Location- and observation time-dependent quantum-tunneling

We investigate quantum tunneling in a translation invariant chain of particles. The particles interact harmonically with their nearest neighbors, except for one bond, which is anharmonic. It is described by a symmetric double well potential. In the first step, we show how the anharmonic coordinate can be separated from the normal modes. This yields a Lagrangian which has been used to study quantum dissipation. Elimination of the normal modes leads to a nonlocal action of Caldeira-Leggett type. If the anharmonic bond defect is in the bulk, one arrives at Ohmic damping, i.e. there is a transition of a delocalized bond state to a localized one if the elastic constant exceeds a critical value $C_{crit}$. The latter depends on the masses of the bond defect. Superohmic damping occurs if the bond defect is in the site $M$ at a finite distance from one of the chain ends. If the observation time $T$ is smaller than a characteristic time $\tau_M \sim M$, depending on the location M of the defect, the behavior is similar to the bulk situation. However, for $T \gg \tau_M$ tunneling is never suppressed.Comment: 17 pages, 2 figure

Conductance of a spin-1 quantum dot: the two-stage Kondo effect

We discuss the physics of a of a spin-1 quantum dot, coupled to two metallic leads and develop a simple model for the temperature dependence of its conductance. Such quantum dots are described by a two-channel Kondo model with asymmetric coupling constants and the spin screening of the dot by the leads is expected to proceed via a two-stage process. When the Kondo temperatures of each channel are widely separated, on cooling, the dot passes through a broad cross-over regime dominated by underscreened Kondo physics. A singular, or non-fermi liquid correction to the conductance develops in this regime. At the lowest temperatures, destructive interference between resonant scattering in both channels leads to the eventual suppression of the conductance of the dot. We develop a model to describe the growth, and ultimate suppression of the conductance in the two channel Kondo model as it is screened successively by its two channels. Our model is based upon large-N approximation in which the localized spin degrees of freedom are described using the Schwinger boson formalism.Comment: 16 pages, 10 figure

Analysis of the Effects of Dam Release Properties and Ambient Groundwater Flow on Surface Water‐Groundwater Exchange Over a 100‐km‐Long Reach

Hydroelectric dams often create highly dynamic downstream flows that promote surface water‐groundwater (SW‐GW) interactions including bank storage, the temporary storage of river water in the riverbank. Previous research on SW‐GW exchanges in dammed rivers has primarily been at single study sites, which has limited the understanding of how these exchanges evolve as dam releases travel downstream. This study evaluates how dam releases affect SW‐GW exchange continuously over a 100‐km distance. This is accomplished by longitudinally routing water releases through a synthetic river and modeling bed and bank fluid and solute exchange across transverse transects spaced along the reach. Peak and square dam release hydrograph shapes with three magnitudes (0.5, 1.0, and 1.5 m) were considered. The effect of four ambient groundwater flow conditions (very slightly losing, neutral, and two gaining from the perspective of the river) was evaluated for each dam release scenario. Both types of dam release shapes cause SW‐GW interaction over the entire 100‐km distance, and our results show that square type releases cause bank storage exchange well beyond this distance. Strongly gaining conditions reduce the amount of exchange and allow flushing of river‐sourced solute out of the bank after the dam pulse has passed. Both neutral and losing conditions have larger fluid and solute flux into the bank and limit the amount of solute that returns to the river. Our results support that river corridors downstream of dams have increased river‐aquifer connectivity and that this enhanced connectivity can extend at least 100 km downstream

Empirical Models for Predicting Water and Heat Flow Properties of Permafrost Soils

Warming and thawing in the Arctic are promoting biogeochemical processing and hydrologic transport in carbon‐rich permafrost and soils that transfer carbon to surface waters or the atmosphere. Hydrologic and biogeochemical impacts of thawing are challenging to predict with sparse information on arctic soil hydraulic and thermal properties. We developed empirical and statistical models of soil properties for three main strata in the shallow, seasonally thawed soils above permafrost in a study area of ~7,500 km2 in Alaska. The models show that soil vertical stratification and hydraulic properties are predictable based on vegetation cover and slope. We also show that the distinct hydraulic and thermal properties of each soil stratum can be predicted solely from bulk density. These findings fill the gap for a sparsely mapped region of the Arctic and enable regional interpolation of soil properties critical for determining future hydrologic responses and the fate of carbon in thawing permafrost

Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients

Background: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. Methods: Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. Results: KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome. Conclusions: In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

Why and How to Write a High-Impact Review Paper: Lessons From Eight Years of Editorial Board Service to Reviews of Geophysics

High-impact review papers describe and synthesize the current state of the art, the open questions and controversies, and provide ideas for future investigations. They are written not only for a specific scientific discipline but also for the broader Earth and space science community. They not only summarize the literature, but they also create a framework from which to understand the progress, problems, and connections between different communities, observations, models, and approaches. Here we describe how to write a high-impact review paper, and why you should consider writing one for Reviews of Geophysics

In Vitro Analysis of Integrated Global High-Resolution DNA Methylation Profiling with Genomic Imbalance and Gene Expression in Osteosarcoma

Genetic and epigenetic changes contribute to deregulation of gene expression and development of human cancer. Changes in DNA methylation are key epigenetic factors regulating gene expression and genomic stability. Recent progress in microarray technologies resulted in developments of high resolution platforms for profiling of genetic, epigenetic and gene expression changes. OS is a pediatric bone tumor with characteristically high level of numerical and structural chromosomal changes. Furthermore, little is known about DNA methylation changes in OS. Our objective was to develop an integrative approach for analysis of high-resolution epigenomic, genomic, and gene expression profiles in order to identify functional epi/genomic differences between OS cell lines and normal human osteoblasts. A combination of Affymetrix Promoter Tilling Arrays for DNA methylation, Agilent array-CGH platform for genomic imbalance and Affymetrix Gene 1.0 platform for gene expression analysis was used. As a result, an integrative high-resolution approach for interrogation of genome-wide tumour-specific changes in DNA methylation was developed. This approach was used to provide the first genomic DNA methylation maps, and to identify and validate genes with aberrant DNA methylation in OS cell lines. This first integrative analysis of global cancer-related changes in DNA methylation, genomic imbalance, and gene expression has provided comprehensive evidence of the cumulative roles of epigenetic and genetic mechanisms in deregulation of gene expression networks

Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization

The cytogenetic characteristics of osteosarcoma (OS) remain controversial. The establishment of a new human OS cell line may improve the characterization. We report the establishment of a new human osteosarcoma cell line, UTOS-1, from a typical osteoblastic OS of an 18-year-old man. Cultured UTOS-1 cells are spindle-shaped, and have been maintained in vitro for over 50 passages in more than 2 years. Xenografted UTOS-1 cells exhibit features typical of OS, such as production of osteoid or immature bone matrix, and proliferation potency in vivo. UTOS-1 also exhibit morphological and immunohistochemical characteristics typical of osteoblastic OS. Chromosomal analysis by G-band show 73~85 chromosomes with complicated translocations. Array CGH show frequent gains at locus DAB2 at chromosome 5q13, CCND2 at 12p13, MDM2 at 12q14.3-q15, FLI and TOP3A at 17p11.2-p12 and OCRL1 at Xq25, and show frequent losses at HTR1B at 6q13, D6S268 at 6q16.3-q21, SHGC17327 at 18ptel, and STK6 at 20q13.2-q13.3. The UTOS-1 cell line may prove useful for biologic and molecular pathogenetic investigations of human OS