TLM modeling and system identification of optimized antenna structures

The transmission line matrix (TLM) method in conjunction with the genetic algorithm (GA) is presented for the bandwidth optimization of a low profile patch antenna. The optimization routine is supplemented by a system identification (SI) procedure. By the SI the model parameters of the structure are estimated which is used for a reduction of the total TLM simulation time. The SI utilizes a new stability criterion of the physical poles for the parameter extraction

Systemic shRNA mediated knock down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation

The metastasis-inducing protein S100A4 was found to be a prognostic indicator for the development of metachronous metastases. S100A4 expression levels correlate with the formation of human colorectal cancer metastases and shorter patients' survival. Inhibition of S100A4 expression in patients might therefore result in decreased metastasis formation and prolonged survival. In the present study, we used shRNA expression plasmids to inhibit S100A4 expression in the colorectal cancer cell lines HCT116, SW620 and DLD-1. Cell lines with reduced S100A4 expression showed reduced cell migration and invasion in vitro. The knock-down of S100A4 expression also led to significantly diminished formation of liver metastases when intrasplenically transplanted in mice (P = 0.004). We then focused on the therapeutic potential of systemically applied shRNA expression plasmids acting on S100A4 via repeated hydrodynamics-based tail vein injection of plasmid DNA. Mice, intrasplenically transplanted with HCT116 cells and treated systemically with S100A4‑shRNA plasmids, showed a decrease of S100A4 and MMP9 expression levels, resulting in significantly reduced liver metastases (P = 0.005). In summary, we show for the first time the intratumoral knock down of S100A4 via systemic application of S100A4‑shRNA plasmid DNA, which restricts metastasis formation in a xenografted mouse model of colorectal cancer

Uptake, biodistribution, and time course of naked plasmid DNA trafficking after intratumoral in vivo jet injection

Nonviral jet injection is an applicable technology for in vivo gene transfer of naked DNA. However, little is known about the biodistribution and clearance of jet-injected DNA, or about its localization within tissue and cells. Therefore, in this study we analyzed the intratumoral and systemic biodistribution of jet-injected naked DNA in human colon carcinoma-bearing NCr-nu/nu mice, which were jet-injected with the pCMVbeta plasmid DNA. Intratumoral and systemic plasmid DNA biodistribution was analyzed 5, 10, 20, and 40 min and 3, 6, 24, 48, and 72 hr after jet injection, using quantitative real-time polymerase chain reaction. In the tumors, a rapid drop in naked DNA load within 24 hr of jet injection was shown. Detailed analysis of intratumoral distribution of rhodamine-labeled DNA revealed the presence of plasmid DNA within tumor cells 5 min after jet injection and further accumulation of significant DNA amounts in the cell nuclei 30 to 60 min after jet injection. In the blood, DNA amounts rapidly dropped within 10 to 40 min of jet injection to less than 0.001 pg of plasmid per 250 ng of tissue DNA and only minimal plasmid DNA dissemination was detected in liver, lung, spleen, kidney, and ovaries, which was cleared 3 to 6 hr after jet injection. By contrast, in heart, bone marrow, and brain almost no plasmid DNA was detectable

Single step tranformation of sulphur to Li₂S₂/Li₂S in Li-S batteries

Lithium-sulphur batteries have generated tremendous research interest due to their high theoretical energy density and potential cost-effectiveness. The commercial realization of Li-S batteries is still hampered by reduced cycle life associated with the formation of electrolyte soluble higher-order polysulphide (Li2Sx, x = 4–8) intermediates, leading to capacity fading, self-discharge, and a multistep voltage profile. Herein, we have realized a practical approach towards a direct transformation of sulphur to Li2S2/Li2S in lithium-sulphur batteries by alteration of the reaction pathway. A coconut shell derived ultramicroporous carbon-sulphur composite cathode has been used as reaction directing template for the sulphur. The lithiation/delithiation and capacity fading mechanism of microporous carbon confined sulphur composite was revealed by analyzing the subsurface using X-ray photoelectron spectroscopy. No higher-order polysulphides were detected in the electrolyte, on the surface, and in the subsurface of the cathode composite. The altered reaction pathway is reflected by a single-step profile in the discharge/charge of a lithium-sulphur cell

On the protection of extrasolar Earth-like planets around K/M stars against galactic cosmic rays

Previous studies have shown that extrasolar Earth-like planets in close-in habitable zones around M-stars are weakly protected against galactic cosmic rays (GCRs), leading to a strongly increased particle flux to the top of the planetary atmosphere. Two main effects were held responsible for the weak shielding of such an exoplanet: (a) For a close-in planet, the planetary magnetic moment is strongly reduced by tidal locking. Therefore, such a close-in extrasolar planet is not protected by an extended magnetosphere. (b) The small orbital distance of the planet exposes it to a much denser stellar wind than that prevailing at larger orbital distances. This dense stellar wind leads to additional compression of the magnetosphere, which can further reduce the shielding efficiency against GCRs. In this work, we analyse and compare the effect of (a) and (b), showing that the stellar wind variation with orbital distance has little influence on the cosmic ray shielding. Instead, the weak shielding of M star planets can be attributed to their small magnetic moment. We further analyse how the planetary mass and composition influence the planetary magnetic moment, and thus modify the cosmic ray shielding efficiency. We show that more massive planets are not necessarily better protected against galactic cosmic rays, but that the planetary bulk composition can play an important role.Comment: 7 figure

Tissue factor expression pattern in human non-small cell lung cancer tissues indicate increased blood thrombogenicity and tumor metastasis

Non-small cell lung cancer (NSCLC) comprises of 75% of all lung cancers. Human full length tissue factor (flHTF), the physiological initiator of blood coagulation, is aberrantly expressed in certain solid tumors. FlHTF and its soluble isoform, alternatively spliced human tissue factor (asHTF), have been shown to contribute to thrombogenicity of the blood of healthy individuals. The aim of this study was to quantify flHTF and asHTF on mRNA and protein levels (using immunohistochemistry, immunoblotting, and ELISA) on a panel of human NSCLC tissue and plasma specimens. The tissue factor (TF) expression of 21 pulmonary adenomatous (AC) and 12 normal healthy tissues was assessed by real-time qRT-PCR. The TF protein concentration was quantified by ELISA in a subset of 11 AC and 9 normal tissue specimens as well as in the plasma of 13 lung cancer patients and 15 healthy controls. We found a significant increase in the ratio of flHTF/HGAPDH mRNA in AC (0.24±0.06 vs. 0.07±0.01; p=0.02 vs. controls) and in asHTF/HGAPDH mRNA (0.027±0.01 vs. 0.004±0.001; p=0.03 AC vs. controls). AsHTF mRNA expression was significantly lower in patients with stage IA disease compared to patients with higher grade stages, pointing to TF as being a marker of malignancy and metastases. TF protein of lung tumors was significantly increased in AC (p=0.004 vs. controls). TF in plasma was up-regulated in lung cancer patients (334.9±95.4 vs. 124.1±14.8 pg/ml; p=0.02 vs. controls). Immunohistochemical and immunoblotting data are in line with the increased TF expression, showing elevated blood thrombogenicity of NSCLC patients. The up-regulation of flHTF and, especially, asHTF in AC suggests not only a raised risk of thrombosis, but also of tumor progression, thereby, indicating a poor prognosis in these patients

Patient-derived xenograft (PDX) models of colorectal carcinoma (CRC) as a platform for chemosensitivity and biomarker analysis in personalized medicine

Patient-derived xenograft (PDX) tumor models represent a valuable platform for identifying new biomarkers and novel targets, to evaluate therapy response and resistance mechanisms. This study aimed at establishment, characterization and therapy testing of colorectal carcinoma-derived PDX. We generated 49 PDX and validated identity between patient tumor and corresponding PDX. Sensitivity of PDX toward conventional and targeted drugs revealed that 92% of PDX responded toward irinotecan, 45% toward 5-FU, 65% toward bevacizumab, and 61% toward cetuximab. Expression of epidermal growth factor receptor (EGFR) ligands correlated to the sensitivity toward cetuximab. Proto-oncogene B-RAF, EGFR, Kirsten rat sarcoma virus oncogene homolog gene copy number correlated positively with cetuximab and erlotinib sensitivity. The mutational analyses revealed an individual mutational profile of PDX and mainly identical profiles of PDX from primary tumor vs corresponding metastasis. Mutation in PIK3CA was a determinant of accelerated tumor doubling time. PDX with wildtype Kirsten rat sarcoma virus oncogene homolog, proto-oncogene B-RAF, and phosphatidylinositol-4,5-bisphosphate 3-kinaseM catalytic subunit alfa showed higher sensitivity toward cetuximab and erlotinib. To study the molecular mechanism of cetuximab resistance, cetuximab resistant PDX models were generated, and changes in HER2, HER3, betacellulin, transforming growth factor alfa were observed. Global proteome and phosphoproteome profiling showed a reduction in canonical EGFR-mediated signaling via PTPN11 (SHP2) and AKT1S1 (PRAS40) and an increase in anti-apoptotic signaling as a consequence of acquired cetuximab resistance. This demonstrates that PDX models provide a multitude of possibilities to identify and validate biomarkers, signaling pathways and resistance mechanisms for clinically relevant improvement in cancer therapy

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice

Modulation of tumour cell growth by tumour-infiltrating leucocytes is of high importance for the biological behaviour of malignant neoplasms. In melanoma, tumour-associated macrophages (TAM) and tumour-infiltrating lymphocytes (TIL) are of particular interest as inhibitors or enhancers of cell growth. Recruitment of leucocytes from the peripheral blood into the tumour site is mediated predominantly by chemotaxins, particularly by the group of chemokines