Current transport mechanisms in GaAs/AlAs tunnel structures grown by metal–organic chemical vapor deposition

Elastic and inelastic tunneling processes are investigated in GaAs–AlAs–GaAs double heterojunctions grown in the [100] direction by metal–organic chemical vapor deposition (MOCVD). The AlAs quantum barriers in the heterostructures studied are doped p-type with Mg. Theoretical calculations of tunneling currents are performed and compared with experimental I–V data. It is found that for structures with thin AlAs barriers, the dominant current transport mechanism at low temperatures is tunneling through the AlAs band gap at both the Gamma and X points. This is consistent with inelastic processes observable in first (dI/dV) and second (d2I/dV2) derivative spectra obtained with modulation techniques. A simple model, developed for calculating impurity-assisted tunneling currents, shows that the role of barrier impurities becomes more important as the barrier is grown thicker. Implications of some of these results for resonant tunneling heterostructures consisting of two AlAs quantum barriers separated by a GaAs quantum well are discussed. Experimental second derivative spectra showing reproducible features are also presented for these double barrier structures

A family of key agreement mechanisms for mission critical communications for secure mobile ad hoc and wireless mesh internetworking

Future wireless networks like mobile ad hoc networks and wireless mesh networks are expected to play important role in demanding communications such as mission critical communications. MANETs are ideal for emergency cases where the communication infrastructure has been completely destroyed and there is a need for quick set up of communications among the rescue/emergency workers. In such emergency scenarios wireless mesh networks may be employed in a later phase for providing advanced communications and services acting as a backbone network in the affected area. Internetworking of both types of future networks will provide a broad range of mission critical applications. While offering many advantages, such as flexibility, easy of deployment and low cost, MANETs and mesh networks face important security and resilience threats, especially for such demanding applications. We introduce a family of key agreement methods based on weak to strong authentication associated with several multiparty contributory key establishment methods. We examine the attributes of each key establishment method and how each method can be better applied in different scenarios. The proposed protocols support seamlessly both types of networks and consider system and application requirements such as efficient and secure internetworking, dynamicity of network topologies and support of thin clients. © 2011 Ioannis G. Askoxylakis et al

Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally-advanced hormone-receptor-positive breast cancer

Background: The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally-advanced hormone- receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment. Methods: 120 post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment. Results: 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI 45.0-71.9) in the anastrozole arm and 53.8% (95% CI 39.5-67.8) in the fulvestrant arm. The breast- conserving surgery rate was 58.9% (95% CI 45.0-71.9) in the anastrozole arm and 50.0% (95% CI 35.8-64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% [95%CI 13.3-21.0] before, 3.2% [95%CI 1.9-5.5] after, n=43; fulvestrant 17.1% [95%CI 13.1-22.5] before, 3.2% [95%CI 1.8-5.7] after, n=38) or between the reduction in Ki-67 in clinical responders and non- responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles. Conclusion: Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients

Electrical studies of single-barrier Hg_(1-x)Cd_x Te heterostructures

We report an experimental study of the electrical properties of single‐barrier Hg_(1−x)Cd_xTe heterostructures grown by molecular‐beam epitaxy. At high temperature, the measured current is interpreted to be the sum of thermionic and tunneling hole currents. This analysis is applied to data from each of three samples, yielding values of the HgTe–CdTe valence‐band discontinuity between 290±50 and 390±75 meV at 300 K. In all three samples, data taken over the range 190–300 K are consistent with a valence‐band offset which decreases at lower temperatures. Current–voltage curves are taken at 4.2 K, yielding a novel single‐barrier negative differential resistance (NDR) due to electron tunneling. Theoretical simulations indicate that ΔE_v must be <100 meV at 4.2 K to produce NDR

Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial

Background: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Patients and methods: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan–Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. Results: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P &lt; 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P &lt; 0.0001). Conclusions: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.</p

p53 as a potential predictive factor of response to chemotherapy: feasibility of p53 assessment using a functional test in yeast from trucut biopsies in breast cancer patients

Assessment of the predictive value of p53 requires the testing of large numbers of samples from patients enrolled in prospective phase III clinical trials. The goal of this study was to determine whether p53 status can be determined by p53 yeast functional assay using the limiting amounts of material that can typically be obtained in prospective phase III trials (particularly when chemotherapy is given before surgery). All patients presenting with a clinically palpable tumour which could be considered large enough to perform a trucut biopsy (⩾2 cm breast tumour) were eligible for this study. Two trucut biopsies and one incisional biopsy were performed on the surgical specimens (mastectomy or tumourectomy). Samples were snap frozen and cryostat sections were taken for histology and p53 testing. Thirty patients were included. Three samples out of 90 failed to give any p53 PCR products, probably because these samples contained almost entirely fibrous tissue. Of the 87 samples that could be tested, the incisional and trucut biopsies results were fully concordant in every case. p53 could be defined in 97% of patients by double trucut biopsy. Eight out of 30 tumours tested were mutant for p53 (27%). p53 status can be reliably determined by yeast assay from single frozen sections of trucut biopsies. Histological examination before p53 testing is essential to exclude cases where the p53 result may reflect only the status of the normal cells in the biopsy

A refined molecular taxonomy of breast cancer

The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER+/PR+/AR+, one was ER−/PR−/AR+ and one was triple negative (AR−/ER−/PR−). ERBB2-amplified tumors were split between the ER−/PR−/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer

A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism