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Inertial particles (i.e. with mass and of finite size) immersed in a fluid in motion are unable to adapt their velocities to the carrying flow and thus they have been the subject of much interest in fluid mechanics. In this paper we consider an ocean setting with inertial particles elastically connected forming a network that floats at the interface with the atmosphere. The network evolves according to a recently derived and validated Maxey–Riley equation for inertial particle motion in the ocean. We rigorously show that, under sufficiently calm wind conditions, rotationally coherent quasigeostrophic vortices (which have material boundaries that resist outward filamentation) always possess finite-time attractors for elastic networks if they are anticyclonic, while if they are cyclonic provided that the networks are sufficiently stiff. This result is supported numerically under more general wind conditions and, most importantly, is consistent with observations of rafts of pelagic Sargassum, for which the elastic inertial networks represent a minimal model. Furthermore, our finding provides an effective mechanism for the long range transport of Sargassum, and thus for its connectivity between accumulation regions and remote sources.

A multinational study of 154 families with PALB2 mutations shows that mutation carriers have a 14% risk of breast cancer by 50 years of age and a 35% risk by 70 years of age, which is similar to the risk associated with BRCA2 mutations. PALB2 (partner and localizer of BRCA2) was originally identified as a BRCA2-interacting protein that is crucial for key BRCA2 genome caretaker functions 1 , 2 ; it was subsequently also shown to interact with BRCA1. 3 Biallelic germline loss-of-function mutations in PALB2 (also known as FANCN ) cause Fanconi’s anemia, whereas monoallelic loss-of-function mutations are associated with an increased risk of breast cancer and pancreatic cancer. 4 Previous studies of familial breast cancer have yielded estimates of risk in association with loss-of-function mutations in PALB2 that are two to four times as high as the risk among non–mutation carriers. 5 – 7 In Finland, the PALB2 . . .

We construct a Markov-chain representation of the surface-ocean Lagrangian dynamics in a region occupied by the Gulf of Mexico (GoM) and adjacent portions of the Caribbean Sea and North Atlantic using satellite-tracked drifter trajectory data, the largest collection so far considered. From the analysis of the eigenvectors of the transition matrix associated with the chain, we identify almost-invariant attracting sets and their basins of attraction. With this information we decompose the GoM’s geography into weakly dynamically interacting provinces, which constrain the connectivity between distant locations within the GoM. Offshore oil exploration, oil spill contingency planning, and fish larval connectivity assessment are among the many activities that can benefit from the dynamical information carried in the geography constructed here.

Recently introduced in oceanography to interpret the near-surface circulation, transition path theory (TPT) is a methodology that rigorously characterizes ensembles of trajectory pieces flowing out from a source last and into a target next, i.e., those that most productively contribute to transport. Here we use TPT to frame, in a statistically more robust fashion than earlier analysis, equatorward routes of North Atlantic Deep Water (NADW) in the subpolar North Atlantic. TPT is applied on all available RAFOS and Argo floats in the area by means of a discretization of the Lagrangian dynamics described by their trajectories. By considering floats at different depths, we investigate transition paths of NADW in its upper (UNADW) and lower (LNADW) layers. We find that the majority of UNADW transition paths sourced in the Labrador and southwestern Irminger Seas reach the western side of a target arranged zonally along the southern edge of the subpolar North Atlantic domain visited by the floats. This is accomplished in the form of a well-organized deep boundary current (DBC). LNADW transition paths sourced west of the Reykjanes Ridge reveal a similar pattern, while those sourced east of the ridge are found to hit the western side of the target via a DBC and also several other places along it in a less organized fashion, indicating southward flow along the eastern and western flanks of the Mid-Atlantic Ridge. Naked-eye inspection of trajectories suggest generally more diffused equatorward NADW routes. A source-independent dynamical decomposition of the flow domain into analogous backward-time basins of attraction, beyond the reach of direct inspection of trajectories, reveals a much wider influence of the western side of the target for UNADW than for LNADW. For UNADW, the average expected duration of the pathways from the Labrador and Irminger Seas was found to be of 2–3 years. For LNADW, the duration was found to be influenced by the Reykjanes Ridge, being as long as 8 years from the western side of the ridge and of about 3 years on average from its eastern side.

In this note, we apply transition path theory (TPT) from Markov chains to shed light on the problem of Iceland–Scotland Overflow Water (ISOW) equatorward export. A recent analysis of observed trajectories of submerged floats demanded revision of the traditional abyssal circulation theory, which postulates that ISOW should steadily flow along a deep boundary current (DBC) around the subpolar North Atlantic prior to exiting it. The TPT analyses carried out here allow attention to be focused on the portions of flow from the origin of ISOW to the region where ISOW exits the subpolar North Atlantic and suggest that insufficient sampling may be biasing the aforementioned demand. The analyses, appropriately adapted to represent a continuous input of ISOW, are carried out on three time-homogeneous Markov chains modeling the ISOW flow. One is constructed using a high number of simulated trajectories homogeneously covering the flow domain. The other two use much fewer trajectories which heterogeneously cover the domain. The trajectories in the latter two chains are observed trajectories or simulated trajectories subsampled at the observed frequency. While the densely sampled chain supports a well-defined DBC, whether this is a peculiarity of the simulation considered or not, the more heterogeneously sampled chains do not, irrespective of the nature of the trajectories used, i.e., observed or simulated. Studying the sampling sensitivity of the Markov chains, we can give recommendations for enlarging the existing float dataset to improve the significance of conclusions about long-time-asymptotic aspects of the ISOW circulation.

Using trajectories from acoustically tracked (RAFOS) floats in the Gulf of Mexico, we construct a geography of its Lagrangian circulation within the 1500–2500-m layer. This is done by building a Markov-chain representation of the Lagrangian dynamics. The geography is composed of weakly interacting provinces that constrain the connectivity at depth. The main geography includes two provinces of near-equal areas separated by a roughly meridional boundary. The residence time is about 4.5 (3.5) years in the western (eastern) province. The exchange between these provinces is effected through a slow cyclonic circulation, which is well constrained in the western basin by preservation of f / H , where f is the Coriolis parameter and H is depth. Secondary provinces of varied shapes covering smaller areas are identified with residence times ranging from about 0.4 to 1.2 years or so. Except for the main provinces, the deep Lagrangian geography does not resemble the surface Lagrangian geography recently inferred from satellite-tracked drifter trajectories. This implies disparate connectivity characteristics with potential implications for pollutant (e.g., oil) dispersal at the surface and at depth. Support for our results is provided by a Markov-chain analysis of satellite-tracked profiling (Argo) floats, which, while forming a smaller dataset and having seemingly different water-following characteristics than the RAFOS floats, replicate the main aspects of the Lagrangian geography. Our results find further validation in independent results from a chemical tracer release experiment.

Infertility due to Gonadotropin-Resistant Ovary Syndrome (GROS) is a rare type of hypergonadotropic hypogonadism. Here, we report an original case of GROS, associated with compound heterozygous follicle-stimulating hormone receptor (FSHR) variants, in a woman who achieved a live birth by in vitro maturation (IVM) of her oocytes. This 31-year-old woman consulted our assisted reproduction center for a second opinion after having been advised, because of pervasive high serum follicle-stimulating hormone (FSH) levels, to pursue in vitro fertilization (IVF) with donor oocytes. She presented with primary infertility and progressively prolonged menstrual cycles. Her serum FSH levels were indeed found to be high, but in discordance with a normal anti-Müllerian hormone (AMH) level and antral follicle count. Genetic investigation found the patient to be compound heterozygous for two FSHR variants: I160T, a known pathologic variant, and N558H, which has never been previously reported. As there was no ovarian response to high daily doses of exogenous gonadotropins, IVM was proposed to the patient with success and she finally delivered at term a healthy boy. Effects of the receptor variants were analyzed in heterologous cells. Whereas the I160T mutation blocked FSHR membrane trafficking and FSH-stimulated cAMP-dependent signaling in transfected CHO cells, the novel variant, N558H, functioned equivalently to wild-type FSHR in the assays employed. In conclusion, IVM should always be offered as a first-line therapy to infertile women presenting with GROS. The N558H variant discovered in FSHR is novel, but its functional significance, if any, is unresolved and merits further investigation as it may be associated with a recessive FSHR-related disorder.

Background:The cell surface glycoprotein E-cadherin (CDH1) is a key regulator of adhesive properties in epithelial cells. Germline mutations in CDH1 are well established as the defects underlying hereditary diffuse gastric cancer (HDGC) syndrome, and an increased risk of lobular breast cancer (LBC) has been described in HDGC kindreds. However, germline CDH1 mutations have not been described in patients with LBC in non-HDGC families. This study aimed to investigate the frequency of germline CDH1 mutations in patients with LBC with early onset disease or family histories of breast cancer without DGC.Methods:Germline DNA was analysed in 23 women with invasive lobular or mixed ductal and lobular breast cancers who had at least one close relative with breast cancer or had themselves been diagnosed before the age of 45 years, had tested negative for a germline BRCA1 or BRCA2 mutation, and reported no personal or family history of diffuse gastric cancer. The full coding sequence of CDH1 including splice junctions was amplified using PCR and screened for mutations using DHPLC and sequencing.Results:A novel germline CDH1 truncating mutation in the extracellular portion of the protein (517insA) was identified in one woman who had LBC at the age of 42 years and a first degree relative with invasive LBC.Conclusions:Germline CDH1 mutations can be associated with invasive LBC in the absence of diffuse gastric cancer. The finding, if confirmed, may have implications for management of individuals at risk for this breast cancer subtype. Clarification of the cancer risks in the syndrome is essential.

BackgroundGermline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition.MethodTo determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions.ResultsNo truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis.ConclusionPotentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent.

The computer-assisted program SiD was developed to assess and select sperm in real time based on motility characteristics. To date, there are limited studies examining the correlation between AI-assisted sperm selection and ICSI outcomes. To address this limit, a total of 646 sibling MII oocytes were randomly divided into two groups as follows: the ICSI group (n = 320): ICSI performed with sperm selected by the embryologist and the ICSI-SiD group (n = 326): ICSI performed with sperm selected using SiD software. Our results show a non-significant trend towards improved outcomes in the ICSI-SiD group across various biological parameters, including fertilization, cleavage, day 3 embryo development, blastocyst development, and quality on day 5. Similarly, we observed a non-significant increase in these outcomes when comparing both groups with sperm selection performed by a junior embryologist. Embryo development was monitored using a timelapse system. Some fertilization events happen significantly earlier when SiD is used for ICSI, but no significant difference was observed in the ICSI-SiD group for other timepoints. We observed comparable cumulative early and clinical pregnancy rates after ICSI-SiD. This preliminary investigation illustrated that employing the automated sperm selection software SiD leads to comparable biological outcomes, suggesting its efficacy in sperm selection.