Strontium optical lattice clocks for practical realization of the metre and secondary representation of the second

We present a system of two independent strontium optical lattice standards probed with a single shared ultra-narrow laser. The absolute frequency of the clocks can be verified by the use of Er:fiber optical frequency comb with the GPS-disciplined Rb frequency standard. We report hertz-level spectroscopy of the clock line and measurements of frequency stability of the two strontium optical lattice clocks.Comment: This is an author-created, un-copyedited version of an article accepted for publication in Meas. Sci. Technol. The publisher is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at doi:10.1088/0957-0233/26/7/07520

A conjectural extension of Hecke’s converse theorem

We formulate a precise conjecture that, if true, extends the converse theorem of Hecke without requiring hypotheses on twists by Dirichlet characters or an Euler product. The main idea is to linearize the Euler product, replacing it by twists by Ramanujan sums. We provide evidence for the conjecture, including proofs of some special cases and under various additional hypotheses

Inflammatory Signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice

<p>Abstract</p> <p>Background</p> <p>Obesity and inflammation are highly integrated processes in the pathogenesis of insulin resistance, diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Molecular mechanisms underlying inflammatory events during high fat diet-induced obesity are poorly defined in mouse models of obesity. This work investigated gene activation signals integral to the temporal development of obesity.</p> <p>Methods</p> <p>Gene expression analysis in multiple organs from obese mice was done with Taqman Low Density Array (TLDA) using a panel of 92 genes representing cell markers, cytokines, chemokines, metabolic, and activation genes. Mice were monitored for systemic changes characteristic of the disease, including hyperinsulinemia, body weight, and liver enzymes. Liver steatosis and fibrosis as well as cellular infiltrates in liver and adipose tissues were analyzed by histology and immunohistochemistry.</p> <p>Results</p> <p>Obese C57BL/6 mice were fed with high fat and cholesterol diet (HFC) for 6, 16 and 26 weeks. Here we report that the mRNA levels of macrophage and inflammation associated genes were strongly upregulated at different time points in adipose tissues (6-16 weeks) and liver (16-26 weeks), after the start of HFC feeding. CD11b⁺and CD11c⁺macrophages highly infiltrated HFC liver at 16 and 26 weeks. We found clear evidence that signals for IL-1β, IL1RN, TNF-α and TGFβ-1 are present in both adipose and liver tissues and that these are linked to the development of inflammation and insulin resistance in the HFC-fed mice.</p> <p>Conclusions</p> <p>Macrophage infiltration accompanied by severe inflammation and metabolic changes occurred in both adipose and liver tissues with a temporal shift in these signals depending upon the duration of HFC feeding. The evidences of gene expression profile, elevated serum alanine aminotransferase, and histological data support a progression towards nonalcoholic fatty liver disease and steatohepatitis in these HFC-fed mice within the time frame of 26 weeks.</p

Identification of potential non-invasive biomarkers in diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by pathogenic variants in the SLC26A2 gene encoding for a cell membrane sulfate/chloride antiporter crucial for sulfate uptake and glycosaminoglycan (GAG) sulfation. Research on a DTD animal model has suggested possible pharmacological treatment approaches. In view of future clinical trials, the identification of non-invasive biomarkers is crucial to assess the efficacy of treatments. Urinary GAG composition has been analyzed in several metabolic disorders including mucopolysaccharidoses. Moreover, the N-terminal fragment of collagen X, known as collagen X marker (CXM), is considered a real-time marker of endochondral ossification and growth velocity and was studied in individuals with achondroplasia and osteogenesis imperfecta. In this work, urinary GAG sulfation and blood CXM levels were investigated as potential biomarkers for individuals affected by DTD. Chondroitin sulfate disaccharide analysis was performed on GAGs isolated from urine by HPLC after GAG digestion with chondroitinase ABC and ACII, while CXM was assessed in dried blood spots. Results from DTD patients were compared with an age-matched control population. Undersulfation of urinary GAGs was observed in DTD patients with some relationship to the clinical severity and underlying SLC26A2 variants. Lower than normal CXM levels were observed in most patients, even if the marker did not show a clear pattern in our small patient cohort because CXM values are highly dependent on age, gender and growth velocity. In summary, both non-invasive biomarkers are promising assays targeting various aspects of the disorder including overall metabolism of sulfated GAGs and endochondral ossification

A Heuristic Based on the Intrinsic Dimensionality for Reducing the Number of Cyclic DTW Comparisons in Shape Classification and Retrieval Using AESA

Cyclic Dynamic Time Warping (CDTW) is a good dissimilarity of shape descriptors of high dimensionality based on contours, but it is computationally expensive. For this reason, to perform recognition tasks, a method to reduce the number of comparisons and avoid an exhaustive search is convenient. The Approximate and Eliminate Search Algorithm (AESA) is a relevant indexing method because of its drastic reduction of comparisons, however, this algorithm requires a metric distance and that is not the case of CDTW. In this paper, we introduce a heuristic based on the intrinsic dimensionality that allows to use CDTW and AESA together in classification and retrieval tasks over these shape descriptors. Experimental results show that, for descriptors of high dimensionality, our proposal is optimal in practice and significantly outperforms an exhaustive search, which is the only alternative for them and CDTW in these tasks

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P &lt; 0.001), age, bisphosphonate use, and rodding (P &lt; 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

Correction to Martin et al. available at: Genes & Development 30 (19): 2158 (http://genesdev.cshlp.org/content/31/9/953.full.pdf+html).Compaction of chromosomes is essential for accurate segregation of the genome duringmitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here,we report that biallelic mutations inNCAPD2,NCAPH, orNCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.This work was supported by funding from the Medical Research Council, the Lister Institute for Preventative Medicine, and the European Research Council (ERC; 281847 to A.P.J.); a Biotechnology and Biological Sciences Research Council grant (BB/ K017632/1 to P.V); a Sir Henry Dale Fellowship (grant 102560/ Z/13/Z to A.J.W.); Medical Research Scotland (to L.S.B.); the Potentials Foundation (to C.A.W.); and the Indian Council of Medical Research (BMS 54/2/2013 to S.R.P). The Deciphering Developmental Disorders Study presents independent research commissioned by the Health Innovation Challenge Fund (grant no. HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant no. WT098051). The views expressed here are those of the authors and not necessarily those of the Wellcome Trust or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83) granted by the Cambridge South Research Ethics Committee, and GEN/ 284/12 granted by the Republic of Ireland. We acknowledge the support of the National Institute for Health Research through the Comprehensive Clinical Research Network

Composition of abyssal macrofauna along the Vema Fracture Zone and the hadal Puerto Rico Trench, northern tropical Atlantic

We analyzed composition and variations in benthic macrofaunal communities along a transect of the entire length of the Vema-Fracture Zone on board of RV Sonne (SO-237) between December 2014 and January 2015 in order to test whether the Mid-Atlantic Ridge serves as a barrier limiting benthic taxon distribution in the abyssal basins on both sides of the ridge or whether the fracture zone permits the migration of species between the western and eastern abyssal Atlantic basins. The Puerto Rico Trench, much deeper than the surrounding abyssal West Atlantic, was sampled to determine whether the biodiversity of its hadal macrofauna differs from that of the abyssal Atlantic. The composition of the macrofauna from the epibenthic sledge catches yielded a total of 21,332 invertebrates. Crustacea occurred most frequently (59%) with 12,538 individuals followed by Annelida (mostly Polychaeta) (26%) with 5,491 individuals, Mollusca (7%) with 1,458 individuals, Echinodermata (4%) with 778 individuals, Nematoda (2%) with 502 individuals and Chaetognatha (1%) with 152 and Porifera (1%) with 131 individuals. All other taxa occurred with overall less than ten individuals (Hemichordata, Phoronida, Priapulida, Brachiopoda, invertebrate Chordata, Echiurida, Foraminifera (here refereed to macrofaunal Komokiacea only), Chelicerata, Platyhelminthes). Within the Crustacea, Peracarida (62.6%) with 7,848 individuals and Copepoda (36.1%) with 44,526 individuals were the most abundant taxa. Along the abyssal Vema-Fracture Zone macrofaunal abundances (ind./1,000 m2) were generally higher on the eastern side, while the highest normalized abundance value was reported in the Puerto Rico Trench at abyssal station 14-1 2,313 individuals/1,000 m2. The lowest abundance was reported at station 11-4 with 120 ind./1,000 m2 located at the western side of the Vema-Fracture Zone. The number of major macrofaunal taxa (phylum, class) ranged between five (stations 12-5, 13-4 and 13-5 at hadal depths in the Puerto Rico Trench) and 14 (station 9-8) in the western abyssal basin of the Vema-Fracture Zone. Differences are seen in the distribution of Porifera at macrofaunal level between eastern and western sides of the Vema-Fracture Zone. Macrofaunal composition of the study area is compared with data from other expeditions in the Atlantic and the northwest Pacific Ocean

Cell cycle regulation of embryonic stem cells and mouse embryonic fibroblasts lacking functional Pax7

The transcription factor Pax7 plays a key role during embryonic myogenesis and in adult organisms in that it sustains the proper function of satellite cells, which serve as adult skeletal muscle stem cells. Recently we have shown that lack of Pax7 does not prevent the myogenic differentiation of pluripotent stem cells. In the current work we show that the absence of functional Pax7 in differentiating embryonic stem cells modulates cell cycle facilitating their proliferation. Surprisingly, deregulation of Pax7 function also positively impacts at the proliferation of mouse embryonic fibroblasts. Such phenotypes seem to be executed by modulating the expression of positive cell cycle regulators, such as cyclin E