Direct observation of a hydrophobic bond in loop-closure of a capped (-OCH2CH2-)n oligomer in water

The small r variation of the probability density P(r) for end-to-end separations of a -CH2CH3 capped (-OCH2CH2-)n oligomer in water is computed to be closely similar to the CH4 ... CH4 potential of mean force under the same circumstances. Since the aqueous solution CH4 ... CH4 potential of mean force is the natural physical definition of a primitive hydrophobic bond, the present result identifies an experimentally accessible circumstance for direct observation of a hydrophobic bond which has not been observed previously because of the low solubility of CH4 in water. The physical picture is that the soluble chain molecule carries the capping groups into aqueous solution, and permits them to find one another with reasonable frequency. Comparison with the corresponding results without the solvent shows that hydration of the solute oxygen atoms swells the chain molecule globule. This supports the view that the chain molecule globule might have a secondary effect on the hydrophobic interaction which is of first interest here. The volume of the chain molecule globule is important for comparing the probabilities with and without solvent because it characterizes the local concentration of capping groups. Study of other capping groups to enable X-ray and neutron diffraction measurements of P(r) is discussed.Comment: 4 pages, 3 figure

Dark matter halos in the multicomponent model. II. Density profiles of galactic halos

The multicomponent dark matter model with self-scattering and inter-conversions of species into one another is an alternative dark matter paradigm that is capable of resolving the long-standing problems of $\Lambda$CDM cosmology at small scales. In this paper, we have studied in detail the properties of dark matter halos with $M \sim 4-5 \times10^{11} M_{\odot}$ obtained in $N$-body cosmological simulations with the simplest two-component (2cDM) model. A large set of velocity-dependent cross-section prescriptions for elastic scattering and mass conversions, $\sigma_s(v)\propto v^{a_s}$ and $\sigma_c(v)\propto v^{a_c}$, has been explored and the results were compared with observational data. The results demonstrate that self-interactions with the cross-section per particle mass evaluated at $v=100$ km s$^{-1}$ being in the range of $0.01\lesssim \sigma_0/m\lesssim 1$ cm$^2$g$^{-1}$ robustly suppress central cusps, thus resolving the core-cusp problem. The core radii are controlled by the values of $\sigma_0/m$ and the DM cross-section's velocity-dependent power-law indices $(a_s,a_c)$, but are largely insensitive to the species' mass degeneracy. These values are in full agreement with those resolving the substructure and too-big-to-fail problems. We have also studied the evolution of halos in the 2cDM model with cosmic time.Comment: 17 pages, 13 figure

Effects of EGFR Expression on Anti-tumor Efficacy of Vandetanib or Cediranib Combined with Radiotherapy (RT) in U87 Human Glioblastoma (GBM) Xenografts

Introduction: Vandetanib is a receptor tyrosine kinase inhibitor (RTKI) with activity against vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). Cediranib is a highly potent VEGF RTKI that inhibits all three VEGF receptors. In this study we investigated the effect of exogenous overexpression of EGFR on sensitivity of human GBM U87 xenografts to vandetanib or cediranib, alone or in combination with RT. American Association for Cancer Research (AACR) 101st Annual Meeting April 17-21, Washington, DC

Single-stage sealing of ceramic tiles by means of high power diode laser radiation

An investigation has been carried out using a 60 W high power diode laser (HPDL) to determine the feasibility of sealing the void between adjoining ceramic tiles with a specially developed grout material. A single-stage process has subsequently been devised using a new grout material which consists of two distinct components: a crushed ceramic tile mix substrate and a glazed enamel surface; the crushed ceramic tile mix provides a tough, inexpensive bulk substrate, whilst the enamel provides an impervious surface glaze. HPDL processing has resulted in crack and porosity free seals produced in normal atmospheric conditions. The single-stage grout is simple to formulate and easy to apply. Tiles were successfully sealed with power densities as low as 750 W/cm2 and at rates of up to 420 mm/min. Bonding of the enamel to the crushed ceramic tile mix was identified as being primarily due to van der Waals forces and, on a very small scale, some of the crushed ceramic tile mix material dissolving into the glaze

Toxicity of Phase I Radiation Oncology Trials: Worldwide Experience

Introduction: Informed consent involves understanding the risks and benefits of trial enrollment. This is challenging in the phase I setting since true quantitative information is never known. We therefore performed an analysis of published radiation oncology (RO) phase I trials emphasizing patient outcomes. To our knowledge, no such systemic analysis has previously been published. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Effect of Cediranib, Temozolamide and Radiotherapy in U87 GBM wtEGFR and EGFRvIII-expressing Xenografts

Introduction: Glioblastomas (GBM) frequently overexpress the epidermal growth factor receptor (wtEGFR) or its mutant, EGFRvIII contributing to radioresistance. New treatment strategies for GBM include blockade of EGFR signaling and angiogenesis. Cediranib (CD) is a highly potent VEGFR-2 RTKI that inhibits all three VEGF receptors. This study investigated the radiosensitizing potential of CD in combination with temozolamide (TMZ) in U87 GBM xenografts expressing wtEGFR or EGFRvIII. Radiation Research Society (RRS) 8th Annual Meeting September 25-29, Maui, H

Evolving Role of Vorinostat Combined with Radiation Therapy in the Treatment of Brain Tumors, from the Lab to the Clinic

Purpose/Objective(s): Radiation therapy (RT) is a critical element in the treatment of both brain metastases and glioblastoma (GBM). Temozolomide (TMZ) has an established role in the upfront treatment of GBM. Down-regulated mismatch repair (MMR) is a known mechanism of resistance to TMZ. Vorinostat (SAHA), an HDAC inhibitor, has successfully been combined with a number of cytotoxic agents, including ionizing radiation (IR). We performed a series of preclinical and clinical studies to examine the role of SAHA in the treatment of brain tumors. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

The development and characteristics of a hand-held high power diode laser-based industrial tile grout removal and single-stage sealing system

As the field of laser materials processing becomes ever more diverse, the high power diode laser (HPDL) is now being regarded by many as the most applicable tool. The commercialisation of an industrial epoxy grout removal and single-stage ceramic tile grout sealing process is examined through the development of a hand-held HPDL device in this work. Further, an appraisal of the potential hazards associated with the use of the HPDL in an industrial environment and the solutions implemented to ensure that the system complies with the relevant safety standards are given. The paper describes the characteristics and feasibility of the industrial epoxy grout removal process. A minimum power density of approximately 3 kW/cm2 was found to exist, whilst the minimum interaction time, below which there was no removal of epoxy tile grout, was found to be approximately 0.5 s. The maximum theoretical removal rate that may be achievable was calculated as being 65.98 mm2/s for a circular 2 mm diameter beam with a power density of 3 kW/cm2 and a traverse speed of 42 mm/s. In addition, the characteristics of the single-stage ceramic tile grout sealing are outlined. The single-stage ceramic tile grout sealing process yielded crack and porosity free seals which were produced in normal atmospheric conditions. Tiles were successfully sealed with power densities as low as 550 W/cm2 and at rates of up to 420 mm/min. In terms of mechanical, physical and chemical characteristics, the single-stage ceramic tile grout was found to be far superior to the conventional epoxy tile grout and, in many instances, matched and occasionally surpassed that of the ceramic tiles themselves

Combination of Vorinostat with Whole-brain Radiotherapy in the Treatment of Brain Metastases

Background: A third of patients with solid malignancies develop brain metastases. Expected overall survival is 4-7 months depending on age, performance status, and extracranial disease. Standard treatment is controversial; however, the majority of patients receive wholebrain radiation therapy at some point. Vorinostat (suberoylanilide hydroxamic acid, SAHA), an FDA-approved HDAC inhibitor, has been demonstrated to radiosensitize tumor cells in vitro, as assessed by both radiation-induced DNA damage and clonogenic cell survival (Munshi et al. Molecular Cancer Therapeutics 5, 1967-1974, 2006). We have shown that vorinostat downregulates key genes involved in double-strand DNA repair (Rad50, Rad51, XRCC2, XRCC3, XRCC6), as assessed by quantitative PCR. This suggests that the drug’s mechanism of radiosensitization is epigenetic coordinated inhibition of the DNA repair process. We hypothesize that the combination of vorinostat with whole-brain radiation therapy will be both safe and efficacious. American Society of Clinical Oncology (ASCO) 46th Annual Meeting June 4-8, Chicago, IL

Functional Antagonism Between Vorinostat and Temozolomide when Combined with Ionizing Radiation (IR) in Glioblastoma

Background: Glioblastoma is the most common primary adult brain tumor. Surgery followed by radiation therapy in combination with temozolomide (Tmz) produces a median survival of 14.6 months. Tmz is a DNA akylating agent that leads to the mispairing of guanine residues with thymine. An intact mismatch-repair mechanism (MMR) converts the mispaired thymine into a lethal double-strand DNA break. Vorinostat (SAHA), an HDAC inhibitor, has been shown to act as a radiosensitizer, possibly through inhibition of DNA repair. SAHA has successfully been combined with a number of cytotoxic agents. We hypothesized that SAHA would further potentiate the radiosensitizing properties of Tmz in glioblastoma. American Association for Cancer Research (AACR) 101st Annual Meeting April 17-21, Washington, D