640 research outputs found
Nonequilibrium Current in the One Dimensional Hubbard Model at Half-Filling
Nonlinear transport in the one dimensional Hubbard model at half-filling
under a finite bias voltage is investigated by the adaptive time-dependent
density matrix renormalization group method. For repulsive on-site interaction,
dielectric breakdown of the Mott insulating ground state to a current-carrying
nonequilibrium steady state is clearly observed when the voltage exceeds the
charge gap. It is found that by increasing the voltage further the
current-voltage characteristics are scaled only by the charge gap and the
scaling curve exhibits almost linear dependence on the voltage whose slope is
suppressed by the electron correlation. In the case of attractive interaction
the linear conductance is the perfect one which agrees with the
prediction by the Luttinger liquid theory.Comment: 4 pages, 7 figure
3D-electrical resistivity tomography monitoring of salt transport in homogeneous and layered soil samples
Monitoring transport of dissolved substances in soil deposits is particularly relevant where safety is concerned, as in the case of geo-environmental barriers. Geophysical methods are very appealing, since they cover a wide domain, localising possible preferential flow paths and providing reliable links between geophysical quantities and hydrological variables. This paper describes a 3D laboratory application of Electrical Resistivity Tomography (ERT) used to monitor solute transport processes. Dissolution and transport tests on both homogeneous and heterogeneous samples were conducted in an instrumented oedometer cell. ERT was used to create maps of electrical conductivity of the monitored domain at different time intervals and to estimate concentration variations within the interstitial fluid. Comparisons with finite element simulations of the transport processes were performed to check the consistency of the results. Tests confirmed that the technique can monitor salt transport, infer the hydro-chemical behaviour of heterogeneous geomaterials and evaluate the performances of clay barrier
Nonâinvasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles
The authors thank J. Bossenga for collecting urine
and P.P. Eijk for their technical assistance in smallRNA
sequencing library preparations.In many cancer types, the expression and function of ~22 nucleotideâlong
microRNAs (miRNA) is deregulated. Mature miRNAs can be stably detected in
extracellular vesicles (EVs) in biofluids, therefore they are considered to have great
potential as biomarkers. In the present study, we investigated whether miRNAs have a
distinct expression pattern in urineâEVs of prostate cancer (PCa) patients compared to
control males. By next generation sequencing, we determined the miRNA expression
in a discovery cohort of 4 control men and 9 PCa patients. miRNAs were validated by
using a stemloop RTâPCR in an independent cohort of 74 patients (26 control and 48
PCaâpatients). Whereas standard mapping protocols identified > 10 PCa associated
miRNAs in urinary EVs, miRâ21, miRâ375 and miRâ204 failed to robustly discriminate
for disease in a validation study with RTâPCRâdetection of mature miRNA sequences. In
contrast, we observed that miRNA isoforms (isomiRs) with 3âČ end modifications were
highly discriminatory between samples from control men and PCa patients. Highly
differentially expressed isomiRs of miRâ21, miRâ204 and miRâ375 were subsequently
validated in an independent group of 74 patients. Receiverâoperating characteristic
analysis was performed to evaluate the diagnostic performance of three isomiRs,
resulting in a 72.9% sensitivity with a high (88%) specificity and an area under the
curve (AUC) of 0.866. In comparison, prostate specific antigen had an AUC of 0.707
and measuring the mature form of these miRNAs yielded a lower 70.8% sensitivity
and 72% specificity (AUC 0.766). We propose that isomiRs may carry discriminatory
information which is useful to generate stronger biomarkers.Stichting Urologie
1973VUmc-CCAWorldwide Cancer Research (AICR)
15-1005KWF-VU-5510Worldwide Cancer Research
15-100
Consequential considerations when mapping tRNA fragments
We examine several of the choices that went into the design of tDRmapper, a recently reported tool for identifying transfer RNA (tRNA) fragments in deep sequencing data, evaluate them in the context of currently available knowledge, and discuss their potential impact on the output that the tool generates
Development of a mouse monoclonal antibody for the detection of asymmetric dimethylarginine of Translocated in LipoSarcoma/FUsed in Sarcoma and its application in analyzing methylated TLS
The Encoding of Temporally Irregular and Regular Visual Patterns in the Human Brain
In the work reported here, we set out to study the neural systems that detect predictable temporal patterns and departures from them. We used functional magnetic resonance imaging (fMRI) to locate activity in the brains of subjects when they viewed temporally regular and irregular patterns produced by letters, numbers, colors and luminance. Activity induced by irregular sequences was located within dorsolateral prefrontal cortex, including an area that was responsive to irregular patterns regardless of the type of visual stimuli producing them. Conversely, temporally regular arrangements resulted in activity in the right frontal lobe (medial frontal gyrus), in the left orbito-frontal cortex and in the left pallidum. The results show that there is an abstractive system in the brain for detecting temporal irregularity, regardless of the source producing it
Autoimmune and autoinflammatory mechanisms in uveitis
The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders
The cytokine tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 have a neuroprotective effect in the central nervous system
<p>Abstract</p> <p>Background</p> <p>Cerebral cortical neurons have a high vulnerability to the harmful effects of hypoxia. However, the brain has the ability to detect and accommodate to hypoxic conditions. This phenomenon, known as preconditioning, is a natural adaptive process highly preserved among species whereby exposure to sub-lethal hypoxia promotes the acquisition of tolerance to a subsequent lethal hypoxic injury. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are found in neurons and their expression is induced by exposure to sub-lethal hypoxia. Accordingly, in this work we tested the hypothesis that the interaction between TWEAK and Fn14 induces tolerance to lethal hypoxic and ischemic conditions.</p> <p>Methods</p> <p>Here we used <it>in vitro </it>and <it>in vivo </it>models of hypoxic and ischemic preconditioning, an animal model of transient middle cerebral artery occlusion and mice and neurons genetically deficient in TWEAK, Fn14, or tumor necrosis factor alpha (TNF-α) to investigate whether treatment with recombinant TWEAK or an increase in the expression of endogenous TWEAK renders neurons tolerant to lethal hypoxia. We used enzyme-linked immunosorbent assay to study the effect of TWEAK on the expression of neuronal TNF-α, Western blot analysis to investigate whether the effect of TWEAK was mediated by activation of mitogen-activated protein kinases and immunohistochemical techniques and quantitative real-time polymerase chain reaction analysis to study the effect of TWEAK on apoptotic cell death.</p> <p>Results</p> <p>We found that either treatment with recombinant TWEAK or an increase in the expression of TWEAK and Fn14 induce hypoxic and ischemic tolerance <it>in vivo </it>and <it>in vitro</it>. This protective effect is mediated by neuronal TNF-α and activation of the extracellular signal-regulated kinases 1 and 2 pathway via phosphorylation and inactivation of the B-cell lymphoma 2-associated death promoter protein.</p> <p>Conclusions</p> <p>Our work indicate that the interaction between TWEAK and Fn14 triggers the activation of a cell signaling pathway that results in the induction of tolerance to lethal hypoxia and ischemia. These data indicate that TWEAK may be a potential therapeutic strategy to protect the brain from the devastating effects of an ischemic injury.</p
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