182 research outputs found
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
Upscaling methane emission hotspots in boreal peatlands
Upscaling the properties and the effects of small-scale surface heterogeneities to larger scales is a challenging issue in land surface modeling. We developed a novel approach to upscale local methane emissions in a boreal peatland from the micro-topographic scale to the landscape-scale. We based this new parameterization on the analysis of the water table pattern generated by the HummockâHollow model, a micro-topography resolving model for peatland hydrology. We introduce this parameterization of methane hotspots in a global model-like version of the HummockâHollow model, that underestimates methane emissions. We tested the robustness of the parameterization by simulating methane emissions for the next century forcing the model with three different RCP scenarios. The Hotspot parameterization, despite being calibrated for the 1976â2005 climatology, mimics the output of the micro-topography resolving model for all the simulated scenarios. The new approach bridges the scale gap of methane emissions between this version of the model and the configuration explicitly resolving micro-topography
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 âshieldâ 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 (HerceptinÂź). 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
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
Electroweak Corrections to the Top Quark Decay
We have calculated the one-loop electroweak corrections to the decay t-> bW+,
including the counterterm for the CKM matrix elements V(tb). Previous
calculations used an incorrect delta V(tb) that led to a gauge dependent
amplitude. However, since the contribution stemming from delta V(tb) is small,
those calculations only underestimate the width by roughly one part in 10^5.Comment: 7 pages, 2 figure
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: 45âGy 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
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 âshieldâ 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 (HerceptinÂź). 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
Reconstructions of biomass burning from sediment charcoal records to improve data-model comparisons
The location, timing, spatial extent, and frequency of wildfires are changing rapidly in many parts of the world, producing substantial impacts on ecosystems, people, and potentially climate. Paleofire records based on charcoal accumulation in sediments enable modern changes in biomass burning to be considered in their long-term context. Paleofire records also provide insights into the causes and impacts of past wildfires and emissions when analyzed in conjunction with other paleoenvironmental data and with fire models. Here we present new 1000 year and 22 000 year trends and gridded biomass burning reconstructions based on the Global Charcoal Database version 3, which includes 736 charcoal records (57 more than in version 2). The new gridded reconstructions reveal the spatial patterns underlying the temporal trends in the data, allowing insights into likely controls on biomass burning at regional to global scales. In the most recent few decades, biomass burning has sharply increased in both hemispheres, but especially in the north, where charcoal fluxes are now higher than at any other time during the past 22 000 {years}. We also discuss methodological issues relevant to data-model comparisons, and identify areas for future research. Spatially gridded versions of the global dataset from GCDv3 are provided to facilitate comparison with and validation of global fire simulations
Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial
Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50âmgâmâ2) and continuous infusional 5-fluorouracil (CI-5FU; 225âmgâmâ2) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4â6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45âmgâmâ2 plus CI-5FU 225âmgâmâ2 was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39â82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45âmgâmâ2 plus CI-5FU 225âmgâmâ2 with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC
Search for a Higgs Boson Decaying to Weak Boson Pairs at LEP
A Higgs particle produced in association with a Z boson and decaying into
weak boson pairs is searched for in 336.4 1/pb of data collected by the L3
experiment at LEP at centre-of-mass energies from 200 to 209 GeV. Limits on the
branching fraction of the Higgs boson decay into two weak bosons as a function
of the Higgs mass are derived. These results are combined with the L3 search
for a Higgs boson decaying to photon pairs. A Higgs produced with a Standard
Model e+e- --> Zh cross section and decaying only into electroweak boson pairs
is excluded at 95% CL for a mass below 107 GeV
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