Electron rescattering at metal nanotips induced by ultrashort laser pulses

We report on the first investigation of plateau and cut-off structures in photoelectron spectra from nano-scale metal tips interacting with few-cycle near-infrared laser pulses. These hallmarks of electron rescattering, well-known from atom-laser interaction in the strong-field regime, appear at remarkably low laser intensities with nominal Keldysh parameters of the order of $\gtrsim 10$. Quantum and quasi-classical simulations reveal that a large field enhancement near the tip and the increased backscattering probability at a solid-state target play a key role. Plateau electrons are by an order of magnitude more abundant than in comparable atomic spectra, reflecting the high density of target atoms at the surface. The position of the cut-off serves as an in-situ probe for the locally enhanced electric field at the tip apex

Ice-age megafauna in Arctic Alaska: extinction, invasion, survival

Radical restructuring of the terrestrial, large mammal fauna living in arctic Alaska occurred between 14,000 and 10,000 years ago at the end of the last ice age. Steppe bison, horse, and woolly mammoth became extinct, moose and humans invaded, while muskox and caribou persisted. The ice age mega fauna was more diverse in species and possibly contained 6x more individual animals than live in the region today. Mega faunal biomass during the last ice age may have been 30x greater than present. Horse was the dominant species in terms of number of individuals. Lions, short-faced bears, wolves, and possibly grizzly bears comprised the predator/scavenger guild. The youngest mammoth so far discovered lived ca 13,800 years ago, while horses and bison persisted on the North Slope until at least 12,500 years ago during the Younger Dry as cold interval. The first people arrived on the North Slope ca 13,500 years ago. Bone-isotope measurements and foot-loading characteristics suggest mega faunal niches were segregated along a moisture gradient, with the surviving species (muskox and caribou) utilizing the warmer and moister portions of the vegetation mosaic. As the ice age ended, the moisture gradient shifted and eliminated habitats utilized by the dry land, grazing species (bison, horse, mammoth). The proximate cause for this change was regional paludification, the spread of organic soil horizons and peat. End-Pleistocene extinctions in arctic Alaska represent local, not global extinctions since the mega faunal species lost there persisted to later times elsewhere. Hunting seems unlikely as the cause of these extinctions, but it cannot be ruled out as the final blow to mega faunal populations that were already functionally extinct by the time humans arrived in the region

Radiocarbon age-offsets in an arctic lake reveal the long-term response of permafrost carbon to climate change

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Biogeosciences 119 (2014): 1630–1651, doi:10.1002/2014JG002688.Continued warming of the Arctic may cause permafrost to thaw and speed the decomposition of large stores of soil organic carbon (OC), thereby accentuating global warming. However, it is unclear if recent warming has raised the current rates of permafrost OC release to anomalous levels or to what extent soil carbon release is sensitive to climate forcing. Here we use a time series of radiocarbon age-offsets (14C) between the bulk lake sediment and plant macrofossils deposited in an arctic lake as an archive for soil and permafrost OC release over the last 14,500 years. The lake traps and archives OC imported from the watershed and allows us to test whether prior warming events stimulated old carbon release and heightened age-offsets. Today, the age-offset (2 ka; thousand of calibrated years before A.D. 1950) and the depositional rate of ancient OC from the watershed into the lake are relatively low and similar to those during the Younger Dryas cold interval (occurring 12.9–11.7 ka). In contrast, age-offsets were higher (3.0–5.0 ka) when summer air temperatures were warmer than present during the Holocene Thermal Maximum (11.7–9.0 ka) and Bølling-Allerød periods (14.5–12.9 ka). During these warm times, permafrost thaw contributed to ancient OC depositional rates that were ~10 times greater than today. Although permafrost OC was vulnerable to climate warming in the past, we suggest surface soil organic horizons and peat are presently limiting summer thaw and carbon release. As a result, the temperature threshold to trigger widespread permafrost OC release is higher than during previous warming events.National Science Foundation. Grant Number: ARC-09021692015-02-2

Connecting Cancer Pathways to Tumor Engines: A Stratification Tool for Colorectal Cancer Combining Human In Vitro Tissue Models with Boolean In Silico Models

To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification

Lymphoma tumor burden before chimeric antigen receptor T-Cell treatment: RECIL vs. Lugano vs. metabolic tumor assessment

Purpose: High tumor burden has emerged as a negative predictor of efficacy in chimeric antigen receptor T-cell therapy (CART) in patients with refractory or relapsed large B-cell lymphoma. This study analyzed the deviation among imaging-based tumor burden (TB) metrics and their association with progression-free (PFS) and overall survival (OS). Materials and methods: In this single-center observational study, we included all consecutively treated patients receiving CD19 CART with available baseline PET-CT imaging. Imaging-based TB was determined based on response evaluation criteria in lymphoma (RECIL), the Lugano criteria, and metabolic tumor volume. Total, nodal and extranodal TB were represented, according to the respective criteria, by sum of longest diameters (TBRECIL), sum of product of perpendicular diameters (TBLugano), and metabolic tumor volume (TBMTV). Correlation statistics were used for comparison. Proportional Cox regression analysis studied the association of TB metrics with PFS and OS. Results: 34 consecutive patients were included (median age: 67 years, 41% female) with total median baseline TBRECIL of 12.5 cm, TBLugano of 4,030 mm2 and TBMTV of 330 mL. The correlation of TBRECIL and TBLugano with TBMTV was strong (ρ=0.744, p50% (HR=2.915, p=0.042), whereas total TBRECIL>50% and total TBLugano>50% were not significant (both p>0.05). None of the total TB metrics were associated with OS (all p>0.05). Conclusion: Pre-CART TB metrics vary significantly based on the assessment method, impacting their association with survival outcomes. The correlation between TBRECIL, TBLugano and TBMTV was influenced by disease phenotype and prior bridging therapy. TB method of assessment must be considered when interpreting the impact of TB on outcomes in clinical trials. Considering the heterogeneity, our results argue for standardization and harmonization across centers