CiteULike: Author Yeo

Establishing clonal cell lines with endothelial-like potential from CD9(hi), SSEA-1(-) cells in embryonic stem cell-derived embryoid bodies.

Q Lian — 2008-08-07T00:15:14-00:00

PLoS ONE, Vol. 1 (2006)

BACKGROUND: Differentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation. METHODOLOGY/PRINCIPAL FINDINGS: We describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods. Using an empirical protocol that we have previously developed to generate embryo-derived RoSH lines with endothelial potential, we first generated E-RoSH lines from mouse ESC-derived embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and E- RoSH lines have similar gene expression profiles (r2 = 0.93) while that between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted that like RoSH cells, E-RoSH cells have an increased propensity to differentiate into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas and differentiate efficiently into endothelial-like cells in vivo and in vitro. Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are CD9(hi), SSEA-1(-) while ESCs are CD9(lo), SSEA-1(+). Isolation of CD9(hi), SSEA-1(-) cells that constituted 1%-10% of EB-derived cultures generated an E-RoSH-like culture with an identical E-RoSH-like gene expression profile (r2 = 0.95) and a propensity to differentiate into endothelial-like cells. CONCLUSIONS: By combining empirical and rational evidence-based methods, we identified definitive selectable surface antigens for the isolation and propagation of lineage-restricted stem cells with endothelial-like potential from mouse ESCs.

Source and Drain Series Resistance Reduction for N-Channel Transistors Using Solid Antimony (Sb) Segregation (SSbS) During Silicidation

HS Wong — 2008-08-07T12:16:43-00:00

Electron Device Letters, IEEE, Vol. 29, No. 7. (2008), pp. 756-758.

<para> We report the first integration of a novel solid Antimony (Sb) segregation (SSbS) process in a transistor fabrication flow. A thin solid Sb layer, which acts as a large source of n-type dopants, was deposited beneath a metallic nickel layer prior to source–drain silicidation. Following nickel silicidation, a very high concentration of Sb was incorporated at the NiSi/Si interface. The SSbS process is demonstrated to reduce the effective Schottky barrier (SB) height and parasitic series resistance in an n-channel field-effect transistor, leading to enhanced drive current performance without degradation in the <emphasis emphasistype="smcaps">OFF </emphasis>-state leakage current. Performance enhancement is also maintained when the supply voltage is reduced from 1.3 to 0.8 V. </para>

Novel Nickel Silicide Contact Technology Using Selenium Segregation for SOI N-FETs With Silicon–Carbon Source/Drain Stressors

HS Wong — 2008-08-07T12:01:38-00:00

Electron Device Letters, IEEE, Vol. 29, No. 8. (2008), pp. 841-844.

<para> We explore a novel silicide contact technology for effective Schottky barrier height <formula formulatype="inline"><tex Notation="TeX">$Phi_rm Bn$</tex></formula> and contact resistance reduction, which is compatible with an advanced silicon–carbon <formula formulatype="inline"><tex Notation="TeX">$(hboxSi_1 - x hboxC_x)$</tex></formula> source/drain (S/D) stressor technology. The new silicide contact technology incorporates selenium (Se) that is coimplanted with S/D dopants into the silicon–carbon S/D prior to nickel silicidation, leading to the segregation of Se at the <formula formulatype="inline"><tex Notation="TeX">$hboxNiSi:C/n-Si_0.99 hboxC_0.01$</tex></formula> interface and the achievement of excellent ohmic contact characteristics. We demonstrate that the Se-coimplantation process contributes to a 23% drive current enhancement in a strained silicon-on-insulator n-MOSFET. The enhancement is attributed to the decrease of external series resistance which is primarily due to the reduction of silicide contact resistance. </para>

Novel Nickel-Alloy Silicides for Source/Drain Contact Resistance Reduction in N-Channel Multiple-Gate Transistors with Sub-35nm Gate Length

RTP Lee — 2008-08-07T11:48:43-00:00

Electron Devices Meeting, 2006. IEDM '06. International (2006), pp. 1-4.

In this work, we examined the Schottky-barrier height modulation of NiSi by the incorporation of aluminum (Al), titanium (Ti), erbium (Er), and ytterbium (Yb) in NiSi to form different NiSi-alloys. Among the NiSi-alloy candidates investigated, it was found that the NiAl-alloy silicide provides the most effective Schottky-barrier height lowering (~250 meV) on n-Si(001) substrates. Integration of NiAl-alloy silicides as the source and drain (S/D) silicide material for multiple-gate transistors (MuGFETs) was explored, and shown to deliver a drive current IDsat enhancement of 34% compared to MuGFETs employing NiSi S/D. We further showed that the novel NiAl-alloy silicidation process is compatible with lattice-mismatched silicon-carbon (SiC) S/D stressors. NiAl-alloy silicide is therefore a promising S/D silicide material for reducing the high parasitic series resistance in narrow fin MuGFETs for enhanced device performance

Achieving Conduction Band-Edge Schottky Barrier Height for Arsenic-Segregated Nickel Aluminide Disilicide and Implementation in FinFETs With Ultra-Narrow Fin Widths

Rinus Lee — 2008-08-07T09:09:40-00:00

Electron Device Letters, IEEE, Vol. 29, No. 4. (2008), pp. 382-385.

In this letter, we report the impact of incorporating aluminum (Al) in nickel aluminide disilcide (NiSi2 -xAIx) on the Schottky-barrier for electrons (PhiB n) in NiSi2-xAlx/Si contacts for parasitic series resistance reduction. A wide range of Al concentration was investigated, and an optimum value was obtained. Based on the optimum Al concentration, arsenic- segregated NiSi2-xAlx (As-segregated NiSi2-xAlx) contacts were shown to achieve conduction band-edge Schottky-barrier heights with PhiB n = 0.133 eV. This novel As-segregated NiSi2-xAlx contact was integrated in FinFETs with a gate length of 80 nm and a fin width (WFin) of 11 nm, demonstrating improvement in current drivability of 30% over FinFETs with As-segregated NiSi contacts. We show that these ultranarrow fins (WFin = 11 nm) can be fully silicided reliably with NiSi2-xAlx, demonstrating scalability and the smallest fully silicided Si fins reported to date. For these ultra-narrow Si fins, we have successfully alleviated the concerns of parasitic series resistance without the use of selective epitaxial raised source and drain technology.

N-channel FinFETs With 25-nm Gate Length and Schottky-Barrier Source and Drain Featuring Ytterbium Silicide

RTP Lee — 2008-08-07T09:06:34-00:00

Electron Device Letters, IEEE, Vol. 28, No. 2. (2007), pp. 164-167.

We have fabricated n-channel 25-nm gate length FinFETs with Schottky-barrier source and drain featuring a self-aligned ytterbium silicide (YbSi1.8). A low-temperature silicidation process was developed for the formation of the low electron barrier height YbSi 1.8 phase, without reaction with SiO2 isolation or SiN spacer materials, enabling integration in a CMOS fabrication process flow. The fabricated device exhibits good device characteristics with a drive current of 241 muA/mum at VDS=VGS-Vt=1 V, Ion/Ioff=104 at VDS=1.1 V, subthreshold swing of 125 mV/decade, and drain-induced barrier lowering of 0.26 V/V

5nm-gate nanowire FinFET

Fu-Liang Yang — 2008-08-06T14:32:26-00:00

VLSI Technology, 2004. Digest of Technical Papers. 2004 Symposium on (2004), pp. 196-197.

A new nanowire FinFET structure is developed for CMOS device scaling into the sub-10 nm regime. Accumulation mode P-FET and inversion mode N-FET with 5 nm and 10 nm physical gate length, respectively, are fabricated. N-FET gate delay (CV/I) of 0.22 ps and P-FET gate delay of 0.48 ps with excellent subthreshold characteristics are achieved, both with very low off leakage cur-rent less than 10 nA/ /spl mu/m. Nanowire FinFET device operation is also explored using 3-D full quantum mechanical simulation.

Cultural user interfaces: a silver lining in cultural diversity

Alvin Yeo — 2007-07-29T23:48:53-00:00

SIGCHI Bull., Vol. 28, No. 3. (July 1996), pp. 4-7.

An article that proposes the concept of Cultural User Interfaces, explains its dimensions and fleshes out the elements of CUIs from 3 different cultures, New Zealand, Malaysia and United States. These elements constitute the content metaphor of each culturally specific UI. The paper also talks about strategies and benefits of CUI.

Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells

Xi Chen — 2008-06-13T18:29:13-00:00

Cell, Vol. 133, No. 6. (13 June 2008), pp. 1106-1117.

Summary Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.

Optimising clinical practice in cancer genetics with cultural competence: lessons to be learned from ethnographic research with Chinese-Australians

Eisenbruch — 2008-07-21T16:13:33-00:00

Social Science & Medicine, Vol. 59, No. 2. (July 2004), pp. 235-248.

Hereditary cancer is about families, and clinicians and genetic counsellors need to understand the cultural beliefs of patients and families about cancer and inheritance. In the light of their kinship patterns Chinese-Australians were chosen for the present study, which aims to determine the explanatory models of inheritance, cancer, and inherited cancer, with a view to identifying the relationship between these culture-specific lay attributions and help-seeking behaviour, and to identify possible barriers to genetic counselling and testing. Qualitative ethnographically informed methodology involving semi-structured interview was used as a method to uncover latent beliefs held by the families who are represented by the subjects. In-depth interviews were conducted with 16 informants of Chinese ethnicity, who had been recruited through two major Sydney familial cancer clinics. We report the attributions of cancer in general, then on inheritance, kinship, genes and genetics and then focus on the way in which these beliefs come together around hereditary cancer. The majority of informants, despite high acculturation and belief in biomedical explanations about hereditary cancer, also acknowledged the influence of traditional family Chinese beliefs, where [`]inheritance' and [`]genetics' were related to retribution for ancestral misdeeds and offending ancestors. Extensive mismatch of attributes and beliefs were identified in those who attended the clinic and senior family members, creating barriers to optimal service utilisation. Three traditional patterns of beliefs were identified: (a) father and mother contributed in equal share to one's genetic makeup, linked to the ying-yang theory; (b) the dominance of life force (yang chi) and the shaping of genes were transmitted through the paternal line; and (c) natural and supernatural forces operated in the cause of hereditary cancer. The study provided guidance for clinical practice. Exploration and acknowledgement of family beliefs, regardless of cultural background and therefore avoiding stereotyping, can enable the clinician to work with the whole family--those who hold Western attributions, those who maintain traditional notions of genetics and inheritance, and those who incorporate both into their belief systems--and provide effective clinical services. Further ethnographic studies are needed, focusing on the Chinese groups who do not attend the clinic and those with lower acculturation and educational levels.

Cortical Folding Patterns and Predicting Cytoarchitecture

Bruce Fischl — 2008-07-16T18:00:37-00:00

Cereb. Cortex, Vol. 18, No. 8. (1 August 2008), pp. 1973-1980.

The human cerebral cortex is made up of a mosaic of structural areas, frequently referred to as Brodmann areas (BAs). Despite the widespread use of cortical folding patterns to perform ad hoc estimations of the locations of the BAs, little is understood regarding 1) how variable the position of a given BA is with respect to the folds, 2) whether the location of some BAs is more variable than others, and 3) whether the variability is related to the level of a BA in a putative cortical hierarchy. We use whole-brain histology of 10 postmortem human brains and surface-based analysis to test how well the folds predict the locations of the BAs. We show that higher order cortical areas exhibit more variability than primary and secondary areas and that the folds are much better predictors of the BAs than had been previously thought. These results further highlight the significance of cortical folding patterns and suggest a common mechanism for the development of the folds and the cytoarchitectonic fields. 10.1093/cercor/bhm225

CRAWDAD workshop 2007

Jihwang Yeo — 2008-07-14T07:23:15-00:00

SIGCOMM Comput. Commun. Rev., Vol. 38, No. 3. (July 2008), pp. 79-82.

Does this band make sense? Limits to expression based cancer studies.

Timothy K Williams — 2008-07-14T03:44:37-00:00

Cancer letters (3 July 2008)

Cancer researchers commonly employ reverse transcriptase polymerase chain reaction (RT-PCR) for gene expression analysis of cancer cells. While this technique is facile and reproducible, it is not without limitations. The human genome contains abundant nearly identical sequences (e.g. pseudogenes) to mRNA transcript sequences, which amplify when performing RT-PCR on samples with even trace amounts of genomic DNA. Such sequences include housekeeping transcripts such as beta-actin and GAPDH. This is also true for numerous gene products whose expression is altered in disease states such as cancer (e.g. pp32). Moreover, we describe that amplification of undesirable sequences is not simply avoided by designing primers spanning multiple exons. We also found that template-specific reverse transcriptase reactions lack the specificity necessary to definitively determine the sense or anti-sense orientation of an mRNA transcript. Given the above mentioned caveats and limitations of expression analysis studies, we encourage cancer investigators to test for the existence of intronless genomic sequences that are similar to the specific transcript of the gene being studied. Further, RNA samples should be completely genomic DNA-free prior to performing RT-PCR based assays. Finally, to ensure reliability of RT-PCR or array results, we recommend not utilizing the widely accepted loading controls, GAPDH and/or beta-actin.

The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians

Dasaradhi Palakodeti — 2008-07-09T16:40:03-00:00

RNA, Vol. 14, No. 6. (1 June 2008), pp. 1174-1186.

PIWI proteins are expressed in germ cells in a wide variety of metazoans, where they participate in the synthesis and function of a novel class of small RNAs called PIWI associated RNAs (piRNAs). One function of piRNAs is to preserve the integrity of the germline genome by silencing transposons, though they also participate in epigenetic and post-transcriptional gene regulation. In the planarian Schmidtea mediterranea, the PIWI proteins SMEDWI-1 and SMEDWI-2 are expressed in neoblasts and SMEDWI-2 is required for regeneration and homeostasis. Here, we identify a diverse population of [~]32-nucleotide small RNAs that strongly resemble vertebrate and insect piRNAs and map to hundreds of thousands of loci in the S. mediterranea genome. The expression of these RNAs occurs predominantly in neoblasts and is not restricted to the germline. RNAi knockdown of either SMEDWI-2 or a newly identified PIWI protein, SMEDWI-3, impairs regeneration and homeostasis and decreases the levels of both piRNAs and neoblasts. Therefore, SMEDWI-2 and SMEDWI-3 are required for piRNA expression, regeneration, and neoblast function in S. mediterranea. 10.1261/rna.1085008

Computer-Assisted Minimally Invasive Total Knee Arthroplasty Compared with Standard Total Knee Arthroplasty. A Prospective, Randomized Study

Andrew Dutton — 2008-07-09T13:36:01-00:00

J Bone Joint Surg Am, Vol. 90, No. 1. (1 January 2008), pp. 2-9.

Background: There is little information on the feasibility of computer navigation when using a minimally invasive approach for total knee arthroplasty, during which the anatomic landmarks for registration may be obscured. The purpose of the present study was to determine the radiographic accuracy of this technique and to compare the rate of functional recovery between patients who underwent computer-assisted minimally invasive arthroplasty and those who underwent conventional total knee arthroplasty. Methods: One hundred and eight consecutive patients were randomized to undergo computer-assisted minimally invasive total knee arthroplasty or conventional total knee arthroplasty. Perioperative pain management was standardized. The clinical parameters, long-leg radiographs, and functional assessment scores were evaluated for six months postoperatively. Results: Patients who underwent computer-assisted minimally invasive total knee arthroplasty had a significantly longer operative time (by a mean of twenty-four minutes) and a significantly shorter inpatient stay (3.3 compared with 4.5 days) in comparison with those who underwent conventional arthroplasty (p [≤] 0.001). Significantly more patients in the computer-assisted minimally invasive total knee arthroplasty group were able to walk independently for more than thirty minutes at one month (p = 0.04). The percentage of patients with a coronal tibiofemoral angle within +/-3degrees of the ideal was 92% for the computer-assisted minimally invasive total knee arthroplasty group, compared with 68% for the conventional total knee arthroplasty group (p = 0.003). Conclusions: Although specific clinical parameters reflect an early increased rate of functional recovery in association with computer-assisted minimally invasive total knee arthroplasty within the first postoperative month, the main advantage of this technique over conventional total knee arthroplasty is improved postoperative radiographic alignment without increased short-term complications. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence. 10.2106/JBJS.F.01148

CRAWDAD: a community resource for archiving wireless data at Dartmouth

Jihwang Yeo — 2008-05-15T05:57:42-00:00

SIGCOMM Comput. Commun. Rev., Vol. 36, No. 2. (April 2006), pp. 21-22.

Onset of buoyancy-driven convection in a liquid-saturated cylindrical porous layer supported by a gas layer

Min Kim — 2008-06-12T18:57:54-00:00

Physics of Fluids, Vol. 20, No. 5. (2008)

The TpsB Translocator HMW1B of Haemophilus influenzae Forms a Large Conductance Channel

Guillaume Duret — 2008-05-30T23:45:25-00:00

J. Biol. Chem., Vol. 283, No. 23. (6 June 2008), pp. 15771-15778.

The Haemophilus influenzae HMW1 adhesin is secreted via the two-partner secretion pathway and requires HMW1B for translocation across the outer membrane. HMW1B belongs to the Omp85-TpsB superfamily of transporters and consists of two structural domains, a C-terminal transmembrane -barrel and an N-terminal periplasmic domain. We investigated the electrophysiological properties of the purified full-length HMW1B and the C-terminal domain using planar lipid bilayers. Both the full-length and the truncated proteins formed conductive pores with a low open probability, two well defined conductance states, and other substates. The kinetic patterns of the two conductance states were distinct, with rapid and frequent transitions to the small conductance state and occasional and more prolonged openings to the large conductance state. The channel formed by the full-length HMW1B showed selectivity for cations, which decreased when measured at pH 5.2, suggesting the presence of acidic residues in the pore. The C-terminal domain of HMW1B was less stable and required reconstitution into liposomes prior to insertion in the bilayer. It formed a channel of smaller conductance but a similar gating pattern as the full-length protein, demonstrating the ability of the last 312 C-terminal amino acids to form a pore and suggesting that the periplasmic domain is not involved in occluding the pore, nor in controlling the inherent basal kinetics of the channel. The HMW1 pro-piece containing the secretion domain, although binding to the channel with high affinity, did not induce channel opening. 10.1074/jbc.M708970200

NONCODING RNAS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM.

Xinwei Cao — 2006-07-06T14:36:10-00:00

Annu Rev Neurosci, Vol. 29 (21 July 2006), pp. 77-103.

The central nervous system (CNS) is arguably one of the most complex systems in the universe. To understand the CNS, scientists have investigated a variety of molecules, including proteins, lipids, and various small molecules. However, one large class of molecules, noncoding RNAs (ncRNAs), has been relatively unexplored. ncRNAs function directly as structural, catalytic, or regulatory molecules rather than serving as templates for protein synthesis. The increasing variety of ncRNAs being identified in the CNS suggests a strong connection between the biogenesis, dynamics of action, and combinatorial regulatory potential of ncRNAs and the complexity of the CNS. In this review, we give an overview of the diversity and abundance of ncRNAs before delving into specific examples that illustrate their importance in the CNS. In particular, we cover recent evidence for the roles of microRNAs, small nucleolar RNAs, retrotransposons, the NRSE small modulatory RNA, and BC1/BC200 in the CNS. Finally, we speculate why ncRNAs are well adapted to improving organism-environment interactions.

Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53.

Yun-Hye Jin — 2008-02-10T11:06:05-00:00

Biochem Biophys Res Commun (1 February 2008)

Sirt2 is a mammalian member of the Sirtuin family of NAD(+) (nicotinamide adenine dinucleotide)-dependent protein deacetylases. Although Sir-2.1 (a Caenorhabditis elegans Sirt2 ortholog) has been reported to interact with PAR-5/FTT-2 (a C. elegans 14-3-3 homolog), the molecular significance of the interaction between Sirt2 and 14-3-3 proteins in mammalian cell is not understood. Here, we report that Sirt2 interacts with 14-3-3 beta and gamma among various 14-3-3 isoforms, and that this interaction is strengthened by AKT. Furthermore, Sirt2 deacetylates and down-regulates the transcriptional activity of p53, and 14-3-3 beta/gamma augment deacetylation and down-regulation of the p53 transcriptional activity by Sirt2 in an AKT-dependent manner. Treatment of cells with nicotinamide, an inhibitor of Sirtuins, relieves the inhibition of p53 by Sirt2 and 14-3-3 beta/gamma. Therefore, our results suggest that the interaction between Sirt2 and 14-3-3 beta/gamma is a novel mechanism for the negative regulation of p53 beside the well-characterized Mdm2-mediated repression.

<emphasis emphasistype="italic">In Situ</emphasis> Surface Passivation and CMOS-Compatible Palladium–Germanium Contacts for Surface-Channel Gallium Arsenide MOSFETs

HC Chin — 2008-05-26T12:19:38-00:00

Electron Device Letters, IEEE, Vol. 29, No. 6. (2008), pp. 553-556.

<para> In this letter, we report a novel n-channel GaAs MOSFET featuring TaN/HfAlO/GaAs gate stack with <emphasis emphasistype="boldital">in situ</emphasis> surface passivation (vacuum anneal and silane treatment), alternative gold-free palladium–germanium (PdGe) source and drain (S/D) ohmic contacts, and silicon plus phosphorus coimplanted S/D regions. With the novel <emphasis emphasistype="boldital">in situ</emphasis> surface passivation, excellent capacitance–voltage characteristics with low-frequency dispersion and small stretch-out can be achieved, indicating low interface state density. This surface-channel GaAs device exhibits excellent transistor output characteristics with a high drain current on/off ratio of <formula formulatype="inline"><tex>$ hbox10^5$</tex> </formula> and a high peak electron mobility of 1230 <formula formulatype="inline"> <tex>$ hboxcm^2/hboxVcdothboxs$</tex></formula>. In addition, gold contamination concerning CMOS technology can be alleviated with the successful integration of low-resistance PdGe ohmic contacts. </para>

Nitrosative protein tyrosine modifications: biochemistry and functional significance.

WS Yeo — 2008-05-24T01:10:38-00:00

BMB reports, Vol. 41, No. 3. (31 March 2008), pp. 194-203.

Nitrosative modifications regulate cellular signal transduction and pathogenesis of inflammatory responses and neurodegenerative diseases. Protein tyrosine nitration is a biomarker of oxidative stress and also influences protein structure and function. Recent advances in mass spectrometry have made it possible to identify modified proteins and specific modified amino acid residues. For analysis of nitrated peptides with low yields or only a subset of peptides, affinity 'tags' can be bait for 'fishing out' target analytes from complex mixtures. These tagged peptides are then extracted to a solid phase, followed by mass analysis. In this review, we focus on protein tyrosine modifications caused by nitrosative stresses and proteomic methods for selective enrichment and identification of nitrosative protein modifications.

Molybdenum metal gate MOS technology for post-SiO2 gate dielectrics

Qiang Lu — 2008-05-21T11:01:05-00:00

Electron Devices Meeting, 2000. IEDM Technical Digest. International (2000), pp. 641-644.

Mo metal gate p-MOSFETs with several advanced gate dielectrics were fabricated. A suitable p-MOSFET work function was achieved and good device characteristics were obtained in all cases. Thermodynamic stability of Mo on Si3N4, ZrO2 and ZrSiO4 was verified by good carrier mobility agreement with the universal mobility model

Dual-metal gate technology for deep-submicron CMOS transistors

Qiang Lu — 2008-05-21T06:17:23-00:00

VLSI Technology, 2000. Digest of Technical Papers. 2000 Symposium on (2000), pp. 72-73.

Dual-metal gate CMOS devices with rapid-thermal chemical vapor deposited (RTCVD) Si3N4 gate dielectric were fabricated using a self-aligned process. The gate electrodes are Ti and Mo for the N- and P-MOSFET respectively. Carrier mobilities are comparable to that predicted by the universal mobility model for SiO2. C-V characteristics show good agreement with a simulation that takes quantum-mechanical effects into account, and clearly display the advantage of metal over poly-Si gates

A 500-Mb/s soft-output Viterbi decoder

Engling Yeo — 2008-05-16T12:02:13-00:00

Solid-State Circuits, IEEE Journal of, Vol. 38, No. 7. (2003), pp. 1234-1241.

Two eight-state 7-bit soft-output Viterbi decoders matched to an EPR4 channel and a rate-8/9 convolutional code are implemented in a 0.18-/spl mu/m CMOS technology. The throughput of the decoders is increased through architectural transformation of the add-compare-select recursion, with a small area overhead. The survivor-path decoding logic of a conventional Viterbi decoder register exchange is adapted to detect the two most likely paths. The 4-mm/sup 2/ chip has been verified to decode at 500 Mb/s with 1.8-V supply. These decoders can be used as constituent decoders for Turbo codes in high-performance applications requiring information rates that are very close to the Shannon limit.

Standards development and diffusion: A case study of RosettaNet

WF Boh — 2008-05-13T14:20:26-00:00

Communications of the ACM, Vol. 50, No. 12. (2007), pp. 57-62.

Some of the effective consortia strategies that are helpful for RosettaNet are discussed. RosettaNet has one of the biggest organizational memberships among supply-chain standards consortia. A main aspect of standards consortia strategies is to build a critical mass of adopters and to involve key players and range of stakeholders in relevant industries. The basis of the RosettaNet standard, Partner Interface Process (PIP), specifies the processes and associated business documents for data exchange among participating organizations. The people responsible for PIPs implementation are assigned to participate in the program. The people responsible for PIPs implementation in their organizations are often assigned to participate in the program. One common RosettaNet policy strategy is to gain help from the country's government. It also has adopted 'hurdle mechanisms', which solve real world problems and move standards setting quickly without compromising quality.

Content-based image retrieval in medical applications: a novel multistep approach

TM Lehmann — 2008-05-11T03:54:16-00:00

Vol. 3972 (2000), pp. 312-320.

this paper, we present an approach for content-based image retrieval in medical applications (IRMA) with particular focus on its semantic layers of information modeling, its hierarchical concept for feature representation and distance computation, and its distributed system architecture for efficient implementation. In addition, we present sample applications to show the general applicability of the concept

eMARP: Enhanced Mobile Agent for RFID Privacy Protection and Forgery Detection

Sang-Soo Yeo — 2008-05-09T20:37:06-00:00

Agent and Multi-Agent Systems: Technologies and Applications (2007), pp. 318-327.

We are sure that RFID system should be a widely used automatic identification system because of its various advantages and applications. However, many people know that invasion of privacy in RFID system is a still critical problem that makes it difficult to be used widely. Many works for solving this problem have focused on developing light-weight cryptographic modules inside of an RFID tag and building communication protocols with the reader or the back-end server. Another approach is use of proxy agents that control communications between the tag and the reader for protecting privacy. In this paper, we present an enhanced version of MARP scheme. We modified the original MARP scheme for reducing the probability of preventing attacker’s eavesdropping and for reducing the communication number of tags. And back-end servers can authenticate mobile agents more easily using public key cryptography in this scheme. Enhanced MARP scheme guarantees not only privacy protection but also forgery detection, and it only needs slight modification in the current tag hardware.

Mind Bomb Is a Ubiquitin Ligase that Is Essential for Efficient Activation of Notch Signaling by Delta

Motoyuki Itoh — 2008-05-08T15:33:58-00:00

Developmental Cell, Vol. 4, No. 1. (January 2003), pp. 67-82.

Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells.

A new supine anterolateral approach to percutaneous ultrasound-guided renal biopsy

Kevin Abbott — 2008-05-05T04:11:51-00:00

Nat Clin Pract Neph, Vol. 4, No. 5. (May 2008), pp. 244-245.

The U95 Protein of Human Herpesvirus 6B Interacts with Human GRIM-19: Silencing of U95 Expression Reduces Viral Load and Abrogates Loss of Mitochondrial Membrane Potential

WM Yeo — 2008-05-01T17:52:40-00:00

J. Virol., Vol. 82, No. 2. (15 January 2008), pp. 1011-1020.

To better understand the pathogenesis of human herpesvirus 6 (HHV-6), it is important to elucidate the functional aspects of immediate-early (IE) genes at the initial phase of the infection. To study the functional role of the HHV-6B IE gene encoding U95, we generated a U95-Myc fusion protein and screened a pretransformed bone marrow cDNA library for U95-interacting proteins, using yeast-two hybrid analysis. The most frequently appearing U95-interacting protein identified was GRIM-19, which belongs to the family of genes associated with retinoid-interferon mortality and serves as an essential component of the oxidative phosphorylation system. This interaction was verified by both coimmunoprecipitation and confocal microscopic coimmunolocalization. Short-term HHV-6B infection of MT-4 T-lymphocytic cells induced syncytial formation, resulted in decreased mitochondrial membrane potential, and led to progressively pronounced ultrastructural changes, such as mitochondrial swelling, myelin-like figures, and a loss of cristae. Compared to controls, RNA interference against U95 effectively reduced the U95 mRNA copy number and abrogated the loss of mitochondrial membrane potential. Our results indicate that the high affinity between U95 early viral protein and GRIM-19 may be closely linked to the detrimental effect of HHV-6B infection on mitochondria. These findings may explain the alternative cell death mechanism of expiration, as opposed to apoptosis, observed in certain productively HHV-6B-infected cells. The interaction between U95 and GRIM-19 is thus functionally and metabolically significant in HHV-6B-infected cells and may be a means through which HHV-6B modulates cell death signals by interferon and retinoic acid. 10.1128/JVI.01156-07

ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis

Georgia Mavria — 2008-04-25T16:27:56-00:00

Cancer Cell, Vol. 9, No. 1. (January 2006), pp. 33-44.

Summary Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase results in loss of bipolarity, detachment, and cell death of isolated endothelial cells and retraction of sprouting tubules. These effects are the consequence of upregulated Rho-kinase signaling. Transient inhibition of Rho-kinase rescues the effects of ERK-MAPK inhibition in vitro and in vivo, promotes sprouting, and increases vessel length in tumors. We propose a regulatory role of Rho-kinase by ERK-MAPK during angiogenesis that acts through the control of actomyosin contractility. Our data delineate a mechanism by which ERK-MAPK promotes endothelial cell survival and sprouting by downregulating Rho-kinase signaling.

Cluster Computing: High-Performance, High-Availability, and High-Throughput Processing on a Network of Computers

Chee Yeo — 2008-04-24T17:10:51-00:00

Handbook of Nature-Inspired and Innovative Computing (2006), pp. 521-551.

Optical study of implantation damage recovery from Si-implanted GaN

James Fellows — 2008-04-24T05:34:14-00:00

Solid State Communications, Vol. 133, No. 4. (January 2005), pp. 213-217.

Comprehensive and systematic optical activation studies of Si-implanted GaN grown on sapphire substrates have been made as a function of ion dose and anneal temperature. Silicon ions were implanted at 200 keV with doses ranging from 1×1013 to 5×1015 cm-2 at room temperature. The samples were proximity cap annealed from 1250 to 1350 °C with a 500-A-thick AlN cap in a nitrogen environment. The results of photoluminescence measurements made at 3 K show a very sharp neutral-donor-bound exciton peak along with a sharp donor-acceptor pair peak after annealing at 1350 °C for 20 s, indicating excellent implantation damage recovery. The results also indicate the AlN cap protected the implanted GaN layer very well during high temperature annealing without creating any significant anneal-induced damage. This observation is consistent with the electrical activation results for these samples.

SIMS backside depth profiling of ultra shallow implants

KL Yeo — 2008-04-24T04:52:30-00:00

Applied Surface Science, Vol. 203-204 (15 January 2003), pp. 335-338.

In secondary ion mass spectrometry depth profiling, a more accurate junction depth can be acquired by sputtering from the backside of the wafer [J. Vac. Sci. Technol. B 16 (1) (1998) 298]. This technique takes advantage of the better depth resolution of the leading edge as compared to the trailing edge [Nucl. Instrum. Meth. B 47 (1990) 223]. By using silicon-on-insulator (SOI) wafers, we have developed a backside depth profiling technique for studying ultra shallow implants. The abrupt interface of the SOI wafer and the large selectivity in chemical etching result in smooth after-etched surfaces, which facilitate high resolution SIMS profiling. The true dopant distribution of B 1 keV implants was studied by performing front and backside depth profiling using SOI substrates. The 7.5 and 0.5 keV O2+ primary ions were used at oblique incidence in a Cameca IMS-6f, with and without oxygen flooding and sample rotation. The effectiveness of backside SIMS profiling of the ultra shallow dopant implants using SOI substrates is evaluated.

Multistage Hierarchical Optimization for Land Use Allocation to Control Nonpoint Source Water Pollution

In Yeo — 2008-04-22T10:08:39-00:00

Managing Watersheds for Human and Natural Impacts, Vol. 178, No. 40763. (2005), pp. 74-74.

To effectively and systematically analyze this complex spatial watershed system, a hierarchical optimization approach is proposed. A top-down land allocation scheme is applied to determine an optimal land allocation, and then to identify spatial locations of protected lands at a high level of spatial resolution (30 m cell). At the top level, the stormwater runoff simulation model is used to generate peak discharge pseudo data, that are input to a regression analysis, where the functional relationship between peak discharge and land-use variables is approximated as a quadratic function (R2=0.98%). This function is then used in an optimization model to allocate future land uses (urban, conservation, and agriculture at the subwatershed/catchement level), in a way that minimizes the resulting peak discharge at the watershed outlet. Then, an integrated hydrological-land use optimization (IHLUO) model scheme is developed to (1) investigate the NPS pollution generation/transport mechanisms and spatial variability/interdependencies of land use change impacts on watershed hydrology, (2) systematically evaluate different land-use patterns and their response to rainfall, and (3) search for the optimal land-use pattern at the cell level. The results are very promising, with a 44% reduction of the peak discharge rate as compared to the rate corresponding to the current land-use pattern. The most downstream and upstream areas are to be protected with more conservation, and most urban activities are allocated to the minimal impact subwatershed. Sensitivity analyses are performed and suggest maintaining at least 30% of the land in a conservation state, developing no more than 12% for urban purposes, and no more than 70% for agricultural purposes. The proposed methodology is applied to the Old Woman Creek watershed, located in the southwestern basin of Lake Erie (Ohio).

Virtual navigation in humans: the impact of age, sex, and hormones on place learning

Ira Driscoll — 2008-04-16T16:30:00-00:00

Hormones and Behavior, Vol. 47, No. 3. (March 2005), pp. 326-335.

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.

Evaluation of the statistical power for multiple tests: a case study.

Adeline Yeo — 2008-04-14T04:20:20-00:00

Pharmaceutical statistics (31 March 2008)

It is challenging to estimate the statistical power when a complicated testing strategy is used to adjust for the type-I error for multiple comparisons in a clinical trial. In this paper, we use the Bonferroni Inequality to estimate the lower bound of the statistical power assuming that test statistics are approximately normally distributed and the correlation structure among test statistics is unknown or only partially known. The method was applied to the design of a clinical study for sample size and statistical power estimation. Copyright (c) 2008 John Wiley & Sons, Ltd.

Resolving rightful ownerships with invisible watermarking techniques: limitations, attacks, and implications

S Craver — 2008-04-02T07:22:41-00:00

Selected Areas in Communications, IEEE Journal on, Vol. 16, No. 4. (1998), pp. 573-586.

Digital watermarks have been proposed as a means for copyright protection of multimedia data. We address the capability of invisible watermarking schemes to resolve copyright ownership. We show that, in certain applications, rightful ownership cannot be resolved by current watermarking schemes alone. Specifically, we attack existing techniques by providing counterfeit watermarking schemes that can be performed on a watermarked image to allow multiple claims of rightful ownership. In the absence of standardization and specific requirements imposed on watermarking procedures, anyone can claim ownership of any watermarked image. In order to protect against the counterfeiting techniques that we develop, we examine the properties necessary for resolving ownership via invisible watermarking. We introduce and study invertibility and quasi-invertibility of invisible watermarking techniques. We propose noninvertible watermarking schemes, and subsequently give examples of techniques that we believe to be nonquasi-invertible and hence invulnerable against more sophisticated attacks proposed in the paper. The attacks and results presented in the paper, and the remedies proposed, further imply that we have to carefully reevaluate the current approaches and techniques in invisible watermarking of digital images based on application domains, and rethink the promises, applications and implications of such digital means of copyright protection

Pancreaticoduodenectomy in the very elderly.

MA Makary — 2008-04-01T20:39:48-00:00

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Vol. 10, No. 3. (March 2006), pp. 347-356.

It is estimated that by 2050, there will be a 300% increase in the elderly population (> or =65 years) and a corresponding increase in elderly patients presenting for surgical evaluation. Surgical decision-making in this population can be difficult because outcomes in the elderly are poorly defined. We reviewed 2698 consecutive pancreaticoduodenectomies (PDs) at our institution over a 35-year period (April 1970 through March 2005), with the last 1000 resections being done in the last 4 years. Data collected included surgical indication, mortality (defined as 30-day or in-hospital mortality), complications, and survival. Patients were divided by age into three groups (<80, 80-89, and > or =90 years) and evaluated using multiple logistic regression. Two hundred seven patients > or =80 years old underwent a PD (7.7% of 2698). Patients 80-89 years of age had a mortality rate of 4.1% (8 of 197) and a complication rate of 52.8% (99 of 197), whereas patients < or =79 years of age had a mortality of 1.7% and a complication rate of 41.6% (P < 0.05). There were no perioperative deaths among the 10 patients > or =90 years of age, and their complication rate was 50% (5 of 10). One-year survival for patients 80-89 years of age was 59.1%, and that for patients > or =90 years was 60%. Age was not an independent risk factor for perioperative mortality and morbidity following PD after adjusting for preoperative comorbidities. We demonstrate that PD can be safely performed in patients over 80 years of age and conclude that age alone should not be a contraindication to pancreatic resection. The advent of improved surgical outcomes and an aging population will likely result in a significant increase in the number of PDs performed in the next few decades.

Semiotics and agents for integrating and navigating through multimedia representations of concepts

Dan Joyce — 2008-03-24T01:27:23-00:00

Storage and Retrieval for Media Databases 2000, Vol. 3972, No. 1. (1999), pp. 120-131.

The purpose of this paper is two-fold. We begin by exploring the emerging trend to view multimedia information in terms of low-level and high-level components; the former being feature-based and the latter the 'semantics' intrinsic to what is portrayed by the media object. Traditionally, this has been viewed by employing analogies with generative linguistics. Recently, a new perceptive based on the semiotic tradition has been alluded to in several papers. We believe this to be a more appropriate approach. From this, we propose an approach for tackling this problem which uses an associative data structure expressing authored information together with intelligent agents acting autonomously over this structure. We then show how neural networks can be used to implement such agents. The agents act as 'vehicles' for bridging the gap between multimedia semantics and concrete expressions of high-level knowledge, but we suggest that traditional neural network techniques for classification are not architecturally adequate.

Using audio and video features to classify the most dominant person in a group meeting

Hayley Hung — 2008-03-22T20:59:13-00:00

(2007), pp. 835-838.

Contribution of HIF-1α or HIF-2α to erythropoietin expression: in vivo evidence based on chromatin immunoprecipitation

Eun-Jin Yeo — 2008-03-07T12:22:43-00:00

Annals of Hematology, Vol. 87, No. 1. (21 January 2008), pp. 11-17.

Abstract Circulating erythropoietin (EPO) is mainly produced by the kidneys and mediates erythrogenesis in bone marrow and nonhematopoietic cell survival. EPO is also produced in other tissues where it functions as a paracrine. Moreover, the hypoxic induction of EPO is known to be mediated by HIF-1α and HIF-2α, but it remains obscure as to which of these two mediators mainly contributes to EPO expression. Thus, we designed in vivo experiments to evaluate the contributions made by HIF-1α and HIF-2α to EPO expression. In mice exposed to mild whole body hypoxia, HIF-1α and HIF-2α were both induced in all tissues examined. However, EPO mRNA was expressed in kidney and brain, but not in liver and lung. Likewise, chromatin immunoprecipitation (CHIP) analyses demonstrated that HIF-1α or HIF-2α binding to the EPO gene increased under hypoxic conditions only in kidney and brain. A comparison of CHIP data and EPO mRNA levels suggested that, during mild hypoxia, renal EPO transcription is induced equally by HIF-1α and HIF-2α, but that brain EPO is mainly induced during hypoxia by HIF-2α. Thus, HIF-1α and HIF-2α appear to contribute to EPO expression tissue specifically.

A generalized finite-difference (GFD) ALE scheme for incompressible flows around moving solid bodies on hybrid meshfree-Cartesian grids

CS Chew — 2007-08-01T12:45:16-00:00

Journal of Computational Physics, Vol. 218, No. 2. (1 November 2006), pp. 510-548.

A scheme using the mesh-free generalized finite differencing (GFD) on flows past moving bodies is proposed. The aim is to devise a method to simulate flow past an immersed moving body that avoids the intensive remeshing of the computational domain and minimizes data interpolation associated with the established computational fluid methodologies; as such procedures are time consuming and are a significant source of error in flow simulation. In the present scheme, the moving body is embedded and enveloped by a cloud of mesh-free nodes, which convects with the motion of the body against a background of Cartesian nodes. The generalized finite-difference (GFD) method with weighted least squares (WLS) approximation is used to discretize the two-dimensional viscous incompressible Navier-Stokes equations at the mesh-free nodes, while standard finite-difference approximations are applied elsewhere. The convecting motion of the mesh-free nodes is treated by the Arbitrary Lagrangian-Eulerian (ALE) formulation of the flow equations, which are solved by a second-order Crank-Nicolson based projection method. The proposed numerical scheme was tested on a number of problems including the decaying-vortex flow, external flows past moving bodies and body-driven flows in enclosures.

Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum

Daniel Kohane — 2008-02-11T21:51:30-00:00

Journal of Biomedical Materials Research Part A, Vol. 77A, No. 2. (2006), pp. 351-361.

Drug delivery to the peritoneum is hampered by rapid clearance, and could be improved by application of controlled release technology. We investigated the suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co-glycolic) acid (PLGA), a biodegradable polymer with generally excellent biocompatibility commonly used for controlled drug release. We injected 90 kDa PLGA microparticles, 5-250 ?m in diameter, into the murine peritoneum, in dosages of 10-100 mg (n = 3-5 per group). We found a high incidence of polymeric residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-?m microparticles caused adhesions in 83% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles >5 ?m in diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma irradiated) caused fewer adhesions (16.7%) with a similar incidence of residue. Nanoparticles (265 nm) of 90 kDa PLGA also caused much fewer adhesions (6.3% of animals), possibly because they were cleared from the peritoneum within 2 days, and sequestered in the spleen and liver, where foamy macrophages were noted. The effect of sterilization technique on the incidence of adhesion formation is also studied. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

Inference of splicing regulatory activities by sequence neighborhood analysis.

MB Stadler — 2008-02-25T21:24:40-00:00

PLoS Genet, Vol. 2, No. 11. (24 November 2006)

Sequence-specific recognition of nucleic-acid motifs is critical to many cellular processes. We have developed a new and general method called Neighborhood Inference (NI) that predicts sequences with activity in regulating a biochemical process based on the local density of known sites in sequence space. Applied to the problem of RNA splicing regulation, NI was used to predict hundreds of new exonic splicing enhancer (ESE) and silencer (ESS) hexanucleotides from known human ESEs and ESSs. These predictions were supported by cross-validation analysis, by analysis of published splicing regulatory activity data, by sequence-conservation analysis, and by measurement of the splicing regulatory activity of 24 novel predicted ESEs, ESSs, and neutral sequences using an in vivo splicing reporter assay. These results demonstrate the ability of NI to accurately predict splicing regulatory activity and show that the scope of exonic splicing regulatory elements is substantially larger than previously anticipated. Analysis of orthologous exons in four mammals showed that the NI score of ESEs, a measure of function, is much more highly conserved above background than ESE primary sequence. This observation indicates a high degree of selection for ESE activity in mammalian exons, with surprisingly frequent interchangeability between ESE sequences.

A Combinatorial Code for Splicing Silencing: UAGG and GGGG Motifs.

Kyoungha Han — 2005-05-03T09:03:19-00:00

PLoS Biol, Vol. 3, No. 5. (19 April 2005)

Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5'-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19) of the glutamate NMDA R1 receptor (GRIN1) transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes.

Inflammatory Aetiology of Human Myometrial Activation Tested Using Directed Graphs

Andrew Bisits — 2008-02-19T18:43:48-00:00

PLoS Computational Biology, Vol. 1, No. 2. (1 July 2005), e19.

There are three main hypotheses for the activation of the human uterus at labour: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from the literature to develop causal pathway models for the activation of human myometrium. The data provided quantitative RT-PCR results on key genes from samples taken before and during labour. Principal component analysis showed that pre-labour samples form a homogenous group compared to those during labour. We therefore modelled the alternative causal pathways in non-labouring samples using directed graphs and statistically compared the likelihood of the different models using structural equations and D-separation approaches. Using the computer program LISREL, inflammatory activation as a primary event was highly consistent with the data (p = 0.925), progesterone withdrawal, as a primary event, is plausible (p = 0.499), yet comparatively unlikely, oxytocin receptor mediated initiation is less compatible with the data (p = 0.091). DGraph, a software program that creates directed graphs, produced similar results (p = 0.684, p = 0.280, and p = 0.04, respectively). This outcome supports an inflammatory aetiology for human labour. Our results demonstrate the value of directed graphs in determining the likelihood of causal relationships in biology in situations where experiments are not possible.

Comprehensive mathematical simulation of functional magnetic resonance imaging time series including motion-related image distortion and spin saturation effect

Boklye Kim — 2008-02-04T17:14:08-00:00

Magnetic Resonance Imaging, Vol. 26, No. 2. (February 2008), pp. 147-159.

There has been vast interest in determining the feasibility of functional magnetic resonance imaging (fMRI) as an accurate method of imaging brain function for patient evaluations. The assessment of fMRI as an accurate tool for activation localization largely depends on the software used to process the time series data. The performance evaluation of different analysis tools is not reliable unless truths in motion and activation are known. Lack of valid truths has been the limiting factor for comparisons of different algorithms. Until now, currently available phantom data do not include comprehensive accounts of head motion. While most fMRI studies assume no interslice motion during the time series acquisition in fMRI data acquired using a multislice and single-shot echo-planar imaging sequence, each slice is subject to a different set of motion parameters. In this study, in addition to known three-dimensional motion parameters applied to each slice, included in the time series computation are geometric distortion from field inhomogeneity and spin saturation effect as a result of out-of-plane head motion. We investigated the effect of these head motion-related artifacts and present a validation of the mapping slice-to-volume (MSV) algorithm for motion correction and activation detection against the known truths. MSV was evaluated, and showed better performance in comparison with other widely used fMRI data processing software, which corrects for head motion with a volume-to-volume realignment method. Furthermore, improvement in signal detection was observed with the implementation of the geometric distortion correction and spin saturation effect compensation features in MSV.

Lot-to-lot inconsistency of anticardiolipin reagents.

DM Hoefner — 2008-01-14T08:55:43-00:00

Clin Chem, Vol. 48, No. 9. (September 2002)