Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval

Loss of the short arm of chromosome 1 is frequently observed in many tumor types, including melanoma. We recently localized a third melanoma susceptibility locus to chromosome band 1p22. Critical recombinants in linked families localized the gene to a 15-Mb region between D1S430 and D1S2664. To map the locus more finely we have performed studies to assess allelic loss across the region in a panel of melanomas from 1p22-linked families, sporadic melanomas, and melanoma cell lines. Eighty percent of familial melanomas exhibited loss of heterozygosity (LOH) within the region, with a smallest region of overlapping deletions (SRO) of 9 Mb between D1S207 and D1S435. This high frequency of LOH makes it very likely that the susceptibility locus is a tumor suppressor. In sporadic tumors, four SROs were defined. SRO1 and SRO2 map within the critical recombinant and familial tumor region, indicating that one or the other is likely to harbor the susceptibility gene. However, SRO3 may also be significant because it overlaps with the markers with the highest 2-point LOD score (D1S2776), part of the linkage recombinant region, and the critical region defined in mesothelioma. The candidate genes PRKCL2 and GTF2B, within SRO2, and TGFBR3, CDC7, and EVI5, in a broad region encompassing SRO3, were screened in 1p22-linked melanoma kindreds, but no coding mutations were detected. Allelic loss in melanoma cell lines was significantly less frequent than in fresh tumors, indicating that this gene may not be involved late in progression, such as in overriding cellular senescence, necessary for the propagation of melanoma cells in culture.

Modeling perceived collision risk in port water navigation

An increase in the likelihood of navigational collisions in port waters has put focus on the collision avoidance process in port traffic safety. The most widely used on-board collision avoidance system is the automatic radar plotting aid which is a passive warning system that triggers an alert based on the pilot’s pre-defined indicators of distance and time proximities at the closest point of approaches in encounters with nearby vessels. To better help pilot in decision making in close quarter situations, collision risk should be considered as a continuous monotonic function of the proximities and risk perception should be considered probabilistically. This paper derives an ordered probit regression model to study perceived collision risks. To illustrate the procedure, the risks perceived by Singapore port pilots were obtained to calibrate the regression model. The results demonstrate that a framework based on the probabilistic risk assessment model can be used to give a better understanding of collision risk and to define a more appropriate level of evasive actions.

Hierarchical modeling of perceived collision risks in port fairways

Navigational collisions are one of the major safety concerns in many seaports. Despite the extent of recent works done on port navigational safety research, little is known about harbor pilot’s perception of collision risks in port fairways. This paper uses a hierarchical ordered probit model to investigate associations between perceived risks and the geometric and traffic characteristics of fairways and the pilot attributes. Perceived risk data, collected through a risk perception survey conducted among the Singapore port pilots, are used to calibrate the model. Intra-class correlation coefficient justifies use of the hierarchical model in comparison with an ordinary model. Results show higher perceived risks in fairways attached to anchorages, and in those featuring sharper bends and higher traffic operating speeds. Lesser risks are perceived in fairways attached to shoreline and confined waters, and in those with one-way traffic, traffic separation scheme, cardinal marks and isolated danger marks. Risk is also found to be perceived higher in night.

Perceived collision risks in anchorages : a hierarchical ordered probit analysis

Navigational collisions are a major safety concern in many seaports. Despite the recent advances in port navigational safety research, little is known about harbor pilot’s perception of collision risks in anchorages. This study attempts to model such risks by employing a hierarchical ordered probit model, which is calibrated by using data collected through a risk perception survey conducted on Singapore port pilots. The hierarchical model is found to be useful to account for correlations in risks perceived by individual pilots. Results show higher perceived risks in anchorages attached to intersection, local and international fairway; becoming more critical at night. Lesser risks are perceived in anchorages featuring shoreline in boundary, higher water depth, lower density of stationary ships, cardinal marks and isolated danger marks. Pilotage experience shows a negative effect on perceived risks. This study indicates that hierarchical modeling would be useful for treating correlations in navigational safety data.

The Arabidopsis thaliana double-stranded RNA binding protein DRB1 directs guide strand selection from microRNA duplexes

In Arabidopsis thaliana (Arabidopsis), DICER-LIKE1 (DCL1) functions together with the double-stranded RNA binding protein (dsRBP), DRB1, to process microRNAs (miRNAs) from their precursor transcripts prior to their transfer to the RNA-induced silencing complex (RISC). miRNA-loaded RISC directs RNA silencing of cognate mRNAs via ARGONAUTE1 (AGO1)-catalyzed cleavage. Short interefering RNAs (siRNAs) are processed from viral-derived or transgene-encoded molecules of doublestranded RNA (dsRNA) by the DCL/dsRBP partnership, DCL4/DRB4, and are also loaded to AGO1-catalyzed RISC for cleavage of complementary mRNAs. Here, we use an artificial miRNA (amiRNA) technology, transiently expressed in Nicotiana benthamiana, to produce a series of amiRNA duplexes with differing intermolecular thermostabilities at the 5′ end of duplex strands. Analyses of amiRNA duplex strand accumulation and target transcript expression revealed that strand selection (amiRNA and amiRNA*) is directed by asymmetric thermostability of the duplex termini. The duplex strand possessing a lower 59 thermostability was preferentially retained by RISC to guide mRNA cleavage of the corresponding target transgene. In addition, analysis of endogenous miRNA duplex strand accumulation in Arabidopsis drb1 and drb2345 mutant plants revealed that DRB1 dictates strand selection, presumably by directional loading of the miRNA duplex onto RISC for passenger strand degradation. Bioinformatic and Northern blot analyses of DCL4/DRB4-dependent small RNAs (miRNAs and siRNAs) revealed that small RNAs produced by this DCL/dsRBP combination do not conform to the same terminal thermostability rules as those governing DCL1/DRB1-processed miRNAs. This suggests that small RNA processing in the DCL1/DRB1-directed miRNA and DCL4/DRB4-directed sRNA biogenesis pathways operates via different mechanisms.

Hairpin RNAs derived from RNA polymerase II and polymerase III promoter-directed transgenes are processed differently in plants

RNA polymerase III (Pol III) as well as Pol II (35S) promoters are able to drive hairpin RNA (hpRNA) expression and induce target gene silencing in plants. siRNAs of 21 nt are the predominant species in a 35S Pol II line, whereas 24- and/or 22-nucleotide (nt) siRNAs are produced by a Pol III line. The 35S line accumulated the loop of the hpRNA, in contrast to full-length hpRNA in the Pol III line. These suggest that Pol II and Pol III-transcribed hpRNAs are processed by different pathways. One Pol III transgene produced only 24-nt siRNAs but silenced the target gene efficiently, indicating that the 24-nt siRNAs can direct mRNA degradation; specific cleavage was confirmed by 59 rapid amplification of cDNA ends (RACE). Both Pol II- and Pol III-directed hpRNA transgenes induced cytosine methylation in the target DNA. The extent of methylation is not correlated with the level of 21-nt siRNAs, suggesting that they are not effective inducers of DNA methylation. The promoter of a U6 transgene was significantly methylated, whereas the promoter of the endogenous U6 gene was almost free of cytosine methylation, suggesting that endogenous sequences are more resistant to de novo DNA methylation than are transgene constructs. Published by Cold Spring Harbor Laboratory Press. Copyright © 2008 RNA Society.

Modeling of protein signaling networks in clinical proteomics

Molecular interactions that underlie pathophysiological states are being elucidated using techniques that profile proteomicend points in cellular systems. Within the field of cancer research, protein interaction networks play pivotal roles in the establishment and maintenance of the hallmarks of malignancy, including cell division, invasion, and migration. Multiple complementary tools enable a multifaceted view of how signal protein pathway alterations contribute to pathophysiological states.One pivotal technique is signal pathway profiling of patient tissue specimens. This microanalysis technology provides a proteomic snapshot at one point in time of cells directly procured from the native context of a tumor micro environment. To study the adaptive patterns of signal pathway events over time, before and after experimental therapy, it is necessary to obtain biopsies from patients before, during, and after therapy. A complementary approach is the profiling of cultured cell lines with and without treatment. Cultured cell models provide the opportunity to study short-term signal changes occurring over minutes to hours. Through this type of system, the effects of particular pharmacological agents may be used to test the effects of signal pathway inhibition or activation on multiple endpoints within a pathway. The complexity of the data generated has necessitated the development of mathematical models for optimal interpretation of interrelated signaling pathways. In combination,clinical proteomic biopsy profiling, tissue culture proteomic profiling, and mathematical modeling synergistically enable a deeper understanding of how protein associations lead to disease states and present new insights into the design of therapeutic regimens.

The complete mitochondrial genome of Spilonota lechriaspis Meyrick (Lepidoptera: Tortricidae)

We determined the nucleotide sequence of the mitochondrial genome (mtgenome) of Spilonota lechriaspis Meyrick (Lepidoptera: Tortricidae). The entire closed circular molecule is 15,368 bp and contains 37 genes with the typical gene complement and order for lepidopteran mtgenomes. All tRNAs except tRNASer(AGN) can be folded into the typical cloverleaf secondary structures. The protein-coding genes (PCGs) have typical mitochondrial start codons, with the exception of COI, which uses the unusual CGA one as is found in all other Lepidoptera sequenced to date. In addition, six of 13 PCGs harbor the incomplete termination codons, a single T. The A+T-rich region contains some conserved structures that are similar to those found in other lepidopteran mtgenomes, including a structure combining the motif 'ATAGA', a 19-bp poly(T) stretch and three microsatellite (AT)n elements which are part of larger 122+ bp macrorepeats. This is the first report of macrorepeats in a lepidopteran mtgenome.

Design of a nonlinear excitation controller using inverse filtering for transient stability enhancement

This paper proposes a nonlinear excitation controller to improve transient stability, oscillation damping and voltage regulation of the power system. The energy function of the predicted system states is used to obtain the desired flux for the next time step, which in turn is used to obtain a supplementary control input using an inverse filtering method. The inverse filtering technique enables the system to provide an additional input for the excitation system, which forces the system to track the desired flux. Synchronous generator flux saturation model is used in this paper. A single machine infinite bus (SMIB) test system is used to demonstrate the efficacy of the proposed control method using time-domain simulations. The robustness of the controller is assessed under different operating conditions.

Utilizing reactive capability of PV inverters and battery systems to improve voltage profile of a residential distribution feeder

Significant increase in installation of rooftop Photovoltaic (PV) in the Low-Voltage (LV) residential distribution network has resulted in over voltage problems. Moreover, increasing peak demand creates voltage dip problems and make voltage profile even worse. Utilizing the reactive power capability of PV inverter (RCPVI) can improve the voltage profile to some extent. Resistive caharcteristic (higher R/X ratio) limits the effectiveness of reactive power to provide voltage support in distribution network. Battery Energy Storage (BES), whereas, can store the excess PV generation during high solar insolation time and supply the stored energy back to the grid during peak demand. A coordinated algorithm is developed in this paper to use the reactive capability of PV inverter and BES with droop control. Proposed algorithm is capable to cater the severe voltage violation problem using RCPVI and BES. A signal flow is also mentioned in this research work to ensure smooth communication between all the equipments. Finally the developed algorithm is validated in a test distribution network.

A model predictive approach for community battery energy storage system optimization

This paper presents an efficient algorithm for optimizing the operation of battery storage in a low voltage distribution network with a high penetration of PV generation. A predictive control solution is presented that uses wavelet neural networks to predict the load and PV generation at hourly intervals for twelve hours into the future. The load and generation forecast, and the previous twelve hours of load and generation history, is used to assemble load profile. A diurnal charging profile can be compactly represented by a vector of Fourier coefficients allowing a direct search optimization algorithm to be applied. The optimal profile is updated hourly allowing the state of charge profile to respond to changing forecasts in load.

Axial capacity of barrette piles embedded in gravel layer

In this paper, the axial performance of two heavily instrumented barrette piles, with and without grouting, socket into gravel layer in Taipei are evaluated based on the results of pile load tests. Both piles are 44 m long with the same dimension of 0.8 by 2.7 m, installed by hydraulic long bucket. One of the piles with toe grouting was socket 6 m into gravel layer and the other pile without toe grouting was socket 3 m into gravel layer. The load versus displacement relationships at pile head, the t-z curves of upper soil layers and of bottom gravel layer, and the tip resistance versus displacement relationships are important concerns and are presented in the paper. The t-z curves interpreted from the measured data along depth are also simulated by the hyperbolic model.

An efficient forward-backward algorithm to MSDEPP including batteries and voltage control devices

Electric distribution networks are now in the era of transition from passive to active distribution networks with the integration of energy storage devices. Optimal usage of batteries and voltage control devices along with other upgrades in network needs a distribution expansion planning (DEP) considering inter-temporal dependencies of stages. This paper presents an efficient approach for solving multi-stage distribution expansion planning problems (MSDEPP) based on a forward-backward approach considering energy storage devices such as batteries and voltage control devices such as voltage regulators and capacitors. The proposed algorithm is compared with three other techniques including full dynamic, forward fill-in, backward pull-out from the point of view of their precision and their computational efficiency. The simulation results for the IEEE 13 bus network show the proposed pseudo-dynamic forward-backward approach presents good efficiency in precision and time of optimization.

Stability synthesis of power hardware-in-the-loop (PHIL) simulation

A virtual power system can be interfaced with a physical system to form a power hardware-in-the-loop (PHIL) simulation. In this scheme, the virtual system can be simulated in a fast parallel processor to provide near real-time outputs, which then can be interfaced to a physical hardware that is called the hardware under test (HuT). Stable operation of the entire system, while maintaining acceptable accuracy, is the main challenge of a PHIL simulation. In this paper, after an extended stability analysis for voltage and current type interfaces, some guidelines are provided to have a stable PHIL simulation. The presented analysis have been evaluated by performing several experimental tests using a Real Time Digital Simulator (RTDS™) and a voltage source converter (VSC). The practical test results are consistent with the proposed analysis.