Photocontrol of artificial transcription factors

The design of a photoswitchable homeodomain artificial transcription factor (PATF), modelled on an engrailed homeodomain, for the purpose of controlling DNA binding affinity and controlling the transcription process in cells using light has been investigated. This study was conducted using a 3,3’-bis(sulfo)- 4,4’bis(chloroacetamino)azobenzene crosslinker, alkylated between two cysteine residues with different spacings (i, i+4, i, i+7 and i, i+11) and either a rigid or flexible linker domain. In previous studies, basic leucine zipper transcription activators have been photocontrolled in living cells by incorporating a photoswitchable azobenzene crosslinker. Circular dichroism spectroscopy showed the conformation of crosslinked PATF (XLPATF) peptides (i, i+11 spacing) containing rigid and flexible linkers could be controlled reversibly by light. Fluorescence anisotropy experiments using labelled DNA confirmed the in vitro DNA binding affinity of PATF was considerably higher with the crosslinker in the trans (ground state) configuration than in the cis (photoexcited state) configuration. Further studies of peptides with i, i+4 and i, i+7 spacings with a semirigid and rigid linker domains showed increased binding affinity with the crosslinker in the cis configuration. Initiation of transcription was investigated by an in vitro transcription assay to measure the ability of PATF molecules to moderate the production of RNA by irradiation with UV light. PATF molecules with i, i+11 spacings showed increased transcriptional activation with the crosslinker in the ground state configuration and i, i+4 and i, i+7 spacings resulted in increased transcription activation with the crosslinker in the excited state conformation. Control of 50% of transcriptional activity was achieved for i, i+11 v spacings, and PATFs with a rigid linker domain were more effective switches than those with flexible linkers. Using i, i+4 and i, i+7 spacings in PATFs resulted in a lower degree of control but, as anticipated, transcriptional activation was increased after irradiation

Hearing screening outcomes in pediatric critical care survivors: a 1-year report

Background Hearing loss is a potentially serious complication that can occur after surviving a critical illness. Study on screening for hearing problems in pediatric critical care survivors beyond the neonatal period is lacking. This study aimed to identify the prevalence of abnormal hearing screening outcomes using transitory evoked otoacoustic emission (TEOAE) screening in children who survived critical illness and to find possible associating factors for abnormal hearing screening results. Methods This study was a single-center, prospective, observational study. All children underwent otoscopy to exclude external and middle ear abnormalities before undergoing TEOAE screening. The screening was conducted before hospital discharge. Descriptive statistics, chi-square, and logistic regression tests were used for data analysis. Results A total of 92 children were enrolled. Abnormal TEOAE responses were identified in 26 participants (28.3%). Children with abnormal responses were significantly younger than those with normal responses with a median age of 10.0 months and 43.5 months, respectively (P<0.001). Positive association with abnormal responses was found in children younger than 12 months of age (adjusted odds ratio [OR], 3.07; 95% confidence interval [CI], 1.06–8.90) and children with underlying genetic conditions (adjusted OR, 6.95; 95% CI, 1.49–32.54). Conclusions Our study demonstrates a high prevalence of abnormal TEOAE screening responses in children surviving critical illness, especially in patients younger than 12 months of age. More extensive studies should be performed to identify the prevalence and associated risk factors of hearing problems in critically ill children

Solenergins barriärer rivs med användbarhetsdesign : Vintern kommer

Photovoltaics has so far not seen much success in Sweden. Recent studies have shown that one of the reasons could be a lack of understanding of the technology, and a feeling that the lack of energy production during winter when a house’s energy consumption is the highest makes photovoltaics uninteresting. The ongoing research project Holistic business models and ICT solutions for prosumers seeks to increase the use of photovoltaics in Sweden, and have created business model concepts in an attempt to break perceived barriers of photovoltaics. My task in this project was to design a tailor made ICT solution with the users’ needs in focus. A series of interviews were conducted with households interested in photovoltaics to investigate what information is relevant to understand the business model, and create a starting point for the design process. To ensure a high level of usability of the ICT solution, an iterative design process was conducted with user tests between iterations. This resulted in a low fidelity prototype of a smartphone application, consisting of greyscale mockups. The prototype has as much as possible taken the interviewed households’ wishes into account, while adhering to design principles set for usability design. The interviews and user tests also gave some new insights into the informants’ attitudes towards the business model suggested by the research project, which is discussed at the end of the report.Solenergi har ännu inte lyckats få ett stort genombrott i Sverige. Nyligen utförda studier har visat att detta delvis kan bero på bristande förståelse för teknologin, men även en känsla av att det inte är till någon nytta då vi förbrukar som mest energi under vintern, när solceller knappt producerar någonting.  Det pågående forskningsprojektet Holistiska affärsmodeller och IT-stöd för prosumenter har som mål att öka användningen av solenergi i Sverige, och har utvecklat koncept av affärsmodeller med mål att överkomma de upplevda barriärer som är förknippade med solenergi. Min uppgift i projektet var att designa ett skräddarsytt IT-stöd för en av dessa affärsmodeller med användaren i fokus. En intervjuserie utfördes med hushåll som är intresserade av solenergi för att ta reda på vilken information som är relevant för användaren för att förstå affärsmodellen. Detta låg sedan till grund för en iterativ designprocess med fokus på hög användbarhet där användartest genomfördes mellan varje iteration. Detta resulterade i en prototyp av en smartphone applikation som består av mockups i gråskala. Prototypen har i största möjliga mål anpassats till de intervjuade hushållens önskemål, men tonvikt lades vid att uppfylla designkriterier som säkerställer hög användbarhet. Intervjuerna och användartesterna gav även nya insikter om informanternas inställning till affärsmodellen som ligger till grund för IT-stödet, och detta diskuteras i slutet av rapporten.

Comparison of three non-invasive hemodynamic monitoring methods in critically ill children.

INTRODUCTION:Hemodynamic parameters measurements were widely conducted using pulmonary artery catheter (PAC) with thermodilution as a reference standard. Due to its technical difficulties in children, transthoracic echocardiography (TTE) has been widely employed instead. Nonetheless, TTE requires expertise and is time-consuming. Noninvasive cardiac output monitoring such as ultrasonic cardiac output monitor (USCOM) and electrical velocimetry (EV) can be performed rapidly with less expertise requirement. Presently, there are inconsistent evidences, variable precision, and reproducibility of EV, USCOM and TTE measurements. Our objective was to compare USCOM, EV and TTE in hemodynamic measurements in critically ill children. MATERIALS AND METHODS:This was a single center, prospective observational study in critically ill children. Children with congenital heart diseases and unstable hemodynamics were excluded. Simultaneous measurements of hemodynamic parameters were conducted using USCOM, EV, and TTE. Inter-rater reliability was determined. Bland-Altman plots were used to analyse agreement of assessed parameters. RESULTS:Analysis was performed in 121 patients with mean age of 4.9 years old and 56.2% of male population. Interrater reliability showed acceptable agreement in all measured parameters (stroke volume (SV), cardiac output (CO), velocity time integral (VTI), inotropy (INO), flow time corrected (FTC), aortic valve diameter (AV), systemic vascular resistance (SVR), and stroke volume variation (SVV); (Cronbach's alpha 0.76-0.98). Percentages of error in all parameters were acceptable by Bland-Altman analysis (9.2-28.8%) except SVR (30.8%) and SVV (257.1%). CONCLUSION:Three noninvasive methods might be used interchangeably in pediatric critical care settings with stable hemodynamics. Interpretation of SVV and SVR measurements must be done with prudence

Comparison of three non-invasive hemodynamic monitoring methods in critically ill children - Fig 4

<p>Bland-Altman analysis of afterload: Systemic vascular resistance (A) Systemic vascular resistance index (B). X-axis illustrated average measurements of standard from using ICON. Y-axis demonstrated mean bias using USCOM.</p

Comparison of three non-invasive hemodynamic monitoring methods in critically ill children - Fig 2

<p>Bland-Altman analysis of overall results: Cardiac output (A), cardiac index (B). X-axis illustrated average measurements of standard from using TTE. Y-axis demonstrated mean bias using other modalities.</p

Comparison of three non-invasive hemodynamic monitoring methods in critically ill children - Fig 3

<p>Bland-Altman analysis of preload: Stroke volume (A), Corrected flow time (B) and Stroke volume variation (C). X-axis illustrated average measurements of standard from using TTE or ICON. Y-axis demonstrated mean bias using other modalities.</p

Flow diagram showing the screening and enrollment of patients.

<p>Flow diagram showing the screening and enrollment of patients.</p