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1.
Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.  相似文献   
2.
Carbon contamination from the carbon paper/dies during spark-plasma-sintering (SPS) processing was examined in the MgAl2O4 spinel. The carbon contamination sensitively changes with the heating rate during the SPS processing. At the high heating rate of 100 °C/min, the carbon contamination having organized structures occurred over almost the entire area from the surface to deep inside the SPSed spinel disk. In contrast, at the slow heating rate of 10 °C/min, the carbon contamination having disordered structures occurred only around the surface area. The carbon phases transform into high pressure CO/CO2 gases by post-annealing in air and lead to pore formation along the grain junctions. The pore formation significantly occurs at the high heating rate due to the large amount of the contaminant carbon phases. This suggests that if once the carbon contamination was formed in the materials, it is very difficult to remove the carbon phases from the materials.  相似文献   
3.
McEliece public-key cryptosystem (PKC) is one of a few alternatives for the current PKCs that are mostly based on either the integer factoring problem (IFP) or the discrete logarithm problem (DLP) that would be solved in polynomial time after the emergence of quantum computers. The security of the McEliece PKC is based on the decoding problem and it is known that it satisfies, with an appropriate conversion, the strongest security notion, i.e., INDistinguishability of encryption against adaptively Chosen-Ciphertext Attacks (IND-CCA2), in the random oracle model under the assumption that the underlying primitive McEliece PKC satisfies a weak security notion of One-Wayness against Chosen-Plaintext Attacks (OW-CPA). OW-CPA is said to be satisfied if it is infeasible for chosen plaintext attacks to recover the whole plaintext of an arbitrarily given ciphertext. Currently, the primitive McEliece PKC satisfies OW-CPA if a parameter n/spl ges/2048 with optimum t and k is chosen since the binary work factor for (n,k,t)=(2048,1278,70) to break it with the best CPA is around 2/sup 106/, which is infeasible even if world-wide computational power is used. While the binary work factor for the next smaller parameter n=1024 is in a gray level of 2/sup 62/, it will be improved by applying Loidreau's modification that employs Frobenius automorphism in Goppa codes. In this paper, we carefully investigate the one-wayness of the Loidreau's modified McEliece PKC against ever known CPAs and new CPAs we propose, and then show that it certainly improves the one-wayness against ever known CPAs but it is vulnerable against our new CPAs. Thus, it is rather harmful to apply the new modification to the McEliece PKC.  相似文献   
4.
The porcine antral follicles, 3-6 mm in diameter, were dissected from the ovaries of mature pigs, and then granulosa and cumulus cells were isolated from each follicle. In atretic follicles, high activity of neutral Ca2+/Mg2+-dependent endonuclease and DNA ladder formation, estimated by electrophoresis, were noted in granulosa cells but not in cumulus cells. Extremely low activity of the endonuclease and no DNA ladder formation were observed in both types of cells obtained from healthy follicles. Moreover, apoptotic cells were observed histochemically among granulosa cells only. A good correlation (r = 0.987) between the endonuclease activity of granulosa cells and the progesterone/estradiol ratio of follicular fluid in each follicle was found. These results suggest that apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pigs.  相似文献   
5.
Vaccination with peptides that induce a specific immune response is a potential prophylactic or therapeutic strategy against viral infections and tumors. Because of the extensive polymorphism of the HLA loci, synthetic peptide vaccines must consist of a cocktail of peptides that bind specifically to different HLA molecules. Such cocktails should be optimized for the target population as each population has its specific HLA gene frequencies. To achieve maximum population coverage with a minimum number of peptides, information is needed on the ranking of the most frequent HLA phenotypes. We introduce the minimal phenotype panel, which is the smallest combination of HLA antigens selected so that the proportion of individuals in a population that express at least one of the antigens in the panel exceeds a desired minimum value. We developed a method for assembling minimal phenotype panels based on known HLA class I gene frequencies. We give an example based on a set of 2446 well-defined HLA-typed, random, healthy, unrelated, Dutch Caucasoid individuals. In addition, we discuss the possibility of assembling minimal phenotype panels based on two-locus haplotypes, which enables the assembly of phenotype panels from the antigens of both loci.  相似文献   
6.
This review is written to evaluate the stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug. This discussion will be useful in the development of knowledge about stereoselective cutaneous hydrolysis and its influence on stereoselective transdermal transport of many other chiral prodrugs and drugs. Propranolol prodrugs undergo stereoselective hydrolysis in hairless mouse skin homogenate and in excised skin samples during permeation; the stereoselectivity is markedly biased towards hydrolysis of the (R) isomer. Unlike the liver, the esterase activity of the skin is high in its cytosolic fraction. Most of the lipophilic propranolol prodrugs cause stereoselective permeation across hairless mouse skin. A mechanism of stereoselective permeation of propranolol prodrug across the skin has been proposed, which indicates that the stereoselectivity in permeation is resulted from the stereoselective hydrolysis of lipophilic prodrug during permeation.  相似文献   
7.
A high-performance liquid chromatographic (HPLC) separation of diacylglycerol acetates to quantitatite disaturated species of lung phosphatidylcholine (PC) was studied. The diacylglycerol acetates were applied on a reversed phase column, eluted by an isocratic solvent, acetonitrile/isopropanol/water (35:15:1, v/v/v) at a flow rate of 1 ml/min, and detected by differential refractometry (RI). This isocratic HPLC method was useful to separate disaturated species from the others of lung PC. The quantitative analysis of the molecular species separated by HPLC was studied by RI detection. Chroamtograms obtained by RI detection and radioactivity determination of diacylglycerol [3H]acetates prepared by [3H]acetic anhydride were almost identical. The RI detector responsed in the same degree for different, authentic standards of diacylglycerol acetates. The detection limit with RI detection was about 30 nmoles. Molecular species of PCs from human lung and carcinoma tissues were analyzed by this HPLC method. The contents of disaturated species were very similar to those reported previously. These results indicate that RI detection is very useful in the nmole range for the quantitative analysis among the molecular species containing disaturated species.  相似文献   
8.
9.
The Co/MFI(SiO2/Al2O3 = 30) were prepared by a precipitation method with NaOCl in alkali solutions exhibited high activities to N2 at 250 °C for the selective catalytic reduction (SCR) of NOx. These catalysts showed two UV–vis bands at 700 and 400 nm, indicating the presence of octahedral Co(III) as well as tetrahedral Co(II). The high SCR activity over such Co(III, II)/MFI(30) seems to come from Co(III)---O moieties. The Co(II)MFI(30) catalysts prepared from Co(II)Cl2 exhibited low SCR activities due to the presence of tetrahedral Co(II) ions in MFI. Less CO formation occurred over Co/MFI catalysts. The Fe/MFI(30) catalyst exhibited high activity due to the presence of some Fe---O species in MFI but more amount of CO were produced during SCR. H/MFI(30) catalyst exhibited a good SCR activity. However, more amount of carbonaceous deposits were produced on it. The correlation between acid concentration and SCR activity was discussed over H/MFIs.  相似文献   
10.
A study of the pyrolysis of an aqueous solution of manganese nitrate in the presence of silver compounds has been carried out. Thermal analysis showed that the MnO2 formation temperature and the transformation temperature from MnO2 to Mn2O3 shifted towards a lower temperature in the presence of silver acetate. A large particle-size and high crystallinity MnO2 was formed; this may be a useful method of making an excellent tantalum capacitor with high capacitance.  相似文献   
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