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Asplenium L. is a sub-cosmopolitan genus of ferns comprising approximately 700 species. It includes various ploidy-leveled taxa, and, in particular, polyploid species occupy a higher proportion than diploid species within the genus. In addition, it is regarded as an essential process to confirm the cytotype of taxa because the ploidy level is sometimes used to identify a particular taxon in Asplenium. In the case of A. prolongatum, two cytotypes, tetraploid and hexaploid, have been reported in Japanese and Chinese populations. However, to date, there have been no attempts to confirm the ploidy of the Korean species. In the present study, we investigated the cytotype of Korean A. prolongatumusing chromosome counting and genome size measurements, and we found that two cytotypes, hexaploid (2n = 6x = 216) and octaploid (2n = 8x = 288), were distributed in Jeju Island, Korea. To the best of our knowledge, this is the first report of a neo-cytotype of A. prolongatum. The hexaploids mostly had empty, shrunken sporangia, which is one of the traits observed in sterile hybrid ferns. From these results, it was concluded that A. prolongatumhas three cytotypes: tetraploid, hexaploid, and octaploid.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid β plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aβ deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aβ burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.

In this paper, a simple practical method to estimate the drag of Super-Cavitating Underwater Vehicles (SCUV) is proposed that can obtain the drag with only principal dimensions in an initial design stage. SCUV is divided into cavitator, forebody, afterbody, base, and control fin and the drag of each part is estimated. The formulas for the drag coefficient are proposed for the disk and cone type cavitators and wedges used as control fins. The formulas are a function of cavitation number, cone or wedge angle, and Reynolds number. This method can confirm the drag characteristics of SCUV that the drag hump appears according to the coverage of the body by the cavity and the cavitator drag remains only when the entire body is covered by cavity. Applying this method to SCUV of various shapes, it is confirmed that the effects of cavitating and non-cavitating conditions, cavitator and body shape, and speed could be found.

A numerical analysis is carried out for the marine propellers in open water conditions to investigate the effect of the wall treatments in model and full scale. The standard wall function to apply the low of the wall and the two layer zonal model to calculate the whole boundary layer for a transition phenomenon are used with one turbulence model. To determine an appropriate distance of the first grid point from the wall when using the wall function, a formula based on Reynolds number is suggested, which can estimate the maximum y+ satisfying the logarithmic law. In the model scale, it is confirmed that a transition calculation is required for a model scale propeller with low Reynolds number that the transient region appears widely. While in the full scale, the wall function calculation is recommended for efficient calculations due to the turbulence dominant flow for large Reynolds number.

Flush ostial occlusion of the superficial femoral artery (SFA) is challenging for endovascular treatment. Neither ipsilateral nor contralateral access is easy. The drawback of ipsilateral common femoral artery (CFA) access is that the CFA is too short for catheter manipulation and sheath engagement. Contralateral retrograde CFA access could have merit, but it has the drawback of poor pushability and torquability in the manipulation of devices. The most challenging part of flush ostial occlusion is the difficulty of wire engagement into the SFA orifice. We describe a case of successful treatment of a flush-occluded long SFA lesion using ultrasound-guided direct ipsilateral ostial access.

We describe a mechanism by which the anti-apoptotic B cell lymphoma 2 (Bcl-2) protein is downregulated to induce apoptosis. ARTS (Sept4_i2) is a tumor suppressor protein that promotes cell death through specifically antagonizing XIAP (X-linked inhibitor of apoptosis). ARTS and Bcl-2 reside at the outer mitochondrial membrane in living cells. Upon apoptotic induction, ARTS brings XIAP and Bcl-2 into a ternary complex, allowing XIAP to promote ubiquitylation and degradation of Bcl-2. ARTS binding to Bcl-2 involves the BH3 domain of Bcl-2. Lysine 17 in Bcl-2 serves as the main acceptor for ubiquitylation, and a Bcl-2 K17A mutant has increased stability and is more potent in protection against apoptosis. Bcl-2 ubiquitylation is reduced in both XIAP- and Sept4/ARTS-deficient MEFs, demonstrating that XIAP serves as an E3 ligase for Bcl-2 and that ARTS is essential for this process. Collectively, these results suggest a distinct model for the regulation of Bcl-2 by ARTS-mediated degradation.

Thiopurines have a narrow therapeutic range because of frequent toxicity (i.e. marrow suppression), which is only partly explained by TPMTgenetic polymorphisms, especially within Asian populations. Recent studies have identified NUDT15variation as another important factor affecting thiopurine metabolism. In this study, a total of four NUDT15coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal) were genotyped in 920 Korean individuals using direct sequencing of NUDT15for the first time in a Korean population. The allele frequencies were 86.7% for NUDT15*1, and 4.4, 6.9, 0.4, 1.1, and 0.50% for *2, *3, *4, *5, and *6, respectively. The NUDT15phenotypes based on diplotypes included normal activity (n=692), intermediate activity (n=209), and low activity (n=19), occurring in 75.2, 22.7, and 2.1% of the population, respectively. This study was the first to report NUDT15variants other than NUDT15*3in the Korean population and more individuals who were categorized as having intermediate or low NUDT15activity in our study than in previously reported studies in the Korean population (24.8 vs. 19.4%, P<0.05). This study is useful for future clinical studies on thiopurine pharmacogenetics and dosage adjustment in the Korean population.

For the blind calculation of the International Collaborative Standard Problem (ICSP) experiment on heavy water reactor moderator subcooling requirements, the COMSOL Multiphysics code is used to simulate plastic deformation of a pressure tube (PT) as a result of the interaction of stress and temperature. It is shown that the thermal stress model of COMSOL is compatible to simulate the multiple heat transfers (including the radiation heat transfer and heat conduction) and stress strain in the simplified two-dimensional problem. The benchmark test result for radiation heat transfer is in good agreement with the analytical solution for the concentric configuration of PT and calandria tube (CT). Since the original strain model of COMSOL only considers an elastic deformation with thermal expansion coefficient, the PT/CT contact cannot be predicted in the ICSP. Therefore, the plastic deformation model by the Shewfelt and Godin, widely used in the fuel channel analysis of CANadian Deuterium Uranium (CANDU) reactor, is implemented to the strain equation of COMSOL. The heat-up of PT, the strain rate, and the contact time of the PT/CT are calculated with the boundary conditions (BCs) given for blind calculation of the ICSP experiment.The result shows a sudden expansion of the inner concentric PT within a few milliseconds. This unsteady simulation should be helpful for the conceptual design of experiment as well as for the understanding of multiphysics inside the fuel channels of the CANDU reactor.

We report 2 cases of pseudostenosis of the external iliac artery (EIA) combined with aortoiliac occlusive disease. Both cases were treated successfully by aortobi-iliac bypass surgery instead of aortobi-femoral bypass. Pseudostenoses of the EIA disappeared in the postoperative computed tomographic angiography. We are not aware of previous reports of similar findings. Pseudostenosis should be considered if the EIA shows diffuse narrowing without wall irregularity in combination with severe stenosis or occlusion of the common iliac artery.

A numerical calculation with the commercial computational fluid dynamics code CFX-14.0 was conducted for a test facility simulating the Canadian deuterium uranium moderator thermal–hydraulics. Two kinds of moderator thermal–hydraulic tests at Stern Laboratories Inc. were performed in the full geometric configuration of the Canadian deuterium uranium moderator circulating vessel, which is called a calandria tank, housing a matrix of horizontal rod bundles simulating calandria tubes. The first of these tests is the pressure drop measurement of a cross flow in the horizontal rod bundles. The other is the local temperature measurement on the cross section of the horizontal cylinder vessel simulating the calandria system. In the present study, the full geometric details of the calandria tank are incorporated in the grid generation of the computational domain to which the boundary conditions for each experiment are applied. The numerical solutions are reviewed and compared with the available test data.

This paper presents a new estimation method of full scale propulsive performance for the pulling type podded propeller. In order to estimate the drag of pod housing, a drag velocity ratio, which includes the effects of podded propeller loading and Reynolds number, is presented and evaluated through the comparison of model test and numerical analysis. By separating the thrust of propeller blade and the drag of pod housing, extrapolation method of pod housing drag to full scale is deduced, and correction method of propeller blade thrust and torque to full scale is presented. This study utilized the drag coefficient ratio of the pod housing as a measure for expanding it to full scale, but in order to increase the accuracy of performance evaluation, additional study is necessary on the method for the full scale expansion via separating the drag of pod body, strut and fin which consist the pod housing.

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1G93A) transgenic mice. The hNPs were engineered to express brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), VEGF, neurotrophin-3 (NT-3), or glial cell-derived neurotrophic factor (GDNF), respectively, by adenoviral vector and GDNF by lentiviral vector before transplantation. Donor-derived cells engrafted and migrated into the spinal cord or brain of ALS mice and differentiated into neurons, oligodendrocytes, or glutamate transporter-1 (GLT1)-expressing astrocytes while some cells retained immature markers. Transplantation of GDNF- or IGF-1-expressing hNPs attenuated the loss of motor neurons and induced trophic changes in motor neurons of the spinal cord. However, improvement in motor performance and extension of lifespan were not observed in all hNP transplantation groups compared to vehicle-injected controls. Moreover, the lifespan of GDNF-expressing hNP recipient mice by lentiviral vector was shortened compared to controls, which was largely due to the decreased survival times of female animals. These results imply that although implanted hNPs differentiate into GLT1-expressing astrocytes and secrete GFs, which maintain dying motor neurons, inadequate trophic support could be harmful and there is sexual dimorphism in response to GDNF delivery in ALS mice. Therefore, additional therapeutic approaches may be required for full functional recovery.

Xanthohumol (XH), the principal prenylflavonoid of the hop plant (Humulus lupulus L.), dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis in B16 melanoma cells, with little cytotoxicity at the effective concentrations. Decreased melanin content was accompanied by reduced tyrosinase enzyme activity, protein and mRNA expression. The levels of tyrosinase-related protein 1 and 2 mRNAs were decreased by XH. XH also inhibited a-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. XH downregulated the protein and mRNA expression of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of key melanogenic enzymes. These results suggest that XH might act as a hypo-pigmenting agent through the downregulation of MITF in the cAMP-dependent melanogenic pathway.

This paper presents a study on the relationship between feedrate and fatigue life of Al7075-T6 specimens before and after shotpeening. For this purpose, six groups of specimens, each of which consists of eight specimens, were first machined at six different feedrates (0.05, 0.10, 0.15, 0.20, 0.25, 0.30 mm/rev). Half of eight specimens in each group were then peened and the others remained un-peened. Next, the fatigue life was measured by using 4-point rotary bending machine. One observation was that the fast the feedrate was, the large the mean diameter of a specimen was. To apply the same bending stresses in all cases, different loading conditions were thus recalculated and applied to specimens based on their mean diameters. Finally, the effect of feedrate on the fatigue life was estimated by comparing twelve sets of specimens (six groups times two sets, peened and un-peened).

Trimellitic anhydride (TMA) is widely used industrially to make epoxy and alkyd resins, plasticizers and surfactants. The purpose of this study was to investigate whether contact hypersensitivity (CHS) is induced by repeated TMA challenge and the role of TNF-a and IgE in the TMA-induced CHS. The repetition of the challenge enlarged the extent of an early and a late phase of CHS in TNF-a+/+ (B6129SF2/J) and Balb/c mice. In the late phase of TMA-induced CHS, the peak of ear swelling responses by single challenge showed at 24 h after challenge, but the peak was observed at 8 h after repeated challenge. In the TNF-a knockout TNF-a-/- (B6;129S-Tnf(tm1Gk1) mice, the repetition of the TMA challenges enlarged the extent of the late phase of CHS, but less than those in TNF-a+/+ mice. Injection of anti-TNF-a antibody into the peritoneal cavity of Balb/c mice significantly decreased the extent of the late phase of CHS. Subcutaneous injection of anti-IgE antibody into Balb/c mice also decreased the extent of the late phase of CHS in dose-dependent manner. Histologically, infiltration of polymorphonuclear leukocytes and eosinophils was more pronounced in repeatedly TMA-challenged TNF-a+/+ and Balb/c mice than in the TNF-a-/- mice and anti-TNF-a or anti-IgE antibodies treated Balb/c mice. These results indicate that mice sensitized by TMA could possibly offer a useful model to study the mechanism of CHS, and TNF-a and IgE may act as potential modulators in the late phase of TMA-induced CHS. Neutralization of TNF-a and IgE by anti-TNF-a or anti-IgE antibodies may provide therapeutic tools for the treatment of TMA-induced CHS.

CXCR3 binding chemokines play a key role in recruitment of inflammatory cells into an organ transplant. This study addresses the question of whether urinary excretion of these chemokines correlates with acute rejection in a baboon kidney transplantation model.

Isotropic NdFeB powders were blended with pure Zn and Sn powders by planetary ball milling. The mixed powders were compacted by the current applied pressing (CA-press) process and subsequently deformed by the current applied deformation (CA-deformation) process. The coercivity of CA-pressed magnets was nearly the same regardless of milling time; however, the coercivity of CA-deformed magnets decreased with an increase of milling time. The addition of Zn or Sn at less than 1 wt% resulted in an increase of coercivity and anti-corrosion properties of the CA-pressed isotropic magnets and CA-deformed anisotropic magnets. CA-deformed NdFeB magnets with 0.3 wt% Zn or Sn addition consisted of smaller grains and showed about 80% higher coercivity than additive-free magnets. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The inhomogeneity in microstructure and magnetic properties of a ring magnet prepared by backward extrusion with a current-applied pressure-assisted process has been investigated. The initial part (top part) of a ring magnet prepared by back extrusion shows a high coercivity which is comparable to the raw powder. It exhibits isotropic characteristics along the three orthogonal directions probably due to small deformation. The last part (bottom part) of the ring magnet has a a low coercivity with large grains because high current flows through the pressurized punches during the whole deformation process as to increase the temperature and grain growth. The middle part is under an appropriate deformation with short time exposure at high temperature, therefore it maintains a relatively high remanent polarization with high coercivity. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

This study assesses the safety and efficacy of the novel human anti-human CD154 monoclonal antibody ABI793 in rhesus monkeys.

AbstractAn integral response scaling method for reduced-height test facilities is described and validated for the local and the integral phenomena using the RELAP5 thermal-hydraulic code. In the present schematic scaling methodology, the scaling laws are generated from four scaling analyses: three-dimensional differential equation-based scaling analysis, one-dimensional differential equation-based scaling analysis, component-based scaling analysis, and overall integral scaling analysis. Through use of integral response function, scaling parameters related to four types of requirements are identified: time scaling, initial-condition scaling, transient scaling, and bifurcation-phenomena scaling requirements. In the present scaling method, flow velocities in the vertical channel and at break locations of the scaled-down model can be preserved setting up the scaling as τR= lR. The significance of the velocity preservation in the reduced-height facility is demonstrated by the RELAP5 code.To validate the present scaling method, similarity criteria from the integral response scaling method are applied to the scaled-down model of the Korea Standard Nuclear Power Plant simulating core boil-off process during midloop operation. The scaled-down model is basically developed with the length and area scales of 1/5 and 1/100, respectively. The integral simulation and local calculations for pot-boiling, blowdown, heat transfer in the steam generator, and off-take are conducted for a loss of RHR during the midloop operation to show the preservation of the similarity criteria using RELAP5.It turns out that the scaled-down model based on the present scaling method maintains well the similarity of the nondimensional parameters for the local phenomena. Furthermore, the integral simulation indicates that there are no noteworthy differences in the general trends between the prototype and scaled models.

Atrial natriuretic peptide (ANP), a 28 amino acid basic polypeptide, is known to induce histamine release from human and rat mast cells in vitro and cause a wheel formation in rat skin. However, cellular events associated with histamine release are not clearly understood. In this study, we have examined the calcium flux and cGMP formation associated with histamine release in the ANP-treated mast cells. ANP, in vitro, induced mast cell degranulation and histamine release in a dose-dependent manner. ANP also induced an enhanced calcium uptake into cells and increased the cellular level of cGMP in mast cells. A high level of calcium in the media caused an inhibition of ANP-dependent histamine release but enhanced the level of intracellular cGMP of mast cells. ANP inducing a dose-dependent increase in vascular permeability of rat skin was confirmed by the extravasation of the circulating Evans blue. The results indicate ANP induced the histamine release and an increase in vascular permeability through mast cell degranulation in cGMP-independent and calcium uptake-dependent manner.

In this study, a numerical investigation of the flow quality and total head loss of a large cavitation tunnel is conducted. Excluding the impeller, the entire tunnel is modeled, and calculations are conducted for the test section's maximum speed of 15 m/s. The numerical study showed that an edge chamfer eliminates the pressure drop in the test section, resulting in a constant cavitation number downstream, and that a diverging top diffuser, as opposed to a flat top, induces upward flow at the exit of the test section. Also, the effectiveness of the flow straightener and honeycomb in reducing turbulence has been validated. In the test section, the turbulence intensity is 0.10% and the uniformity is 0.20%. The 2nd corner has the highest head loss due to the shaft. Due to the relatively high speed, significant head losses are observed in the test section, diffuser, and first corner.

The improvement of RELAP5/MOD3.1 code predictive capability for steam condensation on an inclined surface is investigated.In modeling the secondary condensers with RELAP5, two problems were encountered with respect to condensation in vertically stacked tube walls: the capability for turbulent film condensation and the effect of the wall node size on the prediction of condensation heat transfer coefficients (HTCs). The code original model based on the Nusselt model for laminar film condensation is extended to the turbulent film condensation by introducing two previously developed models into the code.The code is further improved to properly take into account the condensation length over many nodings. To eliminate the dependence on the node size in predicting the condensation HTC of the code, film Reynolds numbers at each node are calculated recursively to track the growing condensate film thickness along the condensation length.The modified version is tested under idealized boundary conditions and with the simulation of secondary condensers and is compared with an analytical solution and the original code. It turns out that the simulation results by this modified version are independent of the node size and are in better agreement with the analytical solution than those by the original one.

•Long lesion length≥15cm is an independent predictive factor of severe dissection.•Occlusion or stenosis≥70% is an independent predictive factor of severe dissection.•Severe calcification is a protective factor against severe dissection.•Using a scoring balloon can reduce the occurrence of severe dissections.

The author reflects on the underlying crisis associated with the fundamental perception and growth in Korea. It claims that the crisis can never be solved without correcting the wrong perceptions on the country's real condition. An analysis of the post-crisis decade evaluation is offered, as well as some questions on the factors that contributed to the said difficulty. It informs that the country's economy has historically grown by depending on financial leverage.

The article focuses on the marine transportation industry of Korea. It states that the country is a leader in building ships but lacks in ship owners. It mentions that it is not easy for the country to have ship owners in form of companies but if it works on the concept of ship owner then it can do away with constraints. It highlights that the country needs to focus on finance for marine transportation.

The article focuses on the failure of the so-called "graphite-type capitalism," and the demand for a new type of capitalism, supported by abundant social liquidity between classes and bonding between social layers. It focuses on how closed access to social mobility and problems in inter-class movement, affects the development of capitalist society. It says that business enterprises including small companies should be allowed to grow in a true capitalist society.

Prostate-derived vesicles provide sperm with calcium signaling proteins required for progesterone-induced motility.