Processing of Dielectric Materials and Metals with ps Laserpulses

Since industrial suited ps laser systems are available, the cold ablation with ultrashort laser pulses is of huge interest when high requirements concerning accuracy, surface roughness and heat affected zone are demanded. Interesting applications lie within the fields of surface and 3-d structuring of metals, semiconductors (especially flexible solar cells) and dielectric materials with direct and induced processes. For a profitable industrial use of this technology high process efficiency is required which is confirmed by the development of the corresponding systems towards high average powers up to several 10 W. Beside the pulse duration, which is given by the laser system, the user has a wide variety of parameters, e.g. fluence, repetition rate, wavelength and marking speed, to optimize structuring processes. For a given average power there exist optimal laser parameters to achieve a maximal volume ablation rate. To take benefit of this maximum ablation rate, to simultaneously prevent harmful effects (particle shielding, surface melting) and to achieve the requirements concerning surface quality and accuracy, adapted structuring strategies have to be used. This can lead to equipment needs of the beam guiding system which are often not accomplishable and therefore to the demand for new technologies which have to be developed

Micro structuring of transparent materials with NIR ns-laser pulses

A current challenge in laser processing is high precision micromachining of transparent materials, e.g. to manufacture micro-optical elements. This can be achieved amongst others by using laser induced backside wet etching. Research has been done by several groups in the last years. Most of the published results were obtained by using UV excimer lasers. Our approach deals withthe implementation of the technique for NIR laser sources. We investigated the effects of different pulse widths and repetitionrates on laser induced back side wet etching for 1064nm wavelength and for different absorbers

Super-high-resolution Earth observation datasets of North American permafrost landscapes

While temperatures are increasing on the global scale, the Arctic regions are especially vulnerable to this changing climate and landscapes underlain by permafrost experience increased thaw and degradation. The enhanced warming of organic-rich frozen ground can have severe consequences on infrastructure and ecosystems and is projected to become a highly relevant driver of greenhouse gas fluxes into the atmosphere. Degrading permafrost landscapes occur extensively in vast areas of the North American Arctic, directly affecting communities and ecosystems. To identify and quantify these widespread degradation phenomena over vast areas, we require highest-resolution Earth observation dataset that we collect during aerial imaging campaigns. We here report on observations and first results from three airborne campaigns in 2018, 2019 and 2021. We performed large-scale monitoring of permafrost-affected areas in northern Canada and Alaska, focusing on sites that experienced disturbances in the past or recently. This included sites with vulnerable settlements, coastal erosion, thaw slumping, lake expansion and drainage, ice-wedge degradation and thaw subsidence, fire scars, pingos, methane seeps, and sites affected by beaver activities. All surveys were flown with the Alfred Wegener Institute's Polar-5 and -6 scientific airplanes at 500-1500 m altitude above terrain. The onboard sensor, the Modular Aerial Camera System (MACS), a very-high-resolution multispectral camera developed by the German Aerospace Center, operated in the visible (RGB) and near-infrared (NIR) domain. From the comprehensive collection of multiple TB of gathered data, super-high-resolution (up to 7 cm/px) RGB+NIR image mosaics and stereophotogrammetric digital surface models were derived. By presenting the data and first analyses, we would like to invite the community to discuss best use for maximized benefit of the data, in order to substantially contribute to our understanding of permafrost thaw dynamics

Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

Background: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. Methods: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). Results: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. Conclusions: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therap

Detecting Activation of Ribosomal Protein S6 Kinase by Complementary DNA and Tissue Microarray Analysis

Background: Studies by comparative genomic hybridization (CGH) have shown that chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We used microarray analyses to measure the expression levels of genes in this region and to explore their prognostic importance. Methods: A microarray that contained 4209 complementary DNA (cDNA) clones was used to identify genes that are overexpressed in the MCF-7 breast cancer cell line as compared with normal mammary tissue. Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region. Northern and western blot analyses were used to measure S6K gene and protein expression, and an enzymatic assay was used to measure S6K activity. Tumor tissue microarray analysis was used to study amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the relationship between amplification and prognosis was analyzed. The Kaplan-Meier method was used for data analysis, and the log-rank test was used for statistical analysis. All P values are two-sided. Results: S6K was amplified and highly overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of 668 primary breast tumors, and a statistically significant association between amplification and poor prognosis (P = .0021) was observed. Amplification of both S6K and HER-2 implied particularly poor survival (P = .0001). Conclusions: The combination of CGH information with cDNA and tissue microarray analyses can be used to identify amplified and overexpressed genes and to evaluate the clinical implications of such genes and genomic rearrangements. S6K is likely to be one of the genes at 17q23 that is amplified during oncogenesis and may adversely affect the prognosis of patients with this amplificatio

Use of surrogate endpoints in healthcare policy : proposal for consistent adoption of a validation framework

We propose a three step framework for the evaluation of surrogate endpoints for health policy decisions on health technologies

FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas

In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an association of reduced FOCAD gene copy number with overall survival of patients with astrocytic gliomas, and addressed the molecular mechanisms that govern the suppressive effect of focadhesin on glioma growth. FOCAD loss was associated with inferior outcome in patients with isocitrate dehydrogenase 1 or 2 (IDH)-mutant astrocytic gliomas of WHO grades II-IV. Multivariate analysis considering age at diagnosis as well as IDH mutation, MGMT promoter methylation, and CDKN2A/B homozygous deletion status confirmed reduced FOCAD gene copy number as a prognostic factor for overall survival. Using a yeast two-hybrid screen and pull-down assays, tubulin beta-6 and other tubulin family members were identified as novel focadhesin-interacting partners. Tubulins and focadhesin co-localized to centrosomes where focadhesin was enriched in proximity to centrioles. Focadhesin was recruited to microtubules via its interaction partner SLAIN motif family member 2 and reduced microtubule assembly rates, possibly explaining the focadhesin-dependent decrease in cell migration. During the cell cycle, focadhesin levels peaked in G2/M phase and influenced time-dependent G2/M progression potentially via polo like kinase 1 phosphorylation, providing a possible explanation for focadhesin-dependent cell growth reduction. We conclude that FOCAD loss may promote biological aggressiveness and worsen clinical outcome of diffuse astrocytic gliomas by enhancing microtubule assembly and accelerating G2/M phase progression

Airborne LiDAR and stereo-photogrammetric characterization of permafrost landscapes and thaw subsidence

Rapid climate change in the northern high latitudes has a strong impact on permafrost stability, apparent as coastal erosion, subsidence, or lake dynamics with potentially severe consequences for local communities and ecology. In a rapidly warming Arctic, the monitoring of these processes is essential to understand and predict permafrost dynamics over the upcoming decades. These landscape dynamics are highly diverse, localized, but widely distributed and require datasets with very high spatial resolution, which are barely achieved by satellite data alone. Repeat observations over several years allow for unprecedented insights into highly critical landscape dynamics and the potential integration with and validation of more coarse resolution satellite data. AWI’s research aircraft (Polar-5 and Polar-6) were equipped with airborne LiDAR (full-waveform, multi-echo) as well with experimental modular sensors such as the DLR-developed multi-spectral optical Modular Airborne Camera System (MACS) with a spatial resolution of few cm, stereo capabilities and a very broad radiometric range. The incoming data stream of acquired laser return point cloud data as well as hundreds of thousands of high-resolution images for individual campaigns poses new challenges of handling and processing large data volumes. Here we present an overview about past and upcoming flight campaigns in Alaska and northwestern Canada. Furthermore, we will show applications of the acquired datasets, such as assessments of subsidence, coastal erosion or infrastructure development

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratificatio