Enumerative aspects of the Gross-Siebert program

We present enumerative aspects of the Gross-Siebert program in this introductory survey. After sketching the program's main themes and goals, we review the basic definitions and results of logarithmic and tropical geometry. We give examples and a proof for counting algebraic curves via tropical curves. To illustrate an application of tropical geometry and the Gross-Siebert program to mirror symmetry, we discuss the mirror symmetry of the projective plane.Comment: A version of these notes will appear as a chapter in an upcoming Fields Institute volume. 81 page

Nonlinear compressible finite viscoleasticity of epoxy-based polymers

Epoxy-based polymers are widely used in the semiconductor industry as thermal and/or electrical interfaces and as encapsulating material. In the automotive industry, epoxy-based molding compounds (EMCs) are often used to protect not only the single IC packages but also the entire electronic control units (ECUs) (or the power modules). The stress caused by the mismatch of the coefficient of thermal expansion (CTE) between EMC and adjacent materials is one of the major causes for premature failure. In the temperature range of interest, the mold material used in the specific applications exhibits a highly nonlinear behavior. Especially around the glass transition temperature, a dominant nonlinear viscous characteristic of the mold material can be observed. During operation of the aforementioned applications, the epoxy-based polymers are subjected to elevated temperatures around the glass transition temperature, where the material exhibits significant volumetric viscosity in addition to shear viscosity. Traditionally, the nonlinear viscoelastic constitutive models do not consider the volumetric viscoelastic behavior examined in epoxy-based polymers at elevated temperatures. In this contribution, we present the theoretical modeling of these materials. On the theoretical side, we propose a new finite viscoelastic constitutive model, which accounts for the nonlinear volumetric and isochoric viscoelasticity observed in this class of materials. To this end, the polymer network is additively decomposed into a strong elastic network and a superimposed secondary network responsible for rate-dependent response. A nonlinear equation is proposed for the evolution of the viscous deformations in the sense of Dal (2011, Ph.D. thesis, TU Dresden). Regarding an accelerated product development process using commercial software packages, accurate and predictive material modeling is vital. The proposed model is proven to be a very powerful tool for accelerating the development process of electronic control units or power modules by better prediction and evaluation of the limits

Silencer of death domains controls cell death through tumour necrosis factor-receptor 1 and caspase-10 in acute lymphoblastic leukemia

Resistance to apoptosis remains a significant problem in drug resistance and treatment failure in malignant disease. NO-aspirin is a novel drug that has efficacy against a number of solid tumours, and can inhibit Wnt signaling, and although we have shown Wnt signaling to be important for acute lymphoblastic leukemia (ALL) cell proliferation and survival inhibition of Wnt signaling does not appear to be involved in the induction of ALL cell death. Treatment of B lineage ALL cell lines and patient ALL cells with NO-aspirin induced rapid apoptotic cell death mediated via the extrinsic death pathway. Apoptosis was dependent on caspase-10 in association with the formation of the death-inducing signaling complex (DISC) incorporating pro-caspase-10 and tumor necrosis factor receptor 1 (TNF-R1). There was no measurable increase in TNF-R1 or TNF-α in response to NO-aspirin, suggesting that the process was ligand-independent. Consistent with this, expression of silencer of death domain (SODD) was reduced following NO-aspirin exposure and lentiviral mediated shRNA knockdown of SODD suppressed expansion of transduced cells confirming the importance of SODD for ALL cell survival. Considering that SODD and caspase-10 are frequently over-expressed in ALL, interfering with these proteins may provide a new strategy for the treatment of this and potentially other cancers.10 page(s

<i>para</i>-NO-ASA results in activation of executioner caspases and mitochondrial depolarization.

<p>(A) Cleavage of caspase-3 in NALM6 cells by intracellular flow cytometry following 6 hour exposure to 10 µM <i>para</i>-NO-ASA. (B) Caspase-3 activation as measured by flow cytometry, in NALM6 cells untreated or treated with 5 µM or 10 µM <i>para</i>-NO-ASA for the given time. Bars indicate the mean and s.d. of 3 independent experiments. (C) Western blot analysis of PARP activation in NALM6 cells stimulated with the indicated concentrations of <i>para</i>-NO-ASA for 12 hours. The cleaved (89 kD) and uncleaved (116 kD) forms of PARP are indicated. Data is representative of 2 independent experiments. (D) NALM6 cells were treated with 5 µM <i>para</i>-NO-ASA or vehicle for 6 hours and assessed for ΔΨ_m using TMRM to label cells with polarized mitochondria, and apoptosis using annexin V and 7AAD. Representative plots are shown and the mean percentage of cells from 2 experiments in each quadrant indicated. (E) Representative histograms showing cytochrome c release following exposure of NALM6 cells to 5 µM para-NO-ASA for 6 hours. The thin line represents isotype control (Iso) staining and the heavy line cytochrome c (Cyto c) staining. (F) Quantitation of cytochrome c release at the indicated time points following addition of 5 µM <i>para</i>-NO-ASA. The mean and s.d. of replicates is shown. *p = 0.02. (G) NALM6 cells were pre-treated with 100 µM Z-VAD or 2.5 mM NAC for 1 hour prior to exposure to 5 µM <i>para</i>-NO-ASA for 6 h the mean ± s.e. is shown (n≥5). *p<0.05 compared to NO-ASA alone.</p

SODD is over-expressed in ALL cells and expression is required for ALL cell growth.

<p>(A) SODD expression was determined by semi-quantitative RT-PCR in NALM6 and REH cells treated with 10 µM <i>para</i>-NO-ASA for 12 h. (B) SODD expression was determined by western blotting following treatment with 10 µM <i>para</i>-NO-ASA for the indicated times. (C) Western blot analysis of SODD in normal peripheral blood mononuclear cells (PBMC), indicated cell lines (upper blots) or patient samples (lower blots). Patient samples had been expanded in NOD/SCID mice to obtain sufficient cells for Western blotting. (D) NALM6 transduced with lentiviral constructs expressing GFP alone (Control) or containing one of two shRNA specific for SODD (SODD1 and SODD2). The level of SODD protein (D) was determined in LK63 cells after 44 days in culture while mRNA levels were assessed in NALM6 cells on day 6 of culture by qRT-PCR and was normalised to the levels of GAPDH (E). The mean and s.e.m. of three independent experiments is shown. (F) The total cell number (left panels), and the percentage (centre panels) and total number of GFP+ transduced cells (right panels) was monitored over time. The mean and s.d. of duplicate cultures is shown.</p

Schematic diagram illustrating the proposed mechanism of action of <i>para</i>-NO-ASA.

<p><i>para</i>-NO-ASA down regulates SODD allowing self-aggregation, or enhancing TNF-α-induced, activation of signalling through TNF-R1. TNF-R1 signalling triggers the extrinsic apoptosis cascade including cleavage of pro-caspase-10 and Bid, mitochondrial depolarization, outer membrane permeabilization and release of cytochrome c. This is followed by cleavage of pro-caspase-9 and the executioner caspases-3 and -7. While signalling through TNF-R1 can activate NF-κB this may be suppressed by caspase-mediated cleavage of TRAF. In contrast, TNF-R2 signal induces cell survival and proliferation pathways, predominantly through NF-κB but also MAPK signalling. In ALL cells where SODD is over expressed, exogenous TNF-α is likely to predominantly signal through TNF-R2 resulting in increased survival and proliferation. Activating TNF-R1 by down regulation of SODD provides a mechanism for inducing cell death without increasing proliferation and survival signals. FADD, Fas-associated death domain; IKK, inhibitor of κB kinase; I-κB, inhibitor of κB; TRADD, TNF-R1-associated death domain; TRAF, TNF receptor-associated factor.</p

<i>para</i>-NO-ASA induces formation of the death initiating signalling complex containing caspase-10 and suppression of SODD.

<p>(A) NALM6 and LK63 cell lines were treated with 10 µM <i>para</i>-NO-ASA for 6 h and labelled for surface TNF-R1 (left panels). (B) NALM6 and REH cells were treated with <i>para</i>-NO-ASA for 6 h and assessed for TNF-α production by flow cytometry. PBMC treated with 50 ng/ml PMA and 1 µg/ml ionomycin are included as a positive control. The percentage of cells expressing TNF-α is shown on each plot. (C) NALM6 cells were treated with TNF-α (100 ng/ml), or <i>para</i>-NO-ASA (10 µM) as indicated and cell lysates prepared. TNF-R1 was immunoprecipitated and recovered complexes probed for caspase-10 or TNF-R1.</p