Descent Via Isogeny on Elliptic Curves with Large Rational Torsion Subgroups.

We outline PARI programs which assist with various algorithms related to descent via isogeny on elliptic curves. We describe, in this context, variations of standard inequalities which aid the computation of members of the Tate-Shafarevich group. We apply these techniques to several examples: in one case we use descent via 9-isogeny to determine the rank of an elliptic curve; in another case we find nontrivial members of the 9-part of the Tate-Shafarevich group, and in a further case, nontrivial members of the 13-part of the Tate-Shafarevich group

STRESS SENSITIVITY OF MERCURY INJECTION MEASUREMENTS

Many petrophysical properties (e.g. permeability, electrical resistivity etc.) of tight rocks are very stress sensitive. However, most mercury injection measurements are made using an instrument that does not apply a confining pressure to the samples. Here we further explore the implications of the use and analysis of data from mercury injection porosimetry or mercury capillary pressure measurements (MICP). Two particular aspects will be discussed. First, the effective stress acting on samples analysed using standard MICP instruments (i.e. Micromeritics Autopore system) is described. Second, results are presented from a new mercury injection porosimeter that is capable of injecting mercury at up to 60,000 psi into 1.5 or 1 in core plugs while keeping a constant net stress up to 15,000 psi. This new instrument allows monitoring of the electrical conductivity across the core during the test so that an accurate threshold pressure can be determined. Although no external confining pressure is applied (unconfined) when using the standard MICP instrument, this doesn’t mean that the measurements can be considered as unstressed. Instead, the sample is under isostatic compression by the mercury until it enters the pore space of the sample. As an approximation, the stress that the mercury places on the sample is equal to its threshold pressure. Thus, the permeability calculated from standard MICP data is equivalent to that measured at its threshold pressure. Not all the samples have the same stress dependency thus comparing measured permeabilities at a single stress with values calculated from standard MICP data, corresponding at different threshold pressures, can lead to erroneous correlations. Therefore, the estimation of permeabilities from standard MICP data can be flawed and uncertain unless the stress effect is included. Results obtained from the new mercury injection system, porosimeter under net stress, are radically different from those obtained from standard MICP instruments such as the Autopore IV. In particular, the measurements at reservoir conditions produce threshold pressures that are three times higher and pore throat sizes that are 1/3rd of those measured by the standard MICP instrument. The results clearly indicate that calculating capillary height functions, sealing capacity, etc. from the standard instrument can lead to large errors that can have significant impact on subsurface characterization

Social factors, diet and breast cancer in a northern Italian population.

The relation of breast cancer to social and dietary variables was evaluated in a case-control study of 368 women with breast cancer admitted to the General Hospital of Pordenone (a town in the eastern side of Northern Italy) and 373 age-matched controls. Occupation was related to the risk of breast cancer, housewives and non-manual workers (teachers and other professionals, clerical workers, etc.) showing relative risks of 1.7 and 2.4 respectively when compared to women occupied in agriculture. The role of education was apparently less important, and not statistically significant. The risk was higher in women who were obese, the trend of increasing risk with increasing body mass index being confined to post-menopausal women. When indicators of dietary fat intake were analysed, a significantly increased risk was found with more frequent consumption of milk and dairy products but the risk estimates were only slightly above unity with reference to meat consumption. Women who drank alcoholic beverages showed a relative risk of 2.5 compared to women who had never drunk, when allowance was made for all identified potential confounding factors. The association between alcohol and breast cancer was not explained by the other dietary variables considered, and the risk estimates were higher for women who drank more wine, or more than one type of alcoholic beverage. Thus, the findings of the present study give evidence in favour of the hypothesis that alcohol consumption is related to the risk of breast cancer

Multi-salinity core flooding study in clay-bearing sandstones, a contribution to geothermal reservoir characterisation

Porosity and permeability measurements aid the characterisation of geothermal reservoirs as they improve understanding of the impact of rock–fluid interactions during the life cycle of wells. Core flooding experiments can help us comprehend the rock–brine electrochemical system as critical parameters like salinity, pH, temperature, or pressure change. If the clay mineral content is significant it can reduce permeability and porosity since these particles can block the pore throat network connectivity through clay migration or swelling. A multi-salinity experiment was conducted in three tight clay-bearing (kaolinite, chlorite, and glauconite) sandstones to study the impact of clay on their petrophysical properties. The experiment consisted of core-flooding brines with salinities of 75 000–200 000 and 0–50 000 ppm NaCl at very low flow rates. Electrical resistivity, the differential pressure across the sample, outlet brine electrical conductivity, and brine permeability were measured. Pore size distribution was acquired by measuring nuclear magnetic resonance (NMR) T2 relaxation time. Cation-exchange capacity (CEC) was derived using the Waxman and Smits (1968) approach. The derived CECs were 71.5, 4.7, and 3.6 meq per 100 g for the kaolinite, chlorite, and glauconite sandstones, respectively. Kaolinite was the least water-sensitive as its permeability decreased uniformly. Chlorite and glauconite were more water-sensitive as in the low salinity range; their permeability increased, and both displayed a bimodal NMR T2 distribution and pore size rearrangement towards the mesoporosity and macroporosity range, indicating that the cation-exchange site prevailed within the pore space. This investigation highlights the importance of ensuring that appropriate fluid chemistry is used on brines flowing in clay-bearing geothermal reservoirs

Gold nanoparticles radio-sensitize and reduce cell survival in lewis lung carcinoma

It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After treatment with 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damage when compared to treatment with particles only and radiation alone. This radio-sensitization was further translated into a reduction in cell survival demonstrated by clonogenicity. This work indicates that GNPs of both sizes induce DNA damage in LLC cells at the tested concentrations, whereas the 37.4 nm particle size treatment group demonstrated greater significance in vitro. The presented data aids in the evaluation of the radiobiological response of Lewis lung carcinoma cells treated with gold nanoparticles

Description of chemical transport in laboratory rock cores using the continuous random walk formalism

We investigate chemical transport in laboratory rock cores using unidirectional pulse tracer experiments. Breakthrough curves (BTCs) measured at various flow rates in one sandstone and two carbonate samples are interpreted using the one-dimensional Continuous Time Random Walk (CTRW) formulation with a truncated power law (TPL) model. Within the same framework, we evaluate additional memory functions to consider the Advection-Dispersion Equation (ADE) and its extension to describe mass exchange between mobile and immobile solute phases (Single-Rate Mass Transfer model, SRMT). To provide physical constraints to the models, parameters are identified that do not depend on the flow rate. While the ADE fails systematically at describing the effluent profiles for the carbonates, the SRMT and TPL formulations provide excellent fits to the measurements. They both yield a linear correlation between the dispersion coefficient and the Péclet number (DL Pe for 10 < (Pe) < 100), and the longitudinal dispersivity is found to be significantly larger than the equivalent grain diameter, De. The BTCs of the carbonate rocks show clear signs of nonequilibrium effects. While the SRMT model explicitly accounts for the presence of microporous regions (up to 30% of the total pore space), in the TPL formulation the time scales of both advective and diffusive processes (t1 (Pe) and t2) are associated with two characteristic heterogeneity length scales (d and l, respectively). We observed that l 2.5 × De and that anomalous transport arises when ld (1). In this context, the SRMT and TPL formulations provide consistent, yet complementary, insight into the nature of anomalous transport in laboratory rock cores

Acetylsalicylic acid prevents intermittent hypoxia-induced vascular remodeling in a murine model of sleep apnea

Study objectives: Chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA), induces accelerated atherogenesis as well as aorta vascular remodeling. Although the cyclooxygenase (COX) pathway has been proposed to contribute to the cardiovascular consequences of OSA, the potential benefits of a widely employed COX-inhibitor such (acetylsalicylic acid, ASA) on CIH-induced vascular pathology are unknown. Therefore, we hypothesized that a common non-selective COX inhibitor such as ASA would attenuate the aortic remodeling induced by CIH in mice. Methods: 40 wild-type C57/BL6malemice were randomly allocated to CIH or normoxic exposures (N) and treated with daily doses of ASA or placebo for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization (ED), elastin fragmentation (EF), length between fragmented fiber endpoints (LFF), aortic wall collagen abundance (AC) and mucoid deposition (MD) were assessed. Results: Compared to N, CIH promoted significant increases in IMT (52.58 ± 2.82μm vs. 46.07 ± 4.18μm, p < 0.003), ED (25.29 ± 14.60% vs. 4.74 ± 5.37%, p < 0.001), EF (5.80 ± 2.04 vs. 3.06 ± 0.58, p < 0.001), LFF (0.65 ± 0.34% vs. 0.14 ± 0.09%, p < 0.001), AC (3.43 ± 1.52% vs. 1.67 ± 0.67%, p < 0.001) and MD (3.40 ± 2.73 μm2 vs. 1.09 ± 0.72 μm2, p < 0.006). ASA treatment mitigated the CIH-induced alterations in IMT: 44.07 ± 2.73μm; ED: 10.57 ± 12.89%; EF: 4.63 ± 0.88; LFF: 0.25 ± 0.17% and AC: 0.90 ± 0.13% (p<0.05 for all comparisons). Conclusions: ASA prevents the CIH-induced aortic vascular remodeling, and should therefore be prospectively evaluated as adjuvant treatment in patients with OSA.This work was supported by the Spanish Respiratory Society (SEPAR), SOCAP, the Associació Lleidatana de Respiratori (ALLER), and the Spanish Fondo de Investigaciones Sanitarias (PI14/00486 and PI14-00004), Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”. DG is supported by National Institutes of Health grant HL130984

The Messinian Salinity Crisis as a trigger for high pore pressure development in the Western Mediterranean

Evaporites are typically described as impermeable seals that create some of the world’s highest reservoir pressures beneath the salt seal. However, several laboratory studies demonstrate that evaporites can retain open pore spaces that hydraulically connect the sediments above and below them in sedimentary basins. During the Messinian Salinity Crisis (5.97 to 5.33 Ma), up to 2400 m thickness of evaporites were rapidly deposited in the Western Mediterranean, which may have generated high pore fluid overpressure in the basin sediments. Here we use one‐dimensional numerical modelling to quantify the temporal evolution of overpressure at two distinct locations of the Western Mediterranean, the Liguro‐Provençal and Algero‐Balearic basins, from the Miocene to Present. We reconstruct the sedimentation history of the basin, considering disequilibrium compaction as an overpressure mechanism and constraining model parameters (such as permeability and porosity) using laboratory experiments and the literature. In the Liguro‐Provençal basin the highest overpressure of 11.2 MPa occurs within the halite during deposition of Pliocene to Quaternary sediment, while in the Algero‐Balearic basin at the base of the Emile Baudot Escarpment, the highest overpressure of 3.1 MPa also occurs within the halite but during stage 3 of the Messinian Salinity Crisis (5.55 to 5.33 Ma). In the Algero‐Balearic basin an overpressure of 3.1 MPa could have been sufficient to hydro fracture the sediments, which agrees with the development of fluid escape features observed on seismic reflection profiles. In general, our models with evaporite deposition rates above 20 m kyr‐1 and permeabilities below 10‐18 m2, suggest that high overpressure, approaching lithostatic, can be generated in salt basins

Changes in local tissue microenvironment in response to subcutaneous long-acting delivery of tenofovir alafenamide in rats and non-human primates

Several implantable long-acting (LA) delivery systems have been developed for sustained subcutaneous administration of tenofovir alafenamide (TAF), a potent and effective nucleotide reverse transcriptase inhibitor used for HIV pre-exposure prophylaxis (PrEP). LA platforms aim to address the lack of adherence to oral regimens, which has impaired PrEP efficacy. Despite extensive investigations in this field, tissue response to sustained subcutaneous TAF delivery remains to be elucidated as contrasting preclinical results have been reported in the literature. To this end, here we studied the local foreign body response (FBR) to sustained subdermal delivery of three forms of TAF, namely TAF free base (TA

Antiviral potency of long-acting islatravir subdermal implant in SHIV-infected macaques

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded a mean viral load reduction of -2.30 ± 0.53 lo