spike

Purpose • To assess the short term effects of intravitreal Lucentis (IVTL) on intraocular pressure in patients with ocular hypertension and glaucoma • To determine rate of anterior chamber paracentesis (ACP) required post-injection according to departmental protocol Methods This was a prospective, observational study carried out between August 2011 and February 2012 in the Department of Ophthalmology, Maidstone Hospital. 24 participants (13 female, 11 male) with established ocular hypertension (OHT) or glaucoma were chosen from a cohort of patients receiving intravitreal (IVTL) Ranibizumab (Lucentis) treatment for wet age related macular degeneration (wARMD). Apraclonidine 1% was given pre-injection, and baseline IOP was measured 30 min. after this, just before IVTL. IOP was measured at baseline, within 1 min of injection, 5 min, 15 min, 30 min up to 60min following a single IVTL treatment. Anterior paracentesis was performed if: • Immediate post injection IOP > 50mm Hg and OHT • Immediate post injection IOP > 40 mm Hg and there was evidence of disc damage only • Immediate post injection IOP > 30mm Hg with evidence of disc damage and visual field loss Results 79.2% had diagnosed disc damage and visual field loss (glaucoma); 12.5% had disc damage only (pre-perimetric glaucoma), whereas the remaining 8.3% had no evidence of disc damage or visual field loss i.e. ocular hypertension (OHT). Administration of Apraclonidine 1% prior to IVTL did not cause a statistically significant IOP reduction in patients with OHT and glaucoma (paired Student’s t-test P = 0.368). Immediately post injection, mean IOP was 41.54mm Hg (SD 14.1, 95% CI 37.20 to 45.88; Paired T test results P <0.0001,) which confirmed a statistically significant difference between baseline and immediate post injection IOP. 13 out of 24 (58%) of the study patients required anterior chamber paracentesis (ACP) post IVTL according to our devised protocol. There was no statistically significant difference in baseline IOP between the paracentesis and non-paracentesis groups (p=0.4). The presence of a bleb post injection had no statistically significant bearing on immediate post intravitreal IOP (p=0.3). ACP performed at 1min restored IOP to a safer level at 5min in all cases thus treated. Conclusions IVTL appears to cause a significant but transient rise in IOP which is reduced after a mean time of 5 minutes. Although the clinical significance of this IOP spike is still unknown, extreme care must be taken in patients with ocular hypertension and glaucoma particularly those with established disc damage and visual field loss. Apraclonidine 1% appears to have a limited role in the prophylactic lowering of IOP pre-injection. The authors propose the use of the formulated anterior chamber paracentesis protocol for IOP management in patients with OHT and glaucoma receiving intravitreal anti-VEGF treatment.

Related the physio-pathological process of COVID-19 disease it is interesting to focus to the aspect. Played by interaction of Sars-Cov-2 protein with integrins of human epithelial pulmonary cell. A bio molecular approach help in to deeply verify the involved factors and the results of this Activation RGD mediated. Of Great interest also the relationship with some vaccine strategy followed by the various pharmaceutical industry. The results of this work will be useful to think modification in some vaccine increasing the global safety and related some rare ADR.

Related the need to search new strategy in vaccine design in order to reduce also some rare effect like trombosys for some registered products it is interesting the role played by the SPIKE RGD domain. The binding with molecules like Fibronectin is a process that must to be deeply investigated. A better understanding in this process can be used to improve safety of the new generation of COVID vaccine. The rare effect like thrombosis recognized by regulatory agency produced a modification of technical data sheet of some vaccine so the phenomena Is interesting to be more investigated. Spike protein and its domains are involved in producing pathological effect of the COVID-19 disease. What it is interesting is that some pathological effect of this pathology are similar to some rare side effect produced by some COVID-19 vaccine classes. After a review of interesting literature related this topics is submitted an experimental projects able to verify in vitro the spike procoaugulant property.

The harmattan season, which is a period characterized by low temperature, dry air and increased air pollution leads to widespread airborne disease and exacerbation of pre-existing conditions, should be recognized as a period of potential risk of high COVID-19 infection rates. This period also coincides with the Christmas season which comes with so many festivities and can become a COVID-19 super-spreader. With many Nigerians now abandoning the non-pharmaceutical protection measures against COVID-19, the harmattan season and the forthcoming spike in social gatherings might usher in the second wave of the virus which can potentially be more catastrophic. There is need for the Nigerian government to start planning and instituting new protection measures and guidelines for safe Christmas celebration while also educating and encouraging the populace to adopt the protection measures recommended by experts.

Related the extremely transmittable abilities of SARS-CoV-2,a harmonious virus to the bat CoV, gets transmitted by three principal processes-- the inhalation of droplets from the SARS-CoV-2 infected person, contacting to the person, and by the surfaces and materials defiled with the virus. Whereupon bat Coronavirus is mostly like the pandemic causing virus SARS-CoV-2, bats are often deliberated and figured out as a possible primary host although no intermediate has not been defined yet in the wherewithal of transmission. The Spike Glycoprotein plays an important role in the case of penetration with the assistance of the ACE2 receptor and the Receptor Binding Domain. In the human body, infiltrating the nucleic acid into host cells, SARS-CoV-2 attacks one cell and one by one into the whole human body; therefore, infected cases are found symptomatic and asymptomatic considering the immune power. Patients with cardiovascular disease or diabetes proceed with their treatment with ACE2 often; therefore, there might be a high chance of getting infected. Whereas the SARS-CoV-2 infects the blood and then lungs, Antigens improvement can be better in order to avoid high-complicated effects. Currently, no vaccination or no accurate cure and treatment has not been defined. An explanation with analysis on SARS-CoV-2 has been performed from the aspect of virology, immunology and molecular biology. Several relevant figures have been included hereby in order to a better understanding of the very concept.

COVID-19 virus structural components: The 2019-nCoV, also called SARS-CoV-2, was first reported in Wuhan, China in December 2019. The disease was named Coronavirus Disease 2019 (COVID-19) and the virus responsible for it as the COVID-19 virus, respectively, by WHO. The 2019-nCoV has a round, elliptic or pleomorphic form with a diameter of 60–140 nm. It has single-stranded RNA genome containing 29891 nucleotides, a lipid shell, and spike, envelope, membrane and hemagglutinin-esterase (HE) proteins. Steps in progression of COVID-19 illness: Once inside the airways, the S protein on the viral surface recognizes and mediates the attachment to host ACE-2 receptors and gains access to endoplasmic reticulum. The HE protein facilitates the S protein-mediated cell entry and virus spread through the mucosa, helping the virus to attack the ACE2-bearing cells lining the airways and infecting upper as well as lower respiratory tracts. With the dying cells sloughing down and filling the airways, the virus is carried deeper into the lungs. In addition, the virus is able to infect ACE2-bearing cells in other organs, including the blood vessels, gut and kidneys. With the viral infestation, the activated immune system leads to inflammation, pyrexia and pulmonary edema. The hyperactivated immune response, called cytokine storm in extreme cases, can damage various organs apart from lungs and increases susceptibility to infectious bacteria especially in those suffering from chronic diseases. The current therapeutics for COVID-19: At present, there is no specific antiviral treatment available for the disease. The milder cases may need no treatment. In moderate to severe cases, the clinical management includes infection prevention and control measures, and symptomatic and supportive care, including supplementary oxygen therapy. In the critically ill patients, mechanical ventilation is required for respiratory failure and hemodynamic support is imperative for managing circulatory failure and septic shock. Conclusion: Confusion, despair and hopes: There is no vaccine for preexposure prophylaxis or postexposure management. There are no specific approved drugs for the treatment for the disease. A number of drugs approved for other conditions as well as several investigational drugs are being canned and studied in several clinical trials for their likely role in COVID-19 prophylaxis or treatment. The future seems afflicted with dormant therapeutic options as well as faux Espoir or false hopes. As obvious, not all clinical trials will be successful, but having so many efforts in progress, some may succeed and provide a positive solution. Right now, though, confusion and despair prevail.

The nemesis: SARS-CoV-2 pandemic: Leaving in its wake millions of infections, accompanied by an immense magnitude of morbidity and multitude of mortality, and an unfathomable economic toll, the COVID-19 pandemic has led to a global calamity. An effective and safe COVID-19 vaccine is urgently needed to prevent the disease, thwart the complications and avert deaths resulting from unrestrained transmission of the infection. The hubris: Vaccine development: While most of the platforms of vaccine candidates have focused on the spike (S) protein and its variants as the primary antigen of COVID-19 infection, various techniques involved include nucleic acid technologies (RNA and DNA), non-replicating viral vectors, peptides, recombinant proteins, live attenuated and inactivated viruses. There are novel vaccine technologies being developed using next-generation strategies for precision and flexibility for antigen manipulation relating to SARS-CoV-2 infection mechanisms. The elpis: Updates and prospects: There were nine different technology platforms under research and development to create an effective vaccine against COVID 19. Although there are no licensed vaccines against COVID-19 yet, there are various potential vaccine candidates under development and advanced clinical trials. Out of them, one having undergone phase III clinical trials, has become available in some countries for use among the high-risk groups following emergency use authorization. Other COVID-19 vaccines may soon follow the suit. Conclusion: Hopes and concerns: The hope of benefiting from the vaccine to the extent that it may be the only way to tide over and control the COVID-19 pandemic, is accompanied by the likely fear of adverse effects and opposition in public for COVID-19 vaccination, including the vaccine hesitancy. Further, there is concern among scientific circles that vaccine may have opposite of the desired effect by causing antibody-dependent disease enhancement.

Introduction: SARS-CoV-2 life cycle: The disease which reportedly began in Chinese city Wuhan in November-December 2019 manifesting as severe respiratory illness, soon spread to various parts of the world, and was named COVID-19, and declared a pandemic by WHO. The life cycle of SARS-CoV-2 begins with membrane fusion mediated by Spike (S) protein binding to the ACE2 receptors. Following viral entry and release of genome into the host cell cytoplasm there occurs replication and transcription to generate viral structural and non-structural proteins. Finally, VLPs are produced and the mature virions are released from the host cell. Immunogenicity of the spike protein: The S protein is considered the main antigenic component among structural proteins of SARS-CoV-2 and responsible for inducing the host immune response. The neutralising antibodies (nAbs) targeting the S protein are produced and may confer a protective immunity against the viral infection. Further, the role of the S protein in infectivity also makes it an important tool for diagnostic antigen-based testing and vaccine development. The S-specific antibodies, memory B and circulating TFH cells are consistently elicited following SARS-CoV-2 infection, and COVID-19 vaccine shots in clinical trials. The emerging SARS-CoV-2 variants: The early genomic variations in SARS-CoV-2 have gone almost unnoticed having lacked an impact on disease transmission or its clinical course. Some of the recently discovered mutations, however, have impact on transmissibility, infectivity, or immune response. One such mutation is the D614G variant, which has increased in prevalence to currently become the dominant variant world-over. Another, relatively new variant, named VUI-202012/01 or B.1.1.7 has acquired 17 genomic alterations and carries the risk of enhanced infectivity. Further, its potential impact on vaccine efficacy is a worrisome issue. Conclusion: THE UNMET CHALLENGES: COVID-19 as a disease and SARS-CoV-2 as its causative organism, continue to remain an enigma. While we continue to explore the agent factors, disease transmission dynamics, pathogenesis and clinical spectrum of the disease, and therapeutic modalities, the grievous nature of the disease has led to emergency authorizations for COVID-19 vaccines in various countries. Further, the virus may continue to persist and afflict for years to come, as future course of the disease is linked to certain unknown factors like effects of seasonality on virus transmission and unpredictable nature of immune response to the disease.

The halophyte Distichlis palmeri (Vasey) is a plant resource with high potential to be harvested in the coastal areas of northwestern Mexico; enlarge the knowledge and domestication for its incursion into the agricultural sector, plays an important role for arid areas with saline intrusion problems. However, its productivity depends on the supplementary supply of nitrogen, as well as other essential macro and micronutrients. The microorganisms considered beneficial are an alternative to chemical fertilization, highlighting those Plant Growth Promoting Bacteria (PGPB). In the present study, the inoculation of the Bacillus amyloliquefaciens (B.a.) as a halobacterium PGPB was evaluated to know the response in seeds of Distichlis spicatai obtained from natural population from colorado river in Delta north of the Gulf of California. Wild seed was collected and germinated previously inoculated with B. a., and sowed in germinated beds. Later, seedlings were planted under field and salinity conditions in the coast of Hermosillo, Sonora. Three treatments were examined (T1: B.a., T2: Chemical fertilization, T3: Negative control), with four repetitions each treatment. Each repetition consisted of experimental plots of 5 x 5 m, with a separation of 1 m between them. The harvest was carried out 600 days after sowing. The results indicate that treatments inoculated with halobacteria B.a., showed significant results in crude protein, non-protein nitrogen, neutral detergent fiber and acid detergent fiber, as well as spike length and number of seeds. The results obtained suggests the feasibility of biofertilizers where biomass and seed production are significant compared to non-inoculated controls.

Related COVID vaccine production many different strategies was followed by the producers. Observing some rare event of thrombosis after some COVID-19 vaccination, it is interesting to verify if the Target used for the manufacturing can be involved in a different procoagulant activity or not. Some vaccine are suspended in some country or under a deep new verify- investigation by the regulatory agency. (EU or USA). This fact it is relevant. The target SPIKE-PROTEIN FULL LENGTH modified or not or towards the RBD domain can be a relevant factor.

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) originally emerged in China during December 2019 and had become a global pandemic by March 2020. COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Two other coronaviruses have caused world-wide outbreaks in the past two decades, namely SARS-CoV (2002–2003) and Middle East respiratory syndrome coronavirus (MERS-CoV) (2012–present). The surface spike glycoprotein (S), which is critical for virus entry through engaging the host receptor and mediating virus host membrane fusion, is the major antigen of coronaviruses. Recent studies provide molecular insights into antibody recognition of SARS-CoV-2. In this review, we discuss the relationship between the spike glycoprotein of SARS-CoV-2 and its receptor, angiotensin converting enzyme 2 (ACE2) including the latest findings.

COVID-19 is a disease that is caused by SARS-CoV-2 and very speedily spreading all over the world. The blood group’s effect on COVID-19 is not clear. The main aim of this article is to determine the relationship between sensitivity of COVID-19 and ABO blood group. For this study we have observed that the individuals with blood group A are at higher risk of getting COVID-19 because they contain the higher concentration of Angiotensin-converting enzyme-2 that provide the site to virus for entry. But in other blood groups the natural Anti A antibodies block the interaction between host receptor and virus and disturb their interaction. Certain studies show that the infectivity and mortality rate in covid patients is not affected by AB blood group system. But according to research, increased ventilator usage, ICU stay was observed in critically ill patients with AB blood group than of other blood groups. O blood group has proved to be protective against SARS-CoV-2 due to the presence of both anti-A and anti-B antibodies as they prevent the binding of the spike protein S of the virus with the ACE2 receptors which are present on the surface of cells. Moreover, furin also plays a major role in penetration of virus in the host cells. Furin is required for the activation of the spike protein S of the virus and due to the low efficiency of furin cleavage in blood group O it is protected from SARS-CoV-2 and other chronic diseases. Mortality rate of covid 19 depends upon the environmental factors, number of people living in the area and also some economic factors. The different strains of COVID-19 effect the different people differently and as the time passes the strain of COVID-19 has changed and thus according to this the mortality rate of different provinces and areas varies due to environmental factors. Pregnant women have no any kind of transportation of covid to their fetuses but mostly patients of blood group A are being affected by COVID-19 and hence their fetuses are somehow effected. And those pregnant women having blood group O does not have any risk of COVID-19 of severe stages.

SARS-CoV-2 is a virus that has a positive-sense, single-stranded RNA genome that encodes 4 structural proteins, the main one being the S protein (Spike) responsible for mediating with ACE2 and TMPRSS2 for entry into the host cell. The study of single nucleotide polymorphisms (SNPs) of ACE2 and TMPRSS2 can elucidate their possible intervention in the action of the protein, its activity, and the gene expression of encoding these enzymes, which may increase susceptibility to viral infection. From this, literature searches were carried out until December 2021, listing 11,820 publications for literary analysis on the described genetic variations of these protein structures, as well as their relation and influence on the pathology. It was possible to conclude that there is a great influence exerted by genetic variability in ACE2 and TMPRSS2 increasing the ability of the virus to bind to the host cell and the development of COVID-19 with complications. 

Polychlorinated dibenzo-p-dioxins, dibenzofurans and dioxin-like polychlorinated biphenyls are persistent organic pollutants (POPs), which in recent years received huge attention due to their extreme stability, high potential toxicity and bioaccumulation in food chains. The main source of human exposure to these compounds is discovered in foods of animal origin, especially foods rich in fat. The target of the present study was to set up an analytical method for the determination of PCDDs/PCDFs and DL-PCB in vegetable oils, sunflower meals, sunflower seeds, rapeseeds and milk powder. The first step consisted of a semi-automatic Soxhlet extraction for 3 hours, by using a mixture of Hexane: Acetone – 80:20, followed by acid digestion with 55% acid silica and filtration. After concentration, the extract is purified on a multilayer column (silica gel, silica-KOH, silica-H2SO4 anhydrous Na2SO4) followed by an alumina column separation in two fractions (first fraction containing PCDDs/PCDFs and second containing only PCBs). The purified extract was then analyzed by GC/MS/MS. The newly developed approach in our lab was capable to reduce the overall time of sample preparation to seven hours/ per sample. Since the method shows good mean recoveries for all labeled congeners spiked in the samples (for PCDDs/PCDFs – 80% - 110%, for DL-PCBs – 70% - 85%), we assumed the absence of overestimation or underestimation in the analyzed samples.

Introduction: Myopia is a refractive disorder commonly diagnosed in childhood that follows a progressive course. It is considered a global epidemic with nearly 23% of the world’s population being diagnosed with this condition. Moreover, myopia is increasing in prevalence worldwide, demonstrated by studies in Asian and Western populations. This has important implications as myopic progression to high myopia is associated with significant morbidity and visual disability if left untreated. Of these treatments, the pharmacologic agent atropine has demonstrated the greatest efficacy in reducing myopia progression.Case report: This is a case report of an 11-year-old male treated with 0.01% atropine drops for myopia progression that developed new-onset seizures. The seizures were characterized as benign epilepsy with central temporal spikes and ceased when drops were discontinued. Discussion: Atropine 1% drops have previously been associated with new or increased seizure activity in a handful of case reports, however, it is our knowledge that this is the first report associated with 0.01% drops. This is important given the growing use of 0.01% drops as well as higher concentrations such as 0.025 % and 0.05% for the treatment of pediatric myopia. Conclusion: While it cannot be proven that the drops were causative in the seizure events, it is important to consider prior seizures as a relative contraindication to the use of these drops.  Atropine has the potential to exacerbate seizure activity, so it is possible that the 0.01% atropine drops played a role in the patient’s seizures. Also, any diagnosis of new-onset seizures in pediatric patients should prompt discontinuation of drops at seizure onset.

Today, it is well known that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has four types of proteins within its structure, between them the spike protein (S). The infection mechanism is carried out by the entry of the virus into the human host cell through the S protein, which strongly interacts with the human cell receptor angiotensin-converting enzyme 2 (ACE2). In this work, we propose an atomic model of the Receptor Binding Domain (RBD) of the S spike protein of the wild-type SARS-CoV-2 virus. The molecular structure of the model was composed of 50 amino acids that were chemically bonded, starting with Leucine and ending with one amino acid Tyrosine. The novelty of our work lies in the importance of knowing the sites and zones of maximum reactivity of the RBD from the fundamental levels of quantum mechanics considering the atomic structure of matter. For this, the local and global reactivity indices of the RBD were calculated, such as frontier orbitals, Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), Fukui indices, chemical potential, chemical hardness, electrophilicity index; with this, it will be possible to know what type of molecules are more likely to interact with the RBD structure, and in this way, new knowledge will be generated at the quantum, atomic and molecular level to inhibit the virulent effects of wild-type SARS-CoV-2. Finally, in order to identify the functional groups within the most stable structure and thereby verify the future reactions that can be carried out between the RBD structure and biomolecules, the Infrared (IR) absorption spectrum was calculated. For this work, we used Material Studio v6.0 which uses the density functional theory (DFT) implemented in its DMol3 computational code. The IR spectrum was obtained using the Spartan ‘94 computer code. One novelty would be that we found nine amino acids more that could make the RBD and ACE2 binding further the already known. Thus, the Mulliken charge distribution indicates that the highest concentrations of positive and negative charge are found in the zones 477S, 478T, 484E, and 501N amino acids letting ionic or Van der Waals possible interactions with other structures.

This study aimed to investigate the effects of colchicine treatment on the reproductive traits and grain yield of two species of Acha, Digitaria exilis and Digitaria iburua. Colchicine, a mitotic inhibitor, is known for inducing polyploidy and altering plant characteristics. The study focused on evaluating number of spikes, spike length, number of seeds per spike, and grain yield per hectare. The experiment was conducted in a randomized complete block design with three replications. The treatment groups included colchicine-treated plants at varying concentrations (0.05, 0.10, 0.15, and 0.20 g/dL) and control plants (untreated). The colchicine treatment involved the soaking of both Acha species in the colchicine solution for a period of 24 hours. While the control groups were soaked in distilled water. The results showed that colchicine treatment significantly affected the agronomic traits and grain yield of both Digitaria exilis and Digitaria iburua. Colchicine treatment led to an increase in the number of spikes (5.80 and 9.90 for D. exilis and D. iburua respectively), spike length (13.60 cm and 19.50 cm for D. exilis and D. iburua respectively), and number of seeds per spike (168.30 and 253.30 for D. exilis and D. iburua respectively), compared to the control group. Additionally, the grain yield per hectare was significantly higher (427.80gha-1 and 2126.70gha-1 for D. exilis and D. iburua respectively) in the colchicine-treated group. These findings suggest that colchicine treatment can effectively enhance the agronomic traits and grain yield of both Digitaria exilis and Digitaria iburua. The induced polyploidy through colchicine treatment likely contributed to the observed improvements in plant productivity. Further research is warranted to investigate the underlying mechanisms and to optimize the colchicine treatment protocol for Acha cultivation and improvement.

Bloodstain Pattern Analysis (BPA) is a crucial forensic technique in crime scene investigation, employing the interpretation of blood spatter patterns to reconstruct event sequences and determine spatial relationships between victims and surfaces. This study explores BPA’s application in forensic science, emphasizing its role in establishing links between crimes and culprits, as posited by Edmond Locard’s exchange principle. The research examines how bloodstain shape, size, and distribution reveal critical information about impact angles, areas of convergence, and points of origin, while also providing insights into blood flow direction, force applied, suspect positioning, and weapons used. The investigation delves into various bloodstain types, including void patterns, spikes, and satellite stains, and their formation on different surfaces. To enhance understanding of blood behaviour from various sources, the study compares blood samples from three species: human (Homo sapiens), obtained from a professional doctor from discarded piles with precaution from a government hospital in Laxmangarh, Rajasthan and goat (Capra aegagrus hircus), and chicken (Gallus gallus domesticus), obtained from butcher shops in Laxmangarh, Rajasthan. The experimental setup involves dropping blood from a height of 50 centimetre’s and measuring the resulting stain dimensions. This comprehensive approach to BPA research aims to refine crime scene analysis techniques, ultimately contributing to more accurate event reconstructions and enhanced forensic investigations. The study underscores the importance of BPA in modern forensic science while acknowledging the need for its integration with other investigative methods to ensure robust and reliable crime scene interpretations.

Background: Human 30kb coronaviruses entered through the ACE-2 receptors causing fibrosis of the lungs and causing six million deaths worldwide. Here, we have investigated the mutations, deletions and insertions of the recent JN.1 omicron coronaviruses to demonstrate that coronaviruses have reached the pre-elimination stage. Methods: We multi-aligned the genomes of recent JN.1 variants using NCBI Virus Portal and CLUSTAL-Omega. The spike proteins are multi-aligned using MultAlin software and CLUSTAL-Omega.Results: The 17MPLF spike insertion was confirmed to compensate 24LPP, 31S, 69HV, 145Y, 211N and 483V deletions. The 49nt deletions in the 3’-UTR were found in 4997 JN.1 sequences although 26nt deletion was initiated previously in JN.1 as well as BA.5, BF.7, BQ.1 and XBB.1.5 omicron viruses. We first compare 3-D structures of spike proteins with or without 17MPLF four amino acids insertion and nine amino acids deletions using SWISS MODELLING. The JN.1 viruses caused a more stable trimeric spike involving Thr342, Lys436, Lys440, His441, Ser442, Gly443, Tyr445, Lys479, Ser489, Tyr490, Arg493, Pro494, Thr495, and Gln501 amino acids to interact with ACE-2 receptors. The FLiRT spike mutations were found in most KP.2 variants and other changes occurred at the NH2 terminus.Conclusion: We claimed that pre-death changes were initiated in JN.1 COVID-19 lineages and computer simulation showed that the Howard spike with 17MPLF spike insertion appeared more stable than the Oppentrons-spike without 17MPLF insertion. Surely, conflicts of COVID-19 spike sequences must be resolved.

Bifurcation analysis and Multiobjective Nonlinear Model Predictive Control (MNLMPC) calculations were performed on a model of circadian oscillations of the Period (PER) and Timeless (TIM) proteins in Drosophila. The MATLAB program MATCONT was used to perform the bifurcation analysis. The optimization language PYOMO was used along with the state-of-the-art global optimization solvers IPOPT and BARON for the MNLMPC calculations. The bifurcation analysis revealed oscillation causing Hopf bifurcations while the MNLMPC calculations revealed the existence of spikes in the control profiles. Both Hopf bifurcation points and the control profile spikes were eliminated using an activation factor involving the hyperbolic tangent function.