88 research outputs found

    Joinability of Particulate Reinforced Alumix 231 Based Composite Materials Produced by Powder Metallurgy Route

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    In the present study, weldability of Alumix 231 based composite materials reinforced with Al₂O₃ and B₄C and produced by powder metallurgy route is investigated. Various amounts of (0, 5, 10, and 15% wt.)Al₂O₃ and B₄C powders are added to the pre-alloyed Alumix 231 (Al—2.5% Cu—0.5% Mg—14% Si) powders separately and then mixed in a three-dimensional mixer for 45 min. Powders are compacted and sintered in an argon atmosphere at 640°C for 4 h. Produced blocks are welded by the Tungsten Inert Gas (TIG) welding at 25 V, 197 A and 14 l/min shielded gas flow in commercially pure argon atmosphere. Macro- and microexamination together with some mechanical properties of the welded area are studied. The results show that, although high amount of particles resulted in a decrease in the density, these composite materials can still be welded by the TIG welding method successfully.Исследуется свариваемость произведённых методом порошковой металлургии композитных материалов на основе Alumix 231, армированных Al₂O₃ и B₄C. Различные количества (0, 5, 10 и 15 масс.%) порошков Al₂O₃ и B₄C по отдельности добавлялись в предварительно сплавленные порошки Alumix 231 (Al—2,5% Cu—0,5% Mg—14% Si), а затем перемешивались в трёхмерном миксере в течение 45 минут. Затем порошки прессовались и спекались в атмосфере аргона при 640°C в течение 4 часов. Полученные блоки сваривались вольфрамовой сваркой в атмосфере инертного газа при 25 В, 197 А и потоке инертного газа в 14 л/мин в атмосфере технически чистого аргона. Были проведены макро- и микроисследования некоторых механических свойств сварной зоны. Их результаты показали, что, хотя оказалось большое количество частиц с пониженной плотностью, эти композитные материалы могут быть успешно сварены методом вольфрамовой сварки в атмосфере инертного газа.Досліджується зварюваність вироблених методою порошкової металургії композитних матеріялів на основі Alumix 231, армованих Al₂O₃ і B₄C. Різні кількості (0, 5, 10 і 15 мас.% ) порошків Al₂O₃ і B₄C окремо додавалися у попередньо стоплені порошки Alumix 231 (Al—2,5% Cu—0,5% Mg—14% Si), а потім перемішувалися в тривимірному міксері впродовж 45 хвилин. Потім порошки пресувалися та спікалися в атмосфері арґону при 640°C впродовж 4 годин. Одержані блоки зварювалися вольфрамовим зваренням в атмосфері інертного газу при 25 В, 197 А та потоці інертного газу у 14 л/хв. в атмосфері технічно чистого арґону. Було виконано макро- та мікродослідження деяких механічних властивостей зварної зони. їх результати показали, що, хоча виявилася велика кількість частинок зі зниженою густиною, ці композитні матеріяли можуть бути успішно зварені методою вольфрамового зварювання в атмосфері інертного газу

    Brain function assessment in different conscious states

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    Background: The study of brain functioning is a major challenge in neuroscience fields as human brain has a dynamic and ever changing information processing. Case is worsened with conditions where brain undergoes major changes in so-called different conscious states. Even though the exact definition of consciousness is a hard one, there are certain conditions where the descriptions have reached a consensus. The sleep and the anesthesia are different conditions which are separable from each other and also from wakefulness. The aim of our group has been to tackle the issue of brain functioning with setting up similar research conditions for these three conscious states.Methods: In order to achieve this goal we have designed an auditory stimulation battery with changing conditions to be recorded during a 40 channel EEG polygraph (Nuamps) session. The stimuli (modified mismatch, auditory evoked etc.) have been administered both in the operation room and the sleep lab via Embedded Interactive Stimulus Unit which was developed in our lab. The overall study has provided some results for three domains of consciousness. In order to be able to monitor the changes we have incorporated Bispectral Index Monitoring to both sleep and anesthesia conditions.Results: The first stage results have provided a basic understanding in these altered states such that auditory stimuli have been successfully processed in both light and deep sleep stages. The anesthesia provides a sudden change in brain responsiveness; therefore a dosage dependent anesthetic administration has proved to be useful. The auditory processing was exemplified targeting N1 wave, with a thorough analysis from spectrogram to sLORETA. The frequency components were observed to be shifting throughout the stages. The propofol administration and the deeper sleep stages both resulted in the decreasing of N1 component. The sLORETA revealed similar activity at BA7 in sleep (BIS 70) and target propofol concentration of 1.2 μg/mL.Conclusions: The current study utilized similar stimulation and recording system and incorporated BIS dependent values to validate a common approach to sleep and anesthesia. Accordingly the brain has a complex behavior pattern, dynamically changing its responsiveness in accordance with stimulations and states. © 2010 Ozgoren et al; licensee BioMed Central Ltd

    Role of protein kinase C and epidermal growth factor receptor signalling in growth stimulation by neurotensin in colon carcinoma cells

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    <p>Abstract</p> <p>Background</p> <p>Neurotensin has been found to promote colon carcinogenesis in rats and mice, and proliferation of human colon carcinoma cell lines, but the mechanisms involved are not clear. We have examined signalling pathways activated by neurotensin in colorectal and pancreatic carcinoma cells.</p> <p>Methods</p> <p>Colon carcinoma cell lines HCT116 and HT29 and pancreatic adenocarcinoma cell line Panc-1 were cultured and stimulated with neurotensin or epidermal growth factor (EGF). DNA synthesis was determined by incorporation of radiolabelled thymidine into DNA. Levels and phosphorylation of proteins in signalling pathways were assessed by Western blotting.</p> <p>Results</p> <p>Neurotensin stimulated the phosphorylation of both extracellular signal-regulated kinase (ERK) and Akt in all three cell lines, but apparently did so through different pathways. In Panc-1 cells, neurotensin-induced phosphorylation of ERK, but not Akt, was dependent on protein kinase C (PKC), whereas an inhibitor of the β-isoform of phosphoinositide 3-kinase (PI3K), TGX221, abolished neurotensin-induced Akt phosphorylation in these cells, and there was no evidence of EGF receptor (EGFR) transactivation. In HT29 cells, in contrast, the EGFR tyrosine kinase inhibitor gefitinib blocked neurotensin-stimulated phosphorylation of both ERK and Akt, indicating transactivation of EGFR, independently of PKC. In HCT116 cells, neurotensin induced both a PKC-dependent phosphorylation of ERK and a metalloproteinase-mediated transactivation of EGFR that was associated with a gefitinib-sensitive phosphorylation of the downstream adaptor protein Shc. The activation of Akt was also inhibited by gefitinib, but only partly, suggesting a mechanism in addition to EGFR transactivation. Inhibition of PKC blocked neurotensin-induced DNA synthesis in HCT116 cells.</p> <p>Conclusions</p> <p>While acting predominantly through PKC in Panc-1 cells and via EGFR transactivation in HT29 cells, neurotensin used both these pathways in HCT116 cells. In these cells, neurotensin-induced activation of ERK and stimulation of DNA synthesis was PKC-dependent, whereas activation of the PI3K/Akt pathway was mediated by stimulation of metalloproteinases and subsequent transactivation of the EGFR. Thus, the data show that the signalling mechanisms mediating the effects of neurotensin involve multiple pathways and are cell-dependent.</p

    Weaning practices in phenylketonuria vary between health professionals in Europe

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    Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey (R)) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17-26 weeks in 85% (n=81/95) of centres, > 26 weeks in 12% (n=11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n=56/95) and fruit (34%, n=32/95). A Phe exchange system to allocate dietary Phe was used by 52% (n=49/95) of centres predominantly from Northern and Southern Europe and 48% (n=46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods. A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n=39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n=35/95) at infant age > 1y mainly from Southern Europe. 53% (n=50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.Peer reviewe

    Early feeding practices in infants with phenylketonuria across Europe

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    Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey (R) questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months. 53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, >= 26 weeks in 12% and <17 weeks in 3%. Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.Peer reviewe

    Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

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    Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

    Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

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    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]
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