An efficient technique for excess loop delay compensation in continuous-time ΔΣ modulators

A highly-digital technique is proposed for excess loop delay (ELD) compensation in multi-bit continuous-time ΔΣ modulators. A digitally controlled reference switching matrix is used to replace the power-hungry signal adder and extra DAC driving the quantizer, which are commonly used in ELD compensation. With the proposed technique, the feedback DAC is embedded in the quantizer and implemented by a few switches. Thus it allows low voltage and low-power operation.This paper is a postprint of a paper submitted to and accepted for publication in Electronics Letters and is subject to Institution of Engineering and Technology Copyright. The copy of record is available at IET Digital Library. It can be found at: http://digital-library.theiet.org/content/journals/el

Teraohm on-chip resistance realisation using switched capacitor topologies

Two large-resistance realisation schemes are proposed using switched-capacitor circuits. The equivalent resistance of the array realisation increases as the third power of the number of capacitor pairs, and that of the ladder realisation increases exponentially. The equivalent resistance for the ladder scheme also grows with the capacitance ratio. Using these schemes, large resistances can be fabricated with standard CMOS process in an affordable chip area. Simulation results show that very low pole frequency (~ 9 Hz in the example) can be achieved with practical element values, and with a capacitance spread of only 10 in a three-stage ladder.This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the Institution of Engineering and Technology and can be found at: http://digital-library.theiet.org/content/journals/el

Multi-Step Extended-Counting Analog-to- Digital Converters

Extended-counting A/D converters are proposed which achieve a high accuracy by performing the conversion in several cycles. During the first cycle, the circuit performs as an incremental ADC, while during the remaining ones it acts as a multi-slope counting converter. With only one opamp and a single-slope ADC, the accuracy is comparable to that of a second-order incremental ADC. A three-step A/D converter using only a single opamp and a two-slope ADC achieves an accuracy comparable to that of a third-order incremental ADC, but with much higher power efficiency.Keywords: second-order incremental ADC, analogue-digital conversion, operational amplifiers, third-order incremental ADC, multislope counting converter, multistep extended-counting analogue-to-digital converters, counting circuits, single-slope ADC, single opamp, two-slope ADC, circuit performance, extended-counting A-D converters, three-step A/D converter, power efficiencyThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by IEEE-Institute of Electrical and Electronics Engineers and can be found at: http://ieeexplore.ieee.org/xpl/RecentIssue.jsp?punumber=2220. ©2013 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works

Noise-Shaping SAR ADC Using Three Capacitors

In this letter, a simple and highly efficient successive-approximation Registers (SAR) ADC realization is proposed. It requires an op-amp, a comparator and only three equal-valued capacitors. The proposed scheme is insensitive to the capacitor parasitics, and has a small capacitance spread. With an oversampled scheme, it also allows noise-shaping the remaining quantization error. It is well-suited for low-frequency instrumentation and measurement applications, and for use in extended-counting ADCs.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by IEEE-Institute of Electrical and Electronics Engineers and can be found at: http://ieeexplore.ieee.org/xpl/RecentIssue.jsp?punumber=2220. ©2013 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works

A Two-Step Incremental Analog-to-Digital Converter

A new incremental ADC is proposed which extends the order of a conventional incremental ADC from N to (2N-1) by way of a two-step operation. For a given conversion time, the duration of each step can be optimized. For an Nth-order IADC, the performance is equivalent to that of a (2N-1)-order converter. However, it only needs the same circuitry as the Nth-order one. The new IADC is hence more accurate, and also much more power-efficient than the conventional ones.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by IEEE-Institute of Electrical and Electronics Engineers and can be found at: http://ieeexplore.ieee.org/xpl/RecentIssue.jsp?punumber=2220. ©2013 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.Keywords: two-step incremental analogue-to-digital converter, power-efficient IADC, analogue-digital conversion, incremental ADC, two-step operatio

Flavour Changing Neutral Higgs Boson Decays from Squark - Gluino Loops

We study the flavour changing neutral Higgs boson decays that can be induced from genuine supersymmetric particles at the one-loop level and within the context of the Minimal Supersymmetric Standard Model. We consider all the possible flavour changing decay channels of the three neutral Higgs bosons into second and third generation quarks, and focus on the Supersymmetric-QCD corrections from squark-gluino loops which are expected to provide the dominant contributions. We assume here the more general hypothesis for flavour mixing, where there is misalignment between the quark and squark sectors, leading to a flavour non-diagonal squark mass matrix. The form factors involved, and the corresponding Higgs partial decay widths and branching ratios, are computed both analytically and numerically, and their behaviour with the parameters of the Minimal Supersymmetric Standard Model and with the squark mass mixing are analyzed in full detail. The large rates found, are explained in terms of the non-decoupling behaviour of these squark-gluino loop corrections in the scenario with very large supersymmetric mass parameters. Our results show that if these decays are seen in future colliders they could provide clear indirect signals of supersymmetry.Comment: 32 Pages and 12 PostScript Level 2 Figures. Some references adde

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Productive Parvovirus B19 Infection of Primary Human Erythroid Progenitor Cells at Hypoxia Is Regulated by STAT5A and MEK Signaling but not HIFα

Human parvovirus B19 (B19V) causes a variety of human diseases. Disease outcomes of bone marrow failure in patients with high turnover of red blood cells and immunocompromised conditions, and fetal hydrops in pregnant women are resulted from the targeting and destruction of specifically erythroid progenitors of the human bone marrow by B19V. Although the ex vivo expanded erythroid progenitor cells recently used for studies of B19V infection are highly permissive, they produce progeny viruses inefficiently. In the current study, we aimed to identify the mechanism that underlies productive B19V infection of erythroid progenitor cells cultured in a physiologically relevant environment. Here, we demonstrate an effective reverse genetic system of B19V, and that B19V infection of ex vivo expanded erythroid progenitor cells at 1% O2 (hypoxia) produces progeny viruses continuously and efficiently at a level of approximately 10 times higher than that seen in the context of normoxia. With regard to mechanism, we show that hypoxia promotes replication of the B19V genome within the nucleus, and that this is independent of the canonical PHD/HIFα pathway, but dependent on STAT5A and MEK/ERK signaling. We further show that simultaneous upregulation of STAT5A signaling and down-regulation of MEK/ERK signaling boosts the level of B19V infection in erythroid progenitor cells under normoxia to that in cells under hypoxia. We conclude that B19V infection of ex vivo expanded erythroid progenitor cells at hypoxia closely mimics native infection of erythroid progenitors in human bone marrow, maintains erythroid progenitors at a stage conducive to efficient production of progeny viruses, and is regulated by the STAT5A and MEK/ERK pathways

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe