SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant.

Copy-number variants (CNVs) represent a significant interpretative challenge, given that each CNV typically affects the dosage of multiple genes. Here we report on five individuals with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects who harbor overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo dissection of the CNV showed discrete contributions of the planar cell polarity effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components. Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional testing of this allele in vivo and in vitro showed that the mutation perturbs the relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency of downstream PUF60 targets. These data inform the functions of two genes not associated previously with human genetic disease and demonstrate how CNVs can exhibit complex genetic architecture, with the phenotype being the amalgam of both discrete dosage dysfunction of single transcripts and also of binary genetic interactions.

3G SGSN Toiminnallisuustestauksen Automatisointi

3G SGSN (3rd Generation Serving GPRS Support Node) onUMTS (Universal Mobile Telecommunications System) pakettiverkon verkkoelementti, joka toimii linkkinä ulkoisen verkon(kuten Internet) ja radioverkon välillä. 3G SGSN ylläpitää tilaajan tietoja ja paikannustietoja päätelaitteen liikkuessa verkon sisällä ja välittää myös dataa ulkoisen verkon ja mobiilipäätelaitteen välillä. Tämän diplomityön aiheena on 3G SGSN toiminnallisuus-testauksen automatisointi. Työssä kehitetään 3G SGSN toiminnallisuustestaukseen soveltuva testauksen automatisointijärjestelmä Linux-ympäristössä AuTS (Automated Test Sequences)-automatisointityökalulla. Kehitystyöhön kuuluu järjestelmän suunnittelu ja toteutus. Toteutettu automatisointijärjestelmä suorittaa 3G SGSN toiminnallisuustestauksen istunnon- ja liikkuvuudenhallinnan testitapauksia.Suoritettujen testitapausten tuloksista luodaan HTML (Hypertext Markup Language)-raportti, joka sisältää tiedot ja analyysit suoritetuista testitapauksista sekä linkit testitapausten lokitietoihin. Hyvä automatisointi vaatii suunnittelua, jossa huomioidaan käytettävyys ja ylläpidettävyys. Näihin ominaisuuksiin on toteutuksessa kiinnitetty erityistä huomiota. Lopputuloksena saatiin toimiva automatisointijärjestelmä, joka osoittaa automatisoinnin tuovan huomattavia etuja toiminnallisuustestauksen tehokkuuteen. Työssä käsitelläänmyös ohjelmistotestausta sekä testauksen automatisointia ja niiden periaatteita.

Test automation scheme for LTE core network element

Modern sophisticated telecommunication devices require even more and more comprehensive testing to ensure quality. The test case amount to ensure well enough coverage of testing has increased rapidly and this increased demand cannot be fulfilled anymore only by using manual testing. Also new agile development models require execution of all test cases with every iteration. This has lead manufactures to use test automation more than ever to achieve adequate testing coverage and quality. This thesis is separated into three parts. Evolution of cellular networks is presented at the beginning of the first part. Also software testing, test automation and the influence of development model for testing are examined in the first part. The second part describes a process which was used to implement test automation scheme for functional testing of LTE core network MME element. In implementation of the test automation scheme agile development models and Robot Framework test automation tool were used. In the third part two alternative models are presented for integrating this test automation scheme as part of a continuous integration process. As a result, the test automation scheme for functional testing was implemented. Almost all new functional level testing test cases can now be automated with this scheme. In addition, two models for integrating this scheme to be part of a wider continuous integration pipe were introduced. Also shift from usage of a traditional waterfall model to a new agile development based model in testing stated to be successful.

Ohjelmistotestauksen käytänteet Suomessa

Ohjelmistotestauksen merkitys on kasvanut sen mukaan mitä enemmän ohjelmisto-tuotteet vaikuttavat jokapäiväisesseen elämämme. Tämän vuoksi yritysten investointien ja laadunvarmentamisen yhteys on ilmeinen. Organisaatiot panostavat yhä enemmän ei–funktionaaliseen testaukseen, kuten turvallisuuden, suorituskyvyn ja käytettävyyden testaamiseen. Tämän työn tarkoituksena on tutkia ohjelmistotestauksen nykytilannetta Suomessa. Syy tähän on uudistaa ja parantaa ohjelmistotestauksen kurssitarjontaa Turun yliopistossa vastaamaan parhaalla mahdollisella tavalla yritysten tarvetta. Opinnäyte on toteutettu replikaatio-tutkimuksena. Pääosa kyselystä sisältää kysymyksiä ohjelmistotestauksen menetelmistä ja työkaluista testausprosessin toimintojen aikana. Lisäksi on yleisiä kysymyksiä yrityksistä ja niiden ohjelmistotestausympäristöistä. Kyselyssä otetaan myös kantaa yritysten käyttämiin monenlaisiin testaus-tasoihin, -tyyppeihin ja testauksessa kohdattuihin haasteisiin. Tämä opinnäyte perustuu testausprosessistandardeihin. Ohjelmistotestausstandardit ovat keskeisessä asemassa tässä työssä, vaikka ne ovat olleet viime aikoina vahvan kritiikin kohteena. Epäilys standardien välttämättömyyteen on syntynyt muutoksista ohjelmistokehityksessä. Tämä työ esittelee tulokset ohjelmistotestauksen käytännöistä. Tuloksia on verrattu aiheeseen liittyvän aiemman kyselyn (Lee, Kang, & Lee, 2011) tuloksiin. Ajanpuutteen havaitaan olevan suuri haaste ohjelmistotestauksessa. Ketterä ohjelmistokehitys on saavuttanut suosiota kaikissa vastaajien yrityksissä. Testauksen menetelmät ja työkalut testauksen arviointiin, suunnitteluun ja raportointiin ovat hyvin vähäisessä käytössä. Toisaalta testauksen menetelmien ja työkalujen käyttö automaattiseen testauksen toteuttamiseen ja virheiden hallintaan on lisääntynyt. Järjestelmä-, hyväksyntä-, yksikkö- ja integraatiotestaus ovat käytössä kaikkien vastaajien edustamissa yrityksissä. Kaikkien vastaajien mielestä regressio- sekä tutkiva- ja ei-funktionaalinen testaus ovat tärkeitä tekniikoita.

Ganho de força e função em idosos por treino isométrico com e sem resposta visual

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prova estética e funcional: uma decisão em conjunto

An important phase of rehabilitation treatment, is the aesthetic and functional testing, performed with the patient. Its relevance is because at this time it’s possible to have a very faithful preview of the final result of the prosthesis, but, if necessary, still allow changes. Therefore, the objective of this review is to describe didactically the clinical steps and factors that should be examined by the dentist at the moment of aesthetic and functional testing of a complete denture. This clinical stage basically involves four requirements to be analyzed: mechanical, functional, aesthetic and phonetic. After the jointly analysis with all the requirements, the patient must approve, preferably in writing, the completion of the prosthesis. In case of need for any changes, this is when it should be performed, followed by new aesthetic and functional testing. It should be noted that the patient’s opinion is always sovereign in deciding to end the denture.

Protective Effect of Human Endogenous Retrovirus K dUTPase Variants on Psoriasis Susceptibility

Previous genetic and functional studies have implicated the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the major histocompatibility complex region as a candidate psoriasis gene. Here, we describe a variant discovery and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy controls. Five common HERV-K dUTPase variants were found to be highly associated with psoriasis, with the strongest association occurring at the missense single-nucleotide polymorphism (SNP) rs3134774 (K158R, P=3.28 x 10(-15), odds ratio = 2.36 (95% confidence interval: 1.91-2.92)). After adjusting the association of the HERV-K dUTPase variants for the potential confounding effects of HLA alleles associated with psoriasis, the HERV-K SNPs rs9264082 and rs3134774 remained significantly associated. Haplotype analysis revealed that HERV-K haplotypes containing the non-risk alleles for rs3134774 and rs9264082 significantly reduced the risk of psoriasis. Functional testing showed higher antibody responses against recombinant HERV-K dUTPase in psoriasis patients compared with controls (P<0.05), as well as higher T-cell responses against a single HERV-K dUTPase peptide (P<0.05). Our data support an independent role for the HERV-K dUTPase on psoriasis susceptibility, and suggest the need for additional studies to clarify the role of this dUTPase in the pathogenesis of psoriasis. Journal of Investigative Dermatology (2012) 132, 1833-1840; doi:10.1038/jid.2012.69; published online 22 March 2012

Reliable and Variation-Tolerant Interconnection Network for Low Power MPSOCS

Multi-Processor SoC (MPSOC) design brings to the foreground a large number of challenges, one of the most prominent of which is the design of the chip interconnection. With a number of on-chip blocks presently ranging in the tens, and quickly approaching the hundreds, the novel issue of how to best provide on-chip communication resources is clearly felt. Scaling down of process technologies has increased process and dynamic variations as well as transistor wearout. Because of this, delay variations increase and impact the performance of the MPSoCs. The interconnect architecture inMPSoCs becomes a single point of failure as it connects all other components of the system together. A faulty processing element may be shut down entirely, but the interconnect architecture must be able to tolerate partial failure and variations and operate with performance, power or latency overhead. This dissertation focuses on techniques at different levels of abstraction to face with the reliability and variability issues in on-chip interconnection networks. By showing the test results of a GALS NoC testchip this dissertation motivates the need for techniques to detect and work around manufacturing faults and process variations in MPSoCs’ interconnection infrastructure. As a physical design technique, we propose the bundle routing framework as an effective way to route the Network on Chips’ global links. For architecture-level design, two cases are addressed: (I) Intra-cluster communication where we propose a low-latency interconnect with variability robustness (ii) Inter-cluster communication where an online functional testing with a reliable NoC configuration are proposed. We also propose dualVdd as an orthogonal way of compensating variability at the post-fabrication stage. This is an alternative strategy with respect to the design techniques, since it enforces the compensation at post silicon stage.

Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-Pick Type C patient

New treatment options for Niemann-Pick Type C (NPC) have recently become available. To assess the efficiency and efficacy of these new treatment markers for disease status and progression are needed. Both the diagnosis and the monitoring of disease progression are challenging and mostly rely on clinical impression and functional testing of horizontal eye movements. Diffusion tensor imaging (DTI) provides information about the microintegrity especially of white matter. We show here in a case report how DTI and measures derived from this imaging method can serve as adjunct quantitative markers for disease management in Niemann-Pick Type C. Two approaches are taken--first, we compare the fractional anisotropy (FA) in the white matter globally between a 29-year-old NPC patient and 18 healthy age-matched controls and show the remarkable difference in FA relatively early in the course of the disease. Second, a voxelwise comparison of FA values reveals where white matter integrity is compromised locally and demonstrate an individualized analysis of FA changes before and after 1year of treatment with Miglustat. This method might be useful in future treatment trials for NPC to assess treatment effects.

Regulation and structure of YahD, a copper-inducible / serine hydrolase of Lactococcus lactis IL1403

Lactococcus lactis IL1403 is a lactic acid bacterium that is used widely for food fermentation. Copper homeostasis in this organism chiefly involves copper secretion by the CopA copper ATPase. This enzyme is under the control of the CopR transcriptional regulator. CopR not only controls its own expression and that of CopA, but also that of an additional three operons and two monocistronic genes. One of the genes under the control of CopR, yahD, encodes an α/β-hydrolase. YahD expression was induced by copper and cadmium, but not by other metals or oxidative or nitrosative stress. The three-dimensional structure of YahD was determined by X-ray crystallography to a resolution of 1.88 Å. The protein was found to adopt an α/β-hydrolase fold with the characteristic Ser-His-Asp catalytic triad. Functional testing of YahD for a wide range of substrates for esterases, lipases, epoxide hydrolases, phospholipases, amidases and proteases was, however, unsuccessful. A copper-inducible serine hydrolase has not been described previously and YahD appears to be a new functional member of this enzyme family.

Nano-mechanical transduction of polymer micro-cantilevers to detect bio-molecular interactions

Using variothermal polymer micro-injection molding, disposable arrays of eight polymer micro-cantilevers each 500 μm long, 100 μm wide and 25 μm thick were fabricated. The present study took advantage of an easy flow grade polypropylene. After gold coating for optical read-out and asymmetrical sensitization, the arrays were introduced into the Cantisens(®) Research system to perform mechanical and functional testing. We demonstrate that polypropylene cantilevers can be used as biosensors for medical purposes in the same manner as the established silicon ones to detect single-stranded DNA sequences and metal ions in real-time. A differential signal of 7 nm was detected for the hybridization of 1 μM complementary DNA sequences. For 100 nM copper ions the differential signal was found to be (36 ± 5) nm. Nano-mechanical sensing of medically relevant, nanometer-size species is essential for fast and efficient diagnosis.

Influencia del estilo de vida y la funcionalidad sobre la calidad de vida relacionada con la salud en población mexicana con salud comprometida

Este estudio tiene como objetivo estudiar la influencia de los factores del estilo de vida y funcionalidad sobre la calidad de vida relacionada con la salud (CVRS) en población con salud comprometida. Método: 139 sujetos formaron parte de este estudio divididos en cuatro grupos de enfermedades co-morbidas (sobrepeso-obesidad, diabetes, hipertensión e hiperlipidemias). El estilo de vida se determinó mediante la encuesta FANTASTIC, calidad de vida relacionada con la salud mediante el SF-36 y la funcionalidad con los Test Sentar y Lenvantar (TSL) e Ir y Venir (TIV). Los resultados nos muestras un estilo de vida excelente influye positivamente sobre la Compuesta Salud Física y Compuesta Salud Mental (p < 0.05) en relación estilo de vida inferiores (bueno, regular y bajos) y no influye sobre la capacidad funcional (TSL y TIV). Además, diferentes condiciones de enfermedades co-morbidas (SO vs SOD vs SODT vs ODTH) parecen no afectar la CVRS, y si la capacidad funcional (p < 0.05). Conclusiones: niveles excelentes de estilo de vida influyen positivamente sobre la CVRS específicamente sobre los aspectos físicos y mentales. Las pruebas funcionales de TSL y TIV parecen ser útiles para diferencias los niveles funcionales en población con salud comprometida o población con enfermedades co-morbidas

Influencia del estilo de vida y la funcionalidad sobre la calidad de vida relacionada con la salud en población mexicana con salud comprometida

Este estudio tiene como objetivo estudiar la influencia de los factores del estilo de vida y funcionalidad sobre la calidad de vida relacionada con la salud (CVRS) en población con salud comprometida. Método: 139 sujetos formaron parte de este estudio divididos en cuatro grupos de enfermedades co-morbidas (sobrepeso-obesidad, diabetes, hipertensión e hiperlipidemias). El estilo de vida se determinó mediante la encuesta FANTASTIC, calidad de vida relacionada con la salud mediante el SF-36 y la funcionalidad con los Test Sentar y Lenvantar (TSL) e Ir y Venir (TIV). Los resultados nos muestras un estilo de vida excelente influye positivamente sobre la Compuesta Salud Física y Compuesta Salud Mental (p < 0.05) en relación estilo de vida inferiores (bueno, regular y bajos) y no influye sobre la capacidad funcional (TSL y TIV). Además, diferentes condiciones de enfermedades co-morbidas (SO vs SOD vs SODT vs ODTH) parecen no afectar la CVRS, y si la capacidad funcional (p < 0.05). Conclusiones: niveles excelentes de estilo de vida influyen positivamente sobre la CVRS específicamente sobre los aspectos físicos y mentales. Las pruebas funcionales de TSL y TIV parecen ser útiles para diferencias los niveles funcionales en población con salud comprometida o población con enfermedades co-morbidas

Influencia del estilo de vida y la funcionalidad sobre la calidad de vida relacionada con la salud en población mexicana con salud comprometida

Este estudio tiene como objetivo estudiar la influencia de los factores del estilo de vida y funcionalidad sobre la calidad de vida relacionada con la salud (CVRS) en población con salud comprometida. Método: 139 sujetos formaron parte de este estudio divididos en cuatro grupos de enfermedades co-morbidas (sobrepeso-obesidad, diabetes, hipertensión e hiperlipidemias). El estilo de vida se determinó mediante la encuesta FANTASTIC, calidad de vida relacionada con la salud mediante el SF-36 y la funcionalidad con los Test Sentar y Lenvantar (TSL) e Ir y Venir (TIV). Los resultados nos muestras un estilo de vida excelente influye positivamente sobre la Compuesta Salud Física y Compuesta Salud Mental (p < 0.05) en relación estilo de vida inferiores (bueno, regular y bajos) y no influye sobre la capacidad funcional (TSL y TIV). Además, diferentes condiciones de enfermedades co-morbidas (SO vs SOD vs SODT vs ODTH) parecen no afectar la CVRS, y si la capacidad funcional (p < 0.05). Conclusiones: niveles excelentes de estilo de vida influyen positivamente sobre la CVRS específicamente sobre los aspectos físicos y mentales. Las pruebas funcionales de TSL y TIV parecen ser útiles para diferencias los niveles funcionales en población con salud comprometida o población con enfermedades co-morbidas

Influencia del estilo de vida y la funcionalidad sobre la calidad de vida relacionada con la salud en población mexicana con salud comprometida

Este estudio tiene como objetivo estudiar la influencia de los factores del estilo de vida y funcionalidad sobre la calidad de vida relacionada con la salud (CVRS) en población con salud comprometida. Método: 139 sujetos formaron parte de este estudio divididos en cuatro grupos de enfermedades co-morbidas (sobrepeso-obesidad, diabetes, hipertensión e hiperlipidemias). El estilo de vida se determinó mediante la encuesta FANTASTIC, calidad de vida relacionada con la salud mediante el SF-36 y la funcionalidad con los Test Sentar y Lenvantar (TSL) e Ir y Venir (TIV). Los resultados nos muestras un estilo de vida excelente influye positivamente sobre la Compuesta Salud Física y Compuesta Salud Mental (p < 0.05) en relación estilo de vida inferiores (bueno, regular y bajos) y no influye sobre la capacidad funcional (TSL y TIV). Además, diferentes condiciones de enfermedades co-morbidas (SO vs SOD vs SODT vs ODTH) parecen no afectar la CVRS, y si la capacidad funcional (p < 0.05). Conclusiones: niveles excelentes de estilo de vida influyen positivamente sobre la CVRS específicamente sobre los aspectos físicos y mentales. Las pruebas funcionales de TSL y TIV parecen ser útiles para diferencias los niveles funcionales en población con salud comprometida o población con enfermedades co-morbidas