Atf6alpha impacts cell number by influencing survival, death and proliferation

BACKGROUND: A growing body of literature suggests the cell-intrinsic activity of Atf6alpha during ER stress responses has implications for tissue cell number during growth and development, as well as in adult biology and tumorigenesis [1]. This concept is important, linking the cellular processes of secretory protein synthesis and endoplasmic reticulum stress response with functional tissue capacity and organ size. However, the field contains conflicting observations, especially notable in secretory cell types like the pancreatic beta cell. SCOPE OF REVIEW: Here we summarize current knowledge of the basic biology of Atf6alpha, along with the pleiotropic roles Atf6alpha plays in cell life and death decisions and possible explanations for conflicting observations. We include studies investigating the roles of Atf6alpha in cell survival, death and proliferation using well-controlled methodology and specific validated outcome measures, with a focus on endocrine and metabolic tissues when information was available. MAJOR CONCLUSIONS: The net outcome of Atf6alpha on cell survival and cell death depends on cell type and growth conditions, the presence and degree of ER stress, and the duration and intensity of Atf6alpha activation. It is unquestioned that Atf6alpha activity influences the cell fate decision between survival and death, although opposite directions of this outcome are reported in different contexts. Atf6alpha can also trigger cell cycle activity to expand tissue cell number through proliferation. Much work remains to be done to clarify the many gaps in understanding in this important emerging field

Correction to: Towards achieving nanofinish on silicon (Si) wafer by μ-wire electro-discharge machining

[No abstract available]This work was supported by the Fundamental Research Grant (FRGS/1/2014/TK01/UIAM/02/2) sponsored by the Ministry of Higher Education Malaysia. Authors also acknowledge the research support provided by the International Islamic University Malaysia

Endoplasmic Reticulum Stress Induced Proliferation Remains Intact in Aging Mouse beta-Cells

Aging is associated with loss of proliferation of the insulin-secreting beta-cell, a possible contributing factor to the increased prevalence of type 2 diabetes in the elderly. Our group previously discovered that moderate endoplasmic reticulum (ER) stress occurring during glucose exposure increases the adaptive beta-cell proliferation response. Specifically, the ATF6alpha arm of the tripartite Unfolded Protein Response (UPR) promotes beta-cell replication in glucose excess conditions. We hypothesized that beta-cells from older mice have reduced proliferation due to aberrant UPR signaling or an impaired proliferative response to ER stress or ATF6alpha activation. To investigate, young and old mouse islet cells were exposed to high glucose with low-dose thapsigargin or activation of overexpressed ATF6alpha, and beta-cell proliferation was quantified by BrdU incorporation. UPR pathway activation was compared by qPCR of target genes and semi-quantitative Xbp1 splicing assay. Intriguingly, although old beta-cells had reduced proliferation in high glucose compared to young beta-cells, UPR activation and induction of proliferation in response to low-dose thapsigargin or ATF6alpha activation in high glucose were largely similar between young and old. These results suggest that loss of UPR-led adaptive proliferation does not explain the reduced cell cycle entry in old beta-cells, and raise the exciting possibility that future therapies that engage adaptive UPR could increase beta-cell number through proliferation even in older individuals

ER Stress and ATF6alpha potently induce S-Phase in Old Mouse Beta Cells Cultured Ex-Vivo in High Glucose

Aging is associated with a loss of proliferation of the insulin-secreting beta cell, a possible contributing factor to the greatly increased rate of type-2 diabetes in the elderly. A landmark study from our lab previously illustrated that mild endoplasmic reticulum (ER) stress drives beta cell proliferation specifically through ATF6α, one arm of the tripartite Unfolded Protein Response (UPR). It is unknown if old beta cells differ from young beta cells in UPR signaling or proliferative response to ER stress or ATF6α activation. To investigate, young and old mouse islets were cultured ex vivo in high glucose, and beta cell proliferation was quantified by BrdU incorporation after treatment with low dose thapsigargin or activation of overexpressed ATF6α. In addition, levels of UPR signaling were compared by semi-quantitative Xbp1 splicing assay. Interestingly, although old beta cells displayed reduced proliferation in glucose compared to young beta cells, their proliferative response to low-dose thapsigargin and ATF6α activation were nearly identical, and no difference was found in Xbp1 splicing under high glucose or high ER stress conditions. These results suggest that the aged mouse beta cell does not have impaired UPR-responsive proliferation or aberrant UPR signaling when cultured ex viv

Energy efficient dual axis solar tracking system using IOT

With the increasing demand for energy, traditional sources are becoming scarce and the need to transition to non-traditional sources of energy is urgent. Solar energy is an inexhaustible form of energy that can be easily tapped from different parts of the world and converted to electrical energy by using devices such as solar panels. However, the output power of these photovoltaic (PV) panels is not constant as the sun moves from east to west and its angle of incidence varies with the season and time of the day. To maximize energy output from the solar panel, a dual-axis solar tracker (DAST) is necessary to rotate the panel about its horizontal and vertical axes. This system will ensure efficient tracking of the sun and optimal energy output from the solar panel. The proposed system will respond within the 0.2 s to store the data in database. The whole 24 h data of solar panel is utilized in the preferred system to analyse the data to validate the robustness of the system. The proposed system uses a microcontroller to adjust the position of the solar panel based on the movement of the sun, while the performance of the tracker is monitored through the use of Internet of Things (IoT) connected via Wi-Fi

An experimental investigation on the effect of nanopowder for micro-wire electro discharge machining of gold coated silicon

Micro Wire Electro Discharge Machining (μ-WEDM) is a type of electro-discharge machining (EDM) process where the wire is used instead of a rigid tool. It is a reliable and precise machining process, which is commonly used to produce various complex structural shapes for a wide range of industrial applications. However, to machine a semiconductor material of high resistivity like silicon (Si) requires more advanced processing to produce larger electrical sparks during the μ-WEDM operation. Current (μ-WEDM) technology is not enough to realize a stable machining environment for Si. In this research, a new type of μ-WEDM process for Si machining was investigated. At first, Si was temporarily coated with gold and then nanopowder mixed dielectric medium was used for the WEDMing process. The main purpose of this work is to investigate the effects of different nanopowder concentrations on two important response factors such as material removal rate (MRR) and spark gap (SG). In this regard, the μ-WEDMing of gold coated silicon was carried out in pure dielectric EDM oil and also in three different concentrations (0.1g/L,1g/L,2g/L) of nanopowder mixed dielectric oil to conduct an initial study with the aim to achieve better machining accuracy and stability. Based on the experimental investigations, the MRR were found to be increased on average minimum ∼ 1% to maximum ∼ 33% respectively for different carbon concentrations, as compared to machining in the pure dielectric medium. The spark gap was also observed to be increased by a significant margin on average of ∼ 2% to up to ∼ 159% than without using any nanopowder concentration, correspondingly

IOT based adjustment mechanism for direct reference model adaptive IMC to support voltage sag in DFIG wind farm

Sustainable energy sources are valuable energy sources.Renewable energy production boosts the economic status of a country. Wind energy is one of the most abundant renewable energy sources, and as a result, the technology to harvest energy from the wind is growing rapidly around the world. As load centers are far away from renewable energy sources, electricity must be transferred over long distances. The most common problems with power fluctuations are caused by long-range voltage sag riding (VSRT). DFIG (Doubly Fed Induction Generator) is very popular in wind energy conversion systems due to its variable speed, high energy collection, efficiency, excellent design and unique control of phase side converters and rotor side converters. Wind speed monitoring is done with the help of Internet of Things (IOT). This paper described the use of training networks in developing adjustment algorithms for direct reference model adaptive IMC for DFIG wind farms. Here, a novel training-based neural network MIT (NNMIT) adjustment mechanism using neural network method is developed and implemented in direct reference model adaptive IMC to improve the performance of the controller during voltage sag. Direct and quadrature axis rotor current controllers are developed and the resulting DFIG is balanced with the FuzzyMIT correction mechanism in the sag ride through the conditions in the wind farm. Improvements across the voltage sag are identified and presented using NNMIT. The proposed NNMIT attain 0.15% torque ripple and 1 ms response time better than the existing FuzzyMIT method. The proposed method preserves high accuracy ranges of 97.88% than the existing method. This approach gives better performance than other control design methods which assume that the flux in the stator is constant in amplitude

Synthesis and characterization of L-threonine ammonium bromide: grown on single crystal with experimental studies on NLO

L-threonine ammonium bromide (LTAB) is a significant nonlinear optical (NLO) material. The crystal has been grown by the slow evaporation technique (SET). Ammonium bromide has properties, which are that of chiral molecules and zwitterions environmental benefits due to advance NLO properties of LTAB. L-threonine-doped ammonium bromide crystals are grown using SET at ambient temperature. In this study, the unit cell factors are derived from X-ray diffraction (XRD) studies. The powder XRD spectra suggests the formation of orthorhombic crystal system. Fourier transform infrared spectroscopy (FTIR) analysis depicts the different functional groups offered in the grown crystals. The study of optical transmittance was done by crystals utilizing ultraviolet, visible, spectral analytical methods. Further, the minimum cutoff wavelength of the grown crystal has been recognized as 220 nm. The overall result of the second harmonic generation (SHG) efficiency is depicted higher and nearly around LTAB obtained crystal which is greater than potassium dihydrogen phosphate (KDP). It proves the potential application of LTAB crystal in optoelectronic industries.We would like to acknowledge the Department of Science and Technology (DST, Delhi), Government of India, for the award of DST-FIRST Level-1(SR/FST/PS-1/2018/35) scheme to the Department of Physics. We appreciate the KLEF for offering infrastructure, facilities, basic found (Perform basic instruments) and support for the current investigation.Scopu

Role of pars plana vitrectomy and membrane peel in vitreomacular traction associated with retinal vasoproliferative tumors.

To report a case of retinal vasoproliferative tumor (VPT) with secondary epiretinal membrane (ERM) formation and vitreo-macular traction managed by pars plana vitrectomy (PPV) and membrane peel. A 29-year-old male was referred for management of decreased vision in the right eye (OD) for 1 week. Presenting visual acuity was 20/50 Snellen feet (ft) OD, and fundus examination showed an ERM associated with a reddish-yellow mass in the inferotemporal quadrant with overlying exudation, hemorrhage, and subretinal fluid consistent with VPT, and cryotherapy was recommended. Two months later, there was complete tumor regression, but there was decreased vision from progressive vitreomacular traction to 20/400 ft. PPV with combined ERM and internal limiting membrane (ILM) peel were performed with resolution of vitreomacular traction and improvement of visual acuity to 20/50 ft at 6 months. PPV with combined ERM and ILM peel is effective for vision loss secondary to ERM and vitreomacular traction associated with retinal VPT

Unified design method of time delayed PI controller for first order plus dead-time process models with different dead-time to time constant ratio

The time delay element present in the PI controller brings dead-time compensation capability and shows improved performance for dead-time processes. However, design of robust time delayed PI controller needs much responsiveness for uncertainty in dead-time processes. Hence in this paper, robustness of time delayed PI controller has been analyzed for First Order plus Dead-Time (FOPDT) process model. The process having dead-time greater than three times of time constant is very sensitive to dead-time variation. A first order filter is introduced to ensure robustness. Furthermore, integral time constant of time delayed PI controller is modified to attain better regulatory performance for the lag-dominant processes. The FOPDT process models are classified into dead-time/lag dominated on the basis of dead-time to time constant ratio. A unified tuning method is developed for processes with a number of dead-time to time constant ratio. Several simulation examples and experimental evaluation are exhibited to show the efficiency of the proposed unified tuning technique. The applicability to the process models other than FOPDT such as high-order, integrating, right half plane zero systems are also demonstrated via simulation examples