bluuebunny/crossref_metadata_2025 huggingface dataset:
Age as a Predictive Factor in Glioblastomas: Population-Based Study
Authors: Kita Daisuke , Ciernik Ilja F. , Vaccarella Salvatore , Franceschi Silvia , Kleihues Paul , Lütolf Urs M. , Ohgaki Hiroko
Published: March 2009

We evaluated 715 glioblastoma patients diagnosed during 1980–1994 in the Canton of Zurich, Switzerland, to provide information on how patients were treated at the population level. Despite a general policy during the study period of treatment by surgical intervention aimed at maximum tumor removal followed by radiotherapy, there was a marked tendency toward limited treatment with advancing patient age. Of those younger than 65 years, 82% were treated either with surgery followed by radiotherapy, surgery alone or radiotherapy alone, versus 47% of patients 65 years or older. Only 25% of patients older than 75 years underwent surgery and/or radiotherapy, while the remaining patients were given best supportive care (BSC). The mean ages of patients were 54.5 years for those treated with surgery and radiotherapy, 58.3 years for surgery alone, 62.2 years for radiotherapy alone and 69.2 years for BSC. Among patients who were treated with surgery plus radiotherapy and those treated with radiotherapy alone, younger patients (<60 years) had a significantly higher survival rate than older patients (≥60 years). In contrast, no significant difference in survival was observed between younger and older patients treated with surgery alone or receiving BSC, suggesting that lower survival rates in elderly patients with glioblastoma may be at least in part due to a lesser response to radiotherapy.
Persistent Cloaca Presenting with Persistent Massive Fetal Ascites Resulting from Severely Compromised Urinary Function
Authors: Motoi Mukai , Satoshi Ibara , Takatsugu Maeda , Masato Kamitomo , Yuko Maruyama , Takuya Tokuhisa , Yuka Fujie , Yusuke Nakazawa , Takeshi Utsunomiya , Kenji Sumi , Tatsuo Ohshiro , Tetsuo Ono , Hiroyuki Noguchi , Seiro Machigashira
Published: March 2009

Persistent cloaca (PC) is a rare abnormality characterized by a direct communication between the gastrointestinal, urinary and genital structures. We report a case of PC presenting with persistent massive fetal ascites. Postpartum examination demonstrated a long and narrow common channel of PC. Fetal ascites is caused by urinary drainage through the fallopian tubes into the abdominal cavity. Usually it occurs temporarily and disappears with the subsequent development of intrapelvic cysts. A long and narrow common channel of PC has been found to contribute to the persistent ascites.
Intravenous Iron Sucrose Changes the Intraperitoneal Homeostasis
Authors: Bręborowicz A. , Połubinska A. , Kupczyk M. , Wanic-Kossowka M. , Oreopoulos D.G.
Published: March 2009

Background/Aims: Intravenous iron infusion is the accepted way of supplementation of that compound in uremic patients. The aim of the study was to evaluate whether this treatment affects intraperitoneal homeostasis in patients on peritoneal dialysis. Methods: Blood and peritoneal dialysate samples were collected from 10 patients treated with continuous ambulatory peritoneal dialysis who were given 100 mg iron sucrose (IS) intravenously. Systemic and peritoneal permeability as well as transperitoneal transport were studied. The effect of spent dialysate was tested in vitro on human peritoneal mesothelial cells (MCs). Results: Dialysate total iron was increased (+19%, p < 0.01) during intravenous infusion of IS. Immediately after infusion the concentration of 8-OHdG was increased in plasma (+10%, p < 0.01) and in dialysate (+5%, p < 0.05). IS infusion caused a transient decrease in peritoneal permeability to protein (–42%, p < 0.05) and glucose (–30%, p < 0.01) and a reduction in dialysate cell count (–58%, p < 0.05). During the exchange dialysate hyaluronan was increased by 27% (p < 0.01). Spent dialysate, tested ex vivo on cultured MC, induced oxidative stress (+39%, p < 0.01), slowed their proliferation (–20%, p < 0.01), and stimulated MCP-1 synthesis (+46%, p < 0.01). Iron content in MCs exposed to dialysate obtained after IS infusion was increased by 32% (p < 0.01). Conclusion: Intravenous infusion of IS causes oxidative stress and inflammation within peritoneal MCs which may impair viability of the peritoneum.
FHL-2 Suppresses VEGF-Induced Phosphatidylinositol 3-Kinase/Akt Activation via Interaction With Sphingosine Kinase-1
Authors: Hayashi Hiroki , Nakagami Hironori , Takami Yoichi , Koriyama Hiroshi , Mori Masaki , Tamai Katsuto , Sun Jianxin , Nagao Kaori , Morishita Ryuichi , Kaneda Yasufumi
Published: March 2009

Objective—

In the functional screening of a human heart cDNA library to identify a novel antiangiogenic factor, the prime candidate gene was “four-and-a-half LIM only protein-2” (FHL-2). The goal of this study is to clear the mechanism of antiangiogenic signaling of FHL-2 in endothelial cells (ECs).

Methods and Results—

Overexpressed FHL-2 strongly inhibited vascular endothelial growth factor (VEGF)-induced EC migration. In the angiogenic signaling, we focused on sphingosine kinase-1 (SK1), which produces sphingosine-1-phosphate (S1P), a bioactive sphingolipid, as a potent angiogenic mediator in ECs. Immunoprecipitation and immunostaining analysis showed that FHL-2 might bind to SK1. Importantly, overexpression of FHL-2 in ECs inhibited VEGF-induced SK1 activity, phosphatidylinositol 3-kinase activity, and phosphorylation of Akt and eNOS. In contrast, overexpression of FHL-2 had no effect on S1P-induced Akt phosphorylation. Interestingly, VEGF stimulation decreased the binding of FHL-2 and SK1. Depletion of FHL-2 by siRNA increased EC migration accompanied with SK1 and Akt activation, and increased the expression of VEGF receptor-2 which further enhanced VEGF signaling. Furthermore, injection of FHL-2 mRNA into Xenopus embryos resulted in inhibition of vascular network development, assessed by in situ hybridization with endothelial markers.

Conclusions—

FHL-2 may regulate phosphatidylinositol 3-kinase/Akt via direct suppression of the SK1-S1P pathway in ECs.
Proteomic Analysis of Defined HDL Subpopulations Reveals Particle-Specific Protein Clusters
Authors: Davidson W. Sean , Silva R.A. Gangani D. , Chantepie Sandrine , Lagor William R. , Chapman M. John , Kontush Anatol
Published: March 2009

Objective—

Recent proteomic studies have identified multiple proteins that coisolate with human HDL. We hypothesized that distinct clusters of protein components may distinguish between physicochemically-defined subpopulations of HDL particles, and that such clusters may exert specific biological function(s).

Methods and Results—

We investigated the distribution of proteins across 5 physicochemically-defined particle subpopulations of normolipidemic human HDL (HDL2b, 2a, 3a, 3b, 3c) fractionated by isopycnic density gradient ultracentrifugation. Liquid chromatography/electrospray mass spectrometry identified a total of 28 distinct HDL-associated proteins. Using an abundance pattern analysis of peptide counts across the HDL subfractions, these proteins could be grouped into 5 distinct classes. A more in-depth correlational network analysis suggested the existence of distinct protein clusters, particularly in the dense HDL3 particles. Levels of specific HDL proteins, primarily apoL-I, PON1, and PON3, correlated with the potent capacity of HDL3 to protect LDL from oxidation.

Conclusions—

These findings suggest that HDL is composed of distinct particles containing unique (apolipo)protein complements. Such subspeciation forms a potential basis for understanding the numerous observed functions of HDL. Further work using additional separation techniques will be required to define these species in more detail.
Age-Related Left Ventricular Remodeling and Associated Risk for Cardiovascular Outcomes
Authors: Cheng Susan , Fernandes Verônica R.S. , Bluemke David A. , McClelland Robyn L. , Kronmal Richard A. , Lima João A.C.
Published: March 2009

Background—

Age-related alterations of left ventricular (LV) structure and function that may predispose to cardiovascular events are not well understood.

Methods and Results—

We used cardiac MRI to examine age-related differences in LV structure and function in 5004 participants without overt cardiovascular disease when enrolled in the Multi-Ethnic Study of Atherosclerosis; 1099 participants received additional strain analyses by MRI tagging. We also assessed the relation of age-associated remodeling with cardiovascular outcomes using Cox proportional hazard models adjusting for cardiovascular risk factors. Although LV mass decreased with age (−0.3 g per year), the mass-to-volume ratio markedly increased (+5 mg/mL per year,
P
<0.0001), driven by a substantial reduction in end-diastolic volume (−0.8 mL per year,
P
<0.0001). Age was also associated with a significant fall in stroke volume (−0.4 mL per year,
P
<0.0001), along with strain patterns reflecting systolic (
P
<0.0001) as well as diastolic (
P
<0.01) myocardial dysfunction—despite a modestly enhanced ejection fraction (+0.1% per year,
P
<0.0001). Increased mass-to-volume ratio conferred a significant risk for total cardiovascular events; this trend was strongest among younger (<65 years; hazard ratio, 3.69 [CI, 1.34 to 10.10]) versus older (≥65 years; hazard ratio, 1.68 [CI 0.77 to 3.68]) individuals with the highest compared to lowest mass-to-volume ratio quintile (P
interaction
=0.013).

Conclusions—

Age is associated with a phenotype of LV remodeling marked by increased mass-to-volume ratio and accompanied by systolic as well as diastolic myocardial dysfunction that is not reflected by preserved ejection fraction. This pattern of ventricular remodeling confers significant cardiovascular risk, particularly when present earlier in life.
Discrete- and Continuous-Time Probabilistic Models and Algorithms for Inferring Neuronal UP and DOWN States
Authors: Chen Zhe , Vijayan Sujith , Barbieri Riccardo , Wilson Matthew A. , Brown Emery N.
Published: March 2009

UP and DOWN states, the periodic fluctuations between increased and decreased spiking activity of a neuronal population, are a fundamental feature of cortical circuits. Understanding UP-DOWN state dynamics is important for understanding how these circuits represent and transmit information in the brain. To date, limited work has been done on characterizing the stochastic properties of UP-DOWN state dynamics. We present a set of Markov and semi-Markov discrete- and continuous-time probability models for estimating UP and DOWN states from multiunit neural spiking activity. We model multiunit neural spiking activity as a stochastic point process, modulated by the hidden (UP and DOWN) states and the ensemble spiking history. We estimate jointly the hidden states and the model parameters by maximum likelihood using an expectation-maximization (EM) algorithm and a Monte Carlo EM algorithm that uses reversible-jump Markov chain Monte Carlo sampling in the E-step. We apply our models and algorithms in the analysis of both simulated multiunit spiking activity and actual multi- unit spiking activity recorded from primary somatosensory cortex in a behaving rat during slow-wave sleep. Our approach provides a statistical characterization of UP-DOWN state dynamics that can serve as a basis for verifying and refining mechanistic descriptions of this process.
Randomized Shortest-Path Problems: Two Related Models
Authors: Saerens Marco , Achbany Youssef , Fouss François , Yen Luh
Published: March 2009

This letter addresses the problem of designing the transition probabilities of a finite Markov chain (the policy) in order to minimize the expected cost for reaching a destination node from a source node while maintaining a fixed level of entropy spread throughout the network (the exploration). It is motivated by the following scenario. Suppose you have to route agents through a network in some optimal way, for instance, by minimizing the total travel cost—nothing particular up to now—you could use a standard shortest-path algorithm. Suppose, however, that you want to avoid pure deterministic routing policies in order, for instance, to allow some continual exploration of the network, avoid congestion, or avoid complete predictability of your routing strategy. In other words, you want to introduce some randomness or unpredictability in the routing policy (i.e., the routing policy is randomized). This problem, which will be called the randomized shortest-path problem (RSP), is investigated in this work. The global level of randomness of the routing policy is quantified by the expected Shannon entropy spread throughout the network and is provided a priori by the designer. Then, necessary conditions to compute the optimal randomized policy—minimizing the expected routing cost—are derived. Iterating these necessary conditions, reminiscent of Bellman's value iteration equations, allows computing an optimal policy, that is, a set of transition probabilities in each node. Interestingly and surprisingly enough, this first model, while formulated in a totally different framework, is equivalent to Akamatsu's model ( 1996 ), appearing in transportation science, for a special choice of the entropy constraint. We therefore revisit Akamatsu's model by recasting it into a sum-over-paths statistical physics formalism allowing easy derivation of all the quantities of interest in an elegant, unified way. For instance, it is shown that the unique optimal policy can be obtained by solving a simple linear system of equations. This second model is therefore more convincing because of its computational efficiency and soundness. Finally, simulation results obtained on simple, illustrative examples show that the models behave as expected.
An Original Case of Tin Dental Fillings from 18th Century Northern France
Authors: Bertrand B. , Colard T. , Lacoche C. , Salomé J.F. , Vatteoni S.
Published: March 2009

During the 18th century, France was the leader in the field of dentistry, exemplified by Pierre Fauchard (1678–1761), who was given the title “the father of modern dentistry” for his comprehensive work, Le Chirurgien Dentiste. This paper examines an 18th century dental treatment in a barely 50-year-old male whose body was excavated from Saint Amé’s Collegiate Church, Douai, France. This individual had 6 dental restorations, exceptional for that period. All fillings were on the occlusal surfaces of molars and extended at least to the superficial dentin. Panoramic and retro-alveolar radiography confirmed the presence of a radio-opaque filling material, and x-ray fluorescence (XRF) and x-ray diffraction analyses demonstrated the exclusive presence of tin in these restorations.
Fracture Modes in Human Teeth
Authors: Lee J.J.-.W. , Kwon J.-Y. , Chai H. , Lucas P.W. , Thompson V.P. , Lawn B.R.
Published: March 2009

The structural integrity of teeth under stress is vital to functional longevity. We tested the hypothesis that this integrity is limited by fracture of the enamel. Experiments were conducted on molar teeth, with a metal rod loaded onto individual cusps. Fracture during testing was tracked with a video camera. Two longitudinal modes of cracking were observed: median cracking from the contact zone, and margin cracking along side walls. Median cracks initiated from plastic damage at the contact site, at first growing slowly and then accelerating to the tooth margin. Margin cracks appeared to originate from the cemento-enamel junction, and traversed the tooth wall adjacent to the loaded cusp from the gingival to the occlusal surface. All cracks remained confined within the enamel shell up to about 550 N. At higher loads, additional crack modes—such as enamel chipping and delamination—began to manifest themselves, leading to more comprehensive failure of the tooth structure.
Predictors of Dental Caries Progression in Primary Teeth
Authors: Ismail A.I. , Sohn W. , Lim S. , Willem J.M.
Published: March 2009

The current evidence on the role of the social, behavioral, and community determinants of dental caries is based on cross-sectional analyses. The available evidence has not been based on analysis of multiple determinants within the same population. This longitudinal study addresses both of these limitations. The study included data from 788 dyads of children and their caregivers (77% follow-up), who were examined in 2002–03 and 2004–05. The families were assessed by calibrated dentists for severity of caries at both time periods. Additionally, the caregivers answered questionnaires administered by trained interviewers. The caries increment was adjusted for reversals. Significant predictors of higher caries increment were higher consumption of soda drinks, older age of child, greater weight-for-age, fewer dental treatment visits, higher baseline caries levels of children and their caregivers, dental fatalism, and neighborhood disadvantage status. The selected risk factors in the final model explained about 20% of the variation in the increment.
“Talk to Me—I'm Human”: The Story of a Girl, Her Personhood, and the Failures of Health Care
Authors: Speraw Susan
Published: March 2009

Perspectives on the concept of personhood and its relationship to health care delivery are considered in the context of the life of an adolescent with multiple disabilities. One phenomenological interview lasting 3 hours illuminated life-long experiences of suffering, healing, and the quest to be treated as human, as perceived by a 16-year-old girl disfigured by multiple cancer treatments. Age-appropriate development is the ground of her existence, whereas the quality of relationships with care providers and the extent to which they demonstrate regard for her value as a person are figural. Health care providers have often failed to interact with her in ways supporting dignity and growth, treating her with “care” that is antithetical to the aims of their professions. The case has relevance for health care education and practice, challenging professionals to examine their views on personhood and self-care agency, and the ways in which those views impact the care they provide.
The State of Synapses in Fragile X Syndrome
Authors: Pfeiffer Brad E. , Huber Kimberly M.
Published: March 2009

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and a leading genetic cause of autism. There is increasing evidence in both FXS and other forms of autism that alterations in synapse number, structure, and function are associated and contribute to these prevalent diseases. FXS is caused by loss of function of the Fmr1 gene, which encodes the RNA binding protein, fragile X mental retardation protein (FMRP). Therefore, FXS is a tractable model to understand synaptic dysfunction in cognitive disorders. FMRP is present at synapses where it associates with mRNA and polyribosomes. Accumulating evidence finds roles for FMRP in synapse development, elimination, and plasticity. Here, the authors review the synaptic changes observed in FXS and try to relate these changes to what is known about the molecular function of FMRP. Recent advances in the understanding of the molecular and synaptic function of FMRP, as well as the consequences of its loss, have led to the development of novel therapeutic strategies for FXS.
Serial PEF measurement is superior to cross-shift change in diagnosing occupational asthma
Authors: Park D. , Moore V. C. , Burge C. B. S. G. , Jaakkola M. S. , Robertson A. S. , Burge P. S.
Published: March 2009

Cross-shift measurements of peak expiratory flow (PEF) are commonly employed in the diagnosis of occupational asthma, although evidence for this approach is lacking. The current paper presents an evaluation of the technique.

Mean changes in PEF across morning/day shifts were compared between workers with occupational asthma, confirmed using specific challenge testing, and non-working asthmatics. Individuals were divided into a development set, used to identify the optimum cross-shift change for diagnosing occupational asthma, and an evaluation set, used to test the sensitivity and specificity of this value. Comparative analysis of serial PEF records was performed using the Oasys-2 computerised system.

A cross-shift decrease in PEF of 5 L·min−1achieved acceptable specificity in the development set. Applied to the evaluation set, this cut-off had a specificity of 90.9% and a sensitivity of 50%. Sensitivity could not be improved without unacceptable compromise to specificity. Analysis of serial PEF records using linear discriminant analysis identified occupational asthma with a sensitivity of 83.3% and a specificity of 90.9%. Serial analysis using mean work/rest day PEF comparison had a sensitivity of 66.7% and a specificity of 100%.

Cross-shift changes in PEF in morning/day-shift workers have poor sensitivity in diagnosing occupational asthma, and are inferior to serial techniques.
Evidence of a tick RNAi pathway by comparative genomics and reverse genetics screen of targets with known loss-of-function phenotypes in Drosophila
Authors: Kurscheid Sebastian , Lew-Tabor Ala E , Rodriguez Valle Manuel , Bruyeres Anthea G , Doogan Vivienne J , Munderloh Ulrike G , Guerrero Felix D , Barrero Roberto A , Bellgard Matthew I
Published: March 2009

Background

The Arthropods are a diverse group of organisms including Chelicerata (ticks, mites, spiders), Crustacea (crabs, shrimps), and Insecta (flies, mosquitoes, beetles, silkworm). The cattle tick, Rhipicephalus (Boophilus) microplus, is an economically significant ectoparasite of cattle affecting cattle industries world wide. With the availability of sequence reads from the first Chelicerate genome project (the Ixodes scapularis tick) and extensive R. microplus ESTs, we investigated evidence for putative RNAi proteins and studied RNA interference in tick cell cultures and adult female ticks targeting Drosophila homologues with known cell viability phenotype.

Results

We screened 13,643 R. microplus ESTs and I. scapularis genome reads to identify RNAi related proteins in ticks. Our analysis identified 31 RNAi proteins including a putative tick Dicer, RISC associated (Ago-2 and FMRp), RNA dependent RNA polymerase (EGO-1) and 23 homologues implicated in dsRNA uptake and processing. We selected 10 R. microplus ESTs with >80% similarity to D. melanogaster proteins associated with cell viability for RNAi functional screens in both BME26 R. microplus embryonic cells and female ticks in vivo. Only genes associated with proteasomes had an effect on cell viability in vitro. In vivo RNAi showed that 9 genes had significant effects either causing lethality or impairing egg laying.

Conclusion

We have identified key RNAi-related proteins in ticks and along with our loss-of-function studies support a functional RNAi pathway in R. microplus. Our preliminary studies indicate that tick RNAi pathways may differ from that of other Arthropods such as insects.
Application of principal component analysis and a fuzzy C-means clustering algorithm to wear debris morphology classification
Authors: Wu J P , Yan X P , Jin Z M , Tipper J L , Yuan C Q , Zhou X C
Published: March 2009

The application of principal component analysis (PCA) and fuzzy C-means clustering algorithm to the classification of ultrahigh molecular weight polyethylene (UHMWPE) wear debris from artificial joints has been described in this article. Wear particles were extracted and isolated from peri-prosthetic tissues collected during revision surgery, which was revised for loosening. The implant life of the hip prosthesis was 12 years. The particles were examined by scanning electron microscopy. Digitized particle images were analysed on a computer by specially developed software ‘Image-Pro Plus’. The following 19 numerical descriptors were used to characterize the particles: particle area, length, width, perimeter, boundary fractal dimension, and shape parameters such as form factor, roundness, convexity, aspect ratio, and others. PCA algorithm was applied to reduce the amount of parameters to simplify the following calculation. Furthermore, main factors and important parameters such as mean diameter, equivalent circle diameter, and perimeter were found out by PCA. However, C-means clustering algorithm was applied to classify the UHMWPE wear debris into 4–7 clusters. The Xie—Beni index was introduced to determine the optimal number of clusters and illuminate the clustering validity. The result of the calculation indicates that five clusters is the optimal clustering number. The feature of the debris in each cluster is also described in this article.
Description of joint constraints in the floating frame of reference formulation
Authors: Korkealaakso P , Mikkola A , Rantalainen T , Rouvinen A
Published: March 2009

This article presents the modelling principles of the joint constraints for flexible multibody systems. The joints are composed using three basic constraint primitives which are derived including their first and second time derivatives as well as the components of the Jacobian matrix. The description of the derived components of constraint primitives can be used to develop a library of kinematic joints to use in multibody codes. In this study, the equations of motion are defined using generalized Newton—Euler equations where the deformations are accounted for by using the floating frame of reference formulation with modal coordinates. The deformation modes used in the floating frame of reference formulation are obtained from the finite-element analysis by employing the lumped mass matrix. Dynamic analysis of a mechanism consisting of rigid and flexible bodies is used to illustrate the validity of the constraint formulation.
Non-linear vibration signature analysis of a high-speed rotating shaft due to ball size variations and varying number of balls
Authors: Upadhyay S H , Jain S C , Harsha S P
Published: March 2009

In this article, a mathematical model has been developed to predict the non-linear dynamic behaviour of a high-speed unbalanced rotating shaft due to ball size variations and varying number of balls. In the mathematical formulation, the contact between balls and inner/outer races is considered as a non-linear spring, whose stiffness is obtained using Hertzian elastic deformation theory. A detailed contact-damping model reflecting the influences of the surface profiles and the speeds of both contacting elements is developed and applied in the rolling element bearing formulation. This formulation also accounts for sources of non-linearity such as Hertzian contact force, varying number of balls, and off-sized balls resulting transition from non-contact to contact state between balls and races. The equations of motion of a rolling element bearing are formulated using Lagrange's equation considering the vibration characteristics of individual constituents such as inner race, outer race, rolling elements, and shaft. To overcome the strong non-linearity of the governing equations of motion, a modified Newmark-β time integration technique has been used to solve the equations of motion numerically. All results have been presented in the form of fast Fourier transformations and Poincaré maps. The highest radial vibrations due to ball size variation are at a speed of the number of balls times the cage speed (ω= kωcage Hz). The other vibrations due to ball size variation also occurr at ( X± k ωcage), where k is a constant. When the number of balls is increased, the centre of oscillations approaches zero, implying a stiffer system. From this it can be predicted that increasing the number of balls will reduce the effect of the BPF. Hence it is implied from the analysis that the number of balls and the size variation of balls are important parameters and should be considered at the design stage.
The C-terminal half of human Ago2 binds to multiple GW-rich regions of GW182 and requires GW182 to mediate silencing
Authors: Lian Shang L. , Li Songqing , Abadal Grant X. , Pauley Brad A. , Fritzler Marvin J. , Chan Edward K.L.
Published: March 2009

MicroRNA (miRNA)-mediated silencing is a post-transcriptional mechanism that regulates translation of mRNAs primarily via their 3′-UTR. Ago2 binds miRNA directly and is the core component of miRNA-induced silencing complex. GW182 is another important factor in miRNA-mediated silencing, and its interaction with Ago2 is evolutionarily conserved. However, the GW182-Ago2 interaction in humans has not been characterized thoroughly, and the role of GW182 in the mammalian miRNA pathway remains unclear. In the current study, we generated a set of GST-, green fluorescence protein (GFP)-, or 3xFlag-tagged deletion constructs of GW182 and Ago2 to further analyze GW182-Ago2 interactions. The C-terminal half of Ago2 interacted with four nonoverlapping GW-rich regions of GW182, and this interaction recruited Ago2 to GWB. Furthermore, the interaction with GW182 was observed in all four human Ago proteins. Most interestingly, tethering the C-terminal half of Ago2 to the 3′-UTR of reporter mRNA recapitulated translational repression comparable to that of tethered Ago2, and this repression was greatly impaired upon GW182 knockdown. In comparison, the N-terminal half of Ago2 did not bind GW182 and did not retain the repression function of Ago2. Our data strongly support a model in which Ago2 recruits GW182 to the 3′-UTR of mRNA to mediate silencing, and suggest that GW182 may contribute to enhancement in translational repression by interacting with multiple Ago proteins from multiple miRNA target sites in the same or adjacent 3′UTR.
Optimization of linear double-stranded RNA for the production of multiple siRNAs targeting hepatitis C virus
Authors: Shin Duckhyang , Lee Hyeon , Kim Soo In , Yoon Yeup , Kim Meehyein
Published: March 2009

RNA interference (RNAi)-based gene silencing possesses great therapeutic potential for inhibiting replication of human viruses such as hepatitis C virus (HCV). However, one of the putative limitations for its use as a therapy is the rapid emergence of escape variants. These contain deletions or mutations within the viral genome sequences complementary to the small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) being used for treatment. As a potential solution to this problem, we constructed an expression system for duplex RNAs harboring two siRNA units using convergent H1 and U6 Pol III promoters. Here, the length and orientation of the transcript, tandem siRNA (tsiRNA), were optimized to be processed by the intracellular ribonuclease Dicer into functional siRNAs targeting different sequences. Assessment in transfected cells indicates that the length of the tsiRNA duplex (40–42 base pairs) is more critical for both siRNA-producing capacity and gene silencing activity than the orientation of each siRNA unit. In Huh7 cells replicating full-length HCV RNA, expression of length-optimized tsiRNA inhibited viral protein levels as efficiently as a single 21-nucleotide siRNA-expression construct, without affecting miRNA maturation or induction of an interferon response. We verified that the anti-viral activity of tsiRNA was achieved by precise cleavage of two target sites. A distinct advantage of this strategy is that each side of the optimized linear duplex RNA could enter into the Dicer-mediated processing machinery, thus likely providing more equal and efficient production of multiple siRNAs required for reducing the chance of viral escape.
Eyewitness identification tests
Authors: Brewer Neil , Palmer Matthew A.
Published: March 2009

When investigating crimes police frequently use eyewitness identification tests such as lineups in an attempt to establish the culprit's identity. It is now well documented that witnesses commonly make mistakes, sometimes identifying innocent suspects or failing to identify the culprit. Lineup administrators also make mistakes in the sense that they use procedures that increase the likelihood of eyewitness error. Eyewitness memory research has provided a basis for many useful guidelines regarding the conduct of identification tests. Here, we review the relevant research underpinning effective procedures for lineup construction, lineup presentation, recording the witness's decision, and providing feedback to the witness. The systematic implementation of these guidelines is likely to reduce significantly the extent of eyewitness errors at the identification test and improve the probative value of courtroom testimony about identity. However, further significant advances may well require the development of novel procedures for accessing witnesses' memories.
Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency
Authors: Conway G S , Szarras-Czapnik M , Racz K , Keller A , Chanson P , Tauber M , Zacharin M , _ _
Published: March 2009

Objective

Discontinuation of growth hormone (GH) therapy on completion of linear growth may adversely affect bone mineral density (BMD) in young adults with childhood-onset GH-deficiency (GHD). In the present study, we analyzed the impact of GH treatment on bone in young adults with GHD.

Methods

BMD at the lumbar spine (L2–L4), total hip, and total body was measured at baseline and after 24 months in a cohort of young adults (18–25 years; n=160) with severe GHD treated with GH during childhood who were randomized to GH (n=109) or no treatment (n=51) in a multicenter, multinational, open-label study. GH starting doses (0.2 mg/day (males), 0.4 mg/day (females)) were increased after 1 month to 0.6 mg/day (males) and 0.9 mg/day (females) and then to 1.0 mg/day (males) and 1.4 mg/day (females) at 3 months for the remainder of the study.

Results

After 24 months, lumbar spine BMD had increased significantly more in GH-treated patients than in controls (6 vs 2%; estimated treatment difference; 3.5% (95% confidence interval, 1.52–5.51) P<0.001). GH also had a significant positive effect on total hip BMD (P=0.015). Total body BMD was unchanged from baseline (P=0.315).

Conclusions

In young adults treated for childhood-onset GHD, there is a beneficial effect of continued GH treatment on BMD in adult life. Twenty-four months of GH treatment in these young adults was associated with an estimated 3.5% greater increase in BMD of the lumbar spine compared with controls.
Simulation of Coagulation, Flocculation, and Sedimentation
Authors: Smoczynski L. , Bukowski Z. , Wardzynska R. , Zaleska‐Chrost B. , Dluzynska K.
Published: March 2009

The computer program ZB2 was used to study simulated coagulation, flocculation, and sedimentation. The effect of the initial velocity of soil particles on the values of reaction‐rate constants was investigated. In this respect, the results obtained with the program ZB2 corresponded to the theory and realities of coagulation carried out under practical conditions. The effect of coagulant excess/deficiency on the formation of the first floc and on the rate of coagulation of 50% of a soil was also estimated. An increase in simulated coagulant excess caused a decrease in the simulated rate of soil coagulation. In this respect, the results obtained with the program ZB2 did not correspond to the realities of coagulation carried out under practical conditions. An attempt was made to explain this inconsistency referring to the coagulation‐flocculation theory. The simulation program ZB2 may provide a basis for developing “local” programs simulating coagulation‐flocculation, which can be successfully applied at wastewater treatment plants.
Learning technology standardization: Making sense of it all
Authors: Duval Erik
Published: March 2009

In this paper, we analyze the role of technical standards in the domain of learning technology, focusing on the way they enable interoperability. We briefly explain some of the alternatives to open and accredited standards and how they impact on the community. The standardization process is analyzed in some detail and the most relevant organizations involved are briefly surveyed. We provide an overview and taxonomy of the more widely adopted standards and specifications.
Design of a multimedia content-delivery service architecture for 3rd generation networks
Authors: Calvagna Andrea
Published: March 2009

The Virtual Home Environment (VHE) has been introduced as an abstract concept enabling users to access and personalize their subscribed services whatever the terminal they use and whatever the underlying network used. Much effort is currently being spent upon the challenging task to provide an architectural solution and an implementation of the VHE, providing ubiquitous service availability, personalized user interfaces and session mobility while users are roaming or changing their equipment. In this paper we present a multimedia delivery service, one of the VHE services selected to demonstrate its features, showing its interconnection with the so far defined VESPER VHE architecture.
Case completion and similarity in case-based reasoning
Authors: Burkhard H-D.
Published: March 2009

Case Completion investigates cases for complex problem solving tasks using Case-Based Reasoning. Such tasks consist of several steps, and related cases should support each intermediate decision. Related cases are of a constraint like style and need the handling of partial matching for retrieval. Related similarity measures are investigated, and the implementation by Case Retrieval Nets is proposed.
Improving categorical data clustering algorithm by weighting uncommon attribute value matches
Authors: He Zengyou , Xu Xiaofei , Deng Shenchun
Published: March 2009

This paper presents an improved Squeezer algorithm for categorical data clustering by giving greater weight to uncommon attribute value matches in similarity computations. Experimental results on real life datasets show that, the modified algorithm is superior to the original Squeezer algorithm and other clustering algorithm with respect to clustering accuracy.
Common web application attack types and security using ASP.NET
Authors: Jovicic Bojan , Simic Dejan
Published: March 2009

Web applications security is one of the most daunting tasks today, because of security shift from lower levels of ISO OSI model to application level, and because of current situation in IT environment. ASP.NET offers powerful mechanisms to render these attacks futile, but it requires some knowledge of implementing Web application security. This paper focuses on attacks against Web applications, either to gain direct benefit by collecting private information or to disable target sites. It describes the two most common Web application attacks: SQL Injection and Cross Site Scripting, and is based on author?s perennial experience in Web application security. It explains how to use ASP.NET to provide Web applications security. There are some principles of strong Web application security which make up the part of defense mechanisms presented: executing with least privileged account, securing sensitive data (connection string) and proper exception handling (where the new approach is presented using ASP.NET mechanisms for centralized exception logging and presentation). These principles help raise the bar that attacker has to cross and consequently contribute to better security.
OORS: An object-oriented rewrite system
Authors: Gebhard Gernot , Lucas Philipp
Published: March 2009

Retargeting a compiler?s back end to a new architecture is a time-consuming process. This becomes an evident problem in the area of programmable graphics hardware (graphics processing units, GPUs) or embedded processors, where architectural changes are faster than elsewhere. We propose the object-oriented rewrite system OORS to overcome this problem. Using the OORS language, a compiler developer can express the code generation and optimization phase in terms of cost-annotated rewrite rules supporting complex non-linearmatching and replacing patterns. Retargetability is achieved by organizing rules into profiles, one for each supported target architecture. Featuring a rule and profile inheritance mechanism, OORS makes the reuse of existing specifications possible. This is an improvement regarding traditional approaches. Altogether OORS increases the maintainability of the compiler?s back end and thus both decreases the complexity and reduces the effort of the retargeting process. To show the potential of this approach, we have implemented a code generation and a code optimization pattern matcher supporting different target architectures using the OORS language and introduced them in a compiler of a programming language for CPUs and GPUs.
Constructing program animations using a pattern based approach
Authors: Cruz da , Henriques Rangel , Varanda João
Published: March 2009

The aim of this paper is to discuss how our pattern-based strategy for the visualization of data and control flow can effectively be used to animate the program and exhibit its behavior. That result allows us to propose its use for Program Comprehension. The animator uses well known compiler techniques to inspect the source code in order to extract the necessary information to visualize it and understand program execution. We convert the source program into an internal decorated (or attributed) abstract syntax tree and then we visualize the structure by traversing it, and applying visualization rules at each node according to a pre-defined rule-base. In order to calculate the next step in the program execution, a set of rewriting rules are applied to the tree. The visualization of this new tree is shown and the program animation is constructed using an iterative process. No changes are made in the source code, and the execution is simulated step by step. Several examples of visualization are shown to illustrate the approach and support our idea of applying it in the context of a Program Comprehension environment.
Integration of the ST language in a model-based engineering environment for control systems: An approach for compiler implementation
Authors: Ferreira Elisabete , Paulo Rogério , da Cruz , Henriques Pedro
Published: March 2009

In the context of the INTEGRA project, compilation and code generation features for behavior definition are to be integrated in an existing model-based engineering environment for control systems. The devised compiler architecture is domain-specific and provides support for multiple input languages and multiple target platforms. In this paper we discuss an architectural approach in which the compiling process is organized in two different stages: the compiling stage and the linking stage. The compiling stage generates target independent code from possibly multiple input languages. The linking stage assembles precompiled code modules and generates a target specific executable code for a given virtual machine. To be more specific this paper describes the integration of the ST language in the tool core meta-model and the ST compiler is presented as an application case study. .
KAT and PHL in Coq
Authors: Pereira David , Moreira Nelma
Published: March 2009

In this article we describe an implementation of Kleene algebra with tests (KAT) in the Coq theorem prover. KAT is an equational system that has been successfully applied in program verification and, in particular, it subsumes the propositional Hoare logic (PHL). We also present an PHL encoding in KAT, by deriving its deduction rules as theorems of KAT. Some examples of simple program's formal correctness are given. This work is part of a study of the feasibility of using KAT in the automatic production of certificates in the context of (source-level) Proof-Carrying-Code (PCC). .
Targeting G-Quadruplex DNA with Small Molecules
Authors: Luedtke Nathan W.
Published: March 2009

Despite a recent explosion of interest in G-quadruplex DNA, most fundamental questions regarding the possible presence and function of these intriguing structures in vivo remain unanswered. Cell-permeable G-quadruplex specific probes should provide researchers with new tools
for studying these alternately folded DNA structures and their potential involvement in gene expression, chromosome stability, viral integration, and recombination. In this review, a survey of the binding affinity, specificity, and biological/pharmacological activities of some well-characterized
G-quadruplex ligands is presented along with the potential importance of G-quadruplex DNA in vivo.
FNA of misclassified primary malignant neoplasms of the thyroid: Impact on clinical management
Authors: Faquin William C. , Izquierdo Roberto , Khurana Kamal K.
Published: March 2009

Background:

Fine needle aspiration (FNA) cytology is a popular, reliable and cost effective technique for the diagnosis of thyroid lesions. The aim of our study was to review cases of misclassified primary malignant neoplasms of the thyroid by FNA, and assess the causes of cytologic misdiagnosis and their impact on clinical management.

Methods:

Clinical data, FNA smears and follow-up surgical specimens of cases diagnosed with primary thyroid carcinoma were reviewed.

Results:

Of the 365 cases with a malignant diagnosis by FNA over a period of 11 years, nine (2.4 %) were identified with discrepant histologic diagnosis with regard to the type of primary thyroid malignancy. In addition, four cases were added from the consultation files of the Massachusetts General Hospital. Areas of difficulty contributing to misclassification included overlapping cytologic features (n = 6), rarity of tumors (n = 3), and sampling limitations (n = 4). Of the 13 cases, 12 underwent total or near total thyroidectomy and one patient had concurrent surgical biopsy. Measurement of serum calcitonin levels in one case, with an initial cytologic diagnosis of medullary carcinoma, prevented unnecessary lymph node dissection. Misclassification of medullary carcinoma as papillary carcinoma precluded lymph node dissection in one case. Further management decisions were based on the final histologic diagnosis and did not require additional surgery. Two cases of undifferentiated (anaplastic) thyroid carcinoma were misdiagnosed as papillary thyroid carcinoma. Both patients received total thyroidectomies, which may not otherwise have been performed.

Conclusions:

A small subset of primary malignant neoplasms of the thyroid may be misclassified with regard to the type of malignancy on FNA. The majority of primary malignant neoplasms diagnosed on FNA require thyroidectomy. However, initial cytologic misclassification of medullary carcinoma or undifferentiated carcinoma as other malignant neoplasms or vice versa may have an impact on clinical management.
Pleomorphic adenoma with squamous and appendageal metaplasia mimicking mucoepidermoid carcinoma on cytology
Authors: Batrani Meenakshi , Kaushal Manju , Sen A. K. , Yadav Rajbala , Chaturvedi N. K.
Published: March 2009

Background:

Histological diversity is the hallmark of pleomorphic adenoma, the most common salivary gland tumor. It may cause difficulty in cytological interpretation, due to limited and selective sampling.

Case presentation:

A 16-year-old female patient presented with right cheek swelling. Fine needle aspiration cytology showed squamous cells, basaloid cells, and foamy cells, along with extracellular keratin and foreign body giant cells. Characteristic metachromatic fibrillary chondromyxoid stroma, which is usually seen in pleomorphic adenoma, was not seen in the aspirate. A diagnosis of mucoepidermoid carcinoma was given on cytology. Subsequent resection revealed an encapsulated pleomorphic adenoma, with extensive squamous metaplasia and appendageal differentiation on histology.

Conclusion:

This case illustrates that pleomorphic adenoma with squamous metaplasia presents a potential for misinterpretation as mucoepidermoid carcinoma on cytology. We discuss the various pitfalls and the features that are helpful in distinguishing these two lesions.
A generalized method of dimensional analysis
Authors: Quraishi M. S. , Fahidy T. Z.
Published: March 2009

A systematic procedure of constructing dimensionless groups via a constitutive matrix is described. The method is independent of the system of units chosen for the purpose of analysis.