Motoneurone synchronization for intercostal and abdominal muscles: interneurone influences in two different species

The contribution of branched-axon monosynaptic inputs in the generation of short-term synchronization of motoneurones remains uncertain. Here, synchronization was measured for intercostal and abdominal motoneurones supplying the lower thorax and upper abdomen, mostly showing expiratory discharges. Synchronization in the anaesthetized cat, where the motoneurones receive a strong direct descending drive, is compared with that in anaesthetized or decerebrate rats, where the direct descending drive is much weaker. In the cat, some examples could be explained by branched-axon monosynaptic inputs, but many others could not, by virtue of peaks in cross-correlation histograms whose widths (relatively wide) and timing indicated common inputs with more complex linkages, e.g., disynaptic excitatory. In contrast, in the rat, correlations for pairs of internal intercostal nerves were dominated by very narrow peaks, indicative of branched-axon monosynaptic inputs. However, the presence of activity in both inspiration and expiration in many of the nerves allowed additional synchronization measurements between internal and external intercostal nerves. Time courses of synchronization for these often consisted of combinations of peaks and troughs, which have never been previously described for motoneurone synchronization and which we interpret as indicating combinations of inputs, excitation of one group of motoneurones being common with either excitation or inhibition of the other. Significant species differences in the circuits controlling the motoneurones are indicated, but in both cases, the roles of spinal interneurones are emphasised. The results demonstrate the potential of motoneurone synchronization for investigating inhibition and have important general implications for the interpretation of neural connectivity measurements by cross-correlation

Multivariate discrimination and the Higgs + W/Z search

A systematic method for optimizing multivariate discriminants is developed and applied to the important example of a light Higgs boson search at the Tevatron and the LHC. The Significance Improvement Characteristic (SIC), defined as the signal efficiency of a cut or multivariate discriminant divided by the square root of the background efficiency, is shown to be an extremely powerful visualization tool. SIC curves demonstrate numerical instabilities in the multivariate discriminants, show convergence as the number of variables is increased, and display the sensitivity to the optimal cut values. For our application, we concentrate on Higgs boson production in association with a W or Z boson with H -> bb and compare to the irreducible standard model background, Z/W + bb. We explore thousands of experimentally motivated, physically motivated, and unmotivated single variable discriminants. Along with the standard kinematic variables, a number of new ones, such as twist, are described which should have applicability to many processes. We find that some single variables, such as the pull angle, are weak discriminants, but when combined with others they provide important marginal improvement. We also find that multiple Higgs boson-candidate mass measures, such as from mild and aggressively trimmed jets, when combined may provide additional discriminating power. Comparing the significance improvement from our variables to those used in recent CDF and DZero searches, we find that a 10-20% improvement in significance against Z/W + bb is possible. Our analysis also suggests that the H + W/Z channel with H -> bb is also viable at the LHC, without requiring a hard cut on the W/Z transverse momentum.Comment: 41 pages, 5 tables, 29 figure

Errors in chromosome segregation during oogenesis and early embryogenesis

Errors in chromosome segregation occurring during human oogenesis and early embryogenesis are very common. Meiotic chromosome development during oogenesis is subdivided into three distinct phases. The crucial events, including meiotic chromosome pairing and recombination, take place from around 11 weeks until birth. Oogenesis is then arrested until ovulation, when the first meiotic division takes place, with the second meiotic division not completed until after fertilization. It is generally accepted that most aneuploid fetal conditions, such as trisomy 21 Down syndrome, are due to maternal chromosome segregation errors. The underlying reasons are not yet fully understood. It is also clear that superimposed on the maternal meiotic chromosome segregation errors, there are a large number of mitotic errors taking place post-zygotically during the first few cell divisions in the embryo. In this chapter, we summarise current knowledge of errors in chromosome segregation during oogenesis and early embryogenesis, with special reference to the clinical implications for successful assisted reproduction

Heavy Squarks at the LHC

The LHC, with its seven-fold increase in energy over the Tevatron, is capable of probing regions of SUSY parameter space exhibiting qualitatively new collider phenomenology. Here we investigate one such region in which first generation squarks are very heavy compared to the other superpartners. We find that the production of these squarks, which is dominantly associative, only becomes rate-limited at mSquark > 4(5) TeV for L~10(100) fb-1. However, discovery of this scenario is complicated because heavy squarks decay primarily into a jet and boosted gluino, yielding a dijet-like topology with missing energy (MET) pointing along the direction of the second hardest jet. The result is that many signal events are removed by standard jet/MET anti-alignment cuts designed to guard against jet mismeasurement errors. We suggest replacing these anti-alignment cuts with a measurement of jet substructure that can significantly extend the reach of this channel while still removing much of the background. We study a selection of benchmark points in detail, demonstrating that mSquark= 4(5) TeV first generation squarks can be discovered at the LHC with L~10(100)fb-1

Surviving a transfixing gunshot wound to the head 70 years ago.

Surviving a gunshot wound to the head is a rare event, particularly in the past when medical treatment was much less advanced than it is today. Moreover, the finding of such a case as an identified specimen within a museum collection is even more uncommon. This led us to report on this unique case in this paper as it poses a challenge to forensic anthropology and provides a unique educational oppourtunity. The skull from the Collection at the Cranium Museum in the Department of Morphology and Genetic at the Federal University of São Paulo (UNIFESP) dates back to 1946. For trauma registration the bone location, severity, trauma aetiology, trauma classification, description, callus formation, periosteal reaction, degree and success of repair, and an estimate of the time elapsed since the trauma, were all assessed. To explore the case radiologically a CT scan of the skull was performed. Considering the survival of the patient and the morphology of the wound it is likely that the injury was caused by a small calibre, low-velocity gunshot. The bullet path shows an almost vertical direction on the right side of the individual's splanchno and neurocranium. The path of the projectile is consistent with a suicide attempt, although the possibility of a homicide simulating a suicide cannot be discarded. This case highlights how informative such cases can be to the practice of forensic anthropology

Anoxia- and hypoxia-induced expression of LDH-A* in the Amazon Oscar, Astronotus crassipinis

Adaptation or acclimation to hypoxia occurs via the modulation of physiologically relevant genes, such as erythropoietin, transferrin, vascular endothelial growth factor, phosphofructokinase and lactate dehydrogenase A. In the present study, we have cloned, sequenced and examined the modulation of the LDH-A gene after an Amazonian fish species, Astronotus crassipinis (the Oscar), was exposed to hypoxia and anoxia. In earlier studies, we have discovered that adults of this species are extremely tolerant to hypoxia and anoxia, while the juveniles are less tolerant. Exposure of juveniles to acute hypoxia and anoxia resulted in increased LDH-A gene expression in skeletal and cardiac muscles. When exposed to graded hypoxia juveniles show decreased LDH-A expression. In adults, the levels of LDH-A mRNA did not increase in hypoxic or anoxic conditions. Our results demonstrate that, when given time for acclimation, fish at different life-stages are able to respond differently to survive hypoxic episodes

Prediction of leak flow rate in plastic water distribution pipes using vibro-acoustic measurements

Leakage from water distribution systems is a worldwide issue with consequences including loss of revenue, health and environmental concerns. Leaks have typically been found through leak noise correlation by placing sensors either side of the leak and recording and analysing its vibro-acoustic emission. While this method is widely used to identify the location of the leak, the sensors also record data that could be related to the leak’s flow rate, yet no reliable method exists to predict leak flow rate in water distribution pipes using vibro-acoustic emission. The aim of this research is to predict leak flow rate in medium-density polyethylene pipe using vibro-acoustic emission signals. A novel experimental methodology is presented whereby circular holes of four sizes are tested at several leak flow rates. Following the derivation of a number of features, least squares support vector machines are used in order to predict leak flow rate. The results show a strong correlation highlighting the potential of this technique as a rapid and practical tool for water companies to assess and prioritise leak repair

Astrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetamine

Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT— Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-030647 (PTDC/ SAU-TOX/30647/2017) in TS lab. FEDER Portugal (Norte-01-0145-FEDER000008000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); FCOMP-01-0124-FEDER-021333). CCP and RS hold employment contracts financed by national funds through FCT –in the context of the program-contract described in paragraphs 4, 5, and 6 of art. 23 of Law no. 57/ 2016, of August 29, as amended by Law no. 57/2017 of July 2019. TC, TOA, AFT, JB, AIS and AM were supported by FCT (SFRH/BD/117148/2016, SFRH/BD/147981/2019, 2020.07188.BD, PD/BD/135450/2017, SFRH/BD/144324/2019, and IF/00753/2014). Work in JBR lab was supported by the FCT project PTDC/ MED-NEU/31318/2017. JFO was also supported by FCT projects PTDC/MED-NEU/31417/2017 and POCI-01- 0145-FEDER-016818; Bial Foundation Grants 207/14 and 037/18, by National funds, through FCT - project UIDB/50026/2020; and by the projects NORTE-01-0145-FEDER000013 and NORTE-01-0145-FEDER-000023, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Funding of i3S Scientific Platforms: Advanced Light Microscopy (ALM), a member of the national infrastructure PPBI-Portuguese Platform of BioImaging (POCI-01–0145-FEDER022122); and Genomics through GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by FCT