Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma.

PURPOSE We investigated aberrant methylation patterns in esophageal adenocarcinoma and correlated the findings to patient survival and tumor recurrence. EXPERIMENTAL DESIGN Gene promoter methylation was performed in 82 samples from 41 esophagectomy patients consisting of 41 adenocarcinoma samples, each with its adjacent nonmalignant tissue, which included one sample with Barretts metaplasia. The methylation status of seven genes was determined. Epigenetic silencing was confirmed using immunohistochemical staining. Kaplan-Meier plots were constructed using disease-specific survival as the primary end point and the interval from surgery to tumor recurrence as the secondary end point. The association of clinicopathological and biomolecular risk factors to survival and recurrence was performed using the Log-rank test and Cox proportional hazards model for multivariate analysis. RESULTS Methylation frequencies of the genes analyzed were APC, 68%; E-cadherin, 66%; O(6)-methylguanine DNA methyltransferase, 56%; ER, 51%; p16, 39%; DAP-kinase, 19%; and TIMP3, 19%. DNA methylation of some genes individually showed only trends toward diminished survival, whereas patients whose tumors had >50% of their gene profile methylated had both significantly poorer survival (P = 0.04) and earlier tumor recurrence (P = 0.05) than those without positive methylation. By multivariate analysis, the hazard ratios (HRs) with positive methylation status were more powerful predictors of survival [HR 2.7 (1.14-6.45; 95% confidence interval)] and tumor recurrence [HR 2.5 (1.11-5.6)] than age (HR 2.03 and 1.96, respectively) or stage (HR 1.48 and 1.67, respectively). CONCLUSIONS Our data suggest that positive methylation status for multiple genes in esophageal adenocarcinoma is a predictor of poor prognosis.
Narratives in the Network: Interactive Methods for Mining Cell Signaling Networks

In this article, we describe our work on graph mining as applied to the cellular signaling pathways in the Signal Transduction Knowledge Environment (STKE). We present new algorithms and a graphical tool that can help biologists discover relationships between pathways by looking at structural overlaps within the database. We address the problem of determining pathway relationships by using two data mining approaches: clustering and storytelling. In the first approach, our tool brings similar pathways to the same cluster, and in the second, our tool determines intermediate overlapping pathways that can lead biologists to new hypotheses and experiments regarding relationships between the pathways. We formulate the problem of discovering pathway relationships as a subgraph discovery problem and propose a new technique called Subgraph-Extension Generation (SEG), which outperforms the traditional Frequent Subgraph Discovery (FSG) approach by magnitudes. Our tool provides an interface to compare these two approaches with a variety of similarity measures and clustering techniques as well as in terms of computational performance measures such as runtime and memory consumption.
Thymic dependence of loss of tolerance in mixed allogeneic bone marrow chimeras after depletion of donor antigen. Peripheral mechanisms do not contribute to maintenance of tolerance.

A nonmyeloablative conditioning regimen has recently been developed that allows allogeneic marrow engraftment with induction of permanent mixed chimerism and donor-specific tolerance across fully MHC-mismatched allogeneic barriers. We recently demonstrated that tolerance can be broken in these chimeras by administration of an anti-donor class I-specific monoclonal antibody that eliminates donor hematopoietic cells. We have now investigated the role of the thymus in the loss of tolerance observed when chimerism is eliminated in this manner. Mixed chimeras were prepared in B10 (H2b) recipients by treatment with depleting anti-CD4 and anti-CD8 mAbs, 3-Gy whole body irradiation, and 7-Gy thymic irradiation, followed by B10.A (H2a) bone marrow transplantation. Chimeras were thymectomized 7 weeks later, and were either untreated or were depleted of donor cells with anti-donor class I (Dd-specific) mAb 34-2-12. Control chimeras that were not thymectomized also received anti-donor monoclonal antibodies or no further treatment. Of the four groups, only euthymic animals that were depleted of donor antigen showed a loss of tolerance, as evidenced by rejection of B10.A skin grafts. In contrast to untreated control and thymectomized, anti-Dd-treated chimeras, these euthymic anti-Dd-treated chimeras showed significant recovery of Vbeta11+ T cells, which can recognize Mtv antigens presented by donor I-E molecules. The requirement for a thymus for loss of tolerance in the absence of donor antigen was verified in an adoptive transfer model, in which chimera (B10.A-->B10) spleen cells were depleted of donor-type cells ex vivo, adoptively transferred into B6 nu/nu mice, and then further depleted of donor-type antigen with monoclonal antibody treatment in vivo. These B6 nu/nu mice maintained donor-specific tolerance to B10.A skin grafts. The absence of active suppression as a potent mechanism of tolerance in long-term mixed chimeras was confirmed by the loss of mixed chimerism and of tolerance that was readily induced by injection of naive host-type spleen cells. Together, our results suggest that in mixed allogeneic chimeras, intrathymic clonal deletion, and not peripheral suppression or anergy, is the major mechanism maintaining donor-specific tolerance.
The Role of Discrete Emotions in Predicting Counterproductive Work Behavior

The current study investigates how discrete negative emotions are related to specific facets of counterproductive work behaviors (CWB). The sample consisted of 241 employees who reported their frequency of experiencing negative emotions and their frequency of committing CWBs in the workplace. For 103 employees, supervisor reports of employee CWB were also obtained. The findings provide evidence that a wide range of negative emotions are related to most of the sub facets of CWB. There was also some evidence that supervisor reports differ systematically from employee reports of CWB. The theoretical, methodological, and organizational implications are discussed.
CT Attachment trauma and the developing right brain : Origins of pathological dissociation AU

The concept of dissociation has a long history of bridging psychiatry, psychology, and neurology. Because dissociation is inextricably linked to trauma, theoretical and clinical models of dissociation have spanned the psychological and biological realms. Although the relationship between childhood trauma and dissociation was noted at the end of the nineteenth century, only recently has a developmental perspective been used to understand dissociation’s etiological mechanisms. Dissociative phenomena are now being viewed through an interdisciplinary lens.
The Thinking Ape : Evolutionary Origins of Intelligence

Introduction: the limits of fossil evidence 1. Taxonomy and the reconstruction of evolution 2. What is intelligence and what is it for? 3. How animals learn 4. Why animals learn better in social groups 5. Imitative behaviour in animals 6. Understanding how things work 7. Understanding minds: doing and seeing, knowing and thinking 8. What use is a theory of mind? 9. Planning and thinking ahead 10. Apes and language 11. Food for thought 12. Machiavellian intelligence 13. Testing the theories 14. Taking stock
Regulation of the Cdk inhibitor p27 and its deregulation in cancer

p27 is a cell cycle inhibitor whose cellular abundance increases in response to many antimitogenic stimuli. In this review, we summarize the current knowledge on p27 function and its regulation by synthesis and by ubiquitin‐mediated degradation. Importantly, p27 degradation is enhanced in many aggressive human tumors. The frequency with which this is observed suggests that loss of p27 may confer a growth advantage to these cancers. From a practical point of view, immunodetection of p27 in tumors may prove to be useful in the assessment of prognosis and may ultimately influence the therapy of this disease. J. Cell. Physiol. 183:10–17, 2000. © 2000 Wiley‐Liss, Inc.
Design, implementation and evaluation of an efficient opportunistic retransmission protocol

This paper presents an efficient opportunistic retransmission protocol (PRO, Protocol for Retransmitting Opportunistically) to improve the performance of IEEE 802.11 WLANs. PRO is a link-layer protocol that allows overhearing nodes to function as relays that retransmit on behalf of the source after they learn about a failed transmission. Relays with stronger connectivity to the destination have a higher chance of delivering the packet than the source does, thereby resulting in a more efficient use of the channel. PRO has four main features. First, channel reciprocity coupled with a run-time calibration process is used to estimate the instantaneous link quality to the destination. Second, a local qualification process filters out poor relays early. Third, a distributed relay selection algorithm chooses the best set of eligible relays among all qualified relays and prioritizes them. Finally, 802.11e Enhanced Distributed Channel Access (EDCA) is leveraged to make sure high priority relays transmit with high probability. PRO is designed to coexist with legacy 802.11 stations. We have implemented PRO in the driver of a commodity wireless card. Our extensive evaluation on both a controlled testbed and in the real world shows that PRO boosts throughput in diverse wireless environments, and especially in when there is significant contention for the channels, under fading, and with user mobility.
Information sharing between family members of children with intellectual disability: future perspectives of ICT

Children with intellectual disabilities (ID) can benefit greatly from technologies, when the technologies fit with their motivations and interaction needs. This paper investigates literature on how families of children with ID become aware of and adopt technologies, in order to identify the current practices and opportunities for better support for families. The analysis and findings point to the difficulties faced and the need for creating a sustainable web-based community that can effectively disseminate and share knowledge about how technologies are used and what technologies are needed. A video-based sharing community is proposed and the form that this community might take is then discussed.
Phase 2a Study of Ataluren-Mediated Dystrophin Production in Patients with Nonsense Mutation Duchenne Muscular Dystrophy

Background Approximately 13% of boys with Duchenne muscular dystrophy (DMD) have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124) enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins. Methods This Phase 2a open-label, sequential dose-ranging trial recruited 38 boys with nonsense mutation DMD. The first cohort (n = 6) received ataluren three times per day at morning, midday, and evening doses of 4, 4, and 8 mg/kg; the second cohort (n = 20) was dosed at 10, 10, 20 mg/kg; and the third cohort (n = 12) was dosed at 20, 20, 40 mg/kg. Treatment duration was 28 days. Change in full-length dystrophin expression, as assessed by immunostaining in pre- and post-treatment muscle biopsy specimens, was the primary endpoint. Findings Twenty three of 38 (61%) subjects demonstrated increases in post-treatment dystrophin expression in a quantitative analysis assessing the ratio of dystrophin/spectrin. A qualitative analysis also showed positive changes in dystrophin expression. Expression was not associated with nonsense mutation type or exon location. Ataluren trough plasma concentrations active in the mdx mouse model were consistently achieved at the mid- and high- dose levels in participants. Ataluren was generally well tolerated. Interpretation Ataluren showed activity and safety in this short-term study, supporting evaluation of ataluren 10, 10, 20 mg/kg and 20, 20, 40 mg/kg in a Phase 2b, double-blind, long-term study in nonsense mutation DMD. Trial Registration ClinicalTrials.gov NCT00264888
Age differences in target identification as a function of retinal location and noise level: examination of the useful field of view.

Foveal and peripheral target detection were compared in young adults (M age = 22 years) and older adults (M age = 66 years) who were optically corrected for the viewing distance. In a two-alternative, forced-choice task, target letters were presented at 0 degree to 10.5 degrees from fixation. Targets were presented alone, flanked on each side by one noise element (i.e., nontarget letter), or embedded in a horizontal row of 19 noise elements. An Age X Noise Level X Location interaction was obtained, wherein age differences were largest for peripheral targets presented in noise. Slope analyses of latency data showed that the performance of young adults in the high-noise condition was most similar to that of older adults in the low-noise condition. At the functional level, results indicated that aging is associated with a restricted useful field of view. In addition, the data suggest that age differences in search can be described by a model in which older adults take smaller perceptual samples from the visual scene and scan these samples more slowly than do the young adults.
Repair of Infarcted Myocardium by Autologous Intracoronary Mononuclear Bone Marrow Cell Transplantation in Humans

Background—Experimental data suggest that bone marrow–derived cells may contribute to the healing of myocardial infarction (MI). For this reason, we analyzed 10 patients who were treated by intracoronary transplantation of autologous, mononuclear bone marrow cells (BMCs) in addition to standard therapy after MI. Methods and Results—After standard therapy for acute MI, 10 patients were transplanted with autologous mononuclear BMCs via a balloon catheter placed into the infarct-related artery during balloon dilatation (percutaneous transluminal coronary angioplasty). Another 10 patients with acute MI were treated by standard therapy alone. After 3 months of follow-up, the infarct region (determined by left ventriculography) had decreased significantly within the cell therapy group (from 30±13 to 12±7%, P =0.005) and was also significantly smaller compared with the standard therapy group (P =0.04). Likewise, infarction wall movement velocity increased significantly only in the cell therapy group (from 2.0±1.1 to 4.0±2.6 cm/s, P =0.028). Further cardiac examinations (dobutamine stress echocardiography, radionuclide ventriculography, and catheterization of the right heart) were performed for the cell therapy group and showed significant improvement in stroke volume index, left ventricular end-systolic volume and contractility (ratio of systolic pressure and end-systolic volume), and myocardial perfusion of the infarct region. Conclusions—These results demonstrate for the first time that selective intracoronary transplantation of autologous, mononuclear BMCs is safe and seems to be effective under clinical conditions. The marked therapeutic effect may be attributed to BMC-associated myocardial regeneration and neovascularization.
Succeedings of the 8th international workshop on software specification and design

The 8th International Workshop on Software Specification and Design (IWSSD-8) was held at Schloss Velen, Germany, in March 1996. In order to foster informed and fruitful discussions, the workshop was an invitation-only event of limited size. Based on formal submissions, approximately 60 people were selected and invited. Like its predecessors, IWSSD-8 maintained the principle that the accepted papers should serve as background material for the workshop. Therefore, the workshop did not include formal paper presentations, but rather provided an opportunity to engage in real work, with intensive discussions focussed around major themes. Each theme was discussed in a separate working group directed by a Working Group Chair who organized their group members so as to discuss the research issues of that particular theme. This year the themes selected were Requirements Engineering, Design Engineering, Software Architecture, and Concurrency/Distribution.IWSSD has established a tradition of using "case studies" as a focus for individual working groups. These case studies, supplied in advance to participants, have proved to be a fruitful way of working. Evidence of this can be seen most clearly in the "succeedings" or workshop reports which have followed previous workshops. It was decided that for IWSSD-8, in order to provide common ground between the themes, a single common case study should be used. The "Report on the Inquiry into the London Ambulance Service" was selected, with each theme drawing on it in a manner appropriate to their own interests and concerns.The London Ambulance Service (LAS) is briefly summarized below and discussed in the first paper appearing in the proceedings. The case study was presented in a plenary session at the beginning of the workshop and the findings of the different working groups presented and discussed at the end of the workshop, again in a plenary session. In order to make best use of the time available, working group members were asked to prepare for the workshop by familiarizing themselves with the case study and the major issues in their area relevant to that case study. We believe that this format made it both attractive and rewarding for people to attend, and was a major reason for the success of this workshop.
Roche Lobe Sizes in Deep-MOND Gravity

MOdified Newtonian Dynamics (MOND) is evolving from an empirical to a decent theory respect- ing fundamental physics after Bekenstein (2004) showed that lensing and Hubble expansion can be modeled rigourously in a Modified Relativity. The degeneracy of MOND with Dark Matter can be broken if we examine the non-linear MONDian Poisson's equation in detail. Here we study the effect of tides for a binary stellar system or a baryonic satellite-host galaxy system. We show that the Roche lobe is more squashed than the Newtonian case due to the anisotropic dilation effect in deep-MOND. We prove analytically that the Roche lobe volume scales linearly with the "true" baryonic mass ratio in both Newtonian and deep-MOND regimes, insensitive to the modification to the inertia mass. Hence accurate Roche radii of satellites can break the degeneracy of MOND and dark matter theory. Globular clusters and dwarf galaxies of comparable luminosities and distances show a factor of ten scatter in limiting radii; this is difficult to explain in any "mass-tracing-light" universe. The results here are generalizable to the intermediate MOND regime for a wide class of gravity modification function µ(g) (Zhao and Tian, astro-ph/0511754).
Changes in the Sleep and Waking EEGs of Nondemented and Demented Elderly Subjects

Sleep and waking EEGs from 11 healthy nondemented elderly men and from ten inpatients for whom the diagnosis was probable senile dementia of Alzheimer's type (SDAT), were monitored in the subjects' typical home or ward environments or in the sleep laboratory, according to their customary sleep schedules. Aged normal subjects (age range, 56–85 years) had less Stage 3 and Stage 4 sleep, less REM sleep, and more wakefulness than normally observed in young adults. Patients with SDAT (age range, 56–88 years) had even less Stage 3 sleep, no Stage 4 sleep, and very little REM sleep, and experienced fragmentation of their sleep, with frequent awakenings. These sleep variables were significantly different in the SDAT and control groups (MANOVA). Examination of the 24‐hour plots of sleep/waking patterns revealed prominent fragmentation of the diurnal sleep/waking rhythm in SDAT patients, with frequent daytime napping and nighttime periods of wakefulness. In addition, significant group differences were observed for the EEG variable, dominant occipital frequency. More qualitative EEG variables (diffuse slowing, spindle activity, and paroxysmal discharges) also differed between groups. It is suggested that correlative neuropathologic data might provide an understanding of the basis for the sleep, EEG, and mental‐function factors that undergo change in SDAT.
Antiviral therapy: current concepts and practices

Drugs capable of inhibiting viruses in vitro were described in the 1950s, but real progress was not made until the 1970s, when agents capable of inhibiting virus-specific enzymes were first identified. The last decade has seen rapid progress in both our understanding of antiviral therapy and the number of antiviral agents on the market. Amantadine and ribavirin are available for treatment of viral respiratory infections. Vidarabine, acyclovir, ganciclovir, and foscarnet are used for systemic treatment of herpesvirus infections, while ophthalmic preparations of idoxuridine, trifluorothymidine, and vidarabine are available for herpes keratitis. For treatment of human immunodeficiency virus infections, zidovudine and didanosine are used. Immunomodulators, such as interferons and colony-stimulating factors, and immunoglobulins are being used increasingly for viral illnesses. While resistance to antiviral drugs has been seen, especially among AIDS patients, it has not become widespread and is being intensely studied. Increasingly, combinations of agents are being used: to achieve synergistic inhibition of viruses, to delay or prevent resistance, and to decrease dosages of toxic drugs. New approaches, such as liposomes carrying antiviral drugs and computer-aided drug design, are exciting and promising prospects for the future.
Russian Jews in the Global City of Toronto: A Pilot Study of Identity and Social Integration

La communaute des anciens Juifs sovietiques dans le Grand Toronto a beaucoup augmente depuis 15 ans, a la fois par immigration directe depuis les pays de l’ex-URSS et par re-migration de Juifs russes depuis Israel. Peu d’etudes canadiennes sur les experiences de reinstallation des Juifs russes se sont penchees jusqu’a present sur les questions d’identite juive et de modification de cette identite avec la migration. Cette etude ethnique exploratoire est basee sur des entretiens, des discussions de groupe et l’observation des contextes de vie des immigrants avec l’intention de comparer quelques aspects essentiels de l’integration entre Juifs arrives directement de l’ex-URSS et Juifs ayant d’abord migre vers Israel. Les recits collectes pour cette etude portent sur differents points : causes de la migration vers le Canada, difficultes d’entree sur le marche du travail canadien, perception des niveaux de vie, difficultes specifiques aux couples d’immigrants, aux jeunes et aux personnes âgees, liens transnationaux avec d’autres branches de la diaspora juive russe. Les resultats indiquent des differences notables entre les deux groupes, en particulier dans l’adaptation au marche du travail et les processus familiaux. En general, les migrants de seconde migration sont mieux armes pour le mode de vie et l’economie occidentale et ont plus de points d’ancrage dans la societe canadienne que ceux qui arrivent directement de l’ex-URSS.