophthalmitis caused by <it>Scopulariopsis </it>spp. is a very rare condition. The two cases were successfully treated with local and systemic antifungal therapy.</p

Substrate binding and translocation of the serotonin transporter studied by docking and molecular dynamics simulations

The serotonin (5-HT) transporter (SERT) plays an important role in the termination of 5-HT-mediated neurotransmission by transporting 5-HT away from the synaptic cleft and into the presynaptic neuron. In addition, SERT is the main target for antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs). The three-dimensional (3D) structure of SERT has not yet been determined, and little is known about the molecular mechanisms of substrate binding and transport, though such information is very important for the development of new antidepressant drugs. In this study, a homology model of SERT was constructed based on the 3D structure of a prokaryotic homologous leucine transporter (LeuT) (PDB id: 2A65). Eleven tryptamine derivates (including 5-HT) and the SSRI (S)-citalopram were docked into the putative substrate binding site, and two possible binding modes of the ligands were found. To study the conformational effect that ligand binding may have on SERT, two SERT–5-HT and two SERT–(S)-citalopram complexes, as well as the SERT apo structure, were embedded in POPC lipid bilayers and comparative molecular dynamics (MD) simulations were performed. Our results show that 5-HT in the SERT–5-HTB complex induced larger conformational changes in the cytoplasmic parts of the transmembrane helices of SERT than any of the other ligands. Based on these results, we suggest that the formation and breakage of ionic interactions with amino acids in transmembrane helices 6 and 8 and intracellular loop 1 may be of importance for substrate translocation

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO)

<p>Abstract</p> <p>Background</p> <p>The effects of the olive oil-rich Mediterranean diet on breast cancer risk might be underestimated when HER2 (<it>ERB</it>B2) oncogene-positive and HER2-negative breast carcinomas are considered together. We here investigated the anti-HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil (EVOO) in cultured human breast cancer cell lines.</p> <p>Methods</p> <p>Solid phase extraction followed by semi-preparative high-performance liquid chromatography (HPLC) was used to isolate phenolic fractions from commercial EVOO. Analytical capillary electrophoresis coupled to mass spectrometry was performed to check for the composition and to confirm the identity of the isolated fractions. EVOO polyphenolic fractions were tested on their tumoricidal ability against HER2-negative and HER2-positive breast cancer <it>in vitro </it>models using MTT, crystal violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic fractions on the expression and activation status of HER2 oncoprotein were evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively.</p> <p>Results</p> <p>Among the fractions mainly containing the <it>single phenols </it>hydroxytyrosol and tyrosol, the <it>polyphenol acid </it>elenolic acid, the <it>lignans </it>(+)-pinoresinol and 1-(+)-acetoxypinoresinol, and the <it>secoiridoids </it>deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (<it>i.e. </it>secoiridoids and lignans) were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2 protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation in a dose- and time-dependent manner. EVOO polyphenols-induced HER2 downregulation occurred regardless the molecular mechanism contributing to HER2 overexpression (<it>i.e</it>. naturally by gene amplification and ectopically driven by a viral promoter). Pre-treatment with the proteasome inhibitor MG132 prevented EVOO polyphenols-induced HER2 depletion.</p> <p>Conclusion</p> <p>The ability of EVOO-derived polyphenols to inhibit HER2 activity by promoting the proteasomal degradation of the HER2 protein itself, together with the fact that humans have safely been ingesting secoiridoids and lignans as long as they have been consuming olives and OO, support the notion that the stereochemistry of these phytochemicals might provide an excellent and safe platform for the design of new HER2-targeting agents.</p

GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER⁺) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER⁺breast cancer cells</p> <p>Methods</p> <p>We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined.</p> <p>Results</p> <p>GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole.</p> <p>Conclusion</p> <p>Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER⁺breast cancer.</p