Changepoint detection in base-resolution methylome data reveals a robust signature of methylated domain landscape

ABSTRACTLotta Dalenius Hahlin (2010) Mentorskap utifrån ett lösningsinriktat fokus. (Mentorship based on a solution-oriented focus. Skolutveckling och ledarskap, Lärarutbildningen halvfart/distans, Malmö HögskolaMånga elever hoppar av sin gymnasieutbildning pga. av olika orsaker. En av orsakerna kan vara att eleven inte har tillräckligt stöd i sin mentor på skolan. En mentor skall ju inte bara ta hand om elevens studiemässiga resultat utan får även ta hand om de många sociala frågor som ofta uppstår runt eleven. Kan det vara så att mentorn behöver en ram och metod att arbeta utifrån för att kunna stödja eleverna på bästa sätt?Syftet med arbetet är att beskriva den metodik som ligger bakom ett lösningsinriktat mentorskap,och att skapa ett kompendium av användbara verktyg utifrån lösningsinriktad pedagogik. Detta kompendium kan mentorn använda som mall/ram i sin arbetsuppgift som mentor.Forskningen tyder på att lyckade och bra samtal bygger på bra förberedelse, på öppna frågor och på ömsesidig respekt för varandra och att man använder sig av ett visst förhållningssätt gentemot varandra. Vidare pekar litteraturstudien på att mentorssamtalet bör ha tydliga mål och en gemensam uppfattning om vad man vill komma fram till för att eleven skall nå ökat ansvar, större självinsikt och önskat läge.Arbetet tar upp de olika verktyg som man främst använder inom lösningsinriktade metoder, och är utifrån litteraturen kommenterat för att ge en grundläggande kunskap och förförståelse för läsaren.Genom att som resultat skapa ett kompendium som mentorer kan använda i sitt arbete med det dagliga samtalet med eleverna, vill uppsatsen beskriva och ge grundläggande kunskap om de verktyg som finns i den lösningsinriktade verktygslådan. Syftet nås även med en enkätundersökning där mentorer som fått pröva på metoden plockat ut fördelar och nackdelar med metoden.Uppsatsen visar att regelbunden användning och övning krävs för att kunna tillgodogöra sig metoden, och även att mentorn genomgår en grundläggande utbildning. Den kommer också att visa att vinsterna och fördelarna med metoden överstiger de eventuella nackdelar som kan uppstå när man som mentor börjar arbeta med metoden

Efficacy of soft palatal augmentation prosthesis for oral functional rehabilitation in patients with dysarthria and dysphagia: a protocol for a randomised controlled trial

Introduction Palatal augmentation prosthesis (PAP) is used in patients with articulation and swallowing disorders caused by postoperative loss of tongue tissue due to tongue cancer, cerebrovascular disease sequelae and age-related hypofunction. We have previously reported a newly designed soft PAP fabricated using an thermoplastic material that is particularly appropriate for early intervention. However, the effect of soft PAP on oral function improvement remains to be elucidated. The aim of this study is to investigate whether soft PAP can improve dysarthria and dysphagia occurring as cerebrovascular disease sequelae. Methods and analysis This prospective, randomised, controlled trial will compare the immediate and training effects of rehabilitation using soft PAP with those of rehabilitation without using it. Primary outcomes are the single-word intelligibility test score and pharyngeal transit time (PTT). Secondary outcomes are tongue function (evaluated based on maximum tongue pressure, repetitions of tongue pressure and endurance of tongue pressure), articulation function (evaluated based on speech intelligibility, oral diadochokinesis, Voice-Related Quality of Life (V-RQOL)) and swallowing function (evaluated using Eating Assessment Tool-10). The study results will help determine the efficacy of Soft PAP in improving functional outcomes of word intelligibility and PTT. We hypothesised that early rehabilitation using Soft PAP would more effectively improve articulation and swallowing function compared with conventional rehabilitation without using soft PAP. Ethics and dissemination Ethical approval was obtained from the Okayama University Certified Review Board. The study findings will be published in an open access, peer-reviewed journal and presented at relevant conferences and research meetings

Attempt to Generate Uniform Magnetic Field by Face-to-Face Magnet System Containing HTS Bulk Magnets

In order to develop small-scale nuclear magnetic resonance devices, the authors have been developing uniform magnetic fields in the space between the face-to-face settled magnetic poles which contain HTS bulk magnets. Since the NMR magnets in general require highly uniform field, it was expected to be difficult to form such homogeneous magnetic-field distribution with use of HTS bulk magnet, because the bulk magnets is characterized by its inhomogeneous magnetic field showing steep gradient. The authors modified the shape of the field distribution from convex to concave by attaching an iron plate on the pole surface. Then, the magnets were then settled face-to-face with various gaps, and the magnetic-field uniformity was estimated in the space. In order to detect the NMR signals, the field uniformity less than 1,500 ppm should be required after the former results on the hollow-type magnets. When we combined the concave and convex field distributions to compensate the uneven field distributions, the best uniformity reached 358 ppm in the 30 mm gaps, which exceeded the target value. In addition, we numerically simulated the feasible performance in this configuration, which resulted in obtaining the best uniformity of 30 ppm at 1.1 T at 7 mm distant from the pole surface in the gap of 30 mm. This result suggested that the concave and convex magnetic field distributions compensate the field uniformity with each other with keeping the magnetic field strength in the gap

Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer.

MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., AsPC1), whereas other pancreatic cancer cells (e.g., BxPC3) exhibited little response to hypoxia. Interestingly, these low-responsive cells have highly methylated CpG motifs within the hypoxia responsive element (HRE, 5\u27-RCGTG-3\u27), a binding site for HIF1α. Thus, we investigated the demethylation effects of CpG at HRE on the hypoxic induction of MUC17. Treatment of low-responsive cells with 5-aza-2\u27-deoxycytidine followed by additional hypoxic incubation resulted in the restoration of hypoxic MUC17 induction. Furthermore, DNA methylation of HRE in pancreatic tissues from patients with PDACs showed higher hypomethylation status as compared to those from non-cancerous tissues, and hypomethylation was also correlated with MUC17 mRNA expression. Taken together, these findings suggested that the HIF1α-mediated hypoxic signal pathway contributes to MUC17 expression, and DNA methylation of HRE could be a determinant of the hypoxic inducibility of MUC17 in pancreatic cancer cells

Pitch Count Limit for Youth Baseball Pitchers

Background: Reducing the number of pitches thrown is regarded as the most effective way to prevent throwing injuries in youth baseball pitchers. However, few studies have compared the effectiveness of limiting the pitch count versus the limiting the number of innings pitched in terms of elbow injuries. Hypothesis: We hypothesized that, compared with inning limits, pitch count limits would lead to greater decreases in elbow pain, range of motion deficits, positive moving valgus stress test results, and the risk of capitellar osteochondritis dissecans (OCD). Study Design: Cohort study; Level of evidence, 3. Methods: This study retrospectively reviewed baseball pitchers aged 8 to 12 years in 2017 and 2018. Inning and pitch count limits in games were set to a daily maximum of 7 innings in 2017 and 70 pitches in 2018. Elbow pain, range of motion, and moving valgus stress test results were evaluated. The presence of capitellar OCD was assessed on ultrasonographic and radiographic images. Results: A total of 352 pitchers in 2017 and 367 pitchers in 2018 participated. The mean pitch count per game was lower in the pitch count limit (CL) group (52.5 ± 16.0) than in the inning limit (IL) group (98.2 ± 19.5) (P < .001). Compared with the IL group, the CL group had significantly lower rates of elbow pain (40.9% vs 31.9%, respectively; P = .01) and reduced flexion (19.0% vs 10.6%, respectively; P = .001). Multivariate analysis revealed a significant association between elbow pain and age in both the IL and the CL groups (P < .0001 and P = .02, respectively) and between OCD and elbow pain in the CL group (P = .04). Conclusion: A pitch count limit of ≤70 pitches per day for baseball pitchers ≤12 years could be more protective against elbow pain and reduced flexion than a limit of ≤7 innings per day, but it may not be effective for reducing the risk of capitellar OCD

Attempt to Generate a Strong and Uniform Magnetic Field by Face-to-face HTS Bulk Elements in a Magnet System

AbstractA unique experimental attempt aiming to obtain a uniform magnetic field space as required for NMR has been carried out with use of HTS bulk magnets. The magnetic poles were activated as 1.8 T (North) and 1.4 T (South) at 30K by applyinga pulsed magnetic field up to 7 T, and positioned face-to-face with gaps less than 70mm. The uniformity of the magnetic field required for detecting the NMR signals isless than 1,500ppm at more than 0.3 T in the cross sectional plane of 2 x 2 mm2. After thepreliminary trials whichrevealed auniformity of 5,421ppm at 0.44 T in a70mm gap, we attached a ferromagnetic iron plate to a magnetic pole surface to change the magnetic field distribution to be concave. The best uniformity of 358ppm at 1.11 T was obtained at 9mm distance from the iron plate surface in a gap of 30mm. It is stated that the concave magnetic field distribution was compensated by the counter conical-shape field, resulting in the uniform field plane

An investigation of volute cross-sectional shape on turbocharger turbine under pulsating conditions in internal combustion engine

Engine downsizing is a proven method for CO2 reduction in Internal Combustion Engine (ICE). A turbocharger, which reclaims the energy from the exhaust gas to boost the intake air, can effectively improve the power density of the engine thus is one of the key enablers to achieve the engine downsizing. Acknowledging its importance, many research efforts have gone into improving a turbocharger performance, which includes turbine volute. The cross-section design of a turbine volute in a turbocharger is usually a compromise between the engine level packaging and desired performance. Thus, it is beneficial to evaluate the effects of cross-sectional shape on a turbine performance. This paper presents experimental and computational investigation of the influence of volute cross-sectional shape on the performance of a radial turbocharger turbine under pulsating conditions. The cross-sectional shape of the baseline volute (denoted as Volute B) was optimized (Volute A) while the annulus distribution of area-to-radius ratio (A/R) for the two volute configurations are kept the same. Experimental results show that the turbine with the optimized volute A has better cycle averaged efficiency under pulsating flow conditions, for different loadings and frequencies. The advantage of performance is influenced by the operational conditions. After the experiment, a validated unsteady computational fluid dynamics (CFD) modeling was employed to investigate the mechanism by which performance differs between the baseline volute and the optimized version. Computational results show a stronger flow distortion in spanwise direction at the rotor inlet with the baseline volute. Furthermore, compared with the optimized volute, the flow distortion is more sensitive to the pulsating flow conditions in the baseline volute. This is due to the different secondary flow pattern in the cross-sections, hence demonstrating a direction for desired volute cross-sectional shape to be used in a turbocharger radial turbine for internal combustion engine