The Use of Pluripotent Stem Cell for Personalized Cell Therapies against Neurological Disorders

Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells

Glucose repression of the Escherichia coli sdhCDAB operon, revisited: regulation by the CRP·cAMP complex

Expression of the Escherichia coli sdhCDAB operon encoding the succinate dehydrogenase complex is regulated in response to growth conditions, such as anaerobiosis and carbon sources. An anaerobic repression of sdhCDAB is known to be mediated by the ArcB/A two-component system and the global Fnr anaerobic regulator. While the cAMP receptor protein (CRP) and Cra (formerly FruR) are known as key mediators of catabolite repression, they have been excluded from the glucose repression of the sdhCDAB operon. Although the glucose repression of sdhCDAB was reported to involve a mechanism dependent on the ptsG expression, the molecular mechanism underlying the glucose repression has never been clarified. In this study, we re-examined the mechanism of the sdhCDAB repression by glucose and found that CRP directly regulates expression of the sdhCDAB operon and that the glucose repression of this operon occurs in a cAMP-dependent manner. The levels of phosphorylated enzyme IIA(Glc) and intracellular cAMP on various carbon sources were proportional to the expression levels of sdhC-lacZ. Disruption of crp or cya completely abolished the glucose repression of sdhC-lacZ expression. Together with data showing correlation between the intracellular cAMP concentrations and the sdhC-lacZ expression levels in several mutants and wild type, in vitro transcription assays suggest that the decrease in the CRP·cAMP level in the presence of glucose is the major determinant of the glucose repression of the sdhCDAB operon

Validation study of the Dinamap ProCare 200 upper arm blood pressure monitor in children and adolescents

PurposeTo validate the Dinamap ProCare 200 blood pressure (BP) monitor against a mercury sphygmomanometer in children 7 to 18 years old in accordance with the 2010 International Protocol of European Society of Hypertension (ESH-IP2) and the British Hypertension Society (BHS) protocol.MethodsForty-five children were recruited for the study. A validation procedure was performed following the protocol based on the ESH-IP2 and BHS protocols for children and adolescents. Each subject underwent 7 sequential BP measurements alternatively with a mercury sphygmomanometer and the test device by trained nurses. The results were analyzed according to the validation criteria of ESH-IP2.ResultsThe mean (±SD) difference in the absolute BP values between test device and mercury sphygmomanometer readings was 1.85±1.65 mmHg for systolic BP (SBP) and 4.41±3.53 mmHg for diastolic BP (DBP). These results fulfilled the Association for the Advancement of Medical Instrumentation criterion of a mean±SD below 5±8 mmHg for both SBP and DBP. The percentages of test device-observer mercury sphygmomanometer BP differences within 5, 10, and 15 mmHg were 96%, 100%, and 100% for SBP, and 69%, 92%, and 100% for DBP, respectively, in the part 1 analysis; both SBP and DBP passed the part 1 criteria. In the part 2 analysis, SBP passed the criteria but DBP failed.ConclusionAlthough the Dinamap ProCare 200 BP monitor failed an adapted ESH-IP2, SBP passed. When comparing BP readings measured by oscillometers and mercury sphygmomanometers, one has to consider the differences between them, particularly in DBP, because DBP can be underestimated

Teleconnections of the Quasi‐Biennial Oscillation in a multi‐model ensemble of QBO‐resolving models

The Quasi-biennial Oscillation (QBO) dominates the interannual variability of the tropical stratosphere and influences other regions of the atmosphere. The high predictability of the QBO implies that its teleconnections could lead to increased skill of seasonal and decadal forecasts provided the relevant mechanisms are accurately represented in models. Here modelling and sampling uncertainties of QBO teleconnections are examined using a multi-model ensemble of QBO-resolving atmospheric general circulation models that have carried out a set of coordinated experiments as part of the Stratosphere-troposphere Processes And their Role in Climate (SPARC) QBO initiative (QBOi). During Northern Hemisphere winter, the stratospheric polar vortex in most of these models strengthens when the QBO near 50 hPa is westerly and weakens when it is easterly, consistent with, but weaker than, the observed response. These weak responses are likely due to model errors, such as systematically weak QBO amplitudes near 50 hPa, affecting the teleconnection. The teleconnection to the North Atlantic Oscillation is less well captured overall, but of similar strength to the observed signal in the few models that do show it. The models do not show clear evidence of a QBO teleconnection to the Northern Hemisphere Pacific-sector subtropical jet

Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

IntroductionDespite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. MethodsHere, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. ResultsDifferential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. DiscussionAberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression

Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/β-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model

Bone morphogenetic protein-2 (BMP-2) is used in the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery. However, high doses are associated with side effects such as inflammation and osteophytes. In this study, we performed spinal fusion surgery on mini-pigs using BMP-2 and a HA/β-TCP hydrogel carrier, and evaluated the degree of fusion and osteophyte growth according to time and dosage. Increasing the dose of BMP-2 led to a significantly higher fusion rate than was observed in the control group, and there was no significant difference between the 8-week and 16-week samples. We also found that the HA + β-TCP hydrogel combination helped maintain the rate of BMP-2 release. In conclusion, the BMP-2-loaded HA/β-TCP hydrogel carrier used in this study overcame the drawback of potentially causing side effects when used at high concentrations by enabling the sustained release of BMP-2. This method is also highly efficient, since it provides mineral matter to accelerate the fusion rate of the spine and improve bone quality

Momentum Flux of Convective Gravity Waves Derived from an Offline Gravity Wave Parameterization. Part II: Impacts on the Quasi-Biennial Oscillation

The characteristics of small-scale convective gravity waves (CGWs; horizontal wavelengths <100 km) and their contributions to the large-scale flow in the stratosphere, including the quasi-biennial oscillation (QBO), are investigated using an offline calculation of a source-dependent, physically based CGW parameterization with global reanalysis data from 1979 to 2010. The CGW momentum flux (CGWMF) and CGW drag (CGWD) are calculated from the cloud top (source level) to the upper stratosphere using a Lindzen-type wave propagation scheme. The 32-yr-mean CGWD exhibits large magnitudes in the tropical upper stratosphere and near the stratospheric polar night jet (~60°). The maximum positive drag is 0.1 (1.5) m s−1 day−1, and the maximum negative drag is −0.9 (−0.7) m s−1 day−1 in January (July) between 3 and 1 hPa. In the tropics, the momentum forcing by CGWs at 30 hPa associated with the QBO in the westerly shear zone is 3.5–6 m s−1 month−1, which is smaller than that by Kelvin waves, while that by CGWs in the easterly shear zone (3.1–6 m s−1 month−1) is greater than that by any other equatorial planetary waves or inertio-gravity waves (inertio-GWs). Composite analyses of the easterly QBO (EQBO) and westerly QBO (WQBO) phases reveal that the zonal CGWMF is concentrated near 10°N and that the negative (positive) CGWD extends latitudinally to ±20° (±10°) at 30 hPa. The strongest (weakest) negative CGWD is in March–May (September–November) during the EQBO, and the strongest (weakest) positive CGWD is in June–August (March–May) during the WQBO. The CGWMF and CGWD are generally stronger during El Niño than during La Niña in the equatorial region

Effective Channel-Independent Inverse Characterization Method for Display Device

This paper proposes a channel-independent inverse characterization process based on the GOG model for a display device. The CIEXYZ values for each of RGB channel can estimated from nine channel-independent interpolation TRCs (Tone Response Curves), and the result of this characterization method is better than that from conventional three channel-independent interpolation TRCs. However inverse characterization is impossible when using nine channel-independent interpolation TRCs, as the CIEXYZ values that correspond to each RGB values are inseparable directly. Accordingly, inverse characterization is usually implemented using the 3D-LUT (Look-Up Table) method. Yet, although the result of a 3D-LUT is accurate, creating the LUT requires a lot of memory space and considerable amount of measurements. Therefore, an accurate inverse characterization method is proposed based on the simple modeling of channeldependent values and nine channel inverse processes based on the GOG model. CIEXYZ values are computed for three normalized luminance values using an inverse matrix. The channel-dependent values are subtracted from the normalized luminance values that are generated by an overlapped spectral distribution of the primary digital values based on modeling the channel-dependent values. Each of the three normalized luminance values is modified into the corresponding nine channel TRCs using a gamma correction of each channel and modifying the tone response curve. The digital values are estimated by the nine channel-independent interpolation TRCs based on an inverse GOG model using the parameters of forward characterization, considering weighting factors. Three digital values are determined for each RGB channel based on the maximum CIEXYZ values for each red, green, and blue channel. As such, the proposed method reduces the time complexity and number of measurements required for accuracy. 1