Two novel mutations of Wiskott–Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling

AbstractWiskott–Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326–1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study

Measurement of Planetary Boundary Layer Winds with Scanning Doppler Lidar

The accurate measurement of wind profiles in the planetary boundary layer (PBL) is important not only for numerical weather prediction, but also for air quality modeling. Two wind retrieval methods using scanning Doppler light detection and ranging (lidar) measurements were compared and validated with simultaneous radiosonde soundings. A comparison with 17 radiosonde sounding profiles showed that the sine-fitting method was able to retrieve a larger number of data points, but the singular value decomposition method showed significantly smaller bias (0.57 m s(-1)) and root-mean-square error (1.75 m s(-1)) with radiosonde soundings. Increasing the averaging time interval of radial velocity for obtaining velocity azimuth display scans to 15 min resulted in better agreement with radiosonde soundings due to the signal averaging effect on noise. Simultaneous measurements from collocated wind Doppler lidar and aerosol Mie-scattering lidar revealed the temporal evolution of PBL winds and the vertical distribution of aerosols within the PBL

Development of the Methodology for Application of Revised Source Term to Operating Nuclear Power Plants in Korea

ABSTRACT Considering the current trend in applying the revised source term proposed by NUREG-1465 to the nuclear power plants in the U. S., it is expected that the revised source term will be applied to the Korean operating nuclear power plants in the near future, even though the exact time can not be estimated. To meet the future technical demands, it is necessary to prepare the technical system including the related regulatory requirements in advance. In this research, therefore, it is intended to develop the methodology to apply the revised source term to operating nuclear power plants in Korea. Several principles were established to develop the application methodologies. First, it is not necessary to modify the existing regulations about source term (i.e., any back-fitting to operating nuclear plants is not necessary). Second, if the pertinent margin of safety is guaranteed, the revised source term suggested by NUREG-1465 may be useful to full application. Finally, a part of revised source term could be selected to application based on the technical feasibility. As the results of this research, several methodologies to apply the revised source term to the Korean operating nuclear power plants have been developed, which include 1) the selective (or limited) application to use only some of all the characteristics of the revised source term, such as release timing of fission products and chemical form of radio-iodine and 2) the full application to use all the characteristics of the revised source term. The developed methodologies are actually applied to Ulchin 3&4 units and their application feasibilities are reviewed. The results of this research are used as either a manual in establishing the plan and the procedure for applying the revised source term to the domestic nuclear plant from the utility's viewpoint; or a technical basis of revising the related regulations from the regulatory body's viewpoint

Protective Effectiveness of Hantavirus Vaccine

A case-control study in the Republic of Korea evaluated the protective effectiveness of the hantavirus vaccine. Point estimates showed increasing effectiveness with increasing numbers of doses received: 25% for one dose, 46% for two doses, and 75% for three doses. All 95% confidence intervals overlapped zero; therefore, the findings could be due to chance

Meteorological characteristics and assessment of the effect of local emissions during high PM10 concentration in the Seoul Metropolitan Area

In this study, we investigate the meteorological characteristics and the effect of local emissions during high PM10 concentrations in the Seoul Metropolitan Area (SMA) by utilizing data from a high-resolution urban meteorological observation system network (UMS-Seoul) and The Air Pollution Model (TAPM). For a detailed analysis, days with PM10 concentrations higher than 80 ??g m-3 for daily average PM10 concentration (classified as unhealthy by the Korean Ministry of Environment) in the Seoul Metropolitan Area (SMA) were classified into 3 Cases. Case I was defined as when the prevailing effect was from outside the SMA. Case II was defined as when the prevailing effect was a local effect with outside. Case III was defined as when the prevailing effect was local. Overall, high PM10 concentrations in the SMA mostly occurred under weak migratory anticyclone systems over the Korean Peninsula during warm temperatures. Prior to the PM10 concentration reaching the peak concentration, the pattern in each case was distinctive. After peak concentrations, however, the pattern for the 3 cases became less distinct. This study showed that nearly 50% of the high PM10 concentrations in the SMA occurred in spring and were governed by the conditions for Case II more than these for Cases I and III. In spring, the main sources of the high PM10 concentrations in the SMA were local emissions due to the predominance of weak winds and local circulation. The simulation showed that the non-SMA emissions were about 63 to 73% contribution to the spring high PM10 concentrations in the SMA. Specifically, local point sources including industrial combustion, electric utility, incineration and cement production facilities scattered around the SMA and could account for PM10 concentrations more than 10 ??g m-3 in the SMA

Effect of olmesartan and amlodipine on serum angiotensin-(1–7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension

Background Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1–7) [Ang-(1–7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1–7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. Methods This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20mg of olmesartan (N = 40) or 5mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1–7) from baseline to week 24. Results Both olmesartan and amlodipine treatment for 24weeks decreased systolic and diastolic blood pressures significantly by > 18mmHg and > 8mmHg, respectively. Serum Ang-(1–7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5pg/mL → 46.2 ± 59.4pg/mL) than by amlodipine treatment (29.2 ± 38.9pg/mL → 31.7 ± 26.0pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42ng/mL → 6.74 ± 0.39ng/mL by olmesartan treatment vs. 6.43 ± 0.23ng/mL → 6.61 ± 0.42ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1–7) levels (r =  − 0.252 and r =  − 0.299, respectively). The change in Ang-(1–7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1–7) levels were an independent predictor of a reduction in albuminuria. Conclusions These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1–7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. Trial registration: ClinicalTrials.gov NCT05189015.This research was funded by Daiichi Sankyo Co., Seoul, South Korea through a subcontract with SNUBH (Seongnam, Republic of Korea). The funding agency had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Recurred pneumocephalus in a head trauma patient following positive pressure mask ventilation during induction of anesthesia -A case report-

Pneumocephalus is a condition which usually results from head trauma. It has been known that iatrogenic pneumocephalus can occur as a complication of positive pressure mask ventilation during induction of anesthesia or ventilatory care for head trauma patients. We report a case of mask ventilation during anesthesia induction in a 50-year-old male patient with head trauma. Initial pneumocephalus associated with cerebrospinal fluid leakage was diagnosed immediate following head injury involving facial sinuses. He was managed with emergent lumbar drainage and supportive care. Pneumocephalus recurred following positive pressure mask ventilation (PPMV) during anesthesia induction for surgery on the right arm. Recurred pneumocephalus was managed with high flow oxygen and supportive care. Anesthesiologists should be aware of pneumocephalus as a potential complication of PPMV in head trauma patients, even after resolution of previous pneumocephalus

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts

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