Measuring dependence in multivariate time series is tantamount to modeling its dynamic structure in space and time. In risk management, the nonnormal behavior of most financial time series calls for ...non-Gaussian dependences. The correct modeling of non-Gaussian dependences is, therefore, a key issue in the analysis of multivariate time series. In this article we use copula functions with adaptively estimated time-varying parameters for modeling the distribution of returns. Furthermore, we apply copulae to the estimation of Value-at-Risk of portfolios and show their better performance over the RiskMetrics approach.
OSIRIS, the Scientific Imaging System onboard the Rosetta mission, has been acquiring images of the nucleus of the comet 67P/Churyumov-Gerasimenko since August 2014 with a resolution that allows a ...detailed analysis of its surface. Indeed, data reveal a complex surface morphology that is likely the expression of different processes that occurred at different times on the cometary nucleus. In order to characterize these different morphologies and better understand their distribution, we performed a geologic mapping of comet's 67P northern hemisphere in which features have been distinguished based on their morphological, textural and stratigraphic characteristics. For this purpose we used NAC images acquired on August and September 2014 with a spatial scale ranging from 1.2 to 2.4 m/pixel. Several different geologic units have been identified on the basis of their different surface textures, granulometry, and morphology. Some of these units are distinctive and localised, whereas others are more common and distributed all over the northern hemisphere. Moreover, different types of linear features have been distinguished on the basis of their morphology. Some of these lineaments have never been observed before on a comet and can offer important clues on the internal structures of the nucleus itself. The geologic mapping results presented here will allow us to better understand the processes that affected the nucleus’ surface and thus the origin and evolutionary history of comet 67P/Churyumov-Gerasimenko.
Type I IFN regulates different aspects of the immune response, inducing a cell-mediated immunity. We have recently shown that the infection of dendritic cells (DC) with Mycobacterium tuberculosis ...(Mtb) induces IFN-alpha. In this work we have monitored a rapid induction of IFN-beta followed by the delayed production of the IFN-alpha1 and/or -alpha13 subtypes. The Mtb infection rapidly activates the NF-kappaB complex and stimulates the phosphorylation of IFN regulatory factor (IRF)-3, events known to induce IFN-beta expression in viral infection. In turn, the autocrine production of IFN-beta induces the IFN-stimulated genes that contain binding sites for activated STATs in their promoters. Among the IFN-stimulated genes induced in DC through STAT activation are IRF-1 and IRF-7. The expression of IRF-1 appears to be dependent on the sequential activation of NF-kappaB and STAT-1. Once expressed, IRF-1 may further stimulate the transcription of IFN-beta. Induction of IRF-7 is also regulated at the transcriptional level through the binding of phosphorylated STAT-1 and STAT-2, forming the IFN-stimulated gene factor-3 complex. In turn, the IRF-1 and IRF-7 expression appears to be required for the delayed induction of the IFN-alpha1/13 genes. Although correlative, our results strongly support the existence of a cascade of molecular events in Mtb-infected DC. Upon infection, constitutively expressed NF-kappaB and IRF-3 are activated and likely contribute to the rapid IFN-beta expression. In turn, IFN-beta-induced IRF-1 and IRF-7 may cooperate toward induction of IFN-alpha1/13 if infection persists and these factors are activated.
Patients with coronary artery disease (CAD) are at high risk for reactivation of the varicella zoster virus (VZV) and development of herpes zoster (HZ). Here, we found that macrophages from patients ...with CAD actively suppress T cell activation and expansion, leading to defective VZV-specific T cell immunity. Monocyte-derived and plaque-infiltrating macrophages from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1 (PD-L1), thereby providing negative signals to programmed death-1.sup.+ (PD-1.sup.+) T cells. We determined that aberrant PD-L1 expression in patient-derived macrophages was metabolically controlled. Oversupply of the glycolytic intermediate pyruvate in mitochondria from CAD macrophages promoted expression of PD-L1 via induction of the bone morphogenetic protein 4/phosphorylated SMAD1/5/IFN regulatory factor 1 (BMP4/p-SMAD1/5/IRF1) signaling pathway. Thus, CAD macrophages respond to nutrient excess by activating the immunoinhibitory PD-1/PD-L1 checkpoint, leading to impaired T cell immunity. This finding indicates that metabolite-based immunotherapy may be a potential strategy for restoring adaptive immunity in CAD.
Recently, p-channel metal-oxide-semiconductor (pMOS) transistors were suggested as fit for the task of detecting and quantifying ionizing radiation dose. Linearity, small detection volume, fast ...readout, portability, low power consumption and low radiation attenuation are some of the pMOS advantages over PIN diode and thermoluminiscent dosimeters. A hand-held measurement system using a low power commercial off-the-shelf pMOSas the sensor would have a clear advantage due to the lower cost incurred by a standard technological process. In this research work, we tested the commercial device 3N163 regarding its behaviouras an X-ray sensor, as well as its possible application as a heavy-ion detector. To study the radiation effects of X-rays, a XRD-7000 (Shimadzu) X-ray diffraction setup was used to produce 10-keV effective energy photons. Heavy ions tests involved 12C, 16O, 19F, 28Si, 35Cl, 63Cu and 107Ag beams scattered at 15° by a 275 μg cm2 gold target, which provide LETs (Linear Energy Transfer) from 4 to 40 MeV mg cm2. The signal readout was done using a 1 GHz oscilloscope with a 10-Gsamples s conversion rate, high enough to permit the recording of transient pulses in the drain current. In this case, an ion can cause a current signal proportional to the ion beam used. Through this study it was found that a simple commercial pMOS device can be reliably used as a detector of X-rays as well as heavy ion detector.
The Drain Induced Barrier Lowering (DIBL) behavior in Ultra-Thin Body and Buried oxide (UTBB) transistors is investigated in details in the temperature range up to 150°C, for the first time to the ...best of our knowledge. The analysis is based on experimental data, physical device simulation, compact model (SPICE) simulation and previously published models. Contrary to MASTAR prediction, experiments reveal DIBL increase with temperature. Physical device simulations of different thin-film fully-depleted (FD) devices outline the generality of such behavior. SPICE simulations, with UTSOI DK2.4 model, only partially adhere to experimental trends. Several analytic models available in the literature are assessed for DIBL vs. temperature prediction. Although being the closest to experiments, Fasarakis’ model overestimates DIBL(T) dependence for shortest devices and underestimates it for upsized gate lengths frequently used in ultra-low-voltage (ULV) applications. This model is improved in our work, by introducing a temperature-dependent inversion charge at threshold. The improved model shows very good agreement with experimental data, with high gain in precision for the gate lengths under test.
Enzyme inhibitors minimize the degradation of unprotected collagen of dentin promoted by matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs). As the evidence of their effect on the root ...canal is limited, this study aimed to evaluate the role of EDTA, chlorhexidine and E-64 as antiproteolytic agents on the bond strength (BS) of glass-fiber posts in root canals.
Ninety-six bovine roots were distributed in groups for each time point (n = 8). Adper Scotchbond Multipurpose (MP)/ RelyX ARC system was used to lute the post according to the treatment: negative control (NC)- water, EDTA- 17% ethylenediaminetetraacetic acid, CHX- 2% digluconate chlorhexidine, E-64-5- 5μM E-64, E-64-10- 10μM E-64 and positive control (PC)- MP associated with activator/ catalyst. Then, slices were subjected to push-out test (0.5mm/min) after 24h/6 mons. Data were analyzed by three-way ANOVA/Tukey tests. Failure modes were analyzed (40×).
The factors treatment, time, root canal third and the interaction between treatment and time were statistically significant. At 24h, no negative interactions were observed among the root dentin, bonding system and post. At 6 mons, CHX improved the BS for middle and apical root thirds.
CHX was able to promote beneficial BS after 6 mons, which was not noted for any other tested enzyme inhibitors.
In addition to their antibiotic potency, β-lactams have recently been investigated as inhibitors of serine proteinase such as leukocyte elastase (LE), released by inflammatory cells. We describe the ...synthesis of a series of 4-alkylidene-β-lactams, and investigate how substitutions on C-3, C-4, and
N-1 of the β-lactam ring affect the activity of human LE and gelatinases MMP-2 and MMP-9. LE activity was measured using a chromogenic substrate, while gelatin-zymography assay was used to evaluate gelatinase activity. We demonstrate that C-4 unsaturation on the β-lactam ring determines the degree of biological activity, with a selectivity over LE by 3-1-(
tert-butyldimethylsilyloxy)-ethyl derivatives (lowest IC
50 was 4
μM), and over gelatinase MMP-2 by C-3-unsubstituted 4-1-ethoxycarbonyl-ethylidene-β-lactams (lowest IC
50 was 60
μM). (3
S)-3-(1
R)-1-hydroxyethyl-4-(1-ethoxycarbonyl)-ethylidene-azetidin-2-one inhibits gelatinase MMP-9. The compounds tested showed no cytotoxicity against NIH-3T3 murine fibroblasts. This is the first example of beta-lactams inhibiting metallo-proteinases instrumental in cancer invasion and angiogenesis. These molecules are good candidates for prototype drugs showing selective antibiotic, anti-inflammatory, and anti-invasion properties.
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