julilili42/papers huggingface dataset:
Oncogenic Stress Induced by Acute Hyper-Activation of Bcr-Abl Leads to Cell Death upon Induction of Excessive Aerobic Glycolysis
2011-09-20

In response to deregulated oncogene activation, mammalian cells activate disposal programs such as programmed cell death. To investigate the mechanisms behind this oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways. This resulted in a delayed necrosis-like cell death starting not before 48 hours after imatinib withdrawal. Cell death was preceded by enhanced glycolysis, glutaminolysis, and amino acid metabolism leading to elevated ATP and protein levels. This enhanced metabolism could be linked to induction of cell death as inhibition of glycolysis or glutaminolysis was sufficient to sustain cell viability. Therefore, these data provide first evidence that metabolic changes induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress-induced cell death.During the first 30 hours after imatinib deprivation, Bcr-Abl hyper-activation did not affect proliferation but resulted in cellular swelling, vacuolization, and induction of eIF2α phosphorylation, CHOP expression, as well as alternative splicing of XPB, indicating endoplasmic reticulum stress response. Cell death was dependent on p38 and RIP1 signaling, whereas classical death effectors of ER stress, namely CHOP-BIM were antagonized by concomitant up-regulation of Bcl-xL.Screening of 1,120 compounds for their potential effects on oncogenic stress-induced cell death uncovered that corticosteroids antagonize cell death upon Bcr-Abl hyper-activation by normalizing cellular metabolism. This protective effect is further demonstrated by the finding that corticosteroids rendered lymphocytes permissive to the transforming activity of Bcr-Abl. As corticosteroids are used together with imatinib for treatment of Bcr-Abl positive acute lymphoblastic leukemia these data could have important implications for the design of combination therapy protocols.In conclusion, excessive induction of Warburg type metabolic alterations can cause cell death. Our data indicate that these metabolic changes are major mediators of oncogenic stress induced by Bcr-Abl.
Best Practices for Justifying Fossil Calibrations
2011-09-21

Our ability to correlate biological evolution with climate change, geological evolution, and other historical patterns is essential to understanding the processes that shape biodiversity. Combining data from the fossil record with molecular phylogenetics represents an exciting synthetic approach to this challenge. The first molecular divergence dating analysis (Zuckerkandl and Pauling 1962) was based on a measure of the amino acid differences in the hemoglobin molecule, with replacement rates established (calibrated) using paleontological age estimates from textbooks (e.g., Dodson 1960). Since that time, the amount of molecular sequence data has increased dramatically, affording ever-greater opportunities to apply molecular divergence approaches to fundamental problems in evolutionary biology.
Molecular Diagnosis of Channelopathies, Epilepsies, Migraine, Stroke and Dementias
2011-09-21

Objectives: These EFNS guidelines on the molecular diagnosis of channelopathies, including epilepsy and migraine, as well as stroke and dementia, are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. Search strategy: To collect data about the planning, conditions and performance of molecular diagnosis of these disorders, a literature search of various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations were reviewed. Results: The best level of evidence for genetic testing recommendation (Level B) can be found for a small number of syndromes, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, severe myoclonic epilepsy of infancy, familial recurrent haemorrhages, familial Alzheimer's disease and frontotemporal lobar degeneration. Good practice points can be formulated for a number of other disorders. Conclusion: These guidelines are provisional and the availability of molecular-genetic epidemiological data in the future about the neurogenetic disorders under discussion will allow improved recommendation with an increased level of evidence.
Molecular Diagnosis of Mitochondrial Disorders
2011-09-21

Objectives: These EFNS guidelines are designed to provide practical help for the general neurologist to make appropriate use of molecular genetics for diagnosing mitochondrial disorders (MIDs), which are gaining increasing attention and are now more frequently diagnosed due to improved diagnostic tools. Background: Since the publication of the first EFNS guidelines on the molecular diagnosis of inherited neurological diseases in 2001, rapid progress has been made in this field, necessitating an updated version. Search strategy: To collect data on the molecular diagnosis of MIDs, a search for literature in various electronic databases, such as the Cochrane library, Medline, OMIM, GENETEST and Embase, was carried out and original papers, meta-analyses, review papers and guideline recommendations were reviewed. Results: The guidelines summarize the possibilities and limitations of molecular genetic diagnosis of MIDs and provide practical recommendations and diagnostic criteria in accordance with the EFNS Scientific Committee to guide the molecular diagnostic work-up of MIDs. Recommendations: The proposed guidelines suggest an approach to the molecular diagnosis of MIDs that is accessible to general neurologists.
A unique case of follicular lymphoma provides insights to the clonal evolution from follicular lymphoma in situ to manifest follicular lymphoma
2011-09-22

To the editor: Follicular lymphoma in situ (FLIS) is characterized by the presence of a B-cell population with immunophenotypic and genotypic features of follicular lymphoma (FL) but exclusively localized to germinal centers (GCs) in morphologically reactive lymph nodes.[1][1] FLIS lesions are
Persistence and Availability of Web Services in Computational Biology
2011-09-22

We have conducted a study on the long-term availability of bioinformatics Web services: an observation of 927 Web services published in the annual Nucleic Acids Research Web Server Issues between 2003 and 2009. We found that 72% of Web sites are still available at the published addresses, only 9% of services are completely unavailable. Older addresses often redirect to new pages. We checked the functionality of all available services: for 33%, we could not test functionality because there was no example data or a related problem; 13% were truly no longer working as expected; we could positively confirm functionality only for 45% of all services. Additionally, we conducted a survey among 872 Web Server Issue corresponding authors; 274 replied. 78% of all respondents indicate their services have been developed solely by students and researchers without a permanent position. Consequently, these services are in danger of falling into disrepair after the original developers move to another institution, and indeed, for 24% of services, there is no plan for maintenance, according to the respondents. We introduce a Web service quality scoring system that correlates with the number of citations: services with a high score are cited 1.8 times more often than low-scoring services. We have identified key characteristics that are predictive of a service's survival, providing reviewers, editors, and Web service developers with the means to assess or improve Web services. A Web service conforming to these criteria receives more citations and provides more reliable service for its users. The most effective way of ensuring continued access to a service is a persistent Web address, offered either by the publishing journal, or created on the authors' own initiative, for example at http://bioweb.me. The community would benefit the most from a policy requiring any source code needed to reproduce results to be deposited in a public repository.
Bringing back monad comprehensions
2011-09-22

This paper is about a Glasgow Haskell Compiler (GHC) extension that generalises Haskell's list comprehension notation to monads. The monad comprehension notation implemented by the extension supports generator and filter clauses, as was the case in the Haskell 1.4 standard. In addition, the extension generalises the recently proposed parallel and SQL-like list comprehension notations to monads. The aforementioned generalisations are formally defined in this paper. The extension will be available in GHC 7.2.
Bringing back monad comprehensions
2011-09-22

This paper is about a Glasgow Haskell Compiler (GHC) extension that generalises Haskell's list comprehension notation to monads. The monad comprehension notation implemented by the extension supports generator and filter clauses, as was the case in the Haskell 1.4 standard. In addition, the extension generalises the recently proposed parallel and SQL-like list comprehension notations to monads. The aforementioned generalisations are formally defined in this paper. The extension will be available in GHC 7.2. This paper gives several instructive examples that we hope will facilitate wide adoption of the extension by the Haskell community. We also argue why the do notation is not always a good fit for monadic libraries and embedded domain-specific languages, especially for those that are based on collection monads. Should the question of how to integrate the extension into the Haskell standard arise, the paper proposes a solution to the problem that led to the removal of the monad comprehension notation from the language standard.
Non-axisymmetric Torsional Oscillations of Relativistic Stars
2011-09-22

We examine the non-axisymmetric Alfvén oscillations of relativistic stars with a strong dipole magnetic fields, where we have done the 2D simulation. We find that the spectrum of non-axisymmetric axial-type Alfvén oscillations is discrete as well as the axisymmetric polar Alfvén oscillations, in contrast to the spectrum of axisymmetric axial Alfvén oscillations which is continuum. We also show the dependence of Alvén frequency on the strength of magnetic field and find that such frequencies are smaller than those of the axisymmetric axial Alfvén oscillations. That is, to explain the observed evidence of quasi-periodic oscillations in the soft gamma repeaters, the non-axisymmetric axial oscillations could also play an important role.
The Blood-Brain Barrier in Brain Tumours
2011-09-22

The literature on glioblastoma is increasingly concerned with genetic pathways to and genomic analyses of glioblastoma (Ohgaki et al., 2004; Parsons et al., 2008). Mutations of numerous genes were demonstrated to be involved in the development of brain tumours; however, in most cases the mechanistic roles of these mutated genes in the dysregulation of the cells of tumour origin are not understood in functional terms, but are used for molecular diagnostics (Riemenschneider et al., 2010). Moreover, several potential biomarkers of glioblastoma were identified and classified for clinical prognosis without precise knowledge of their function (Sreekanthreddy et al., 2010). A new dimension of brain tumour research has been reached by the detection of cancer stem cells in glioblastoma which were identified as a small subpopulation of brain tumour propagating cells (Huang et al., 2010; Tabatabai & Weller, 2011). A link between glioblastoma stem cells and tumour vascularization has been established by the first description of the possibility that tumour vessels can be recruited from glioblastoma stem cells (Ricci-Vitiani et al., 2010). This opens a new field concerning the plasticity of tumour vessel endothelial cells including their lost or undifferentiated barrier properties. Since the clinical signs of the glioblastoma are connected to the intracerebral pressure due to edemas, understanding the alterations of the blood-brain barrier (BBB) is of central importance. For this reason, we will begin this chapter on the blood-tumour barrier with the description of cell biological aspects of the healthy BBB. The BBB is responsible for the homeostasis of the microenvironment in the neural parenchyma and essential for normal function of the brain. In the strict sense, it is located in the endothelial cells and restricts the paracellular diffusion of hydrophilic molecules by both complex tight junctions (Reese & Karnovsky, 1967; Brightman & Reese, 1969) and a low degree of transcytosis (Peters et al., 1991). This implies the necessity of various specific transporters for providing the brain with compounds essential for brain energy metabolism (Begley, 2004). It is generally accepted now that astrocytes play a decisive role in the maintenance if not induction of the BBB (Abbott et al., 2006; Wolburg et al., 2009). But we have to be aware that the mechanism by which this maintenance or induction of the BBB is performed, is not understood so far. In any case, in the mature brain, the astrocytes embrace the vessels by sending an endfoot towards the perivascular basal lamina (Mathiisen et al., 2010). It has
The saccadic spike artifact in MEG
2011-09-23

Electro- and magnetoencephalography (EEG/MEG) are the means to investigate the dynamics of neuronal activity non-invasively in the human brain. However, both EEG and MEG are also sensitive to non-neural sources, which can severely complicate the interpretation. The saccadic spike potential (SP) at saccade onset has been identified as a particularly problematic artifact in EEG because it closely resembles synchronous neuronal gamma band activity. While the SP and its confounding effects on EEG have been thoroughly characterized, the corresponding artifact in MEG, the saccadic spike field (SF), has not been investigated. Here we provide a detailed characterization of the SF. We simultaneously recorded MEG, EEG, gaze position and electrooculogram (EOG). We compared the SF in MEG for different saccade sizes and directions and contrasted it with the well-known SP in EEG. Our results reveal a saccade amplitude and direction dependent, lateralized saccadic spike artifact, which was most prominent in the gamma frequency range. The SF was strongest at frontal and temporal sensors but unlike the SP in EEG did not contaminate parietal sensors. Furthermore, we observed that the source configurations of the SF were comparable for regular and miniature saccades. Using distributed source analysis we identified the sources of the SF in the extraocular muscles. In summary, our results show that the SF in MEG closely resembles neuronal activity in frontal and temporal sensors. Our detailed characterization of the SF constitutes a solid basis for assessing possible saccadic spike related contamination in MEG experiments.
Power in group contexts: The influence of group status on promotion and prevention decision making
2011-09-23

This research examines how group status affects the impact of individual power positions on promotion versus prevention choices in group decision making. We consider that high power not only implies control, but also indicates responsibility for the achievement of group goals. We argue that the nature of these goals depends on the current status of the group. In Experiment 1, individuals who were accorded high power showed more promotion‐oriented decisions in the low group status condition while decisions were more prevention oriented under high group status. Experiment 2 replicated these effects, and further demonstrated that they only emerge when those in power are explicitly made accountable for the achievement of group goals. These results are discussed in relation to regulatory focus theory, power theories, and the role of social identities and group goals in group dynamics.
Self-consistent description of shape coexistence in the A≃100 Zr nuclei
2011-09-23

The shape transition, shape coexistence, and shape mixing characterizing the netron-rich Zr nuclei in the A≃100 region are consistently described at low and high spin states in the frame of the complex Excited Vampir variational approach using a realistic effective interaction obtained from Bonn A potential in a large model space. The influence of the shape mixing on the structure and dynamics of the investigated Zr isotopes is discussed and comparison with the available data is presented.
Crossover between different regimes of inhomogeneous superconductivity in planar superconductor-ferromagnet hybrids
2011-09-23

We studied experimentally the effect of a stripelike domain structure in a ferromagnetic BaFe12O19 substrate on the magnetoresistance of a superconducting Pb microbridge. The system was designed in such a way that the bridge is oriented perpendicular to the domain walls. It is demonstrated that depending on the ratio between the amplitude of the nonuniform magnetic field B-0, induced by the ferromagnet, and the upper critical field H-c2 of the superconducting material, the regions of the reverse-domain superconductivity in the H-T plane can be isolated or can overlap (H is the external magnetic field, T is temperature). The latter case corresponds to the condition B-0/H-c2 &lt; 1 and results in the formation of superconductivity above the magnetic domains of both polarities. We discovered the regime of edge-assisted reverse-domain superconductivity, corresponding to localized superconductivity near the edges of the bridge above the compensated magnetic domains. Direct verification of the formation of inhomogeneous superconducting states and external-field-controlled switching between the normal state and inhomogeneous superconductivity were obtained by low-temperature scanning laser microscopy.
GERDA - a new neutrinoless double beta experiment using76Ge
2011-09-23

The search for neutrinoless double beta decay (0νßß) has been a very active field for the last decades. While double beta decay has been observed, 0νßß decay still waits for its experimental proof. The GErmanium Detector Array (GERDA) uses 76Ge, an ideal candidate as it is acting as source and detector simultaneously. Germanium detectors, isotopically enriched in 76Ge are submerged directly into an ultra pure cryo liquid, which serves as coolant and radiation shield. This concept will allow to reduce the background by up to two orders of magnitude with respect to earlier experiments. GERDA has been constructed in hall A of the underground laboratory LNGS of the INFN in Italy. The experiment started recently with a test run.
The effect of temporal distance on comparative visual search
2011-09-23

The spatial distance between two simultaneous presented pictures determines comparative visual search (CVS) behavior. With increasing distance, humans conduct fewer gaze-shifts between two simultaneously presented pictures when searching differences, suggesting a higher use of the visual short-term memory (VSTM). Previous research examined search behavior with pictures presented next to each other thus not only varying spatial but also temporal distances as the gaze-shift duration increases with increasing distance between picture pairs. In this study we examined the contribution of pure temporal distances to the trade-off between the number of changes between pictures and VSTM use. We hypothesized that longer temporal distances between two alternating images leads to higher VSTM use. We further hypothesized a higher use of chunking strategies for participants with domain knowledge. Prior to the search task participants received either stimulus-related or -unrelated information thus manipulating domain knowledge. Participants had to search for differences between two pictures of a pendulum clock that were presented on one display one at a time. They could alternate between them by pressing a key. The change was delayed by 120 or 500 ms. We measured the number of shifts between the pictures and recorded gaze behavior. Results showed a trade-off between the number of shifts between pictures and the temporal distance. This replicates effects known from CVS with pure temporal instead of both temporal and spatial distances. Further, participants with domain knowledge conducted a smaller number of shifts in both distance conditions suggesting a higher use of chunking strategies. Eye tracking data complement the findings. Participants who received domain knowledge showed a fewer number of fixations and smaller saccade amplitudes. This is in line with findings in eye tracking literature. In sum, there is an influence of domain knowledge on the replicated trade-off in a temporal CVS paradigm.
Maintaining visual attention across abrupt spatiotemporal discontinuities: The role of feature information
2011-09-23

When spatiotemporal continuity of attended objects is disrupted, object correspondence needs to be established to maintain attentional selection. Spatial configurations are insufficient for establishing object correspondence as demonstrated by impaired multiple object tracking across abrupt scene rotations. The contribution of object features for establishing object correspondence in attentive tracking is unknown. Although object features are poorly retained during attentive tracking when retention is explicitly tested, tracking performance increases if objects stay uniquely colored during movement. We report three experiments examining the impact of briefly shown feature information on maintaining visual spatial attention across spatiotemporal discontinuities elicited by abrupt scene rotations. In Experiment 1, participants tracked 3–5 out of 10 objects in a 3D-scene lasting 6 seconds. In half of the trials we introduced abrupt scene rotations of 30° after 3 seconds. After 2.5 s all objects changed their color for 1000 ms, thus staying colored across scene rotations. Object colors were either unique or homogeneous. Unique object colors improved tracking across abrupt scene rotations. In Experiment 2 and 3, we manipulated whether color information was available to establish correspondence at the abrupt scene rotations. We introduced two 500 ms color intervals, one before and one after the scene rotation. They were separated by 0 ms (replicating the 1000 ms interval in Experiment 1), 500 ms, or 1000 ms to the abrupt scene rotation each. Between color intervals objects were white. The advantage of unique color information was higher when unique colors were present at the time of the scene rotation. When colors were restricted to equidistant gradations of a hue of 153–207 degree in HSV color space (thus preventing verbalization strategies) the feature effect was present with colors at the time of the scene rotation only. We conclude that feature information is used to maintain visual spatial attention across abrupt spatiotemporal discontinuities.