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1.
Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.  相似文献   
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Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.  相似文献   
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Tsay  Ming-yueh  Tseng  Yu-wei  Wu  Tai-luan 《Scientometrics》2019,121(3):1323-1338
Scientometrics - In this study, scholarly communication systems provided by commercial services and open access systems are examined on the basis of the comprehensiveness and uniqueness of their...  相似文献   
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Currently, ethnic and racial minority individuals represent a large proportion of the U.S. population, and researchers expect that they will represent the majority of the population by 2050. This shift in U.S. demographics calls for a greater awareness and integration of cultural issues into the assessment and treatment of ethnically and linguistically diverse clients. This article examines the unique beliefs and manifestations of illnesses among Haitians in connection with the American Psychological Association's (APA, 2002) Multicultural Guidelines. The authors use a common culture-bound syndrome, Séizisman, to illustrate the cultural beliefs, assessment, and treatment of illnesses among Haitians. In so doing, they demonstrate how to incorporate the APA Multicultural Guidelines into treatment with clients of diverse cultural and racial backgrounds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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Ho  Y. S.  Chiu  C. H.  Tseng  T. M.  Chiu  W. T. 《Scientometrics》2003,57(3):369-376
Honour Index (HoI), a method to evaluate research performance within different research fields, was derived from the impact factor (IF). It can be used to rate and compare different categories of journals. HoI was used in this study to determine the scientific productivity of stem cell research in the Asian Four Dragons (Hong Kong, Singapore, South Korea and Taiwan) from 1981 to 2001. The methodology applied in this study represents a synthesis of universal indicator studies and bibliometric analyses of subfields at the micro-level. We discuss several comparisons, and conclude the developmental trend in stem cell research for two decades. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   
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Applies the technique of parallel processing to concept learning. A parallel version-space learning algorithm based upon the principle of divide-and-conquer is proposed. Its time complexity is analyzed to be O(k log2n) with n processors, where n is the number of given training instances and k is a coefficient depending on the application domains. For a bounded number of processors in real situations, a modified parallel learning algorithm is then proposed. Experimental results are then performed on a real learning problem, showing that our parallel learning algorithm works, and being quite consistent with the results of theoretical analysis. We conclude that when the number of training instances is large, it is worth learning in parallel because of its faster execution  相似文献   
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Packet scheduling in a WCDMA system poses a new challenge due to its nature of variable bit rates and location-dependent, time-varying channel conditions. In this work, three new downlink scheduling algorithms for a WCDMA base station are proposed to support multimedia transmissions. Using a credit management and a compensation mechanism, our algorithms provide rate guarantee and fair access to mobile terminals. In particular, we propose to allow a user to simultaneously use multiple OVSF codes in a time-sharing manner, which we call a multicode, shared model. Using multiple codes allows us to compensate those users suffering from bad communication quality or even errors. The proposed schemes can tolerate a multistate link condition (compared to the typically assumed two-state, or good-or-bad, link condition) by adjusting the number of OVSF codes and the spreading factor of each code. Simulation results show that the proposed schemes do achieve higher bandwidth utilization while keeping transmission delay low.  相似文献   
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