Evolution of gas-filled nanocracks in crystalline solids

In this work, the evolution of gas-filled cracks under gas implantation and subsequent annealing is studied on the basis of an elastic continuum approach. The observed growth limitation of He-filled nanocracks in SiC is attributed to their stabilization by the formation of circular dislocation dipoles. The formation and Ostwald ripening of bubble-loop complexes at elevated temperatures is modeled in terms of gas atom exchange between such complexes coupled. with local matrix atom exchange between bubbles and loops of the same complex. The scaling laws derived for the time dependence of bubble and loop sizes are found to be in good agreement with experimental data

Tissue engineering a fetal membrane

The aim of this study was to construct an artificial fetal membrane (FM) by combination of human amniotic epithelial stem cells (hAESCs) and a mechanically enhanced collagen scaffold containing encapsulated human amniotic stromal fibroblasts (hASFs). Such a tissue-engineered FM may have the potential to plug structural defects in the amniotic sac after antenatal interventions, or to prevent preterm premature rupture of the FM. The hAESCs and hASFs were isolated from human fetal amniotic membrane (AM). Magnetic cell sorting was used to enrich the hAESCs by positive ATP-binding cassette G2 selection. We investigated the use of a laminin/fibronectin (1:1)-coated compressed collagen gel as a novel scaffold to support the growth of hAESCs. A type I collagen gel was dehydrated to form a material mimicking the mechanical properties and ultra-structure of human AM. hAESCs successfully adhered to and formed a monolayer upon the biomimetic collagen scaffold. The resulting artificial membrane shared a high degree of similarity in cell morphology, protein expression profiles, and structure to normal fetal AM. This study provides the first line of evidence that a compacted collagen gel containing hASFs could adequately support hAESCs adhesion and differentiation to a degree that is comparable to the normal human fetal AM in terms of structure and maintenance of cell phenotype

Point defect dynamics in bcc metals

We present an analysis of the time evolution of self-interstitial atom and vacancy (point defect) populations in pure bcc metals under constant irradiation flux conditions. Mean-field rate equations are developed in parallel to a kinetic Monte Carlo (kMC) model. When only considering the elementary processes of defect production, defect migration, recombination and absorption at sinks, the kMC model and rate equations are shown to be equivalent and the time evolution of the point defect populations is analyzed using simple scaling arguments. We show that the typically large mismatch of the rates of interstitial and vacancy migration in bcc metals can lead to a vacancy population that grows as the square root of time. The vacancy cluster size distribution under both irreversible and reversible attachment can be described by a simple exponential function. We also consider the effect of highly mobile interstitial clusters and apply the model with parameters appropriate for vanadium and $\alpha-$iron.Comment: to appear in Phys. Rev.

Gene expression analysis to detect disseminated tumor cells in the bone marrow of triple-negative breast cancer patients predicts metastatic relapse

PURPOSE: Disseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse. METHODS: Using a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM specimens. To validate findings from a subset of 28 triple-negative breast cancer (TNBC) patients in the initial 70 patient cohort, an independent set of pre-therapeutic BM specimens from 16 TNBC patients was analyzed. RESULTS: Expression of each of the 46 gene transcripts was highly variable between patients. Individual gene expression was detected in 0-84% of BM specimens analyzed and all but two patient BM specimens expressed at least one transcript. Among a subset of 28 patients with TNBC, positivity of one or more of eight transcripts correlated with time to distant relapse (p = 0.03). In an independent set of 16 triple-negative patient BM samples, detection of five of these same eight gene transcripts also correlated with time to distant relapse (p = 0.03) with a positive predictive value of 89%. CONCLUSIONS: We identified a set of gene transcripts whose detection in the BM of TNBC patients, prior to any treatment intervention, predicts time to first distant relapse, thus identifying a TNBC patient population which requires additional treatment intervention. Because these genes are presumably expressed in populations of DTCs and many encode proteins that are known therapeutic targets (e.g., ERBB2), these results also suggest a potential approach for targeted DTC therapy to mitigate distant metastases in TNBC

In vitro model suggests oxidative stress involved in keratoconus disease

Keratoconus (KC) affects 1:2000 people and is a disorder where cornea thins and assumes a conical shape. Advanced KC requires surgery to maintain vision. The role of oxidative stress in KC remains unclear. We aimed to identify oxidative stress levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs). Cells were cultured in 2D and 3D systems. Vitamin C (VitC) and TGF-β3 (T3) were used for 4 weeks to stimulate self-assembled extracellular matrix (ECM). No T3 used as controls. Samples were analyzed using qRT-PCR and metabolomics. qRT-PCR data showed low levels of collagen I and V, as well as keratocan for HKCs, indicating differentiation to a myofibroblast phenotype. Collagen type III, a marker for fibrosis, was up regulated in HKCs. We robustly detected more than 150 metabolites of the targeted 250 by LC-MS/MS per condition and among those metabolites several were related to oxidative stress. Lactate levels, lactate/malate and lactate/pyruvate ratios were elevated in HKCs, while arginine and glutathione/oxidized glutathione ratio were reduced. Similar patterns found in both 2D and 3D. Our data shows that fibroblasts exhibit enhanced oxidative stress compared to keratocytes. Furthermore the HKC cells exhibit the greatest level suggesting they may have a myofibroblast phenotype

Gene expression analysis to detect disseminated tumor cells in the bone marrow of triple-negative breast cancer patients predicts metastatic relapse

PURPOSE: Disseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse. METHODS: Using a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM specimens. To validate findings from a subset of 28 triple-negative breast cancer (TNBC) patients in the initial 70 patient cohort, an independent set of pre-therapeutic BM specimens from 16 TNBC patients was analyzed. RESULTS: Expression of each of the 46 gene transcripts was highly variable between patients. Individual gene expression was detected in 0-84% of BM specimens analyzed and all but two patient BM specimens expressed at least one transcript. Among a subset of 28 patients with TNBC, positivity of one or more of eight transcripts correlated with time to distant relapse (p = 0.03). In an independent set of 16 triple-negative patient BM samples, detection of five of these same eight gene transcripts also correlated with time to distant relapse (p = 0.03) with a positive predictive value of 89%. CONCLUSIONS: We identified a set of gene transcripts whose detection in the BM of TNBC patients, prior to any treatment intervention, predicts time to first distant relapse, thus identifying a TNBC patient population which requires additional treatment intervention. Because these genes are presumably expressed in populations of DTCs and many encode proteins that are known therapeutic targets (e.g., ERBB2), these results also suggest a potential approach for targeted DTC therapy to mitigate distant metastases in TNBC

A prospective trial comparing FDG-PET/CT and CT to assess tumor response to cetuximab in patients with incurable squamous cell carcinoma of the head and neck

Computed tomography (CT), the standard method to assess tumor response to cetuximab in incurable squamous cell carcinoma of the head and neck (SCCHN), performs poorly as judged by the disparity between high disease control rate (46%) and short time to progression (TTP) (70 days). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT is an alternative method to assess tumor response. The primary objective of this prospective trial was to evaluate the metabolic response of target lesions, assessed as the change in maximum standardized uptake value (SUV(max)) on FDG-PET/CT before and after 8 weeks (cycle 1) of cetuximab. Secondary objectives were to compare tumor response by CT (RECIST 1.0) and FDG-PET/CT (EORTC criteria) following cycle 1, and determine TTP with continued cetuximab administration in patients with disease control by CT after cycle 1 but stratified for disease control or progression by FDG-PET/CT. Among 27 patients, the mean percent change of SUV(max) of target lesions after cycle 1 was −21% (range: +72% to −81%); by FDG-PET/CT, partial response (PR)/stable disease (SD) occurred in 15 patients (56%) and progression in 12 (44%), whereas by CT, PR/SD occurred in 20 (74%) and progression in 7 (26%). FDG-PET/CT and CT assessments were discordant in 14 patients (P = 0.0029) and had low agreement (κ = 0.30; 95% confidence interval [CI]: 0.12, 0.48). With disease control by CT after cycle 1, median TTP was 166 days (CI: 86, 217) if the FDG-PET/CT showed disease control and 105 days (CI: 66, 159) if the FDG-PET/CT showed progression (P < 0.0001). Median TTP of the seven patients whose post cycle 1 CT showed progression compared to the 12 whose FDG-PET/CT showed progression were similar (53 [CI: 49, 56] vs. 61 [CI: 50, 105] days, respectively). FDG-PET/CT may be better than CT in assessing benefit of cetuximab in incurable SCCHN

Improved semiclassical density matrix: taming caustics

We present a simple method to deal with caustics in the semiclassical approximation to the thermal density matrix of a particle moving on the line. For simplicity, only its diagonal elements are considered. The only ingredient we require is the knowledge of the extrema of the Euclidean action. The procedure makes use of complex trajectories, and is applied to the quartic double-well potential.Comment: 20 pages, 7 figures. Revised version, accepted for publication in Phys. Rev.