Clinical Significance of Homologous Recombination Deficiency Score Testing in Endometrial Cancer

Objectives: Homologous recombination deficiency (HRD) score is related to chemotherapy response in breast and ovarian cancers. The role of HRD is unknown in endometrial cancer. We examined the relationship between HRD score and survival in a cohort of endometrial cancer patients and with tumor growth using murine orthotopic models. Methods: TCGA was queried to determine frequency and clinical significance of alterations in the HR pathway in endometrial cancer. 137 formalin-fixed paraffin-embedded endometrioid adenocarcinoma patient samples were tested for HRD score, microsatellite instability (MSI) and high mutation load (HML) using a next generation sequencing assay targeting the coding regions of 43 genes and 54,091 genome wide single nucleotide polymorphisms (SNPs) developed by Myriad Genetics. The HRD score is the sum of three previously described scores (loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition) that quantitate genome rearrangement. Clinical records were obtained. HRD scores were also generated on a panel of established endometrial cancer cell lines and their in vivo growth and response to olaparib and chemotherapy were assessed. Tumor growth and patterns of metastatic spread were assessed in orthotopic mouse models of endometrial cancer. Results: Median age at diagnosis was 62 years. The majority of patients presented with early stage disease (54%, 11%, 27%, 8% stage I, II, III, IV respectively), and FIGO grade 2 histology (1%, 73%, 26% grade 1, 2, 3). HRD scores were generated for 112 patient samples, MSI status was determined for 126 samples, and HML status determined for 137 samples. The median HRD score was 3. Patients with HRD score ≥ 10 trended toward worse survival as compared to patients with HRD score \u3c10 \u3e(P=0.17). Hec1a cell line (HRD score = 19) was highly sensitive to olaparib and was selected for in vivo use. At the time of necropsy, mice injected with Hec1a and treated with PARP inhibitor had significantly decreased tumor growth and HR function as compared with untreated controls, regardless of BRCA1 function. Conclusions: High HRD score was associated with worse survival in our patient cohort. Our findings support the use of HRD score in guiding the choice of adjuvant therapy for patients with advanced endometrial cancer

A multi-blob representation of semi-dilute polymer solutions

A coarse-grained multi-blob description of polymer solutions is presented, based on soft, transferable effective interactions between bonded and non-bonded blobs. The number of blobs is chosen such that the blob density does not exceed their overlap threshold, allowing polymer concentrations to be explored deep into the semi-dilute regime. This quantitative multi-blob description is shown to preserve known scaling laws of polymer solutions and provides accurate estimates of amplitudes, while leading to orders of magnitude increase of simulation efficiency and allowing analytic calculations of structural and thermodynamic properties.Comment: 4 pages, 4 figure

Models of electrolyte solutions from molecular descriptions: The example of NaCl solutions

We present a method to derive implicit solvent models of electrolyte solutions from all-atom descriptions; providing analytical expressions of the thermodynamic and structural properties of the ions consistent with the underlying explicit solvent representation. Effective potentials between ions in solution are calculated to perform perturbation theory calculations, in order to derive the best possible description in terms of charged hard spheres. Applying this method to NaCl solutions yields excellent agreement with the all-atom model, provided ion association is taken into account.Comment: 4 pages, 5 figure

Experimental Investigation of Impact-Induced Molecular Desorption by 4.2 MeV/u Pb ions

In preparation for the heavy ion program of the LHC, accumulation and cooling test with lead ion beams have been performed in the LEAR storage ring. These tests have revealed that due to the unexpected, large outgassing of the vacuum system, the dynamic pressure of the ring could not be maintained low enough to reach the required beam intensities. To determine the actions necessary to lower the dynamic pressure rise, an experimental program has been initiated for measuring the molecular desorption yields of stainless steel vacuum chambers by the impact of 4.2 MeV/u lead ions with the charge states +27 and +53. The test chambers were exposed either at grazing or at perpendicular incidence. Different surface treatments are reported in terms of the molecular desorption yields for H2, CH4, CO and CO2. Unpexpected large values of molecular yields per incident ion up to 2x104 molecules/ion have been observed. The implications of these results for the vacuum system of the future ion accumulator ring (LEIR) and possible remedies to reduce the vacuum degradation will be discussed

Exact Renormalization Group : A New Method for Blocking the Action

We consider the exact renormalization group for a non-canonical scalar field theory in which the field is coupled to the external source in a special non linear way. The Wilsonian action and the average effective action are then simply related by a Legendre transformation up to a trivial quadratic form. An exact mapping between canonical and non-canonical theories is obtained as well as the relations between their flows. An application to the theory of liquids is sketched

Origin of the Universal Roughness Exponent of Brittle Fracture Surfaces: Correlated Percolation in the Damage Zone

We suggest that the observed large-scale universal roughness of brittle fracture surfaces is due to the fracture process being a correlated percolation process in a self-generated quadratic damage gradient. We use the quasi-static two-dimensional fuse model as a paradigm of a fracture model. We measure for this model, that exhibits a correlated percolation process, the correlation length exponent nu approximately equal to 1.35 and conjecture it to be equal to that of uncorrelated percolation, 4/3. We then show that the roughness exponent in the fuse model is zeta = 2 nu/(1+2 nu)= 8/11. This is in accordance with the numerical value zeta=0.75. As for three-dimensional brittle fractures, a mean-field theory gives nu=2, leading to zeta=4/5 in full accordance with the universally observed value zeta =0.80.Comment: 4 pages RevTeX

Distinguishing fractional and white noise in one and two dimensions

We discuss the link between uncorrelated noise and Hurst exponent for one and two-dimensional interfaces. We show that long range correlations cannot be observed using one-dimensional cuts through two-dimensional self-affine surfaces whose height distributions are characterized by a Hurst exponent lower than -1/2. In this domain, fractional and white noise are not distinguishable. A method analysing the correlations in two dimensions is necessary. For Hurst exponents larger than -1/2, a crossover regime leads to a systematic over estimate of the Hurst exponent.Comment: 3 pages RevTeX, 4 Postscript figure

Transport Coefficients of the Yukawa One Component Plasma

We present equilibrium molecular-dynamics computations of the thermal conductivity and the two viscosities of the Yukawa one-component plasma. The simulations were performed within periodic boundary conditions and Ewald sums were implemented for the potentials, the forces, and for all the currents which enter the Kubo formulas. For large values of the screening parameter, our estimates of the shear viscosity and the thermal conductivity are in good agreement with the predictions of the Chapman-Enskog theory.Comment: 11 pages, 2 figure

Intermittent permeation of cylindrical nanopores by water

Molecular Dynamics simulations of water molecules in nanometre sized cylindrical channels connecting two reservoirs show that the permeation of water is very sensitive to the channel radius and to electric polarization of the embedding material. At threshold, the permeation is {\emph{intermittent}} on a nanosecond timescale, and strongly enhanced by the presence of an ion inside the channel, providing a possible mechanism for gating. Confined water remains surprisingly fluid and bulk-like. Its behaviour differs strikingly from that of a reference Lennard-Jones fluid, which tends to contract into a highly layered structure inside the channel.Comment: 4 pages, 4 figure

The Iowa Homemaker vol.9, no.5

Guide Our Giving by Bessie Hammer, page 1 Art Expression for the Child by Joanne M. Hansen, page 2 What About the Glamour? by Nielsine Hansen, page 3 Death to the Clothes Moth by Jean B. Guthrie, page 4 Long or Short? by Irene Evinger and Lillian Goodrow, page 4 Homemaker’s Books by Dorothy Parkhurst, page 5 4-H Club by Esther Sietman, page 6 State Association by Marcia E. Turner, page 8 Editorial, page 11 Alumnae News by Dorothy B. Anderson, page 1