High precision results for a two-point boundary value problem

AbstractIn this note we establish results of high accuracy for the two-point boundary value problem 1.(1a) y″ = n sinh ny with the boundary conditions2.(1b) y (0) = 0, y (1) = 1, where n is real and positive. At the same time a derivation of the approximation for large n3.(2) y′(0) = 8 e−n(1 − 2e−n/2 + 2e−n), which is deduced in [1] from numerical results, is obtained in the course of the development

You won't believe this old test … that does cheap single-cell mutation detection.

Detecting mutations in single cells from cancer specimens is now a major area of translational research. In a recent article in this journal, Khalique et al validated an immunohistochemistry assay for ARID1A that reliably identifies loss of function mutations in single cells in tissue sections. This work exemplifies best practice for developing and orthogonally validating immunohistochemical assays to provide clearly interpretable mutational results with spatial context

Targeting STAT3 by HO3867 induces apoptosis in ovarian clear cell carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138398/1/ijc30847.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138398/2/ijc30847_am.pd

Multisite gynecologic endometrioid adenocarcinomas: Can mutation profiling be used to distinguish synchronous primary cancers from metastases?

It is well recognized that some patients with endometrioid gynecological cancers have tumors arising in multiple sites (ovary, endometrium, and endometriosis) at the time of diagnosis. Molecular analysis has helped discern whether these multisite cancers represent synchronous primary tumors or alternatively metastatic disease. We present a complex case of a patient with endometrioid carcinomas arising in multiple sites. We discuss the use of mutation profiling to discern clonality and highlight how this information may inform the clinical management of such cases

The Oncogenic Roles of DICER1 RNase IIIb Domain Mutations in Ovarian Sertoli-Leydig Cell Tumors

AbstractDICER1, an endoribonuclease required for microRNA (miRNA) biogenesis, is essential for embryogenesis and the development of many organs including ovaries. We have recently identified somatic hotspot mutations in RNase IIIb domain of DICER1 in half of ovarian Sertoli-Leydig cell tumors, a rare class of sex-cord stromal cell tumors in young women. These hotspot mutations lost IIIb cleavage activity of DICER1 in vitro and failed to produce 5p-derived miRNAs in mouse Dicer1-null ES cells. However, the oncogenic potential of these hotspot DICER1 mutations has not been studied. Here, we further revealed that the global expression of 5p-derived miRNAs was dramatically reduced in ovarian Sertoli-Leydig cell tumors carrying DICER1 hotspot mutations compared with those without DICER1 hotspot mutation. The miRNA production defect was associated with the deregulation of genes controlling cell proliferation and the cell fate. Using an immortalized human granulosa cell line, SVOG3e, we determined that the D1709N-DICER1 hotspot mutation failed to produce 5p-derived miRNAs, deregulated the expression of several genes that control gonadal differentiation and cell proliferation, and promoted cell growth. Re-expression of let-7 significantly inhibited the growth of D1709N-DICER1 SVOG3e cells, accompanied by the suppression of key regulators of cell cycle control and ovarian gonad differentiation. Taken together, our data revealed that DICER1 hotspot mutations cause systemic loss of 5p-miRNAs that can both drive pseudodifferentiation of testicular elements and cause oncogenic transformation in the ovary

Partialization losses of ON/OFF operation of waterto- water refrigeration/heat-pump units

[EN] This paper presents the results of an experimental campaign for the characterization of the dynamic behavior of a water-to-water refrigeration/heat-pump unit under ON/OFF operation. The unit was previously tested at different water inlet temperatures under steady state conditions, and a very good agreement was found between the instantaneous dynamic performance of the heat pump and the corresponding quasi-steady state operation. In parallel, a series of tests were carried out to quantify the coefficient of performance (COP) degradation as a function of the load ratio, and a simple formula for the Part Load Factor is presented. Results lead to the conclusion that the only non-negligible factor in the COP degradation is the stand-by electrical consumption during the OFF period, especially at low load ratios. Finally, it is concluded that the minimization of the stand-by consumption is a key point for the future improvement of the seasonal performance of water-to-water systems.This research has been partially funded by the European FP7 framework project "Advanced ground source heat pump systems for heating and cooling in Mediterranean climate" (GROUND-MED) and the Spanish Ministry of Economy and Competitiveness (MINECO) through the project "Estudio de evaporadores y condensadores basados en tecnologia de minicanales para su aplicaciOn en equipos de aire acondicionado, refrigeraciOn y bomba de calor estacionarios" with reference DPI2011-26771-C02-01. The authors gratefully acknowledge their financial support.Corberán, JM.; D.Donadello; Martínez Galván, IO.; Montagud, C. (2013). Partialization losses of ON/OFF operation of waterto- water refrigeration/heat-pump units. International Journal of Refrigeration. 36(8):2251-2261. https://doi.org/10.1016/j.ijrefrig.2013.07.002S2251226136

Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A mutational status in gynaecological cancers

ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ARID1A defects. However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for mutation status has not fully been established for patient stratification in clinical trials. Here we tested whether ARID1A IHC could reliably predict ARID1A mutations identified by next‐generation sequencing. Three commercially available antibodies – EPR13501 (Abcam), D2A8U (Cell Signaling), and HPA005456 (Sigma) – were optimised for IHC using cell line models and human tissue, and screened across a cohort of 45 gynaecological tumours. IHC was scored independently by three pathologists using an immunoreactive score. ARID1A mutation status was assessed using two independent sequencing platforms and the concordance between ARID1A mutation and protein expression was evaluated using Receiver Operating Characteristic statistics. Overall, 21 ARID1A mutations were identified in 14/43 assessable tumours (33%), the majority of which were predicted to be deleterious. Mutations were identified in 6/17 (35%) ovarian clear cell carcinomas, 5/8 (63%) ovarian endometrioid carcinomas, 2/5 (40%) endometrial carcinomas, and 1/7 (14%) carcinosarcomas. ROC analysis identified greater than 95% concordance between mutation status and IHC using a modified immunoreactive score for all three antibodies allowing a definitive cut‐point for ARID1A mutant status to be calculated. Comprehensive assessment of concordance of ARID1A IHC and mutation status identified EPR13501 as an optimal antibody, with 100% concordance between ARID1A mutation status and protein expression, across different gynaecological histological subtypes. It delivered the best inter‐rater agreement between all pathologists, as well as a clear cost‐benefit advantage. This could allow patients to be accurately stratified based on their ARID1A IHC status into early phase clinical trials.Gynaecological Cancer Fund The Royal Marsden Cancer Charity Breast Cancer Now . Grant Numbers: PRJNA432413 , PRJNA432343 Cancer Research UK The Monument Trust NHS NIHR Royal Marsden Hospital Biomedical Research Centre NCBI Sequence Read Archiv

INTENSE THERMAL NEUTRON FIELDS FROM A MEDICAL-TYPE LINAC: THE E_LIBANS PROJECT

The e_LiBANS project aims at producing intense thermal neutron fields for diverse interdisciplinary irradiation purposes. It makes use of a reconditioned medical electron LINAC, recently installed at the Physics Department and INFN in Torino, coupled to a dedicated photo-converter, developed within this collaboration, that uses (\u3b3,n) reaction within high Z targets. Produced neutrons are then moderated to thermal energies and concentrated in an irradiation volume. To measure and to characterize in real time the intense field inside the cavity new thermal neutron detectors were designed with high radiation resistance, low noise and very high neutron-to-photon discrimination capability. This article offers an overview of the e_LiBANS project and describes the results of the benchmark experiment