bluuebunny/crossref_metadata_2025 huggingface dataset:
Proterozoic gneisses of the Malton Complex, near Valemount, British Columbia: U–Pb ages and Nd isotopic signatures
Authors: McDonough Michael R. , Parrish Randall R.
Published: April 2010

Proterozoic gneisses of the Malton Complex in the vicinity of Valemount, British Columbia, occur in a series of lithologically and structurally complex, fault-bounded slices of crystalline basement and interleaved cover. Gneisses of the Malton Complex span the Southern Rocky Mountain Trench and underlie the western part of the Rocky Mountain fold and thrust belt and the eastern part of the Omineca Belt of the Canadian Cordillera. Structural and stratigraphic relationships indicate that they formed the basement upon which an enigmatic quartzite unit and the Late Proterozoic Windermere Supergroup were deposited.The Yellowjacket and Bulldog gneisses, on the east side of the Rocky Mountain Trench, have yielded four U–Pb zircon crystallization ages of ca. 1870 Ma, with εNd(T) values of −2.6 to −3.4. The Hugh Allan gneiss, also on the east side of the trench but separated from the Yellowjacket gneiss by a major thrust fault, includes leucocratic granite gneiss having a zircon U–Pb age of [Formula: see text], which has intruded an older (undated) lithologically heterogeneous assemblage of gneiss. The basal Windermere succession of the Valemount region is inferred to be younger than ca. 740 Ma, since these intrusions are not found within the Late Proterozoic stratified rocks.Augen granitoid orthogneiss of the Malton Range on the west side of the Rocky Mountain Trench has been dated as [Formula: see text] using zircons. A second sample yields data suggesting an age between 2050 and 2100 Ma, but its interpretation is uncertain because of scatter in analyses and possible zircon inheritance. The latter sample has an εNd(T) at 1990 Ma of −2.6. Nd model ages for the Malton, Yellowjacket, and Bulldog samples range from 2.45 to 2.56 Ga, indicating that the igneous protoliths were derived from a source that probably had some component of Archean crustal material involved.The U–Pb ages and Nd model ages are quite similar to those of rocks underlying portions of Alberta and the western Canadian Shield, specifically the Fort Simpson terrane, the Great Bear magmatic zone, and parts of the Thelon–Taltson arc. This evidence, as well as structural and stratigraphic arguments, links the Malton Complex gneisses with those of the Canadian Shield, precluding their derivation by large-magnitude displacements from the southwestern United States. Structural analysis indicates that they restore to locations 100–200 km southwest of their present exposure.Structural, stratigraphic, and isotopic data indicate that the Southern Rocky Mountain Trench is not a suture.
Age and geological setting of Gold Creek gneiss, crystalline basement of the Windermere Supergroup, Cariboo Mountains, British Columbia
Authors: Murphy Donald C. , Walker R. T. , Parrish R. R.
Published: April 2010

Gold Creek gneiss, the most recently discovered body of crystalline basement in the Canadian Cordillera, is a northwest-trending granitic to dioritic orthogneiss straddling the eastern end of the Canoe River valley, near the southeastern end of the Cariboo Mountains. U–Pb geochronometry of zircons from two samples of quartz diorite orthogneiss from two separate localities yielded similar, nearly linear, discordant arrays with upper intercepts of 2.08 Ga. The patterns of discordance in both samples preclude assigning a precise age, although a date between 2.0 and 2.1 Ga is geologically reasonable.North of Canoe River, Gold Creek gneiss is inferred to be nonconformably overlain by quartzite and marble, which in turn are inferred to be unconformably overlain by a conglomerate- and diamictite-bearing unit at the base of the lower Kaza Group of the Windermere Supergroup. In contrast with other exposures of basement and cover in the area, neither contact is marked by anomalously high strain or mylonitic rocks. Gold Creek gneiss therefore represents the crystalline basement upon which the Windermere Supergroup was deposited.Gold Creek gneiss occurs in a multiply deformed domain bounded on the north by the Purcell thrust and on the east by the North Thompson – Albreda fault (NTAF), an Eocene, down-to-the-west normal fault. Gneiss and overlying Windermere Supergroup are folded by the Canoe River anticline and lie in the hanging wall of a recently identified folded, premetamorphic, southwest-vergent shear zone, the Sir Arthur Meighen thrust. The footwall consists of Mica Creek succession, a sequence of metaclastic rocks, amphibolite, and marble which is in part equivalent to the Windermere Supergroup but may include younger rocks. Hanging wall and footwall rocks and structures are folded by Early Cretaceous, synmetamorphic, northeast-vergent folds.Gold Creek and Malton gneisses are both in the hanging wall of the Purcell thrust but on opposite sides of the NTAF. Strike separation of the Purcell thrust across the NTAF suggests 0.5–4.5 km of normal displacement, affirming earlier estimates of displacement based on geobarometry. This amount of displacement and the consideration that Gold Creek gneiss is thrust over Mica Creek succession, which structurally overlies Malton gneiss along Malton décollement, preclude the interpretation that Gold Creek and Malton gneisses were physically continuous prior to displacement on the NTAF. It is more likely that Gold Creek gneiss lies in the hanging wall of Malton décollement and would restore an unknown distance to the southwest along it. Gold Creek gneiss also lies in the hanging wall of Monashee décollement and would restore at least as far southwest as the western edge of Monashee Complex, or over 100 km.
OPTIMAL TESTING RESOURCE ALLOCATION FOR MODULAR SOFTWARE CONSIDERING COST, TESTING EFFORT AND RELIABILITY USING GENETIC ALGORITHM
Authors: KAPUR P. K. , AGGARWAL ANU. G. , KAPOOR KANICA , KAUR GURJEET
Published: April 2010

The demand for complex and large-scale software systems is increasing rapidly. Therefore, the development of high-quality, reliable and low cost computer software has become critical issue in the enormous worldwide computer technology market. For developing these large and complex software small and independent modules are integrated which are tested independently during module testing phase of software development. In the process, testing resources such as time, testing personnel etc. are used. These resources are not infinitely large. Consequently, it is an important matter for the project manager to allocate these limited resources among the modules optimally during the testing process. Another major concern in software development is the cost. It is in fact, profit to the management if the cost of the software is less while meeting the costumer requirements. In this paper, we investigate an optimal resource allocation problem of minimizing the cost of software testing under limited amount of available resources, given a reliability constraint. To solve the optimization problem we present genetic algorithm which stands up as a powerful tool for solving search and optimization problems. The key objective of using genetic algorithm in the field of software reliability is its capability to give optimal results through learning from historical data. One numerical example has been discussed to illustrate the applicability of the approach.
ROUTING PATH OPTIMIZAION TO MAXIMIZE THE LIFETIME OF WIRELESS SENSOR NETWORK
Authors: MANJUNATHA P. , VERMA A. K. , SRIVIDYA A.
Published: April 2010

Wireless sensor network (WSN) consists of a large number of sensor nodes which are able to sense their environment and communicate with each other using wireless interface. However these sensor nodes are constrained in energy capacity. The lifetimes of sensor node and sensor network mainly depends upon these energy resources. To increase the life time of sensor network, many approaches have been proposed to optimize the energy usage. All these proposed protocols mainly use minimum hop or minimum energy path. Continuously using the shortest path will deplete energy of the nodes at a much faster rate and causes network partition. This paper proposes an energy efficient routing protocol to extend the network lifetime for delay constrained network. Each sensor node selects the optimized path for forwarding packets to the base station based on routing metrics. Proposed studies and simulation results shows that the protocol put forward in the paper can achieve higher network lifetime by striking a balance between the delay and power consumption in comparison to other routing protocols.
SAFETY BASED MAINTENANCE CONCEPT
Authors: PAPIC LJUBISA , ARONOV JOSEPH , PANTELIC MILORAD
Published: April 2010

Effective maintenance concept of the system has been developed and proposed on the basis of universal possible usages analysis of corrective, periodically preventive, predictive, proactive and safety based maintenance concepts in modern conditions. Starting from certain advantages and disadvantages of each concept, effective maintenance concept of the system was reached by balanced approach, i.e. their appropriate combination. However, it has been indicated that traditionally used systems reliability characteristics are not sufficient for complete description of their effectiveness. It was established as a reason that reliability characteristics do not indicate function disturbance level during system operation. It is suggested on new safety assess indicators adoption in system operation stage based on disturbance sequence modeling. It is very important that inappropriate maintenance concept must not put under question safety, i.e. cause system accident condition. Any accident condition would result with staff health and life threats and great economical losses through reengineering and system launch costs. Because of that safety based maintenance concept was consided in this work.
RESIDENTIAL CUSTOMERS' OUTAGE COST ANALYSIS FOR URBAN AND SEMI-URBAN AREAS IN A DEVELOPING COUNTRY
Authors: KARKI NAVA RAJ , VERMA AJIT KUMAR , KARKI RAJESH , MISHRA ARBIND KUMAR
Published: April 2010

This paper discusses cost of unreliability of electricity supply to the residential customers. Electricity supply outage cost is evaluated by customers' survey technique for urban and semi-urban residential areas of a developing country. The energy consumption pattern of urban and sub-urban areas is determined. Electricity supply outage cost is evaluated using both preparatory action approach and contingent valuation method. A detailed breakdown of customer's average outages costs for a entire day based on 8 three-hourly time durations are obtained that give easily understandable figures to the utilities. The power consumption pattern obtained are in close agreement with the utility's load curve. A MATLAB based computer program using Least Square Error Approximation is used to evaluate the outage cost.
A SOFT-LINK SPECTRAL MODEL FOR LINK PREDICTION
Authors: CELIKYILMAZ ASLI
Published: April 2010

Unsupervised spectral clustering methods can yield good performance when identifying crisp clusters with low complexity since the learning algorithm does not rely on finding the local minima of an objective function and rather uses spectral properties of the graph. Nonetheless, the performance of such approaches are usually affected by their uncertain parameters. Using the underlying structure of a general spectral clustering method, in this paper a new soft-link spectral clustering algorithm is introduced to identify clusters based on fuzzy k-nearest neighbor approach. We construct a soft weight matrix of a graph by identifying the upper and lower boundaries of learning parameters of the similarity function, specifically the fuzzifier parameter (fuzziness) of the Fuzzy k-Nearest Neighbor algorithm. The algorithm allows perturbations on the graph Laplace during the learning stage by the changes on such learning parameters. With the empirical analysis using an artificial and a real textual entailment dataset, we demonstrate that our initial hypothesis of implementing soft links for spectral clustering can improve the classification performance of final outcome.
EFFECTIVE AND EFFICIENT VIDEO HIGH-LEVEL SEMANTIC RETRIEVAL USING ASSOCIATIONS AND CORRELATIONS
Authors: LIN LIN , SHYU MEI-LING
Published: April 2010

Two important approaches in multimedia information retrieval are classification and the ranking of the retrieved results. The technique of performing classification using Association Rule Mining (ARM) has been utilized to detect the high-level features from the video, taking advantages of its high efficiency and accuracy. Motivated by the fact that the users are only interested in the top-ranked relevant results, ranking strategies have been adopted to sort the retrieved results. In this paper, an effective and efficient video high-level semantic retrieval framework that utilizes associations and correlations to retrieve and rank the high-level features is developed. The n-feature-value pair rules are generated using a combined measure based on (1) the existence of the (n - 1)-feature-value pairs, where n is larger than 1, (2) the correlation between different n-feature-value pairs and the concept classes through Multiple Correspondence Analysis (MCA), and (3) the similarity representing the harmonic mean of the inter-similarity and intra-similarity. The final association classification rules are selected by using the calculated similarity values. Then our proposed ranking process uses the scores that integrate the correlation and similarity values to rank the retrieved results. To show the robustness of the proposed framework, experiments with 15 high-level features (concepts) and benchmark data sets from TRECVID and comparisons with 6 other well-known classifiers are presented. Our proposed framework achieves promising performance and outperforms all the other classifiers. Moreover, the final ranked retrieved results are evaluated by the mean average precision measure, which is commonly used for performance evaluation in the TRECVID community.
The role of spermidine/spermine N1-acetyltransferase in endotoxin-induced acute kidney injury
Authors: Zahedi Kamyar , Barone Sharon , Kramer Debora L. , Amlal Hassane , Alhonen Leena , Jänne Juhani , Porter Carl W. , Soleimani Manoocher
Published: April 2010

The expression of catabolic enzymes spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMO) increases after ischemic reperfusion injury. We hypothesized that polyamine catabolism is upregulated and that this increase in catabolic response contributes to tissue damage in endotoxin-induced acute kidney injury (AKI). SSAT mRNA expression peaked at threefold 24 h following LPS injection and returned to background levels by 48 h. The activity of SSAT correlated with its mRNA levels. The expression of SMO also increased in the kidney after LPS administration. Serum creatinine levels increased significantly at ∼15 h, peaking by 24 h, and returned to background levels by 72 h. To test the role of SSAT in endotoxin-induced AKI, we injected wild-type (SSAT-wt) and SSAT-deficient (SSAT-ko) mice with LPS. Compared with SSAT-wt mice, the SSAT-ko mice subjected to endotoxic-AKI had less severe kidney damage as indicated by better preservation of kidney function. The role of polyamine oxidation in the mediation of kidney injury was examined by comparing the severity of renal damage in SSAT-wt mice treated with MDL72527, an inhibitor of both polyamine oxidase and SMO. Animals treated with MDL72527 showed significant protection against endotoxin-induced AKI. We conclude that increased polyamine catabolism through generation of by-products of polyamine oxidation contributes to kidney damage and that modulation of polyamine catabolism may be a viable approach for the treatment of endotoxin-induced AKI.
The Influence of the Consistency of Postsaccadic Visual Errors on Saccadic Adaptation
Authors: Havermann Katharina , Lappe Markus
Published: April 2010

The saccadic system is a prime example of motor control without continuous visual feedback. These systems suffer from a strong vulnerability against disturbances. The mechanism of saccadic adaptation allows adjustment of saccades to alterations arising not only from anatomical changes but also from external changes. The weighting of errors according to their reliability provides a strong benefit for an optimized control system. Thus the consistency of visual error should influence the characteristics of adaptation. In the typical adaptation paradigm a visual error is introduced by stepping the target during the saccade by a given amount. In this paradigm, the retinal error varies with the accuracy of the saccade and the step size. To study the influence of error consistency we use a variant of the adaptation paradigm which allows to specify a constant error size. Intrasaccadic target step sizes were calculated with respect to the predicted landing position of each individual saccade. The consistency of the visual error was varied by introducing different levels of noise to the intrasaccadic target step. Different mean intrasaccadic target step sizes were examined: positive target step, negative target step, and a condition in which the mean of the error distribution was clamped to the fovea. In all three conditions saccadic adaptation was strongest when the error was consistent and became weaker as the error became more variable. These results show that saccadic adaptation takes not only the average error but also the consistency of the error into account.
Sensory Modulation of Locomotor-Like Membrane Oscillations in Hb9-Expressing Interneurons
Authors: Hinckley Christopher A. , Wiesner Eric P. , Mentis George Z. , Titus David J. , Ziskind-Conhaim Lea
Published: April 2010

The central pattern generator can generate locomotor-like rhythmic activity in the spinal cord in the absence of descending and peripheral inputs, but the motor pattern is regulated by feedback from peripheral sensory inputs that adjust motor outputs to external stimuli. To elucidate the possible role of Hb9-expressing interneurons (Hb9 INs) in the locomotor circuitry, we investigated whether their induced oscillatory activity is modulated by low-threshold afferents in the isolated spinal cords of neonatal Hb9:eGFP transgenic mice. Low-intensity stimulation of segmental afferents generated short-latency, monosynaptic excitatory responses in 62% of Hb9 INs. These were associated with longer-latency (∼13 ms) excitatory postsynaptic currents that were evoked in all Hb9 INs, probably by slow conducting afferents that synapse directly onto them. Concomitant morphological analysis confirmed that afferent axons with immunoreactive expression of vesicular glutamate transporter-1 and parvalbumin, presumably from primary afferents, contacted somata and dendrites of all Hb9 INs. Most of the putative synaptic contacts were on distal dendrites that extended to an area with profuse afferent projections. We next examined whether low-threshold afferents in upper (flexor-related) and lower (extensor-related) lumbar segments altered the timing of neurochemically induced locomotor-like rhythms in Hb9 INs and motoneurons. Excitation of flexor-related afferents during the flexor phase delayed the onset of subsequent cycles in both Hb9 INs and segmental motoneurons while maintaining the phase relationship between them. The in-phase correlation between voltage oscillations in Hb9 INs and motor bursts also persisted during the two- to threefold increase in cycle period triggered by extensor-related afferents. Our findings that low-threshold, presumably muscle afferents, synapse directly onto these interneurons and perturb their induced locomotor-like membrane oscillations in a pattern that remains phase-locked with motor bursts support the hypothesis that Hb9 INs are part of the sensorimotor circuitry that regulates the pattern of locomotor rhythms in the isolated cord.
Probing With and Into Fingerprints
Authors: Dahiya Ravinder S. , Gori Monica
Published: April 2010

A recent report by Scheibert et al. highlights the role of fingerprints in enhancing tactile sensitivity. By scanning a surface with a biometric force sensor they demonstrate the dominance of the frequencies that fall within the optimal sensitivity range of Pacinian afferents. The sensor, in this study, has a soft cover patterned with parallel ridges—mimicking the fingerprints. However, the skin structure is quite complex. Elasticity of the skin varies with depth and the ridge like pattern is comprised of not just papillary ridges or fingerprints. Besides fingerprints there exist intermediate ridges, positioned exactly under the papillary ridges, and limiting ridges at dermis-epidermis junction. These structures are usually considered as single unit. If so, it is important to revisit and see if the role of fingerprints remains the same, should the sensor cover have both fingerprints and intermediate ridges.
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
Authors: De Strooper Bart
Published: April 2010

Alzheimer disease is characterized by the accumulation of abnormally folded protein fragments, i.e., amyloid beta peptide (Aβ) and tau that precipitate in amyloid plaques and neuronal tangles, respectively. In this review we discuss the complicated proteolytic pathways that are responsible for the generation and clearance of these fragments, and how disturbances in these pathways interact and provide a background for a novel understanding of Alzheimer disease as a multifactorial disorder. Recent insights evolve from the static view that the morphologically defined plaques and tangles are disease driving towards a more dynamic, biochemical view in which the intermediary soluble Aβ oligomers and soluble tau fragments are considered as the main mediators of neurotoxicity. The relevance of proteolytic pathways, centered on the generation and clearance of toxic Aβ, on the cleavage and nucleation of tau, and on the general proteostasis of the neurons, then becomes obvious. Blocking or stimulating these pathways provide, or have the potential to provide, interesting drug targets, which raises the hope that we will be able to provide a cure for this dreadful disorder.
Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear
Authors: Pape Hans-Christian , Pare Denis
Published: April 2010

The last 10 years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate in the development and/or maintenance of human anxiety disorders. The simplicity and robustness of this learning paradigm, coupled with the fact that the underlying circuitry is evolutionarily well conserved, make it an ideal model to study the basic biology of memory and identify genetic factors and neuronal systems that regulate the normal and pathological expressions of learned fear. Critical advances have been made in determining how modified neuronal functions upon fear acquisition become stabilized during fear memory consolidation and how these processes are controlled in the course of fear memory extinction. With these advances came the realization that activity in remote neuronal networks must be coordinated for these events to take place. In this paper, we review these mechanisms of coordinated network activity and the molecular cascades leading to enduring fear memory, and allowing for their extinction. We will focus on Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses.
Dividing Genetic Computation Method for Robust Receding Horizon Control Design
Authors: Kawabe Tohru
Published: April 2010

A new robust Receding Horizon Control (RHC) design approach for the sampled-data systems is proposed. The approach is based on a dividing genetic computation of minimax optimization for a robust finite receding horizon control problem. Numerical example is given to show the effectiveness of the proposed method.
Epidemiologic Determinants Affecting Cigarette Smoking Cessation: A Retrospective Study in a National Health System (SSN) Treatment Service in Rome (Italy)
Authors: Marino Maria Giulia , Fusconi Elisabetta , Magnatta Rosanna , Panà Augusto , Maurici Massimo
Published: April 2010

This retrospective study aims to evaluate epidemiologic characteristics of patients attending stop smoking courses, based on group therapy, testing their influence on smoking cessation in univariate and multivariate model. A total of 123 patients were included in this study. Mean age was 53 (). Sixty-seven percent were women. At the end of the courses 66% of patients stopped smoking, after 12 months only 39% remained abstinent. Patients younger than 50 years statistically tended to continue smoking 6 months ( 1.49, C.I. 95%: 1.06–2.44) and 12 months ( 1.37, C.I. 95%: 1.02–2.52) after the end of the courses. A low self-confidence in quitting smoking was significantly related to continuing tobacco consumption after 6 months ( 1.84, C.I. 95%: 1.14–2.99). Low adherence to therapeutic program was statistically associated to maintenance of tobacco use at 6 months ( 1.76, C.I. 95%: 1.32–2.35) and 12 months ( 1.45, C.I. 95%: 1.11–1.88). This association was confirmed at 6 months in the analysis performed on logistic regression model ().
[Retracted] Some Properties of Fuzzy Quasimetric Spaces
Authors: Mohamad Abdul
Published: April 2010

Some properties of fuzzy quasimetric spaces are studied. We prove that the topology
induced by any ‐complete fuzzy‐quasi‐space is a ‐complete quasimetric space. We
also prove Baire′s theorem, uniform limit theorem, and second countability result for fuzzy
quasi‐metric spaces.
The Bisecting GlcNAc on N-Glycans Inhibits Growth Factor Signaling and Retards Mammary Tumor Progression
Authors: Song Yinghui , Aglipay Jason A. , Bernstein Joshua D. , Goswami Sumanta , Stanley Pamela
Published: April 2010

The branching of complex N-glycans attached to growth factor receptors promotes tumor progression by prolonging growth factor signaling. The addition of the bisecting GlcNAc to complex N-glycans by Mgat3 has varying effects on cell adhesion, cell migration, and hepatoma formation. Here, we show that Chinese hamster ovary cells expressing Mgat3 and the polyoma middle T (PyMT) antigen have reduced cell proliferation and growth factor signaling dependent on a galectin lattice. The Mgat3 gene is not expressed in virgin mammary gland but is upregulated during lactation and is expressed in mouse mammary tumor virus (MMTV)/PyMT tumors. Mice lacking Mgat3 that cannot transfer the bisecting GlcNAc to N-glycans acquire PyMT-induced mammary tumors more rapidly and have an increased tumor burden, increased migration of tumor cells, and increased early metastasis to lung. Tumors and tumor-derived cells lacking Mgat3 exhibit enhanced signaling through the Ras pathway and reduced amounts of functionally glycosylated α-dystroglycan. Constitutive overexpression of an MMTV/Mgat3 transgene inhibits early mammary tumor development and tumor cell migration. Thus, the addition of the bisecting GlcNAc to complex N-glycans of mammary tumor cell glycoprotein receptors is a cell autonomous mechanism serving to retard tumor progression by reducing growth factor signaling. Cancer Res; 70(8); 3361–71. ©2010 AACR.
Identification of a Cholangiocarcinoma-Like Gene Expression Trait in Hepatocellular Carcinoma
Authors: Woo Hyun Goo , Lee Jeong-Hoon , Yoon Jung-Hwan , Kim Chung Yong , Lee Hyo-Suk , Jang Ja June , Yi Nam-Joon , Suh Kyung-Suk , Lee Kuhn Uk , Park Eun Sung , Thorgeirsson Snorri S. , Kim Yoon Jun
Published: April 2010

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major adult liver cancers. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. Here, we applied an integrative oncogenomic approach to address the clinical and functional implications of the overlapping phenotype between these tumors. By performing gene expression profiling of human HCC, CHC, and CC, we identified a novel HCC subtype, i.e., cholangiocarcinoma-like HCC (CLHCC), which expressed cholangiocarcinoma-like traits (CC signature). Similar to CC and CHC, CLHCC showed an aggressive phenotype with shorter recurrence-free and overall survival. In addition, we found that CLHCC coexpressed embryonic stem cell–like expression traits (ES signature) suggesting its derivation from bipotent hepatic progenitor cells. By comparing the expression of CC signature with previous ES-like, hepatoblast-like, or proliferation-related traits, we observed that the prognostic value of the CC signatures was independent of the expression of those signatures. In conclusion, we suggest that the acquisition of cholangiocarcinoma-like expression traits plays a critical role in the heterogeneous progression of HCC. Cancer Res; 70(8); 3034–41. ©2010 AACR.
NKX3.1 Activates Cellular Response to DNA Damage
Authors: Bowen Cai , Gelmann Edward P.
Published: April 2010

The prostate-specific tumor suppressor homeodomain protein NKX3.1 is inactivated by a variety of mechanisms in the earliest phases of prostate carcinogenesis and in premalignant regions of the prostate gland. The mechanisms by which NKX3.1 exercises tumor suppression have not been well elucidated. Here, we show that NKX3.1 affects DNA damage response and cell survival after DNA damage. NKX3.1 expression in PC-3 prostate cancer cells enhances colony formation after DNA damage but has minimal effect on apoptosis. NKX3.1 also diminishes and regulates total cellular accumulation of γH2AX. Endogenous NKX3.1 in LNCaP cells localizes to sites of DNA damage where it affects the recruitment of phosphorylated ATM and the phosphorylation of H2AX. Knockdown of NKX3.1 in LNCaP cells attenuates the acute responses of both ATM and H2AX phosphorylation to DNA damage and their subnuclear localization to DNA damage sites. NKX3.1 expression enhances activation of ATM as assayed by autophosphorylation at serine 1981 and activation of ATR as assayed by phosphorylation of CHK1. An inherited mutation of NKX3.1 that predisposes to early prostate cancer and attenuates in vitro DNA binding was devoid of the ability to activate ATM and to colocalize with γH2AX at foci of DNA damage. These data show a novel mechanism by which a homeoprotein can affect DNA damage repair and act as a tumor suppressor. Cancer Res; 70(8); 3089–97. ©2010 AACR.
Targeted Inhibition of Replication Protein A Reveals Cytotoxic Activity, Synergy with Chemotherapeutic DNA-Damaging Agents, and Insight into Cellular Function
Authors: Shuck Sarah C. , Turchi John J.
Published: April 2010

Targeting uncontrolled cell proliferation and resistance to DNA-damaging chemotherapeutics with a single agent has significant potential in cancer treatment. Replication protein A (RPA), the eukaryotic ssDNA-binding protein, is essential for genomic maintenance and stability via roles in both DNA replication and repair. We have identified a novel small molecule that inhibits the in vitro and cellular ssDNA-binding activity of RPA, prevents cell cycle progression, induces cytotoxicity, and increases the efficacy of chemotherapeutic DNA-damaging agents. These results provide new insight into the mechanism of RPA-ssDNA interactions in chromosome maintenance and stability. This represents the first molecularly targeted eukaryotic DNA-binding inhibitor and reveals the utility of targeting a protein-DNA interaction as a therapeutic strategy for cancer treatment. Cancer Res; 70(8); 3189–98. ©2010 AACR.
Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity
Authors: Kang Tae Heung , Noh Kyung Hee , Kim Jin Hee , Bae Hyun Cheol , Lin Ken Y. , Monie Archana , Pai Sara I. , Hung Chien-Fu , Wu T.-C. , Kim Tae Woo
Published: April 2010

Tumor immune escape is a major obstacle in cancer immunotherapy, but the mechanisms involved remain poorly understood. We have previously developed an immune evasion tumor model using an in vivo immune selection strategy and revealed Akt-mediated immune resistance to antitumor immunity induced by various cancer immunotherapeutic agents. In the current study, we used microarray gene analysis to identify an Akt-activating candidate molecule overexpressed in immune-resistant tumors compared with parental tumors. X-linked lymphocyte-regulated protein pM1 (XLR) gene was the most upregulated in immune-resistant tumors compared with parental tumor cells. Furthermore, the retroviral transduction of XLR in parental tumor cells led to activation of Akt, resulting in upregulation of antiapoptotic proteins and the induction of immune resistance phenotype in parental tumor cells. In addition, we found that transduction of parental tumor cells with other homologous genes from the mouse XLR family, such as synaptonemal complex protein 3 (SCP3) and XLR-related, meiosis-regulated protein (XMR) and its human counterpart of SCP3 (hSCP3), also led to activation of Akt, resulting in the upregulation of antiapoptotic proteins and induction of immune resistance phenotype. Importantly, characterization of a panel of human cervical cancers revealed relatively higher expression levels of hSCP3 in human cervical cancer tissue compared with normal cervical tissue. Thus, our data indicate that ectopic expression of XLR and its homologues in tumor cells represents a potentially important mechanism for tumor immune evasion and serves as a promising molecular target for cancer immunotherapy. Cancer Res; 70(8); 3062–70. ©2010 AACR.
Extracellular Signal-Regulated Kinase 8–Mediated c-Jun Phosphorylation Increases Tumorigenesis of Human Colon Cancer
Authors: Xu Yan-Ming , Zhu Feng , Cho Yong-Yeon , Carper Andria , Peng Cong , Zheng Duo , Yao Ke , Lau Andy T.Y. , Zykova Tatyana A. , Kim Hong-Gyum , Bode Ann M. , Dong Zigang
Published: April 2010

Extracellular signal-regulated kinase 8 (ERK8), a recently discovered member of the mitogen-activated protein kinase protein family, has been less studied than other family members, leaving its physiologic functions mostly unknown. The biological consequences of overexpression of ERK8 in JB6 Cl41 epidermal skin cells or knockdown of ERK8 in HCT15 colorectal cancer cells was studied. Kinase assays and transient transfection experiments were performed to study the signaling pathway between ERK8 and c-Jun. We found that ERK8 is relatively highly expressed in HCT15 human colorectal cancer cells and plays an important role in the promotion and progression of colorectal cancer. ERK8 promoted neoplastic transformation, and knockdown of ERK8 in HCT15 colorectal cancer cells reduced the tumorigenic properties of these cell lines. Furthermore, a direct interaction between ERK8 and c-Jun was shown. With epidermal growth factor treatment, overexpression of ERK8 in JB6 Cl41 cells caused an increased phosphorylation of c-Jun at Ser63 and Ser73, resulting in increased activator protein-1 transactivation. In contrast, knockdown of ERK8 in HCT15 colorectal cancer cells blocked c-Jun phosphorylation. The interaction between ERK8 and c-Jun seems to increase the tumorigenic properties of HCT15 colorectal cancer cells. Thus, ERK8-regulated signaling might serve as a potential therapeutic target in colorectal cancer. Cancer Res; 70(8); 3218–27. ©2010 AACR.
Association of Fatty Acid Desaturase Gene Polymorphisms with Blood Lipid Essential Fatty Acids and Perinatal Depression among Canadian Women: A Pilot Study
Authors: Xie Lin , Innis Sheila M.
Published: April 2010

Aims: The FADS1/FADS2 gene cluster encodes Δ-5 and Δ-6 desaturase, rate-limiting enzymes in metabolism of linoleic (LA) to arachidonic (ARA) and α-linolenic to eicosapentaenoic and docosahexaenoic acid (DHA). Single nucleotide polymorphisms (SNPs) in FADS1/FADS2 contribute to variability in blood lipid fatty acids. Altered n–6 and n–3 fatty acids have been related to perinatal depression (PPD). Methods: We genotyped rs174553, rs99780, rs174575, and rs174583 in FADS1/FADS2, analyzed blood lipid fatty acids and assessed PPD risk as an Edinburgh Postnatal Depression Scale (EPDS) score ≧10 for 69 pregnant women. Results: 21, 12 and 15% women had an EPDS score ≧10 at 36 weeks’ gestation, 2 and 6 months postpartum, respectively. Quantitative trait analysis showed an association between rs174575 and PPD risk at 36 weeks’ gestation and 6 months postpartum. With haplotype ACCC (major alleles) for rs174553, rs99780, rs174575, rs174583, respectively, as reference, GTCT was positively associated with PPD risk at 36 weeks’ gestation, p = 0.028, and higher LA and lower ARA in plasma (p = 0.0001, p < 0.0001) and RBC ethanolamine phospholipids (p = 0.007, p = 0.005). Conclusions: We show that SNPs in FADS1/FADS2 are associated with higher blood lipid LA and lower ARA and PPD risk.
Structuring Public Engagement for Effective Input in Policy Development on Human Tissue Biobanking
Authors: O’Doherty K.C. , Hawkins A.
Published: April 2010

We begin with the premise that human tissue biobanking is associated with ethical ambiguities and regulatory uncertainty, and that public engagement is at least one important element in addressing such challenges. One is then confronted with how to achieve public engagement that is both meaningful and effective. In particular, how can public engagement on the topic of biobanking be implemented so that (a) it is perceived broadly as legitimate and (b) the results of the engagement are relevant and useful to the institutional and regulatory context? In this paper we build on previous work that has addressed the former point and focus primarily on the latter. We argue that one way to increase the likelihood of results of public engagement being taken up in policy is through framing the issues that are deliberated by members of the public based in part on the practical policy questions for which input is sought. In this approach, we move discussion on the social and ethical implications of biobanking from abstract principles, to their consideration in the context of local biobanking practices. This is illustrated using a practical example involving a public engagement conducted to inform institutional policy for biobanking in British Columbia, Canada.
The Value of Using Top-Down and Bottom-Up Approaches for Building Trust and Transparency in Biobanking
Authors: Meslin E.M.
Published: April 2010

With the domestic and international proliferation of biobanks and their associated connections to health information databases, scholarly attention has been turning from the ethical issues arising from the construction of biobanks to the ethical issues that emerge in their operation and management. Calls for greater transparency in governance structures, coupled with stern reminders of the value of maintaining public trust, are seen as critical components in the success of these resources. Two different approaches have been adopted for addressing these types of ethical issues: the first is a ‘top-down’ approach which focuses on developing policy, procedures, regulations and guidelines to aid decision-makers. The second is a ‘bottom-up’ approach, which begins with those who are most affected by the issues and attempts to inductively develop consensus recommendations and policy. While both approaches have merit, I argue that more work needs to be done on ‘bottom-up’ strategies if trust and transparency are to be more than mere slogans. Using 2 case examples from Indiana, the paper summarizes data from a set of surveys we recently conducted that address issues arising from biobanks that provide some insight into issues associated with trust and transparency.
Non-Invasive Prenatal Diagnosis Using Cell-Free Fetal DNA Technology: Applications and Implications
Authors: Hall A. , Bostanci A. , Wright C.F.
Published: April 2010

Cell-free fetal DNA and RNA circulating in maternal blood can be used for the early non-invasive prenatal diagnosis (NIPD) of an increasing number of genetic conditions, both for pregnancy management and to aid reproductive decision-making. Here we present a brief review of the scientific and clinical status of the technology, and an overview of key ethical, legal and social issues raised by the analysis of cell-free fetal DNA for NIPD. We suggest that the less invasive nature of the technology brings some distinctive issues into focus, such as the possibility of broader uptake of prenatal diagnosis and access to the technology directly by the consumer via the internet, which have not been emphasised in previous work in this area. We also revisit significant issues that are familiar from previous debates about prenatal testing. Since the technology seems to transect existing distinctions between screening and diagnostic tests, there are important implications for the form and process involved in obtaining informed consent or choice. This analysis forms part of the work undertaken by a multidisciplinary group of experts which made recommendations about the implementation of this technology within the UK National Health Service.
On Track? Using the Human Genome Epidemiology Roadmap
Authors: Little J. , Hawken S.
Published: April 2010

This paper considers the potential value of genomic information, comments on the nature of evidence about this potential value, particularly on genetic association studies, points out the need for a roadmap, outlines steps in a roadmap that was developed within the Human Genome Epidemiology Network (HuGENet), discusses progress with these steps, and comments on future directions.
A European Survey on Biobanks: Trends and Issues
Authors: Zika E. , Paci D. , Braun A. , Rijkers-Defrasne S. , Deschênes M. , Fortier I. , Laage-Hellman J. , Scerri C.A. , Ibarreta D.
Published: April 2010

Biobanks have recently gained great significance for research and personalised medicine, being recognised as a crucial infrastructure. At the same time, the widely varied practices in biobanking may also pose a barrier to cross-border research and collaboration by limiting access to samples and data. Nevertheless, the extent of the actual activities and the impact of the level of networking and harmonisation have not been fully assessed. To address these issues and to obtain missing knowledge on the extent of biobanking in Europe, the Institute for Prospective Technological Studies (IPTS) of the European Commission’s Joint Research Centre, in collaboration with the European Science and Technology Observatory (ESTO), conducted a survey among European biobanks. In total, 126 biobanks from 23 countries responded to the survey. Most of them are small or medium-sized public collections set up either for population-based or disease-specific research purposes. The survey indicated a limited networking among the infrastructures. The large majority of them are stand-alone collections and only about half indicated to have a policy for cross-border sharing of samples. Yet, scientific collaborations based on the use of each biobank appear to be prominent. Significant variability was found in terms of consent requirements and related procedures as well as for privacy and data protection issues among the biobanks surveyed. To help promote networking of biobanks and thus maximise public health benefits, at least some degree of harmonisation should be achieved.
An Application Framework for Controlling an Avatar in a Desktop-Based Virtual Environment via a Software SSVEP Brain–Computer Interface
Authors: Faller Josef , Müller-Putz Gernot , Schmalstieg Dieter , Pfurtscheller Gert
Published: April 2010

This paper presents a reusable, highly configurable application framework that seamlessly integrates SSVEP stimuli within a desktop-based virtual environment (VE) on standard PC equipment. Steady-state visual evoked potentials (SSVEPs) are brain signals that offer excellent information transfer rates (ITR) within brain–computer interface (BCI) systems while requiring only minimal training. Generating SSVEP stimuli in a VE allows for an easier implementation of motivating training paradigms and more realistic simulations of real-world applications. EEG measurements on seven healthy subjects within three scenarios (Button, Slalom, and Apartment) showed that moving and static software generated SSVEP stimuli flickering at frequencies of up to 29 Hz proved suitable to elicit SSVEPs. This research direction could lead to vastly improved immersive VEs that allow both disabled and healthy users to seamlessly communicate or interact through an intuitive, natural, and friendly interface.
OpenViBE: An Open-Source Software Platform to Design, Test, and Use Brain–Computer Interfaces in Real and Virtual Environments
Authors: Renard Yann , Lotte Fabien , Gibert Guillaume , Congedo Marco , Maby Emmanuel , Delannoy Vincent , Bertrand Olivier , Lécuyer Anatole
Published: April 2010

This paper describes the OpenViBE software platform which enables researchers to design, test, and use brain–computer interfaces (BCIs). BCIs are communication systems that enable users to send commands to computers solely by means of brain activity. BCIs are gaining interest among the virtual reality (VR) community since they have appeared as promising interaction devices for virtual environments (VEs). The key features of the platform are (1) high modularity, (2) embedded tools for visualization and feedback based on VR and 3D displays, (3) BCI design made available to non-programmers thanks to visual programming, and (4) various tools offered to the different types of users. The platform features are illustrated in this paper with two entertaining VR applications based on a BCI. In the first one, users can move a virtual ball by imagining hand movements, while in the second one, they can control a virtual spaceship using real or imagined foot movements. Online experiments with these applications together with the evaluation of the platform computational performances showed its suitability for the design of VR applications controlled with a BCI. OpenViBE is a free software distributed under an open-source license.
The Ranking of the Goods at Philebus 66a-67b
Authors: Lang P. M.
Published: April 2010

At the very end of Plato’s Philebus Socrates and Protarchus place the goods of a human life in a hierarchy (66a-67b). Previous interpretations of this passage have concentrated upon its relevance to the good human life, including the allowance of (true and pure) pleasures. This view picks up Plato’s metaphor of a mixture of reason and pleasure, but the ranking of the goods is emphatically a vertical stratification and not a mixture in which all elements are equally fundamental. In this article I argue that each and all of the higher ranked goods are necessary conditions for the goods of the level immediately below. The ranking represents an attempt to identify as far as possible what is responsible for the characteristics of the good in human life, and therefore to narrow down the definition of the good itself.
Sex Discrimination within Kuwaiti Family Law. Part 1
Authors: Alessa Amani Saleh
Published: April 2010

Family Law in Middle Eastern countries in general and in Kuwait in particular has always been an example of the subordination of women in areas such as marriage, divorce, alimony, and custody. Since Family Law is based on the Shari'a, some jurisprudents claim that it is fair to all women and that claiming otherwise is speaking against the Shari'a. However, this article is meant to get to the root of Family Law articles that show unjust treatment of women. Much of such injustice depends on the opinions of some jurisprudents with no evidence from either the Qur'ān or the Hadīth, while other articles that are rooted in the Qur'ān can be interpreted in different ways that provide a certain degree of justice to women.