Yield-driven power-delay-optimal CMOS full-adder design complying with automotive product specifications of PVT variations and NBTI degradations

We present the detailed results of the application of mathematical optimization algorithms to transistor sizing in a full-adder cell design, to obtain the maximum expected fabrication yield. The approach takes into account all the fabrication process parameter variations specified in an industrial PDK, in addition to operating condition range and NBTI aging. The final design solutions present transistor sizing, which depart from intuitive transistor sizing criteria and show dramatic yield improvements, which have been verified by Monte Carlo SPICE analysis

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Design centering/yield optimization of power aware band pass filter based on CMOS current controlled current conveyor (CCCII+)

Process variability are getting worse with the scaled technologies especially below 90 nm, therefore for the reliable fabrication outcome, the effect of both the local and global process variability should be taken into account. In this paper, verification, sizing and design centering/yield optimization for the robust second generation current controlled current conveyor (CCCII+) and CCCII+ based band pass filter for low power without degrading other performances values have been presented. Current conveyors (CC) based applications are getting significant attention in current analog ICs design due to their higher band-width, greater linearity, larger dynamic range, simpler circuitry, lower power consumption. Moreover CCCII has the advantage of electronic tunability at its intrinsic resistance terminal via a bias current. The net lists of CCCII+ and band pass filter circuits have been simulated in Eldo using the 65 nm CMOS mixed signal low-K TSMC process development kit (PDK) with 1.2 V, low-Vt devices with statistical models. All analysis, sizing and optimization have been performed using the WiCkeDTM tool at worst case operating conditions. Monte Carlo analysis has also been performed to verify the robustness of the circuit. © 2012 Elsevier Ltd. All rights reserved

Optimal NBTI degradation and PVT variation resistant device sizing in a full adder cell

Aging phenomena, on top of process variations along with temperature and supply voltage variations, translate into complex degradation effects on the required performance and yield of nanoscale circuits. The proposed paper focuses on the development of mathematically optimal circuit sizing for yield maximization on the case study of a CMOS full adder circuit. The final cell design is robust against NBTI aging effects, impact of statistical (global and mismatch) and operating variation of temperature and supply voltage. Monte Carlo analysis has been carried out to verify the estimated yields. The demonstrated technique can be extended to a library of optimally designed digital cells. © 2015 IEEE

Drosophila Ror is a nervous system-specific co-receptor for Wnt ligands

Wnt ligands are secreted glycoproteins that control many developmental processes and are crucial for homeostasis of numerous tissues in the adult organism. Signal transduction of Wnts involves the binding of Wnts to receptor complexes at the surface of target cells. These receptor complexes are commonly formed between a member of the Frizzled family of seven-pass transmembrane proteins and a co-receptor, which is usually a single-pass transmembrane protein. Among these co-receptors are several with structural homology to receptor tyrosine kinases, including Ror, PTK7, Ryk and MUSK. In vertebrates, Ror-2 and PTK7 are important regulators of planar cell polarity (PCP). By contrast, PCP phenotypes were not reported for mutations in off-track (otk) and off-track2 (otk2), encoding the Drosophila orthologs of PTK7. Here we show that Drosophila Ror is expressed in the nervous system and localizes to the plasma membrane of perikarya and neurites. A null allele of Ror is homozygous viable and fertile, does not display PCP phenotypes and interacts genetically with mutations in otk and otk2. We show that Ror binds specifically to Wingless (Wg), Wnt4 and Wnt5 and also to Frizzled2 (Fz2) and Otk. Our findings establish Drosophila Ror as a Wnt co-receptor expressed in the nervous system

The PTK7-Related Transmembrane Proteins Off-track and Off-track 2 Are Co-receptors for <i>Drosophila</i> Wnt2 Required for Male Fertility

<div><p>Wnt proteins regulate many developmental processes and are required for tissue homeostasis in adult animals. The cellular responses to Wnts are manifold and are determined by the respective Wnt ligand and its specific receptor complex in the plasma membrane. Wnt receptor complexes contain a member of the Frizzled family of serpentine receptors and a co-receptor, which commonly is a single-pass transmembrane protein. Vertebrate protein tyrosine kinase 7 (PTK7) was identified as a Wnt co-receptor required for control of planar cell polarity (PCP) in frogs and mice. We found that flies homozygous for a complete knock-out of the <i>Drosophila</i> PTK7 homolog <i>off track</i> (<i>otk</i>) are viable and fertile and do not show PCP phenotypes. We discovered an <i>otk</i> paralog (<i>otk2</i>, <i>CG8964</i>), which is co-expressed with <i>otk</i> throughout embryonic and larval development. Otk and Otk2 bind to each other and form complexes with Frizzled, Frizzled2 and Wnt2, pointing to a function as Wnt co-receptors. Flies lacking both <i>otk</i> and <i>otk2</i> are viable but male sterile due to defective morphogenesis of the ejaculatory duct. Overexpression of Otk causes female sterility due to malformation of the oviduct, indicating that Otk and Otk2 are specifically involved in the sexually dimorphic development of the genital tract.</p></div

Otk and Otk2 bind to Wnt2.

<p>(A) Otk and Otk2 co-precipitate <i>Drosophila</i> Wnt2. Otk-GFP or Otk2-GFP and Wnt2-Myc expression vectors were transfected as indicated in Drosophila S2r+ cells. Cell lysates were immunoprecipitated and analyzed by Western Blot with the indicated antibodies. IP, Immunoprecipitation; WB, Western Blot. (B–D) Wnt2 protein binds to S2 cells transfected with Otk-GFP or Otk2-GFP. S2 cells transfected with Otk-GFP (B), Otk2-GFP (C) and DE-Cadherin-GFP (D) were incubated with conditioned medium from S2 cells producing Wnt2-Myc and subsequently stained with anti-Myc antibody. GFP signals are shown in (B–D), Myc signal is shown in (B′–D′), DAPI staining is shown in (B″–D″) and the merged images in (B‴–D‴). Scale bar: 20 µm.</p

Off-track (Otk) and Off-track2 (CG8964, Otk2) are paralogs evolved by gene duplication.

<p>(A) Phylogenetic tree representation of an alignment of sequences from different species homologous to <i>Drosophila</i> Otk. Blast-P of Dm-Otk in <i>Drosophila</i> returned Dm-CG8964 (Otk2) as the best hit; Dm-Ror and Dm-Heartless-A were the second and third hit, repectively. Blast-P of Dm-Otk in Mouse returned Mm-PTK7 as the best hit, while Mm-FGF receptor3 was the second best hit. Blast-P of Dm-Otk in Human returned Hs-PTK7 as the best hit. ClustalW alignment of these sequences and Neighbor-Joining tree confirms that the PTK7 branch is separated from the other proteins by a bootstrap value of 100. In this branch, two <i>Drosophila</i> genes, but only one in the other species can be found. (B) Protein structures of Otk and Otk2. Domains were predicted using the SMART sequence analysis tool. Dm, <i>Drosophila melanogaster</i>; Mm, <i>Mus musculus</i>; Hs, <i>Homo sapiens</i>.</p

Biochemical interactions of Off-track and Off-track2.

<p>(A, B) Otk and Otk2 form homooligomers and heterooligomers. Otk-Myc or Otk2-Myc and Otk-GFP or Otk2-GFP expression vectors were transfected as indicated in <i>Drosophila</i> S2r+ cells. Relevant bands corresponding to tagged Otk and Otk2 are marked by an asterisk in the bottom right panel of (A). (C) Homo- and heterodimerization of Otk and Otk2 requires the transmembrane domain. Otk-Myc or Myc-tagged Otk deletion contructs and Otk-GFP or Otk2-GFP expression vectors were transfected as indicated in <i>Drosophila</i> S2r+ cells. OtkDeltaCy lacks the cytoplasmic domain (aa 776–1033) and OtkDeltaEx lacks the extracellular domain (aa 2–474). (D) Off-track and Off-track2 interact with Frizzled1 and Frizzled2. Otk-GFP or Otk2-GFP and Fz1-Myc or Fz2-Myc expression vectors were transfected as indicated in <i>Drosophila</i> S2r+ cells. Cell lysates were immunoprecipitated and analyzed by Western Blot with the indicated antibodies. IP, Immunoprecipitation; WB, Western Blot.</p

<i>otk, otk2^D72</i> homozygous mutant males are sterile.

<p><i>otk, otk2^D72</i> homozygous mutant males are sterile.</p