Intermixing at the InxSy/Cu2ZnSn(S,Se)4 Heterojunction and Its Impact on the Chemical and Electronic Interface Structure

We report on the chemical and electronic structure of the interface between a thermally co-evaporated InxSy buffer and a Cu2ZnSn(S,Se)4 (CZTSSe) absorber for thin-film solar cells. To date, such cells have achieved energy conversion efficiencies up to 8.6%. Using surface-sensitive X-ray and UV photoelectron spectroscopy, combined with inverse photoemission and bulk-sensitive soft X-ray emission spectroscopy, we find a complex character of the buffer layer. It includes oxygen, as well as selenium and copper that diffused from the absorber into the InxSy buffer, exhibits an electronic band gap of 2.50 ± 0.18 eV at the surface, and leads to a small cliff in the conduction band alignment at the InxSy/CZTSSe interface. After an efficiency-increasing annealing step at 180 °C in nitrogen atmosphere, additional selenium diffusion leads to a reduced band gap at the buffer layer surface (2.28 ± 0.18 eV)

Impact of depth of response on survival in patients treated with cobimetinib ± vemurafenib: pooled analysis of BRIM-2, BRIM-3, BRIM-7 and coBRIM.

BackgroundThis pooled analysis investigated the prognostic value of depth of response in two cohorts of patients with BRAFV600-mutated metastatic melanoma treated with vemurafenib or cobimetinib plus vemurafenib.MethodsThe data were pooled from BRIM-2, BRIM-3, BRIM-7 and coBRIM. Association of depth of response with survival was estimated by Cox proportional hazards regression, adjusted for clinically relevant covariates. Depth of response was analysed in previously identified prognostic subgroups based on disease characteristics and gene signatures.ResultsGreater tumour reduction and longer time to maximal response were significantly associated with longer progression-free survival (PFS) and overall survival (OS) when evaluated as continuous variables. Patients with the deepest responses had long-lasting survival outcomes (median PFS: 14 months; OS: 32 months with vemurafenib; not estimable with cobimetinib plus vemurafenib). Cobimetinib plus vemurafenib improved depth of response versus vemurafenib monotherapy regardless of other prognostic factors, including gene signatures.ConclusionsGreater depth of response was associated with improved survival, supporting its utility as a measure of treatment efficacy in melanoma and further evaluation of its incorporation into existing prognostic models. Cobimetinib plus vemurafenib improved outcomes across quartiles of response regardless of prognostic factors or gene signatures and provided durable survival benefits in patients with deep responses

High Prevalence of Hypovitaminosis D in Adolescents Attending a Reference Centre for the Treatment of Obesity in Switzerland.

Hypovitaminosis D is common in populations with obesity. This study aimed at assessing (1) the prevalence of hypovitaminosis D and (2) the associations between vitamin D levels and cardiovascular risk factors in adolescents attending a reference centre for the treatment of obesity. Cross-sectional pilot study conducted in the paediatric obesity unit of the Lausanne university hospital, Switzerland. Participants were considered eligible if they (1) were aged between 10 to 16.9 years and (2) consulted between 2017 and 2021. Participants were excluded if (1) they lacked vitamin D measurements or (2) the vitamin D measurement was performed one month after the base anthropometric assessment. Hypovitaminosis D was considered if the vitamin D level was <30 ng/mL (<75 nmol/L). Severe obesity was defined as a BMI z-score > 3 SD. We included 52 adolescents (31% girls, mean age 13 ± 2 years, 33% with severe obesity). The prevalence of hypovitaminosis D was 87.5% in girls and 88.9% in boys. The vitamin D levels were inversely associated with BMI, Spearman r and 95% CI: -0.286 (-0.555; -0.017), p = 0.037; they were not associated with the BMI z-score: -0.052 (-0.327; 0.224), p = 0.713. The vitamin D levels were negatively associated with the parathormone levels (-0.353 (-0.667; -0.039), p = 0.028) and positively associated with the calcium levels (0.385 (0.061; 0.708), p = 0.020), while no association was found between vitamin D levels and blood pressure and lipid or glucose levels. almost 9 out of 10 adolescents with obesity in our cohort presented with hypovitaminosis D. Hypovitaminosis D does not seem to be associated with a higher cardiovascular risk profile in this group

The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

First observation of excited states in 173Hg

The neutron-deficient nucleus 173Hg has been studied following fusion-evaporation reactions. The observation of gamma rays decaying from excited states are reported for the first time and a tentative level scheme is proposed. The proposed level scheme is discussed within the context of the systematics of neighbouring neutron-deficient Hg nuclei. In addition to the gamma-ray spectroscopy, the alpha decay of this nucleus has been measured yielding superior precision to earlier measurements.Comment: 5 pages, 4 figure