Karst processes are of primary importance for the generation of secondary porosity and permeability in carbonate reservoirs and aquifers. The topic investigated in this study are the effects of the ...facies and stratigraphy of different layers on the vertical distribution of solution cavities formed by hypogenic fluids in a carbonate sequence. This work uses the Toca da Boa Vista (TBV) and Toca da Barriguda (TBR) caves as analogues of carbonate reservoirs that are affected by karst processes. These are two different caves that are 400 m apart but exhibit the same geological characteristics and occur in the Neoproterozoic Salitre Formation (700-560 Ma), São Francisco Craton, Brazil. These caves form the longest cave system in South America, with conduits of lengths ∼107 km (TBV) and ∼34 km (TBR). Previous studies of these caves indicated their hypogene origins. These caves developed by an ascending fluid flow, mainly along fractures. The fluid then flowed laterally and was influenced by the following five stratigraphic units, from the bottom to the top: (1) cross-bedded oolitic grainstone, (2) fine grainstone with chert nodules, (3) microbial carbonate, (4) interbedded fine siliciclastics and marls, and (5) crystalline grainstone interfingered with chert layers. Units 4 and 5 formed a stratigraphic seal. Units 1, 2, and 3 below the seal supported the lateral redistribution of flow and respective conduit development. Therefore, these units exhibit a high degree of karstification. Veins related to the first fluid phases that compose a hydrothermal mineral assemblage cut across these units. We conclude that stratigraphic control is important for determining the architecture of the hypogenic cave system at the local scale.
•We study the lithostratigraphy and vein mineralogy of giant hypogenic caves.•Vein hypogene infillings include a hydrothermal assemblage of minerals.•The caves comprise a conduit-seal system in the carbonate-siliciclastic unit.•Lateral flow followed the dissolution of ascending fluids through vertical fractures.•Local stratigraphy controls the horizontal dissolution and karst development.
Introduction: Glioblastoma and anaplastic astrocytoma are two of the most aggressive and common glioma malignancies in adults. These high-grade gliomas (HGG) universally recur despite aggressive ...treatment modalities and have a median overall survival (mOS) of approximately 14 months from initial diagnosis. Upon recurrence, there is no standard of care and these patients have a dismal prognosis of around 9 months at time of recurrence.
Areas covered: In this article, we assess the newly published phase I data of Toca 511 and Toca FC, a two-drug combination therapy for recurrent HGG (rHGG) tumors, for effectiveness and safety.
Expert opinion: These early studies provide very encouraging results for Toca 511 and Toca FC in rHGG. This therapy had a response rate of 11.3% and a mOS of 11.9 months in 56 patients, an improvement compared to historical controls. Furthermore, all responders were complete responses after extended follow-up. The drug is well tolerated for most patients. Responders tended to be young and have high-performance scores prior to beginning therapy, but more studies are necessary to understand the patient profile that receives the most benefit. Randomized-controlled trials are warranted for Toca 511 and Toca FC to confirm drug efficacy.
Angiogenesis is a dynamic morphogenetic process that refers to the growth of new blood vessels from the pre-existing vessels and is critical for tissue repair during wound healing. In adult normal ...tissues, quiescent endothelial cells and pericytes maintain vascular integrity, whereas angiogenesis is immediately induced upon tissue injury, thereby forming neovascular networks to maintain homeostasis. However, impaired angiogenesis results in development of chronic and non-healing wounds in various diseases such as diabetes and peripheral artery diseases. Zebrafish are a vertebrate model organism widely used for studying many medical and life science fields. Indeed, the molecular and cellular mechanisms underlying regulation of wound angiogenesis have recently been studied by performing fluorescence-based live-imaging of adult zebrafish. In this review, we describe how endothelial cells and pericytes establish neovascular networks during wound angiogenesis and also introduce a novel role of blood flow-driven intraluminal pressure in regulating angiogenesis during wound healing.
This paper focuses in the description, radiocarbon dating and isotopic analyses (δ13C, δ18O) of new fossils of Panthera onca from the late Pleistocene of the Brazilian Intertropical Region. This ...paper focuses on the paleoecology of this large cat and is of major importance to understand ecological niches in evolutionary time. Radiocarbon datings and stable isotope compositions (carbon and oxygen) were determined from the structural carbonate of enamel for two fossils of Panthera onca found in two caves in Bahia, Brazil. Isotopic data available of large faunivores and other extinct and extant herbivorous taxa from the late Pleistocene of the Brazilian Intertropical Region were used for paleoecological interpretations. Carbon and oxygen isotopic values from P. onca allow us to suggest that these individuals lived in arboreal savanna habitat between 26 and 33 kyr BP, could reach 209 kg and feed mainly on Nothrotherium maquinense, Tapirus terrestris and Alouatta sp., being a specialist. The isotopic niche overlap with Smilodon populator and Arctotherium wingei was high, while with Protocyon troglodytes was low. In the late Pleistocene P. onca probably suffer high ecological pressure by S. populator, while with A. wingei this could not occur, as this species could be mainly herbivorous.
•Two new records of Panthera onca fossils in caves of Bahia, Brazil.•Both remains are from the late Pleistocene (29 ka and 36 ka).•Body mass estimation varied between 89 kg and 209 kg.•The isotopic diet of P. onca was based mainly in ground sloths, tapirs and monkeys.•onca probably suffer high ecological pressure by S. populator.
NASA has been developing and testing a water recovery system for over two decades to minimize the amount of water required for long duration human space missions. A key system component is the total ...organic carbon analyzer (TOCA) that determines if the recovered water is below the toxicology-defined health limit of 5 mg/L TOC and is safe to drink. The TOCA is composed of a liquid phase loop and a gas phase loop. The TOCA employs an oxidizer to convert the organics in the liquid phase to carbon dioxide (CO2) and a liquid–gas separator to isolate the CO2 for measurement in the gas phase by infrared spectroscopy. In an effort to reduce the consumables, mass, volume, and power of the system, we investigated the ability of surface-enhanced Raman spectroscopy (SERS), and Raman spectroscopy to measure 5 mg/L carbon in water. The SERS measurement employed silver colloids to increase sensitivity, while the Raman measurements used multiple mirrors to increase sensitivity. Here, we present SERS measurements of carbonate (CO3=) at 3 mg/L carbon and Raman measurements of CO2 at 9 mg/L carbon in the effluent water of a new oxidizer being developed for a future TOCA. Both SERS and Raman techniques can determine TOC in the liquid phase, eliminating the need for the gas phase loop and associated supplies and replacement components, which could effectively decrease the size and weight of the current TOCA by as much as 50%.
Graphical Abstract
Barremian–Aptian (Lower Cretaceous) Pre-Salt lacustrine carbonates host large petroleum reservoirs in South Atlantic rift basins, yet remain poorly studied, in part due to the scarcity of lacustrine ...carbonate reservoirs throughout the geological record. This review provides an integrated discussion of the current state of knowledge on the coquina play, having been deposited in extensive rift lakes during the early stages of the opening of the South Atlantic. Thick successions of coquina are recorded from the Santos to Sergipe-Alagoas basins and the Kwanza to Gabon basins on the Brazilian and West African continental margins, respectively. Coquinas exhibit similarities in depositional processes across the South Atlantic, however, have distinct diagenetic histories and stratigraphic stacking patterns, having been deposited in lakes with different geologies, climates and water chemistries. West African coquinas exhibit depositional characteristics that are indicative of deposition on distally steepened ramps and rimmed platforms, and accordingly, facies are somewhat different to those in Brazilian basins, which were deposited on low angle ramps. As petroleum exploration continues into ultra-deep waters on the Brazilian and West African margins, accurate facies models will be important for the predictability of carbonate reservoir intervals. To this end, onshore outcrop in the Sergipe-Alagoas Basin has revealed that the molluscan faunas have marine origins, suggesting that facies patterns may be more complex than previously considered. It is hoped that this review will provide the impetus for further research on the coquinas, especially given the presence of poorly studied, easily accessible onshore outcrops.
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•Pre-Salt coquinas exhibit significant variability in stratigraphy and facies across basins.•Facies associations are complex due to rapid vertical and lateral facies heterogeneity.•Latitudinal climatic variations facilitated differences in stratigraphic stacking patterns.•Reservoir quality is enhanced by hydrothermal dolomitisation, fracturing and dissolution.
The abrupt climate event Younger Dryas (YD) has been extensively studied; however, its structure is still poorly understood. Climate in northeastern Brazil is very sensitive to the latitudinal ...position of the intertropical convergence zone (ITCZ) associated with abrupt climate change in the Atlantic. Here, we report changes in the ITCZ position within the YD by using precise speleothem multiproxy records from northeastern Brazil. We provide evidence for a gradual northward migration of the ITCZ preceding poleward shifts of the westerlies and the polar front in northern high latitudes within the YD. This can be attributed to gradual increase in atmospheric CO2 concentration as a consequence of the weakening Atlantic Meridional Overturning Circulation (AMOC). We suggest that a persistent increase in atmospheric CO2 might have triggered a resumption of the AMOC and reorganization of the atmosphere circulation in the Atlantic during the mid‐YD.
Plain Language Summary
The Younger Dryas (YD) is the most recent millennial‐scale abrupt climate event in Earth history. Although its origin has been extensively studied, its structure is still poorly understood. Climate in northeastern Brazil is very sensitive to the latitudinal position of the intertropical convergence zone (ITCZ) responds to abrupt climate change in the Atlantic (e.g., YD). By using stable isotope and trace element proxy records of speleothem from Toca da Boa Vista Cave, northeastern Brazil, together with other paleoclimatic records in the Atlantic realm, we provide evidence for a gradual northward migration of the ITCZ preceding poleward shifts of the westerlies and the polar front in northern high latitudes within the YD. This can be attributed to a gradual increase in atmospheric CO2 concentration under the situation of weakening Atlantic Meridional Overturning Circulation (AMOC). A persistent increase in atmospheric CO2 concentration might have triggered a resumption of the AMOC and reorganization of the atmosphere circulation in the Atlantic during the mid‐YD.
Key Points
Speleothem and other paleoclimate records confirm a wet climate in tropical South America within the Younger Dryas
Precise speleothem multiproxy records reflect a bipartition of the Younger Dryas precipitation in northeastern Brazil
Gradual South‐North climate transition in the Atlantic responded to a gradual increase in atmospheric CO2 within the YD
The objective of our study was to examine, in addition to using the TOCA Football System tool and training method, the effect of a 10-week intervention on elite youth athletes in terms of their ...sport-specific motor skills and anthropometric variables.
The study covered a group of 32 young players practicing football (U14) (13.45 ± 0.64 years). The junior U14 footballers were randomly assigned to an intervention or TOCA group (TG,
= 15, 13.25 ± 0.58 years) and a control group (CG,
= 17, 13.63 ± 0.66 years). Before starting the test, we performed full anthropometric measurements and assessed the sample's agility with and without the ball and their sport-specific endurance. The measurements were then repeated after the 10-week intervention.
Within-group analysis showed significant improvements in muscle mass (
< 0.001), sport-specific endurance (
< 0.001), (
< 0.004) and agility (in TG) both with and without the ball (
= 0.002), (
= 0.004) however, we did not find a significant change in body fat percentage in either group (
= 0.988,
= 0.288). In the CG, "agility with the ball" changed significantly only (
= 0.023). In the between-group analysis with a repeated-measures analysis of variance (mixed-design ANOVA), there was no significant interaction in any performance variables. The main findings of this study indicate that a TOCA Football training program in addition to normal training during the in-season period does not produce additional effects in anthropometric factors, sport-specific endurance and agility performance with the ball (dribbling) and without the ball in comparison with the control condition.
From a practical point of view, the presented anthropometric and physical profiles of players can be useful for football coaches in optimizing soccer training. Overall, it also can be concluded that the device can be safely used in the sensitive age group in terms of the development of motor skills since we did not find any negative effects during the use of the device in terms of the parameters we examined. In addition to the expansion of the number of elements and the inclusion of other age groups, it is advisable to carry out further complex tests, as the TOCA Football System offers many research opportunities.
When and how did the first human beings settle in the American continent? Numerous data, from archaeological researches as well as from palaeogenetics, anthropological and environmental studies, have ...led to partially contradictory interpretations in recent years, often because of the lack of a reliable chronological framework. The present study contributes to the establishment of such a framework using luminescence techniques to date a Brazilian archaeological site, the Toca da Tira Peia. It constitutes an exemplary case study: all our observations and measurements tend to prove the good integrity of the site and the anthropological nature of the artifacts and we are confident in the accuracy of the luminescence dating results. All these points underline the importance of the Toca da Tira Peia. The results bring new pieces of evidence of a human presence in the north-east of Brazil as early as 20,000 BC. The Toca da Tira Peia thus contributes to the rewriting of the history of the peopling of the American continent.
► The Toca da Tira Peia Rockshelter is a Brazilian archaeological site (Piauí). ► All observations and data lead us to conclude that the artifacts are truly cultural. ► OSL dating has been performed on the sediments. ► The results bring new evidence of a human presence in Brazil as early as 20,000 BC.
Prodrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. ...Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.
Here we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor models, employing both human glioma xenografts in immunodeficient hosts and syngeneic murine gliomas in immunocompetent hosts.
In both models, a single injection of replicating vector followed by prodrug administration achieved long-term survival benefit. In the immunodeficient model, tumors recurred repeatedly, but bioluminescence imaging of tumors enabled tailored scheduling of multicycle prodrug administration, continued control of disease burden, and long-term survival. In the immunocompetent model, complete loss of tumor signal was observed after only 1-2 cycles of prodrug, followed by long-term survival without recurrence for >300 days despite discontinuation of prodrug. Long-term survivors rejected challenge with uninfected glioma cells, indicating immunological responses against native tumor antigens, and immune cell depletion showed a critical role for CD4+ T cells.
These results support dual mechanisms of action contributing to the efficacy of RRV-mediated prodrug-activator gene therapy: long-term tumor control by prodrug conversion-mediated cytoreduction, and induction of antitumor immunity.
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