Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

BACKGROUND: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin). OBJECTIVE: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc. METHODS: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA. RESULTS: Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 μg/mL) compared with those with PAPA syndrome (116 ± 74 μg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1. CONCLUSION: Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

Työpöytäsovellus Adobe Air -tekniikalla

Työn kirjallinen osuus aloitettiin kertaamalla lyhyesti web-sovellukset ja niiden ominaisuudet. Tekniikan kehittyminen on mahdollistanut rikkaat Internet-sovellukset, joiden periaate ja toiminta esitettiin, ja lisäksi perehdyttiin rikkaiden Internet-sovellusten vaatimuksiin. Adobe Air on käyttöjärjestelmäriippumaton ajoympäristö työpöytäsovellusten toteuttamiseen web-tekniikoilla. Air-tekniikkaan tutustuttiin käymällä läpi ajoympäristön tärkeimmät komponentit ja niiden merkitys sekä Air-sovelluksen tietoturvamalli. Air-sovellus voidaan toteuttaa vaihtoehtoisilla sovellustekniikoilla, jotka esitellään lyhyesti ja pohditaan valintaan vaikuttavia ominaisuuksia. Lisäksi esitettiin sovelluskehitykseen tarjolla olevia työkaluja ja Air-sovelluskehityksen ominaispiirteitä.Työssä toteutettiin Asiakasselain-sovellus, jonka on tarkoitus korvata tulevaisuudessa tällä hetkellä käytössä oleva Asiakaspääte-sovellus. Asiakasselaimen avulla asiakas voi etsiä tuotteita ja lisätietoja tavarataloissa. Air-sovelluksen sovellustekniikaksi valittiin HTML/Ajax-tekniikka. Sovellus hyödyntää tavaratalon varasto-tietokantaa sekä verkko-kaupan kuva- ja tuoteinformaatiota. Työn päätavoitteena oli tutustua Adobe Air -tekniikkaan ja sen tarjoamiin mahdollisuuksiin. Air osoittautui mielenkiintoiseksi ja helpoksi vaihtoehdoksi työpöytäsovelluksen toteutta-misessa perinteisillä web-tekniikoilla.

Air de Tancrede avec Variations pour le Piano Forte par Gelinek

Simananniemen käsikirjoituskokoelma.

Perspectives thérapeutiques dans la prise en charge de l'acouphène subjectif chronique [Therapeutic perspectives in the treatment of chronic subjective tinnitus].

There are no effective therapies for the treatment of chronic subjective tinnitus. The present study aims to compare two therapeutic approaches: Tinnitus Retraining Therapy (TRT) and a Biopsychosocial Approach (BPS). Results show no difference in evolution of tinnitus' perception between the beginning of the study and after 12 months of treatment in both treatment groups. Important anxiety could be a factor contributed towards the abandonment or ineffectiveness of treatments. Patients with more biopsychosocial comorbidities are more receptive to therapies. The practicioners therefore must assess specific needs, comorbidities and biopsychosocial profiles of patients suffering from tinnitus.

Air d’armade

Soitinnus: sooloääni. Simananniemen käsikirjoituskokoelma.

Price differences between domestic and international air markets : an empirical application to routes from Gran Canaria

In this paper we examine whether airline prices on national routes are higher than those charged on international routes. Drawing on a database prepared specifically for this study, we estimate a pricing equation for all routes originating from Gran Canaria, Canary Islands, Spain; differentiating between national and international routes. A key difference between these two route types is that island residents benefit from discounts on domestic flights. When controlling for variables related to airline characteristics, market structure and demand, we find that national passengers who are non-residents on the islands are paying higher prices than international passengers.

Prise en charge des facteurs de risque des maladies cardiovasculaires: qu'est-ce qui a vraiment changé en 15 ans [Management of cardiovascular diseases in adults from 1999 to 2014: what has really changed?].

Every year, a considerable number of clinical guidelines for the management of cardiovascular risk factors are issued. It may give the idea that this area is constantly evolving with regular changes for ambulatory clinical practice, including family medicine. Sometimes important differences between the various recommendations are observed. This led us to wonder about the evolution of recommendations for the management of diabetes, dyslipidemia and high blood pressure over time. This article presents a historical review of US and European recommendations between 1999 and 2014 to highlight what has actually changed.

Developing service offering of an air freight carrier

The thesis examined service offering development of an air freight carrier from the customers' point of view. The study was limited to the biggest business clients of the carrier. Service offering development can be divided into service concept, process and system. The thesis was based on these three themes and quality. Compared to product development, systematic and well-structured service development has been studied little, especially in business market. However, service development is a current issue. Due to growing competition companies should carefully listen to their clients' needs and respond to them by offering right services. Methodology of the thesis is qualitative and representatives of three forwarding companies were interviewed. It was found out that the forwarding companies consider themselves as partners of the airline. In addition to general reliability, the customers value the most fluent terminal processes and electronic communication.

Life cycle costs in heating, ventilation and air-conditioning systems with drive

Energy consumption and energy efficiency have become an issue. Energy consumption is rising all over the world and because of that, and the climate change, energy is becoming more and more expensive. Buildings are major consumers of energy, and inside the buildings the major consumers are heating, ventilation and air-conditioning systems. They usually run at constant speed without efficient control. In most cases HVAC equipment is also oversized. Traditionally heating, ventilation and air-conditioning systems have been sized to meet conditions that rarely occur. The theory part in this thesis represents the basics of life cycle costs and calculations for the whole life cycle of a system. It also represents HVAC systems, equipment, systems controls and ways to save energy in these systems. The empirical part of this thesis represents life cycle cost calculations for HVAC systems. With these calculations it is possible to compute costs for the whole life cycle for the wanted variables. Life cycle costs make it possible to compare which variable causes most of the costs from the whole life point of view. Life cycle costs were studied through two real life cases which were focused on two different kinds of HVAC systems. In both of these cases the renovations were already made, so that the comparison between the old and the new, now existing system would be easier. The study indicates that energy can be saved in HVAC systems by using variable speed drive as a control method.

Air services on thin routes : Regional versus low-cost airlines

An examination of the impact in the US and EU markets of two major innovations in the provision of air services on thin routes - regional jet technology and the low-cost business model - reveals significant differences. In the US, regional airlines monopolize a high proportion of thin routes, whereas low-cost carriers are dominant on these routes in Europe. Our results have different implications for business and leisure travelers, given that regional services provide a higher frequency of flights (at the expense of higher fares), while low-cost services offer lower fares (at the expense of lower flight frequencies).

Sensitive photonic system to measure oxidative potential of airborne nanoparticles and ROS levels in exhaled air

A photonic system has been developed that enables sensitive quantitative determination of reactive oxygen species (ROS) - mainly hydrogen peroxide (H2O2) - in aerosol samples such as airborne nanoparticles and exhaled air from patients. The detection principle relies on the amplification of the absorbance under multiple scattering conditions due to optical path lengthening [1] and [2]. In this study, the presence of cellulose membrane that acts as random medium into the glass optical cell considerably improved the sensitivity of the detection based on colorimetric FOX assay (FeII/orange xylenol). Despite the loss of assay volume (cellulose occupies 75% of cell volume) the limit of detection is enhanced by one order of magnitude reaching the value of 9 nM (H2O2 equivalents). Spectral analysis is performed automatically with a periodicity of 5 to 15 s, giving rise to real-time ROS measurements. Moreover, the elution of air sample into the collection chamber via a micro-diffuser (impinger) enables quantitative determination of ROS contained in or generated from airborne samples. As proof-of-concept the photonic ROS detection system was used in the determination of both ROS generated from traffic pollution and ROS contained in the exhaled breath as lung inflammation biomarkers.

Prise en charge de la candidose oesophagienne en médecine de premier recours [Management of the esophageal candidiasis by the primary care physician].

La candidose oesophagienne est l'une des infections opportunistes les plus fréquentes chez les patients infectés par le VIH. Ce diagnostic se rencontre également chez des patients sans immunodéficience manifeste. Certains facteurs de risque sont également associés à cette pathologie, tels que les traitements corticoïdes systémiques et inhalés ou les traitements par inhibiteurs de la pompe à protons et les antihistaminiques H2. En l'absence de facteur de risque identifié, un déficit immunitaire primaire devrait être recherché. La prévention de la candidose oesophagienne est basée en premier lieu sur l'identification des facteurs de risque, ainsi qu'un meilleur contrôle de ceux-ci. Cet article présente en détail la physio-pathologie, la clinique et la prise en charge par le médecin de premier recours de la candidose oesophagienne. Nous aborderons également les moyens de prévention de la candidose oesophagienne quand il y a lieu. Esophageal candidiasis is one of the most common opportunistic infections in patients infected by human immunodeficiency virus (HIV). This pathology is also found in patients without overt immunodeficiency. Other risk factors are known to be associated with this disease like inhaled or systemic corticosteroid treatment or proton-pump inhibitors and H2 receptor antagonists. In the absence of identified risk factors, a primary immune deficiency should be sought. Prevention of esophageal candidiasis is based primarily on the identification of risk factors, and a better control of them. This article presents a review of the physiopathology, clinical presentation and management of esophageal candidiasis by primary care physicians. We will also discuss ways of preventing esophageal candidiasis when necessary.

Nouveautés dans l'ostéogenèse imparfaite: de la recherche à la prise en charge multidisciplinaire [News in osteogenesis imperfecta: from research to clinical management]

Osteogenesis imperfecta (OI) is a rare genetic disease. Today we are able to propose an adapted and efficient management to the patients with this rare disorder (and their families) thanks to a strong collaboration of clinicians and researchers. Recent knowledge regarding the genetics of OI permits an accurate diagnosis of the specific type of OI and its own molecular mechanism, a genetic counseling for family planning and prenatal diagnosis, and in addition more targeted therapeutic options. A specific support with re-education for patients with OI is necessary and efficient. To optimize patient care, a multidisciplinary consultation is proposed at the CHUV, moreover a web site is available for patients, families and therapists: www.infomaladiesrares.ch