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Sensors ◽  
2022 ◽  
Vol 22 (2) ◽  
pp. 528
Author(s):  
Aitizaz Ali ◽  
Muhammad Fermi Pasha ◽  
Jehad Ali ◽  
Ong Huey Fang ◽  
Mehedi Masud ◽  
...  

Due to the value and importance of patient health records (PHR), security is the most critical feature of encryption over the Internet. Users that perform keyword searches to gain access to the PHR stored in the database are more susceptible to security risks. Although a blockchain-based healthcare system can guarantee security, present schemes have several flaws. Existing techniques have concentrated exclusively on data storage and have utilized blockchain as a storage database. In this research, we developed a unique deep-learning-based secure search-able blockchain as a distributed database using homomorphic encryption to enable users to securely access data via search. Our suggested study will increasingly include secure key revocation and update policies. An IoT dataset was used in this research to evaluate our suggested access control strategies and compare them to benchmark models. The proposed algorithms are implemented using smart contracts in the hyperledger tool. The suggested strategy is evaluated in comparison to existing ones. Our suggested approach significantly improves security, anonymity, and monitoring of user behavior, resulting in a more efficient blockchain-based IoT system as compared to benchmark models.


2021 ◽  
Author(s):  
Patrick Emery ◽  
Radhika Joshi ◽  
Yao Cai ◽  
Yomgliang Xia ◽  
Joanna Chiu

Temperature compensation is a critical feature of circadian rhythms, but how it is achieved remains elusive. Here, we uncovered the important role played by the Drosophila PERIOD (PER) phosphodegron in temperature compensation. Using CRISPR-Cas9, we introduced a series of mutations that altered three Serines (S44, 45 and 47) belonging to the PER phosphodegron, the functional homolog of mammalian PER2’s S487 phosphodegron, which impacts temperature compensation. While all three Serine to Alanine substitutions lengthened period at all temperatures tested, temperature compensation was differentially affected. S44A and S45A substitutions caused decreased temperature compensation, while S47A resulted in overcompensation. These results thus reveal unexpected functional heterogeneity of phosphodegron residues in thermal compensation. Furthermore, mutations impairing phosphorylation of the per^s phosphocluster decreased thermal compensation, consistent with its inhibitory role on S47 phosphorylation. Interestingly,the S47A substitution caused increased accumulation of hyper-phosphorylated PER at warmer temperatures. This finding was corroborated by cell culture assays in which S47A caused excessive temperature compensation of phosphorylation-dependent PER degradation. Thus, we show a novel role of the PER phosphodegron in temperature compensation through temperature-dependent modulation of the abundance of hyper-phosphorylated PER. Our work also reveals interesting mechanistic convergences and differences between mammalian and Drosophila temperature compensation of the circadian clock.


2021 ◽  
pp. 1-22
Author(s):  
Simone Cubeda ◽  
Luca Andrei ◽  
Luca Innocenti ◽  
Fabrizio Paone ◽  
Lorenzo Cocchi ◽  
...  

Abstract In the recent years Additive Manufacturing (AM) methods are getting more and more attractive and feasible for the realization of components and subcomponents of gas turbines. They are receiving much attention since, on one hand, the manufacturing of complex 3D geometries is allowed and, on the other, manufacturing and delivery times can be cut down. At the current state of the art, to the authors' knowledge only few applications have yet been commercialized relatively to cooling holes, due to the intrinsic difficulties associated with such a critical feature. Lately, Baker Hughes is studying the possibility to manufacture film-cooling holes via the DMLM technology in order to exploit the flexibility of such innovative manufacturing method and hence eliminate additional processes and lead time. From the open literature it is known that additively manufactured holes can have a more irregular shape and higher roughness than traditional ones, which may lead not only to a reduction in coolant flow but more importantly to a decay of the film-cooling adiabatic effectiveness. For this reason, a test campaign has been conducted in collaboration with the University of Florence (Italy) with the objective of characterizing the performance (minimum passage diameter, flow check and adiabatic effectiveness) of AM vs traditional cylindrical holes on simple-geometry coupons built upon different construction angles. Results were then analyzed in order to fully compare the performance of AM vs traditional film-cooling holes at different operating regimes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ilaria Piccialli ◽  
Roselia Ciccone ◽  
Agnese Secondo ◽  
Francesca Boscia ◽  
Valentina Tedeschi ◽  
...  

The remodelling of neuronal ionic homeostasis by altered channels and transporters is a critical feature of the Alzheimer’s disease (AD) pathogenesis. Different reports converge on the concept that the Na+/Ca2+ exchanger (NCX), as one of the main regulators of Na+ and Ca2+ concentrations and signalling, could exert a neuroprotective role in AD. The activity of NCX has been found to be increased in AD brains, where it seemed to correlate with an increased neuronal survival. Moreover, the enhancement of the NCX3 currents (INCX) in primary neurons treated with the neurotoxic amyloid β 1–42 (Aβ1–42) oligomers prevented the endoplasmic reticulum (ER) stress and neuronal death. The present study has been designed to investigate any possible modulation of the INCX, the functional interaction between NCX and the NaV1.6 channel, and their impact on the Ca2+ homeostasis in a transgenic in vitro model of AD, the primary hippocampal neurons from the Tg2576 mouse, which overproduce the Aβ1–42 peptide. Electrophysiological studies, carried in the presence of siRNA and the isoform-selective NCX inhibitor KB-R7943, showed that the activity of a specific NCX isoform, NCX3, was upregulated in its reverse, Ca2+ influx mode of operation in the Tg2576 neurons. The enhanced NCX activity contributed, in turn, to increase the ER Ca2+ content, without affecting the cytosolic Ca2+ concentrations of the Tg2576 neurons. Interestingly, our experiments have also uncovered a functional coupling between NCX3 and the voltage-gated NaV1.6 channels. In particular, the increased NaV1.6 currents appeared to be responsible for the upregulation of the reverse mode of NCX3, since both TTX and the Streptomyces griseolus antibiotic anisomycin, by reducing the NaV1.6 currents, counteracted the increase of the INCX in the Tg2576 neurons. In agreement, our immunofluorescence analyses revealed that the NCX3/NaV1.6 co-expression was increased in the Tg2576 hippocampal neurons in comparison with the WT neurons. Collectively, these findings indicate that NCX3 might intervene in the Ca2+ remodelling occurring in the Tg2576 primary neurons thus emerging as a molecular target with a neuroprotective potential, and provide a new outcome of the NaV1.6 upregulation related to the modulation of the intracellular Ca2+ concentrations in AD neurons.


2021 ◽  
Vol 118 (50) ◽  
pp. e2110055118
Author(s):  
Wen-Yi Low ◽  
Shuhua Thong ◽  
Shu-Sin Chng

The hallmark of the gram-negative bacterial envelope is the presence of the outer membrane (OM). The OM is asymmetric, comprising lipopolysaccharides (LPS) in the outer leaflet and phospholipids (PLs) in the inner leaflet; this critical feature confers permeability barrier function against external insults, including antibiotics. To maintain OM lipid asymmetry, the OmpC-Mla system is believed to remove aberrantly localized PLs from the OM and transport them to the inner membrane (IM). Key to the system in driving lipid trafficking is the MlaFEDB ATP-binding cassette transporter complex in the IM, but mechanistic details, including transport directionality, remain enigmatic. Here, we develop a sensitive point-to-point in vitro lipid transfer assay that allows direct tracking of [14C]-labeled PLs between the periplasmic chaperone MlaC and MlaFEDB reconstituted into nanodiscs. We reveal that MlaC spontaneously transfers PLs to the IM transporter in an MlaD-dependent manner that can be further enhanced by coupled ATP hydrolysis. In addition, we show that MlaD is important for modulating productive coupling between ATP hydrolysis and such retrograde PL transfer. We further demonstrate that spontaneous PL transfer also occurs from MlaFEDB to MlaC, but such anterograde movement is instead abolished by ATP hydrolysis. Our work uncovers a model where PLs reversibly partition between two lipid-binding sites in MlaC and MlaFEDB, and ATP binding and/or hydrolysis shift this equilibrium to ultimately drive retrograde PL transport by the OmpC-Mla system. These mechanistic insights will inform future efforts toward discovering new antibiotics against gram-negative pathogens.


Author(s):  
Tole Sutikno ◽  
Hendril Satrian Purnama ◽  
Anggit Pamungkas ◽  
Abdul Fadlil ◽  
Ibrahim Mohd Alsofyani ◽  
...  

<span>The use of the internet of things (IoT) in solar photovoltaic (PV) systems is a critical feature for remote monitoring, supervising, and performance evaluation. Furthermore, it improves the long-term viability, consistency, efficiency, and system maintenance of energy production. However, previous researchers' proposed PV monitoring systems are relatively complex and expensive. Furthermore, the existing systems do not have any backup data, which means that the acquired data could be lost if the network connection fails. This paper presents a simple and low-cost IoT-based PV parameter monitoring system, with additional backup data stored on a microSD card. A NodeMCU ESP8266 development board is chosen as the main controller because it is a system-on-chip (SOC) microcontroller with integrated Wi-Fi and low-power support, all in one chip to reduce the cost of the proposed system. The solar irradiance, ambient temperature, PV output voltage and PV output current, are measured with photo-diodes, DHT22, impedance dividers and ACS712. While, the PV output power is a product of the PV voltage and PV current. ThingSpeak, an open-source software, is used as a cloud database and data monitoring tool in the form of interactive graphics. The results showed that the system was designed to be highly accurate, reliable, simple to use, and low-cost.</span>


2021 ◽  
Vol 229 (4) ◽  
pp. 230-235 ◽  
Author(s):  
John H. Krantz

Abstract. For 25 years, the web has been used for psychological research ( Krantz et al., 1997 ; Reips, 1997 ). While many areas of psychology have benefitted from the increased access to participants and other benefits of web-based research, one area of psychology has rarely taken advantage of the online format, that is, sensation and perception. Largely, sensation and perception research has not used the web because of the need for carefully calibrated equipment to successfully run their experiments. However, there may be classes of phenomena in our sensory processes that might be studied online where the equipment and stimuli vary. Suppose the critical feature of the stimulus is an abstraction of the physical stimulus that does not vary with different displays. In that case, these features can be successfully studied online, meaning that results from online studies will match those from controlled laboratories. This study will examine the Ebbinghaus illusion to illustrate the successful use of the web for perceptual research. The implications and some discussion of types of perceptual studies conducted on the web will be discussed.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260526
Author(s):  
Yasutaka Miyachi ◽  
Taiyi Kuo ◽  
Jinsook Son ◽  
Domenico Accili

Beta cell failure is a critical feature of diabetes. It includes defects of insulin production, secretion, and altered numbers of hormone-producing cells. In previous work, we have shown that beta cell failure is mechanistically linked to loss of Foxo1 function. This loss of function likely results from increased Foxo1 protein degradation, due to hyperacetylation of Foxo1 from increased nutrient turnover. To understand the mechanisms of Foxo1-related beta cell failure, we performed genome-wide analyses of its target genes, and identified putative mediators of sub-phenotypes of cellular dysfunction. Chromatin immunoprecipitation analyses demonstrated a striking pattern of Foxo1 binding to the promoters of a cluster of aldo-ketoreductases on chromosome 13: Akr1c12, Akr1c13, Akr1c19. Of these, Akr1c19 has been reported as a marker of Pdx1-positive endodermal progenitor cells. Here we show that Akr1c19 expression is dramatically decreased in db/db islets. Thus, we investigated whether Akr1c19 is involved in beta cell function. We performed gain- and loss-of-function experiments in cultured beta cells and generated Akr1c19 knockout mice. We show that Foxo1 and HNF1a cooperatively regulate Akr1c19 expression. Nonetheless, functional characterization of Akr1c19 both using islets and knockout mice did not reveal abnormalities on glucose homeostasis. We conclude that reduced expression of Akr1c19 is not sufficient to affect islet function.


2021 ◽  
Vol 8 (12) ◽  
pp. 161
Author(s):  
Yukiharu Sugimura ◽  
Sebastian Bauer ◽  
Moritz Benjamin Immohr ◽  
Derik Franz Hermsen ◽  
Ralf Westenfeld ◽  
...  

Despite the critical feature of heparin-induced thrombocytopenia (HIT) for patients on mechanical circulatory support, reports on its incidence and outcome are still scarce. Thus, we report on clinical features of HIT in patients under Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) support for acute cardiogenic shock (CS) by focusing on observed thrombotic events. Between November 2018 and December 2020, a total of 56 consecutive patients were enrolled in a single-center retrospective study. A total of 21 patients (37.5%) were tested for HIT, and 6 (10.7%) proved positive for HIT at 10.5 ± 2.89 days after the first heparin administration during current admission. Interestingly, thrombocyte counts dropped under Impella support in all groups (all cases, no HIT test, and HIT negative group: p < 0.001, HIT-positive group: p = 0.001). All HIT-positive patients were switched from heparin to argatroban. HIT-associated thrombotic events were observed in two cases resulting in Impella dysfunction due to pump thrombosis (n = 1) and left ventricular (LV) thrombus formation (n = 1). Under large Impella support, the prevalence of HIT was relatively high. Further, thrombocytopenia does not deliver a high specificity in the setting of Impella 5+ support. Considering HIT manifestation, a routine HIT test may be considered to avoid critical thrombotic adverse events.


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