Exploring microstructure and petrophysical properties of microporous volcanic rocks through 3D multiscale and super-resolution imaging.

Digital rock physics offers powerful perspectives to investigate Earth materials in 3D and non-destructively. However, it has been poorly applied to microporous volcanic rocks due to their challenging microstructures, although they are studied for numerous volcanological, geothermal and engineering applications. Their rapid origin, in fact, leads to complex textures, where pores are dispersed in fine, heterogeneous and lithified matrices. We propose a framework to optimize their investigation and face innovative 3D/4D imaging challenges. A 3D multiscale study of a tuff was performed through X-ray microtomography and image-based simulations, finding that accurate characterizations of microstructure and petrophysical properties require high-resolution scans (≤ 4 µm/px). However, high-resolution imaging of large samples may need long times and hard X-rays, covering small rock volumes. To deal with these limitations, we implemented 2D/3D convolutional neural network and generative adversarial network-based super-resolution approaches. They can improve the quality of low-resolution scans, learning mapping functions from low-resolution to high-resolution images. This is one of the first efforts to apply deep learning-based super-resolution to unconventional non-sedimentary digital rocks and real scans. Our findings suggest that these approaches, and mainly 2D U-Net and pix2pix networks trained on paired data, can strongly facilitate high-resolution imaging of large microporous (volcanic) rocks.

Engineering Auxetic Cylinders and Intestine to Improve Longitudinal Intestinal Lengthening and Tailoring Procedure.

Auxetic materials can be exploited for coupling different types of tissues. Herein, we designed a material where the microorganism metabolic activity yields the formation of buckled/collapsed bubbles within gelling silicone cylinders thus providing auxetic properties. The finite element model of such hollow auxetic cylinders demonstrated the tubular structure to promote worm-like peristalsis. In this scenario, the described hybrid auxetic structures may be applied to the longitudinal intestinal lengthening and tailoring procedure to promote enteral autonomy in short bowel syndrome. The presented material and analytical design synergistic approach offer a pioneering step for the clinical translation of hybrid auxetic materials.

Effects of the Storage Conditions on the Stability of Natural and Synthetic Cannabis in Biological Matrices for Forensic Toxicology Analysis: An Update from the Literature.

The use and abuse of cannabis, be it for medicinal or recreational purposes, is widely spread among the population. Consequently, a market for more potent and consequently more toxic synthetic cannabinoids has flourished, and with it, the need for accurate testing of these substances in intoxicated people. In this regard, one of the critical factors in forensic toxicology is the stability of these drugs in different biological matrices due to different storage conditions. This review aims to present the most updated and relevant literature of studies performed on the effects of different storage conditions on the stability of cannabis compounds present in various biological matrices, such as blood and plasma, urine, and oral fluids, as well as in alternative matrices, such as breath, bile fluid, hair, sweat, cerumen, and dried blood spots.

Pomegranate fruit juice adulteration with apple juice: detection by UV-visible spectroscopy combined with multivariate statistical analysis.

Pomegranate is rich in high value nutritional substances known to be beneficial against several diseases and its use in medicine is known since ancient times. Due to its properties and delicious taste, pomegranate fresh fruit juices demand has been growing worldwide and its adulteration is becoming a problem. Low-cost, user friendly and fast detection methods are therefore desirable in order to easily and rapidly detect adulteration of short shelf-life fresh fruit juices. For this purpose fresh squeezed arils pomegranate juice samples adulterated with less expensive apple juice concentrate were investigated by UV-visible spectroscopy combined with multivariate statistical analysis. Unsupervised principle component analysis (PCA), supervised projection to latent structure discriminant analysis (PLS-DA) and orthogonal projection to latent structure discriminant analysis (OPLS-DA) were performed on the full spectra. OPLS-DA analysis of UV-visible spectra proved to be a suitable method to detect pomegranate juices adulterated by more than 20% v/v apple juice concentrate.

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress.

Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth muscle actin and type I collagen. EndMT is involved in many chronic and fibrotic diseases and appears to be regulated by complex molecular mechanisms and different signaling pathways. Recent evidence suggests that small RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are crucial mediators of EndMT. Furthermore, EndMT and miRNAs are both affected by oxidative stress, another key player in the pathophysiology of diabetic fibrotic complications. In this review, we provide an overview of the primary redox signals underpinning the diabetic-associated fibrotic process. Then, we discuss the current knowledge on the role of small RNAs in the regulation of EndMT in diabetic retinopathy, nephropathy, cardiomyopathy, and atherosclerosis and highlight potential links between oxidative stress and the dyad small RNAs-EndMT in driving these pathological states.

Reference intervals for Cu, Mg, and Zn in captive gyrfalcons and other falcon species in the United Arab Emirates.

Falconry is a long-standing tradition in the United Arab Emirates (UAE), and in 2016, falconry was included by UNESCO in the list of intangible cultural heritage of humanity. The health and wellness of falconry raptors is a priority for the local culture; plasma chemistry analysis plays an important role in monitoring, assessing, and managing diseases in avian patients. Imbalances of Cu, Mg, and Zn have been linked to several diseases in avian species; therefore, determining the reference intervals (RIs) of these minerals has important implications in the clinical management of falcons. We determined the RIs in plasma for Cu, Mg, and Zn in captive (falconry-managed) falcons according to the Quality Assurance and Laboratory Standards Committee of the American Society for Veterinary Clinical Pathology, and the Clinical Laboratory Standards Institute guidelines. Blood chemistry analyses were carried out on 252 clinically healthy falcons examined at the Dubai Falcon Hospital in the UAE: 124 gyrfalcons (Falco rusticolus) and 128 falcons of other species. We observed no significant variation in RIs of Cu (1.5-7.0 µmol/L), Mg (0.49-0.78 mmol/L), or Zn (11.8-34.1 µmol/L) based on different species or sex.

Disposition of posaconazole after single oral administration in large falcons (Falco spp): Effect of meal and dosage and a non-compartmental model to predict effective dosage.

Posaconazole has been used anecdotally to treat aspergillosis in falcons resistant to voriconazole. In human medicine, it is used prophylactically in immunosuppressed human subjects with invasive pulmonary aspergillosis. So far, no studies have been performed in birds. The aim of this study was to evaluate the in-vivo pharmacokinetic behavior of oral posaconazole after a single administration in six large falcons (i.e gyrfalcons, saker falcons). Posaconazole oral suspension (Noxafil, 40 mg/ml, Schering-Plough) was administered per os without meal in a single dosage of 12.5 mg/kg in 3 falcons. A comparison was done in two more falcons, one with a natural fatty meal at the same single dose, and one with a natural fatty meal and a higher dosage (20 mg/kg). Finally, six falcons received posaconazole pre-dissolved in corn oil with a natural low-fat meal in the higher single dose (20 mg/kg). No side effects were observed in the falcons in any of the experiments. In starved state posaconazole was poorly absorbed, more so than in other species. As expected, absorption of posaconazole was higher with the administration of meal or in the presence of plant (corn) oil, with a fourfold increase in apparent bioavailability. Despite the preferential absorption in the presence of fat, for both dosing schemes the AUC24 : MIC ratio was lower than described in human medicine to achieve a therapeutic effect. The AUCinf : MIC which is an indicator of efficacy after steady-state, while variable, did indicate that the drug is worth trying when susceptibility testing shows to be the only effective drug. LAY ABSTRACT: The focus of this work is to determine the pharmacokinetic parameters of oral posaconazole in large falcons for the first time after a single dose. Posaconazole has higher bioavailability when administered with meal and fatty components. No adverse reactions have been observed. The ratio of the area under the curve (AUC24) to minimum inhibitory concentration was lower compared to the therapeutic level in human.

The current status of avian aspergillosis diagnoses: Veterinary practice to novel research avenues.

Aspergillus fungal infections continue to be a significant cause of morbidity and mortality in birds that can, in part, be attributed to the lack of a diagnostic "gold standard" for Aspergillus infection, and which delays the diagnosis, treatment, and outcome of avian patients. At present, none of the available methods in veterinary care can detect aspergillosis early enough and with the accuracy, precision, and specificity required of an ideal diagnostic tool. Therefore, researching methods of Aspergillus detection is still an active area of inquiry, and novel techniques continue to emerge. This review will provide a brief overview of current clinical methods, with an emphasis on avian care, in addition to a series of techniques in development that could offer distinct advantages over existing methods.

First detection of Cryptosporidium parvum in falcons (Falconiformes): Diagnosis, molecular sequencing, therapeutic trial and epidemiological assessment of a possible emerging disease in captive falcons.

Cryptosporidiosis in raptors and falcons is well-known to be caused by Cryptosporidium baileyi and associated mainly with respiratory pathology. This report presents the diagnosis of an atypical cryptosporidiosis event caused by Cryptosporidium parvum, that to the authors' knowledge, is a case observed for the first time in falcons. Two falcons (Gyrfalcon x Peregrine hybrids) were presented for annual check without any clinical signs. Hematology, biochemistry, fecal and crop parasitology, radiographic and endoscopic examinations were performed. Endoscopy revealed microcystic formation of the caudal lung field in the two falcons, adhesions and air sac alterations. Sampling and subsequent cytology revealed fungal spores and acid fast stain organisms (identified as Cryptosporidium spp.). Feces and affected lung tissue was further send for Cryptosporidium spp.-DNA detection. Fecal samples and lung tissue tested positive for Cryptosporidium spp. gp60 gene by PCR. By sequence analysis of the gp60 gene locus, diagnosis of C. parvum was confirmed with 100% homology. Despite the fact that falcons didn't recover after 1 month of therapy, eight months after the initial examination they were clinically healthy and had satisfactory flying performance. No other falcons were observed with C. parvum infections in the facility so far. The possible source, infection route and implications are discussed.

Probabilistic-numerical assessment of pyroclastic current hazard at Campi Flegrei and Naples city: Multi-VEI scenarios as a tool for "full-scale" risk management.

The Campi Flegrei volcanic field (Italy) poses very high risk to the highly urbanized Neapolitan area. Eruptive history was dominated by explosive activity producing pyroclastic currents (hereon PCs; acronym for Pyroclastic Currents) ranging in scale from localized base surges to regional flows. Here we apply probabilistic numerical simulation approaches to produce PC hazard maps, based on a comprehensive spectrum of flow properties and vent locations. These maps are incorporated in a Geographic Information System (GIS) and provide all probable Volcanic Explosivity Index (VEI) scenarios from different source vents in the caldera, relevant for risk management planning. For each VEI scenario, we report the conditional probability for PCs (i.e., the probability for a given area to be affected by the passage of PCs in case of a PC-forming explosive event) and related dynamic pressure. Model results indicate that PCs from VEI<4 events would be confined within the Campi Flegrei caldera, PC propagation being impeded by the northern and eastern caldera walls. Conversely, PCs from VEI 4-5 events could invade a wide area beyond the northern caldera rim, as well as part of the Naples metropolitan area to the east. A major controlling factor of PC dispersal is represented by the location of the vent area. PCs from the potentially largest eruption scenarios (analogous to the ~15 ka, VEI 6 Neapolitan Yellow Tuff or even the ~39 ka, VEI 7 Campanian Ignimbrite extreme event) would affect a large part of the Campanian Plain to the north and the city of Naples to the east. Thus, in case of renewal of eruptive activity at Campi Flegrei, up to 3 million people will be potentially exposed to volcanic hazard, pointing out the urgency of an emergency plan. Considering the present level of uncertainty in forecasting the future eruption type, size and location (essentially based on statistical analysis of previous activity), we suggest that appropriate planning measures should face at least the VEI 5 reference scenario (at least 2 occurrences documented in the last 10 ka).

Petrological and seismic precursors of the paroxysmal phase of the last Vesuvius eruption on March 1944.

Abrupt transitions in style and intensity are common during volcanic eruptions, with an immediate impact on the surrounding territory and its population. Defining the factors trigger such sudden shifts in the eruptive behavior as well as developing methods to predict such changes during volcanic crises are crucial goals in volcanology. In our research, the combined investigation of both petrological and seismic indicators has been applied for the first time to a Vesuvius eruption, that of March 1944 that caused the present dormant state of the volcano. Our results contribute to elucidate the evolution of the conduit dynamics that generated a drastic increase in the Volcanic Explosivity Index, associated to the ejection of huge amount of volcanic ash. Remarkably, our study shows that the main paroxysm was announced by robust changes in petrology consistent with seismology, thus suggesting that the development of monitoring methods to assess the nature of ejected juvenile material combined with conventional geophysical techniques can represent a powerful tool for forecasting the evolution of an eruption towards violent behavior. This in turn is a major goal in volcanology because this evidence can help decision-makers to implement an efficient safety strategy during the emergency (scale and pace of evacuation).

Rapid differentiation in a sill-like magma reservoir: a case study from the campi flegrei caldera.

In recent decades, geophysical investigations have detected wide magma reservoirs beneath quiescent calderas. However, the discovery of partially melted horizons inside the crust is not sufficient to put constraints on capability of reservoirs to supply cataclysmic eruptions, which strictly depends on the chemical-physical properties of magmas (composition, viscosity, gas content etc.), and thus on their differentiation histories. In this study, by using geochemical, isotopic and textural records of rocks erupted from the high-risk Campi Flegrei caldera, we show that the alkaline magmas have evolved toward a critical state of explosive behaviour over a time span shorter than the repose time of most volcanic systems and that these magmas have risen rapidly toward the surface. Moreover, similar results on the depth and timescale of magma storage were previously obtained for the neighbouring Somma-Vesuvius volcano. This consistency suggests that there might be a unique long-lived magma pool beneath the whole Neapolitan area.

Lethal thermal impact at periphery of pyroclastic surges: evidences at Pompeii.

BACKGROUND: The evaluation of mortality of pyroclastic surges and flows (PDCs) produced by explosive eruptions is a major goal in risk assessment and mitigation, particularly in distal reaches of flows that are often heavily urbanized. Pompeii and the nearby archaeological sites preserve the most complete set of evidence of the 79 AD catastrophic eruption recording its effects on structures and people. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigate the causes of mortality in PDCs at Pompeii and surroundings on the bases of a multidisciplinary volcanological and bio-anthropological study. Field and laboratory study of the eruption products and victims merged with numerical simulations and experiments indicate that heat was the main cause of death of people, heretofore supposed to have died by ash suffocation. Our results show that exposure to at least 250 degrees C hot surges at a distance of 10 kilometres from the vent was sufficient to cause instant death, even if people were sheltered within buildings. Despite the fact that impact force and exposure time to dusty gas declined toward PDCs periphery up to the survival conditions, lethal temperatures were maintained up to the PDCs extreme depositional limits. CONCLUSIONS/SIGNIFICANCE: This evidence indicates that the risk in flow marginal zones could be underestimated by simply assuming that very thin distal deposits, resulting from PDCs with poor total particle load, correspond to negligible effects. Therefore our findings are essential for hazard plans development and for actions aimed to risk mitigation at Vesuvius and other explosive volcanoes.

Thyroid function and structure are affected in childhood obesity.

OBJECTIVE: Alterations in thyroid function are reported in obesity, although no relevant data exist on the thyroid structure of these patients and the frequency of autoimmunity. The aim of our study was to evaluate the involvement of the thyroid gland in a large group of obese children. DESIGN: This was a cross-sectional study. METHODS: The study was conducted between March 2004 and December 2007 in 186 overweight and obese children. In all subjects, serum free T(3), free T(4), TSH, antithyroid antibodies, and a thyroid ultrasound were assessed. A total ot 40 healthy children matched for age and of normal weight for height served as controls. RESULTS: A total of 23 children (12.4%) showed antithyroid antibodies and an ultrasound pattern suggestive of Hashimoto's thyroiditis (group A). Of them, 20 (10.8%) showed antithyroid antibodies and normal ultrasound (group B). A total of 70 subjects (37.6%) showed absent antithyroid antibodies and an ultrasound pattern suggestive of Hashimoto's thyroiditis (group C), and 73 children (39.2%) showed no thyroid antibodies with normal ultrasound (group D). TSH was higher in groups A and C compared with groups B and C, and controls (P < 0.05). Mean free T(4) was lower in group B (P < 0.05) than in controls, whereas free T(3) was higher in group C than in controls (P < 0.05). TSH and body mass index sd scores were significantly correlated in group C (P < 0.001), and TSH was also significantly associated with the degree of thyroid structure alterations (P < 0.05). CONCLUSION: Obese children frequently show alterations of thyroid structure and function that are not completely explained by the presence of an autoimmune involvement.

Prematurity may be a risk factor for thyroid dysfunction in childhood.

CONTEXT: Children born prematurely and/or small for gestational age (SGA) frequently show disturbances in thyroid function. OBJECTIVE: The objective of the study was to determine the role played either by size or gestational age on subsequent thyroid function. DESIGN AND SETTING: This cross-sectional study was conducted at a tertiary referral hospital. PATIENTS: A total of 117 children, 88 of whom were SGA (mean age 7.8 +/- 2.5 yr) and 29 appropriate for gestational age (AGA) (mean age 8.1 +/- 1.9 yr), were selected for the study. MAIN OUTCOME MEASURES: We evaluated TSH, free T(4), free T(3), urinary iodine, and antithyroid antibodies, and all patients underwent a thyroid ultrasound. Insulin sensitivity was assessed with the quantitative insulin sensitivity check index. RESULTS: TSH and free T3 were not significantly different in the two groups, whereas free T4 was higher in the AGA group (P < 0.005). Interestingly, four AGA (13.8%) and 17 SGA (19.3%) patients had TSH levels above the upper limit of normality. Thyroid volume was normal and thyroid autoimmunity was excluded. Urinary iodine was also similar in the two groups (115 +/- 66 vs. 143 +/- 87); however, in both groups there were some children [15 AGA (51%) and 13 SGA (14.7%) (P < 0.001)] with a mild to moderate iodine deficiency. By multiple regression analysis, gestational age was found to be the only determinant of TSH serum levels. Insulin sensitivity was the same in both groups of children and similar to controls. CONCLUSIONS: Some children born prematurely, independently from their birth size, frequently have disturbances of the hypothalamus-pituitary-thyroid axis later in life.

The Avellino 3780-yr-B.P. catastrophe as a worst-case scenario for a future eruption at Vesuvius.

A volcanic catastrophe even more devastating than the famous anno Domini 79 Pompeii eruption occurred during the Old Bronze Age at Vesuvius. The 3780-yr-B.P. Avellino plinian eruption produced an early violent pumice fallout and a late pyroclastic surge sequence that covered the volcano surroundings as far as 25 km away, burying land and villages. Here we present the reconstruction of this prehistoric catastrophe and its impact on the Bronze Age culture in Campania, drawn from an interdisciplinary volcanological and archaeoanthropological study. Evidence shows that a sudden, en masse evacuation of thousands of people occurred at the beginning of the eruption, before the last destructive plinian column collapse. Most of the fugitives likely survived, but the desertification of the total habitat due to the huge eruption size caused a social-demographic collapse and the abandonment of the entire area for centuries. Because an event of this scale is capable of devastating a broad territory that includes the present metropolitan district of Naples, it should be considered as a reference for the worst eruptive scenario at Vesuvius.

The preferred conformation of the tripeptide Ala-Phe-Ala in water is an inverse gamma-turn: implications for protein folding and drug design.

Recent studies have provided evidence that peptides as short as tripeptides do adopt preferred conformations. Here we report that the tripeptide Ala-Phe-Ala (AFA) in aqueous solution preferentially forms an inverse gamma-turn. Circular dichroism (CD) indicated the presence of a predominant turn structure, and Fourier transform infrared (FTIR) bands suggested the presence of a gamma-turn forming a bifurcated H-bond with the solvent molecules. The high-resolution structure was obtained by a combined use of NMR spectroscopy and calculations. On the basis of 30 unambiguous ROESY-derived distance restraints (including the Halpha-NH NOE between Ala(1) and Ala(3) and a hydrogen bond between the CO group of Ala(1) and the NH group of Ala(3)), calculations clearly demonstrated the presence of an inverse gamma-turn centered on Phe(2). From NOE data, we estimated a mole fraction for the gamma-turn of 0.65. Since for AFA an extended beta-strand was also reported [Eker, F., Griebenow, K., Cao, X., Nafie, L. A., and Schweitzer-Stenner, R. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 10054-10059], we investigated the possibility that gamma-turn and beta-strand may represent two major conformations. By using a best-fit procedure that calculated experimental NOEs as weighted averages of the effects originating from both structures, we were able to calculate with good accuracy the backbone NOEs at 280 K in terms of the two limiting conformers, yielding a mole fraction for the gamma-turn and beta-strand conformations of 0.60 and 0.40, respectively, in good agreement with those found by NOE data. The implication of the existence of a preferred conformation by a small structural element is discussed in the context of the nucleation of protein folding events and the design of small peptide and peptidomimetic drugs.

Enhancement by effectors and substrate nucleotides of R1-R2 interactions in Escherichia coli class Ia ribonucleotide reductase.

Ribonucleotide reductases are a family of essential enzymes that catalyze the reduction of ribonucleotides to their corresponding deoxyribonucleotides and provide cells with precursors for DNA synthesis. The different classes of ribonucleotide reductase are distinguished based on quaternary structures and enzyme activation mechanisms, but the components harboring the active site region in each class are evolutionarily related. With a few exceptions, ribonucleotide reductases are allosterically regulated by nucleoside triphosphates (ATP and dNTPs). We have used the surface plasmon resonance technique to study how allosteric effects govern the strength of quaternary interactions in the class Ia ribonucleotide reductase from Escherichia coli, which like all class I enzymes has a tetrameric alpha(2) beta(2) structure. The component alpha(2)called R1 harbors the active site and two types of binding sites for allosteric effector nucleotides, whereas the beta(2) component called R2 harbors the tyrosyl radical necessary for catalysis. Our results show that only the known allosteric effector nucleotides, but not non-interacting nucleotides, promote a specific interaction between R1 and R2. Interestingly, the presence of substrate together with allosteric effector nucleotide strengthens the complex 2-3 times with a similar free energy change as the mutual allosteric effects of substrate and effector nucleotide binding to protein R1 in solution experiments. The dual allosteric effects of dATP as positive allosteric effector at low concentrations and as negative allosteric effector at high concentrations coincided with an almost 100-fold stronger R1-R2 interaction. Based on the experimental setup, we propose that the inhibition of enzyme activity in the E. coli class Ia enzyme occurs in a tight 1:1 complex of R1 and R2. Most intriguingly, we also discovered that thioredoxin, one of the physiological reductants of ribonucleotide reductases, enhances the R1-R2 interaction 4-fold.

The NMR structure of the sensory domain of the membranous two-component fumarate sensor (histidine protein kinase) DcuS of Escherichia coli.

The structure of the water-soluble, periplasmic domain of the fumarate sensor DcuS (DcuS-pd) has been determined by NMR spectroscopy in solution. DcuS is a prototype for a sensory histidine kinase with transmembrane signal transfer. DcuS belongs to the CitA family of sensors that are specific for sensing di- and tricarboxylates. The periplasmic domain is folded autonomously and shows helices at the N and the C terminus, suggesting direct linking or connection to helices in the two transmembrane regions. The structure constitutes a novel fold. The nearest structural neighbor is the Per-Arnt-Sim domain of the photoactive yellow protein that binds small molecules covalently. Residues Arg107, His110, and Arg147 are essential for fumarate sensing and are found clustered together. The structure constitutes the first periplasmic domain of a two component sensory system and is distinctly different from the aspartate sensory domain of the Tar chemotaxis sensor.