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Gastro-intestinal stromal tumors and acute myeloid leukemia induced by activating stem cell factor receptor tyrosine kinase (KIT) mutations are highly malignant. Less clear is the role of KIT mutations in the context of breast cancer. Treatment success of KIT-induced cancers is still unsatisfactory because of primary or secondary resistance to therapy. Mouse models offer essential platforms for studies on molecular disease mechanisms in basic cancer research. In the course of the Munich N-ethyl-N-nitrosourea (ENU) mutagenesis program a mouse line with inherited polycythemia was established. It carries a base-pair exchange in the Kit gene leading to an amino acid exchange at position 824 in the activation loop of KIT. This KIT variant corresponds to the N822K mutation found in human cancers, which is associated with imatinib-resistance. C3H KitN824K/WT mice develop hyperplasia of interstitial cells of Cajal and retention of ingesta in the cecum. In contrast to previous Kit-mutant models, we observe a benign course of gastrointestinal pathology associated with prolonged survival. Female mutants develop mammary carcinomas at late onset and subsequent lung metastasis. The disease model complements existing oncology research platforms. It allows for addressing the role of KIT mutations in breast cancer and identifying genetic and environmental modifiers of disease progression.

The vast majority of patients with myeloproliferative neoplasms (MPN), polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis, acquire driver mutations in the JAK2, MPL or CALR gene. Clustering of MPN is seen in select families, but in most pedigrees the MPN-predisposing change has not been determined and affected individuals somatically acquire one of the three above mentioned driver mutations. In contrast, a small number of individuals with hereditary thrombocythemia (HT) carry constitutive alterations, for example in the TPO or the LNK (SH2B3) gene.1–4 Acquired mutations in LNK, a negative regulator of JAK2 signaling, rarely occur in both sporadic and familial MPN cases.1,2 In the latter, they do not segregate with disease phenotype and diseased individuals acquire a concomitant MPN driver mutation.2 It, therefore, appears unlikely that mutant LNK acts as a driver in MPN.

26th European Photovoltaic Solar Energy Conference and Exhibition; 2943-2946, Structuring of thin-film photovoltaic modules requires basic knowledge of the laser – thin-film interaction in order to adapt the accessible laser parameters, like wavelength, power, repetition rate and scribing speed whilst taking into account the specific material properties of the layer. We have studied the nanosecond laserablation behavior of corresponding layers (i) of silicon based thin-film solar cells with a-Si/μc-Si tandem absorber type and (ii) of back contact and absorber layer of CIGSe solar cells. The respective ablation threshold fluences were determined as integrative parameters describing the specific laser – material interaction. For the threshold determination we used two different methods and developed a new analytical approach taking into account scribing through the glass substrate as it is preferred for most structuring processes. This was done by analyzing the thin film ablation results by means of optical microscopy, profilometry, scanning electron microscopy (SEM). Moreover, we determined the incubation coefficient of the regarded material layers which allows us to predict quantitatively the influence of the spot overlap on the scribing threshold.

Primary myelofibrosis (PMF) is characterized by increased number of hematopoietic progenitors and a dysmegakaryopoiesis which supports the stromal reaction defining this disease. We showed that increased ligand (FL) levels in plasma, hematopoietic progenitors, and stromal cells from PMF patients were associated with upregulation of the cognate Flt3 receptor on megakaryocytic (MK) cells. This connection prompted us to study a functional role for the FL/Flt3 couple in PMF dysmegakaryopoiesis, as a route to reveal insights into pathobiology and therapy in this disease. Analysis of PMF CD34+ and MK cell transcriptomes revealed deregulation of the mitogen-activated protein kinase (MAPK) pathway along with Flt3 expression. In PMF patients, a higher proportion of circulating Flt3+CD34+CD41+ cells exhibited an increased MAPK effector phosphorylation independently of Jak2V617F mutation. Activation of FL/Flt3 axis in PMF MK cell cultures, in response to FL, induced activation of the p38–MAPK cascade, which is known to be involved in inflammation, also increasing expression of its target genes (NFATC4, p53, AP-1, IL-8). Inhibiting Flt3 or MAPK or especially p38 by chemical, antibody, or silencing strategies restored megakaryopoiesis and reduced phosphorylation of Flt3 and p38 pathway effectors, confirming the involvement of Flt3 in PMF dysmegakaryopoiesis via p38 activation. In addition, in contrast to healthy donors, MK cells derived from PMF CD34+ cells exhibited an FL-induced migration that could be reversed by p38 inhibition. Taken together, our results implicate the FL/Flt3 ligand–receptor complex in PMF dysmegakaryopoiesis through persistent p38–MAPK activation, with implications for therapeutic prospects to correct altered megakaryopoiesis in an inflammatory context. Cancer Res; 71(8); 2901–15. ©2011 AACR.

26th European Photovoltaic Solar Energy Conference and Exhibition; 2540-2543, Manufacturing of CIGSe thin film solar modules involves typically one laser structuring step (P1) and two mechanical structuring steps (P2 and P3) for serial interconnection. In our approach, complete laser structuring is successfully demonstrated by application of short nanosecond laser pulses (

24th European Photovoltaic Solar Energy Conference, 21-25 September 2009, Hamburg, Germany; 2763-2765, Recent advances in laser sources and laser scribing process techniques are providing significant improvements in manufacturing throughput, cell efficiencies and production yields for the industrial manufacture of thin film solar cells. Widespread adoption of these improved technologies will contribute to accelerated reductions in manufacturing cost and further enable market adoption of thin film photovoltaic solar cells. We describe a novel new distributed laser scribe system design based on an air bearing linear motion stage which is optimized for high throughput laser scribing of large area glass photovoltaic thin film panels. The design concept is shown in the Fig. 1. This system provides six beam lines, each supplied by an individual compact ExplorerTM laser. Such system enables multiple laser scribes to be “written” through the stationary glass from below at speeds up to 2 m/s yet with very high accuracy (Fig. 2). This is a major improvement on existing designs that incorporate single laser beam split into 4 or 8 beam paths, scanners, mechanical bearings, or require fast movement of the glass substrates and thus are limited in their speed and or accuracy, usable life time, and scalability to larger panel sizes. This large area laser scribe platform is used to characterize the scribing processes in amorphous silicon process type thin film samples, performed by using multi-kHz q-switched solid state lasers laser of ns pulse duration and for panel sizes up to 1.3m×1.1m. The scribe width along the scribe lines, their parallelism and their sensitivity to the ambient temperature conditions were measured and characterized