5,202 research outputs found
Entirely irrelevant distractors can capture and captivate attention
The question of whether a stimulus onset may capture attention when it is entirely irrelevant to the task and even in the absence of any attentional settings for abrupt onset or any dynamic changes has been highly controversial. In the present study, we designed a novel irrelevant capture task to address this question. Participants engaged in a continuous task making sequential forced choice (letter or digit) responses to each item in an alphanumeric matrix that remained on screen throughout many responses. This task therefore involved no attentional settings for onset or indeed any dynamic changes, yet the brief onset of an entirely irrelevant distractor (a cartoon picture) resulted in significant slowing of the two (Experiment 1) or three (Experiment 2) responses immediately following distractor appearance These findings provide a clear demonstration of attention being captured and captivated by a distractor that is entirely irrelevant to any attentional settings of the task
G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial
Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors
Small RNA analysis in Sindbis virus infected human HEK293 cells
In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells
Non-specific binding of antibodies in immunohistochemistry: fallacies and facts
The current protocols for blocking background staining in immunohistochemistry are based on conflicting reports. Background staining is thought to occur as a result of either non-specific antibody (Ab) binding to endogenous Fc receptors (FcRs) or a combination of ionic and hydrophobic interactions. In this study, cell and tissue samples were processed according to routine protocols either with or without a blocking step (goat serum or BSA). Surprisingly, no Abs in samples processed without a blocking step showed any propensity for non-specific binding leading to background staining, implying that endogenous FcRs do not retain their ability to bind the Fc portion of Abs after standard fixation. Likewise, we did not find any non-specific Ab binding ascribable to either ionic or hydrophobic interactions. We determined that traditionally used protein blocking steps are unnecessary in the immunostaining of routinely fixed cell and tissue samples
Characteristics of transposable element exonization within human and mouse
Insertion of transposed elements within mammalian genes is thought to be an
important contributor to mammalian evolution and speciation. Insertion of
transposed elements into introns can lead to their activation as alternatively
spliced cassette exons, an event called exonization. Elucidation of the
evolutionary constraints that have shaped fixation of transposed elements
within human and mouse protein coding genes and subsequent exonization is
important for understanding of how the exonization process has affected
transcriptome and proteome complexities. Here we show that exonization of
transposed elements is biased towards the beginning of the coding sequence in
both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs)
revealed that exonization of transposed elements can be population-specific,
implying that exonizations may enhance divergence and lead to speciation. SNP
density analysis revealed differences between Alu and other transposed
elements. Finally, we identified cases of primate-specific Alu elements that
depend on RNA editing for their exonization. These results shed light on TE
fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure
A review of mid-frequency vibro-acoustic modelling for high-speed train extruded aluminium panels as well as the most recent developments in hybrid modelling techniques
Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer
Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study
The last decade has seen an explosion in models that describe phenomena in
systems medicine. Such models are especially useful for studying signaling
pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to
showcase current mathematical and statistical techniques that enable modelers
to gain insight into (models of) gene regulation, and generate testable
predictions. We introduce a range of modeling frameworks, but focus on ordinary
differential equation (ODE) models since they remain the most widely used
approach in systems biology and medicine and continue to offer great potential.
We present methods for the analysis of a single model, comprising applications
of standard dynamical systems approaches such as nondimensionalization, steady
state, asymptotic and sensitivity analysis, and more recent statistical and
algebraic approaches to compare models with data. We present parameter
estimation and model comparison techniques, focusing on Bayesian analysis and
coplanarity via algebraic geometry. Our intention is that this (non exhaustive)
review may serve as a useful starting point for the analysis of models in
systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte
ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro
<p>Abstract</p> <p>Background</p> <p>Dengue virus (DENV) and West Nile virus (WNV), close siblings of the <it>Flaviviridae </it>family, are the causative agents of Dengue hemorraghic shock or West Nile meningoencephalitis respectively. Vaccines against these two flaviviruses are currently unavailable. Interferon- Stimulated Gene 15 (<it>ISG15</it>), encoding an ubiquitin-like protein, is significantly induced by type I interferons or viral infections. Its roles in viral infections, however, vary with viruses, being either anti- or pro-viral. The exact roles of ISG15 in DENV and WNV infections remain unknown. In the current study, we evaluated the relevancies of ISG15 to DENV and WNV infection of a mouse macrophage cell line RAW264.7.</p> <p>Findings</p> <p>Quantitative PCR showed that mouse <it>Isg15 </it>was dramatically induced in DENV or WNV- infected RAW264.7 cells compared with non-infected cells. <it>Isg15 </it>and two other Jak-Stat related genes, <it>Socs1 </it>and <it>Socs3</it>, were silenced using siRNA mediated RNA interference. The intracellular DENV and WNV loads, as determined by quantitative PCR, were significantly higher in <it>Isg15 </it>silenced cells than control cells. The expression levels of interferon beta 1 (<it>Ifnb1</it>) were increased significantly in <it>Isg15</it>, <it>Socs1 </it>or <it>Socs3 </it>siRNA treated cells. Further investigation indicated that protein modification by ISG15, so called ISGylation, was significantly enhanced in DENV-infected cells compared to that in non-infected cells.</p> <p>Conclusions</p> <p>These findings suggest that ISG15 plays an anti-DENV/WNV function via protein ISGylation.</p
Constraints on Non-Newtonian Gravity from Recent Casimir Force Measurements
Corrections to Newton's gravitational law inspired by extra dimensional
physics and by the exchange of light and massless elementary particles between
the atoms of two macrobodies are considered. These corrections can be described
by the potentials of Yukawa-type and by the power-type potentials with
different powers. The strongest up to date constraints on the corrections to
Newton's gravitational law are reviewed following from the E\"{o}tvos- and
Cavendish-type experiments and from the measurements of the Casimir and van der
Waals force. We show that the recent measurements of the Casimir force gave the
possibility to strengthen the previously known constraints on the constants of
hypothetical interactions up to several thousand times in a wide interaction
range. Further strengthening is expected in near future that makes Casimir
force measurements a prospective test for the predictions of fundamental
physical theories.Comment: 20 pages, crckbked.cls is used, to be published in: Proceedings of
the 18th Course of the School on Cosmology and Gravitation: The Gravitational
Constant. Generalized Gravitational Theories and Experiments (30 April- 10
May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata,
20pp. (Kluwer, in print, 2003
Heterotic Line Bundle Standard Models
In a previous publication, arXiv:1106.4804, we have found 200 models from
heterotic Calabi-Yau compactifications with line bundles, which lead to
standard models after taking appropriate quotients by a discrete symmetry and
introducing Wilson lines. In this paper, we construct the resulting standard
models explicitly, compute their spectrum including Higgs multiplets, and
analyze some of their basic properties. After removing redundancies we find
about 400 downstairs models, each with the precise matter spectrum of the
supersymmetric standard model, with one, two or three pairs of Higgs doublets
and no exotics of any kind. In addition to the standard model gauge group, up
to four Green-Schwarz anomalous U(1) symmetries are present in these models,
which constrain the allowed operators in the four-dimensional effective
supergravity. The vector bosons associated to these anomalous U(1) symmetries
are massive. We explicitly compute the spectrum of allowed operators for each
model and present the results, together with the defining data of the models,
in a database of standard models accessible at
http://www-thphys.physics.ox.ac.uk/projects/CalabiYau/linebundlemodels/index.html.
Based on these results we analyze elementary phenomenological properties. For
example, for about 200 models all dimension four and five proton decay
violating operators are forbidden by the additional U(1) symmetries.Comment: 55 pages, Latex, 3 pdf figure
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