Typing tumors using pathways selected by somatic evolution.

Many recent efforts to analyze cancer genomes involve aggregation of mutations within reference maps of molecular pathways and protein networks. Here, we find these pathway studies are impeded by molecular interactions that are functionally irrelevant to cancer or the patient's tumor type, as these interactions diminish the contrast of driver pathways relative to individual frequently mutated genes. This problem can be addressed by creating stringent tumor-specific networks of biophysical protein interactions, identified by signatures of epistatic selection during tumor evolution. Using such an evolutionarily selected pathway (ESP) map, we analyze the major cancer genome atlases to derive a hierarchical classification of tumor subtypes linked to characteristic mutated pathways. These pathways are clinically prognostic and predictive, including the TP53-AXIN-ARHGEF17 combination in liver and CYLC2-STK11-STK11IP in lung cancer, which we validate in independent cohorts. This ESP framework substantially improves the definition of cancer pathways and subtypes from tumor genome data

The Design of Efficient Internetwork Authentication for Ubiquitous Wireless Communications

A variety of wireless technologies have been standardized and commercialized, but no single solution is considered the best to satisfy all communication needs due to different coverage and bandwidth limitations. Therefore, internetworking between heterogeneous wireless networks is extremely important for ubiquitous and high performance wireless communications. The security problem is one of the major challenges in internetworking. To date, most research on internetwork authentication has focused on centralized authentication approaches, where the home network participates in each authentication process. For high latency between the home and visiting networks, such approaches tend to be inefficient. In this paper, we describe chained authentication, which requires collaboration between adjacent networks without involvement of the home network. After categorizing chained protocols, we propose a novel design of chained authentication methods under 3G-WLAN internetworking. The experiments show that proactive context transfer and ticket forwarding reduce the 3G authentication latency to 36.8% and WLAN EAP-TLS latency to 23.1% when RTT between visiting and home networks is 200 ms

Patient-Specific Fetal Dose Determination for Multi-Target Gamma Knife Radiosurgery: Computational Model and Case Report.

A 42-year-old woman at 29 weeks gestation via in vitro fertilization who presented with eight metastatic brain lesions received Gamma Knife stereotactic radiosurgery (GKSRS) at our institution. In this study, we report our clinical experience and a general procedure of determining the fetal dose from patient-specific treatment plans and we describe quality assurance measurements to guide the safe practice of multi-target GKSRS of pregnant patients. To estimate fetal dose pre-treatment, peripheral dose-to-focal dose ratios (PFRs) were measured in a phantom at the distance approximating the fundus of uterus. Post-treatment, fetal dose was calculated from the actual patient treatment plan. Quality assurance measurements were carried out via the extrapolation dosimetry method in a head phantom at increasing distances along the longitudinal axis. The measurements were then empirically fitted and the fetal dose was extracted from the curve. The computed and measured fetal dose values were compared with each other and associated radiation risk was estimated. Based on low estimated fetal dose from preliminary phantom measurements, the patient was accepted for GKSRS. Eight brain metastases were treated with prescription doses of 15-19 Gy over 143 min involving all collimator sizes as well as composite sector mixed shots. Direct fetal dose computation based on the actual patient's treatment plan estimated a maximum fetal dose of 0.253 cGy, which was in agreement with surface dose measurements at the level of the patient's uterine fundus during the actual treatment. Later phantom measurements also estimated fetal dose to be in the range of 0.21-0.28 cGy (dose extrapolation curve R2 = 0.998). Using the National Council on Radiation Protection and Measurements (NCRP) population-based model, we estimate the fetal risk of secondary malignancy, which is the primary toxicity after 25 weeks gestation, to be less than 0.01%. Of note, the patient delivered the baby via scheduled cesarean section at 36 weeks without complications attributable to the GKSRS procedure. GKSRS of multiple brain metastases was demonstrated to be safe and feasible during pregnancy. The applicability of a general patient-specific fetal dose determination method was also demonstrated for the first time for such a treatment

Breakdown of the perturbative renormalization group at certain quantum critical points

It is shown that the presence of multiple time scales at a quantum critical point can lead to a breakdown of the loop expansion for critical exponents, since coefficients in the expansion diverge. Consequently, results obtained from finite-order perturbative renormalization-group treatments may be not be an approximation in any sense to the true asymptotic critical behavior. This problem manifests itself as a non-renormalizable field theory, or, equivalently, as the presence of a dangerous irrelevant variable. The quantum ferromagnetic transition in disordered metals provides an example.Comment: 4pp, 1 eps fi