1,519 research outputs found

    The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

    Get PDF
    p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

    Comparison of Surface Roughness Prediction with Regression and Tree Based Regressions During Boring Operation

    Get PDF
    Modern manufacturing methods permit the study and prediction of surface roughness since the acquisition of signals and its processing is made instantaneously. With the availability of better computing facilities and newer algorithms in the machine learning domain, online surface roughness prediction will lead to the manufacture of intelligent machines that alert the operator when the process crosses the specified range of roughness. Prediction of surface roughness by multiple linear regression, regression tree and M5P tree methods using multivariable predictors and a single response dependent variable Ra (surface roughness) is attempted. Vibration signal from the boring operation has been acquired for the study that predicts the surface roughness on the inner face of the workpiece. A machine learning approach was used to extract the statistical features and analyzed by four different cases to achieve higher predictability, higher accuracy, low computing effort and reduction of the root mean square error. One case among them was carried out upon feature reduction using Principle Component Analysis (PCA) to examine the effect of feature reduction

    Defects in Friction Stir Welding of Steel

    Get PDF
    Defects associated with friction stir welding of two steel grades including DH36 and EH46 were investigated. Different welding parameters including tool rotational and tool traverse (linear) speeds were applied to understand their effect on weld seam defects including microcracks and voids formation. SEM images and infinite focus microscopy were employed to identify the defects types. Two new defects associated with the friction stir welding process are introduced in this work. The first defect identified in this work is a microcrack found between the plunge and the steady state region and attributed to the traverse moving of the tool with unsuitable speed from the plunge-dwell to the steady state stage. The tool traverse speed has recommended to travel 20 mm more with accelerated velocity range of 0.1 from the maximum traverse speed until reaching the steady state. The maximum recommended traverse speed in the steady state was also suggested to be less than 400 mm/min in order to avoid the lack in material flow. The second type of defect observed in this work was microcracks inside the stirred zone caused by elemental precipitations of TiN. The precipitates of TiN were attributed to the high tool rotational speed which caused the peak temperature to exceed 1200 °C at the top of the stirred zone and based on previous work. The limit of tool rotational speed was recommended to be maintained in the range of 200-500 RPM based on the mechanical experiments on the FSW samples

    Antibacterial Effect of various Concentrations of Sodium Hypochlorite and 2% Chlorhexidine combined with Proteolytic Enzyme against Enterococcus Faecalis Biofilm: An invitro study

    Get PDF
    AIM OF THE STUDY: To evaluate the antibacterial efficacy of various concentrations of sodium hypochlorite and Chlorhexidine combined with proteolytic enzyme in dentin - An invitro study. OBJECTIVES: To evaluate the anti enterococcus faecalis efficacy using various concentrations of sodium hypochlorite (5.25%, 1% & 3%) and 2% Chlorhexidine combined with Trypsin, a proteolytic enzyme in root canal dentin. MATERIALS AND METHODS: Seventy five single rooted teeth were selected and the dentin specimens were prepared from the middle third of the root. Dentin specimens were immersed in peptone agar medium eppendorf tubes. Enterococcus faecalis strains were inoculated and cultured for 21 days at 370c. Then the dentin specimens were exposed to the experimental irrigants (5.25% Naocl, 3% Naocl + trypsin, 1%Naocl+trypsin, 2% chlorhexidine + trypsin, normal saline) and evaluated under confocal laser scanning microscope to determine the antibacterial efficacy of experimental irrigants. RESULTS: The results of the present study showed that all groups exhibited equal antibacterial effect except group 5:(Saline- negative control). There was no significant difference among groups 1,2,3,4.(P value > 0.05). Group 1, 2, 3, 4 showed significant difference when compared to Group 5 (P<0.05). CONCLUSION: There was no significant difference among the groups regarding antienterococcus faecalis activity except negative control. Based on the results of the present study, it can be concluded that the irrigation protocol with 1% trypsin followed by lower concentrations of sodium hypochlorite (1% & 3%) and 1% trypsin followed by 2% chlorhexidine showed equivalent antibacterial effect compared to 5.25% sodium hypochlorite. Further studies are needed to evaluate the effect of trypsin over the physical properties of root canal dentin

    Prevalence of Cardiac Shunt Lesions in patients with Migraine with Aura and without Aura.

    Get PDF
    Migraine headache is a common disabling condition which represents a significant healthcare burden. It is characterised by recurrent disabling attacks of headache associated with nausea, vomiting, hypersenstivity to light, sound, and smell and in a third of patients neurological aura symptoms. These aura symptoms are fully reversible visual, sensory or speech disturbances. Visual disturbances are common and last for 5 – 60 mins. The underlying neurological mechanism for aura is cortical spreading depression. Recent evidence found a significant association between patent foramen ovale and transient global amnesia. This finding prompted the suggestion that paradoxical microembolisation in the vertebrobasilar territory may cause transient global amnesia. Like transient global amnesia, migraine with visual aura is a paroxysmal disturbance in which a sudden dysfunction of cortical areas fed by the terminal branches of the basilar artery is believed to trigger the attack. Arteriovenous shunting of vasoactive substances from the venous to the arterial system through a patent foramen ovale in patents with migraine may affect endothelial function (van mokt et al.). In individuals with a right to left shunt, a lower dose of venous trigger substances may be needed to induce migraine because the shunt permits the pulmonary filter to be bypassed. Many studies have shown migraineurs who experience an aura are more likely to have a patent foramen ovale (48%) than the general population (20%). Right to left cardiac shunt at rest through a patent foramen ovale (PFO) is more common in migraineurs with aura (15%) than in control patients with patent foramen ovale who do not experience migraine (0%). This suggest that interatrial communication may play a role in the pathogenesis of migraines. Closure of patent foramen ovale had resolved symptoms of migraine with aura in 50% of patients and improved symptoms in other 50% of subjects. Many studies have demonstrated closure of patent foramen ovale reduce migraine symptoms . This study investigated the prevalence of cardiac shunt lesions in migraine patients with and without aura. The transesophageal contrast echocardiography has been done to detect intracardiac shunts in migraine patients with and without aura. AIMS AND OBJECTIVES : 1. To evaluate the frequency of cardiac shunt lesions in patients with migraine with aura and migraine without aura. 2. To correlate the variables of migraine with variables of shunt. 3. To compare the results of our study with that reported by other studies performed in various parts of the world. CONCLUSION : 1. The female to male ratio in our study was found to be 2.8:1.Female predilection was more in younger age group <35 years. 2. Shunt lesion was present in 34% of migraine with aura patients. But only in 5% of migraine without aura patients. 3. Osteum secundum type of atrial septal defect was found to be the mo st common shunt lesion in our 24% of migraine with aura patients. 4. Patent foramen ovale was found in 10% of migraine with aura patients. 5. Atrial septal defect of svc type was noticed in only 5% of migraine without aura patients. 6. Statistically significant number of migraine with aura patients had shunt lesions. 7. Transesophageal contrast echocardiography is valuable in patients with migraine more so in aura patients to detect shunt lesions. 8. Closure of the shunt in patients with migraine may ameliorate symptoms

    Novel, Ceramic Membrane System For Hydrogen Separation

    Get PDF
    Separation of hydrogen from coal gas represents one of the most promising ways to produce alternative sources of fuel. Ceramatec, teamed with CoorsTek and Sandia National Laboratories has developed materials technology for a pressure driven, high temperature proton-electron mixed conducting membrane system to remove hydrogen from the syngas. This system separates high purity hydrogen and isolates high pressure CO{sub 2} as the retentate, which is amenable to low cost capture and transport to storage sites. The team demonstrated a highly efficient, pressure-driven hydrogen separation membrane to generate high purity hydrogen from syngas using a novel ceramic-ceramic composite membrane. Recognizing the benefits and limitations of present membrane systems, the all-ceramic system has been developed to address the key technical challenges related to materials performance under actual operating conditions, while retaining the advantages of thermal and process compatibility offered by the ceramic membranes. The feasibility of the concept has already been demonstrated at Ceramatec. This project developed advanced materials composition for potential integration with water gas shift rectors to maximize the hydrogenproduction

    Improvement of Grazing Lands for Better Livestock Production--A Case Study from Chitradurga District in India

    Get PDF
    Chitradurga is a highly drought prone district in the central dry zone of Karnataka, India, with a normal rainfall of 530 mm per annum. Over 85 per cent of cultivable area is rainfed and the livestock plays a vital role in rural income generation in this district. Improper management and overgrazing have resulted in most of the grazing resources declining to a poor, degraded condition. Regeneration of pasture land was vital in the villages due to three reasons - a) people\u27s livelihood dependency on livestock was considerable b) small ruminants played a vital role for landless farmers and c) lack of adequate fodder was a prime factor for low livestock productivity. To improve the livelihood of livestock farmers, a few interventions were made under World Bank funded National Agricultural Innovation Project through consortium approach in 10 project villages. Frequent interactions were held with the local livestock farmers to discuss about the importance of increasing the fodder resources in the villages to improve the income and to sustain their livelihood. They realized the importance of fodder and came forward to take up cultivation of perennial fodders and also, for the revitalization of grazing lands, locally known as kavals. The primary survey in the villages indicated that about 90 to 96 per cent of the small ruminant holders are dependent on these common property grazing resources for the fodder needs. The High Level Panel of Experts on food security and nutrition, constituted by FAO, has emphasized the importance of extending appropriate technologies and inputs, providing the needed credit and ensuring assured and remunerative marketing opportunities to the smallholders (HLPE, 2013). Such measures are also essential for revitalizing the degraded grasslands in this region
    corecore