Current transport and electroluminescence mechanisms in thin SiO2 films containing Si nanocluster-sensitized erbium ions.

We have studied the current transport and electroluminescence properties of metal oxide semiconductor MOS devices in which the oxide layer, which is codoped with silicon nanoclusters and erbium ions, is made by magnetron sputtering. Electrical measurements have allowed us to identify a Poole-Frenkel conduction mechanism. We observe an important contribution of the Si nanoclusters to the conduction in silicon oxide films, and no evidence of Fowler-Nordheim tunneling. The results suggest that the electroluminescence of the erbium ions in these layers is generated by energy transfer from the Si nanoparticles. Finally, we report an electroluminescence power efficiency above 10���3%. �� 2009 American Institute of Physics. doi:10.1063/1.3213386

PPAR-β/δ activation promotes phospholipid transfer protein expression.

The peroxisome proliferator-activated receptor (PPAR)-β/δ has emerged as a promising therapeutic target for treating dyslipidemia, including beneficial effects on HDL cholesterol (HDL-C). In the current study, we determined the effects of the PPAR-β/δ agonist GW0742 on HDL composition and the expression of liver HDL-related genes in mice and cultured human cells. The experiments were carried out in C57BL/6 wild-type, LDL receptor (LDLR)-deficient mice and PPAR-β/δ-deficient mice treated with GW0742 (10mg/kg/day) or a vehicle solution for 14 days. GW0742 upregulated liver phospholipid transfer protein (Pltp) gene expression and increased serum PLTP activity in mice. When given to wild-type mice, GW0742 significantly increased serum HDL-C and HDL phospholipids; GW0742 also raised serum potential to generate preβ-HDL formation. The GW0742-mediated effects on liver Pltp expression and serum enzyme activity were completely abolished in PPAR-β/δ-deficient mice. GW0742 also stimulated PLTP mRNA expression in mouse J774 macrophages, differentiated human THP-1 macrophages and human hepatoma Huh7. Collectively, our findings demonstrate a common transcriptional upregulation by GW0742-activated PPAR-β/δ of Pltp expression in cultured cells and in mouse liver resulting in enhanced serum PLTP activity. Our results also indicate that PPAR-β/δ activation may modulate PLTP-mediated preβ-HDL formation and macrophage cholesterol efflux.

Yrityksen sis��isen kilpailun ja yhteisty��n innovaatiovaikutus ja johtaminen t&k-toiminnassa

Tiedon luomiseen ja hy��dynt��miseen perustuvassa liiketoiminnassa yrityksen kyky luoda tietoa ja k��ytt���� hallussaan olevaa tietoa muodostaa perustan kilpailukyvylle ja kilpailueduille. Tutkielmassa rakennetaan konstruktiivista tutkimusotetta k��ytt��en innovaatioiden synnyn johtamiseen soveltuva toimintamalli Teecen tietoprosesseihin, Nonakan tiedonkonversioprosesseihin ja St��hlen tietoymp��rist��ihin perustuen. Tietoa syntyy esimerkiksi innovaatioissa. Innovaatioiden voidaan katsoa syntyv��n vastakkaisten voimien jatkuvassa vuorovaikutuksessa. T��m�� innovaatioita tuottava mekanismi rakentuu tietoa lis����vist�� ja tietoa j��rjest��vist�� prosesseista, joita voidaan kuvata sek�� seci-prosessin ett�� kolmitasoisen tietoymp��rist��n avulla. Sis��inen kilpailu ja yhteisty�� vaikuttavat t��m��n mekanismin toimintaan. Yhteisty�� lis���� tiedon jakamista ja mahdollistaa radikaalien innovaatioiden ja tuoteinnovaatioiden synnyn. Kilpailun lis����minen v��hent���� keskin��ist�� tiedon jakamista ja siirt���� innovaatioita fokuksen mukaisiin prosessi-innovaatioihin. Kilpailun ja yhteisty��n m����r����n ja keskin��iseen suhteeseen voidaan vaikuttaa kolmitasoisesta tietoymp��rist��mallista johdettujen kolmen erillisen, joskin toisiinsa vaikuttavan, johtamistavoitteen avulla. Mahdollistava johtaminen rakentaa luottamuksen ja yrityksen toiminnan perustaa. Valtuuttava johtaminen houkuttaa yhteisty��h��n mahdollistaen tiedon lis����ntymisen. Ohjaavan johtamisen prosessit viev��t yrityst�� strategian mukaiseen suuntaan hy��dynt��en sis��ist�� kilpailua.

Measurement Properties of the Smartphone-Based B-B Score in Current Shoulder Pathologies.

NlmCategory="UNASSIGNED">This study is aimed at the determination of the measurement properties of the shoulder function B-B Score measured with a smartphone. This score measures the symmetry between sides of a power-related metric for two selected movements, with 100% representing perfect symmetry. Twenty healthy participants, 20 patients with rotator cuff conditions, 23 with fractures, 22 with capsulitis, and 23 with shoulder instabilities were measured twice across a six-month interval using the B-B Score and shoulder function questionnaires. The discriminative power, responsiveness, diagnostic power, concurrent validity, minimal detectable change (MDC), minimal clinically important improvement (MCII), and patient acceptable symptom state (PASS) were evaluated. Significant differences with the control group and significant baseline-six-month differences were found for the rotator cuff condition, fracture, and capsulitis patient groups. The B-B Score was responsive and demonstrated excellent diagnostic power, except for shoulder instability. The correlations with clinical scores were generally moderate to high, but lower for instability. The MDC was 18.1%, the MCII was 25.2%, and the PASS was 77.6. No floor effect was observed. The B-B Score demonstrated excellent measurement properties in populations with rotator cuff conditions, proximal humerus fractures, and capsulitis, and can thus be used as a routine test to evaluate those patients.

Store-operated Ca2+ Entry Mediated by Orai1 and TRPC1 Participates to Insulin Secretion in Rat β-Cells.

Store-operated Ca(2+) channels (SOCs) are voltage-independent Ca(2+) channels activated upon depletion of the endoplasmic reticulum Ca(2+) stores. Early studies suggest the contribution of such channels to Ca(2+) homeostasis in insulin-secreting pancreatic β-cells. However, their composition and contribution to glucose-stimulated insulin secretion (GSIS) remains unclear. In this study, endoplasmic reticulum Ca(2+) depletion triggered by acetylcholine (ACh) or thapsigargin stimulated the formation of a ternary complex composed of Orai1, TRPC1, and STIM1, the key proteins involved in the formation of SOCs. Ca(2+) imaging further revealed that Orai1 and TRPC1 are required to form functional SOCs and that these channels are activated by STIM1 in response to thapsigargin or ACh. Pharmacological SOCs inhibition or dominant negative blockade of Orai1 or TRPC1 using the specific pore mutants Orai1-E106D and TRPC1-F562A impaired GSIS in rat β-cells and fully blocked the potentiating effect of ACh on secretion. In contrast, pharmacological or dominant negative blockade of TRPC3 had no effect on extracellular Ca(2+) entry and GSIS. Finally, we observed that prolonged exposure to supraphysiological glucose concentration impaired SOCs function without altering the expression levels of STIM1, Orai1, and TRPC1. We conclude that Orai1 and TRPC1, which form SOCs regulated by STIM1, play a key role in the effect of ACh on GSIS, a process that may be impaired in type 2 diabetes.

Structural and functional properties of two human FXYD3 (Mat-8) isoforms.

Six of 7 FXYD proteins have been shown to be tissue-specific modulators of Na,K-ATPase. In this study, we have identified two splice variants of human FXYD3, or Mat-8, in CaCo-2 cells. Short human FXYD3 has 72% sequence identity with mouse FXYD3, whereas long human FXYD3 is identical to short human FXYD3 but has a 26-amino acid insertion after the transmembrane domain. Short and long human FXYD3 RNAs and proteins are differentially expressed during differentiation of CaCo-2 cells. Long human FXYD3 is mainly expressed in nondifferentiated cells and short human FXYD3 in differentiated cells and both FXYD3 variants can be co-immunoprecipitated with a Na,K-ATPase antibody. In contrast to mouse FXYD3, which has two transmembrane domains for lack of cleavage of the signal peptide, human FXYD3 has a cleavable signal peptide and adopts a type I topology. After co-expression in Xenopus oocytes, both human FXYD3 variants associate stably only with Na,K-ATPase isozymes but not with H,K-ATPase or Ca-ATPase. Similar to mouse FXYD3, short human FXYD3 decreases the apparent K(+) and Na(+) affinity of Na,K-ATPase over a large range of membrane potentials. On the other hand, long human FXYD3 decreases the apparent K(+) affinity only at slightly negative and positive membrane potentials and increases the apparent Na(+) affinity of Na,K-ATPase. Finally, both short and long human FXYD3 induce a hyperpolarization activated current, similar to that induced by mouse FXYD3. Thus, we have characterized two human FXYD3 isoforms that are differentially expressed in differentiated and non-differentiated cells and show different functional properties.

Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants.

Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient's interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA��) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention.

Paediatric end-of-life care needs in Switzerland: current practices, and perspectives from parents and professionals. A study protocol.

AIM: To present a protocol for a multi-phase study about the current practice of end-of-life care in paediatric settings in Switzerland. BACKGROUND: In Switzerland, paediatric palliative care is usually provided by teams, who may not necessarily have specific training. There is a lack of systematic data about specific aspects of care at the end of a child's life, such as symptom management, involvement of parents in decision-making and family-centred care and experiences and needs of parents, and perspectives of healthcare professionals. DESIGN: This retrospective nationwide multicentre study, Paediatric End-of-LIfe CAre Needs in Switzerland (PELICAN), combines quantitative and qualitative methods of enquiry. METHODS: The PELICAN study consists of three observational parts, PELICAN I describes practices of end-of-life care (defined as the last 4 weeks of life) in the hospital and home care setting of children (0-18 years) who died in the years 2011-2012 due to a cardiac, neurological or oncological disease, or who died in the neonatal period. PELICAN II assesses the experiences and needs of parents during the end-of-life phase of their child. PELICAN III focuses on healthcare professionals and explores their perspectives concerning the provision of end-of-life care. CONCLUSION: This first study across Switzerland will provide comprehensive insight into the current end-of-life care in children with distinct diagnoses and the perspectives of affected parents and health professionals. The results may facilitate the development and implementation of programmes for end-of-life care in children across Switzerland, building on real experiences and needs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01983852.

T Cell Priming by Activated Nlrc5-Deficient Dendritic Cells Is Unaffected despite Partially Reduced MHC Class I Levels.

NLRC5, a member of the NOD-like receptor (NLR) protein family, has recently been characterized as the master transcriptional regulator of MHCI molecules in lymphocytes, in which it is highly expressed. However, its role in activated dendritic cells (DCs), which are instrumental to initiate T cell responses, remained elusive. We show in this study that, following stimulation of DCs with inflammatory stimuli, not only did NLRC5 level increase, but also its importance in directing MHCI transcription. Despite markedly reduced mRNA and intracellular H2-K levels, we unexpectedly observed nearly normal H2-K surface display in Nlrc5(-/-) DCs. Importantly, this discrepancy between a strong intracellular and a mild surface defect in H2-K levels was observed also in DCs with H2-K transcription defects independent of Nlrc5. Hence, alongside with demonstrating the importance of NLRC5 in MHCI transcription in activated DCs, we uncover a general mechanism counteracting low MHCI surface expression. In agreement with the decreased amount of neosynthesized MHCI, Nlrc5(-/-) DCs exhibited a defective capacity to display endogenous Ags. However, neither T cell priming by endogenous Ags nor cross-priming ability was substantially affected in activated Nlrc5(-/-) DCs. Altogether, these data show that Nlrc5 deficiency, despite significantly affecting MHCI transcription and Ag display, is not sufficient to hinder T cell activation, underlining the robustness of the T cell priming process by activated DCs.

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis.

Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called 'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.

Dielectric spectroscopy and thermally stimulated discharge current in PEEK film

The complex permittivity of films of polyether ether ketone (PEEK) has been investigated over a wide range of frequency. There is no relaxation peak in the range of 1Hz to 10(5) Hz but in the low-frequency side (10-4 Hz) there is an evidence of a peak that also can be observed by thermally stimulated discharge current measurements. That peak is related with the glass transition temperature (Tg) of the polymer. The activation energy of the relaxation was found to be 0.44 eV, similar to that of several synthetic polymers. Space charges are important in the conduction mechanism as shown by discharging transient.

Den v��rdande och helande bilden: m��ten med bildkonst i v��rdandets v��rld

Denna v��rdvetenskapliga avhandling syftar till att avt��cka och belysa en v��rdande och helande dimension vid existentiellt lidande patienters m��ten med bildkonst inom v��rdkontext. Kunskapss��kandet sker i tv�� studier. Den f��rsta (studie I) ��r en ikonografi sk tolkning av konstn��ren Matthias Gr��newalds (ca 1460���1528) senmedeltida altarsk��psm��lningar. I studien uttolkas lidandets uttryck och narrativa budskap samt symboliska gestaltningar av v��rdande och helande i valda delar av detta s.k. Isenheimaltares bildprogram. Tolkningen utg��r fr��n rekonstruktionen av altarsk��pets ursprungskontext, det medeltida Isenheimklostret, d��r sv��rt sjuka och d��ende patienter v��rdades. I studie tv�� (II) forts��tter s��kandet i den moderna hospicev��rdens kontext med hj��lp av en kvalitativ intervjustudie som utforskar patienters meningsskapande vid m��ten med sj��lvvald bildkonst (oljem��lningar och akvareller av fi nl��ndska konstn��rer som donerats till det sjukhus d��r intervjustudien gjordes). Forskningsansatsen ��r inspirerad av Hans-Georg Gadamers (1901���2002) hermeneutik. Vidare anv��nds n��gra nyare tolkningsteoretiska ansatser inom bildkonstens omr��de. Forskningens tolkningsresultat visar att bildkonsten har potentialer s��v��l p�� ett milj��estetiskt plan som p�� en djupare individuell symbolniv��. Som designkomponent i v��rdmilj��ns rumsliga gestaltning bygger bildkonsten in estetiska, etiska och andliga kvaliteter utifr��n tidsm��ssiga och kulturella koder. I den medeltida klosterv��rdens kontext sammanf��ll bildkonstens dekorativa betydelse med andliga och helande syften. N��r det g��ller sj��lvvalda konstverk i den moderna v��rdkontexten bidrar de till det enskilda patientrummets atmosf��r p�� ett unikt s��tt utifr��n patientens personlighet och behov. P�� en f��rdjupad m��tesniv��, i samspel med bildens symboliska funktion, sker en inlevelsem��ssig f��rfl yttning in i bildens v��rld. Betraktarens inlevelse aktiveras till en transcenderande r��relse som g��r bortom det faktiska rummets och den reella tidens gr��nser. Vid resor i konstens bildv��rld spelas minnesv��rda h��ndelser upp fr��n det f��rg��ngna, men ��ven framtiden kommer betraktaren till m��tes. I en existentiell livssituation s��ker m��nniskan i konstverkets bildinneh��ll efter symbolisk mening som kan ge svar p�� lidandets fr��gor. Bilderna iscens��tter d�� helande motbilder som utg��r korrektiv i symboliska former n��r olika existentiella f��rluster hotar. N��r livet f��rbleknats av sjukdom besvarar bildv��rlden den lidandes blick med lysande violer som blommar upp, ger livskraft och bekr��ftar personens v��rdighet mitt i det f��rvissnande m��nniskolivet. N��r ��ngest och otrygghet nalkas inbjuds betraktaren till bes��k i landskap som utvidgar sjukhusrummets v��ggar mot hemg��rdens trygghet. D��r livet hotas av f��rg��nglighet tar bildv��rlden m��nniskan med sig till naturens eviga ��terf��delse. Upplevelsen av att vara delaktig i ett st��rre och heligt sammanhang ��ppnar v��gen ut ur lidandets avskurenhet. I medeltidens v��rdkontext erbj��d den sakrala bilden en kollektiv och helande Symbolon som genom sin representationskraft synliggjorde det osynliga. Vid bildm��ten i den moderna hospicev��rdens kontext var det naturteman som gl��ntade p�� d��rren till ���det hemliga rummet i djupet av hj��rtat���. Forskningen antyder att ��ven om meningsskapandet i ett bildm��te ��r avh��ngigt tidsepok, betraktarens f��rf��rst��else och kulturella kontext samt typen av bilder kan bildsymboliken, generellt f��rst��dd som den saknade formen eller det saknade livssammanhanget, framvisa en helande och hoppingivande ordning i lidandets kaos.

Calcium handling by vascular myocytes in hypertension

Calcium ions (Ca2+) trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1) the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2) Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3) intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension

Fast and slow voltage modulation of apical Cl- permeability in toad skin at high [K+]

The influence of voltage on the conductance of toad skin was studied to identify the time course of the activation/deactivation dynamics of voltage-dependent Cl- channels located in the apical membrane of mitochondrion-rich cells in this tissue. Positive apical voltage induced an important conductance inhibition which took a few seconds to fully develop and was instantaneously released by pulse inversion to negative voltage, indicating a short-duration memory of the inhibiting factors. Sinusoidal stimulation at 23.4 mM [Cl-] showed hysteresis in the current versus voltage curves, even at very low frequency, suggesting that the rate of voltage application was also relevant for the inhibition/releasing effect to develop. We conclude that the voltage modulation of apical Cl- permeability is essentially a fast process and the apparent slow components of activation/deactivation obtained in the whole skin are a consequence of a gradual voltage build-up across the apical membrane due to voltage sharing between apical and basolateral membranes