Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects

Segmentation defects of the vertebrae (SDV) are caused by aberrant somite formation during embryogenesis and result in irregular formation of the vertebrae and ribs. The Notch signal transduction pathway plays a critical role in somite formation and patterning in model vertebrates. In humans, mutations in several genes involved in the Notch pathway are associated with SDV, with both autosomal recessive (MESP2, DLL3, LFNG, HES7) and autosomal dominant (TBX6) inheritance. However, many individuals with SDV do not carry mutations in these genes. Using whole-exome capture and massive parallel sequencing, we identified compound heterozygous mutations in RIPPLY2 in two brothers with multiple regional SDV, with appropriate familial segregation. One novel mutation (c.A238T:p.Arg80*) introduces a premature stop codon. In transiently transfected C2C12 mouse myoblasts, the RIPPLY2 mutant protein demonstrated impaired transcriptional repression activity compared with wild-type RIPPLY2 despite similar levels of expression. The other mutation (c.240-4T>G), with minor allele frequency <0.002, lies in the highly conserved splice site consensus sequence 5' to the terminal exon. Ripply2 has a well-established role in somitogenesis and vertebral column formation, interacting at both gene and protein levels with SDV-associated Mesp2 and Tbx6. We conclude that compound heterozygous mutations in RIPPLY2 are associated with SDV, a new gene for this condition. © The Author 2014.

Receptor guanylyl cyclase C (GC-C): regulation and signal transduction

Receptor guanylyl cyclase C (GC-C) is the target for the gastrointestinal hormones, guanylin, and uroguanylin as well as the bacterial heat-stable enterotoxins. The major site of expression of GC-C is in the gastrointestinal tract, although this receptor and its ligands play a role in ion secretion in other tissues as well. GC-C shares the domain organization seen in other members of the family of receptor guanylyl cyclases, though subtle differences highlight some of the unique features of GC-C. Gene knock outs in mice for GC-C or its ligands do not lead to embryonic lethality, but modulate responses of these mice to stable toxin peptides, dietary intake of salts, and development and differentiation of intestinal cells. It is clear that there is much to learn in future about the role of this evolutionarily conserved receptor, and its properties in intestinal and extra-intestinal tissues.

Jet Engine Health Signal Denoising Using Optimally Weighted Recursive Median Filters

The removal of noise and outliers from health signals is an important problem in jet engine health monitoring. Typically, health signals are time series of damage indicators, which can be sensor measurements or features derived from such measurements. Sharp or sudden changes in health signals can represent abrupt faults and long term deterioration in the system is typical of gradual faults. Simple linear filters tend to smooth out the sharp trend shifts in jet engine signals and are also not good for outlier removal. We propose new optimally designed nonlinear weighted recursive median filters for noise removal from typical health signals of jet engines. Signals for abrupt and gradual faults and with transient data are considered. Numerical results are obtained for a jet engine and show that preprocessing of health signals using the proposed filter significantly removes Gaussian noise and outliers and could therefore greatly improve the accuracy of diagnostic systems. [DOI: 10.1115/1.3200907].

Atrial Electric Signal During Sinus Rhythm in Lone Paroxysmal Atrial Fibrillation

Atrial fibrillation (AF) is the most common tachyarrhythmia and is associated with substantial morbidity, increased mortality and cost. The treatment modalities of AF have increased, but results are still far from optimal. More individualized therapy may be beneficial. Aiming for this calls improved diagnostics. Aim of this study was to find non-invasive parameters obtained during sinus rhythm reflecting electrophysiological patterns related to propensity to AF and particularly to AF occurring without any associated heart disease, lone AF. Overall 240 subjects were enrolled, 136 patients with paroxysmal lone AF and 104 controls (mean age 45 years, 75% males). Signal measurements were performed by non-invasive magnetocardiography (MCG) and by invasive electroanatomic mapping (EAM). High-pass filtering techniques and a new method based on a surface gradient technique were adapted to analyze atrial MCG signal. The EAM was used to elucidate atrial activation in patients and as a reference for MCG. The results showed that MCG mapping is an accurate method to detect atrial electrophysiologic properties. In lone paroxysmal AF, duration of the atrial depolarization complex was marginally prolonged. The difference was more obvious in women and was also related to interatrial conduction patterns. In the focal type of AF (75%), the root mean square (RMS) amplitudes of the atrial signal were normal, but in AF without demonstrable triggers the late atrial RMS amplitudes were reduced. In addition, the atrial characteristics tended to remain similar even when examined several years after the first AF episodes. The intra-atrial recordings confirmed the occurrence of three distinct sites of electrical connection from right to left atrium (LA): the Bachmann bundle (BB), the margin of the fossa ovalis (FO), and the coronary sinus ostial area (CS). The propagation of atrial signal could also be evaluated non-invasively. Three MCG atrial wave types were identified, each of which represented a distinct interatrial activation pattern. In conclusion, in paroxysmal lone AF, active focal triggers are common, atrial depolarization is slightly prolonged, but with a normal amplitude, and the arrhythmia does not necessarily lead to electrical or mechanical dysfunction of the atria. In women the prolongation of atrial depolarization is more obvious. This may be related to gender differences in presentation of AF. A significant minority of patients with lone AF lack frequent focal triggers, and in them, the late atrial signal amplitude is reduced, possibly signifying a wider degenerative process in the LA. In lone AF, natural impulse propagation to LA during sinus rhythm goes through one or more of the principal pathways described. The BB is the most common route, but in one-third, the earliest LA activation occurs outside the BB. Susceptibility to paroxysmal lone AF is associated with propagation of the atrial signal via the margin of the FO or via multiple pathways. When conduction occurs via the BB, it is related with prolonged atrial activation. Thus, altered and alternative conduction pathways may contribute to pathogenesis of lone AF. There is growing evidence of variability in genesis of AF also within lone paroxysmal AF. Present study suggests that this variation may be reflected in cardiac signal pattern. Recognizing the distinct signal profiles may assist in understanding the pathogenesis of AF and identifying subgroups for patient-tailored therapy.

GMM based Bayesian approach to speech enhancement in signal transform domain

Considering a general linear model of signal degradation, by modeling the probability density function (PDF) of the clean signal using a Gaussian mixture model (GMM) and additive noise by a Gaussian PDF, we derive the minimum mean square error (MMSE) estimator. The derived MMSE estimator is non-linear and the linear MMSE estimator is shown to be a special case. For speech signal corrupted by independent additive noise, by modeling the joint PDF of time-domain speech samples of a speech frame using a GMM, we propose a speech enhancement method based on the derived MMSE estimator. We also show that the same estimator can be used for transform-domain speech enhancement.

Signal set design for full-diversity low-decoding-complexity differential scaled-unitary STBCs

The problem of designing high rate, full diversity noncoherent space-time block codes (STBCs) with low encoding and decoding complexity is addressed. First, the notion of g-group encodable and g-group decodable linear STBCs is introduced. Then for a known class of rate-1 linear designs, an explicit construction of fully-diverse signal sets that lead to four-group encodable and four-group decodable differential scaled unitary STBCs for any power of two number of antennas is provided. Previous works on differential STBCs either sacrifice decoding complexity for higher rate or sacrifice rate for lower decoding complexity.

Response time measurement in flow induced signal generation on semiconductors

Measurable electrical signal is generated when a gas flows over a variety of solids, including doped semiconductors, even at the modest speed of a few meters per second. The underlying mechanism is an interesting interplay of Bernoulli's principle and the Seebeck effect. The electrical signal depends on the square of Mach number (M) and is proportional to the Seebeck coefficient (S) of the solids. Here we present experimental estimate of the response time of the signal rise and fall process, i.e. how fast the semiconductor materials respond to a steady flow as soon as it is set on or off. A theoretical model is also presented to understand the process and the dependence of the response time on the nature and physical dimensions of the semiconductor material used and they are compared with the experimental observations. (c) 2007 Elsevier B.V. All rights reserved.

Signal set design for full-diversity low-decoding-complexity differential scaled-unitary STBCs

The problem of designing high rate, full diversity noncoherent space-time block codes (STBCs) with low encoding and decoding complexity is addressed. First, the notion of g-group encodable and g-group decodable linear STBCs is introduced. Then for a known class of rate-1 linear designs, an explicit construction of fully-diverse signal sets that lead to four-group encodable and four-group decodable differential scaled unitary STBCs for any power of two number of antennas is provided. Previous works on differential STBCs either sacrifice decoding complexity for higher rate or sacrifice rate for lower decoding complexity.

Julkisen tilan kontrollin ulottuvuuksia : tapaustutkimus Stop Töhryille -projektista.

Tämä tutkielma keskittyy julkisen kaupunkitilan kontrollin eri muotoihin. Ihmiset käyttävät kaupunkitilaa eri tavoin ja eri tarkoituksiin. Tilan sallitut ja kielletyt käyttömuodot ovat aina erilaisten toiveiden yhteensovittamista: yhteisen neuvottelun tulos. Tilaa myös kontrolloidaan vastaamaan erilaisia toiveita ja odotuksia. Tutkielmassa julkisen tilan kontrollin muodot on jaettu kolmeen: tilan fyysinen muokkaaminen, tilan valvonta ja asenteisiin vaikuttaminen esimerkiksi politiikkaohjelmilla. Tärkeimpänä kiinnostuksen kohteena on tilanne, jossa jokin toiminta kielletään kokonaisuudessaan. Tutkielmassa käytetään konkreettisena esimerkkinä yrityksestä kontrolloida tilaa Helsingin kaupungin Stop Töhryille -projektia: kyseessä on tapaustutkimus em. projektista. Projekti toteutettiin vuosina 1998–2008 Helsingin kaupungin rakennusviraston sekä yleisten töiden lautakunnan alaisuudessa. Projektin tavoitteena oli vähentää ja poistaa kaupunkitilassa näkyviä graffiteja. Keinoina tähän oli tekninen siivous, valvonta ja viestintä. Graffitit voidaan nähdä yhtenä keinona vallata tilaa itselle. Tutkimuksen ongelmanasettelun taustalla on pohdinta siitä, kohdistuuko julkisen tilan kontrolli jonkin tietyn toiminnon ei-toivottavuuteen vai kohdistuuko kontrolli tiettyjen toimijoiden ei-toivottavuuteen. Tavoitteena on selvittää, minkälainen tilan kontrolliin tähtäävä ohjelma Stop Töhryille -projekti oli. Tutkimuskysymykset liittyvät siihen, miksi projekti toteutettiin, mihin projektin toimenpiteet kohdistuivat ja miten nollatoleranssi määriteltiin projektissa. Tutkielman teoreettinen viitekehys pohjautuu Jock Youngin määritelmälle nollatoleranssista, nollatoleranssin kritiikille sekä Henri Lefebvren, Don Mitchellin, Andrea Sharkeyn ja Rob Shieldsin kirjoituksiin oikeudesta tilaan. Aineistona käytetään yleisten töiden lautakunnan kokousten esityslista- ja pöytäkirjamateriaalia sekä haastatteluja projektissa mukana olleille tai projektiin vaikuttaneille tahoille (N=4). Analyysin menetelmänä sovelletaan diskurssianalyysiä. Aineiston perusteella voidaan todeta, että projektissa hyödynnettiin laajasti erilaisia kontrollin keinoja. Projektin toimenpiteet keskittyivät alussa enemmän toimintoon (graffitien puhdistamiseen ja ehkäisyyn), mutta viimeisinä vuosina painopiste siirtyi enemmän toimijaan (graffitintekijään). Aineiston analyysissä yhtenä olennaisena toimijaryhmänä esille nousivat nuoret ja nuoriso, jotka mainittiin useaan otteeseen graffitintekijöinä. Tutkielmassa tätä ilmiötä pohditaan Mike Presdeen nuoruuden kriminalisointi -käsitteen sekä Zygmunt Baumanin ulossulkemisen paradigman kautta. Nollatoleranssiretoriikka on löydettävissä projektista kolmella tasolla: ideologisella, toiminnallisella sekä viestinnällisellä. Nollatoleranssia perusteltiin ideologisella tasolla rikottujen ikkunoiden teesillä: pieniä sosiaalisia häiriöitä poistamalla voidaan ehkäistä suuria rikoksia. Tämä perustelu vietiin toiminnalliselle tasolle, jossa häiriökäyttäytyjiä valvottiin ja heille vaadittiin kovia rangaistuksia. Viestinnällä pyrittiin madaltamaan kansalaisten sietokykyä graffiti-ilmiöön ja edesautettiin mahdollisimman laajan kansalais- ja asukasyhteistyön syntymistä. Lisäksi projektissa luotiin aktiivisesti tiedon ja kielen politiikkaa, joissa tuotetaan käsitystä siitä että graffitit lisäävät turvattomuutta ja konstruoidaan sellainen kieli, jossa graffitit nähdään ongelmana.

Search for Pair Production of Supersymmetric Top Quarks in Dilepton Events from pp̅ Collisions at √s=1.96 TeV

We present the results of a search for pair production of the supersymmetric partner of the top quark (the stop quark $\tilde{t}_{1}$) decaying to a $b$-quark and a chargino $\chargino$ with a subsequent $\chargino$ decay into a neutralino $\neutralino$, lepton $\ell$, and neutrino $\nu$. Using a data sample corresponding to 2.7 fb$^{-1}$ of integrated luminosity of $p\bar{p}$ collisions at $\sqrt{s} = 1.96$ TeV collected by the CDF II detector, we reconstruct the mass of candidate stop events and fit the observed mass spectrum to a combination of standard model processes and stop quark signal. We find no evidence for $\pairstop$ production and set 95% C.L. limits on the masses of the stop quark and the neutralino for several values of the chargino mass and the branching ratio ${\cal B}(\chargino\to\neutralino\ell^{\pm}\nu)$.

Search for the supersymmetric partner of the top quark in pp̅ collisions at √s=1.96 TeV

We present a search for the lightest supersymmetric partner of the top quark in proton-antiproton collisions at a center-of-mass energy √s=1.96  TeV. This search was conducted within the framework of the R parity conserving minimal supersymmetric extension of the standard model, assuming the stop decays dominantly to a lepton, a sneutrino, and a bottom quark. We searched for events with two oppositely-charged leptons, at least one jet, and missing transverse energy in a data sample corresponding to an integrated luminosity of 1  fb-1 collected by the Collider Detector at Fermilab experiment. No significant evidence of a stop quark signal was found. Exclusion limits at 95% confidence level in the stop quark versus sneutrino mass plane are set. Stop quark masses up to 180  GeV/c2 are excluded for sneutrino masses around 45  GeV/c2, and sneutrino masses up to 116  GeV/c2 are excluded for stop quark masses around 150  GeV/c2.

Detection of a periodic structure hidden in random background: the role of signal amplitude in the matched filter detection method

The matched filter method for detecting a periodic structure on a surface hidden behind randomness is known to detect up to (r(0)/Lambda) gt;= 0.11, where r(0) is the coherence length of light on scattering from the rough part and 3 is the wavelength of the periodic part of the surface-the above limit being much lower than what is allowed by conventional detection methods. The primary goal of this technique is the detection and characterization of the periodic structure hidden behind randomness without the use of any complicated experimental or computational procedures. This paper examines this detection procedure for various values of the amplitude a of the periodic part beginning from a = 0 to small finite values of a. We thus address the importance of the following quantities: `(a)lambda) `, which scales the amplitude of the periodic part with the wavelength of light, and (r(0))Lambda),in determining the detectability of the intensity peaks.