ABSTRACT Replication of Vibrio cholerae chromosome 2 (Chr2) depends on molec- ular chaperone DnaK to facilitate binding of the initiator (RctB) to the replication ori- gin. The binding occurs at two kinds of site, 12-mers and 39-mers, which promote and inhibit replication, respectively. Here we show that DnaK employs different mechanisms to enhance the two kinds of binding. We found that mutations in rctB that reduce DnaK binding also reduce 12-mer binding and initiation. The initiation defect is suppressed by second-site mutations that increase 12-mer binding only marginally. Instead, they reduce replication inhibitory mechanisms: RctB dimerization and 39-mer binding. One suppressing change was in a dimerization domain which is folded similarly to the initiator of an iteron plasmid—the presumed progenitor of Chr2. In plasmids, DnaK promotes initiation by reducing dimerization. A different mutation was in the 39-mer binding domain of RctB and inactivated it, indicating an alternative suppression mechanism. Paradoxically, although DnaK increases 39-mer binding, the increase was also achieved by inactivating the DnaK binding site of RctB. This result suggests that the site inhibits the 39-mer binding domain (via auto- inhibition) when prevented from binding DnaK. Taken together, our results reveal an important feature of the transition from plasmid to chromosome: the Chr2 initiator retains the plasmid-like dimerization domain and its control by chaperones but uses the chaperones in an unprecedented way to control the inhibitory 39-mer binding.
20 Read more
Taken together, our results show that both 16E7 and 48E7 proteins lead to decrease steady state levels of p130, diminish p130-DREAM complexes and promote the cell to enter S-phase, but that this occurs by com- pletely different mechanisms. More specifically, the re- sults suggest that HPV16 E7 targets p130 predominantly through direct interactions via the LXCXE motif whereas HPV48 E7 disrupts p130-DREAM via CDK2 phosphorylation of p130. It is significant that whereas different HPV E7 types have a wide range of affinity to- wards pocket protein binding, based on their LXCXE motif , HPV48 E7 (which lacks a functional LXCXE motif) demonstrates similar effects on p130-DREAM formation and cell cycle progression compared to HPV16 E7. Pang et al. (2014) reported that the LXCXE motif of HPV16 E7 could promote mitotic gene expression by a pocket protein-independent mechanism; this was associated with
Import of β -oxidation substrates into peroxisomes is mediated by ATP binding cassette (ABC) transporters belonging to subfamily D. In order to enter the β -oxidation pathway, fatty acids are activated by conversion to fatty acyl-CoA esters, a reaction which is catalysed by acyl-CoA synthetases (ACSs). Here, we present evidence for an unusual transport mechanism, in which fatty acyl-CoA substrates are accepted by ABC subclass D protein (ABCD) transporters, cleaved by the transporters during transit across the lipid bilayer to release CoA, and ultimately re-esteriﬁed in the peroxisome lumen by ACSs which interact with the transporter. We propose that this solves the biophysical problem of moving an amphipathic molecule across the peroxisomal membrane, since the intrinsic thioesterase activity of the transporter permits separate membrane translocation pathways for the hydrophobic fatty acid moiety and the polar CoA moiety. The cleavage/re-esteriﬁcation mechanism also has the potential to control entry of disparate substrates into the β -oxidation pathway when coupled with distinct peroxisomal ACSs. A different solution to the movement of amphipathic molecules across a lipid bilayer is deployed by the bacterial lipid-linked oligosaccharide (LLO) ﬂippase, PglK, in which the hydrophilic head group and the hydrophobic polyprenyl tail of the substrate are proposed to have distinct translocation pathways but are not chemically separated during transport. We discuss a speculative alternating access model for ABCD proteins based on the mammalian ABC transporter associated with antigen processing (TAP) and compare it to the novel mechanism suggested by the recent PglK crystal structures and biochemical data.
10 Read more
Although chemotherapy impairs an enormous number of cells in a tumor, but it is understood that the chemotherapy agents are removed from cancer stem cells with the special mechanisms, which might be an important for drug resistance, for instance, overexpression of the ATP-binding cassette (ABC), drug transporters such as ABCB1, which encodes P- glycoprotein, and the ABCG2, which was originally identified in mitoxantrone resistant cells have been shown to keep cancer stem cells away from chemotherapeutic agents. Cancer stem cells share several of normal stem cells possession that provides for a long lifetime, including the relative silence, resistance to drugs and toxins through the expression of drug efflux transporters, an active DNA-repair capacity and a resistance to apoptosis, vascular niche, dormancy, hypoxic stability and enhance activity of repair enzymes. 18-20 Following the cancer cells features mentioned above, these cells remain stable in the patients recovering seemingly or metastasize to distant organs and cause the cancer recurrence. So, the identifying and eliminating these small populations of cancer cells is such a significant help to eliminate the drug resistance.
10 Read more
ABSTRACT: Electricity has been considered as an important component in today’s world. It has been basic part ofnature and is widely used form across the globe. Considering rapid growth of population day by day and conventional energy sources are lessening. These fossil fuels make a lot of pollution which impact on environment. It has become mandatory to obtain energy from a source which is clean, environment friendly and sustainable. Major cities in India have large volume of traffic. Considering it as merit a system is developed to obtain energy from speed breakers which has proven beneficial for cities. The number of vehicle running on the roads are increasing daily. There is tremendous amount of energy (mass) which acts on roads depending on that various types of mechanism have been developed on speed breakers through which electricity is generated. The above paper illustrates on study of mechanisms for generation of electricity from speed breakers which is way more pollution free, cheapest and form a renewable sources of energy. The main objective behind the paper to show the detailed survey of how speed breakers can be now used as a source of power.
To have a further insight on the mechanisms at play during the whole voltammetry curve, one can follow the method developed by Conway  and Dunn  for deconvoluting the two components corresponding to the two values of b mentioned above. Thus, for a series of voltammetries performed at different scan rates, the total current measured at a certain potential i(V), is given by the sum of two components:
Numerous reports have focused on the different mechanisms of MDR in leukemia. These resistance mechanisms include: a) increased drug metabolism due to altered molecular targets; b) defective apoptotic machinery; c) over-expression of efflux pumps, such as P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRP1, MRP2), lung resistance protein/major vault protein, and breast cancer resistance protein (BCRP); d) enzyme-mediated drug resistance mechanisms such as overexpression of glutathione S-transferase; e) microenvironmental resistance; and f) enhanced repair of drug-induced DNA damage. 3,4 It is well known that the appearance of MDR has made
cross-links , fibril-associated non-helical collagens (or FACITs), COMP , small proteoglycans such as decorin , fibromodulin , lumican  and bigli- can , but also tenascin , perlecan , matrilin  and thrombospondin . Although there is some evidence for most of these factors, none of them is by itself entirely consistent with all the experimental obser- vations. In particular none was able to explain why in most tissues the fibril growth is very effectively con- trolled so that the collagen fibrils size is highly uniform and distributed along a narrow Gaussian curve, while in other, and often adjoining, tissues the collagen fibrils are large and inhomogeneous with a distinctive multimodal distribution. The difference between these two classes is so great that it may seem not unreasonable to hypothe- size that two entirely different mechanisms are at work in different tissues.
SKOV3, a human ovarian cancer cell line, has been shown to be able to take up various types of nanoparticles in a caveolin- 1-dependent manner. Therefore, the SKOV3 cell line was used for the second series of experiments. Schematically, we found that: nanoparticles exploited different mechanisms of entry, followed different endocytic routes, and showed different cellular compartmentalization depending on size and type of material; 10 nm naked mesoporous silica nanoparticles showed the highest and 50 nm carboxyl- modified mesoporous silica nanoparticles showed the lowest uptake efficiency, independent of caveolin-1 expression; 30 nm carboxyl-modified polystyrene nanoparticles were biocompatible, although not retained intracellularly for a long time, and did not enter the acidic endocytic pathway, whereas 50 nm amine-modified polystyrene nanoparticles accumulated in lysosomes and were toxic. Uptake of 10 nm mesoporous silica nanoparticles was not affected by serum, whereas 30 nm polystyrene nanoparticles was thus affected.
12 Read more
ABSTRACT: Vegetation cover on soil acts positively in maintaining temperature and soil moisture, yet, it has been imposing specific operational conditions on seeders. The objective of this study was to evaluate performance of different mechanisms regarding straw mobilization, employed in a no-till seeder. The experimental area was conducted on clayey soil under no-tillage with a large quantity of sorghum residue. The experiment was established in a randomized block design, as the treatments consisted of a combination of two mechanisms at front of the furrow opener composed of cutting disc and row cleaners, and three mechanisms behind the seed furrower, covering discs prototype model M1, Spider and commercial model, with the combination of cutting disc and Spider model not being evaluated. We assessed the coverage permanence on soil index, vegetation mass on surface and inside the line. The treatment containing the row cleaner mechanism efficiently removed straw from the surface of sowing line as well as the return one acted on straw replacement. It was identified that use of the cutting disc at the front of seeder contributed to the increase of straw installation inside the line, three times more than in the row cleaner system when operating individually. Covering mechanism with row cleaners reduced straw inside the line and kept line covering similar to treatment of cutting disc operating alone.
The extracts most efficient for DPPH radical scavenging among the varieties tested was IZ 64 (378 µg/mL). Other Morus extracts have also been reported to be active in this assay (Arabshahi-Delouee and Urooj, 2007). In the present study, activity was detected for extracts from M. alba roots, showing that antioxidant compounds are thoroughly distributed in the plant, not relying only in the fruits. Polyphenols have been reported as potential antioxidants, protecting lipids and proteins against oxidative damage through their ability to scavenger metal ions and oxygen and nitrogen free radicals (Andallu et al., 2014). The correlations found between phenolic compounds of ethanol extracts suggest that they act by different mechanisms of action.
and the sensor response was evaluated as changes in the optical absorption spectra, hydrophobic properties and conductivity at different gas concentra- tions. From UV-Vis results, important changes in the absorption peaks were observed after gas exposure. The morphology of the films before and after gas interaction was obtained by using scanning electron and atomic force micro- scopy. The films morphology showed a degradation after gas adsorption for the metal free system but gas entrapment for the zinc porphyrin film. In or- der to elucidate the gas adsorption phenomena, density functional theory calculations were also performed. Here, it was observed that the porphyrin chemical structure not only affects the gas coordination sites which affect the porphyrin electronic distribution and packing arrangement, but also, deter- mines the gas detection mechanism for sensing applications.
17 Read more
In addition to individual kinks, multiple kinks are also frequently observed in InP NWs. As shown in Figure 6, different shapes, such as zig-zag and rectangle, are com- posed of kinks with different angles mentioned above. They are likely to be formed by the change of growth conditions. At the same time, it is observed that the for- mation of kinks is not related to the substrate tilting during the growth. For the growth substrate without any tilt angle, the InP NWs with kinks were also frequently observed. The occurrence of continuous kinks means that there is a possibility to produce NWs with different shapes in large scale, such as the nanospring produced in ZnO NWs . Our results also call into question how to control the shape and microstructures of NWs by tuning the NW growth conditions in order to satisfy the needs of practical applications.
The present study did not reveal information regard- ing only the sound-producing mechanism in Holocentri- dae. It also showed for the first time that Myripristis and Neoniphon larvae are able to make sounds as soon as they settle on the reef. Except for an obvious differ- ence in size, we did not notice any difference in the sound-producing mechanism between settling larvae and adults. Lo-Yat  found that the duration of the planktonic larval stage in the Rangiroa holocentrids he studied lasted between 40 and 65 days. In Myripristis, we showed the number of pulses and their amplitudes were lower in the larvae than in the adults. Although the mechanisms are not the same, these results are in concordance with studies involving fishes from other taxa: the croaking gourami T. vittata [16,39] and the gurnard E. gurnardus .
12 Read more
available units, either within the same or across different SCSs. However, development is frequently tantamount to an improvement in the accuracy of the functioning of an already available mental unit. This usually implies either a better focusing of the unit on those target elements (environmental or mental) or a better mapping of the possible variations of the unit onto the target elements to which is variation is related. The mechanism which is responsible to bring these changes about is differentiation. An example of differentiation may be the understanding that number names cannot be used in the same way to denote increase in natural numbers and in fractions. The reason is that increase in the former corresponds one-to-one to the sequence of number names whereas fraction names are more complex compositions. For instance, provided that the nominator is the same, larger numbers in the denominator imply a smaller value for the fraction. Hartnett and Gelman (in press) showed that it takes time and effort to differentiate between the many variations of counting or measurement.
77 Read more
Different complications might happen with the traditional implantable cardioverter defibrillator (ICD). Preservation of the peripheral and the central veins in chronic kidney disease is important for successful hemodialysis. Central venous stenosis is frequently observed with transvenous leads and represents a serious condition as the central veins are important for blood return to the right atrium during dialysis. With the subcutaneous ICD, there is no transvenous leads and therefore no related damage to the central veins . Endocardial cardiac rhythm device leads may lead to tricuspid regurgitation (TR) resulting in an increase pressure on the right side of the heart. This would add to the state of chronic volume load in hemodialysis patients leading to signs and symptoms of right sided heart failure . The intravascular location of the leads serve a nidus for bacterial colonization . Instead of utilizing the central veins, subcutaneous ICD does not have any leads, in this way all leads associated complications will be avoided . Its utility is however limited to patients who do not require back up pacing.
Another line of research has focussed mostly on mecha- nisms that may enable reciprocity (e.g. Brosnan & de Waal, 2002; Schino & Aureli, 2010b). A mechanism describes the basal cause of a behaviour or a strategy, which can be cogni- tive in the case of reciprocity (Bateson & Laland, 2013; Tinbergen, 1963). At least four mechanisms have been de- scribed, if again by-products are excluded, like symmetry- based reciprocity, i.e. a response based on symmetrical traits rather than experienced help (de Waal & Luttrell, 1988; but see Campennì & Schino, 2016). First, probably the least cog- nitively demanding form of reciprocity is hard-wired reciprocity (Schino & Aureli, 2017). This is a fixed response to provide help immediately upon the receipt of help. It is most likely confined to distinct settings that do not involve a time delay, partner choice or the flexible use of different commod- ities. Thus, this mechanism is different from all other mecha- nisms that are flexible and require some form of encoding and processing information. Second, attitudinal reciprocity re- quires a cognitive decision with a minimum of information. Here an attitude, i.e. a tag based on the last encounter, is associated with a cooperation partner (Brosnan & de Waal, 2002; de Waal & Brosnan, 2006). This mechanism does not require the memory of the exact levels of help. Instead a gen- eral tag, such as B the partner was nice ^ is sufficient. An im- portant feature of attitudinal reciprocity is that received help will be reciprocated in the next cooperative situation, i.e. short-term reciprocity (Jaeggi, de Groot, Stevens, & van Schaik, 2013). Third, emotion-based reciprocity acts on lon- ger time spans. For that, individuals help selectively those partners with which they associate positive emotions, for ex- ample when being socially bonded (Schino & Aureli, 2009). Because emotional bonds develop as a consequence of help received, the donated help is likely to be returned. This mech- anism leads to balanced relationships in which given and re- ceived favours are correlated over long time frames, i.e. long- term reciprocity. Finally, calculated reciprocity is probably the most cognitively demanding mechanism because individuals calculate how much they need to help another individual based on the memory of the amount of help received by this individual (Brosnan & de Waal, 2002; de Waal & Brosnan, 2006). Similar to attitudinal reciprocity, calculated reciprocity leads to short-term reciprocity in which provided help is de- pendent on previously received help.
18 Read more
As already discussed, currently most of the commercial CPs use „pay as you go‟ based fixed pricing scheme. Amazon has recently introduced spot pricing  which is a dynamic pricing scheme based on user‟s bidding price. It also offers 10 different virtual machine instance configurations, with different prices for each configuration, and practice tiered pricing for storage and bandwidth . This can also be considered as a kind of dynamic pricing, where users can request for custom configurations with multiple resource types .
Cloud computing refers to a set of services and resources offered to its consumers through internet. The user data and applications software shift to highly optimal data i.e. cloud. Either it may be a small or medium business infrastructure must focus on resource and information sharing among various users due to minimization of infrastructure cost. Cloud computing provides a lot of benefit, instead of its security is key inhibitor to cloud adoption. So, Cloud computing has brought various security threats which leads to lack of wide adoption of Cloud computing. This study aims to identify major security threats and security mechanisms and how to assess these security threats or vulnerabilities.
Findings by Haverland (2006) reveal, that research on Europeanisation by case selection is affected by no-variance problems, “following the counterfactual notion of causality, *…+, it is therefore diffi- cult – if not impossible – to establish the causal effect of the EU” (Haverland, 2006, p. 144). Due to the fact that national policy changes, improvements in cooperation or changes in the thinking about activation may have occurred without the influence of the EU, but through either domestic influ- ences (internal pressures) or impacts deriving from globalization (global pressures), there can be a “lack of variation in the independent-EU-level-variable” (Haverland, 2006, p. 135). Internal validity would be challenged here due to the possibility that similar changes might have occurred if the EU did not exist. In order to minimise this no-variance problem within the research, the steering and amplifying effects will be accounted for. 9 Steering effects imply that domestic decisions on imple- menting policies are a response to the ESF and changes would not occur without it, whereas amplify- ing effects mean that, the ESF reinforces domestic changes, but these changes may also have oc- curred if ESF was not available; hence, the ESF facilitates changes in national policies but is not the main driver for the implementation (Zohlnhöfer & Ostheim, 2007). Furthermore, due to the counter- factual concept of causation, Haverland (2006) suggests, that especially in single case studies on Eu- ropeanisation, a non-EU state, that has large similarities with the country of observation, should serve as the ‘control group’. However, as much as this could contribute towards making EU influence most visible and demarcate changes in Spain from other possible factors, that complexity of analysis is not feasible in this Master thesis. Nevertheless, as “in order for *the case+ to serve its function, in order for it to be a case of something, cases must be similar to one another in some *...+ respect” (Gerring, 2001, p. 174), the empirical research on Belgium by Verschraegen et al. (2011) allows to draw valid inferences through Europeanisation mechanisms and their effects on domestic activation policies, which are used for the research on Spain likewise.
54 Read more