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A Disk-On-Module (DOM) is a NAND flash memory-based device with legacy I/O interface which does not require any special device driver due to the presence of flash translation layer (FTL). FTL is an intermediate software layer which makes DOMs look like conventional hard disk drives. Since DOMs are usually used in mass-market consumer electronics devices, they are extremely cost-sensitive; hence FTL should be able to run in a severely resource-constrained environment. In this paper, we propose TinyFTL, a new FTL which employs an efficient memory management scheme for DOMs with a very small amount of memory. TinyFTL divides the mapping information into multiple levels and caches only recently-accessed mapping information in memory. According to experimental evaluation, TinyFTL shows the performance comparable to or better than the existing FTLs with only 4.36.2% of memory requirement (12KB) for 16 GB NAND flash memory. Index Terms--disk-on-module, flash translation layer, NAND flash memory, cache management

Multiple etiologies of liver injury are associated with fibrosis in which the key event is the activation of hepatic stellate cells (HSCs). Although microRNAs (miRNAs) are reportedly involved in fibrogenesis, the complete array of miRNA signatures associated with the disease has yet to be elucidated. Here, deep sequencing analysis revealed that compared to controls, 80 miRNAs were upregulated and 21 miRNAs were downregulated significantly in the thioacetamide (TAA)-induced mouse fibrotic liver. Interestingly, 58 of the upregulated miRNAs were localized to an oncogenic miRNA megacluster upregulated in liver cancer. Differential expression of some of the TAA-responsive miRNAs was confirmed, and their human orthologs were similarly deregulated in TGF-β1-activated HSCs. Moreover, a functional analysis of the experimentally validated high-confidence miRNA targets revealed significant enrichment for the GO terms and KEGG pathways involved in HSC activation and liver fibrogenesis. This is the first comprehensive report of miRNAs profiles during TAA-induced mouse liver fibrosis.

ABSTRACTSevere hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, β) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl−/−mice show more severe symptoms than do wild-type (Axl+/+) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl4). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation.

Even though bupropion is first-line pharmacological agent for smoking cessation, not all the smokers successfully quit smoking by bupropion. It means other factors like genetic predisposition could contribute to the therapeutic outcome.

Excessive internet video game play (EIGP) has emerged as a leading cause of behavioral and developmental problems in adolescents. Recent research has implicated the role of striatal dopaminergic system in the behavioral maladaptations associated with EIGP. This study investigates the reward-dependence characteristics in EIGP adolescents as it potentially relates to genetic polymorphisms of the dopaminergic system and temperament. Seventy-nine male EIGP adolescents and 75 age- and gender-matched healthy comparison adolescents were recruited. Associations were tested with respect to the reward-dependence (RD) scale in Cloninger’s Temperament and Character Inventory and the frequencies of 3 dopamine polymorphisms: Taq1A1 allele of the dopamine D2 receptor (DRD2 Taq1A1) and Val158Met in the Catecholamine-O-Methyltransferase (COMT) genes. The Taq1A1 and low activity (COMTL) alleles were significantly more prevalent in the EIGP group relative to the comparison group. The present EIGP group had significantly higher RD scores than controls. Within the EIGP group, the presence of the Taq1A1 allele correlated with higher RD scores. Our findings suggest that EIGP subjects have higher reward dependency and an increased prevalence of the DRD2 Taq1A1 and COMTLalleles. In particular, the DRD2 Taq1A1 allele seems to be associated with reward dependence in EIGP adolescents.

In the Drosophila RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) direct Argonaute2 (Ago2), an endonuclease, within the RNA-induced silencing complex (RISC) to cleave complementary mRNA targets. In vitro studies have shown that, for each siRNA duplex, RISC retains only one strand, the guide, and releases the other, the passenger, to form a holo-RISC complex. Here, we have isolated a new Ago2 mutant allele and provide, for the first time, in vivo evidence that endogenous Ago2 slicer activity is important to mount an RNAi response in Drosophila. We demonstrate in vivo that efficient removal of the passenger strand from RISC requires the cleavage activity of Ago2. We have also identified a new intermediate complex in the RISC assembly pathway, pre-RISC, in which Ago2 is stably bound to double-stranded siRNA.

High homocysteine serum level has been regarded as one of the important factors that influence the development of schizophrenia. Genetic variations of methylenetetrahydrofolate reductase, which is a main enzyme reducing homocysteine level, are reported in schizophrenic patients. We measured the serum level of homocysteinefolate and methylenetetrahydrofolate reductase C677TA1298C gene polymorphism in 235 patients with schizophrenia. Plasma homocysteine levels were higher and folate levels were lower in patients than in comparison subjects. Variations of C677T were more frequent in patients than in comparison subjects. Patients with the 677TT genotype showed higher homocysteine levels than patients with the CC and CT genotypes. These findings suggest that folate supplement may be beneficial to some schizophrenic patients with homocysteinemia due to the genetic defect of methylenetetrahydrofolate reductase.

We assessed catechol-O-methyltransferase (COMT) polymorphism in 132 first-onset schizophrenic patients and 80 healthy controls. The relationship between COMT polymorphism and cognitive function, aggression and psychiatric symptoms was tested in the schizophrenic group. COMTLcarrier had higher digit span score and lower similarity score than COMTHhomozygote. COMTLcarrier had higher attention and delusion scores and lower inappropriate affect scores than COMTHhomozygote. Attention and delusion scores of COMTLallele were higher than COMTHallele. COMTLgroup had higher aggression than COMTHhomozygote. Our results support the theory that COMTLallele was related with increased tonic dopamine activity and cognitive ‘stability’, which may induce cognitive inflexibility in schizophrenia.

We showed that N-Ethyl-N-Nitrosourea (ENU) induces teratogenesis in larvae of the self-fertilizing fish Rivulus marmoratus. We discuss this and the issue of carcinogenesis caused by ENU. Teratogenesis Carcinog. Mutagen. 22:363–367, 2002. © 2002 Wiley-Liss, Inc.

Glutaryl 7-aminocephalosporanic acid (GL-7-ACA) acylase of Pseudomonassp. strain GK16 catalyzes the cleavage of the amide bond in the GL-7-ACA side chain to produce glutaric acid and 7-aminocephalosporanic acid (7-ACA). The active enzyme is an (αβ)2heterotetramer of two non-identical subunits that are cleaved autoproteolytically from an enzymatically inactive precursor polypeptide. In this study, we prepared and characterized a chemically modified enzyme, and also examined an effect of the modification on enzyme catalysis and autocatalytic processing of the enzyme precursor. We found that treatment of the enzyme with cyanate ion led to a significant loss of the enzyme activity. Structural and functional analyses of the modified enzyme showed that carbamylation of the free α-amino group of the N-terminal Ser-199 of the β subunit resulted in the loss of the enzyme activity. The pH dependence of the kinetic parameters indicates that a single ionizing group is involved in enzyme catalysis with pKa= 6.0, which could be attributed to the α-amino group of the N-terminal Ser-199. The carbamylation also inhibited the secondary processing of the enzyme precursor, suggesting a possible role of the α-amino group for the reaction. Mutagenesis of the invariant N-terminal residue Ser-199 confirmed the key function of its side chain hydroxyl group in both enzyme catalysis and autoproteolytic activation. Partial activity and correct processing of a mutant S199T were in agreement with the general mechanism of N-terminal nucleophile hydrolases. Our results indicate that GL-7-ACA acylase utilizes as a nucleophile Ser-199 in both enzyme activity and autocatalytic processing and most importantly its own α-amino group of the Ser-199 as a general base catalyst for the activation of the hydroxyl group both in enzyme catalysis and in the secondary cleavage of the enzyme precursor. All of the data also imply that GL-7-ACA acylase is a member of a novel class of N-terminal nucleophile hydrolases that have a single catalytic center for enzyme catalysis.

The soldering quality of a Cu ribbon onto the Ag busbars of solar cells is one of the key factors affecting the cell-to-module loss and durability of a silicon photovoltaic module. In this study, we examined the effects of the surface chemistry and morphology of the screen-printed Ag busbars on the solder wettability and bonding uniformity of the Cu ribbon over the length of the busbar during the tabbing process. The surface of the as-fired Ag busbar was covered by a thin glass layer originating from the glass frit contained in the Ag paste. The presence of the thin glass layer significantly decreased the wettability of the solder, leading to the formation of voided regions at the solder/busbar interface. Although it had only a minor influence on solder wettability, increasing the roughness of the busbar surface resulted in the formation of more voided regions at the solder/busbar interface.