Process control of cantilever deflection for sensor application based on optical waveguides

This paper reports on the fabrication of cantilever silicon-on-insulator (SOI) optical waveguides and presents solutions to the challenges of using a very thin 260-nm active silicon layer in the SOI structure to enable single-transverse-mode operation of the waveguide with minimal optical transmission losses. In particular, to ameliorate the anchor effect caused by the mean stress difference between the active silicon layer and buried oxide layer, a cantilever flattening process based on Ar plasma treatment is developed and presented. Vertical deflections of 0.5 mu m for 70-mu m-long cantilevers are mitigated to within few nanometers. Experimental investigations of cantilever mechanical resonance characteristics confirm the absence of significant detrimental side effects. Optical and mechanical modeling is extensively used to supplement experimental observations. This approach can satisfy the requirements for on-chip simultaneous readout of many integrated cantilever sensors in which the displacement or resonant frequency changes induced by analyte absorption are measured using an optical-waveguide-based division multiplexed system.

Experimental Studies on the Kinematics of Cutting in Granular Materials

Slow flow in granular materials is characterized by high solid fraction and sustained inter-particle interaction. The kinematics of trawling or cutting is encountered in processes such as locomotion of organisms in sand; trawl gear movement on a soil deposit; plow movement; movement of rovers, earth moving equipment etc. Additionally, this configuration is very akin to shallow drilling configuration encountered in the mining and petroleum industries. An experimental study has been made in order to understand velocity and deformation fields in cutting of a model rounded sand. Under nominal plane strain conditions, sand is subjected to orthogonal cutting at different tool-rake angles. High-resolution optical images of the region of cutting were obtained during the flow of the granular ensemble around the tool. Interesting kinematics underlying the formation of a chip and the evolution of the deformation field is seen in these experiments. These images are also analyzed using a PIV algorithm and detailed information of the deformation parameters such as velocity, strain rate and volume change is obtained.

Stable hybrid containing haploid genomes of two obligate diploid Candida species

Candida albicans and Candida dubliniensis are diploid, predominantly asexual human-pathogenic yeasts. In this study, we constructed tetraploid (4n) strains of C. albicans of the same or different lineages by spheroplast fusion. Induction of chromosome loss in the tetraploid C. albicans generated diploid or near-diploid progeny strains but did not produce any haploid progeny. We also constructed stable heterotetraploid somatic hybrid strains (2n + 2n) of C. albicans and C. dubliniensis by spheroplast fusion. Heterodiploid (n + n) progeny hybrids were obtained after inducing chromosome loss in a stable heterotetraploid hybrid. To identify a subset of hybrid heterodiploid progeny strains carrying at least one copy of all chromosomes of both species, unique centromere sequences of various chromosomes of each species were used as markers in PCR analysis. The reduction of chromosome content was confirmed by a comparative genome hybridization (CGH) assay. The hybrid strains were found to be stably propagated. Chromatin immunoprecipitation (ChIP) assays with antibodies against centromere-specific histones (C. albicans Cse4/C. dubliniensis Cse4) revealed that the centromere identity of chromosomes of each species is maintained in the hybrid genomes of the heterotetraploid and heterodiploid strains. Thus, our results suggest that the diploid genome content is not obligatory for the survival of either C. albicans or C. dubliniensis. In keeping with the recent discovery of the existence of haploid C. albicans strains, the heterodiploid strains of our study can be excellent tools for further species-specific genome elimination, yielding true haploid progeny of C. albicans or C. dubliniensis in future.

Traffic engineered NoC for streaming applications

Streaming applications demand hard bandwidth and throughput guarantees in a multiprocessor environment amidst resource competing processes. We present a Label Switching based Network-on-Chip (LS-NoC) motivated by throughput guarantees offered by bandwidth reservation. Label switching is a packet relaying technique in which individual packets carry route information in the form of labels. A centralized LS-NoC Management framework engineers traffic into Quality of Service (QoS) guaranteed routes. LS-NoC caters to the requirements of streaming applications where communication channels are fixed over the lifetime of the application. The proposed NoC framework inherently supports heterogeneous and ad hoc system-on-chips. The LS-NoC can be used in conjunction with conventional best effort NoC as a QoS guaranteed communication network or as a replacement to the conventional NoC. A multicast, broadcast capable label switched router for the LS-NoC has been designed. A 5 port, 256 bit data bus, 4 bit label router occupies 0.431 mm(2) in 130 nm and delivers peak bandwidth of 80 Gbits/s per link at 312.5 MHz. Bandwidth and latency guarantees of LS-NoC have been demonstrated on traffic from example streaming applications and on constant and variable bit rate traffic patterns. LS-NoC was found to have a competitive AreaxPower/Throughput figure of merit with state-of-the-art NoCs providing QoS. Circuit switching with link sharing abilities and support for asynchronous operation make LS-NoC a desirable choice for QoS servicing in chip multiprocessors. (C) 2013 Elsevier B.V. All rights reserved.

TCP: thread contention predictor for parallel programs

With proliferation of chip multicores (CMPs) on desktops and embedded platforms, multi-threaded programs have become ubiquitous. Existence of multiple threads may cause resource contention, such as, in on-chip shared cache and interconnects, depending upon how they access resources. Hence, we propose a tool - Thread Contention Predictor (TCP) to help quantify the number of threads sharing data and their sharing pattern. We demonstrate its use to predict a more profitable shared, last level on-chip cache (LLC) access policy on CMPs. Our cache configuration predictor is 2.2 times faster compared to the cycle-accurate simulations. We also demonstrate its use for identifying hot data structures in a program which may cause performance degradation due to false data sharing. We fix layout of such data structures and show up-to 10% and 18% improvement in execution time and energy-delay product (EDP), respectively.

A power-scalable RF CMOS receiver for 2.4 GHz Wireless Sensor Network applications

A power scalable receiver architecture is presented for low data rate Wireless Sensor Network (WSN) applications in 130nm RF-CMOS technology. Power scalable receiver is motivated by the ability to leverage lower run-time performance requirement to save power. The proposed receiver is able to switch power settings based on available signal and interference levels while maintaining requisite BER. The Low-IF receiver consists of Variable Noise and Linearity LNA, IQ Mixers, VGA, Variable Order Complex Bandpass Filter and Variable Gain and Bandwidth Amplifier (VGBWA) capable of driving variable sampling rate ADC. Various blocks have independent power scaling controls depending on their noise, gain and interference rejection (IR) requirements. The receiver is designed for constant envelope QPSK-type modulation with 2.4GHz RF input, 3MHz IF and 2MHz bandwidth. The chip operates at 1V Vdd with current scalable from 4.5mA to 1.3mA and chip area of 0.65mm2.

System-level SoC near-field (NF) emissions: Simulation to measurement correlation

As System-on-Chip (SoC) designs migrate to 28nm process node and beyond, the electromagnetic (EM) co-interactions of the Chip-Package-Printed Circuit Board (PCB) becomes critical and require accurate and efficient characterization and verification. In this paper a fast, scalable, and parallelized boundary element based integral EM solutions to Maxwell equations is presented. The accuracy of the full-wave formulation, for complete EM characterization, has been validated on both canonical structures and real-world 3-D system (viz. Chip + Package + PCB). Good correlation between numerical simulation and measurement has been achieved. A few examples of the applicability of the formulation to high speed digital and analog serial interfaces on a 45nm SoC are also presented.

Time-Based All-Digital Technique for Analog Built-in Self-Test

A scheme for built-in self-test of analog signals with minimal area overhead for measuring on-chip voltages in an all-digital manner is presented. The method is well suited for a distributed architecture, where the routing of analog signals over long paths is minimized. A clock is routed serially to the sampling heads placed at the nodes of analog test voltages. This sampling head present at each test node, which consists of a pair of delay cells and a pair of flip-flops, locally converts the test voltage to a skew between a pair of subsampled signals, thus giving rise to as many subsampled signal pairs as the number of nodes. To measure a certain analog voltage, the corresponding subsampled signal pair is fed to a delay measurement unit to measure the skew between this pair. The concept is validated by designing a test chip in a UMC 130-nm CMOS process. Sub-millivolt accuracy for static signals is demonstrated for a measurement time of a few seconds, and an effective number of bits of 5.29 is demonstrated for low-bandwidth signals in the absence of sample-and-hold circuitry.

Transcriptional Repression of Tumor Suppressor CDC73, Encoding an RNA Polymerase II Interactor, by Wilms Tumor 1 Protein (WT1) Promotes Cell Proliferation IMPLICATION FOR CANCER THERAPEUTICS

The Wilms tumor 1 gene (WT1) can either repress or induce the expression of genes. Inconsistent with its tumor suppressor role, elevated WT1 levels have been observed in leukemia and solid tumors. WT1 has also been suggested to act as an oncogene by inducing the expression of MYC and BCL-2. However, these are only the correlational studies, and no functional study has been performed to date. Consistent with its tumor suppressor role, CDC73 binds to RNA polymerase II as part of a PAF1 transcriptional regulatory complex and causes transcriptional repression of oncogenes MYC and CCND1. It also represses beta-catenin-mediated transcription. Based on the reduced level of CDC73 in oral squamous cell carcinoma (OSCC) samples in the absence of loss-of-heterozygosity, promoter methylation, and mutations, we speculated that an inhibitory transcription factor is regulating its expression. The bioinformatics analysis predicted WT1 as an inhibitory transcription factor to regulate the CDC73 level. Our results showed that overexpression of WT1 decreased CDC73 levels and promoted proliferation of OSCC cells. ChIP and EMSA results demonstrated binding of WT1 to the CDC73 promoter. The 5-azacytidine treatment of OSCC cells led to an up-regulation of WT1 with a concomitant down-regulation of CDC73, further suggesting regulation of CDC73 by WT1. Exogenous CDC73 attenuated the protumorigenic activity of WT1 by apoptosis induction. An inverse correlation between expression levels of CDC73 and WT1 was observed in OSCC samples. These observations indicated that WT1 functions as an oncogene by repressing the expression of CDC73 in OSCC. We suggest that targeting WT1 could be a therapeutic strategy for cancer, including OSCC.

Luminescent Molecular Sensors for Assessment of Temperature Field in Machining

A new technique based on luminescent molecular sensors is utilized in these series of experiments for measurement of temperatures in material removal processes. 2-Dimensional machining of metals at low speeds and surface grinding configurations are used as the model experimental systems to understand the efficacy of this experimental technique. The experiments were conducted with a series of luminescent sensors and binder combinations for the temperature measurement. The luminescence of the sensor was measured through a charge-coupled device imaging camera, and intensive calibration exercises were performed on these sensors. Excellent agreement in the temperature fields measured through this new experimental approach and traditional infrared thermography is seen here. This technique offers the unique capability of allowing measurement of temperatures in the presence of a lubricant, akin to manufacturing conditions in situ. Extension of the technique to measure the temperature field at the tool-chip contact is described.

Rad51-Rad52 Mediated Maintenance of Centromeric Chromatin in Candida albicans

Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence. However, the non-genetic determinants of centromere identity are not clearly defined. While multiple mechanisms, individually or in concert, may specify centromeres epigenetically, most studies in this area are focused on a universal factor, a centromere-specific histone H3 variant CENP-A, often considered as the epigenetic determinant of centromere identity. In spite of variable timing of its loading at centromeres across species, a replication coupled early S phase deposition of CENP-A is found in most yeast centromeres. Centromeres are the earliest replicating chromosomal regions in a pathogenic budding yeast Candida albicans. Using a 2-dimensional agarose gel electrophoresis assay, we identify replication origins (ORI7-LI and ORI7-RI) proximal to an early replicating centromere (CEN7) in C. albicans. We show that the replication forks stall at CEN7 in a kinetochore dependent manner and fork stalling is reduced in the absence of the homologous recombination (HR) proteins Rad51 and Rad52. Deletion of ORI7-RI causes a significant reduction in the stalled fork signal and an increased loss rate of the altered chromosome 7. The HR proteins, Rad51 and Rad52, have been shown to play a role in fork restart. Confocal microscopy shows declustered kinetochores in rad51 and rad52 mutants, which are evidence of kinetochore disintegrity. CENP-A(CaCse4) levels at centromeres, as determined by chromatin immunoprecipitation (ChIP) experiments, are reduced in absence of Rad51/Rad52 resulting in disruption of the kinetochore structure. Moreover, western blot analysis reveals that delocalized CENP-A molecules in HR mutants degrade in a similar fashion as in other kinetochore mutants described before. Finally, co-immunoprecipitation assays indicate that Rad51 and Rad52 physically interact with CENP-A(CaCse4) in vivo. Thus, the HR proteins Rad51 and Rad52 epigenetically maintain centromere functioning by regulating CENP-A(CaCse4) levels at the programmed stall sites of early replicating centromeres.

Incipient straining in severe plastic deformation methods

Knowledge of the plasticity associated with the incipient stage of chip formation is useful toward developing an understanding of the deformation field underlying severe plastic deformation processes. The transition from a transient state of straining to a steady state was investigated in plane strain machining of a model material system-copper. Characterization of the evolution to a steady-state deformation field was made by image correlation, hardness mapping, load analysis, and microstructure characterization. Empirical relationships relating the deformation heterogeneity and the process parameters were found and explained by the corresponding effects on shear plane geometry. The results are potentially useful to facilitate a framework for process design of large strain deformation configurations, wherein transient deformation fields prevail. These implications are considered in the present study to quantify the efficiency of processing methods for bulk ultrafine-grained metals by large strain extrusion machining and equal channel angular pressing.

A MICROMACHINED WIDE-BAND IN-PLANE SINGLE-AXIS CAPACITIVE ACCELEROMETER WITH A DISPLACEMENT-AMPLIFYING COMPLIANT MECHANISM

With the premise that electronic noise dominates mechanical noise in micromachined accelerometers, we present here a method to enhance the sensitivity and resolution at kHz bandwidth using mechanical amplification. This is achieved by means of a Displacement-amplifying Compliant Mechanism (DaCM) that is appended to the usual sensing element comprising a proof-mass and a suspension. Differential comb-drive arrangement is used for capacitive-sensing. The DaCM is designed to match the stiffness of the suspension so that there is substantial net amplification without compromising the bandwidth. A spring-mass-lever model is used to estimate the lumped parameters of the system. A DaCM-aided accelerometer and another without a DaCM-both occupying the same footprint-are compared to show that the former gives enhanced sensitivity: 8.7 nm/g vs. 1.4 nm/g displacement at the sensing-combs under static conditions. A prototype of the DaCM-aided micromachined acclerometer was fabricated using bulk-micromachining. It was tested at the die-level and then packaged on a printed circuit board with an off-the-shelf integrated chip for measuring change in capacitance. Under dynamic conditions, the measured amplification factor at the output of the DaCM was observed to be about 11 times larger than the displacement of the proof-mass and thus validating the concept of enhancing the sensitivity of accelerometers using mechanical amplifiers. The measured first in-plane natural frequency of the fabricated accelerometer was 6.25 kHz. The packaged accelerometer with the DaCM was measured to have 26.7 mV/g sensitivity at 40 Hz.

Evidence that TSC2 acts as a transcription factor and binds to and represses the promoter of Epiregulin

The TSC2 gene, mutated in patients with tuberous sclerosis complex (TSC), encodes a 200 kDa protein TSC2 (tuberin). The importance of TSC2 in the regulation of cell growth and proliferation is irrefutable. TSC2 in complex with TSC1 negatively regulates the mTOR complex 1 (mTORC1) via RHEB in the PI3K-AKT-mTOR pathway and in turn regulates cell proliferation. It shows nuclear as well as cytoplasmic localization. However, its nuclear function remains elusive. In order to identify the nuclear function of TSC2, a whole-genome expression profiling of TSC2 overexpressing cells was performed, and the results showed differential regulation of 266 genes. Interestingly, transcription was found to be the most populated functional category. EREG (Epiregulin), a member of the epidermal growth factor family, was found to be the most downregulated gene in the microarray analysis. Previous reports have documented elevated levels of EREG in TSC lesions, making its regulatory aspects intriguing. Using the luciferase reporter, ChIP and EMSA techniques, we show that TSC2 binds to the EREG promoter between -352 bp and -303 bp and negatively regulates its expression. This is the first evidence for the role of TSC2 as a transcription factor and of TSC2 binding to the promoter of any gene.

A Digital Frequency Multiplication Technique for Energy Efficient Transmitters

A logic gate-based digital frequency multiplication technique for low-power frequency synthesis is presented. The proposed digital edge combining approach offers broadband operation with low-power and low-area advantages and is a promising candidate for low-power frequency synthesis in deep submicrometer CMOS technologies. Chip prototype of the proposed frequency multiplication-based 2.4-GHz binary frequency-shift-keying (BFSK)/amplitude shift keying (ASK) transmitter (TX) was fabricated in 0.13-mu m CMOS technology. The TX achieves maximum data rates of 3 and 20 Mb/s for BFSK and ASK modulations, respectively, consuming a 14-mA current from 1.3 V supply voltage. The corresponding energy efficiencies of the TX are 3.6 nJ/bit for BFSK and 0.91 nJ/bit for ASK modulations.