Characterization of Transmission Losses

In this paper, characterizing transmission losses according to their origin is carried out. Transmission loss is decomposed into three components. The first is due to the current flow from generators to loads. The second is due to the circulating current between generators. The third represents the contribution of network structure and controls to increasing or decreasing transmission losses. Analytical proofs of the proposed loss decomposition are presented along with methods of allocating each component to the parties contributing to it. Illustration on simple dc and ac systems is presented. Results of application of the proposed method compared with other methods are also presented.

2.4 GHz high-efficiency power-combining Class-E amplifier with transmission-line harmonic traps

Experimental assessments of the modified power-combining Class-E amplifier are described. The technique used to combine the output of individual power amplifiers (PAs) into an unbalanced load without the need for bulky transformers permits the use of small RF chokes useful for the deployment in the EER transmitter. The modified output load network of the PA results in excellent 50 dBc and 46 dBc second and third-harmonic suppressions, dispensing the need for additional lossy filtering block. Operating from a 3.2 V dc supply voltage, the PA exhibits 64% drain efficiency at 24 dBm output power. Over a wide bandwidth of 350 MHz, drain efficiency of better than 60% at output power higher than 22 dBm were achieved. © 2010 IEICE Institute of Electronics Informati.

Design technique for mm-wave IC realization of the load network of switched-mode class-EF power amplifier

Analysis and synthesis of the new Class-EF power amplifier (PA) are presented in this paper. The proposed circuit offers means to alleviate some of the major issues faced by existing Class-EF and Class-EF PAs, such as (1) substantial power losses due to parasitic resistance of the large inductor in the Class-EF load network, (2) unpredictable behaviour of practical lumped inductors and capacitors at harmonic frequencies, and (3) deviation from ideal Class-EF operation mode due to detrimental effects of device output inductance at high frequencies. The transmission-line load network of the Class-EF PA topology elaborated in this paper simultaneously satisfies the Class-EF optimum impedance requirements at fundamental frequency, second, and third harmonics as well as simultaneously providing matching to the circuit optimum load resistance for any prescribed system load resistance. Furthermore, an elegant solution using an open and short-circuit stub arrangement is suggested to overcome the problem encountered in the mm-wave IC realizations of the Class-EF PA load network due to lossy quarter-wave line. © 2010 IEICE Institute of Electronics Informati.

The Interlaboratory Robustness Of Next-Generation Sequencing (IRON) Study Phase II: Deep-Sequencing Analyses Of Hematological Malignancies Performed In 8,867 Cases By An International Network Involving 27 Laboratories

Introduction: Amplicon deep-sequencing using second-generation sequencing technology is an innovative molecular diagnostic technique and enables a highly-sensitive detection of mutations. As an international consortium we had investigated previously the robustness, precision, and reproducibility of 454 amplicon next-generation sequencing (NGS) across 10 laboratories from 8 countries (Leukemia, 2011;25:1840-8).

Aims: In Phase II of the study, we established distinct working groups for various hematological malignancies, i.e. acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and multiple myeloma. Currently, 27 laboratories from 13 countries are part of this research consortium. In total, 74 gene targets were selected by the working groups and amplicons were developed for a NGS deep-sequencing assay (454 Life Sciences, Branford, CT). A data analysis pipeline was developed to standardize mutation interpretation both for accessing raw data (Roche Amplicon Variant Analyzer, 454 Life Sciences) and variant interpretation (Sequence Pilot, JSI Medical Systems, Kippenheim, Germany).

Results: We will report on the design, standardization, quality control aspects, landscape of mutations, as well as the prognostic and predictive utility of this assay in a cohort of 8,867 cases. Overall, 1,146 primer sequences were designed and tested. In detail, for example in AML, 924 cases had been screened for CEBPA mutations. RUNX1 mutations were analyzed in 1,888 cases applying the deep-sequencing read counts to study the stability of such mutations at relapse and their utility as a biomarker to detect residual disease. Analyses of DNMT3A (n=1,041) were focused to perform landscape investigations and to address the prognostic relevance. Additionally, this working group is focusing on TET2, ASXL1, and TP53 analyses. A novel prognostic model is being developed allowing stratification of AML into prognostic subgroups based on molecular markers only. In ALL, 1,124 pediatric and adult cases have been screened, including 763 assays for TP53 mutations both at diagnosis and relapse of ALL. Pediatric and adult leukemia expert labs developed additional content to study the mutation incidence of other B and T lineage markers such as IKZF1, JAK2, IL7R, PAX5, EP300, LEF1, CRLF2, PHF6, WT1, JAK1, PTEN, AKT1, IL7R, NOTCH1, CREBBP, or FBXW7. Further, the molecular landscape of CLL is changing rapidly. As such, a separate working group focused on analyses including NOTCH1, SF3B1, MYD88, XPO1, FBXW7 and BIRC3. Currently, 922 cases were screened to investigate the range of mutational burden of NOTCH1 mutations for their prognostic relevance. In MDS, RUNX1 mutation analyses were performed in 977 cases. The prognostic relevance of TP53 mutations in MDS was assessed in additional 327 cases, including isolated deletions of chromosome 5q. Next, content was developed targeting genes of the cellular splicing component, e.g. SF3B1, SRSF2, U2AF1, and ZRSR2. In BCR-ABL1-negative MPN, nine genes of interest (JAK2, MPL, TET2, CBL, KRAS, EZH2, IDH1, IDH2, ASXL1) have been analyzed in a cohort of 155 primary myelofibrosis cases searching for novel somatic mutations and addressing their relevance for disease progression and leukemia transformation. Moreover, an assay was developed and applied to CMML cases allowing the simultaneous analysis of 25 leukemia-associated target genes in a single sequencing run using just 20 ng of starting DNA. Finally, nine laboratories are studying CML, applying ultra-deep sequencing of the BCR-ABL1 tyrosine kinase domain. Analyses were performed on 615 cases investigating the dynamics of expansion of mutated clones under various tyrosine kinase inhibitor therapies.

Conclusion: Molecular characterization of hematological malignancies today requires high diagnostic sensitivity and specificity. As part of the IRON-II study, a network of laboratories analyzed a variety of disease entities applying amplicon-based NGS assays. Importantly, the consortium not only standardized assay design for disease-specific panels, but also achieved consensus on a common data analysis pipeline for mutation interpretation. Distinct working groups have been forged to address scientific tasks and in total 8,867 cases had been analyzed thus far.

Edge-preserving self-healing: Keeping network backbones densely connected

Healing algorithms play a crucial part in distributed peer-to-peer networks where failures occur continuously and frequently. Whereas there are approaches for robustness that rely largely on built-in redundancy, we adopt a responsive approach that is more akin to that of biological networks e.g. the brain. The general goal of self-healing distributed graphs is to maintain certain network properties while recovering from failure quickly and making bounded alterations locally. Several self-healing algorithms have been suggested in the recent literature [IPDPS'08, PODC'08, PODC'09, PODC'11]; they heal various network properties while fulfilling competing requirements such as having low degree increase while maintaining connectivity, expansion and low stretch of the network. In this work, we augment the previous algorithms by adding the notion of edge-preserving self-healing which requires the healing algorithm to not delete any edges originally present or adversarialy inserted. This reflects the cost of adding additional edges but more importantly it immediately follows that edge preservation helps maintain any subgraph induced property that is monotonic, in particular important properties such as graph and subgraph densities. Density is an important network property and in certain distributed networks, maintaining it preserves high connectivity among certain subgraphs and backbones. We introduce a general model of self-healing, and introduce xheal+, an edge-preserving version of xheal[PODC'11]. © 2012 IEEE.

Managerial failure in mid-Victorian Britain?: Corporate expansion during a promotion boom

This article examines the mid-1840s expansion of the British railway network, which was associated with a large deterioration in shareholder value. Using a counterfactual approach and new data on railway competition, we argue that the expansion of the railway companies, and their subsequent decline in financial performance, was not due to managerial failure. Rather, the promotion of new routes by established railways and mergers with other companies was part of a managerial strategy to maintain incumbent positions, and may have been preferable to not expanding whilst their competitors did.

Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled 'reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers. © 2012 Biek et al.

Secure Transmission in Spectrum Sharing MIMO Networks with Generalized Antenna Selection over Nakagami-m Channels

In this paper, we investigate the secrecy outage performance of spectrum sharing multiple-input multiple-output networks using generalized transmit antenna selection with maximal ratio combining over Nakagami-m channels. In particular, the outdated channel state information is considered at the process of antenna selection due to feedback delay. Considering a practical passive eavesdropper scenario, we derive the exact and asymptotic closed-form expressions of secrecy outage probability, which enable us to evaluate the secrecy performance with high efficiency and present a new design insight into the impact of key parameters on the secrecy performance. In addition, the analytical results demonstrate that the achievable secrecy diversity order is only determined by the parameters of the secondary network, while other parameters related to primary or eavesdropper’s channels have a significantly impact on the secrecy coding gain. 

Cell cycle-coupled expansion of AR activity promotes cancer progression

The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention.