Noise modeling for RF CMOS circuit simulation

The RF noise in 0.18-/spl mu/m CMOS technology has been measured and modeled. In contrast to some other groups, we find only a moderate enhancement of the drain current noise for short-channel MOSFETs. The gate current noise on the other hand is more significantly enhanced, which is explained by the effects of the gate resistance. The experimental results are modeled with a nonquasi-static RF model, based on channel segmentation, which is capable of predicting both drain and gate current noise accurately. Experimental evidence is shown for two additional noise mechanisms: 1) avalanche noise associated with the avalanche current from drain to bulk and 2) shot noise in the direct-tunneling gate leakage current. Additionally, we show low-frequency noise measurements, which strongly point toward an explanation of the 1/f noise based on carrier trapping, not only in n-channel MOSFETs, but also in p-channel MOSFETs.     

Finding the number of clusters in ordered dissimilarities

As humans, we have innate faculties that allow us to efficiently segment groups of objects. Computers, to some degree, can be programmed with similar categorical capabilities, which stem from exploratory data analysis. Out of the various subsets of data reasoning, clustering provides insight into the structure and relationships of input samples situated in a number of distributions. To determine these relationships, many clustering methods rely on one or more human inputs; the most important being the number of distributions, c, to seek. This work investigates a technique for estimating the number of clusters from a general type of data called relational data. Several numerical examples are presented to illustrate the effectiveness of the proposed method.     

Clustering in ordered dissimilarity data

This paper presents a new technique for clustering either object or relational data. First, the data are represented as a matrix D of dissimilarity values. D is reordered to D * using a visual assessment of cluster tendency algorithm. If the data contain clusters, they are suggested by visually apparent dark squares arrayed along the main diagonal of an image I( D *) of D *. The suggested clusters in the object set underlying the reordered relational data are found by defining an objective function that recognizes this blocky structure in the reordered data. The objective function is optimized when the boundaries in I( D *) are matched by those in an aligned partition of the objects. The objective function combines measures of contrast and edginess and is optimized by particle swarm optimization. We prove that the set of aligned partitions is exponentially smaller than the set of partitions that needs to be searched if clusters are sought in D . Six numerical examples are given to illustrate various facets of the algorithm. © 2009 Wiley Periodicals, Inc.     

Employing CRISPR-Cas9 to Generate CD133 Synthetic Lethal Melanoma Stem Cells

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC) implicated in tumorigenesis, invasion, and drug resistance, and is characterized by the elevated expression of stem cell markers, including CD133. The siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRAS^Q61K and NRAS^Q61R drivers, after CRISPR-Cas9 CD133 knockout or Dox-inducible expression of CD133. MACS-sorted CD133(+) BAKP cells were conditionally reprogrammed to derive BAKR cells with sustained CD133 expression and MIC features. Compared to BAKP, CD133(+) BAKR exhibit increased cell survival and reduced apoptosis in response to trametinib or the chemotherapeutic dacarbazine (DTIC). CRISPR-Cas9-mediated CD133 knockout in BAKR cells (BAKR-KO) re-sensitized cells to trametinib. CD133 knockout in BAKP and POT cells increased trametinib-induced apoptosis by reducing anti-apoptotic BCL-xL, p-AKT, and p-BAD and increasing pro-apoptotic BAX. Conversely, Dox-induced CD133 expression diminished apoptosis in both trametinib-treated cell lines, coincident with elevated p-AKT, p-BAD, BCL-2, and BCL-xL and decreased activation of BAX and caspases-3 and -9. AKT1/2 siRNA knockdown or inhibition of BCL-2 family members with navitoclax (ABT-263) in BAKP-KO cells further enhanced caspase-mediated apoptotic PARP cleavage. CD133 may therefore activate a survival pathway where (1) increased AKT phosphorylation and activation induces (2) BAD phosphorylation and inactivation, (3) decreases BAX activation, and (4) reduces caspases-3 and -9 activity and caspase-mediated PARP cleavage, leading to apoptosis suppression and drug resistance in melanoma. Targeting nodes of the CD133, AKT, or BCL-2 survival pathways with trametinib highlights the potential for combination therapies for NRAS-mutant melanoma stem cells for the development of more effective treatments for patients with high-risk melanoma.     

Low-Loss Patterned Ground Shield Interconnect Transmission Lines in Advanced IC Processes

In this paper, we provide an extensive experimental and theoretical study of the benefits of patterned ground shield interconnect transmission lines over more conventional layouts in advanced integrated-circuit processes. As part of this experimental work, we present the first comparative study taken on truly differential transmission line test structures. Our experimental results obtained on transmission lines with patterned ground shields are compared against a predictive compact equivalent-circuit model. This model employs exact closed-form expressions for the inductances, and describes key performance figures such as characteristic impedance and attenuation loss with excellent accuracy     

Evaluation of the premier EHEC assay for detection of Shiga toxin-producing Escherichia coli

An enzyme-linked immunosorbent assay for the detection of Shiga toxins (Premier EHEC assay; Meridian Diagnostics, Inc.) was compared to conventional sorbitol-MacConkey culture for the recovery of enterohemorrhagic Escherichia coli. A total of 74 enteric pathogens, including 8 E. coli O157:H7 isolates, were recovered from 974 stool specimens. Two of these specimens were not tested by Premier assaying due to insufficient sample and are not considered in the data analysis. The Premier EHEC assay detected the 6 evaluable specimens which were culture positive for E. coli O157:H7 and identified an additional 10 specimens as containing Shiga toxin. Seven isolates were recovered from these 10 specimens by an immunoblot assay and were confirmed as toxin producers by a cytotoxin assay. Of these seven, four isolates were serotype O157:H7, one was O26:NM, one was O6:H-, and one was O untypeable:H untypeable. Three specimens contained Shiga toxin by both EHEC immunoassaying and cytotoxin testing; however, no cytotoxin-producing E. coli could be recovered. The sorbitol-MacConkey method had a sensitivity and a specificity of 60 and 100%, respectively, while the Premier EHEC assay had a sensitivity and a specificity of 100 and 99.7%, respectively, for E. coli O157:H7 only. The Premier EHEC assay also detected an additional 20% Shiga toxin-producing E. coli (STEC) that were non-O157:H7. Thus, the Premier EHEC assay is a sensitive and specific method for the detection of all STEC isolates. Routine use would improve the detection of E. coli O157:H7 and allow for determination of the true incidence of STEC other than O157:H7. The presence of blood in the stool and/or the ages of the patients were poor predictors of the presence of STEC. Criteria need to be determined which would allow for the cost-effective incorporation of this assay into the routine screen for enteric pathogens in high-risk individuals, especially children.     

Nicolog: A simple yet powerful cc(FD) language

In this paper, we describe Nicolog, a language with capabilities similar to recently developed constraint logic programming (CLP) languages such as CLP(BNR), clp(FD), and cc(FD). Central to Nicolog are projection constraints (PCs), a sublanguage for compiling and optimizing constraint propagation in numeric and Boolean domains. PCs are an interesting generalization of the indexical constraints introduced in cc(FD) and also found in clp(FD). Nicolog compiles a very general class of built-in constraints into equivalent sets of PCs, allowing an arbitrary mixture of integer (easily extensible to real) and Boolean operations. Nicolog also lets the user program PCs directly, making it possible to implement new sophisticated propagation procedures. We show that PCs are a simple, efficient, and flexible way to implement most of the propagation procedures possible in other FD CLP systems. These include procedures for cardinality, constructive disjunction, implication, and mixed Boolean/numeric constraints. Empirical results with a simple prototype Nicolog implementation based on the WAM architecture show it can solve hard problems with speed comparable to the fastest existing CLP systems.     

<Emphasis Type="Italic">Arabidopsis thaliana:</Emphasis> A New Test Species for Phytotoxic Bioassays

Lettuce seeds (Lactuca sativa L.) and other crop species are often used in phytotoxic bioassays that are designed to detect allelochemicals. The seeds of these species are considered ideal because they are readily available, germinate rapidly and uniformly, and are routinely used in laboratories around the world. Despite their common use, however, the seeds of these species are often not as sensitive or responsive to some phytotoxic chemicals as are the seeds of other species. While searching for a more sensitive test species for phytotoxic bioassays, the Columbia ecotype of Arabidopsis thaliana exhibited greater sensitivity to seven potent allelochemicals than did lettuce seeds, which, in some cases, did not respond at all to those substances. Sensitivity satisfies one of the criteria for selecting a test species for bioassays. We now report on the results of our study and offer additional reasons for using A. thaliana seeds.