1,018 research outputs found

    Comparing two-phase locking and optimistic concurrency control protocols in multiprocessor real-time databases

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    Previous studies (Haritsa et al., 1990) have shown that optimistic concurrency control (OCC) generally performs better than lock-based protocols in disk-based real-time database systems (RTDBS). We compare the two concurrency control protocols in both disk-based and memory-resident multiprocessor RTDBS. Based on their performance characteristics, a new lock-based protocol, called two phase locking-lock write all (2PL-LW), is proposed. The results of our performance evaluation experiments show that different characteristics of the two environments indeed have great impact on the protocols' performance. We identify such system characteristics and show that our new lock-based protocols, 2PL-LW, is better than OCC in meeting transaction deadlines in both disk-based and memory-resident RTDBS.published_or_final_versio

    Splice variants of DOMINO control Drosophila circadian behavior and pacemaker neuron maintenance.

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    Circadian clocks control daily rhythms in behavior and physiology. In Drosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons generating locomotor rhythms. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify the Drosophila SWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM in circadian neurons eliminates morning anticipatory activity under light dark cycle and impairs behavioral rhythmicity in constant darkness. Interestingly, the two major splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion mainly leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period without affecting the circadian rhythmicity. Both DOM-A and DOM-B bind to the promoter regions of key pacemaker genes period and timeless, and regulate their protein expression. However, we identify that only DOM-A is required for the maintenance of sLNvs and transcription of pdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that two splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance

    Persistent Expression Changes of Fibrosis-Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

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    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 12% of very fine respirable dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dustinduced changes of the expression of fibrosisrelated genes, and to identify specific signaling pathways involved in lunar dustinduced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in noseonly inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 milligrams per cubic meters of lunar dust. Five rats per group were euthanized at 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The bronchoalveolar lavage fluid (BALF) was collected by lavaging with phosphatebuffered saline (PBS). A zymosaninduced luminolbased chemiluminescence assay was used to assess the activity of BAL cells. The lavaged lung tissue was snap frozen in LN2 and total RNA was isolated using the Qigen RNeasy kit. The expression of 84 fibrosisrelated genes were analyzed using the RT2 Profiler PCR Array technique. The expression of 18 genes of interest were further measured using realtime PCR technique in all the samples. 10 out of 18 genes of interest showed persistently significant expression changes in the local lung tissue exposed to lunar dust, indicating a prolonged proinflammatory response. The expressions of several of these genes were dose and timedependent and were significantly correlated with other pathological parameters. The potential signaling pathways and upstream regulators were further analyzed using IPA pathway analysis tool based on the gene expression data. The data presented in this study, for the first time, explore the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dustinduced toxicity in humans on earth

    Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

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    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 12% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in noseonly inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dosedependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue

    The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury

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    Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents. Mechanistically, we found that AIM2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. Our results suggest that AIM2 may be a new therapeutic target for ionizing radiation exposure

    Structure of the Ī³-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-Ī³-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

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    Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific Ī³-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8ā€…Ć… resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-Ī³-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and Ī³-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-Ī³-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

    Liver transplantation for acute-on-chronic liver failure

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    Purpose: To evaluate the outcome of liver transplantation for acute-on-chronic liver failure. Patients and methods: From November 1991 to December 2007, 517 patients underwent liver transplantation at Queen Mary Hospital, Hong Kong. Among them, 149 had acute-on-chronic liver failure as defined in the recent Asian Pacific Association for the Study of Liver Consensus Meeting. Their clinical data were reviewed and their survival outcomes were compared with those of patients who underwent liver transplantation for fulminant hepatic failure and for cirrhosis only in the same period. Results: The patients with acute-on-chronic liver failure included 50 patients having acute exacerbation of chronic hepatitis B and 99 cirrhotic patients with acute deterioration. Their median model for end-stage liver disease scores were 35 and 37, respectively. Preoperative infection (35%), hepatorenal syndrome (38%), and respiratory failure (28.8%) were common. One hundred and three patients received living donor liver grafts and 46 patients received deceased donor liver grafts. The hospital mortality rate was 4.7%. The 5-year survival rates were 93.2% for patients with acute exacerbation of chronic hepatitis B and 90.5% for cirrhotic patients with acute deterioration. The results were similar to those of the patients with fulminant hepatic failure (n = 37) and the patients having cirrhosis only (n = 301). Conclusions: Liver transplantation for acute-on-chronic liver failure is life-saving, and the survival rates it attains are similar to those attained by transplantation for other liver conditions.published_or_final_versionSpringer Open Choice, 21 Feb 201

    Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

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    The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78ā€…Ć… resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-Ī±-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other Ī±-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

    Hamiltonian Description of Composite Fermions: Magnetoexciton Dispersions

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    A microscopic Hamiltonian theory of the FQHE, developed by Shankar and myself based on the fermionic Chern-Simons approach, has recently been quite successful in calculating gaps in Fractional Quantum Hall states, and in predicting approximate scaling relations between the gaps of different fractions. I now apply this formalism towards computing magnetoexciton dispersions (including spin-flip dispersions) in the Ī½=1/3\nu=1/3, 2/5, and 3/7 gapped fractions, and find approximate agreement with numerical results. I also analyse the evolution of these dispersions with increasing sample thickness, modelled by a potential soft at high momenta. New results are obtained for instabilities as a function of thickness for 2/5 and 3/7, and it is shown that the spin-polarized 2/5 state, in contrast to the spin-polarized 1/3 state, cannot be described as a simple quantum ferromagnet.Comment: 18 pages, 18 encapsulated ps figure
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