The Expected Perimeter in Eden and Related Growth Processes

Following Richardson and using results of Kesten on First-passage percolation, we obtain an upper bound on the expected perimeter in an Eden Growth Process. Using results of the author from a problem in Statistical Mechanics, we show that the average perimeter of the lattice animals resulting from a very natural family of "growth histories" does not obey a similar bound.Comment: 11 page

Implications of land use change in tropical Northern Africa under global warming

A major link between climate and humans in Northern Africa, and the Sahel in particular, is land use and associated land cover change, mainly where subsistence farming prevails. Here we assess possible feedbacks between the type of land use and harvest intensity and climate by analyzing a series of idealized GCM experiments using the MPI-ESM. The base line for these experiments is a simulation forced by the RCP8.5 scenario which includes strong greenhouse gas emissions and anthropogenic land cover changes. The anthropogenic land cover changes in the RCP8.5 scenario include a mixture of pasture and agriculture. In subsequent simulations, we replace the entire area affected by anthropogenic land cover change in the region between the Sahara in the North and the Guinean Coast in the South (4 to 20° N) by either pasture or agriculture, respectively. In a second setup we vary the amount of harvest in case of agriculture. The RCP8.5 base line simulation reveals strong changes in mean agriculture and monsoon rainfall. In comparison with these changes, any variation of the type of land use in the study area leads to very small, mostly insignificantly small, additional differences in mean temperature and annual precipitation change in this region. Within the uncertainty of the representation of land use in current ESMs, our study suggests marginal feedback between land use changes and climate changes triggered by strong greenhouse gas emissions. Hence as a good approximation, climate change can be considered as external driver in models of land-use – conflict dynamics when seasonal or mean values are used as external driver

Comparing modelled fire dynamics with charcoal records for the Holocene

An earth system model of intermediate complexity (CLIMate and BiosphERe – CLIMBER-2) and a land surface model (JSBACH), which dynamically represent vegetation, are used to simulate natural fire dynamics through the last 8000 yr. Output variables of the fire model (burned area and fire carbon emissions) are used to compare model results with sediment-based charcoal reconstructions. Several approaches for processing model output are also tested. Charcoal data are reported in Z-scores with a base period of 8000–200 BP in order to exclude the strong anthropogenic forcing of fire during the last two centuries. The model–data comparison reveals a robust correspondence in fire activity for most regions considered, while for a few regions, such as Europe, simulated and observed fire histories show different trends. The difference between modelled and observed fire activity may be due to the absence of anthropogenic forcing (e.g. human ignitions and suppression) in the model simulations, and also due to limitations inherent to modelling fire dynamics. The use of spatial averaging (or Z-score processing) of model output did not change the directions of the trends. However, Z-score-transformed model output resulted in higher rank correlations with the charcoal Z-scores in most regions. Therefore, while both metrics are useful, processing model output as Z-scores is preferable to areal averaging when comparing model results to transformed charcoal records

Optical response of ferromagnetic YTiO_3 studied by spectral ellipsometry

We have studied the temperature dependence of spectroscopic ellipsometry spectra of an electrically insulating, nearly stoichiometric YTiO_3 single crystal with ferromagnetic Curie temperature T_C = 30 K. The optical response exhibits a weak but noticeable anisotropy. Using a classical dispersion analysis, we identify three low-energy optical bands at 2.0, 2.9, and 3.7 eV. Although the optical conductivity spectra are only weakly temperature dependent below 300 K, we are able to distinguish high- and low-temperature regimes with a distinct crossover point around 100 K. The low-temperature regime in the optical response coincides with the temperature range in which significant deviations from Curie-Weiss mean field behavior are observed in the magnetization. Using an analysis based on a simple superexchange model, the spectral weight rearrangement can be attributed to intersite d_i^1d_j^1 \longrightarrow d_i^2d_j^0 optical transitions. In particular, Kramers-Kronig consistent changes in optical spectra around 2.9 eV can be associated with the high-spin-state (^3T_1) optical transition. This indicates that other mechanisms, such as weakly dipole-allowed p-d transitions and/or exciton-polaron excitations, can contribute significantly to the optical band at 2 eV. The recorded optical spectral weight gain of 2.9 eV optical band is significantly suppressed and anisotropic, which we associate with complex spin-orbit-lattice phenomena near ferromagnetic ordering temperature in YTiO_3

Paracrine delivery of therapeutic biologics for cancer

A fundamental goal of cancer drug delivery is to achieve sufficient levels within the tumour without leading to high systemic concentrations that might cause off-target toxicities. In situ production of protein-based therapeutics by tumour cells provides an attractive alternative to treatment with repeated high bolus injections, as secretion by the tumour itself could provide high local concentrations that act in a paracrine fashion over an extended duration. For this purpose, we have developed a non-oncolytic adenoviral delivery system that allows for targeting of Ad5 to discrete cell types by redirecting viral tropism to cell surface biomarkers through the use of interchangeable adapters. Furthermore, we recently described the engineering of a protein-based ‘shield’ that is coated on the Ad5 capsid, which, together with the retargeting adapters, allows for improved tumour specificity and prevention of viral clearance. To test this delivery strategy in vivo, SCID-beige mice bearing orthotopic BT474 xenografts were treated with three doses of either a cancerspecific, non-replicative Ad5 that encodes a secreted anti-HER2 antibody, trastuzumab, in its genome, or with the protein therapeutic itself (Herceptin®). We have employed state-of-the-art whole tumour clearing and imaging with confocal microscopy at high spatial resolution in 3D to assess biodistribution, and large volumetric imaging has revealed that the secreted therapeutic diffuses significantly throughout the tumour leading to a therapeutic effect and delayed tumour outgrowth. Moreover, the systemic concentration of antibody is significantly reduced with viral delivery, suggesting that paracrine delivery may be a promising strategy for delivery of biologics with narrow therapeutic indices

The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus

Pretherapeutic identification of oesophageal squamous cell carcinomas that will respond to neoadjuvant chemoradiotherapy is an important attempt for improvement of patient's prognosis. In the current study, pretherapeutic biopsies from 94 oesophageal squamous cell carcinomas (cT3, cN0/+, cM0) in patients who underwent neoadjuvant chemoradiotherapy (RCTx: 45 Gy plus cisplatin and 5-fluorouracil) and subsequent oesophagectomy in the setting of a single-centre prospective treatment trial were investigated by means of immunohistochemistry. Expression of proteins involved in DNA repair and/or cell-cycle regulation, that is p53, p53 (phosphorylated at Ser15), EGFR, ATM protein kinase (phosphorylated at Ser1981) and checkpoint kinase 2 (CHK2) (phosphorylated at Thr68) was correlated with the response to RCTx and with overall survival. Tumours that were positive for CHK2 expression more frequently showed clinically determined regression after RCTx (69.4%) than tumours that were negative for CHK2 expression (32.1%; P=0.0011), whereas other parameters did not correlate with tumour regression. Expression of ATM correlated with expression of CHK2 (P=0.0061) and p53-phospho (P=0.0064). Expression of p53 correlated with expression of p53-phospho (P<0.0001). In contrast to clinical and histopathological response evaluation, none of the molecular parameters under investigation correlated with overall survival. In conclusion, expression analysis of p53, EGFR CHK2 and ATM has no predictive value in multimodally treated oesophageal squamous cell carcinoma