We present recent observations of Sudden Phase Anomalies due to subionospheric propagation anomalies produced by solar X‐ray flares. We use the new South America VLF Network (SAVNET) to study 471 ...ionospheric events produced by solar flares during the period May 2006 to July 2009 which corresponds to the present minimum of solar activity. For this activity level, we find that 100% of the solar flares with a X‐ray peak flux above 5 × 10−7 W/m2 in the 0.1–0.8 nm wavelength range produce a significant ionospheric disturbance, while the minimum X‐ray flux needed to do so is about 2.7 × 10−7 W/m2. We find that this latter minimum threshold is dependent on the solar cycle, increasing when the Sun is more active, thus confirming that the low ionosphere is more sensitive during periods of low solar activity. Also, our findings are in agreement with the idea that the ionospheric D‐region is formed and maintained by the solar Lyman‐α radiation outside solar flare periods.
Sepsis is a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection. To date, there is no specific treatment established for sepsis. In the extracellular ...compartment, purines such as adenosine triphosphate (ATP) and adenosine play essential roles in the immune/inflammatory responses during sepsis and septic shock. The balance of extracellular levels among ATP and adenosine is intimately involved in the signals related to immune stimulation/immunosuppression balance. Specialized enzymes, including CD39, CD73, and adenosine deaminase (ADA), are responsible to metabolize ATP to adenosine which will further sensitize the P2 and P1 purinoceptors, respectively. Disruption of the purinergic pathway had been described in the sepsis pathophysiology. Although purinergic signaling has been suggested as a potential target for sepsis treatment, the majority of data available were obtained using pre-clinical approaches. We hypothesized that, as a reflection of deregulation on purinergic signaling, septic patients exhibit differential measurements of serum, neutrophils and monocytes purinergic pathway markers when compared to two types of controls (healthy and ward). It was observed that ATP and ADP serum levels were increased in septic patients, as well as the A2a mRNA expression in neutrophils and monocytes. Both ATPase/ADPase activities were increased during sepsis. Serum ATP and ADP levels, and both ATPase and ADPase activities were associated with the diagnosis of sepsis, representing potential biomarkers candidates. In conclusion, our results advance the translation of purinergic signaling from pre-clinical models into the clinical setting opening opportunities for so much needed new strategies for sepsis and septic shock diagnostics and treatment.
We analyze in detail the zonal velocities of large‐scale ionospheric plasma depletions over two conjugate stations inferred from OI 630 nm airglow all‐sky images obtained during the Conjugate Point ...Equatorial Experiment (COPEX) campaign carried out in Brazil between October and November 2002. The conjugate stations were Boa Vista (BV) (geogr. 2.8N, 60.7W, dip angle 22.0°N) and Campo Grande (CG) (geogr. 20.5S, 54.7W, dip angle 22.32°S). Over Campo Grande, the zonal velocities were measured also by a system of spaced GPS scintillation receivers. The airglow zonal velocities at the conjugate sites were seen to agree very closely, except for a slightly increased velocity over CG which we attribute to the presence of the geomagnetic anomaly. The results show a high degree of alignment of the bubbles along the geomagnetic field lines during the bubble development phase and as the bubbles travel eastward, thereby suggesting that the neutral zonal wind effect in the zonal plasma motion is an integrated effect along the flux tube. The zonal velocities obtained from the GPS technique were always larger than those calculated by the airglow technique, which permitted observation of zonal plasma velocity shear between the altitudes of the airglow emitting layer and of the GPS scintillation. Theoretical ambient plasma zonal velocities calculated using the formulations by Haerendel et al. (1992) and Eccles (1998) are compared with the experimental results. Our results also reveal some degree of dependence of the zonal velocities on the solar flux (F10.7) and magnetic (Kp) indices during the COPEX period.
Ionospheric perturbations in possible association with the 2010 Haiti earthquake occurred on 12 January 2010 (with a magnitude of 7.0 and depth of 10 km) are investigated on the basis of ...subionospheric propagation data from the NAA transmitter on the east coast of the USA to a VLF receiving station in Peru. The local nighttime VLF amplitude data are extensively investigated during the period from the beginning of October 2009 to the end of March 2010, in which the trend (nighttime average amplitude), dispersion and nighttime fluctuation are analysed. It is found that a clear precursory ionosphere perturbation is detected just around New Years day of 2010, about 12 days before the main shock, which is characterised by the simultaneous decrease in the trend and the increases in dispersion and nighttime fluctuation. An additional finding might be the presence of the effect of the Earth's tide one and two months before the main shock, which can only be seen for a huge EQ.
Ionospheric vertical sounding observations are being carried out at Sao Jose dos Campos (23.2°S, 45.9°W; dip latitude 17.6°S), Brazil, under the southern crest of the equatorial ionization anomaly ...(EIA) since August 2000. In this paper, we present and discuss the observations of daytime F2‐layer stratification near the crest of EIA, for the first time, under magnetically quiet high solar activity conditions. Three examples and a year of statistics are presented. The F2‐layer stratification and F3‐layer were observed between 10:40 and 11:45 UT on 31 December 2000, between 13:30 and 14:30 UT on 1 January 2001, and between 13:15 and 15:15 UT on 11 February 2001. The statistics during September 2000 to August 2001 shows that the F3‐layer occurs only for 66 days (18% occurrence), and it occurs only during September–February (spring–summer), with maximum occurrence in September–October and longest duration in February. The F2‐layer stratification seems to be associated with gravity waves (GWs), which have periods of about 30–60 min, downward phase velocities of about 60–140 m/s, and vertical wavelengths of about 200–500 km. The presence of powerful gravity waves in a vertically extended F‐layer seems to stratify the F2‐layer and produce the F3‐layer. Because the stratifications are observed during geomagnetically quiet periods, the source of the gravity waves are most likely to be associated with local tropospheric disturbances and not with high‐latitude disturbances.
Glioblastoma (GB) is the most common and aggressive form of primary brain tumor, in which the presence of an inflammatory environment, composed mainly by tumor-associated macrophages (TAMs), is ...related to its progression and development of chemoresistance. Toll-Like Receptors (TLRs) are key components of the innate immune system and their expression in both tumor and immune-associated cells may impact the cell communication in the tumor microenvironment (TME), further modeling cancer growth and response to therapy. Here, we investigated the participation of TLR4-mediated signaling as a mechanism of induced-immune escape in GB. Initially, bioinformatics analysis of public datasets revealed that TLR4 expression is lower in GB tumors when compared to astrocytomas (AST), and in a subset of TAMs. Further, we confirmed that TLR4 expression is downregulated in chemoresistant GB, as well as in macrophages co-cultured with GB cells. Additionally, TLR4 function is impaired in those cells even following stimulation with LPS, an agonist of TLR4. Finally, experiments performed in a cohort of clinical primary and metastatic brain tumors indicated that the immunostaining of TLR4 and CD45 are inversely proportional, and confirmed the low TLR4 expression in GBs. Interestingly, the cytoplasmic/nuclear pattern of TLR4 staining in cancer tissues suggests additional roles of this receptor in carcinogenesis. Overall, our data suggest the downregulation of TLR4 expression and activity as a strategy for GB-associated immune escape. Additional studies are necessary to better understand TLR4 signaling in TME in order to improve the benefits of immunotherapy based on TLR signaling.
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•TLR4 expression and functionality are downregulated in glioblastoma (GB) cells and in TAM.•Chemoresistant GB exhibit low TLRs expression compared to non-resistant cells.•TLR4 and CD45 expression is inversely proportional in tumor clinical samples.•TLR4 downregulation in GB/TAM as a strategy of tumor-associated immune evasion
We present a unified algorithm for the collisional interchange instabilities (Rayleigh‐Taylor and gradient drift instabilities) occurring in the F and E regions of the equatorial ionosphere. The ...similar underlying mechanism of both instabilities enables us to derive the general two‐dimensional continuity and potential equations. The equations are integrated numerically to study the nonlinear evolution of the polarization field (fringe field) associated with the generalized Rayleigh‐Taylor instability. In particular, the effects of the fringe field into the equatorial E and transition (or valley) regions are investigated. The characteristics of the fringe field beneath the F region are investigated quantitatively for the first time. It is shown that the fringe field is capable of transporting plasma from the region where ions are highly magnetized (i.e., from the valley region). It is further shown that only under strongly driven but realistic conditions, the fringe field recognizes the part of the E region plasma where ions are marginally magnetized. The E region irregularities which are often located in such a region (near 120 km) during evening and nighttime can be effectively convected by the fringe field across the valley region and to the higher altitudes. On the other hand, because of the small ratio of ion‐gyro‐frequency to collision frequency below 120–115 km altitude the fringe field is unable to convect the E region irregularities lying below this region. These characteristics are important in the context of observed valley region echoes which are yet to be explained quantitatively.
Cervical cancer is the fourth most common cancer affecting women worldwide. Among many factors, the presence of cancer stem cells, a subpopulation of cells inside the tumor, has been associated with ...a worse prognosis. Considering the importance of gene expression studies to understand the biology of cervical cancer stem cells (CCSC), this work identifies stable reference genes for cervical cancer cell lines SiHa, HeLa, and ME180 as well as their respective cancer stem‐like cells. A literature review was performed to identify validated reference genes currently used to normalize RT‐qPCR data in cervical cancer cell lines. Then, cell lines were cultured in regular monolayer or in a condition that favors tumor sphere formation. RT‐qPCR was performed using five reference genes: ACTB, B2M, GAPDH, HPRT1, and TBP. Stability was assessed to validate the selected genes as suitable reference genes. The evaluation validated B2M, GAPDH, HPRT1, and TBP in these experimental conditions. Among them, GAPDH and TBP presented the lowest variability according to the analysis by Normfinder, Bestkeeper, and ΔCq methods, being therefore the most adequate genes to normalize the combination of all samples. These results suggest that B2M, GAPDH, HPRT1, and TBP are suitable reference genes to normalize RT‐qPCR data of established cervical cancer cell lines SiHa, HeLa, and ME180 as well as their derived cancer stem‐like cells. Indeed, GAPDH and TBP seem to be the most convenient choices for studying gene expression in these cells in monolayers or spheres.
Abstract Introduction There is growing evidence that mesenchymal stem cells (MSCs) can be important players in the tumor microenvironment. They can affect the glioma progression through the ...modulation of different genes. This modulation can be evaluated through a very useful model, treating the tumor cells with MSC-conditioned medium. However, for an accurate and reliable gene expression analysis, normalization of gene expression data against reference genes is a prerequisite. Methods We performed a systematic review in an attempt to find a reference gene to use when analyzing gene expression in C6 glioma cells lines. Considering that we were not able to find a reference gene originated by an appropriate validation, in this study we evaluated candidate genes to be used as reference gene in C6 cells under different treatments with adipose-derived stem cells conditioned medium (CM-ADSCs). β-actin (ACTB); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); hypoxanthine-guanine phosphoribosyltransferase I (HPRT-1); TATA box binding protein (TBP) and beta-2-microglobulin (B2 M) were evaluated by real-time reverse transcription PCR (RT-qPCR). The mean Cq, the maximum fold change (MFC) and NormFinder software were used for reference gene evaluation and selection. Results The GAPDH and ACTB genes have been the most widely used reference genes to normalize among the different investigated genes in our review, however, controversially these genes underwent a substantial variability among the genes evaluated in the present work. Individually, TBP gene was more stable when compared with other genes analyzed and the combination of TBP and HPRT-1 was even more stable. Conclusion These results evidence the importance of appropriate validation of reference genes before performing qPCR experiments. Besides, our data will contribute with researchers that work analyzing the role of ADSCs in glioma microenvironment through gene expression.
High-voltage transmission networks represent a large electrical circuit just above the ground subjected to a number of transient overcharges of various kinds, some of which may lead to failures. Some ...failures might be related to anomalies of the geophysical environment. We have analyzed one unprecedented long series of transmission grid failures (9 years) on high-voltage networks located in São Paulo state, southeastern Brazil, from 1998 to 2006, which includes an important fraction of the past solar activity cycle 23. Ninety-five distinct failure causes were given by the power line operator to explain the transmission grid shut downs. Most failures were attributed to atmospheric discharges, corresponding to 1,957 failures out of a total of 4,572 for the whole period at 138 kV, and 170 out of 763 at 440 kV, respectively. They correspond to less than one ten thousandth of the actual number of atmospheric discharges recorded in the same area, demonstrating the grid’s high resilience to breakdowns due to lightning. A clear concentration of failures in the region’s thunderstorm season has been found. A significant 67 and 77 % reduction in the number of failure rates per year has been found for the 138 and 440 kV grids, respectively, for the period studied, in good correspondence with the decay in the sunspot numbers. No obvious correlation was found between power failures and the planetary index of geomagnetic activity or major geomagnetic storms in the period, either on short or on long time scales. Assuming that the dependence of the electrosphere/ionosphere-ground coupling on the external geophysical environment plays a major role in explaining the reduction in power failures as the solar cycle wanes, it is suggested that the increase in atmosphere conductivity caused by the larger cosmic ray flux then reduces the threshold voltage required to produce lightning strokes, so reducing their effectiveness in disrupting high-voltage power lines.
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