Reindeer in tundra ecosystems: the challenges of understanding system complexity

complexit

DeltaNp63alpha-Mediated Induction of Epidermal Growth Factor Receptor Promotes Pancreatic Cancer Cell Growth and Chemoresistance

Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to current chemotherapy regimens, in part due to alterations in the p53 tumor suppressor pathway. p53 homolog p63 is a transcription factor essential for the development and differentiation of epithelial surfaces. However its function in cancer is controversial and its role in PDAC is not known. We discovered that ΔNp63α was the predominantly expressed p63 variant in pancreatic cancer cell lines. ΔNp63α protein and mRNA levels were high in T3M4, BxPC3 and COLO-357 pancreatic cancer cells and low in ASPC-1 and PANC-1 cells. Overexpression of ΔNp63α in PANC-1 cells and shRNA-mediated knockdown in T3M4 cells indicated that ΔNp63α promoted anchorage-dependent and -independent growth, motility and invasion, and enhanced resistance to cisplatin-induced apoptosis. Epidermal growth factor receptor (EGFR) signaling pathways contribute to the biological aggressiveness of PDAC, and we found that the motogenic effects of ΔNp63α were augmented in presence of EGF. Ectopic expression of ΔNp63α resulted in upregulation of EGFR and β1-integrin in PANC-1 cells. Conversely, ΔNp63α knockdown had an opposite effect in T3M4 cells. ΔNp63α potentiated EGF-mediated activation of ERK, Akt and JNK signaling. Chromatin immunoprecipitation and functional reporter assays demonstrated that ΔNp63α activated EGFR transcription. 14-3-3σ transcription was also positively regulated by ΔNp63α and we have previously shown that 14-3-3σ contributes to chemoresistance in pancreatic cancer cell lines. Conversely, shRNA-mediated knockdown of 14-3-3σ led to abrogation of the ΔNp63α effects on cell proliferation and invasion. Thus, p53 homolog ΔNp63α enhances the oncogenic potential of pancreatic cancer cells through trans-activation of EGFR and 14-3-3σ

Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma.

B-cell receptor (BCR) signaling pathway inhibitors (including Bruton’s tyrosine kinase [BTK] inhibitors, and phosphatidylinositol-3 kinase inhibitors [PI3Ki]) have shown clinical efficacy in non-Hodgkin lymphoma (NHL). However, responses to these agents have been limited in depth and duration. This may be due to resistance to PI3Kδ and BTK inhibitors as monotherapy. The emergence of resistant clones may be addressed by combining these 2 classes of drugs. Furthermore, tolerability of these drug classes has been a concern. Combination therapy using lower doses of one or more classes of inhibitor may address some limitations

Cohesive strength of nanocrystalline ZnO:Ga thin films deposited at room temperature

In this study, transparent conducting nanocrystalline ZnO:Ga (GZO) films were deposited by dc magnetron sputtering at room temperature on polymers (and glass for comparison). Electrical resistivities of 8.8 × 10-4 and 2.2 × 10-3 Ω cm were obtained for films deposited on glass and polymers, respectively. The crack onset strain (COS) and the cohesive strength of the coatings were investigated by means of tensile testing. The COS is similar for different GZO coatings and occurs for nominal strains approx. 1%. The cohesive strength of coatings, which was evaluated from the initial part of the crack density evolution, was found to be between 1.3 and 1.4 GPa. For these calculations, a Young's modulus of 112 GPa was used, evaluated by nanoindentation

Follicular Lymphoma: Recent and Emerging Therapies, Treatment Strategies, and Remaining Unmet Needs

Follicular lymphoma (FL) is a heterogeneous disease with varying prognosis owing to differences in clinical, laboratory, and disease parameters. Although generally considered incurable, prognosis for early- and advanced-stage disease has improved because of therapeutic advances, several of which have resulted from elucidation of the biologic and molecular basis of the disease. The choice of treatment for FL is highly dependent on patient and disease characteristics. Several tools are available for risk stratification, although limitations in their routine clinical use exist. For limited disease, treatment options include radiotherapy, rituximab monotherapy or combination regimens, and surveillance. Treatment of advanced disease is often determined by tumor burden, with surveillance or rituximab considered for low tumor burden and chemoimmunotherapy for high tumor burden disease. Treatment for relapsed or refractory disease is influenced by initial first-line therapy and the duration and quality of the response. Presently, there is no consensus for treatment of patients with early or multiply relapsed disease; however, numerous agents, combination regimens, and transplant options have demonstrated efficacy. Although the number of therapies available to treat FL has increased together with an improved understanding of the underlying biologic basis of disease, the best approach to select the most appropriate treatment strategy for an individual patient at a particular time continues to be elucidated. This review considers prognostication and the evolving treatment landscape of FL, including recent and emergent therapies as well as remaining unmet needs. Implications for Practice: In follicular lymphoma, a personalized approach to management based on disease biology, patient characteristics, and other factors continues to emerge. However, application of current management requires an understanding of the available therapeutic options for first-line treatment and knowledge of current development in therapies for previously untreated and for relapsed or refractory disease. Thus, this work reviews for clinicians the contemporary data in follicular lymphoma, from advances in characterizing disease biology to current treatments and emerging novel therapies

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

Peer reviewe

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe