A nonparametric procedure to assess the accuracy of the normality assumption for annual rainfall totals, based on the marginal statistics of daily rainfall: an application to the NOAA/NCDC rainfall database

We develop a nonparametric procedure to assess the accuracy of the normality assumption for annual rainfall totals (ART), based on the marginal statistics of daily rainfall. The procedure is addressed to practitioners and hydrologists that operate in data-poor regions. To do so we use 1) goodness-of-fit metrics to conclude on the approximate convergence of the empirical distribution of annual rainfall totals to a normal shape and classify 3007 daily rainfall time series from the NOAA/NCDC Global Historical Climatology Network database, with at least 30 years of recordings, into Gaussian (G) and non-Gaussian (NG) groups; 2) logistic regression analysis to identify the statistics of daily rainfall that are most descriptive of the G/NG classification; and 3) a random-search algorithm to conclude on a set of constraints that allows classification of ART samples on the basis of the marginal statistics of daily rain rates. The analysis shows that the Anderson–Darling (AD) test statistic is the most conservative one in determining approximate Gaussianity of ART samples (followed by Cramer–Von Mises and Lilliefors’s version of Kolmogorov–Smirnov) and that daily rainfall time series with fraction of wet days fwd < 0.1 and daily skewness coefficient of positive rain rates skwd > 5.92 deviate significantly from the normal shape. In addition, we find that continental climate (type D) exhibits the highest fraction of Gaussian distributed ART samples (i.e., 74.45%; AD test at α = 5% significance level), followed by warm temperate (type C; 72.80%), equatorial (type A; 68.83%), polar (type E; 62.96%), and arid (type B; 60.29%) climates

Combined microwave ablation and osteosynthesis for long bone metastases

Background and Objectives: The purpose of this study was to evaluate the feasibility, safety and efficacy of microwave ablation (MWA) in combination with open surgery nail positioning for the treatment of fractures or impending fractures of long bone metastases. Material and Methods: Eleven patients (four men, seven women) with painful bone metastases of the humerus, femur or tibia with non-displaced fractures (one case) or impending fractures (10 cases) underwent open MWA in combination with osteosynthesis by locked nail positioning. Pain intensity was measured using a VAS score before and after treatment. CT or MRI were acquired at one month before and 1, 3, 6, 12 and 18 months after treatment. Results: All procedures were successfully completed without major complications. The level of pain was significantly reduced one month after treatment. For the patients with humerus metastases, the complete recovery of arm use took 8 weeks, while for the patients with femoral metastases the complete recovery of walking capacity took 11 weeks. The VAS score ranged from 7 (4–9) before treatment to 1.5 (0–2.5) after treatment. During a mid-term follow-up of 18 months (range 4–29 months), none of the patients showed tumor relapse or new fractures in the treated site. Two patients died due to tumor disease progression. Conclusion: Results of this preliminary study suggest that combined MWA and surgical osteosynthesis with locked nails is a safe and effective treatment for pathological fractures or malignant impending fractures of long bone metastases of the humerus, femur and tibia. Further analyses with larger cohorts are warranted to confirm these findings

A synoptic study of phytoplankton in the deep lakes south of the Alps (lakes Garda, Iseo, Como, Lugano and Maggiore)

This paper presents a synoptic account of the most important results emerging from studies on the phytoplankton communities in the deep southern subalpine lakes Garda, Iseo, Como, Lugano and Maggiore (DSL) in the second half of the 1990s. At present, the trophogenic layers of these lakes are trophically different, ranging from the oligo-mesotrophy of lakes Maggiore and Garda to the meso-eutrophy of lakes Iseo and Lugano. The research confirmed the existence of a common pool of species developing in the DSL, as already suggested by early studies conducted on a seasonal basis from the end of the 1970s to the first half of the 1980s. However, multivariate analyses (Correspondence Analysis, CA, and a subsequent application of Non Metric Multidimensional Scaling) demonstrated that the species in this common pool were developing differently or exclusively along a geographic and a trophic gradient. The major differences in the geographic distribution were found between the easternmost lakes (Garda and Iseo) and those farthest to the West (Lugano and, partly, Maggiore), with intermediate characteristics in Lake Como. These differences were due mainly to changes in the dominance relationships and only secondarily to compositional changes. The detection of the ultimate causes of these differences should take into account other factors not considered in the paper (i.e. the specific analysis of the food webs, local climatic conditions, hydrology and seasonal input of nutrients). Despite the observed differences, common patterns in the sequence of seasonal assemblages in the DSL could be recognised and defined. The second gradient in the species distribution identified by CA was strongly correlated with the principal trophic descriptors (algal biomass and total phosphorus); this meant that the phytoplankton taxa could be ranked along a trophic spectrum, from oligotrophy to eutrophy. A brief examination of the main differences which have historically arisen with the progress of eutrophication in the DSL showed that the species identified in this study as being indicative of more eutrophic conditions were increasing in importance in some of the lakes

The periodicity of phytoplankton in Lake Constance (Bodensee) in comparison to other deep lakes of central Europe

Phytoplankton periodicity has been fairly regular during the years 1979 to 1982 in Lake Constance. Algal mass growth starts with the vernal onset of stratification; Cryptophyceae and small centric diatoms are the dominant algae of the spring bloom. In June grazing by zooplankton leads to a lsquoclear-water phasersquo dominated by Cryptophyceae. Algal summer growth starts under nutrient-saturated conditions with a dominance of Cryptomonas spp. and Pandorina morum. Depletion of soluble reactive phosphorus is followed by a dominance of pennate and filamentous centric diatoms, which are replaced by Ceratium hirundinella when dissolved silicate becomes depleted. Under calm conditions there is a diverse late-summer plankton dominated by Cyanophyceae and Dinobryon spp.; more turbulent conditions and silicon resupply enable a second summer diatom growth phase in August. The autumnal development leads from a Mougeotia — desmid assemblage to a diatom plankton in late autumn and winter. Inter-lake comparison of algal seasonality includes in ascending order of P-richness Königsee, Attersee, Walensee, Lake Lucerne, Lago Maggiore, Ammersee, Lake Zürich, Lake Geneva, Lake Constance. The oligotrophic lakes have one or two annual maxima of biomass; after the vernal maximum there is a slowly developing summer depression and sometimes a second maximum in autumn. The more eutrophic lakes have an additional maximum in summer. The number of floristically determined successional stages increases with increasing eutrophy, from three in Königsee and Attersee to eight in Lake Geneva and Lake Constance

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Mice Lacking Alkbh1 Display Sex-Ratio Distortion and Unilateral Eye Defects

Escherichia coli AlkB is a 2-oxoglutarate- and iron-dependent dioxygenase that reverses alkylated DNA damage by oxidative demethylation. Mouse AlkB homolog 1 (Alkbh1) is one of eight members of the newly discovered family of mammalian dioxygenases.In the present study we show non-Mendelian inheritance of the Alkbh1 targeted allele in mice. Both Alkbh1(-/-) and heterozygous Alkbh1(+/-) offspring are born at a greatly reduced frequency. Additionally, the sex-ratio is considerably skewed against female offspring, with one female born for every three to four males. Most mechanisms that cause segregation distortion, act in the male gametes and affect male fertility. The skewing of the sexes appears to be of paternal origin, and might be set in the pachythene stage of meiosis during spermatogenesis, in which Alkbh1 is upregulated more than 10-fold. In testes, apoptotic spermatids were revealed in 5-10% of the tubules in Alkbh1(-/-) adults. The deficiency of Alkbh1 also causes misexpression of Bmp2, 4 and 7 at E11.5 during embryonic development. This is consistent with the incompletely penetrant phenotypes observed, particularly recurrent unilateral eye defects and craniofacial malformations.Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development in mice

Deletion of the Pluripotency-Associated Tex19.1 Gene Causes Activation of Endogenous Retroviruses and Defective Spermatogenesis in Mice

As genetic information is transmitted through successive generations, it passes between pluripotent cells in the early embryo and germ cells in the developing foetus and adult animal. Tex19.1 encodes a protein of unknown function, whose expression is restricted to germ cells and pluripotent cells. During male spermatogenesis, Tex19.1 expression is highest in mitotic spermatogonia and diminishes as these cells differentiate and progress through meiosis. In pluripotent stem cells, Tex19.1 expression is also downregulated upon differentiation. However, it is not clear whether Tex19.1 has an essential function in germ cells or pluripotent stem cells, or what that function might be. To analyse the potential role of Tex19.1 in pluripotency or germ cell function we have generated Tex19.1−/− knockout mice and analysed the Tex19.1−/− mutant phenotype. Adult Tex19.1−/− knockout males exhibit impaired spermatogenesis. Immunostaining and histological analysis revealed defects in meiotic chromosome synapsis, the persistence of DNA double-strand breaks during meiosis, and a loss of post-meiotic germ cells in the testis. Furthermore, expression of a class of endogenous retroviruses is upregulated during meiosis in the Tex19.1−/− testes. Increased transposition of endogenous retroviruses in the germline of Tex19.1−/− mutant mice, and the concomitant increase in DNA damage, may be sufficient to disrupt the normal processes of recombination and chromosome synapsis during meiosis and cause defects in spermatogenesis. Our results suggest that Tex19.1 is part of a specialised mechanism that operates in the germline to repress transposable genetic elements and maintain genomic stability through successive generations

The Onconeural Antigen cdr2 Is a Novel APC/C Target that Acts in Mitosis to Regulate C-Myc Target Genes in Mammalian Tumor Cells

Cdr2 is a tumor antigen expressed in a high percentage of breast and ovarian tumors and is the target of a naturally occurring tumor immune response in patients with paraneoplastic cerebellar degeneration, but little is known of its regulation or function in cancer cells. Here we find that cdr2 is cell cycle regulated in tumor cells with protein levels peaking in mitosis. As cells exit mitosis, cdr2 is ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) and rapidly degraded by the proteasome. Previously we showed that cdr2 binds to the oncogene c-myc, and here we extend this observation to show that cdr2 and c-myc interact to synergistically regulate c-myc-dependent transcription during passage through mitosis. Loss of cdr2 leads to functional consequences for dividing cells, as they show aberrant mitotic spindle formation and impaired proliferation. Conversely, cdr2 overexpression is able to drive cell proliferation in tumors. Together, these data indicate that the onconeural antigen cdr2 acts during mitosis in cycling cells, at least in part through interactions with c-myc, to regulate a cascade of actions that may present new targeting opportunities in gynecologic cancer