Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Sputtered Fe1·5CoNi0.5 coating: An improved protective coating for SOFC interconnect applications

In an attempt to optimize the properties of FeCoNi coating for planar solid oxide fuel cell (SOFC) interconnect application, the coating composition is modified by increasing the ratio of Fe/Ni. An Fe_1·5CoNi_0.5 (Fe:Co:Ni = 1.5:1:0.5, atomic ratio) metallic coating is fabricated on SUS 430 stainless steel by magnetron sputtering, followed by oxidation in air at 800°C. The Fe_1·5CoNi_0.5 coating is thermally converted to (Fe,Co,Ni)₃O₄ and (Fe,Co,Mn,Ni)₃O₄ without (Ni,Co)O particles. After oxidation for 1680 h, no further migration of Cr is detected in the thermally converted coating region. A low oxidation rate of 5.9 × 10^?14 g² cm^?4 s^?1 and area specific resistance of 12.64 mΩ·cm² is obtained for Fe_1·5CoNi_0.5 coated steels.     

Secure image encryption scheme using 4D-Hyperchaotic systems based reconfigurable pseudo-random number generator and S-Box

This paper introduces the design of a hardware efficient reconfigurable pseudorandom number generator (PRNG) using two different feedback controllers based four-dimensional (4D) hyperchaotic systems i.e. Hyperchaotic-1 and -2 to provide confidentiality for digital images. The parameter's value of these two hyperchaotic systems is set to be a specific value to get the benefits i.e. all the multiplications (except a few multiplications) are performed using hardwired shifting operations rather than the binary multiplications, which doesn't utilize any hardware resource. The ordinary differential equations (ODEs) of these two systems have been exploited to build a generic architecture that fits in a single architecture. The proposed architecture provides an opportunity to switch between two different 4D hyperchaotic systems depending on the required behavior. To ensure the security strength, that can be also used in the encryption process in which encrypt the input data up to two times successively, each time using a different PRNG configuration. The proposed reconfigurable PRNG has been designed using Verilog HDL, synthesized on the Xilinx tool using the Virtex-5 (XC5VLX50T) and Zynq (XC7Z045) FPGA, its analysis has been done using Matlab tool. It has been found that the proposed architecture of PRNG has the best hardware performance and good statistical properties as it passes all fifteen NIST statistical benchmark tests while it can operate at 79.101-MHz or 1898.424-Mbps and utilize only 0.036 %, 0.23 %, and 1.77 % from the Zynq (XC7Z045) FPGA's slice registers, slice LUTs, and DSP blocks respectively. Utilizing these PRNGs, we design two 16 × 16 substitution boxes (S-boxes). The proposed S-boxes fulfill the following criteria: Bijective, Balanced, Non-linearity, Dynamic Distance, Strict Avalanche Criterion (SAC) and BIC non-linearity criterion. To demonstrate these PRNGs and S-boxes, a new three different scheme of image encryption algorithms have been developed: a) Encryption using S-box-1, b) Encryption using S-box-2 and, c) Two times encryption using S-box-1 and S-box-2. To demonstrate that the proposed cryptosystem is highly secure, we perform the security analysis (in terms of the correlation coefficient, key space, NPCR, UACI, information entropy and image encryption quantitatively in terms of (MSE, PSNR and SSIM)).     

Public perceptions on artificial intelligence driven disaster management: Evidence from Sydney,Melbourne and Brisbane

In recent years, artificial intelligence (AI) is being increasingly utilised in disaster management activities. The public is engaged with AI in various ways in these activities. For instance, crowdsourcing applications developed for disaster management to handle the tasks of collecting data through social media platforms, and increasing disaster awareness through serious gaming applications. Nonetheless, there are limited empirical investigations and understanding on public perceptions concerning AI for disaster management. Bridging this knowledge gap is the justification for this paper. The methodological approach adopted involved: Initially, collecting data through an online survey from residents (n = 605) of three major Australian cities; Then, analysis of the data using statistical modelling. The analysis results revealed that: (a) Younger generations have a greater appreciation of opportunities created by AI-driven applications for disaster management; (b) People with tertiary education have a greater understanding of the benefits of AI in managing the pre- and post-disaster phases, and; (c) Public sector administrative and safety workers, who play a vital role in managing disasters, place a greater value on the contributions by AI in disaster management. The study advocates relevant authorities to consider public perceptions in their efforts in integrating AI in disaster management.     

Colossal dielectric response and relaxation behavior in novel system of Zr4+ and Nb5+ co-substituted CaCu3Ti4O12 ceramics

In this work, we developed a novel system of isovalent Zr⁴⁺ and donor Nb⁵⁺ co-doped CaCu₃Ti₄O₁₂ (CCTO) ceramics to enhance dielectric response. The influences of Zr⁴⁺ and Nb⁵⁺ co-substituting on the colossal dielectric response and relaxation behavior of the CCTO ceramics fabricated by a conventional solid-phase synthesis method were investigated methodically. Co-doping of Zr⁴⁺ and Nb⁵⁺ ions leads to a significant reduction in grain size for the CCTO ceramics sintered at 1060 °C for 10 h. XRD and Raman results of the CaCu₃Ti_3.8-xZr_xNb_0.2O₁₂ (CCTZNO) ceramics show a cubic perovskite structure with space group Im-3. The first principle calculation result exhibits a better thermodynamic stability of the CCTO structure co-doped with Zr⁴⁺ and Nb⁵⁺ ions than that of single-doped with Zr⁴⁺ or Nb⁵⁺ ion. Interestingly, the CCTZNO ceramics exhibit greatly improved dielectric constant (~10⁵) at a frequency range of 10²–10⁵ Hz and at a temperature range of 20–210 °C, indicating a giant dielectric response within broader frequency and temperature ranges. The dielectric properties of CCTZNO ceramics were analyzed from the viewpoints of defect-dipole effect and internal barrier layer capacitance (IBLC) model. Accordingly, the immensely enhanced dielectric response is primarily ascribed to the complex defect dipoles associated with oxygen vacancies by co-doping Zr⁴⁺ and Nb⁵⁺ ions into CCTO structure. In addition, the obvious dielectric relaxation behavior has been found in CCTZNO ceramics, and the relaxation process in middle frequency regions is attributed to the grain boundary response confirmed by complex impedance spectroscopy and electric modulus.     

Use of a smartphone-based Student Response System in large active-learning Chemical Engineering Thermodynamics classrooms

Smartphones are a promising tool as student response systems (SRS) for interactive teaching due to their widespread diffusion. Here, the main purpose is to assess the efficacy of smartphone-based SRS in large classroom settings of undergraduate Thermodynamics, as representative of engineering courses requiring high-level cognitive skills for problem solving. Four sets of multiple-choice questions were presented during the course. Overall, the results refer to 1055 students between control and SRS classes, each corresponding to a3 years period.One of the main results of this work is the strong linear correlation between the average questionnaire score and the final exam grade (R² = 0.91). A similar correlation, although with a lower value of R², is already found in the first questionnaire, thus showing the SRS high predictive power of class performance. The results of this study provide guidance for a quantitative use of smartphone-based SRS in teaching basic disciplines. The SRS monitoring capability allows early detection of struggling students, thus paving the way to personalized tutoring and improved student engagement in active learning practices. This approach is especially important in emergency situations, such as the SARS-Cov-2 pandemic, when distance learning is widely adopted, and remote interactive tools are highly needed.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Effect of spheroidized microstructure on the impact toughness and electrochemical performance of a high-carbon steel

The influence of cementite spheroidization on the impact toughness and electrochemical properties of a high-carbon steel has been thoroughly investigated in this study. Heavy warm rolling, followed by 2 h of annealing, has resulted in near-complete spheroidization, leading to a microstructure consisting of nano-cementite globules dispersed in the ultrafine-grained ferritic matrix. The Charpy impact test exhibited superior impact toughness with increased spheroidization. It is validated by the presence of abundant dimples in the fractographs of spheroidized specimens, in contrast to the as-received one that experienced a brittle failure due to its lamellar pearlitic structure. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) carried out in a 3.5% NaCl solution revealed that the corrosion resistance of the alloy gets improved with the increase in the degree of spheroidization. This is attributed to the lower susceptibility of the spheroidized specimen to microgalvanic corrosion owing to the minimum area of contact between nano-spheroidized cementite and ferrite, as elucidated with the help of EIS results aided by equivalent electrical circuit model.     

Synthesis,characterization and charge transport properties of Pr–Ni Co-doped SrFe2O4 spinel for high frequency devices applications

Ferrites are materials of interest due to their broad applications in high technological devices and a lot of research has been focused to synthesize new ferrites. In this regard, an effort has been devoted to synthesize spinel Pr–Ni co-substituted strontium ferrites with a nominal formula of Sr_1-xPr_xFe_2-yNi_yO₄ (0.0 ≤ x ≤ 0.1, 0.0 ≤ y ≤ 1.0). The cubic structure of pure and Pr–Ni co-substituted strontium ferrite samples calcinated at 1073 K for 3 h has been confirmed through X-ray diffraction (XRD). Average sizes of crystallites (18–25 nm) have been estimated from XRD analysis and nanometer particle sizes of synthesized ferrites have been further verified by scanning electron microscopy (SEM). SEM results have also shown that particles are mostly agglomerated and all the samples possess porosity. It has been observed that at 298 K, the values of resistivity (ρ) increase, while that of AC conductivity, dielectric loss, and dielectric constants decrease with increasing amounts of Pr³⁺ and Ni²⁺ ions. The values of dielectric parameters initially decrease with frequency and later become constant and can be explained on the basis of dielectric polarization. Electrochemical impedance spectroscopy (EIS) studies show that the charge transport phenomenon in ferrite materials is mainly controlled via grain boundaries. Overall, synthesized ferrite materials own enhanced resistivity values in the range of 1.38 × 10⁹–1.94 × 10⁹ Ω cm and minimum dielectric losses, which makes them suitable candidates for high frequency devices applications.