Computerized ionospheric tomography with the IRI model

Abstract Computerized ionospheric tomography (CIT) is a method to estimate ionospheric electron density distribution by using the global positioning system (GPS) signals recorded by the GPS receivers. Ionospheric electron density is a function of latitude, longitude, height and time. A general approach in CIT is to represent the ionosphere as a linear combination of basis functions. In this study, the model of the ionosphere is obtained from the IRI in latitude and height only. The goal is to determine the best representing basis function from the set of Squeezed Legendre polynomials, truncated Legendre polynomials, Haar Wavelets and singular value decomposition (SVD). The reconstruction algorithms used in this study can be listed as total least squares (TLS), regularized least squares, algebraic reconstruction technique (ART) and a hybrid algorithm where the reconstruction from the TLS algorithm is used as the initial estimate for the ART. The error performance of the reconstruction algorithms are compared with respect to the electron density generated by the IRI-2001 model. In the investigated scenario, the measurements are obtained from the IRI-2001 as the line integral of the electron density profiles, imitating the total electron content estimated from GPS measurements. It has been observed that the minimum error between the reconstructed and model ionospheres depends on both the reconstruction algorithm and the basis functions where the best results have been obtained for the basis functions from the model itself through SVD

Final structure & design parameters of TARLA RF system

Doğan, Mehmet Sinan (Dogus Author) -- Conference full title: 5th International Particle Accelerator Conference, IPAC 2014; International Congress Center DresdenDresden; Germany; 15 June 2014 through 20 June 2014Turkish Accelerator and Radiation Laboratory in Ankara (TARLA) is an oscillator mode IR-FEL facility which is under construction since 2011. ELBE licensed superconducting modules housing TESLA RF cavities have been manufacturing for one year and the first module will be delivered in 2015. He Cryogenic System has also started to be manufacturing at similar time with the accelerator structures. It will be delivered in 2014. High Power RF amplifiers are started to tender procedures and delivery time is planning as 2015. The installation of high power transmission lines have to be completed at the same time with the delivery date of HPRF amplifiers to test the cavities and amplifiers. In this study, the final structural design of high power RF transmission lines and design parameters of RF amplifiers for TARLA is discussed

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62)

Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia

Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer's disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity, while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia

Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD. Here, we investigated the effect of PKLR in in vivo model and performed drug repositioning to identify a drug candidate for treatment of NAFLD. Methods: Tissue samples from liver, muscle, white adipose and heart were obtained from control and PKLR knockout mice fed with chow and high sucrose diets. Lipidomics as well as transcriptomics analyses were conducted using these tissue samples. In addition, a computational drug repositioning analysis was performed and drug candidates were identified. The drug candidates were both tested in in vitro and in vivo models to evaluate their toxicity and efficacy. Findings: The Pklr KO reversed the increased hepatic triglyceride level in mice fed with high sucrose diet and partly recovered the transcriptomic changes in the liver as well as in other three tissues. Both liver and white adipose tissues exhibited dysregulated circadian transcriptomic profiles, and these dysregulations were reversed by hepatic knockout of Pklr. In addition, 10 small molecule drug candidates were identified as potential inhibitor of PKLR using our drug repositioning pipeline, and two of them significantly inhibited both the PKLR expression and triglyceride level in in vitro model. Finally, the two selected small molecule drugs were evaluated in in vivo rat models and we found that these drugs attenuate the hepatic steatosis without side effect on other tissues. Interpretation: In conclusion, our study provided biological insights about the critical role of PKLR in NAFLD progression and proposed a treatment strategy for NAFLD patients, which has been validated in preclinical studies. Funding: ScandiEdge Therapeutics and Knut and Alice Wallenberg Foundation

Comparison of 3 T and 1.5 T for T2* magnetic resonance of tissue iron.

BACKGROUND: T2* magnetic resonance of tissue iron concentration has improved the outcome of transfusion dependant anaemia patients. Clinical evaluation is performed at 1.5 T but scanners operating at 3 T are increasing in numbers. There is a paucity of data on the relative merits of iron quantification at 3 T vs 1.5 T. METHODS: A total of 104 transfusion dependent anaemia patients and 20 normal volunteers were prospectively recruited to undergo cardiac and liver T2* assessment at both 1.5 T and 3 T. Intra-observer, inter-observer and inter-study reproducibility analysis were performed on 20 randomly selected patients for cardiac and liver T2*. RESULTS: Association between heart and liver T2* at 1.5 T and 3 T was non-linear with good fit (R (2) = 0.954, p < 0.001 for heart white-blood (WB) imaging; R (2) = 0.931, p < 0.001 for heart black-blood (BB) imaging; R (2) = 0.993, p < 0.001 for liver imaging). R2* approximately doubled between 1.5 T and 3 T with linear fits for both heart and liver (94, 94 and 105 % respectively). Coefficients of variation for intra- and inter-observer reproducibility, as well as inter-study reproducibility trended to be less good at 3 T (3.5 to 6.5 %) than at 1.5 T (1.4 to 5.7 %) for both heart and liver T2*. Artefact scores for the heart were significantly worse with the 3 T BB sequence (median 4, IQR 2-5) compared with the 1.5 T BB sequence (4 [3-5], p = 0.007). CONCLUSION: Heart and liver T2* and R2* at 3 T show close association with 1.5 T values, but there were more artefacts at 3 T and trends to lower reproducibility causing difficulty in quantifying low T2* values with high tissue iron. Therefore T2* imaging at 1.5 T remains the gold standard for clinical practice. However, in centres where only 3 T is available, equivalent values at 1.5 T may be approximated by halving the 3 T tissue R2* with subsequent conversion to T2*

Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial

Background: Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered\ua0combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods: Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35\ua0g L-serine (61.75%), 1\ua0g nicotinamide riboside (5%), 2.55\ua0g\ua0N-acetyl-L-cysteine (12.75%), and 3.73\ua0g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28\ua0days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. Results: We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the\ua0CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Conclusion: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration\ua0ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131