Strictly Toral Dynamics

This article deals with nonwandering (e.g. area-preserving) homeomorphisms of the torus $\mathbb{T}^2$ which are homotopic to the identity and strictly toral, in the sense that they exhibit dynamical properties that are not present in homeomorphisms of the annulus or the plane. This includes all homeomorphisms which have a rotation set with nonempty interior. We define two types of points: inessential and essential. The set of inessential points $ine(f)$ is shown to be a disjoint union of periodic topological disks ("elliptic islands"), while the set of essential points $ess(f)$ is an essential continuum, with typically rich dynamics (the "chaotic region"). This generalizes and improves a similar description by J\"ager. The key result is boundedness of these "elliptic islands", which allows, among other things, to obtain sharp (uniform) bounds of the diffusion rates. We also show that the dynamics in $ess(f)$ is as rich as in $\mathbb{T}^2$ from the rotational viewpoint, and we obtain results relating the existence of large invariant topological disks to the abundance of fixed points.Comment: Incorporates suggestions and corrections by the referees. To appear in Inv. Mat

Global surfaces of section in the planar restricted 3-body problem

The restricted planar three-body problem has a rich history, yet many unanswered questions still remain. In the present paper we prove the existence of a global surface of section near the smaller body in a new range of energies and mass ratios for which the Hill's region still has three connected components. The approach relies on recent global methods in symplectic geometry and contrasts sharply with the perturbative methods used until now.Comment: 11 pages, 1 figur

Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients

OBJECTIVES: The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir). PATIENTS AND METHODS: Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23). RESULTS: Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004). CONCLUSIONS: This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen

Joule overheating poisons the fractional ac Josephson effect in topological Josephson junctions

Topological Josephson junctions designed on the surface of a 3D-topological insulator (TI) harbor Majorana bound states (MBS's) among a continuum of conventional Andreev bound states. The distinct feature of these MBS's lies in the $4\pi$-periodicity of their energy-phase relation that yields a fractional ac Josephson effect and a suppression of odd Shapiro steps under $r\!f$ irradiation. Yet, recent experiments showed that a few, or only the first, odd Shapiro steps are missing, casting doubts on the interpretation. Here, we show that Josephson junctions tailored on the large bandgap 3D TI Bi$_2$Se$_3$ exhibit a fractional ac Josephson effect acting on the first Shapiro step only. With a modified resistively shunted junction model, we demonstrate that the resilience of higher order odd Shapiro steps can be accounted for by thermal poisoning driven by Joule overheating. Furthermore, we uncover a residual supercurrent at the nodes between Shapiro lobes, which provides a direct and novel signature of the current carried by the MBS. Our findings showcase the crucial role of thermal effects in topological Josephson junctions and lend support to the Majorana origin of the partial suppression of odd Shapiro steps.Comment: Revised article and Supplemental materia

Co-Housing Rodents with Different Coat Colours as a Simple, Non-Invasive Means of Individual Identification:Validating Mixed-Strain Housing for C57BL/6 and DBA/2 Mice

Standard practice typically requires the marking of laboratory mice so that they can be individually identified. However, many of the common methods compromise the welfare of the individuals being marked (as well as requiring time, effort, and/or resources on the part of researchers and technicians). Mixing strains of different colour within a cage would allow them to be readily visually identifiable, negating the need for more invasive marking techniques. Here we assess the impact that mixed strain housing has on the phenotypes of female C57BL/6 (black) and DBA/2 (brown) mice, and on the variability in the data obtained from them. Mice were housed in either mixed strain or single strain pairs for 19 weeks, and their phenotypes then assessed using 23 different behavioural, morphological, haematological and physiological measures widely used in research and/or important for assessing mouse welfare. No negative effects of mixed strain housing could be found on the phenotypes of either strain, including variables relevant to welfare. Differences and similarities between the two strains were almost all as expected from previously published studies, and none were affected by whether mice were housed in mixed- or single-strain pairs. Only one significant main effect of housing type was detected: mixed strain pairs had smaller red blood cell distribution widths, a measure suggesting better health (findings that now need replicating in case they were Type 1 errors resulting from our multiplicity of tests). Furthermore, mixed strain housing did not increase the variation in data obtained from the mice: the standard errors for all variables were essentially identical between the two housing conditions. Mixed strain housing also made animals very easy to distinguish while in the home cage. Female DBA/2 and C57BL/6 mice can thus be housed in mixed strain pairs for identification purposes, with no apparent negative effects on their welfare or the data they generate. This suggests that there is much value in exploring other combinations of strains

Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility

Surface water monitoring in small water bodies: potential and limits of multi-sensor Landsat time series

Hydrometric monitoring of small water bodies (1–10&thinsp;ha) remains rare, due to their limited size and large numbers, preventing accurate assessments of their agricultural potential or their cumulative influence in watershed hydrology. Landsat imagery has shown its potential to support mapping of small water bodies, but the influence of their limited surface areas, vegetation growth, and rapid flood dynamics on long-term surface water monitoring remains unquantified. A semi-automated method is developed here to assess and optimize the potential of multi-sensor Landsat time series to monitor surface water extent and mean water availability in these small water bodies. Extensive hydrometric field data (1999–2014) for seven small reservoirs within the Merguellil catchment in central Tunisia and SPOT imagery are used to calibrate the method and explore its limits. The Modified Normalised Difference Water Index (MNDWI) is shown out of six commonly used water detection indices to provide high overall accuracy and threshold stability during high and low floods, leading to a mean surface area error below 15&thinsp;%. Applied to 546 Landsat 5, 7, and 8 images over 1999–2014, the method reproduces surface water extent variations across small lakes with high skill (R2 = 0.9) and a mean root mean square error (RMSE) of 9300&thinsp;m2. Comparison with published global water datasets reveals a mean RMSE of 21&thinsp;800&thinsp;m2 (+134&thinsp;%) on the same lakes and highlights the value of a tailored MNDWI approach to improve hydrological monitoring in small lakes and reduce omission errors of flooded vegetation. The rise in relative errors due to the larger proportion and influence of mixed pixels restricts surface water monitoring below 3&thinsp;ha with Landsat (Normalised RMSE&thinsp; = &thinsp;27&thinsp;%). Interferences from clouds and scan line corrector failure on ETM+ after 2003 also decrease the number of operational images by 51&thinsp;%, reducing performance on lakes with rapid flood declines. Combining Landsat observations with 10&thinsp;m pansharpened Sentinel-2 imagery further reduces RMSE to 5200&thinsp;m2, displaying the increased opportunities for surface water monitoring in small water bodies after 2015.</p

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe