Backup Mechanism Research Articles

DNA polymerases ζ and Rev1 mediate error-prone bypass of non-B DNA structures

DNA polymerase ζ (Pol ζ) and Rev1 are key players in translesion DNA synthesis. The error-prone Pol ζ can also participate in replication of undamaged DNA when the normal replisome is impaired. Here we define the nature of the replication disturbances that trigger the recruitment of error-prone polymerases in the absence of DNA damage and describe the specific roles of Rev1 and Pol ζ in handling these disturbances. We show that Pol ζ/Rev1-dependent mutations occur at sites of replication stalling at short repeated sequences capable of forming hairpin structures. The Rev1 deoxycytidyl transferase can take over the stalled replicative polymerase and incorporate an additional ‘C’ at the hairpin base. Full hairpin bypass often involves template-switching DNA synthesis, subsequent realignment generating multiply mismatched primer termini and extension of these termini by Pol ζ. The postreplicative pathway dependent on polyubiquitylation of proliferating cell nuclear antigen provides a backup mechanism for accurate bypass of these sequences that is primarily used when the Pol ζ/Rev1-dependent pathway is inactive. The results emphasize the pivotal role of noncanonical DNA structures in mutagenesis and reveal the long-sought-after mechanism of complex mutations that represent a unique signature of Pol ζ.

Backup and recovery mechanism of Web anti-tamper system based on LZMA and multi-version

Because the functions of backup and recovery are usually ignored in the Web anti-tamper system,a Web anti-tamper system model was proposed in this paper,based on which a safe and efficient remote backup and recovery system was given.The multi-version management technique of backup data was used for restoring the data of different versions and different periods.The Lempel-Ziv-Markov chain Algorithm(LZMA) was used to compress the backup data for improving the disk utilization.The Data Encryption Standard(DES) and File Transfer Protocol(FTP) were used for secure remote data storage and transmission.Finally,the system performance test shows it can effectively backup and recover the Web server data without affecting the Web server load and recover a single page within 100 ms.It is an effective means to solve the Web tampering problem.

DsDNA ASCs for caspase 8-mediated apoptosis

dsDNA ASCs for caspase 8-mediated apoptosis

Malaria Parasite-Synthesized Heme Is Essential in the Mosquito and Liver Stages and Complements Host Heme in the Blood Stages of Infection

Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS), and the last enzyme, ferrochelatase (FC), in the heme-biosynthetic pathway of Plasmodium berghei (Pb). The wild-type and knockout (KO) parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-14C] aminolevulinic acid (ALA). We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.

Research on management system of paperless electronic medical record

This paper discussed on the importance of management system of paperless electronic medical record and pointed out that we would encountered lots of problems during the construction of paperless electronic medical record management system including authenticity,legal effect,similarity,safety,mistakes and missing of medical records.This paper analyzed these problems and proposed corresponding countermeasures including developing safety management system,whole-process monitoring of medical record quality,enhancing archive management,developing backup and recovery mechanisms,improving secrecy and authorization system,promoting borrowing management,performing copy system,strengthening electronic signature management,implementing unique number management and enhancing overall quality of personnel Key words: Paperless; Electronic medical record; Management system

SAT0162 Complexes of anti-CRP autoantibodies and CRP-opsonised apoptotic cell remnants form a pro-inflammatory pathogen in systemic lupus erythematosus

BackgroundAn efficient clearance of dying and dead cells is essential to avoid inflammation and autoimmunity. Therefore, a plethora of opsonizing molecules secures silent clearance [1]. Opsonisation with C-reactive protein (CRP)...

Climatic trends of the equatorial undercurrent: A backup mechanism for sustaining the equatorial Pacific production

The Equatorial Undercurrent (EUC) is the major source of iron to the equatorial Pacific and it is sensitive to climatic changes as other components of the tropical Pacific. This work proposes a methodology based on a Lagrangian approach aimed at understanding the changes in the transport of iron rich waters to the EUC in a future climate change scenario, using climate model data from an Earth system model. A selected set of regions from the northern and southern extra-equatorial Pacific has been chosen. These regions are characterized by the presence of iron sources from continental shelf processes like the Papua New Guinea region and atmospheric deposition like the northern subtropical gyre. The trajectories that reach the EUC during the 20th and the 21st century departing from these areas have been analyzed using a set of statistics designed to determine variations in the amount of transport and in the travel times of the water masses. The transport of waters to the EUC from the north Pacific subtropical gyre and from the Bismarck Sea is projected to increase during the 21st century. The increase is particularly significant for water masses from the northern subtropical gyre, with travel times lower than 10years in the second half of the 21st century. This increased interaction between the extra-tropics and the EUC may bring additional iron-rich waters in the high-nutrient low-chlorophyll region of the equatorial Pacific compatibly with the significant increase of the simulated net primary production found in the biogeochemical model, thus partly offsetting the anticipated decrease of production implied by the surface warming.

Systems Modelling of NHEJ Reveals the Importance of Redox Regulation of Ku70/80 in the Dynamics of DNA Damage Foci

The presence of DNA double-stranded breaks in a mammalian cell typically activates the Non-Homologous End Joining (NHEJ) pathway to repair the damage and signal to downstream systems that govern cellular decisions such as apoptosis or senescence. The signalling system also stimulates effects such as the generation of reactive oxygen species (ROS) which in turn feed back into the damage response. Although the overall process of NHEJ is well documented, we know little of the dynamics and how the system operates as a whole. We have developed a computational model which includes DNA Protein Kinase (DNA-PK) dependent NHEJ (D-NHEJ) and back-up NHEJ mechanisms (B-NHEJ) and use it to explain the dynamic response to damage induced by different levels of gamma irradiation in human fibroblasts. Our work suggests that the observed shift from fast to slow repair of DNA damage foci at higher levels of damage cannot be explained solely by inherent stochasticity in the NHEJ system. Instead, our model highlights the importance of Ku oxidation which leads to increased Ku dissociation rates from DNA damage foci and shifts repair in favour of the less efficient B-NHEJ system.

Cell cycle stage-specific roles of Rad18 in tolerance and repair of oxidative DNA damage

The E3 ubiquitin ligase Rad18 mediates tolerance of replication fork-stalling bulky DNA lesions, but whether Rad18 mediates tolerance of bulky DNA lesions acquired outside S-phase is unclear. Using synchronized cultures of primary human cells, we defined cell cycle stage-specific contributions of Rad18 to genome maintenance in response to ultraviolet C (UVC) and H2O2-induced DNA damage. UVC and H2O2 treatments both induced Rad18-mediated proliferating cell nuclear antigen mono-ubiquitination during G0, G1 and S-phase. Rad18 was important for repressing H2O2-induced (but not ultraviolet-induced) double strand break (DSB) accumulation and ATM S1981 phosphorylation only during G1, indicating a specific role for Rad18 in processing of oxidative DNA lesions outside S-phase. However, H2O2-induced DSB formation in Rad18-depleted G1 cells was not associated with increased genotoxin sensitivity, indicating that back-up DSB repair mechanisms compensate for Rad18 deficiency. Indeed, in DNA LigIV-deficient cells Rad18-depletion conferred H2O2-sensitivity, demonstrating functional redundancy between Rad18 and non-homologous end joining for tolerance of oxidative DNA damage acquired during G1. In contrast with G1-synchronized cultures, S-phase cells were H2O2-sensitive following Rad18-depletion. We conclude that although Rad18 pathway activation by oxidative lesions is not restricted to S-phase, Rad18-mediated trans-lesion synthesis by Polη is dispensable for damage-tolerance in G1 (because of back-up non-homologous end joining-mediated DSB repair), yet Rad18 is necessary for damage tolerance during S-phase.

Big Brains, Meat, Tuberculosis, and the Nicotinamide Switches: Co-Evolutionary Relationships with Modern Repercussions?

Meat-eating was a game changer for human evolution. We suggest that the limiting factors for expanding brains earlier were scarcities of nicotinamide and tryptophan. In humans and some other omnivores, lack of meat causes these deficiencies. Nicotinamide adenine dinucleotide (NADH) is necessary to synthesize adenosine triphosphate (ATP) via either glycolysis or via the mitochondrial respiratory chain. NAD consumption is also necessary for developmental and repair circuits. Inadequate supplies result in “de-evolutionary” brain atrophy, as seen with pellagra. If trophic nicotinamide/tryptophan was a “prime mover” in building bigger brains, back-up mechanisms should have evolved. One strategy may be to recruit extra gut symbionts that produce NADH precursors or export nicotinamide (though this may cause diarrhea). We propose a novel supplier TB that co-evolved early, which did not originally and does not now inevitably cause disease. TB has highly paradoxical immunology for a pathogen, and secretes and is inhibited by nicotinamide and its analogue, isoniazid. Sharp declines in TB and diarrhea correlated with increased meat intake in the past, suggesting that dietary vitamin B3 and tryptophan deficiencies (also associated with poor cognition and decreased lifespans) are still common where meat is unaffordable.

Two Aspect Authentication System Using Secure Mobile Devices

Mobile devices are becoming more pervasive and more advanced with respect to their processing power and memory size. Relying on the personalized and trusted nature of such devices, security features can be deployed on them in order to uniquely identify a user to a service provider. In this paper, we present a strong authentication mechanism that exploits the use of mobile devices to provide a two-aspect authentication system. Our approach uses a combination of one-time passwords, as the first authentication aspect, and credentials stored on a mobile device, as the second aspect, to offer a strong and secure authentication approach. By Adding an SMS-based mechanism is implemented as both a backup mechanism for retrieving the password and as a possible mean of synchronization. We also present an analysis of the security and usability of this mechanism. The security protocol is analyzed against an adversary model; this evaluation proves that our method is safe against various attacks, most importantly key logging, shoulder surfing, and phishing attacks. Our simulation result evaluation shows that, although our technique does add a layer of indirectness that lessens usability; participants were willing to trade-off that usability for enhanced security once they became aware of the potential threats when using an untrusted computer.

LHCb Conditions database operation assistance systems

The Conditions Database (CondDB) of the LHCb experiment provides versioned, time dependent geometry and conditions data for all LHCb data processing applications (simulation, high level trigger (HLT), reconstruction, analysis) in a heterogeneous computing environment ranging from user laptops to the HLT farm and the Grid. These different use cases impose front-end support for multiple database technologies (Oracle and SQLite are used). Sophisticated distribution tools are required to ensure timely and robust delivery of updates to all environments. The content of the database has to be managed to ensure that updates are internally consistent and externally compatible with multiple versions of the physics application software. In this paper we describe three systems that we have developed to address these issues. The first system is a CondDB state tracking extension to the Oracle 3D Streams replication technology, to trap cases when the CondDB replication was corrupted. Second, an automated distribution system for the SQLite-based CondDB, providing also smart backup and checkout mechanisms for the CondDB managers and LHCb users respectively. And, finally, a system to verify and monitor the internal (CondDB self-consistency) and external (LHCb physics software vs. CondDB) compatibility. The former two systems are used in production in the LHCb experiment and have achieved the desired goal of higher flexibility and robustness for the management and operation of the CondDB. The latter one has been fully designed and is passing currently to the implementation stage.

Deployment of TCP University of Bridgeport (UB) to Control Law Enforcement Department over Wireless Mesh Network

Transmission Control Protocol (TCP) is the most reliable protocol. That was previously introduced for wired networks only. Lately the TCP started to act poorly for several factors due to the advent of wireless network. The represented factors which need to be addressed are recovery mechanism, backup mechanism, mobility, congestion window and maximum packet size. Based on existing variants, new were introduced. The most two debated variants are Vegas and Westwood which motivated many researches. However, the number of studies proved that Vegas could perform more efficiency than other variants during the congested network whereas Westwood could consume less bandwidth. Hence, in our previous publications, we already proved by integrating some features of Vegas and Westwood to get better and more stable variant even in high congested network. It is called TCP University of Bridgeport (TCP-UB).Based on a previous simulation, TCP-UB proved a high efficiency, less bandwidth consumption and stability from static and mobility point of view. Therefore, in this paper we are using NS2 simulator to perform TCP-UB over wireless mesh network supported with manhattan mobility model. It provides robust and faster transmission service among several police stations in Connecticut, USA.Furthermore, we are comparing TCP-UB with Vegas and Westwood from a static and mobility point of view based on bandwidth consumption and congestion window scenario. On the basis of findings, we validate that TCP-UB is also better performer even over wireless mesh network.

SSR-CDPS: A Novel Continuous Data Protection System Supporting Service Recovery

With the rapid development of computer networks, invasion and attack becomes more and more frequent in network environment. Therefore, insuring the information system continuously and correctly working has become an urgent problem in the information security field. And continuous data protection (CDP) supporting service recovery provides us a good idea to resolve it. In this article, we have designed and implemented a continuous data protection system supporting service recovery, which is named SSR-CDPS. The basic design idea of the SSR-CDPS architecture is dividing the whole protection process into three stages: monitoring, protecting and recovery. Meanwhile, we propose a multi versioning data backup mechanism for the protecting process and a novel file failure recovery mechanism. Especially, we transfer the full copy operation of file contents into the merely slight modification operation on the FAT table, MFT table or other similar data structures; so that we achieve the aim of greatly reducing the direct disks read and write overhead. The test toward the SSR-CDPS prototype system shows that the system can significantly improve the efficiency of data protection within limited change to the existing file system; thus, it can meet the high real-time and the continuity requirements of the information system recovery applications.

Factors affecting the variability of the central mechanisms for maintaining bilingualism

The article discusses the probable role of many factors that determine the individual variety of the neurophysiological mechanisms that provide the opportunity to learn and use fluently two or more languages. The formation of the speech function is affected by both the general factors for bilinguals and monolinguals, as well as by the specific characteristic of bilingualism. General factors include genetic and environmental impacts explaining the diversity of individual options for the development of the morphofunctional organization of the speech function. Bilinguals, obviously, have an even wider variation of the central maintenance of speech ability, due to the combination of different conditions that influence the language environment, which include the age of second language acquisition, the language proficiency, the linguistic similarity of the languages, the method of their acquisition, intensity of use, and the area where each language is used. The influence of these factors can be mediated in different ways by the individual characteristics of the bilingual’s brain. Being exposed to two languages from the first days of life, the child uses for the development of speech skills the unique features of the brain that exist only at the initial stages of postnatal ontogenesis. At an older age, mastering a second language requires much more effort, when, in the course of maturation, the brain acquires new additional possibilities but permanently loses that special “bonus” that nature gives to a small child only in the first months of life. Large individual variability patterns of activation of the cortex during verbal activity in older bilinguals, compared with the younger ones, allows us to assume that the brain of the older bilingual mastering a new language is forced to manipulate a large number of backup mechanisms, and this is reflected in an increase in the variation of the cerebral processes responsible for speech functions. In addition, there is a serious reason to believe that learning a second language contributes to the expansion of the functional capabilities of the brain and creates the basis for successful cognitive activity.

Estimating the Microtubule GTP Cap Size In Vivo

Microtubules (MTs) polymerize via net addition of GTP-tubulin subunits to the MT plus end, which subsequently hydrolyze to GDP-tubulin in the MT lattice. Relatively stable GTP-tubulin subunits create a "GTP cap" at the growing MT plus end that suppresses catastrophe. To understand MT assembly regulation, we need to understand GTP hydrolysis reaction kinetics and the GTP cap size. In vitro, the GTP cap has been estimated to be as small as one layer (13 subunits) or as large as 100-200 subunits. GTP cap size estimates in vivo have not yet been reported. Using EB1-EGFP as a marker for GTP-tubulin in epithelial cells, we find on average (1) 270 EB1 dimers bound to growing MT plus ends, and (2) a GTP cap size of ∼750 tubulin subunits. Thus, in vivo, the GTP cap is far larger than previous estimates in vitro, and ∼60-fold larger than a single layer cap. We also find that the tail of a large GTP cap promotes MT rescue and suppresses shortening. We speculate that a large GTP cap provides a locally concentrated scaffold for tip-tracking proteins and confers persistence to assembly in the face of physical barriers such as the cell cortex.

Increased lysine production by flux coupling of the tricarboxylic acid cycle and the lysine biosynthetic pathway—Metabolic engineering of the availability of succinyl-CoA in Corynebacterium glutamicum

In this study, we demonstrate increased lysine production by flux coupling using the industrial work horse bacterium Corynebacterium glutamicum, which was mediated by the targeted interruption of the tricarboxylic acid (TCA) cycle at the level of succinyl-CoA synthetase. The succinylase branch of the lysine production pathway functions as the bridging reaction to convert succinyl-CoA to succinate in this aerobic bacterium. The mutant C. glutamicum ΔsucCD showed a 60% increase in the yield of lysine when compared to the advanced lysine producer which was used as parent strain. This mutant was highly vital and exhibited only a slightly reduced specific growth rate. Metabolic flux analysis with 13C isotope studies confirmed that the increase in lysine production was mediated by pathway coupling. The novel strain exhibited an exceptional flux profile, which was closer to the optimum performance predicted by in silico pathway analysis than to the large set of lysine-producing strains analyzed thus far. Fluxomics and transcriptomics were applied as further targets for next-level strain engineering to identify the back-up mechanisms that were activated upon deletion of the enzyme in the mutant strain. It seemed likely that the cells partly recruited the glyoxylate shunt as a by-pass route. Additionally, the α-ketoglutarate decarboxylase pathway emerged as the potential compensation mechanism. This novel strategy appears equally promising for Escherichia coli, which is used in the industrial production of lysine, wherein this bacterium synthesizes lysine exclusively by succinyl-CoA activation of pathway intermediates. The channeling of a high flux pathway into a production pathway by pathway coupling is an interesting metabolic engineering strategy that can be explored to optimize bio-production in the future.

TCP-UB: A New Congestion Aware Transmission Control Protocol Variant

Transmission control protocol (TCP) is a connection oriented protocol for several types of distributed applications. TCP is reliable particularly for traditional fixed networks. With emergence of faster wireless networks, TCP has been performing poorly in its original format. The performance of TCP is affected due to assorted factors including congestion window, maximum packet size, retry limit, recovery mechanism, backup mechanism and mobility. To overcome deficiency of original TCP, Several modifications have been introduced to improve network quality. The mobility is a major hurdle in degrading the performance of mobile wireless networks. In this paper, we introduce and implement new TCP variant University of Bridgeport (UB) that combines the features of TCP Westwood and Vegas. We examine the performance of TCP-UB, Vegas and Westwood using different realistic scenarios. NS2 simulator demonstrates the stability of TCP-UB as compared with TCP Vegas and Westwood in highly congested networks from the mobility point of view.

The role of TLR2 in the host response to pneumococcal pneumonia in absence of the spleen

BackgroundAsplenic individuals are susceptible for overwhelming infection with Streptococcus pneumoniae, carrying a high mortality. Although Toll-like receptor (TLR)-2 is considered the major receptor for Gram-positive bacteria in innate immunity, it does not play a major role in host defense against pneumococcal pneumonia. We wanted to investigate if in absence of an intact spleen as a first line of defense, the role of TLR2 during pneumococcal pneumonia becomes more significant, thereby explaining its insignificant role during infections in immune competent hosts.MethodsWe intranasally infected splenectomized wildtype (WT), TLR2 knock-out (KO) and TLR2/4 double KO mice with either serotype 2 or 3 S. pneumoniae.ResultsThere were no differences between asplenic WT and TLR2KO mice of bacterial loads in lung homogenates and blood, cytokine and chemokine levels in the lungs, and lung pathology scores. TLR2/4 double KO mice were not impaired in bacterial control as well, which indicates that besides the interaction between S. pneumoniae and TLR2, the interaction between pneumolysin and TLR4 does not stimulate antibacterial defense in the asplenic host either.ConclusionsThese results argue against a significant role of TLR2 in host defense during S. pneumoniae pneumonia in the asplenic state. Therefore, other components can provide sufficient backup mechanisms for TLR2 deficiency in the defense against intrapulmonary infections with S. pneumoniae of the otherwise immune competent host.

Restricted processing of glycans by endomannosidase in mammalian cells

Removal of α-glucose residues from nascent glycoproteins in the early secretory pathway is a requirement for further N-glycan maturation. Although deglucosylation is a stepwise process mediated by endoplasmic reticulum-associated glucosidases I and II for most glycoproteins, Golgi endo-α-mannosidase provides a backup mechanism for glycoprotein deglucosylation. Although conserved in mammals, in certain cell lines, endomannosidase activity in vitro appears to differ from its activity in cells following glucosidase inhibition. Here, we show that in bovine cells this is explained by restricted substrate specificity allowing processing of Glc(1)Man(7)GlcNAc(1/2) and Glc(1)Man(5)GlcNAc(1/2) but not fully glucosylated glycans that build up when glucosidases are inhibited. Our data further demonstrate that such specificity is determined genetically rather than post-translationally. We also demonstrate that the bovine endomannosidase is transcriptionally upregulated by comparison with glucosidase II in Madin-Darby bovine kidney cells and speculate that this is to compensate for the reduced catalytic activity as measured in the recombinant form of the enzyme.