NLO QCD corrections to the production of Higgs plus two jets at the LHC

We present the calculation of the NLO QCD corrections to the associated production of a Higgs boson and two jets, in the infinite top-mass limit. We discuss the technical details of the computation and we show the numerical impact of the radiative corrections on several observables at the LHC. The results are obtained by using a fully automated framework for fixed order NLO QCD calculations based on the interplay of the packages GoSam and Sherpa. The evaluation of the virtual corrections constitutes an application of the d-dimensional integrand-level reduction to theories with higher dimensional operators. We also present first results for the one-loop matrix elements of the partonic processes with a quark-pair in the final state, which enter the hadronic production of a Higgs boson together with three jets in the infinite top-mass approximation.Comment: 9 pages, 7 figures, references added, published in Phys.Lett.

Automated one-loop calculations with GoSam 2.0

We present the version 2.0 of the program GoSam, which is a public program package to compute one-loop corrections to multi-particle processes. The extended version of the "Binoth-Les-Houches-Accord" interface to Monte Carlo programs is also implemented. This allows a large flexibility regarding the combination of the code with various Monte Carlo programs to produce fully differential NLO results, including the possibility of parton showering and hadronisation. We describe the new features of the code and illustrate the wide range of applicability for multi-particle processes at NLO, both within and beyond the Standard Model.Comment: 9 pages, talk given at the conference "Loops and Legs in Quantum Field Theory", Weimar, Germany, April 201

GoSam-2.0: a tool for automated one-loop calculations within the Standard Model and beyond

We present the version 2.0 of the program package GoSam for the automated calculation of one-loop amplitudes. GoSam is devised to compute one-loop QCD and/or electroweak corrections to multi-particle processes within and beyond the Standard Model. The new code contains improvements in the generation and in the reduction of the amplitudes, performs better in computing time and numerical accuracy, and has an extended range of applicability. The extended version of the "Binoth-Les-Houches-Accord" interface to Monte Carlo programs is also implemented. We give a detailed description of installation and usage of the code, and illustrate the new features in dedicated examples.Comment: replaced by published version and reference adde

Expression of hypoxia-induced proteins in ductal carcinoma in situ and invasive cancer of the male breast

AIMS: The aim of this study was to determine the role of hypoxia in male breast carcinogenesis by evaluating the expression of the hypoxia-related proteins, hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase IX (CAIX) and glucose transporter-1 (Glut-1), in ductal carcinoma in situ (DCIS) of the male breast in relation to invasive cancer (IC). METHODS: Tumour tissue blocks of 18 cases of pure DCIS, 58 DCIS cases adjacent to IC (DCIS-AIC) and the 58 IC cases were stained by immunohistochemistry for HIF-1α, CAIX and Glut-1, and expression frequencies and patterns (diffuse and/or perinecrotic) were noted. RESULTS: HIF-1α overexpression was observed in 61.1% (11/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 36.2% (21/58) of IC cases (not significant (n.s.)). CAIX overexpression was observed in 16.7% (3/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 24.1% (14/58) of IC cases (n.s.). Glut-1 overexpression was observed in 61.1% (11/18) of pure DCIS, in 75.9% (44/58) of DCIS-AIC and in 62.1% (36/58) of IC cases (n.s.). Expression of hypoxia-related proteins was seen around necrosis in a little over one-third of DCIS cases, and often coincided with expression in adjacent IC when present. All these observations indicate that the hypoxia response is already at its maximum in the preinvasive DCIS stage. CONCLUSIONS: In conclusion, male DCIS frequently shows activated hypoxia response, comparable to male IC. This indicates that the activated hypoxia response previously seen in male IC is not a late bystander but likely a genuine carcinogenetic event

Эффективность комбинированных криоконсервантов, содержащих глицерин или 1,2-пропандиол, при замораживании эритроцитов

Исследовали осмотические свойства эритроцитов, замороженных в комбинированных криоконсервантах, содержащих полимерные непроникающие (декстран, полиэтиленгликоль) и проникающие (глицерин, 1,2-пропандиол) криопротекторы. Установлено, что в эритроцитах, замороженных-отогретых в среде с полимерами, отмечается повышение скорости потока ионов Н+ и осмотической хрупкости в среде, содержащей 0,45–0,9% NaCl. Для сохранения осмотических свойств замороженных- отогретых клеток достаточно включить в среду глицерин или 1,2-пропандиол (1,2-ПД) в концентрации 5%. Полученные результаты позволяют предположить, что криопротекторная эффективность комбинированных криоконсервантов, содержащих непроникающие и проникающие криопротекторы, определяется вкладом различных по механизму действия криозащитных компонентов в суммарную защитную эффективность при замораживании и ослаблением постгипертонического стресса на клетки при размораживании.Досліджували осмотичні властивості еритроцитів, заморожених-відігрітих у комбінованих кріоконсервантах, які містять полімерні непроникаючі (декстран, поліетиленгліколь) і проникаючі (гліцерин, 1,2-пропандіол) кріопротектори. Встановлено, що в еритроцитах, заморожених-відігрітих у середовищі з полімерами, визначається зростання швидкості потоку іонів Н+ і осмотичної крихкості в середовищі, яке містить 0,45–0,9% NaCl. Для збереження осмотичних властивостей заморожених- відігрітих клітин достатньо включити в середовище гліцерин або 1,2-пропандіол в концентрації 5%. Отримані результати дозволяють припустити, що кріопротекторна ефективність комбінованих кріоконсервантів, які містять непроникаючі і проникаючі кріопротектори, визначається внеском різноманітних за механізмом дії кріозахисних компонентів у сумарну захисну ефективність при заморожуванні та послабленням постгіпертонічного стресу на клітини при розморожуванні.The osmotic properties of erythrocytes frozen-thawed in combined cryopreservatives, containing polymeric non-penetrating (dextran, polyethylene glycol) and penetrating (glycerol, 1,2-propane diol) cryoprotectants were studied. It was established that in erythrocytes frozen-thawed in the presence of polymers the increasing of H+ ion flow rate and osmotic fragility in the environment with 0.45–0.9% NaCl was observed. It is sufficient to add 5% glycerol or 1,2-propane diol (1,2-PD) to the medium to preserve osmotic properties of frozen-thawed cells. The obtained results enable to suggest that cryoprotective efficiency of combined cryopreservatives, containing non-penetrating and penetrating cryoprotectants is determined both by the contribution of cryoprotective components differing by action mechanism into th

Transcriptomic properties of her2+ ductal carcinoma in situ of the breast associate with absence of immune cells

SIMPLE SUMMARY: Tumor-infiltrating lymphocytes (TILs) are likely to play a role in the biological behavior of HER2+ ductal carcinoma in situ (DCIS). To prevent invasiveness, the potential of targeted immune-modulating treatment of HER2+ DCIS has been explored. We identified a 29-gene expression profile that was associated with the density of TILs. These genes included CCND3, DUSP10 and RAP1GAP, which may guide towards more rationalized choices with respect to immune-mediated therapy in HER2+ DCIS, such as targeted vaccine therapy. ABSTRACT: The identification of transcriptomic alterations of HER2+ ductal carcinoma in situ (DCIS) that are associated with the density of tumor-infiltrating lymphocytes (TILs) could contribute to optimizing choices regarding the potential benefit of immune therapy. We compared the gene expression profile of TIL-poor HER2+ DCIS to that of TIL-rich HER2+ DCIS. Tumor cells from 11 TIL-rich and 12 TIL-poor DCIS cases were micro-dissected for RNA isolation. The Ion AmpliSeq Transcriptome Human Gene Expression Kit was used for RNA sequencing. After normalization, a Mann–Whitney rank sum test was used to analyze differentially expressed genes between TIL-poor and TIL-rich HER2+ DCIS. Whole tissue sections were immunostained for validation of protein expression. We identified a 29-gene expression profile that differentiated TIL-rich from TIL-poor HER2+ DCIS. These genes included CCND3, DUSP10 and RAP1GAP, which were previously described in breast cancer and cancer immunity and were more highly expressed in TIL-rich DCIS. Using immunohistochemistry, we found lower protein expression in TIL-rich DCIS. This suggests regulation of protein expression at the posttranslational level. We identified a gene expression profile of HER2+ DCIS cells that was associated with the density of TILs. This classifier may guide towards more rationalized choices regarding immune-mediated therapy in HER2+ DCIS, such as targeted vaccine therapy

Nodal-Stage Classification in Invasive Lobular Breast Carcinoma: Influence of Different Interpretations of the pTNM Classification

Purpose Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) -positive patients to select patients with limited or with a high risk of non-SN involvement. Patients and Methods SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed. Results Reclassification according to definitions of EWGBSP and Turner et al resulted in different pN classification in 73 patients (19%). The rate of non-SN involvement in the 40 patients with isolated tumor cells according to Turner et al and with micrometastases according to EWGBSP was 20%, which is comparable to the established rate for micrometastases. The rate of non-SN involvement in the 29 patients with micrometastases according to Turner et al and with macrometastases according to EWGBSP was 48%, which is comparable to the established rate for macrometastases. Therefore, the EWGBSP method to classify SN tumor load better reflected the risk of non-SN involvement than the Turner et al system. Conclusion Compared with the guidelines by Turner et al, the EWGBSP definitions better reflect SN metastatic tumor load and allow better differentiation between patients with lobular breast carcinoma who have a limited or a high risk of non-SN metastases. Therefore, we suggest using the EWGBSP definitions in these patients to select high-risk patients who may benefit from additional local and/or systemic therapy

Using second harmonic generation to predict patient outcome in solid tumors

Abstract Background Over-treatment of estrogen receptor positive (ER+), lymph node-negative (LNN) breast cancer patients with chemotherapy is a pressing clinical problem that can be addressed by improving techniques to predict tumor metastatic potential. Here we demonstrate that analysis of second harmonic generation (SHG) emission direction in primary tumor biopsies can provide prognostic information about the metastatic outcome of ER+, LNN breast cancer, as well as stage 1 colorectal adenocarcinoma. Methods SHG is an optical signal produced by fibrillar collagen. The ratio of the forward-to-backward emitted SHG signals (F/B) is sensitive to changes in structure of individual collagen fibers. F/B from excised primary tumor tissue was measured in a retrospective study of LNN breast cancer patients who had received no adjuvant systemic therapy and related to metastasis-free survival (MFS) and overall survival (OS) rates. In addition, F/B was studied for its association with the length of progression-free survival (PFS) in a subgroup of ER+ patients who received tamoxifen as first-line treatment for recurrent disease, and for its relation with OS in stage I colorectal and stage 1 lung adenocarcinoma patients. Results In 125 ER+, but not in 96 ER-negative (ER-), LNN breast cancer patients an increased F/B was significantly associated with a favorable MFS and OS (log rank trend for MFS: p = 0.004 and for OS: p = 0.03). On the other hand, an increased F/B was associated with shorter PFS in 60 ER+ recurrent breast cancer patients treated with tamoxifen (log rank trend p = 0.02). In stage I colorectal adenocarcinoma, an increased F/B was significantly related to poor OS (log rank trend p = 0.03), however this relationship was not statistically significant in stage I lung adenocarcinoma. Conclusion Within ER+, LNN breast cancer specimens the F/B can stratify patients based upon their potential for tumor aggressiveness. This offers a “matrix-focused” method to predict metastatic outcome that is complementary to genomic “cell-focused” methods. In combination, this and other methods may contribute to improved metastatic prediction, and hence may help to reduce patient over-treatment.http://deepblue.lib.umich.edu/bitstream/2027.42/116036/1/12885_2015_Article_1911.pd