53 research outputs found
Modeling the scaling properties of human mobility
While the fat tailed jump size and the waiting time distributions
characterizing individual human trajectories strongly suggest the relevance of
the continuous time random walk (CTRW) models of human mobility, no one
seriously believes that human traces are truly random. Given the importance of
human mobility, from epidemic modeling to traffic prediction and urban
planning, we need quantitative models that can account for the statistical
characteristics of individual human trajectories. Here we use empirical data on
human mobility, captured by mobile phone traces, to show that the predictions
of the CTRW models are in systematic conflict with the empirical results. We
introduce two principles that govern human trajectories, allowing us to build a
statistically self-consistent microscopic model for individual human mobility.
The model not only accounts for the empirically observed scaling laws but also
allows us to analytically predict most of the pertinent scaling exponents
Tailoring the atomic structure of graphene nanoribbons by STM lithography
The practical realization of nano-scale electronics faces two major
challenges: the precise engineering of the building blocks and their assembly
into functional circuits. In spite of the exceptional electronic properties of
carbon nanotubes only basic demonstration-devices have been realized by
time-consuming processes. This is mainly due to the lack of selective growth
and reliable assembly processes for nanotubes. However, graphene offers an
attractive alternative. Here we report the patterning of graphene nanoribbons
(GNRs) and bent junctions with nanometer precision, well-defined widths and
predetermined crystallographic orientations allowing us to fully engineer their
electronic structure using scanning tunneling microscope (STM) lithography. The
atomic structure and electronic properties of the ribbons have been
investigated by STM and tunneling spectroscopy measurements. Opening of
confinement gaps up to 0.5 eV, allowing room temperature operation of GNR-based
devices, is reported. This method avoids the difficulties of assembling
nano-scale components and allows the realization of complete integrated
circuits, operating as room temperature ballistic electronic devices.Comment: 8 pages text, 5 figures, Nature Nanotechnology, in pres
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)
Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of
patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central
mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL.
However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent
phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL
patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited
increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor
4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of
chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for
p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed
patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to
identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic
cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments
The transcriptional activity of hepatocyte nuclear factor 4 alpha is inhibited via phosphorylation by ERK1/2
Hepatocyte nuclear factor 4 alpha (HNF4alpha) nuclear receptor is a master regulator of hepatocyte development, nutrient transport and metabolism. HNF4alpha is regulated both at the transcriptional and post-transcriptional levels by different mechanisms. Several kinases (PKA, PKC, AMPK) were shown to phosphorylate and decrease the activity of HNF4alpha. Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4alpha. However, based on our previous results we hypothesized that HNF4alpha is also regulated at the post-transcriptional level by ERK1/2. Here we show that ERK1/2 is capable of directly phosphorylating HNF4alpha in vitro at several phosphorylation sites including residues previously shown to be targeted by other kinases, as well. Furthermore, we also demonstrate that phosphorylation of HNF4alpha leads to a reduced trans-activational capacity of the nuclear receptor in luciferase reporter gene assay. We confirm the functional relevance of these findings by demonstrating with ChIP-qPCR experiments that 30-minute activation of ERK1/2 leads to reduced chromatin binding of HNF4alpha. Accordingly, we have observed decreasing but not disappearing binding of HNF4alpha to the target genes. In addition, 24-hour activation of the pathway further decreased HNF4alpha chromatin binding to specific loci in ChIP-qPCR experiments, which confirms the previous reports on the decreased expression of the HNF4a gene due to ERK1/2 activation. Our data suggest that the ERK1/2 pathway plays an important role in the regulation of HNF4alpha-dependent hepatic gene expression
The role of rewards and demands in burnout among surgical nurses
Job rewards have both, an intrinsic and an extrinsic motivational potential, and lead to employees’ development
as well as help them to achieve work goals. Rewards can balance job demands and protect from burnout. Due to changes on
the labour market, new studies are needed. The aim of our study was to examine the role of demands and individual rewards
(and their absence) in burnout among surgical nurses. Materials and Methods: The study was conducted in 2009 and 2010
with 263 nurses who worked in surgical wards and clinics in hospitals in Southern Poland. The hypotheses were tested by
the use of measures of demands and rewards (Effort-Reward Imbalance Questionnaire by Siegrist) and burnout syndrome
(Maslach Burnout Inventory). A cross-sectional, correlational study design was applied. Results: Nurses experienced the
largest deficiencies in salary and prestige. Exhaustion was explained by stronger demands and lack of respect (large effect).
Depersonalization was explained by stronger demands, lack of respect and greater job security (medium effect). Reduced
personal achievement was explained by more demands and greater job security (small effect). Conclusions: Excessive demands and lack of esteem are key reasons for burnout among surgical nurses. Job security can increase burnout when too
many resources are invested and career opportunities do not appear. These results may help to improve human resource
management in the healthcare sector
Glutamate Uptake Triggers Transporter-Mediated GABA Release from Astrocytes
Background: Glutamate (Glu) and c-aminobutyric acid (GABA) transporters play important roles in regulating neuronal activity. Glu is removed from the extracellular space dominantly by glial transporters. In contrast, GABA is mainly taken up by neurons. However, the glial GABA transporter subtypes share their localization with the Glu transporters and their expression is confined to the same subpopulation of astrocytes, raising the possibility of cooperation between Glu and GABA transport processes. Methodology/Principal Findings: Here we used diverse biological models both in vitro and in vivo to explore the interplay between these processes. We found that removal of Glu by astrocytic transporters triggers an elevation in the extracellular level of GABA. This coupling between excitatory and inhibitory signaling was found to be independent of Glu receptor-mediated depolarization, external presence of Ca2+ and glutamate decarboxylase activity. It was abolished in the presence of non-transportable blockers of glial Glu or GABA transporters, suggesting that the concerted action of these transporters underlies the process. Conclusions/Significance: Our results suggest that activation of Glu transporters results in GABA release through reversal of glial GABA transporters. This transporter-mediated interplay represents a direct link between inhibitory and excitatory neurotransmission and may function as a negative feedback combating intense excitation in pathological conditions such as epilepsy or ischemia
Astrocytes convert network excitation to tonic inhibition of neurons
<p>Abstract</p> <p>Background</p> <p>Glutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.</p> <p>Results</p> <p>Here we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na<sup>+ </sup>concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg<sup>2+</sup>] <it>in vitro </it>model of epilepsy. Under <it>in vivo </it>conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.</p> <p>Conclusions</p> <p>The results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamat<it>ergic </it>excitation into GABA<it>ergic </it>inhibition providing an adjustable, <it>in situ </it>negative feedback on the excitability of neurons.</p
Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation
Somatic mutations in the RAS genes are frequent in human tumors, especially in pancreatic, colorectal, and non-small-cell lung cancers. Such mutations generally decrease the ability of Ras to hydrolyze GTP, maintaining the protein in a constitutively active GTP-bound form that drives uncontrolled cell proliferation. Efforts to develop drugs that target Ras oncoproteins have been unsuccessful. Recent emerging data suggest that Ras regulation is more complex than the scientific community has believed for decades. In this review, we summarize advances in the "textbook" view of Ras activation. We also discuss a novel type of Ras regulation that involves direct phosphorylation and dephosphorylation of Ras tyrosine residues. The discovery that pharmacological inhibition of the tyrosine phosphoprotein phosphatase SHP2 maintains mutant Ras in an inactive state suggests that SHP2 could be a novel drug target for the treatment of Ras-driven human cancers
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