Ferritin nanovehicle for targeted delivery of cytochrome C to cancer cells

In this work, we have exploited the unique properties of a chimeric archaeal-human ferritin to encapsulate, deliver and release cytochrome c and induce apoptosis in a myeloid leukemia cell line. The chimeric protein combines the versatility in 24-meric assembly and cargo incorporation capability of Archaeglobus fulgidus ferritin with specific binding of human H ferritin to CD71, the “heavy duty” carrier responsible for transferrin-iron uptake. Delivery of ferritin-encapsulated cytochrome C to the Acute Promyelocytic Leukemia (APL) NB4 cell line, highly resistant to transfection by conventional methods, was successfully achieved in vitro. The effective liberation of cytochrome C within the cytosolic environment, demonstrated by double fluorescent labelling, induced apoptosis in the cancer cells

Fast Risetime Reverse Bias Pulse Failures in SiC PN Junction Diodes

SiC-based high temperature power devices are being developed for aerospace systems which will require high reliability. One behavior crucial to power device reliability. To date, it has necessarily been assumed to date is that the breakdown behavior of SiC pn junctions will be similar to highly reliable silicon-based pn junctions. Challenging this assumption, we report the observation of anomalous unreliable reverse breakdown behavior in moderately doped (2-3 x 10(exp 17) cm(exp -3)) small-area 4H- and 6H-SiC pn junction diodes at temperatures ranging from 298 K (25 C) to 873 K (600 C). We propose a mechanism in which carrier emission from un-ionized dopants and deep level defects leads to this unstable behavior. The fundamental instability mechanism is applicable to all wide bandgap semiconductors whose dopants are significantly un-ionized at typical device operating temperatures

Radiogenomics in clear cell renal cell carcinoma: correlations between advanced CT imaging (texture analysis) and microRNAs expression

Purpose: A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs. Methods: In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort. Results: In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management. Conclusion: In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found

A coherent triggered search for single spin compact binary coalescences in gravitational wave data

In this paper we present a method for conducting a coherent search for single spin compact binary coalescences in gravitational wave data and compare this search to the existing coincidence method for single spin searches. We propose a method to characterize the regions of the parameter space where the single spin search, both coincident and coherent, will increase detection efficiency over the existing non-precessing search. We also show example results of the coherent search on a stretch of data from LIGO's fourth science run but note that a set of signal based vetoes will be needed before this search can be run to try to make detections.Comment: 14 pages, 4 figure

Classical dynamics and stability of collapsing thick shells of matter

We study the collapse towards the gravitational radius of a macroscopic spherical thick shell surrounding an inner massive core. This overall electrically neutral macroshell is composed by many nested delta-like massive microshells which can bear non-zero electric charge, and a possibly non-zero cosmological constant is also included. The dynamics of the shells is described by means of Israel's (Lanczos) junction conditions for singular hypersurfaces and, adopting a Hartree (mean field) approach, an effective Hamiltonian for the motion of each microshell is derived which allows to check the stability of the matter composing the macroshell. We end by briefly commenting on the quantum effects which may arise from the extension of our classical treatment to the semiclassical level.Comment: 16 pages in IOP style, 8 figures, accepted for publication in Class. Quantum Gra

Exploring the Levinthal limit in protein folding

According to the thermodynamic hypothesis, the native state of proteins is uniquely defined by their amino acid sequence. On the other hand, according to Levinthal, the native state is just a local minimum of the free energy and a given amino acid sequence, in the same thermodynamic conditions, can assume many, very different structures that are as thermodynamically stable as the native state. This is the Levinthal limit explored in this work. Using computer simulations, we compare the interactions that stabilize the native state of four different proteins with those that stabilize three non-native states of each protein and find that the nature of the interactions is very similar for all such 16 conformers. Furthermore, an enhancement of the degree of fluctuation of the non-native conformers can be explained by an insufficient relaxation to their local free energy minimum. These results favor Levinthal's hypothesis that protein folding is a kinetic non-equilibrium process.FCT - Foundation for Science and Technology, Portugal [UID/Multi/04326/2013]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientia co e Tecnologico (CNPq

Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

SUMMARY We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade