1,027 research outputs found
Why Some Interfaces Cannot be Sharp
A central goal of modern materials physics and nanoscience is control of
materials and their interfaces to atomic dimensions. For interfaces between
polar and non-polar layers, this goal is thwarted by a polar catastrophe that
forces an interfacial reconstruction. In traditional semiconductors this
reconstruction is achieved by an atomic disordering and stoichiometry change at
the interface, but in multivalent oxides a new option is available: if the
electrons can move, the atoms don`t have to. Using atomic-scale electron energy
loss spectroscopy we find that there is a fundamental asymmetry between
ionically and electronically compensated interfaces, both in interfacial
sharpness and carrier density. This suggests a general strategy to design sharp
interfaces, remove interfacial screening charges, control the band offset, and
hence dramatically improving the performance of oxide devices.Comment: 12 pages of text, 6 figure
A Compromise between Neutrino Masses and Collider Signatures in the Type-II Seesaw Model
A natural extension of the standard gauge
model to accommodate massive neutrinos is to introduce one Higgs triplet and
three right-handed Majorana neutrinos, leading to a neutrino mass
matrix which contains three sub-matrices ,
and . We show that three light Majorana neutrinos (i.e., the mass
eigenstates of , and ) are exactly massless in this
model, if and only if
exactly holds. This no-go theorem implies that small but non-vanishing neutrino
masses may result from a significant but incomplete cancellation between
and terms in the Type-II
seesaw formula, provided three right-handed Majorana neutrinos are of TeV and experimentally detectable at the LHC. We propose three simple
Type-II seesaw scenarios with the flavor symmetry to
interpret the observed neutrino mass spectrum and neutrino mixing pattern. Such
a TeV-scale neutrino model can be tested in two complementary ways: (1)
searching for possible collider signatures of lepton number violation induced
by the right-handed Majorana neutrinos and doubly-charged Higgs particles; and
(2) searching for possible consequences of unitarity violation of the neutrino mixing matrix in the future long-baseline neutrino oscillation
experiments.Comment: RevTeX 19 pages, no figure
An addressable quantum dot qubit with fault-tolerant control fidelity
Exciting progress towards spin-based quantum computing has recently been made
with qubits realized using nitrogen-vacancy (N-V) centers in diamond and
phosphorus atoms in silicon, including the demonstration of long coherence
times made possible by the presence of spin-free isotopes of carbon and
silicon. However, despite promising single-atom nanotechnologies, there remain
substantial challenges in coupling such qubits and addressing them
individually. Conversely, lithographically defined quantum dots have an
exchange coupling that can be precisely engineered, but strong coupling to
noise has severely limited their dephasing times and control fidelities. Here
we combine the best aspects of both spin qubit schemes and demonstrate a
gate-addressable quantum dot qubit in isotopically engineered silicon with a
control fidelity of 99.6%, obtained via Clifford based randomized benchmarking
and consistent with that required for fault-tolerant quantum computing. This
qubit has orders of magnitude improved coherence times compared with other
quantum dot qubits, with T_2* = 120 mus and T_2 = 28 ms. By gate-voltage tuning
of the electron g*-factor, we can Stark shift the electron spin resonance (ESR)
frequency by more than 3000 times the 2.4 kHz ESR linewidth, providing a direct
path to large-scale arrays of addressable high-fidelity qubits that are
compatible with existing manufacturing technologies
Suppression of Lung Tumorigenesis by Leucine Zipper/EF Hand–Containing Transmembrane-1
Leucine zipper/EF hand-containing transmembrane-1 (LETM1) encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. However, a previous study demonstrated that LETM1 served as an anchor protein for complex formation between mitochondria and ribosome, and regulated mitochondrial biogenesis.Therefore, we examine the possibility that LETM1 may function to regulate mitochondria and lung tumor growth. In this study, we addressed this question by studying in the effect of adenovirus-mediated LETM1 in the lung cancer cell and lung cancer model mice. To investigate the effects of adenovirus-LETM1 in vitro, we infected with adenovirus-LETM1 in A549 cells. Additionally, in vivo effects of LETM1 were evaluated on K-ras(LA1) mice, human non-small cell lung cancer model mice, by delivering the LETM1 via aerosol through nose-only inhalation system. The effects of LETM1 on lung cancer growth and AMPK related signals were evaluated. Adenovirus-mediated overexpression of LETM1 could induce destruction of mitochondria of lung cancer cells through depleting ATP and AMPK activation. Furthermore, adenoviral-LETM1 also altered Akt signaling and inhibited the cell cycle while facilitating apoptosis. Theses results demonstrated that adenovirus-LETM1 suppressed lung cancer cell growth in vitro and in vivo.Adenovirus-mediated LETM1 may provide a useful target for designing lung tumor prevention and treatment
Reverse Effect of Mammalian Hypocalcemic Cortisol in Fish: Cortisol Stimulates Ca2+ Uptake via Glucocorticoid Receptor-Mediated Vitamin D3 Metabolism
Cortisol was reported to downregulate body-fluid Ca2+ levels in mammals but was proposed to show hypercalcemic effects in teleostean fish. Fish, unlike terrestrial vertebrates, obtain Ca2+ from the environment mainly via the gills and skin rather than by dietary means, and have to regulate the Ca2+ uptake functions to cope with fluctuating Ca2+ levels in aquatic environments. Cortisol was previously found to regulate Ca2+ uptake in fish; however, the molecular mechanism behind this is largely unclear. Zebrafish were used as a model to explore this issue. Acclimation to low-Ca2+ fresh water stimulated Ca2+ influx and expression of epithelial calcium channel (ecac), 11β-hydroxylase and the glucocorticoid receptor (gr). Exogenous cortisol increased Ca2+ influx and the expressions of ecac and hydroxysteroid 11-beta dehydrogenase 2 (hsd11b2), but downregulated 11β-hydroxylase and the gr with no effects on other Ca2+ transporters or the mineralocorticoid receptor (mr). Morpholino knockdown of the GR, but not the MR, was found to impair zebrafish Ca2+ uptake function by inhibiting the ecac expression. To further explore the regulatory mechanism of cortisol in Ca2+ uptake, the involvement of vitamin D3 was analyzed. Cortisol stimulated expressions of vitamin D-25hydroxylase (cyp27a1), cyp27a1 like (cyp27a1l), 1α-OHase (cyp27b1) at 3 dpf through GR, the first time to demonstrate the relationship between cortisol and vitamin D3 in fish. In conclusion, cortisol stimulates ecac expression to enhance Ca2+ uptake functions, and this control pathway is suggested to be mediated by the GR. Lastly, cortisol also could mediate vitamin D3 signaling to stimulate Ca2+ uptake in zebrafish
Phosphorylation of Nrf2 at Multiple Sites by MAP Kinases Has a Limited Contribution in Modulating the Nrf2-Dependent Antioxidant Response
The bZIP transcription factor Nrf2 has emerged as a pivotal regulator of intracellular redox homeostasis by controlling the expression of many endogenous antioxidants and phase II detoxification enzymes. Upon oxidative stress, Nrf2 is induced at protein levels through redox-sensitive modifications on cysteine residues of Keap1, a component of the E3 ubiquitin ligase that targets Nrf2 for ubiquitin-dependent degradation. The mitogen activated protein kinases (MAPKs) have previously been proposed to regulate Nrf2 in response to oxidative stress. However, the exact role of MAPKs and the underlying molecular mechanism remain poorly defined. Here we report the first evidence that Nrf2 is phosphorylated in vivo by MAPKs. We have identified multiple serine/threonine residues as major targets of MAPK-mediated phosphorylation. Combined alanine substitution on those residues leads to a moderate decrease in the transcriptional activity of Nrf2, most likely due to a slight reduction in its nuclear accumulation. More importantly, Nrf2 protein stability, primarily controlled by Keap1, is not altered by Nrf2 phosphorylation in vivo. These data indicate that direct phosphorylation of Nrf2 by MAPKs has limited contribution in modulating Nrf2 activity. We suggest that MAPKs regulate the Nrf2 signaling pathway mainly through indirect mechanisms
Fatores de risco cardiovascular em pessoas semabrigo e na população geral da cidade do Porto, Portugal
We described the distribution of risk factors for cardiovascular disease among homeless people living in the city of Porto, Portugal. Comparisons were made between subsamples of homeless people recruited in different settings and between the overall homeless sample group and a sample of the general population. All "houseless" individuals attending one of two homeless hostels or two institutions providing meal programs on specific days were invited to participate and were matched with subjects from the general population. We estimated sex, age and education-adjusted prevalence ratios or mean differences. The prevalence of previous illicit drug consumption and imprisonment was almost twice as high among the homeless from institutions providing meal programs. This group also showed lower mean systolic and diastolic blood pressure. Prevalence of smoking was almost 50% higher in the overall homeless group. Mean body mass index and waist circumference were also lower in the homeless group and its members were almost five times less likely to report dyslipidemia. Our findings contribute to defining priorities for interventions directed at this segment of society and to reducing inequalities in this extremely underprivileged populatio
Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer
Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies
Tumor-Derived Microvesicles Induce, Expand and Up-Regulate Biological Activities of Human Regulatory T Cells (Treg)
Background: Tumor-derived microvesicles (TMV) or exosomes are present in body fluids of patients with cancer and might be involved in tumor progression. The frequency and suppressor functions of peripheral blood CD4 + CD25 high FOXP3 + Treg are higher in patients with cancer than normal controls. The hypothesis is tested that TMV contribute to induction/ expansion/and activation of human Treg. Methodology/Principal Findings: TMV isolated from supernatants of tumor cells but not normal cells induced the generation and enhanced expansion of human Treg. TMV also mediated conversion of CD4 + CD25 neg T cells into CD4 + CD25 high FOXP3 + Treg. Upon co-incubation with TMV, Treg showed an increased FasL, IL-10, TGF-b1, CTLA-4, granzyme B and perforin expression (p,0.05) and mediated stronger suppression of responder cell (RC) proliferation (p,0.01). Purified Treg were resistant to TMV-mediated apoptosis relative to other T cells. TMV also increased phospho-SMAD2/3 and phospho-STAT3 expression in Treg. Neutralizing Abs specific for TGF-b1 and/or IL-10 significantly inhibited TMV ability to expand Treg. Conclusions/Significance: This study suggests that TMV have immunoregulatory properties. They induce Treg, promote Treg expansion, up-regulate Treg suppressor function and enhance Treg resistance to apoptosis. Interactions of TMV wit
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