Bremsstrahlung of electrons and yield of neutrons from thick converters, passing of gamma-radiation and neutrons through biological shielding

In GEANT4 spectral-angular distributions of the bremsstrahlung of medium-energy electrons from amorphous targets of different thickness and atomic charge were calculated. The total yield of gamma quanta in the forward hemisphere and at large scattering angles were determined depending on the converter thickness. The difference in the characteristics of gamma radiation for thin and thick targets was shown. The neutron yield is calculated due to photonuclear reactions for various converters. Numerical estimates of the radiation spectra after passing through the biological shielding for neutron and bremsstrahlung were carried out.У GEANT4 розраховано спектрально-кутові розподіли гальмівного гамма випромінювання електронів середніх енергій з аморфних мішеней-конверторів різної товщини і атомного заряду. Визначено повний вихід гамма-квантів у передню півсферу і під великими кутами розсіювання в залежності від товщини конвертора. Показано відмінність характеристик гамма-випромінювання для тонких і товстих мішеней. Проведено розрахунок виходу нейтронів за рахунок фотоядерних реакцій для різних конверторів. Проведено чисельні оцінки спектрів випромінювання після проходження біологічного захисту окремо для нейтронного і гальмівного випромінювань.В GEANT4 рассчитаны спектрально-угловые распределения тормозного гамма-излучения электронов средних энергий из аморфных мишеней-конверторов различной толщины и атомного заряда. Определен полный выход гамма-квантов в переднюю полусферу и под большими углами рассеяния в зависимости от толщины конвертора. Показано различие характеристик гамма- излучения для тонких и толстых мишеней. Проведен расчет выхода нейтронов за счет фотоядерных реакций для различных конверторов. Проведены численные оценки спектров излучения после прохождения биологической защиты отдельно для нейтронного и тормозного излучений

Low-energy X-ray radiation after the biological shielding of electron accelerators

The bremsstrahlung of electrons from thick converters and its passage through concrete shielding of accelerators at different angles to the axis of the electron beam were calculated using GEANT4. Numerical estimates of the residual low-energy component of X-ray radiation after passing through the biological protection were carried out at an electron energy of up to 300 MeV. Additional reasons for the possible appearance of soft X-ray radiation after the shielding are considered. Experimental measurements of the spectral and dosimetric characteristics were performed by a silicon uncooled detector with the energy resolution of ~ 1 keV and spectral sensitivity in the range 5...150 keV. The comparison of the estimated dose (using the number of counts in Si detector) with indications of dosimeters was made.У GEANT4 розраховано гальмівне випромінювання електронів з товстих перетворювачів і проходження випромінювання через бетонне екранування прискорювачів під різними кутами до осі електронного пучка. Проведені численні оцінки залишкової низькоенергетичної складової рентгенівського випромінювання після проходження біологічного захисту при енергії електронів до 300 МеВ. Розглянуто додаткові причини появи м'якого рентгенівського випромінювання після проходження захисту. Експериментальні виміри спектральних та дозиметричних характеристик виконувалися кремнієвим неохолодженим детектором з енергетичним дозволом ~ 1 кеВ і спектральною чутливістю в діапазоні 5...150 кеВ. Проведено порівняння оціночної дози (з використанням кількості відліків у детекторі Si) з показами дозиметрів.В GEANT4 рассчитаны тормозное излучение электронов из толстых конверторов и прохождение излучения через бетонное экранирование ускорителей под разными углами к оси электронного пучка. Проведены численные оценки остаточной низкоэнергетической составляющей рентгеновского излучения после прохождения биологической защиты при энергии электронов до 300 МэВ. Рассмотрены дополнительные причины возможного появления мягкого рентгеновского излучения после прохождения защиты. Экспериментальные измерения спектральных и дозиметрических характеристик выполнялись кремниевым неохлаждаемым детектором с энергетическим разрешением ~ 1 кэВ и спектральной чувствительностью в диапазоне 5...150 кэВ. Проведено сравнение оценочной дозы (с использованием количества отсчетов в детекторе Si) с показаниями дозиметров

Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these \u201chidden responders\u201d may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA) PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. Way et al. develop a machine-learning approach using PanCanAtlas data to detect Ras activation in cancer. Integrating mutation, copy number, and expression data, the authors show that their method detects Ras-activating variants in tumors and sensitivity to MEK inhibitors in cell lines

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy

Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in 3c20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy. Knijnenburg et al. present The Cancer Genome Atlas (TCGA) Pan-Cancer analysis of DNA damage repair (DDR) deficiency in cancer. They use integrative genomic and molecular analyses to identify frequent DDR alterations across 33 cancer types, correlate gene- and pathway-level alterations with genome-wide measures of genome instability and impaired function, and demonstrate the prognostic utility of DDR deficiency scores

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGF\u3b2 signaling, p53 and \u3b2-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies