Second Line Of Defense Research Articles

Response-driven adaptive under frequency load shedding scheme based on energy model

Developing reasonable and effective adaptive under frequency load shedding (AUFLS) schemes is crucial for preventing system frequency drops. In order to overcome the mismatching of event-driven load shedding scheme in the traditional second line of defense, this paper proposes a response-driven AUFLS scheme based on energy model. In this scheme, the energy model is established by the kinetic energy theorem, which represents the equivalent conversion relationship between rotor kinetic energy deviation (KED) and the unbalanced power does work (UPDW) of each component. Furthermore, a kinetic energy margin indicator (KEMI) reflecting the system frequency is introduced, and the minimum load shedding amount (MLSA) corresponding to the critical KEMI is calculated. The comprehensive load shedding allocation weight is established by combining the UPDW of load and shedding costs. The combination of MLSA and comprehensive load allocation weights enables precise control with minimal cost. Modified IEEE 10-generator 39-bus test system and CSEE-SSFS 197-bus real system are used to verify the performance of the proposed AUFLS scheme.

The biology of water homeostasis.

Water homeostasis is controlled by a brain-kidney axis that consists of central osmoreceptors, synthesis and secretion of arginine vasopressin (AVP) and AVP-responsive aquaporin-2 (AQP2) water channels in kidney collecting duct principal cells that facilitate water reabsorption. In addition to AVP, thirst represents a second line of defense to maintain water balance. Water balance disorders arise because of deficiency, resistance or inappropriate secretion of AVP or disturbances in thirst sensation (hypodipsia, polydipsia). People with water balance disorders are prone to develop hyponatremia or hypernatremia, which expose cells to osmotic stress and activate cell volume regulation mechanisms. This review covers several recent insights that have expanded our understanding of central osmoregulation, AQP2 regulation and cell volume regulation. This includes the role of with-no-lysine kinase 1 (WNK1) as a putative central osmolality sensor and, more generally, as an intracellular crowding sensor that coordinates the cell volume rescue response by activating sodium and potassium cotransporters. Furthermore, several new regulators of AQP2 have been identified, including for AVP-dependent AQP2 regulation (yes-associated protein, nuclear factor of activated T-cells, microRNAs) and AVP-independent AQP2 regulation (epidermal growth factor receptor, fluconazole, prostaglandin E2). It is also becoming increasingly clear that long-term cell volume adaptation to chronic hypotonicity through release of organic osmolytes comes at the expense of compromised organ function. This potentially explains the complications of chronic hyponatremia, including cognitive impairment, bone loss and vascular calcification. This review will illustrate why these new insights derived from basic science are also relevant for developing new approaches to treat water balance disorders.

Multi Attribute Trust Aware Routing for Adversary Detection in Wireless Sensor Networks

Security attacks has become major obstacles in Wireless Sensor Networks (WSN) and Trust Aware Routing is second line of defense. With an aim to improve on the existing routing mechanisms, in this paper, we propose Interactive, Onlooker and Capability Trust Aware Routing (IOC-TAR), a multi-trust attribute framework for trust management in WSNs. IOC-TAR employs three trust features to establish a trustworthy relationship between sensor nodes for their cooperation. Interactive trust uses communication interactions, onlooker trust uses neighbor node’s opinions and capability trust uses stability and fault tolerance for trust assessment. For, each node, one composite trust factor is formulated and decides its trustworthiness. Extensive simulation experiments are conducted to evaluate the effectiveness and efficiency of proposed IOC-TAR in the identification of malicious nodes and the provision of attack resilience. The results declare that the IOC-TAR enhances the attack resilience by improving Malicious Detection rate and reducing False Positive Rate.

6652 Precision Diagnostic Approaches for Assessing Clinical Vitamin D Status

Abstract Disclosure: Z. Shahidzadeh Yazdi: None. E.A. Streeten: None. H.B. Whitlatch: Grant Recipient; Self; Regeneron Pharmaceuticals. M.E. Montasser: Grant Recipient; Self; Regeneron Pharmaceuticals. A.L. Beitelshees: None. S.I. Taylor: Consulting Fee; Self; Ionis Pharmaceuticals Inc.. Background . The body has evolved effective homeostatic mechanisms to maintain free 1,25-dihydroxyvitamin D [1,25(OH)2D] within narrow physiological ranges. Using a mathematical model to quantitate 24-hydroxylase activity, we concluded that mild-moderate vitamin D [VitD] deficiency suppresses 24-hydroxylase activity (the first line of defense), thereby suppressing clearance of 1,25(OH)2D. Severe VitD deficiency triggers secondary hyperparathyroidism (the second line of defense) to sustain physiological levels of 1,25(OH)2D. Objective. To compare performance of various indices of VitD status in predicting whether homeostatic mechanisms have been triggered. Methods. We studied 11 otherwise healthy VitD deficient (25-hydroxyvitamin D [25(OH)D] ≤20 ng/mL) participants before and after VitD3 supplementation (50,000 IU once or twice a week depending on BMI for 4-6 weeks). We measured 25(OH)D, 1,25(OH)2D, 24,25-dihydroxyvitamin D [24,25(OH)2D], PTH, and FGF23 before and after VitD3 supplementation. We calculated three VitD metabolite ratios and also a PTH index (i.e., PTH level before divided by PTH level after VitD3 supplementation) to normalize PTH levels relative to each individual’s setpoint. We then compared the correlation between the PTH index and various indices of VitD status. Results. VitD3 supplements induced a 2.7-fold increase (p=0.0006) in mean 25(OH)D and a 4.3-fold increase (p=0.0002) in 24,25(OH)2D, but did not change 1,25(OH)2D, PTH, or FGF23. While relative 24-hydroxylase activity (h) was highly correlated with the 1,25(OH)2D/24,25(OH)2D ratio (ρ2=0.94; p=3E-13), it was less well correlated with the 24,25(OH)2D/25(OH) ratio (ρ2=0.67; p=3E-06) and baseline total 25(OH)D (ρ2=0.72; p=7E-07). Furthermore, we investigated the correlation between the PTH index and baseline 25(OH)D and three VitD metabolite ratios. The correlation coefficient was higher when we plotted the PTH index as a function of baseline 25(OH)D before VitD3 supplementation (R2=0.23; p=2E-06) compared to the correlation of baseline PTH with baseline 25(OH)D (R2=0.08; p=5E-05). While the correlation coefficient for the correlation of PTH index with 1,25(OH)2D/24,25(OH)2D was 0.60 (R2=0.36; p=0.0002), it was 0.44 for 25(OH)D/1,25(OH)2D ratio (R2=0.20; p=0.0001) and 0.35 for the 24,25(OH)2D/25(OH)D ratio (R2=0.12; p=2E-06). Conclusions. Measuring total 25(OH)D level did not provide optimal assessment of clinical VitD status – probably because it does not account for the threefold inter-individual variation in VitD binding protein level. Of all the indices, the 1,25(OH)2D/24,25(OH)2D ratio best predicted triggering of two homeostatic mechanisms: suppression of 24-hydroxylase and induction of secondary hyperparathyroidism due to VitD deficiency. Presentation: 6/2/2024

Key drivers of cybersecurity audit effectiveness: A neo‐institutional perspective

The aim of this paper is to analyse which factors explain the effectiveness of internal audit in providing assurance about cybersecurity risk management. On the basis of neo‐institutional theory, we hypothesize that coercive (cybersecurity regulation), normative (professionalization of internal auditors and Boards) and mimetic forces (outsourcing of cyber security assurance services) positively contribute to cybersecurity audit (CSA) effectiveness. As these forces do not come about in an interest free model, we study the role of and the interaction with other actors who shape the CSA practices—Boards and security experts. We hypothesize that Board's support to CSA and the level of internal auditors' cooperation with the first and the second line of defence positively affect CSA effectiveness. To test our hypothesis, we conducted a survey involving IT auditors and Chief Audit Executives from various industries, organizations of different sizes and countries. We examined the hypothesized relationships in a series of regression analyses. We find that normative forces (professionalization of the internal auditors and Boards' competences), Board's support to CSA and cooperation between the internal audit function (IAF) and the first two line of defence significantly explain the CSA effectiveness. We find no support for the effect of regulation as a coercive force and outsourcing as a mimetic force. We discuss potential reasons for our findings and their implications. The paper is an original analysis that advances our understanding of key drivers of CSA effectiveness and their relationships.

Compilation of Scientific Data for Newly CDSCO-Approved Antidiabetic Drugs in Last Five Years: A Review

Diabetes is a substantial medical problem that is increasing globally due to a rise in sedentary lifestyles, unhealthy eating habits, and obesity rates. There is a tight relationship between diabetes with obesity. Several epidemiological studies suggested that 80% of T2D patients are obese or overweight. Indeed, the immune system assaults the pancreatic beta cells that produce insulin in T1D, an autoimmune disease. High blood sugar levels occur when the body generates very little insulin. is frequently linked to unhealthy habits, including not getting enough exercise, eating poorly, and being overweight. Heart disease, diabetic neuropathy, kidney problems, ketoacidosis, and nerve damage are only some of the many health consequences that are more common with both types. Antidiabetic drugs like metformin can be used to lower the blood glucose level. Sulfonylureas, glinides, and thiazolidinediones are some most common oral antidiabetics (OADs), and for newly analyzed type 2 diabetes, glucosidase inhibitors are cost-effective strategies to improve glycaemic control. As a second line of defense against T2D, you may be prescribed an enzyme inhibitor (DPP-4i), an inhibitor of renal SGLT-2i, or an agonist for glucagon-like peptide-1 receptor. Poor adherence to oral antidiabetic medication regimens is associated with therapy failure and other consequences in patients with type 2 diabetes, which is a collective medical problem. Acarbose, miglitol, alogliptin, sitagliptin, sitagliptin-metformin, tirzepatide, liraglutide, nateglinide, rapeglinide, dopagliflozin, empagliflozin-metformin, glipizide-metformin, glimepiride-pioglitazone, glipizide, rosiglitazone, pioglitazone-alogliptin, and pioglitazone-metformin, among other antidiabetic medications, have been approved for use in India by CDSCO. All across the world, regulatory bodies are in charge of making sure that pharmaceuticals are safe, effective, and up to par at every stage of the drug lifecycle, from development to manufacture to marketing. Their job is to keep the public healthy

Первичный задний капсулорексис: исторические аспекты и современное состояние вопроса

Abstract Primary posterior capsulorexis: historical aspects and the current state of the issue E.V. Egorova, A.O. Direev, S. Fyodorov Eye Microsurgery Federal State Institution, Novosibirsk Branch, Novosibirsk, Russian Federation Research Institute of Internal and Preventive Medicine, Novosibirsk, Russian Federation Purpose. The paper analyzes the data of modern literature (published from 2008 to 2023) on the history and technique of primary posterior capsulorexis (PPC). The fields of application, variations, effectiveness and safety of the procedure are considered. Material and methods. A search for research on the subject of work from 2008 to 2023 was carried out. The search was carried out using Google Academy electronic databases (https://scholar.google.ru/), PubMed (https://www.ncbi.nlm. nih.gov/pubmed/), eLIBRARY.ru (https://www.elibrary.ru/) and foreign and domestic journals devoted to ophthalmology. Results. An analysis of the literature has shown that performing PPC provides high visual results both in comparison with standard cataract surgery and in the case of primary fibrosis of the posterior capsule. The key points of the PPC method are: intact anterior hyaloid membrane, continuous tear-resistant edge of capsulorexis and its size, which allows the preserved part of the PC to provide adequate support for the IOL and form a circular capsule barrier along the edge of its optical part. However, some studies have shown the possibility of partial or complete «closure» of the capsulorexis area by proliferating epithelial cells of the lens (ECL) in adult patients. In pediatric practice, it is well known that posterior hyaloid membrane (PHM) can act as a matrix for the migration of ECL, and the frequency of opacity of the optical axis after PPC reaches 60%. Therefore, in a number of clinics, the standard algorithm for cataract surgery in children includes not only PPC, but also anterior vitrectomy, although this complex approach is not always effective. As a solution to the problem of opacity of the optical axis after PPC, the technique of «capturing the optics» of the IOL was proposed, which permanently eliminates the opacity of the optical axis behind the IOL and significantly reduces fibrosis, especially in combination with polishing the anterior capsule. Conclusion. A large number of studies analyzing the clinical results of the PPC method, performed over several decades with various types of IOLs, leaves no doubt that performing posterior capsulorexis is a well-controlled method that significantly reduces the frequency of secondary cataracts, adding a «second line of defense» without reducing the barrier effect along the optical edge. Key words: anterior hyaloid membrane, Berger’s space, continuous curvilinear capsulorhexis, posterior optic capture

Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial

A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 μg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 μg RH5.1 at 0 and 1 month and 10 μg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 μg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 μg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 μg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per μg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 μg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 μg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.

AN AI-BASED SURVEILLANCE SYSTEM PROPOSAL FOR THE SECOND LINE OF DEFENSE AGAINST IRREGULAR MIGRATION, SMUGGLING, AND TERRORISM: GENDARMERIE ASSESSMENT

Despite the physical and technological measures in place along the border protected by border forces, a significant number of irregular migrants are being apprehended by gendarmerie (Jandarma) elements in the area designated as the second line of defense. This situation poses a crucial responsibility for the Jandarma in the context of preventing irregular migration movements, curbing smuggling activities, and combating terrorism. Therefore, it is proposed that artificial intelligence-supported technological discovery and surveillance measures be implemented in the Jandarma responsibility area behind the border. It is believed that these technological measures could be beneficial in preventing irregular migration movements, restricting smuggling activities, and enhancing effectiveness in the fight against terrorism. The implementation of these measures could contribute to public safety by increasing security and maintaining order. Within the scope of this study, a thermal camera network system powered by solar energy, featuring wireless communication capabilities, and equipped with artificial intelligence analysis, is described. Additionally, the technical architectural features of the system, installation requirements, and details of the artificial intelligence algorithms to be utilized within the system, along with their capabilities and potential algorithm specifics, are explained. The implementation of the proposed system is anticipated to enhance reconnaissance and surveillance capabilities.

Phages enhance both phytopathogen density control and rhizosphere microbiome suppressiveness.

Ralstonia solanacearum is a highly destructive plant-pathogenic bacterium with the ability to cause bacterial wilt in several crucial crop plants. Given the limitations of conventional chemical control methods, the use of bacterial viruses (phages) has been explored as an alternative biological control strategy. In this study, we show that increasing the phage application frequency can improve the density control of R. solanacearum, leading to a significant reduction in bacterial wilt disease. Furthermore, we found that repeated phage application increased the diversity of rhizosphere microbiota and specifically enriched Actinobacterial taxa that showed synergistic pathogen suppression when combined with phages due to resource and interference competition. Together, our study unravels an undiscovered benefit of phages, where phages trigger a second line of defense by the pathogen-suppressing bacteria present in resident microbial communities. Phage therapies could, hence, potentially be tailored according to host microbiota composition to unlock the pre-existing benefits provided by resident microbiota.

The Role of 24-hydroxylase in Homeostatic Regulation of 1,25-dihydroxyvitamin D

Background. Because of the importance of vitamin D (VitD) in calcium balance and bone health, the body has evolved effective homeostatic mechanisms to maintain 1,25-dihydroxyvitamin D [1,25(OH)2D] — the biologically active form — in a narrow physiological range. Objective and hypothesis. We developed a mathematical model to investigate homeostatic mechanisms regulating VitD metabolism with the objective of elucidating regulatory mechanisms maintaining levels of 1,25(OH)2D within a narrow physiological range despite wide variation in availability of VitD. Methods. We studied 11 otherwise healthy VitD deficient [25(OH)D<20 ng/mL] participants before and after VitD3 supplementation (50,000 IU once or twice a week depending on BMI for 4-6 weeks). We measured 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, PTH, and FGF23. We used a 2-tailed paired Student’s t-test to analyze our data; p=0.05 was selected as the criterion for statistical significance. This represents a secondary analysis of a previously published clinical trial [Shahidzadeh Yazdi et al. (2023) J Clin Endocrinol Metab, doi: 10.1210/clinem/dgad554]. Results. VitD3 supplements induced a significant 2.7-fold increase (p=0.0006) in mean 25(OH)D and a 4.3-fold increase (p=0.0002) in 24,25(OH)2D, but did not change 1,25(OH)2D, PTH, or FGF23. Our model showed that 24-hydroxylase activity was regulated over a 10-fold range — with maximal induction for 25(OH)D>50 ng/mL and maximal suppression for 25(OH)D<10-20 ng/mL). Because 24-hydroxylase catalyzes metabolic clearance of 1,25(OH)2D, high levels protect against VitD toxicity and low levels preserve 1,25(OH)2D when VitD is scarce. Thus, suppression of 24-hydroxylase activity is a homeostatic mechanism reflecting the body’s perception of VitD deficiency. Accordingly, measurements of 24,25(OH)2D levels can contribute to assessment of VitD status. However, measurements of total levels of all VitD metabolites [including 24,25(OH)2D] are confounded by the ~3-fold inter-individual variation in VitD binding protein (VDBP) levels. Fortunately, the ratio of 1,25(OH)2D /24,25(OH)2D is independent of VDBP levels. Our analysis suggests that this ratio provides a superior assessment of VitD status compared to the current recommendation to measure total 25(OH)D. For example, 24-hydroxylase activity is highly correlated with 1,25(OH)2D /24,25(OH)2D (ρ2=0.91) but less well correlated with 25(OH)D (ρ2=0.91). Conclusions. The body has two defense mechanisms to protect against VitD deficiency. The first line of defense is suppression of 24-hydroxylase, which is triggered by mild-moderate VitD deficiency and preserves VitD from degradation. However, at times of severe VitD deficiency, the first line of defense may be insuffcient to maintain 1,25(OH)2D in a physiological range. Therefore, the body triggers a second line of defense — secondary hyperparathyroidism, which in turn upregulates 1-hydroxylation and increases production of 1,25(OH)2D. By better understanding the physiology of homeostatic regulation of VitD metabolism, physicians can advance the state-of-the-art in diagnosing and treating VitD deficiency. Funding: R01DK118942; T32DK098107. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Towards a Re-insurance union? SURE as an EU response to preserve jobs in the COVID-19 pandemic

Is the EU evolving towards a Re-Insurance Union? The creation of SURE, an EU financial tool to support national short-time work (STW) schemes in the midst of the pandemic, has revitalized debates on fiscal stabilizers as a means to counter economic downturns and protect jobs within the European Union. Drawing from document analyses and 17 interviews with EU and national stakeholders, this study explores the politics underpinning SURE’s adoption following a decade of heated and unsuccessful debates on the European Unemployment Reinsurance Scheme (EURS). Through the lens of ‘purposeful opportunism’, the article illustrates how the European Commission leveraged prior EURS insights and the emerging consensus on STW schemes to craft SURE in a way which addressed national concerns about EU-wide welfare harmonization, while positioning the EU as a holding environment for national welfare states. Looking ahead, making SURE a permanent ‘second line of defence’ against macroeconomic shocks could contribute to further substantiating new, EU-wide, social rights codified in the European Pillar of Social Rights.

PTI-ETI synergistic signal mechanisms in plant immunity.

Plants face a relentless onslaught from a diverse array of pathogens in their natural environment, to which they have evolved a myriad of strategies that unfold across various temporal scales. Cell surface pattern recognition receptors (PRRs) detect conserved elicitors from pathogens or endogenous molecules released during pathogen invasion, initiating the first line of defence in plants, known as pattern-triggered immunity (PTI), which imparts a baseline level of disease resistance. Inside host cells, pathogen effectors are sensed by the nucleotide-binding/leucine-rich repeat (NLR) receptors, which then activate the second line of defence: effector-triggered immunity (ETI), offering a more potent and enduring defence mechanism. Moreover, PTI and ETI collaborate synergistically to bolster disease resistance and collectively trigger a cascade of downstream defence responses. This article provides a comprehensive review of plant defence responses, offering an overview of the stepwise activation of plant immunity and the interactions between PTI-ETI synergistic signal transduction.

Anticorrosion composite coating based on silver phosphate/poly-phenylene sulfide with excellent hydrophobicity and antimicrobial properties

Combating microbial contamination has been one of the hottest topics in the scientific community. Therefore, antibacterial materials have been rapidly developed and widely used in recent decades. However, developing corrosion-resistant coatings with both hydrophobic and antimicrobial properties remains challenging. This study innovatively mixed polyphenylene sulfide (PPS) resin with Ag3PO4/SiO2 filler, and prepared a hydrophobic antibacterial coating with enhanced corrosion resistance on the tinplate surface through a simple spraying strategy. After testing, the water contact angle of the composite coating is 139.7° ± 1°, and the sliding angle is less than 5° ± 1°. Compared with the pure PPS coating, the corrosion current of the composite coating was reduced by 4 orders of magnitude, with an impedance of 788740 Ω·cm2. After 200 h testing in a salt spray chamber, it still showed excellent corrosion resistance. Excellent hydrophobicity and anti-corrosion properties effectively reduce the adhesion of water, thereby preventing microorganisms from forming biofilms on the coating surface and corroding the substrate. In addition, bacterial tests show that the coating has excellent antibacterial efficacy, effectively inhibiting the reproduction of E. coli and S. aureus, providing a second line of defense to prevent bacteria from adhering to the substrate. Therefore, the multi-faceted characteristics make PPS composite coatings have broad application prospects.

Back-Up Base Excision DNA Repair in Human Cells Deficient in the Major AP Endonuclease, APE1.

Apurinic/apyrimidinic (AP) sites are abundant DNA lesions generated both by spontaneous base loss and as intermediates of base excision DNA repair. In human cells, they are normally repaired by an essential AP endonuclease, APE1, encoded by the APEX1 gene. Other enzymes can cleave AP sites by either hydrolysis or β-elimination in vitro, but it is not clear whether they provide the second line of defense in living cells. Here, we studied AP site repairs in APEX1 knockout derivatives of HEK293FT cells using a reporter system based on transcriptional mutagenesis in the enhanced green fluorescent protein gene. Despite an apparent lack of AP site-processing activity in vitro, the cells efficiently repaired the tetrahydrofuran AP site analog resistant to β-elimination. This ability persisted even when the second AP endonuclease homolog, APE2, was also knocked out. Moreover, APEX1 null cells were able to repair uracil, a DNA lesion that is removed via the formation of an AP site. If AP site hydrolysis was chemically blocked, the uracil repair required the presence of NTHL1, an enzyme that catalyzes β-elimination. Our results suggest that human cells possess at least two back-up AP site repair pathways, one of which is NTHL1-dependent.

Features of the immune response in early period of ixodid tick-borne borreliosis

Lyme borreliosis is a group of transmissible infectious diseases that are similar in etiology, but diverse in clinical manifestations. The development of Lyme disease symptoms is due not only to the activity of the pathogen itself, but also to the result of its interaction with immune system of macroorganism. The first line of defense, represented by a variety of cellular and humoral components of innate immunity, is most rapidly involved in immune response, and it is it that seeks to limit dissemination of the causative agent from the initial site of infection. However, a wide range of protective surface proteins of Borrelia and a number of other structures aimed at avoiding immune mechanisms prevent the destruction of the pathogen. Not the last place in this dynamic process is occupied by ixodid ticks themselves, since the secret of their salivary glands has an inhibitory effect on a number of cells and complement system. In parallel with innate immunity, adaptive immune response factors are activated, serving as a second line of defense. The synthesis of specific antibodies in the early period of Lyme disease has its own ambiguous features, but this does not exclude their importance in fight against borreliosis infection. To date, the issues of interaction with dendritic cells and cytotoxic T-lymphocytes remain less studied. Research of all aspects, including little-studied ones, is extremely important for both practical healthcare and fundamental medicine.

Communication and Content Trust Aware Routing For Clustered IoT Network

Security has become a major concern in practical applications related to Internet of Things, a Trust Aware Routing is found as second line of defence. To ensure a secure and hassle-free communication in IoT, this paper proposes a new routing strategy called as Communication and Content Trust Aware Routing (CCTAR) for Clustered IoT network. CCTAR is applied on a clustered IoT network in which the entire nodes are clustered into different clusters. Distance, initial energy, transmission range, angle of overlap and the sensing range are the fur major metrics used to cluster the network into hierarchical clusters followed by Cluster Head Selection. Next, the Trust Aware routing computes three different trust metrics namely Nobility rust, bilateral trust and Data oriented trust to determine the trustworthiness of Cluster Heads. The experimental evaluation of the proposed mechanism shows its superiority in terms of malicious nodes identification, Storage overhead reduction and Network lifetime improvisation.

The identification of BCL-XL and MCL-1 as key anti-apoptotic proteins in medulloblastoma that mediate distinct roles in chemotherapy resistance

Medulloblastoma is the most common malignant paediatric brain tumour, representing 20% of all paediatric intercranial tumours. Current aggressive treatment protocols and the use of radiation therapy in particular are associated with high levels of toxicity and significant adverse effects, and long-term sequelae can be severe. Therefore, improving chemotherapy efficacy could reduce the current reliance on radiation therapy. Here, we demonstrated that systems-level analysis of basal apoptosis protein expression and their signalling interactions can differentiate between medulloblastoma cell lines that undergo apoptosis in response to chemotherapy, and those that do not. Combining computational predictions with experimental BH3 profiling, we identified a therapeutically-exploitable dependence of medulloblastoma cells on BCL-XL, and experimentally validated that BCL-XL targeting, and not targeting of BCL-2 or MCL-1, can potentiate cisplatin-induced cytotoxicity in medulloblastoma cell lines with low sensitivity to cisplatin treatment. Finally, we identified MCL-1 as an anti-apoptotic mediator whose targeting is required for BCL-XL inhibitor-induced apoptosis. Collectively, our study identifies that BCL-XL and MCL-1 are the key anti-apoptotic proteins in medulloblastoma, which mediate distinct protective roles. While BCL-XL has a first-line role in protecting cells from apoptosis basally, MCL-1 represents a second line of defence that compensates for BCL-XL upon its inhibition. We provide rationale for the further evaluation of BCL-XL and MCL-1 inhibitors in the treatment of medulloblastoma, and together with current efforts to improve the cancer-specificity of BCL-2 family inhibitors, these novel treatment strategies have the potential to improve the future clinical management of medulloblastoma.

Exploring the Impact of Blood Disorders on Dental Caries.

Blood comprises various cellular elements and serves as our immune system's second line of defense. Deviations from its normal composition can have adverse effects on health. At the same time, the oral mucosa in the oral cavity functions as the body's first line of defense, and any anomalies or diseases within it can give rise to both systemic and oral complications. If left untreated, caries can lead to severe tooth damage or extraction, potentially affecting an individual's nutrition and overall health. This review article focuses on the importance of understanding the intricate relationship between blood disorders and oral health. It underscores the profound impact of oral manifestations of blood disorderssuch as β-thalassemia, sickle cell disease, iron deficiency anemia, leukemia, hemophilia, Plummer-Vinson syndrome, erythroblastosis fetalis, Fanconi anemia, cyclic neutropenia, and acute lymphoblastic leukemia on the overall well-being of an individual.

Experimental study of fully bolted joint composed of inner cruciform core and outer sleeve

To realize the ring truss of the long-span cable dome assembled by bolting, this paper proposed an innovative fully bolted joint which is composed of inner cruciform members superposed by angle steels and outer sleeves. It is the internal and external connections that achieve the mechanical performance of this fabricated joint the same as that of the welded joint. The joint has several advantages such as efficient construction, convenient assembly and disassembly and resource conservation. To study the mechanical property of the novel joint, three specimens were designed for low cycle reciprocating loading tests. Particularly, the failure mode, hysteresis performance, skeleton curve, stiffness degradation, ductility, bolt tension, strain distribution and energy dissipation capacity of the specimens were analyzed. According to the results, the hysteresis curves of the specimens were plump, and this joint had excellent stiffness and bending resistance, which was similar to the welded joint. In addition, the internal cruciform members cooperated with the bolts on the flange and played the role of the second line of defense, to ensure the bearing resistance and stiffness of the joint.