Using MERRA Gridded Innovations for Quantifying Uncertainties in Analysis Fields and Diagnosing Observing System Inhomogeneities

MERRA is a NASA reanalysis for the satellite era using a major new version of the Goddard Earth Observing System Data Assimilation System Version 5 (GEOS-5). The project focuses on historical analyses of the hydrological cycle on a broad range of weather and climate time scales and places the NASA EOS suite of observations in a climate context. The characterization of uncertainty in reanalysis fields is a commonly requested feature by users of such data. While intercomparison with reference data sets is common practice for ascertaining the realism of the datasets, such studies typically are restricted to long term climatological statistics and seldom provide state dependent measures of the uncertainties involved. In principle, variational data assimilation algorithms have the ability of producing error estimates for the analysis variables (typically surface pressure, winds, temperature, moisture and ozone) consistent with the assumed background and observation error statistics. However, these "perceived error estimates" are expensive to obtain and are limited by the somewhat simplistic errors assumed in the algorithm. The observation minus forecast residuals (innovations) by-product of any assimilation system constitutes a powerful tool for estimating the systematic and random errors in the analysis fields. Unfortunately, such data is usually not readily available with reanalysis products, often requiring the tedious decoding of large datasets and not so-user friendly file formats. With MERRA we have introduced a gridded version of the observations/innovations used in the assimilation process, using the same grid and data formats as the regular datasets. Such dataset empowers the user with the ability of conveniently performing observing system related analysis and error estimates. The scope of this dataset will be briefly described. We will present a systematic analysis of MERRA innovation time series for the conventional observing system, including maximum-likelihood estimates of background and observation errors, as well as global bias estimates. Starting with the joint PDF of innovations and analysis increments at observation locations we propose a technique for diagnosing bias among the observing systems, and document how these contextual biases have evolved during the satellite era covered by MERRA

Human sperm ion channel (dys)function:implications for fertilization

BACKGROUND: Intensive research on sperm ion channels has identified members of several ion channel families in both mouse and human sperm. Gene knock-out studies have unequivocally demonstrated the importance of the calcium and potassium conductances in sperm for fertility. In both species, the calcium current is carried by the highly complex cation channel of sperm (CatSper). In mouse sperm, the potassium current has been conclusively shown to be carried by a channel consisting of the pore forming subunit SLO3 and auxiliary subunit leucine-rich repeat-containing 52 (LRRC52). However, in human sperm it is controversial whether the pore forming subunit of the channel is composed of SLO3 and/or SLO1. Deciphering the role of the proton-specific Hv1 channel is more challenging as it is only expressed in human sperm. However, definitive evidence for a role in, and importance for, human fertility can only be determined through studies using clinical samples.OBJECTIVE AND RATIONALE: This review aims to provide insight into the role of sperm ion channels in human fertilization as evidenced from recent studies of sperm from infertile men. We also summarize the key discoveries from mouse ion channel knock-out models and contrast the properties of mouse and human CatSper and potassium currents. We detail the evidence for, and consequences of, defective ion channels in human sperm and discuss hypotheses to explain how defects arise and why affected sperm have impaired fertilization potential.SEARCH METHODS: Relevant studies were identified using PubMed and were limited to ion channels that have been characterized in mouse and human sperm. Additional notable examples from other species are included as appropriate.OUTCOMES: There are now well-documented fundamental differences between the properties of CatSper and potassium channel currents in mouse and human sperm. However, in both species, sperm lacking either channel cannot fertilize in vivo and CatSper-null sperm also fail to fertilize at IVF. Sperm-lacking potassium currents are capable of fertilizing at IVF, albeit at a much lower rate. However, additional complex and heterogeneous ion channel dysfunction has been reported in sperm from infertile men, the causes of which are unknown. Similarly, the nature of the functional impairment of affected patient sperm remains elusive. There are no reports of studies of Hv1 in human sperm from infertile men.WIDER IMPLICATIONS: Recent studies using sperm from infertile men have given new insight and critical evidence supporting the supposition that calcium and potassium conductances are essential for human fertility. However, it should be highlighted that many fundamental questions remain regarding the nature of molecular and functional defects in sperm with dysfunctional ion channels. The development and application of advanced technologies remains a necessity to progress basic and clinical research in this area, with the aim of providing effective screening methodologies to identify and develop treatments for affected men in order to help prevent failed ART cycles. Conversely, development of drugs that block calcium and/or potassium conductances in sperm is a plausible strategy for producing sperm-specific contraceptives.</p

Intersection local times of fractional Brownian motions with H∈(0,1)H\in(0,1) as generalized white noise functionals

In $\R^d$, for any dimension $d\geq 1$, expansions of self-intersection local times of fractional Brownian motions with arbitrary Hurst coefficients in $(0,1)$ are presented. The expansions are in terms of Wick powers of white noises (corresponding to multiple Wiener integrals), being well-defined in the sense of generalized white noise functionals.Comment: 17 page

The generation of nonlinear internal waves

Author Posting. © The Oceanography Society, 2012. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 25, No. 2 (2012): 108–123, doi:10.5670/oceanog.2012.46.Nonlinear internal waves are found in many parts of the world ocean. Their widespread distribution is a result of their origin in the barotropic tide and in the variety of ways they can be generated, including by lee waves, tidal beams, resonance, plumes, and the transformation of the internal tide. The differing generation mechanisms and diversity of generation locations and conditions all combine to produce waves that range in scale from a few tens of meters to kilometers, but with all properly described by solitary wave theory. The ability of oceanic nonlinear internal waves to persist for days after generation and the key role internal waves play in connecting large-scale tides to smaller-scale turbulence make them important for understanding the ocean environment.Christopher Jackson gratefully acknowledges the support of the Office of Naval Research through contract N0001409C0224

Complex CatSper-dependent and independent [Ca2⁺]i signalling in human spermatozoa induced by follicular fluid

STUDY QUESTION: Does progesterone in human follicular fluid (hFF) activate CatSper and do other components of hFF modulate this effect and/or contribute separately to hFF-induced Ca2+ signaling?SUMMARY ANSWER: hFF potently stimulates CatSper and increases [Ca2+]i, primarily due to high concentrations of progesterone, however,other components of hFF also contribute to [Ca2+]i signaling, including modulation of CatSper channel activity and inhibition of [Ca2+]i oscillations.WHAT IS KNOWN ALREADY: CatSper, the principal Ca2+ channel in spermatozoa, is progesterone-sensitive and essential for fertility. Both hFF and progesterone, which is present in hFF, influence sperm function and increase their [Ca2+]i.STUDY DESIGN, SIZE, DURATION: This basic medical research study used semen samples from &gt;40 donors and hFF from &gt;50 patients who were undergoing surgical oocyte retrieval for IVF/ICSI.PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen donors and patients were recruited in accordance with local ethics approval (13/ES/0091) from the East of Scotland Research Ethics Service REC1. Activities of CatSper and KSper were assessed by patch clamp electrophysiology. Sperm [Ca2+]i responses were examined in sperm populations and single cells. Computer-assisted sperm analysis (CASA) parameters and penetration into viscous media were used to assess functional effects.MAIN RESULTS AND THE ROLE OF CHANCE: hFF and progesterone significantly potentiated CatSper currents. Under quasiphysiologicalconditions, hFF (up to 50%) failed to alter membrane K+ conductance or current reversal potential. hFF and progesterone (at an equivalent concentration) stimulated similar biphasic [Ca2+]i signals both in sperm populations and single cells. At a high hFF concentration (10%), the sustained (plateau) component of the [Ca2+]i signal was consistently greater than that induced by progesterone alone. In single cell recordings, 1% hFF-induced [Ca2+]i oscillations similarly to progesterone but with 10% hFF generation of [Ca2+]i oscillations was suppressed. After treatment to ‘strip’ lipid-derived mediators, hFF failed to significantly stimulate CatSper currents but induced small [Ca2+]i responsesthat were greater than those induced by the equivalent concentration of progesterone after stripping. Similar [Ca2+]i responses were observed when sperm pretreated with 3 μM progesterone (to desensitize progesterone responses) were stimulated with hFF or stripped hFF. hFF stimulated viscous media penetration and was more effective than the equivalent does of progesterone.LARGE SCALE DATA: N/A.LIMITATIONS, REASONS FOR CAUTION: This was an in vitro study. Caution must be taken when extrapolating these results in vivo.WIDER IMPLICATIONS OF THE FINDINGS: This study directly demonstrates that hFF activates CatSper and establishes that the biologically important effects of hFF reflect, at least in part, action on this channel, primarily via progesterone. However, these experiments also demonstrate that other components of hFF both contribute to the [Ca2+]i signal and modulate the activation of CatSper. Simple in vitro experiments performed out of the context of the complex in vivo environment need to be interpreted with caution

Análise histológica da regeneração óssea guiada utilizando membranas de ácido polilático co-glicólico (PLGA) associado ou não à hidroxiapatita (PLGA + HA) em defeitos ósseos críticos

TCC (graduação) - Universidade Federal de Santa Catarina. Centro de Ciências da Saúde. Odontologia.O objetivo deste estudo foi avaliar in vivo o reparo ósseo utilizando membranas de poliácido lático-co-glicólico (PLGA), associado ou não a hidroxiapatita (HA). Foram utilizados 13 ratos (Rattus novergicus albinus, Wistar) adultos machos (20-24 semanas) pesando aproximadamente 180g. Os animais foram distribuídos em 3 grupos: Controle negativo, no qual foram realizados os defeitos ósseos sem recobrimento com membrana; grupos PLGA e PLGA+HA, nos quais os defeitos ósseos foram recobertos com membrana de PLGA e PLGA+HA, respectivamente. Em cada animal foi realizado um defeito circular de 5mm de diâmetro em cada osso parietal. Os defeitos foram tratados aleatoriamente de acordo com os grupos propostos, totalizando 26 defeitos. As amostras foram coletadas após um período experimental de 30 dias, foram descalcificadas e, em seguida, processadas histologicamente. Em sequência foi realizada a análise morfométrica para avaliação do reparo ósseo. Após 30 dias observou-se formação óssea em todos os grupos do estudo. O grupo PLGA+HA apresentou uma média de área de 1805,2357 ± e um desvio padrão de 1394,93481, enquanto que o grupo PLGA apresentou uma média de 2396,6143 ± com um desvio padrão de 878,75394. Não foi possível estabelecer significância no processo de neoformação óssea entre os grupos da pesquisa (p > 0,05). Uma amostra mais representativa poderá revelar ou não o efeito osteopromotor associado a HA, assim como a associação com uma análise imunohistoquimica de marcadores da formação óssea.The aim of this study was to evaluate in vivo bone repair using a polylactic acid membrane-co-glycolic acid (PLGA), associated with hydroxyapatite (HA). Thirteen (Rattus norvegicus albinus, Wistar) adult males (20-24 weeks) rats weighing approximately 180g were used. The animals were divided into 3 groups: Control group in which the bone defects were realized without covering membrane; PLGA and PLGA + HA groups in which the bone defects were covered with a membrane of PLGA and PLGA + HA, respectively. In each animal a circular diameter 5mm in each parietal bone defect was made. The defects were randomly treated according to the proposed groups, totaling 26 defects. The samples were collected after a trial period of 30 days, decalcified and were followed for histological processing. Sequentially morphometric analysis was performed for evaluation of bone repair. After a period of 30 days bone formation in all study groups was observed. The PLGA + HA group had a mean area of 1805,2357 ± and a standard deviation of 1394,93481, while the PLGA group presented 2396,6143 ± an average standard deviation with a 878,75394. Unable to establish the significance of bone formation process among groups in this research (p > 0,05). A representative sample can reveal whether or not the bone promoter effect is associated with HA, well as the association with an immunohistochemical analysis of markers of bone formation

Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss of CatSper function and compromised fertilizing capacity

STUDY QUESTIONDoes a man (patient 1) with a previously described deficiency in principle cation channel of sperm (CatSper) function have a mutation in the CatSper-epsilon (CATSPERE) and/or CatSper-zeta (CATSPERZ) gene?SUMMARY ANSWERPatient 1 has a homozygous in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE.WHAT IS KNOWN ALREADYCatSper is the principal calcium channel of mammalian spermatozoa. Spermatozoa from patient 1 had a specific loss of CatSper function and were unable to fertilize at IVF. Loss of CatSper function could not be attributed to genetic abnormalities in coding regions of seven CatSper subunits. Two additional subunits (CatSper-epsilon (CATPSERE) and CatSper-zeta (CATSPERZ)) were recently identified, and are now proposed to contribute to the formation of the mature channel complex.STUDY DESIGN, SIZE, DURATIONThis was a basic medical research study analysing genomic data from a single patient (patient 1) for defects in CATSPERE and CATSPERZ.PARTICIPANTS/MATERIALS, SETTING, METHODSThe original exome sequencing data for patient 1 were analysed for mutations in CATSPERE and CATSPERZ. Sanger sequencing was conducted to confirm the presence of a rare variant.MAIN RESULTS AND THE ROLE OF CHANCEPatient 1 is homozygous for an in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE that is predicted to be highly deleterious.LIMITATIONS, REASONS FOR CAUTIONThe nature of the molecular deficit caused by the rs761237686 variant and whether it is exclusively responsible for the loss of CatSper function remain to be elucidated.WIDER IMPLICATIONS OF THE FINDINGSPopulation genetics are available for a significant number of predicted deleterious variants of CatSper subunits. The consequence of homozygous and compound heterozygous forms on sperm fertilization potential could be significant. Selective targeting of CatSper subunit expression maybe a feasible strategy for the development of novel contraceptives.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by project grants from the MRC (MR/K013343/1 and MR/012492/1), Chief Scientist Office/NHS research Scotland. This work was also supported by NIH R01GM111802, Pew Biomedical Scholars Award 00028642 and Packer Wentz Endowment Will to P.V.L. C.L.R.B is the editor-in-chief of Molecular Human Reproduction, has received lecturing fees from Merck and Ferring, and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012–2016)