A facile and straightforward methodology for the preparation of monometallic (copper and palladium) and bimetallic nanocatalysts (NiCu and PdCu) stabilized by a N‐heterocyclic carbene ligand is ...reported. Both colloidal and supported nanoparticles (NPs) on carbon nanotubes (CNTs) were prepared in a one‐pot synthesis with outstanding control on their size, morphology and composition. These catalysts were evaluated in the selective hydrogenation of alkynes and alkynols. PdCu/CNTs revealed an efficient catalytic system providing high selectivity in the hydrogenation of terminal and internal alkynes. Moreover, this catalyst was tested in the semi‐hydrogenation of acetylene in industrially relevant acetylene/ethylene‐rich model gas feeds and showed excellent stability even after 40 h of reaction.
Working alone and together: A facile and straightforward methodology for the preparation of monometallic (copper and palladium) and bimetallic nanocatalysts (NiCu and PdCu) stabilized by a N‐heterocyclic carbene ligand is reported. Both colloidal and supported nanoparticles (NPs) on carbon nanotubes (CNTs) were prepared and tested for selective hydrogenations of alkynes and alkynols.
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions ...have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin's co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.
ABSTRACT
Large-amplitude Sgr A* near-infrared (NIR) flares result from energy injection into electrons near the black hole event horizon. Astrometry data show continuous rotation of the emission ...region during bright flares, and corresponding rotation of the linear polarization angle. One broad class of physical flare models invokes magnetic reconnection. Here, we show that such a scenario can arise in a general relativistic magnetohydrodynamic simulation of a magnetically arrested disc. Saturation of magnetic flux triggers eruption events, where magnetically dominated plasma is expelled from near the horizon and forms a rotating, spiral structure. Dissipation occurs via reconnection at the interface of the magnetically dominated plasma and surrounding fluid. This dissipation is associated with large increases in NIR emission in models of Sgr A*, with durations and amplitudes consistent with the observed flares. Such events occur at roughly the time-scale to re-accumulate the magnetic flux from the inner accretion disc, ≃10 h for Sgr A*. We study NIR observables from one sample event to show that the emission morphology tracks the boundary of the magnetically dominated region. As the region rotates around the black hole, the NIR centroid and linear polarization angle both undergo continuous rotation, similar to the behaviour seen in Sgr A* flares.
The barrier to curing HIV-1 is thought to reside primarily in CD4+ T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in ...viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4+ T cells that remain relatively quiescent.
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•Integration sequencing identifies clonally expanded and single HIV-1 integrations in human subjects•Large clonal families of HIV-1+ cells are likely not part of the latent reservoir•HIV-1 integrates near or into a 30 bp INT-motif found in Alu repeats
HIV-1-infected CD4+ T cells that undergo clonal expansion are able to proliferate because their proviruses are defective. Conversely, the replication-competent reservoir is likely found in the subset of CD4+ T cells that carry unique integrations and remain quiescent.
The Galactic Center black hole Sgr A* is the archetypical example of an underfed massive black hole. The extremely low accretion rate can be understood in radiatively inefficient accretion flow ...models. Testing those models has proven to be difficult due to the lack of suitable probes. Radio and submillimeter polarization measurements constrain the flow very close to the event horizon. X-ray observations resolving the Bondi radius yield an estimate roughly four orders of magnitude further out. Here, we present a new, indirect measurement of the accretion flow density at intermediate radii. We use the dynamics of the gas cloud G2 to probe the ambient density. We detect the presence of a drag force slowing down G2 with a statistical significance of 9 . This probes the accretion flow density at around 1000 Schwarzschild radii and yields a number density of 4 × 103 cm−3. Self-similar accretion models where the density follows a power-law radial profile between the inner zone and the Bondi radius have predicted similar values.
HER2 over-expression is related with a poor prognosis in patients with invasive breast cancer tumors. Clinical associations have reported that somatic mutations of p53 more frequently detected in ...cases of sporadic breast cancer of the HER2 subtypes, besides a high percentage of HER2-amplifying tumors carry germline mutations of p53. The mechanisms responsible for the acquisition of oncogenic functions of p53 mutant proteins (mtp53), known as Gain of Function (GOF), over HER2 expression have not been reported. The objective of this study was to evaluate a possible relationship between p53 mutants and HER2 regulation.
HER2 expression (transcription and protein), as well as HER2 protein stabilization have been evaluated after inducing or silencing of p53 mutants' expression in cell lines. Finally, we evaluated the interaction of the p53 mutants over the HER2 receptor promoter.
Higher HER2 expression in cell lines harboring endogenous mtp53 compared with wt or null expression of p53 cell lines. Transfection of p53 mutants (R248Q and R273C) in cell lines increased the expression of HER2. Silencing of p53 mutants, decrease HER2 expression. The p53 mutants R248Q and R273C significantly increase the luciferase activity on the HER2 promoter, and both mutants also promote acetylation of H3 and H4 histones binding in it.
These findings show for the first time that p53 mutants induce over-expression of HER2 at transcriptional level of the HER2 protein. Our results could have clinical implications in breast cancer and other types of cancer where HER2 is over-expressed and used as a therapy target.
Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that ...stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review.
Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein.
Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her circadian clock, either directly or indirectly via the melatonin rhythm, programs the developing master oscillator of the fetus. Experimental studies have shown that disturbed maternal circadian rhythms, referred to as chronodisruption, and perturbed melatonin cycles have negative consequences for the maturing fetal oscillators, which may lead to psychological and behavioral problems in the newborn. To optimize regular circadian rhythms and prevent disturbances of the melatonin cycle during pregnancy, shift work and bright light exposure at night should be avoided, especially during the last trimester of pregnancy. Finally, melatonin synergizes with oxytocin to promote delivery of the fetus. Since blood melatonin levels are normally highest during the dark period, the propensity of childbirth to occur at night may relate to the high levels of melatonin at this time which work in concert with oxytocin to enhance the strength of uterine contractions.
A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin.
Obtaining "hard" and "crack-resistant" glasses have always been of great important in glass science and glass technology. However, in most commercial glasses both properties are not compatible. In ...this work, colorless and transparent xAl2O3-(100-x)SiO2 glasses (30 ≤ x ≤ 60) were fabricated by the aerodynamic levitation technique. The elastic moduli and Vickers hardness monotonically increased with an increase in the atomic packing density as the Al2O3 content increased. Although a higher atomic packing density generally enhances crack formation in conventional oxide glasses, the indentation cracking resistance increased by approximately seven times with an increase in atomic packing density in binary Al2O3-SiO2 glasses. In particular, the composition of 60Al2O3 • 40SiO2 glass, which is identical to that of mullite, has extraordinary high cracking resistance with high elastic moduli and Vickers hardness. The results indicate that there exist aluminosilicate compositions that can produce hard and damage-tolerant glasses.
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