Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using HPV16E6E7 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+T cell response with minimally a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7,464 specimens (oropharyngeal and cloacal swabs) from poultry and 6,531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n=292) of specimens collected from poultry and 0.2% (n=10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as low pathogenicity avian influenza H5N2 virus of the Eurasian lineage and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP/NS swabs from poultry workers with ARI (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

Automated Machine Learning (AutoML) is revolutionizing how businesses utilize data, making advanced analytics accessible to a broader range of organizations. By automating complex tasks like data preprocessing, model selection, and hyperparameter tuning, AutoML reduces the time and resources needed to develop and deploy machine learning models. This accelerates decision-making and enables quicker responses to market changes. AutoML empowers businesses to build accurate predictive models using sophisticated algorithms, optimizing model performance for reliable insights and better outcomes. A key advantage of AutoML is its accessibility; even organizations without a dedicated data science team can leverage machine learning, reducing technical barriers and democratizing innovation. As businesses grow, AutoML scales to handle larger datasets and more complex problems without extensive manual intervention. AutoML enhances efficiency, accuracy, and scalability, becoming a crucial driver of business innovation and success. The systematic review will examine the bibliometric literature on how AutoML can boost business, analyzing 74 academic and scientific documents from the Scopus database.

In this contribution a new configuration of a DC-DC Boost and Buck-Boost converters is proposed to track sinusoidal signals exactly, with zero tracking error. The stage is conformed by two DC-DC converters connected to the same load, this is, they are not connected in cascade. To track exactly the sinusoidal reference the control scheme is base on the indirect control algorithm and the harmonic balance method. The proposed algorithm considers a second control input with the end of cancel out the second harmonic, this second harmonic is produced by the non linearity of the model and must be cancelled since there must be a single frequency in the output. The result is such that the converters can track sinusoidal signals with exactly zero error, some numerical results are presented to corroborate the proposal.

Cameroon introduced the malaria vaccine in its routine immunization programme on 22 January 2024, in the 42 districts out of 200, among the most at risk of malaria. A cross-sectional analysis of data on vaccine key events in the introduction roadmap and vaccine uptake during the first 30 days was conducted. In addition to available gray literature related to the introduction of the malaria vaccine, data on malaria vaccine uptake by vaccination session, collected through a digital platform, were analyzed. A total of 1,893 reports were received from 22 January 2024 to 21 February 2024 from 766 health facilities (85% of overall completeness). Two regions out of 10 recorded less than 80% of completeness. As of 21 February 2024, 13,811 children have received the first dose of the malaria vaccine, including 7,124 girls (51.6%) and 6,687 boys (48.4%). Thirty six percent of children were vaccinated through outreach sessions versus 61.5% through sessions in fixed posts. The overall monthly immunization coverage with the first dose was 37%. Early results have shown positive attitudes towards and acceptance of malaria vaccines. Suboptimal completeness of data reporting and low coverage highlight persistent gaps and challenges in vaccine rollout.

Underreporting is the main limitation of the spontaneous reporting systems. This study aims to reduce underreporting enhancing public participation in vaccinovigilance through an SMS-based reporting system integrated with electronic immunization registries (IRs). Using the VigiVax software, parents of vaccinated children aged 2 years or younger received a single SMS inquiry about adverse events following immunization (AEFI). Responses were collected, validated by health operators and integrated with the information on IRs. AEFI reports were automatically submitted to the Italian Pharmacovigilance system. Among 254,160 SMS messages sent, corre-sponding to 451,656 administered doses (AD), 71,643 responses were collected (28.2% response rate), 21,231of them (8.3%) reporting an AEFI. After seriousness assessment based on clinical criteria, 50 reports (0,24%) were classified as serious. Among these, causality assessment identi-fied 31 reports at least potentially related to the vaccination (RR: 6.86/100,000 AD). Febrile seizures following MMRV vaccination accounted for 11 of these 31 cases, with an incidence of 32 per 100,000 AD. No fatal outcomes were reported. Our findings support the highly favorable risk profile of pediatric vaccinations and the possibility to improve spontaneous reporting through the integration of digital technologies.

In this study, we demonstrate a high luminous efficacy of 118 lm/W and high reliability through 450°C thermal aging of white LEDs (WLEDs) utilizing four-inch YAG: Ce3+ phosphor-in-glass (PiG) plates designed for vehicle headlights. The sintering process of mixing glass and phosphor typically generates pores, which can scatter light and reduce the luminous efficacy of the fabricated PiG. In this study, we produced four-inch PiG plates under four different fabrication conditions to evaluate their luminous efficacy. Our results revealed that the PiG plate with a thin thickness of 0.08 mm exhibited a 16.83% increase in luminous efficacy compared to the 0.15 mm plate, attributed to reduced light interaction with the pores. Unlike silicone-based phosphor WLEDs, which offer high performance but lower reliability due to the silicone resin's low transition temperature (150°C), our novel thin PiG plate achieves high performance and reliability. This advancement suggests that the proposed thin PiG plate could replace traditional silicone-based phosphors, enabling the development of high-quality WLEDs for vehicle headlights in automotive applications.

A twin prime numbers are two prime numbers which have the difference of 2 exactly. In other words, twin primes is a pair of prime that has a prime gap of two. Sometimes the term twin prime is used for a pair of twin primes; an alternative name for this is prime twin or prime pair. Up to date there is no any valid proof/disproof for twin prime conjecture. Through this research paper, my attempt is to provide a valid disproof for twin prime conjecture.

The global COVID-19 pandemic has affected all spheres of human life, resulting in millions of deaths and overwhelming medical facilities. Moreover, the world has witnessed great financial hardship because of job losses resulting in economic havoc. Many sections of society have contributed in different ways to slow the spread of the virus and protect public health. For example, medical scientists are praised for their efforts to develop COVID-19 vaccines. Clinical trials have shown that the COVID-19 vaccines are highly effective in preventing symptomatic COVID-19 infections. However, many people around the world have been hesitant to get vaccinated. Vaccine misconceptions have emerged and increased due to a combination of factors, including the availability of information on the Internet and the influence of celebrities and opinion leaders. In this context, we have analyzed ChatGPT responses to relevant queries on vaccine misconceptions. The positive responses and supportive opinions provided by the AI chatbot could be instrumental in shaping people’s perceptions of vaccines and in encouraging users to get vaccinated and reduce misconceptions.

Modular inversion on large operands is a time-consuming calculation used in elliptic curve cryptography. Its hardware implementation requires extensive hardware resources such as lookup tables and registers. We investigate state-of-the-art modular inversion algorithms and evaluate the performance and cost of the algorithms and their hardware implementations. We then propose a high-radix modular inversion algorithm aimed at short execution time and low hardware cost. We present a detailed radix-8 hardware implementation based on 256-bit primes in Verilog HDL and compare its cost performance with other implementations. Our implementation on the Altera Cyclone V FPGA chip uses 1227 ALMs (Adaptive logic modules) and 1037 registers. The modular inversion calculation takes 3.67 microseconds. The AT (Area time) factor is 8.30, outperforming other implementations. We also present an implementation of elliptic curve cryptography using the proposed radix-8 modular inversion algorithm. The implementation results also show that our modular inversion algorithm is more efficient in area time than other algorithms.

Let R be a commutative graded ring with unity, S be a multiplicative subset of homogeneous elements of R and P be a graded ideal of R such that P\bigcap S=\emptyset In this article, we introduce several results concerning graded S-prime ideals. Then we introduce the concept of graded weakly S-prime ideals which is a generalization of graded weakly prime ideals. We say that P is a graded weakly S-prime ideal of R if there exists s\in S such that for all x, y\in h(R), if 0\neq xy\in P, then sx\in P or sy\in P. We show that graded weakly S-prime ideals have many acquaintance properties to these of graded weakly prime ideals.

Integer is either a composite number or a prime number. Therefore, detecting composite numbers is important for solving prime numbers. The study of prime numbers, apart from satisfying human curiosity, can be very important. In this article, the order of composite numbers has been detected. And explained with a simple method and a simple function. And, a method has been developed in which all composite numbers and therefore prime numbers can be determined by using the specified methods, functions and formulas.

The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

This paper proposes a novel single-stage buck-boost three-Level neutral-point-clamped (NPC) inverter with two independent dc sources coupled for the grid-tied photovoltaic (PV) application, which can effectively solve the unbalanced operational conditions generally appeared between two coupled independent PV sources induced by the unequal irradiation and temperature distribution. The proposed control scheme can simultaneously guarantee the maximum power point (MPP) operation of both PV sources and maintain the output waveform quality. Compared to the traditional two-stage PV inverter, the proposed NPC inverter could reduce the PV array voltage requirement and dc-link capacitors’ voltage rating, meanwhile show the advantage in operational efficiency. MATLAB simulations and the captured experimental results are presented to show the performance of the proposed three-level inverter.

Let R be a commutative ring with identity and m, n be positive integers. In this paper, we introduce the class of (m,n)-prime ideals which lies properly between the classes of prime and (m,n)-closed ideals. A proper ideal I of R is called (m,n)-prime if for a,b∈R, a^{m}b∈I implies either aⁿ∈I or b∈I. Several characterizations of this new class with many examples are given. Analougus to primary decomposition, we define the (m,n)-decomposition of ideals and show that every ideal in an n-Noetherian ring has an (m,n)-decomposition. Furthermore, the (m,n)-prime avoidance theorem is proved.

In this research first, a sequence of properties called delta is assigned to each prime number and then examined. Deltas are only dependent on the distribution of prime numbers, so the results obtained for the delta distribution can be considered as a proxy for the distribution of prime numbers. The first observation was that these properties are not unique and different prime numbers may have the same value of delta of a given order. It was found that a small number of deltas cover a large portion of prime numbers, so by recognizing repetitive deltas, the next prime numbers can be predicted with a certain probability, but the most important observation of this study is the normal distribution of deltas. This research has not tried to justify the obtained observations and instead of answering the questions, it seeks to ask the right question.

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID- 19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients and with monoclonal antibodies against the viral S-protein. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.

A well-known result of Posner’s second theorem states that if the commutator of each element in a prime ring and its image under a nonzero derivation is central, then the ring is commutative. In the present paper, we extend this bluestocking theorem to an arbitrary ring with involution involving prime ideals. Further, apart from proving several other interesting and exciting results, we establish *-version of Vukman’s theorem [48, Theorem 1]. Precisely, we describe the structure of quotient ring A/L, where A is an arbitrary ring and L is a prime ideal of A. Further, by taking advantage of the *-version of Vukman’s theorem, we show that if a 2-trosion free semiprime ring A with involution admits a nonzero *-centralizing derivation, then A contains a nonzero central ideal. This result is in a spirit of the classical result due to Bell and Martindale [19, Theorem 3]. As the applications, we extends and unify several classical theorems proved in [6],[25,[42], and [48] . Finally, we conclude our paper with a direction for further research.

This Paper intends to introduce the notion of prime ideals of Intuitionistic fuzzy normed Rings and to establish basic properties related to it. It investigates these notions and shown anew Result using intuinistic fuzzy points and non membership function incorparating with t-norm and s-norm to show aome results of fuzzy prime ideal.

When discussing the Diophantine quintic equation $p(a^5 + b^5) = q(c^5 + d^5)$ where p is a prime and q is an integer, there is a clear gap between the mathematical literature and online forums. Because of the intrinsic complexity of parameterizing fifth-degree equations, this equation re- mains largely unexplored. In this work, we approach this quintic problem through algebraic methods with the goal of providing numerical solutions that illuminate its properties and behaviors.Our research uncovers in- triguing patterns and connections that shed light on the enigmatic nature of Diophantine quintic equations in this particular form.

We evaluated the immunogenicity persistence of different immunization regimens of freeze-dried human rabies vaccine (Vero cells) in the 10–60 years age group of the Chinese population. Based on phase III clinical trials of Vero cells, participants who completed the full course of immunization were continuously enrolled in four-dose trial, five-dose, and five-dose control groups. Venous blood samples were collected 12 months after completion of the full immunization for rabies virus-neutralizing antibody (RVNA) testing, and the antibody-positive rate and geometric mean concentration (GMC) were calculated. Analysis of variance was used to compare three groups. The four-dose trial, five-dose trial, and five-dose control groups included 200, 186, and 214 participants, respectively. Twelve months after full immunization, the overall RVNA-positive rates were 97.00%, 93.55%, and 94.86% in the four-dose trial, five-dose control, and five-dose trial groups, respectively. The post-immunization RVNA GMCs values were 2.50, 2.05, and 2.04 IU/mL, respectively, with no statistically significant differences between them. Twelve months after full immunization, the overall RVNA-positive rate remained high, demonstrating satisfactory immunogenicity persistence for both immunization regimens.

This paper presents a new proof of the infinite nature of prime numbers. Grounded in fundamental Set theory and Analysis, the proof uses the method of contradiction to demonstrate the absurdity of assuming the set of all prime numbers to be finite.

Throughout this paper, we will establish a comprehensive theoretical foundation and rigorously develop the methodology to investigate the structure of quotient ring S/P under the influence of symmetric generalized n-derivations, where S represents an arbitrary ring, and P signifies a prime ideal of S satisfying certain algebraic identities acting on prime ideal P without relying on the assumption of primeness or semi-primeness of the ring.

This work is divided into two parts. In the first one the combinatorics of a new class of randomly generated objects, exhibiting the same properties as the distribution of prime numbers, is solved and the probability distribution of the combinatorial counterpart of the n-th prime number is derived, together with an estimate of the prime-counting function π(x). A proposition equivalent to the Prime Number Theorem (PNT) is proved to hold, while the equivalent of the Riemann Hypothesis (RH) is proved to be false with probability 1 (w.p. 1) for this model. Many identities involving Stirling numbers of the second kind and harmonic numbers are found, some of which appear to be new. The second part is dedicated to generalizing the model to investigate the conditions enabling both PNT and RH. A model representing a general class of random integer sequences is found, for which RH holds w.p. 1. The prediction of the number of consecutive prime pairs, as a function of the gap d, is derived from this class of models and the results are in agreement with empirical data for large gaps. A heuristic version of the model, directly related to the sequence of primes, is discussed and new integral lower and upper bounds of π(x) are found.

The maximal prime gaps upper bound problem is one of the major mathematical problems to date. The objective of the current research is to develop a standard which will aid in the understanding of the distribution of prime numbers. This paper presents theoretical results which originated with a researchin the subject of the maximal prime gaps. the document presents the sharpest upper bound for the maximal prime gaps ever developed. The result becomes the Supremum bound on the maximal prime gaps and subsequently culminates with the conclusive proof of the Firoozbakht's Hypothesis No 30. Firoozbakht's Hypothesis implies quite a bold conjecture concerning the maximal prime gaps. In fact it imposes one of the strongest maximal prime gaps bounds ever conjectured. Its truth implies the truth of a greater number of known prime gaps conjectures, simultaneously, the Firoozbakht's Hypothesis disproves a known heuristic argument of Granville and Maier. This paper is dedicated to a fellow mathematician, the late Farideh Firoozbakht.

This paper presents a comprehensive study and the analysis of a topology of a no isolated DC-DC intituled Double Quadratic Boost converter with high static gain. This converter has the main advantage of high static gain and low voltage stress on its switches. The article will first present the theoretical analysis of the converter operating in an open loop. The objective of the work is the mathematical modeling and the control strategy of the converter, as well as the validation through closed-loop experimental results. Besides, we presented the practice test results to demonstrate the operation of the converter, such as the static gain experimental curve, the practice efficiency of the converter, and the control of the output voltage, as well as the capacitor voltage balance control. The authors designed a prototype for 1 kW, with a switching frequency of fs=50kHz, with FPGA-based command and modulation.

In this research paper, a high gain transformer less inverter modeling which is used for the smart grid technology or as the stand alone for home appliances is proposed. The proposed transformer less topology provides a higher voltage gain, low cost, small size and simple control stand alone transformer less inverter for home appliances. The above inverter is modeled by using software which is known as MATLAB/ Simulimk.

To improve the voltage gain of step-up converters, cascaded technique is considered as a possible solution in this paper. By considering the concept of cascading two Z-source networks in a conventional boost converter, the converter takes the advantages of both impedance source and cascaded converters. However, by applying some modifications, the proposed converter provides high voltage gain while the voltage stress of switch and diodes are still low. Moreover, the low input current ripple of the converter makes it absolutely appropriate for photovoltaic applications in order to expand the lifetime of PV panels. After analyzing the operation principles of the proposed converter, simulation and experimental results of a 100W prototype are presented to verify the proposed converter performance.

The Diophantine equation for which p is prime 2^n = p^2 + 7 and n is integers with p > 0, is examined in this work. It is demonstrated by examining the characteristics of the equation that the only solutions meeting these requirements are p = 3 with n = 5 and p = 5 with n = 7. In order to analyze the above equation, it is necessary to look at the properties of primes and how they relate to powers of two. These results advance our knowledge of prime numbers and how they behave in certain mathematical problems.

As most of the videos are destined for human perception, many techniques have been designed to improve video coding based on how the human visual system perceives video quality. In this paper, we propose the use of two perceptual coding techniques, namely contrast masking and texture masking, jointly operating under the High Efficiency Video Coding (HEVC) standard. These techniques aim to improve the subjective quality of the reconstructed video at the same bit rate. For contrast masking, we propose the use of a specific weighting matrix for each block size (from 4×4 up to 32×32). We achieve average Bjøntegaard Delta-Rate (BD-rate) gains of between 2.5% and 4.48%, depending on the perceptual metric and coding mode used. The texture masking scheme is based on the classification of each coding unit, using its mean directional variance features as input to a support vector machine model. According to this classification, the block’s energy, the type of coding unit, and its size, an over-quantization is computed to provide a QP offset (DQP) for this coding unit. By applying both techniques in the HEVC Reference Software, an overall average of 5.79% BD-rate gain is achieved.

Interleaved power factor correction (PFC) is widely used circuit topology due to good efficiency and power density for single-switch boost PFC. As the differential mode (DM) electromagnetic interference (EMI) noise magnitude depends upon the input current ripple, this research details a comprehensive study of DM EMI filter design for interleaved boost PFC with the aim of minimizing the component size. It is also demonstrated that the different numbers of interleaved stages and switching frequency influence the filter attenuation requirement and, thus, the EMI filter size. First, an analytical model is derived on the basis of the Norton equivalent circuit model for the differential mode noises of interleaved boost PFC within the frequency range of 9-500 kHz. The derived model can help identify the optimal phase shifting among the interleaved boost converters in order to minimize the considered differential mode noises at the filter design frequency. So, a novel phase-shift method is developed to get a minimized attenuation required by a filter in Band B. Further, a volume optimization of the required DM filter was introduced based on the calculated filter attenuation and volumetric component parameters. Based on the obtained results, unconventional and conventional phase shifts have demonstrated a good performance in decreasing the EMI filter volume in Band B and Band A, respectively. A 2-kW interleaved PFC case study is presented to verify the theoretical analyses and the impact of phase-shifting on EMI filter size.

Despite the increasing interest in ‘smart city’ initiatives worldwide, current literature still lacks the approaches and models that address challenges in organization and collaboration, which boost sustainability and ‘smartness’ in modern cities. This paper provides an overview of ‘smart city’ ecosystems as a mechanism to promote the expected outcomes of their sustainable development, and highlights the importance of conceptualizing cities from organizational and managerial perspectives. Representative exploratory models of ‘city organization’, which emphasize on the role of ‘governance’ and synergies, are presented to ‘decode’ complex city mechanisms and to determine key components that lead to ‘smart’ initiatives. Interesting case studies and applications are then analysed to examine the practical dimension of these approaches. As a review paper, this article lays out a general framework on the importance of ‘collaboration’, ‘governance’, ‘management’, and ‘ecosystem’. However, 'planning smartly’ and achieving ‘sustainability’ at the level of city ‘organization’ remain as challenges in this pioneering study of smart cities.

Respiratory infections with RSV account for an important part of hospital admissions for acute respiratory infections. Nirsevimab has been developed to reduce the hospital burden RSV (respiratory syncytial virus) infections: Compared with the product previously used, it has a stronger binding capacity to RSV F protein and a high affinity for FcRn (neonatal receptor for the Fc fragment of IgG), which extends its lifespan. Nirsevimab has been shown to be highly effective in reducing hospitalization rates for RSV infections but a large or unknown number of treated subjects have been excluded in clinical and post-marketing studies. However, analysis of these studies cannot exclude that in rare cases, nirsevimab facilitates and worsens RSV infection (or other respiratory infections). This could be attributable to ADE (antibody-dependent-enhancement) which has been observed with RSV F-protein antibodies in inactivated vaccine trials. This risk has been incompletely assessed in preclinical and clinical trials (incomplete exploration of nirsevimab effector functions and pharmacokinetics). ADE by disruption of the immune system (not studied and due to FcRn binding) could explain there is no reduction in all-cause hospital admissions in treated age groups. Given the high price of nirsevimab, the cost-effectiveness of mass immunization campaigns may therefore be debated from an economic as well as a scientific point of view.

Despite global efforts to improve vaccination coverage, the number of zero dose and under immunized children has increased in the African continent, particularly in Nigeria where more than 2.3 million unvaccinated children currently reside, making it the country with highest number of unvaccinated children on the African continent. It is thus imperative to identity barriers and facilitators of immunization in Nigeria with a view to formulate and design targeted interventions that can effectively bridge the immunization gap in Nigeria. In this review, we systematically mapped and summarized existing literature and data on key barriers to vaccine uptake, and facilitators influencing immunization practices in Nigeria. The electronic databases were systematically searched and articles that reported determinants of routine immunization uptake in Nigeria from inception of the databases up till October 2023 were included. The eligible articles were evaluated using a set of pre-defined criteria and the extracted data were analysed and visualized. This scoping review identified barriers spanning logistical, socio-economic, cultural, and healthcare system-related aspects, highlighting the need for a multi-pronged approach to address these challenges. While considerable progress has been made over the years, persistent barriers like distance between area of residence of caregivers and immunization centers, vaccine shortages, poor interpersonal relationship between healthcare workers and caregivers and cultural/religious influences persist. Lastly, collaborative efforts among stakeholders and communities remain paramount in ensuring improved routine immunization coverage across the Nigeria’s diverse socio-cultural landscape.

Prime period sequences can serve as the fundamental tool to construct arbitrary composite period sequences. This is a review study of prime period perfect Gaussian integer sequence (PGIS). When cyclic group {1,2,…,N−1} can be partitioned into k cosets, where N=kf+1 is an odd prime number, the construction of a degree-(k+1) PGIS can be derived from either matching the flat magnitude spectrum criterion or making the sequence with ideal periodic autocorrelation function (PACF). This is a systematic approach of prime period N=kf+1 PGIS construction, and is applied to construct PGISs with degrees 1, 2, 3 and 5. However, for degrees larger than 3, matching either the flat magnitude spectrum or achieving the ideal PACF encounters a great challenge of solving a system of nonlinear constraint equations. To deal with this problem, the correlation and convolution operations can be applied upon PGIS of lower degrees to generate new PGIS with degree-4 and other higher degrees, e.g., 6, 7, 10, 11, 12, 14, 20 and 21 in this paper. In this convolution based scheme, both degree and pattern of a PGIS vary and can be indeterminant, which is rather nonsystematic compared with the systematic approach. The combination of systematic and nonsystematic schemes contributes the great efficiency for constructing abundant PGISs with various degrees and patterns for the associated applications.

We talk about random when it is not possible to determine a pattern on the observed outcomes. A computer follows a sequence of fixed instructions to give any of its output, hence the difficulty of choosing numbers randomly from algorithmic approaches. However, some algorithms based on mathematical formulas like the Linear Congruential algorithm and the Lagged Fibonacci generator appear to produce "true" random sequences to anyone who does not know the secret initial input [1]. Up to now, we cannot rigorously answer the question on the randomness of prime numbers [2, page 1] and this highlights a connection between random number generator and the distribution of primes. From [3] and [4] one sees that it is quite naive to expect good random reproduction with prime numbers. We are, however, interested in the properties underlying the distribution of prime numbers, which emerge as sufficient or insufficient arguments to conclude a proof by contradiction which tends to show that prime numbers are not randomly distributed. To achieve this end, we use prime gap sequence variation. The algorithm that we produce makes possible to deduce, in the case of a binary choice, a uniform behavior in the individual consecutive occurrence of primes, and no uniformity trait when the occurrences are taken collectively.

One of society’s greatest challenges is sequestering vast amounts of carbon to avoid dangerous climate change without driving competition for land and resources. Here we assess the potential of an integrated approach based on enhancement of natural biogeochemical cycles in agro-ecosystems that stimulate carbon capture and storage while increasing resilience and long-term productivity. The method integrates plant photosynthesis in the form of (cover) crops and agroforestry which drives carbon capture. Belowground plant-carbon is efficiently stored as stable soil organic carbon (SOC). Aboveground crop and tree residues are pyrolyzed into biochar, which is applied to the soil reducing carbon release through decomposition. Enhanced weathering of basalt powder worked into the soil further captures and stores carbon, while releasing nutrients and alkalinity. The integrated system is regenerative, through enhanced virtuous cycles that lead to improved plant capture, biomass storage and crop yield, the prerequisites for large-scale carbon sequestration along with food security.

In this paper, based on the pseudo-totem pole (PTP) circuit, a family of five-level PTP dual boost converters (PDBC) is proposed. Dual boost converter has some unique advantages such as no bridge arm shoot-through risk and no switch body diode reverse recovery problem, so that it has a good application prospect. Compared with conventional three-level PTP converters, PDBCs has higher power density, higher efficiency, and low voltage and current stress. The topological derivation process, working principle, modulation and strategy of the topology are analyzed firstly. Further, the number of power devices, the switches voltage and current stress of the proposed topology is analyzed. Finally, a representative five-level PDBC experimental prototype is designed with AC input 220V/50Hz, DC output 400V/1kW, and peak efficiency of 98.27%. The experimental results show that the five-level PDBC proposed in this paper has higher efficiency and verify the correctness of the topology.

In recent years, due to the advancement of machine learning, object detection has become a mainstream task in the computer vision domain. The first phase of object detection is to find the regions where objects can exist. With the improvement of deep learning, traditional approaches such as sliding windows and manual feature selection techniques have been replaced with deep learning techniques. However, object detection algorithms face a problem when performing in low light, challenging weather, and crowded scenes like any other task. Such an environment is termed a challenging environment. This paper exploits pixel-level information to improve detection under challenging situations. To this end, we exploit the recently proposed hybrid task cascade network. This network works collaboratively with detection and segmentation heads at different cascade levels. We evaluate the proposed methods on three complex datasets of ExDark, CURE-TSD, and RESIDE and achieve an mAP of 0.71, 0.52, and 0.43, respectively. Our experimental results assert the efficacy of the proposed approach.

This work studies a novel low voltage (<60 V) hybrid system that supports engine boosting and downsizing in addition to start-stop, regenerative braking, and constrained torque assist/regeneration. The hybrid power split supercharger (PSS) shares a 9 kW motor between supercharging the engine or providing hybrid functionalities through a planetary gear set, a brake and a bypass valve. The PSS operation is limited to only one of the parallel hybrid or boosting modes at a time, necessitating a highly optimized decision making algorithm to select the device mode and power split ratio. In this work an adaptive equivalent consumption minimization strategy (A-ECMS) is developed for energy management of the PSS. The A-ECMS effectiveness is compared against a dynamic programming (DP) solution with full drive cycle preview through hardware-in-the-loop experiments on an engine dynamometer testbed. The experiments show that the PSS with A-ECMS reduces a vehicle fuel consumption by 18.4% over standard FTP75 cycle compared to a baseline turbocharged engine, while global optimal DP solution decreases the fuel consumption by 22.8% compared to baseline.

Mucosal vaccines can target specific mucosal surfaces, such as the respiratory, genital, or intestinal mucosa. Conventional systemic immunization, such as intramuscular injections, do not provide mucosal immunity, including IgA, nor do they prevent pathogens from entering the mucous membranes. Nasal immunization protects mucosal membranes, but nasal antigen presentation appears to entail adjuvant to stimulate immunogenicity. Current treatments for mucosal diseases such as inflammatory bowel disease (IBD) and allergic dermatitis only aimed to temporarily relieve symptoms. Moreover, these treatments not only have drug resistance or side effects, but the disease can recur, leading to switching to other treatments. Therefore, there is a need to develop safe and effective treatments that provide better long-term outcomes to reduce the risk of recurrence. Regulatory T (Treg) cells have been used to suppress inflammation. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Here, a new method of Treg induction through intranasal immunization without adjuvant has been developed to potentially overcome allergies and mucosal inflammation of the lung-gut axis in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies of Treg resilience through clinical translational studies of dietary changes.

Pakistan is one of the few countries where poliovirus transmission still persists, despite intensive efforts to eradicate the disease. Adequate vaccination coverage is essential to achieve polio eradication, but misconceptions about polio vaccines have hindered vaccination efforts. To address this issue, we conducted a mixed-methods study to explore knowledge and perceptions regarding polio disease and immunization in high-risk areas of Pakistan. We collected quantitative data from 3780, 1258, and 2100 households in Karachi, Bajaur, and Pishin, respectively, and supplemented this with qualitative data from focus group discussions and in-depth interviews. Our findings reveal a high level of awareness about polio and its immunization; however, misperceptions about the polio vaccine persist, leading to vaccine refusal for both polio and routine immunization. Our study provides up-to-date data on knowledge and perceptions of polio and its immunization and identifies critical gaps. These findings can inform the development of future strategies and innovative approaches to improve the success of the polio program in Pakistan.

Based on hospital capacities, facts from past experience with the coronavirus disease 2019 (COVID-19) virus and the number of dark infections during the second wave (DII = 2D2), a reasonable limiting value of 140/D2 for the 7-day incidence per 100,000 persons (MSDIHT) and a second wave herd immunization threshold fraction value of 0.26 in Germany were calculated. If the MSDIHT is held below this limiting value, the German hospital system can cope with the number of new seriously infected persons without any triage decisions. On the basis of the SIRV epidemics model, the classical threshold values for herd immunization were calculated for 18 countries. For these countries, the dates regarding when herd immunization against the second COVID-19 wave will be reached were estimated

Since the global request for freight transportation is continuously increasing to face the requirements of the modern economy, 5G infrastructures and companion technologies are becoming essential to support the digital transformation in logistics and transportation, in particular for their capability to allow data collection through a multitude of different sources across the supply chain, improving the connectivity and making more effective the secure and reliable data sharing. The objective of this work is to assess the penetration and implementation levels of innovative technologies to optimize port operations, by interviewing a set of actors and stakeholders directly involved in the logistics chain of ports.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase of systemic antibodies, being higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose 3 occurred and boosted antibody levels in the salivary compartment. These results lead to rethink the current vaccination strategies against COVID-19 and the use of salivary anti-SARS-CoV-2 antibodies for disease surveillance and vaccination follow-up.

Boost-derived converters are most popular in Power Factor Correction AC-DC conversion applications and alternative energy generation systems. The proper operation of such converters relies on housekeeping power supplies providing auxiliary power for their control circuitry. The purpose of this study is to present a design-oriented analysis of a simple, passive, isolated, self-bias circuit that can provide a stabilized voltage for the control circuits of boost-derived converters. The circuit’s output voltage inherently follows the main regulated output and therefore, does not require an additional active control. The paper presents a detailed analysis of the circuit and offers design guidelines. Following the presentation of the basic idea several variations of the circuit, that can be used in special applications, are presented. The feasibility of the proposed bias circuits was verified by simulation and experiment on a laboratory prototype.

Power converters with coupled inductors are very promising due to the high efficiency and high voltage gain. Apart from the aforementioned advantages, the boost-flyback converter reduces the voltage stress on the semiconductors. However, to obtain good performance with high voltage gains, the controller must include two control loops (current and voltage), and a compensation ramp. One of the most used control techniques for power converters is the peak current-mode control with compensation ramp. However, in the case of a boost-flyback converter there is no mathematical expression in the literature, to compute the slope of the compensation ramp. In this paper, a formula to compute the slope of the compensation ramp is proposed in such a way that a stable period-1 orbit is obtained. This formula is based on the values of the circuit parameters, such as inductances, capacitances, input voltage, switching frequency and includes some assumptions related to internal resistances, output voltages, and some other electrical properties related with the physical construction of the circuit. The formula is verified numerically using the saltation matrix and experimentally using a test circuit.

This paper introduces a sliding mode control (SMC) based equivalent control method to a novel high output gain Cuk converter. An additional inductor and capacitor improves the efficiency and output gain of the classical Cuk converter. Classical PI controllers are widely used in DC-DC converters. However, it is a very challenging task to design a single PI controller operating in different load and disturbances. SMC based equivalent control method which achieves a robust operation in a wide operation range is also proposed. Switching frequency is kept constant in appropriate interval in different loading and disturbance conditions by implementing a dynamic hysteresis control method. Numerical simulations conducted on Matlab/Simulink confirm the accuracy of analytical analysis of high output gain modified Cuk converter. In addition, proposed equivalent control method is validated in different perturbations to demonstrate the robust operation in wide operation range.

There is little doubt that final victories over pandemics, such as COVID-19, are attributed to herd immunity, either through post-disease convalescence or active immunization of a high percentage of the world's population with vaccines, demonstrating protection from infection and transmission, being available in large quantities and at reasonable prices. However, it is assumable that humans with immune defects or immune suppression, e.g., as a consequence of allograft transplantation, cannot be immunized actively nor produce sufficient immune responses to prevent SARS-CoV-2 infections. These subjects desperately need other strategies, such as sophisticated protection measures and active immunization. Hypertonic salt solutions attack vulnerable core areas of viruses, i.e., salt denatures surface proteins and thus prohibits virus penetration of somatic cells. It has to be ensured that somatic proteins are not affected by denaturation regarding this unspecific virus protection. Impregnating filtering facepieces with hypertonic salt solutions is a straightforward way to inactivate viruses and other potential pathogens. As a result of the contact of salt crystals on the filtering facepiece, these pathogens become denatured and inactivated almost quantitatively. Such a strategy could be easily applied to fight against the COVID-19 pandemic and other ones that may occur in the future. Another possible tool to fight the COVID-19 pandemic is passive immunization with antibodies against SARS-CoV-2, preferably from human origin. Such antibodies can be harvested from patients´ human sera, which have successfully survived their SARS-CoV-2 infection. The disadvantage of a rapid decrease of the immunoglobulin titer after infection ends can be overcome by immortalizing antibody-producing B-cells via fusion with, e.g., mouse myeloma cells. The resulting monoclonal antibodies are then of human origin and available in, at least theoretically, unlimited amounts. Finally, dry blood spots are a valuable tool for surveilling the population´s immunity.

One of the G protein-coupled receptors, C-C chemokine receptor 5 (CCR5), is an important regulator for the activation of T and B lymphocytes, dendritic cells, natural killer cells, and macrophages. Upon binding to the ligands, CCR5 activates downstream signaling, which plays critical roles in the innate and adaptive immune response through the promotion of lymphocyte migration and the secretion of pro-inflammatory cytokines. Anti-CCR5 monoclonal antibodies (mAbs) have been developed and evaluated in clinical trials for tumors and inflammatory diseases. In this study, we developed novel mAbs for mouse CCR5 (mCCR5) using the N-terminal peptide immunization. Among the established anti-mCCR5 mAbs, C₅Mab-4 (rat IgG_2a, kappa) and C₅Mab-8 (rat IgG₁, kappa), recognized mCCR5-overexpressed Chinese hamster ovary-K1 (CHO/mCCR5) and an endogenously mCCR5-expressing cell line (L1210) by flow cytometry. The dissociation constant (K_D) values of C₅Mab-4 and C₅Mab-8 for CHO/mCCR5 were determined as 3.5 × 10⁻⁸ M and 7.3 × 10⁻⁹ M, respectively. Furthermore, both C₅Mab-4 and C₅Mab-8 could detect mCCR5 by western blotting. These results indicated that C₅Mab-4 and C₅Mab-8 are useful for detecting mCCR5 by flow cytometry and western blotting and provide a possibility to obtain the proof of concept in preclinical studies.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

Sickle cell disease is characterized by stiff, “sickled” red blood cells that have difficulty moving through the bloodstream and do not efficiently carry oxygen. It is an inherited disease with severely limited treatment options, and is caused by a point mutation. Its prevalence in black and brown communities makes the already limited treatment options even less accessible. Base editing and prime editing are two relatively recent discoveries in the field of genome editing and were developed after the groundbreaking discovery of the CRISPR Cas9 system. While not fully tested, they hold a lot of promise in providing alternative treatment options for sickle cell disease. Both editing systems are able to install individual point mutations in the beta globin gene, which is where the sickle cell mutation occurs, and can thus cure sickle cell disease (in theory). In this paper we outline the mechanisms of CRISPR-Cas9 systems and base and prime editing, and provide insight into how to apply them to treat SCD. Further investigation should be done on specific editing systems and designs to use to ensure optimal treatment of SCD.

Let G be a finite group. The prime graph Γ(G) of G is defined as follows: The set of vertices of Γ(G) is the set of prime divisors of |G| and two distinct vertices p and p' are connected in Γ(G), whenever G has an element of order pp'. A non-abelian simple group P is called recognizable by prime graph if for any finite group G with Γ(G)=Γ(P), G has a composition factor isomorphic to P. In [4] proved finite simple groups ²D_n(q), where n ≠ 4k are quasirecognizable by prime graph. Now in this paper we discuss the quasirecognizability by prime graph of the simple groups ²D_2k(q), where k ≥ 9 and q is a prime power less than 10⁵.

This paper presents a new high-efficiency-high-step-up based converter integrating two stype DC-DC Boost and Flyback coupled magnetic converter with recovery stage dedicated to smart HVDC distributed architecture in renewable energy production systems. Appropriate duty cycle ratio assumes that the recovery stage work with parallel charge and discharge to achieve high step-up voltage gain. Besides, the voltage stress on the main switch is reduced with a passive clamp circuit and thus, low on-state resistance Rdson of the main switch can be adopted to reduce conduction losses. The circuit is simple to control. As a final point of this research, the simulation and the prototype investigational results are presented to demonstrate the effectiveness of this proposed converter.

VITEK MS PRIME (bioMerieux), a newly developed Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, alongside VITEK PICKME Pen (PICKME), offers easy sample preparation for bacteria and yeast. VITEK MS PRIME also offers two software platforms for filamentous fungi: the IVD database and the RUO database. Our study evaluated its identification agreement on 320 clinical isolates of bacteria and yeasts, comparing PICKME and traditional wooden toothpick sampling techniques against ASTA Mi-croIDSys Elite results. Additionally, we assessed the IVD (v3.2) and SARAMIS (v4.16) RUO data-bases on 289 filamentous fungi against molecular sequencing. The concordant rates for spe-cies-level identification of bacteria and yeasts were about 89.4% (286/320) between the PICKME and wooden toothpick, about 83.4-85.3% between VITEK MS PRIME and ASTA MicroIDSys Elite. Retesting with PICKME improved concordance to 91.9%. For filamentous fungi, species-level identification reached 71.3% with the IVD database and 85.8% with RUO, which significantly enhanced basidiomycetes' identification from 35.3% to 100%. Some strains in the IVD database, like Aspergillus vesicolor, Exophiala xenobiotica, and Nannizzia gypsea failed to be identified. VITEK MS PRIME with PICKME offers reliable and efficient microorganism identification. For fila-mentous fungi, combining the use of the RUO database can be beneficial, especially for basidi-omycetes.

Dengue virus (DENV), the causative agent of dengue fever (DF), is one of the most important mosquito-borne viruses that can infect humans. Although much effort has been made on prevention and control of dengue, there are currently no anti-viral drugs or worldwide approved vaccines yet. In this study, we immunized six-week-old Balb/c mice with DNA vaccine candidates E and NS1-2a of DENV serotype 2 or the combination of them (E+NS1-2a) via an electroporation (EP)-assisted intramuscular gene delivery system and evaluated the immune response and protection. The highest specific antibody titres and cytokine levels secreted by splenocytes as well as the highest survival rate were observed in the E+NS1-2a group, followed by E group and NS1-2a group. Our data suggested that the combination of E and NS1-2a delivered by EP may be a superior preventive strategy against DENV.

A cursory look at Indian prime time news tells us much about the tone and tenor of the people associated with it. Exaggerations, hyperbole, and tempers run wild and news anchors flail in theatrical rage. News channels and news editors display their ideological affiliations subliminally. These affiliations — a factor of personal political stance, funding bodies, and investors — lead to partisan bias in the framing of news and, in some cases, can easily translate into racial prejudice. In this paper, I examine news coverage related to Muslims in India. I study the coverage of two issues specifically– love jihad and triple talaq –in prime time English news of two channels – Times Now and Republic TV. My analysis of the content, tone, and tenor of their coverage shows that these channels propagate associations between Islam and backwardness, ignorance and violence through consistent employment of the following tropes – ‘Muslim women need to be saved from Muslim men’, ‘Hindu women need to be saved from Muslim men’, and ‘Muslims are not fully Indian – they are anti-national’. I place this study of news media within the current political climate in India and briefly touch on the conversations it guides and provokes. This is also a call for further analysis on this subject to examine and evaluate how discourse manipulates public conversations and policy decisions.

The Riemann zeta function plays a crucial role in number theory and its applications. The Riemann Hypothesis (RH) posits that zeros of other than the trivial ones are located on the line defined by the equation Re(s) =1/2. This paper introduces a novel and straightforward proof of the Riemann Hypothesis. The proof employs a standard method, utilizing the eta function in place of the zeta function, under the assumption that the real part is greater than zero. The equation for the real and imaginary parts of the Riemann zeta function (eta function) is completely separated. Initially, let with s= . The value of the real part is determined by solving the equation, and the process is repeated for identifying the potential roots shared by the two functions, a common value is obtained, leading to a =1/2, which represents the real part of the main root of the function ζ(s). By plotting the zeta function for the obtained a, it is determined that the function has a root only at a =1/2. In another analysis, by identifying the roots of the common potential between the two functions ζ(s) and ζ(1-s), a common value is obtained, which leads to a =1/2. This value represents the real part of the main root of the function ζ(s). Additionally, using a standard method and with the help of two functions ζ(s) and ζ(1-s), the real part of the root of the zeta function is obtained. To create a generator function for prime numbers in terms of b, one can solve the root of the zeta function where it equals one (i.e., and obtain a relationship between b’ and prime numbers. Giving the value of zeta equal to one and s' = a' + ib’, similar to zeta equal to zero, the roots are again placed on the line. Then, by using the zeta function defined by multiplying prime numbers, we arrive at a new meaningful relation between b’ and its corresponding prime number is obtained.

This paper considers the direction of arrival (DOA) estimation problem of phase ambiguity for unfolded coprime linear array (UCLA). The existing most common stacking subarray-based method can tackle the phase ambiguity problem. However, the method is not always true. For a given DOA, it has its corresponding steering vector, but if there are two DOAs which have the same steering vectors with the given DOA for different subarrays, the phase ambiguity problem still arises. A modified method, which defines a decision variable and uses the classic beamforming technique to estimate the DOAs is proposed. However, this method needs additional algorithm to distinguish the true DOAs besides multiple signal classification (MUSIC) spectrum. And sometimes this method is not reliable if the decision variable is not chosen appropriately. Therefore, based on the UCLA, we reconstruct the array to design an improved UCLA called IUCLA. With moving the reference element, the linear relationship among the directional vectors can be broken. In this way, we can directly utilize the MUSIC algorithm to estimate with no additional algorithm. The proposed method can solve the phase ambiguity problem and it does not demand other technique to decrease the complexity. Moreover, the Cramer-Rao Bound (CRB), as the lower bound of the unbiased estimation, is provided and numerical simulations are given to demonstrate the effectiveness and superiority of the proposed method.

In this paper, we study the symmetry between the supersingular prime number according to smallest sphenic number. With this symmetry, we show that the elements of sporadic group generates all prime numbers with the order by a simple application.

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

This paper investigates the safety profile of the Shingrix vaccine, focusing particularly on persistent adverse events post-vaccination. Shingrix, crucial for preventing shingles caused by the varicella-zoster virus, has shown efficacy in clinical trials but is associated with varying degrees of adverse reactions. This retrospective, cross-sectional survey-based study, spanning two years and involving 77 respondents who experienced severe adverse events after vaccination, reveals a spectrum of symptoms ranging from mild to severe, including reports of Guillain-Barré syndrome and neuropathy. These findings underscore the need for ongoing vigilance in vaccine safety monitoring and highlight the importance of personalized care approaches for managing post-vaccination adverse effects. The study aims to contribute to informed decision-making regarding shingles vaccination strategies and calls for continued research into the long-term safety and efficacy of Shingrix.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third dose is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28–61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61–214 days after the second dose, 87,067 (64.1%) infants were vaccinated with the third dose between 151–180 days after the second dose. The time interval distribution for the three doses of hepatitis B vaccine varied across the four provinces or municipalities (P&lt;0.001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine, and training for obstetricians and related personnel.

Neuraminidase (NA)-based immunity could reduce the harmful impact of novel antigenic variants of influenza viruses. Detection of neuraminidase-inhibiting (NI) antibodies in parallel with anti-hemagglutinin (HA) antibodies may enhance research of immunogenicity and duration of antibody response to influenza vaccines. To assess anti-NA antibodies after vaccination with seasonal inactivated influenza vaccines, we used the enzyme-linked lectin assay, and anti-HA antibodies were detected in hemagglutination inhibition assay. The dynamics of anti-NA antibody response differed depending on the virus subtype: antibodies to A/H3N2 virus neuraminidase increased later than antibodies to A/H1N1pdm09 subtype neuraminidase, and persisted longer. In contrast to HA antibodies, the fold increase in antibody titers to NA after vaccination poorly depended on the preexisting level. At the same time, NA antibody level after vaccination directly correlated with titers before vaccination. Difference was found in response to NA antigen between split and subunit adjuvanted vaccines and in NA functional activity in the vaccine formulations.

One of the most important unresolved mysteries in mathematics is the Riemann Hypothesis, which suggests a fundamental connection between the non-trivial zeros of the Riemann zeta function and the distribution of prime numbers. Here, we explore the fascinating union of trigonometric functions, prime numbers, and the Riemann zeta function through an examination of the zeros in the statement ln(sec(π·n log(n))). We demonstrate a strong mathematical connection between these components, providing information on the mysterious properties of prime numbers and their complex relationships to basic mathematical operations. Our thorough investigation adds to the current discussion of the Riemann Hypothesis by offering possible solutions and deepening our comprehension of the intricate relationship between number theory and analytic functions.

Legumes are a diverse and important group of plants that play a vital role in agriculture, food security, and environmental sustainability. Rhizobia are symbiotic bacteria that form nitrogen-fixing nodules on legume roots, providing the plant with a valuable source of nitrogen. Phenolic acids are a group of secondary metabolites produced by plants that have a wide range of biological functions, including defense against pests and diseases, tolerance to abiotic stresses, and nutrient uptake. In the context of climate change and the imperative for sustainable agriculture, this study delves into the dynamic responses of legume species to varying light intensities and their intricate interactions with soil microorganisms. We investigated the impact of light intensity and rhizobial inoculation on the biomass, nitrate reductase, acid phosphatase, and production of phenolic acids in the roots of four legume species, Trifolium repens, Vicia sativa, Ornithopus compressus, and Coronilla juncea. Plants were grown under three light intensity regimes (low, medium, and high) and inoculated with either rhizobia or a non-inoculated control. The results highlights that shaded-light-adapted species, T. repens and V. sativa, increased root exudate production when exposed to high light intensity. This response aligns with their mining strategy, effectively allocating resources to optimize nutrient acquisition under varying conditions. In contrast, species hailing from well- illuminated environments, O. compressus and C. juncea, displayed distinct strategies by significantly increasing biomass under high irradiance, capitalizing on the available light and nutrients. The mining strategy of legumes emerged as a central theme, influencing biomass production, nitrogen dynamics, and enzymatic activities. The strong correlations between biomass and total nitrogen accumulation underscore the role of the mining strategy in efficient nutrient acquisition. Inoculated plants, which rely more on biological nitrogen fixation (BNF), exhibited lower δ15N values, indicative of a successful mining strategy to acquire and utilize atmospheric nitrogen. Enzymatic activities and phenolic acids exhibited significant interspecies variations, reflecting the adaptability of legumes to different light conditions. The findings of this study could be used to develop new strategies for improving legume stress tolerance, nutrient uptake capacity, and rhizosphere health.

The integrated DC-DC converter is appropriate for use in many domains, namely, display, cellular, and portable applications. This paper presents an integrated monolithic voltage-mode DC-DC boost converter with a low-power control circuit. The driver circuit requires an integrated converter to power up a digital logic circuit and converts the unregulated DC input to the controlled DC output at the desired voltage level. It is the integration of both power switches and control circuitry within the same CMOS technology to buck down and boost voltages using a switch mode regulator. In order to increase power efficiency in the DC-DC boost converter that provides low-power operation with a small chip size, a low-voltage operation is applied to the unique circuit characteristic. The operational transconductance amplifier(OTA), comparator, and oscillator in the control circuit are designed with the supply voltage of 3.3V and the operating frequency of 5.5 MHz. A compensator is used to create a pole that has sufficient phase margin for high stability. The DC- DC boost converter is measured in both experiment and simulation. Testing of the proposed circuit on the 0.35μm CMOS process shows that the output transient time of the amplifier can be controlled within of 7μsec and the output voltage is accurately controlled with a ripple ratio of 3%.

(1) Background: Childhood immunization is vital for preventing morbidities and mortalities globally. However, rural Pakistan is facing persistent challenges, particularly after recent global health crises in gauging accurate vaccination coverage estimates. This study aimed to apply a novel Lot Quality Assurance Sampling (LQAS) methodology due to its rapid and reliable estimates of the routine immunization rates among children aged 12-23 months old in Shikarpur, Sindh, and to identify priority areas for future interventions. (2) Methods: A cross-sectional household survey design was adopted for an in-depth assessment of vaccination coverage in a previously under-studied rural context. (3) Results: Data were collected from 1,402 children aged 12-23 months across 47/49 Union Councils in Shikarpur within 141 randomly identified clusters. LQAS was innovatively employed along with GIS Mapping which provided a spatial analysis of the distribution of immunization coverage and the spot map of clusters. The weighted average for fully immunized children was 42.4% after applying Direct Adjustment Method. A steep decline in coverage for each successive vaccine dose was observed, and 39 key priority areas were identified on GIS-based plotting for intensive health interventions. Multivariate Logistic Regression Model further revealed informational gaps and fear of side effects as major barriers to achieving complete immunization. (4) Conclusions: The innovative application of LQAS and GIS Mapping in this study has provided a comprehensive glimpse of its utility in future follow-ups and similar assessments. The findings stress the critical need to tackle the foundational reasons behind the vaccination gaps, with a special focus on enhancing awareness and information dissemination in the key priority areas.

This study aimed to evaluate the impact of the COVID-19 pandemic on routine immunization (RI) programs in six Northern Nigerian states: Bauchi, Borno, Kaduna, Kano, Sokoto, and Yobe. This study compared the programmatic data of 2019 and 2020, as well as survey data collected during the pandemic. RI program variables included service delivery, leadership and governance, monitoring and evaluation/supportive supervision, community engagement, vaccine supply chain and logistics, and finance and financial management. Data were analyzed using SPSS (version 23, IBM), student t-test, and structural equation modelling. The results showed that RI programs were affected by the pandemic in terms of reduced meetings and low completion rates of action points in certain states. However, routine immunization support services increased owing to improved monitoring techniques and consistent vaccine deliveries, with fewer reports of stock-outs. The most significant impact of the pandemic was observed on activities coordinated at the healthcare facility level, whereas those at the state level were less impacted. The major challenges encountered during the pandemic included insufficient supplies and consumables, movement restrictions, shortage of human resources, and fear of infection.

This work describes practical immunization of European sea bass (Dicentrarchus labrax) juveniles against viral nervous necrosis virus (VNNV), a betanodavirus causing worldwide mortalities in many fish species. Protection was obtained with the so called spinycterin vehicles consisting in irreversibly DNA-damaged DNA-repair-less E.coli displaying at their surface a downsized antigen. In this work we, i) maximized bacterial expression levels by downsizing the C protein to a fragment (frgC91-220) containing most of its antigenicity, ii) developed an scalable autoinduction bacterial media based in soy-bean increasing membrane display and reproducibility, iii) enriched surface expression by screening different anchors from several prokaryotic origins (anchor+frgC91-220), iv) preserved frgC91-220 antigenicity by inactivating bacteria by irreversible DNA-damage by means of Ciprofloxacin, and v) increased safety using a repair-less E.coli strain as spinycterin chassis. These second generation of spinycterins protected fish against VNNV challenge with partial (Nmistic+frgC91-220) or 100 % (YBEL+frgC91-220 ) protection, in contrast to those fish immunized with frgC91-220 spinycterins. The proposed spinycterin platform has high levels of environmental safety and cost effectiveness, thus providing potential for small fish vaccines for sustainable aquaculture.

The Food Boost Challenge (FBC) was developed using a participatory action research approach to enhance healthy eating behaviors, here vegetable and fruit products (V&amp;F-products) among adolescents, particularly those with lower education levels. FBC is a quadruple helix innovation process, involving adolescents, (peer)researchers, and food system partners of non-governmental and commercial organizations. In 2021-2022, 34 partners provided both cash and in-kind contributions to join the FBC-community. Phase 1 involved 200 students identifying barriers and drivers for consumption of F&amp;V-products among 1000 pre-vocational adolescents, aged 12-20 years. In phase 2, student teams submitted innovative ideas, resulting in 25 concepts fitting into ≥1 of 4 routes: I) innovative technology for a healthy diet, II) new food products/concepts for adolescents, III) hotspots improving F&amp;V-product experience, and IV) new routes to market. In phase 3 consortia of adolescents, students and partners were formed to develop 10 selected concepts into prototypes, and phase 4 offered teams a national platform. Results show FBC resonates with all stakeholders, generating valuable insights to increase F&amp;V-intake. Prototypes in all 4 routes have been developed, with some already in the implementation stage. Additionally, other regions in the Netherlands have adopted the FBC approach. Overall, FBC is an approach that transforms ideas into actionable measures and shows potential to be adapted to promote various healthy eating behaviors among school students.

Various natural disasters such as floods, fires, earthquakes, etc. have affected human life. Detection and classification of large and small earthquakes caused by natural or abnormal events have been always important to Earth scientist. One of the most important research challenges in this field is the lack of an effective method for identifying and categorizing various types of seismic events at less important and important levels. Based on latest achievements of Data Mining international institutions such as Rexer-KDnugget-Gartner and also newest authentic articles, SVM, KNN, C4.5, MLP are from most important and popular and leading classifiers in data world.Therefor in present study, a boost learning system consisting support vector machine algorithms with linear regression, MLP Neural Network ، C4.5 decision tree and KNN near neighborhood have been utilized in a combined form to detect and categorize micro seismic events. In general, the steps involved in the proposed method are: 1) performing artificial seismic tests, 2) data gathering and analysis, 3) conducting preprocessing and separating training and testing samples, 4) generating relevant models with training samples and detecting and categorizing test samples and 5) extracting a cluster with the maximum candidate using boost learning. After simulations, it was observed that the accuracy of proposed boost method to the best answer was about 6.1% higher compare to other methods and the error rate was 0.082% of recalling. Accuracy of detection and classification to the best answer were also improved compare to other methods up to 2.31% and 6.34%, respectively.

This article provides a proof that the Ramanujan's Inequality given by, \begin{align*} \pi(x)^2 < \frac{e x}{\log x} \pi\left(\frac{x}{e}\right) \end{align*} holds unconditionally for every $x\geq \exp(43.5102146)$. In case for an alternate proof of the result stated above, we shall exploit certain estimates involving the Chebyshev Theta Function, $\vartheta(x)$ in order to derive appropriate bounds for $\pi(x)$, which'll lead us to a much improved condition for the inequality proposed by Ramanujan to satisfy unconditionally.

A prime number is a natural number with no divisors other than itself and the number 1. There are many unsolved problems related to prime numbers. One such problem is finding a general method for identifying prime numbers. Although it is known that all prime numbers fall under the categories of 2, 3, or 6n±1 (where n≥1), a formalized method for eliminating composite numbers (non-prime numbers) from these categories has yet to be developed. This paper aims to explore a possible method for such elimination, which involves checking whether there exists an n that satisfies n = 6km+k+m or n = 6km+k-m (where k and m are non-zero integers). This method is expected to be a major step forward in the derivation of prime numbers.

In this paper, the sequential prime numbers are used as variables for the galactic spiral equations which were developed from the ROTASE model. Special spiral patterns are produced when prime numbers are treated with the unit of radian. The special spiral patterns produced with the first 1000 prime numbers have 20 spirals arranged in two groups. The two groups have perfect central symmetry with each other and are separated with two spiral gaps. The special spiral pattern produced with natural numbers from 1 to 7919 shows 6 spirals in the central area and 44 spirals in the outer area. The whole 7919 spiral points can be plotted with either 6-spiral pattern or 44-spiral pattern. For the spirals only produced by the prime numbers in the 6-spiral pattern plotting, the spiral 2 and spiral 3 each has only one spiral point produced by prime number 2 and 3, respectively, all other spiral points produced by other prime numbers are located on the spiral 1 and spiral 5. The special spiral pattern is well explained with careful analysis, it is concluded that all prime numbers greater than 3 must meet one of the equations: P₁ = 1 + 6 * n (n > 0) P₅ = 5 + 6 * n (n ≥ 0) In other words, every prime number greater than 3 is either a P₁ prime number or a P₅ prime number, no exception. Matching one of the equations is a necessary condition for a number to be a prime number, not a sufficient condition. Hope such sufficient condition can be found in the future. The number of P₁ prime numbers roughly equal the number of P₅ prime number in the first 2 billion prime numbers. The galactic spiral equations with golden angle can duplicate Vogel’s result for the simulation of sunflower seed head pattern, and a pinwheel pattern can be produced also with galactic spiral equations and 1 degree more than golden angle.

Twin prime numbers are two prime numbers which have the difference of 2 exactly. In other words, twin primes is a pair of prime that has a prime gap of two. Sometimes the part “twin prime” is used for a pair of twin primes; an alternative name for this is prime twin or prime pair. Up to date there is no any valid proof/disproof for twin prime conjecture. Through this research paper, my attempt is to provide a valid proof for twin prime conjecture.

The OPV is the vaccine of choice in polio eradication, especially in developing countries, as it has eliminated the wild poliovirus type 2. However, the immunity induced by IPV is better than that induced by the OPV. The present study compared the mucosal and humoral response to poliovirus vaccines administered to previously OPV-immunized children to assess the immunity gap in children at-risk of high poliovirus transmission. This was a community-based three-arm cluster randomized controlled trial conducted from June 2013 to May 2014 in healthy children under five years of age living in three high-risk districts of Pakistan, i.e., Karachi, Kashmore, and Bajaur. 387 clusters were randomized (131 to arm A, 127 to arm B, and 129 to arm C); however, 360 remained in the trial until the end (116 in arm A, 122 in arm B, and 122 in arm C). These clusters were randomly allocated using a computer algorithm to receive routine polio program (bOPV) activities (control, arm A), additional interventions with community mobilization and provision of short-term preventive maternal and child health services and routine immunization, including bOPV via health camps, (arm B), or all interventions of arm B with an additional provision of IPV (arm C ~ bOPV and IPV). Blood and stool samples were collected from a sub-sample to estimate humoral and intestinal immunity. Study findings showed that the serum titers were highest in Group C (IPV+OPV) at the baseline for P1, where its increase over time was also more prominent. Titers for P2 and P3 were statistically significantly higher amongst those who had received a routine OPV dose versus those who had not; this was true for all study groups and visits. In populations with high Oral Polio Vaccine (OPV) failure rates, administering an Inactivated Polio Vaccine (IPV) booster after a minimum of two OPV doses may effectively bridge immunity gaps. The IPV alone offers limited benefits to humoral immunity and doesn't provide intestinal immunity to prevent the infection and propagation of live poliovirus among unexposed populations.

This study aims to implement a SSDBI (single-stage differential boost inverter, SSDBI) applying in a single-stage BESS (battery energy storage system, BESS) topology, which can supply power from lower voltage battery module to AC load. Compared with the common two-stage topology, which has a two-stage converter and higher voltage battery module array, the single-stage topology can reduce the number of cells and components, and improve the power density. In addition, a modified SPWM control was proposed to reduce the control complexity of the SSDBI while improving the THD of the inverter. The modified SPWM control can reduce the duty ratio of the SSDBI and the stress on the components to improve the AC voltage output waveform and reduce the THD value about 2.654%.

Aims. Bone metastases have an incidence of up to 75% in metastatic breast cancer, thanks to the evolution of imaging we can identify them in the oligometastatic phase. With the introduction of target therapies and increasingly effective conjugated antibodies, it is increasingly common to treat patients with radiotherapy although asymptomatic (if single or ≤5 bone lesions). Volumes and doses in this setting do not yet have a clear guidelines. In this study, the aim is to administer to the macroscopically evident disease an ablative dose that favors the local control of disease. Aim of this retrospective analysis is to evaluate the outcome of pts receiving SIB for treatment of bone metastases. Material and Methods. A retrospective analysis including mBC patients (pts) undergone RT on bone metastases was conducted for pts treated between January 2014 and January 2022. Primary endpoint was freedom from local progression (FFLP). Rate of disease progression after radiotherapy (DP-AR) and overall survival (OS) were secondary endpoints. Subgroup analysis (age, immunophenotype, line of therapy) were performed. Results. Among 954 mBC who underwent radiotherapy for metastases, 85 pts underwent SIB-IMRT with a boost on macroscopic lesion of 8-6 Gy in 5 fr. Mean follow up was 41 months (6-61.5 m). Nineteen pts had single bone metastase (22.4%), 20 pts were oligometastatic (23,5%), 46 pts were plurimetastatic (54,1%). FFLP was 17 months (95% CI 3.2-61.5 m). Only 6 pts (7%) had local relapse on SIB-IMRT site during follow up. DP-AR was 13,2 m (95% CI 3.1-56.9 m). OS was 82,7 m (95% CI 10.6-343 m). Local-relapse was not associated with age, immunophenotype or sistemic line ongoing. Among secondary outcomes, DP-AR resulted associated to immunophenotype (p 0.002). DP-AR and OS were not significantly associated with local relapse (respectively p 0.148 and p 0.4). Conclusions. Pts with breast tumor can be treated with SIB-IMRT on bone metastases with a 93% of local control at 17 months from radiotherapy. Further data are needed to individuate pts who can benefit of dose-escalation and also sinergic effect with systemic therapies to possibly increase DP-AR.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

Cystic Fibrosis is a rare genetic disease that affects the transmission of chloride ions due to mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Even though there are nearly 2000 mutations identified to be related to the condition, the most common mutation is F508del; deletion of a phenylalanine residue at 508. On the other hand, G542X which is a Class I mutation is also found very commonly and there are no modulator treatments available for it. Furthermore, it was investigated that R553X mutation can as well be corrected simultaneously with G542X mutation. Therefore, the main focus is on designing a gene therapy project that can correct all these three mutations at once by utilizing the prime editing technique via lipid-based delivery. In this way, the mutations can be edited through plasmids that were designed containing 2 pegRNAs and the Cas enzyme. To implement such an approach efficiently, both ex vivo, an animal model, and in vivo steps are to be designed. For the cell line, fibroblasts are selected due to their simplicity and low cost. The animal model of the experiment is determined to be a ferret concerning the high similarity to the human's CFTR protein and finally, the procedure will follow on a direct application in human Cystic Fibrosis patients. The plasmids are thought to be delivered through a cationic liposome that will reach the lungs with the aid of a nebulizer. At the last stage of the experimental procedure, Sanger Sequencing will be done to see if the desired edit within the CFTR has been performed successfully, and Next Generation Sequencing will be executed to see if there has been an off-target mutation in the remainder of the genome. Whereas for detecting the presence and expression of CFTR protein in humans, immunodetection with flow cytometry will be conducted.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

The development of universal influenza vaccines, i.e. vaccines that can provide broad protection against seasonal and potentially pandemic influenza viruses, has been a priority for more than 20 years. Several approaches have been proposed that redirect the adaptive immune responses from immunodominant hypervariable regions to low-immunogenic but highly conserved regions of viral proteins. Here we induced broadly reactive anti-hemagglutinin (HA) stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HA (cHA). These vaccines contained the HA stalk domain from H1N1pdm09 virus but antigenically unrelated globular head domains from avian influenza viruses H5N1, H8N4 and H9N2. In addition, the source of the viral nucleoprotein (NP) of the LAIV strains was changed from A/Leningrad/17 master donor virus (MDV) to wild-type (WT) H1N1pdm09 virus, in order to induce CD8 T-cell immune responses more relevant to current infections. To avoid any difference in protective effect of the various anti-neuraminidase (NA) antibodies, all LAIVs were engineered to contain the NA gene of Len/17 MDV. Naïve ferrets were immunized with three doses of (i) classical LAIVs containing non-chimeric HA and NP from MDV (LAIVs (NP-MDV)); (ii) cHA-based LAIVs containing NP from MDV (cHA LAIVs (NP-MDV)); and (iii) cHA-based LAIVs containing NP from H1N1pdm09 virus (cHA LAIVs (NP-WT)). A high-dose challenge with H1N1pdm09 virus induced significant pathology in the control, non-immunized ferrets, including high virus titers in respiratory tissues, clinical signs of disease and histopathological changes in nasal turbinates and lung tissues. All three vaccination regimens protected animals from clinical manifestations of disease: immunized ferrets did not lose weight or show clinical symptoms, and their fever was significantly lower than in the control group. Further analysis of virological and pathological data revealed the following hierarchy in the cross-protective efficacy of the vaccines: cHA LAIVs (NP-WT) > cHA LAIVs (NP-MDV) > LAIVs (NP-MDV). This ferret study showed that prototype universal LAIVs that combine the two approaches of inducing anti-HA stalk antibody and more relevant CD8 T-cell immune responses are highly promising candidates for further clinical development.

With the unceasing advancement in wide-bandgap (WBG) semiconductor technology, the minimal reverse-recovery charge Qrr and other more powerful natures of WBG transistors enable totem-pole bridgeless PFC to become a dominant solution for energy storage systems (ESS). This paper focuses on design and implementation of a control structure for a totem-pole boost PFC with newfangled enhancement-mode Gallium Nitride (eGaN) FETs, not only to simplify the control implementation, but also to achieve high power quality and efficiency. The converter is designed to convert a 90-264-VAC input to a 385-VDC output for a 2.6-kW output power. Lastly, to validate the methodology, an experimental prototype is characterized and fabricated. The uttermost efficiency at 230 VAC attains 99.14%. The lowest total harmonic distortion in the current (ITHD) at high line condition (230 V) reaches 1.52% while the power factor gains 0.9985.

Bacillus Calmette-Guérin (BCG) is the only widely used prophylactic tuberculosis (TB) vaccine that can prevent severe TB in infants. However, it provides poor protection in adults, and therefore, there in ongoing research on new TB vaccines and immunization strategies with more durable immune effects. The recombinant BCG and BCG prime-protein booster are two important vaccine strategies that have recently been developed based on BCG and could improve immune responses. In this study, three immune strategies based on four protective antigens, namely, ESAT-6, CFP-10, nPPE18, and nPstS1, were applied to construct recombinant rBCG-EPCP009, EPCP009 subunit protein, and BCG prime-EPCP009 booster vaccine candidates. The short- and long-term immune effects after vaccination in Balb/c mice were evaluated based on humoral immunity, cellular immunity, and the ability of spleen cells to inhibit in vitro mycobacterial growth. At 8 and 12 weeks after the initial immunization, splenocytes from mice inoculated with the BCG prime-EPCP009 protein booster secreted higher levels of PPD- and EPCP009-specific IFN-γ, IL-2, TNF-α, IL-17, GM-CSF, and IL-12 and had a higher IFN-γ⁺CD4⁺ TEM:IL-2⁺CD8⁺ TCM cell ratio than splenocytes from mice inoculated with the rBCG-EPCP009 and EPCP009 proteins. In addition, the EPCPE009-specific IgG2a/IgG1 ratio was slightly higher in the BCG prime-EPCP009 protein booster group than in the other two groups. The in vitro mycobacterial inhibition assay showed that the splenocytes of mice from the BCG prime-EPCP009 protein booster group exhibited stronger inhibition of Mycobacterium tuberculosis （M. tuberculosis）growth than the splenocytes of mice from the other two groups. These results indicate that the BCG prime-EPCP009 protein booster exhibited superior immunogenicity and M. tuberculosis growth inhibition to the parental BCG, rBCG-EPCP009, and EPCP009 proteins under in vitro conditions. Thus, the BCG prime-EPCP009 protein booster may be important for the development of a more effective adult TB vaccine.

The enhancement of health-beneficial omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) contents in the muscle, liver, heart and kidney of Australian prime lambs through pasture grazing and supplementation with oil infused pellets was investigated. Forty-eight first-cross prime lambs were randomly assigned into a split-plot design with pasture type as the main plot effect and pellet supplementation as a sub-plot effect in a feeding trial that lasted for nine weeks. The n-3 LC-PUFA content in Longissimus dorsi muscle of all lambs was well above the 30 mg threshold for “omega-3 source” nutrition claim under the Australian Food Standards and Guidelines. Pasture type impacted the fatty acid contents in muscle, heart and kidney of prime lambs. Lambs grazing cocksfoot only had the highest 18:3n-3 (ALA) and n-3 LC-PUFA contents (67.1 mg/100g and 55.2 mg/100 g, respectively). Supplementation of pellets with or without oil infusion to grazing lambs decreased the ALA and n-3 LC-PUFA contents and increased n-6/n-3 ratio in Longissimus dorsi muscle. The fatty acid content in internal organs of grazing lambs was also affected by pellet supplementation. The liver and kidney of grazing lambs were both “good sources” (60 mg/100 g) of omega-3. The cocksfoot grass showed considerable potential for producing healthy, premium quality meat with high contents of n-3 and n-3 LC-PUFA which may consequently enhance the omega-3 intake of Australian lamb consumers.

Tilapia lake virus (TiLV), a major pathogen of farmed tilapia, is known to be vertically transmitted. Here, we hypothesize that Nile tilapia (Oreochromis niloticus) broodstock immunized with a TiLV inactivated vaccine can mount a protective antibody response and passively transfer maternal antibodies to their fertilized eggs and larvae. To test this hypothesis, three groups of tilapia broodstock, each containing 4 males and 8 females, were immunized with either a heat-killed TiLV vaccine (HKV), a formalin-killed TiLV vaccine (FKV) (both administered at 3.6 ×106 TCID50 per fish), or with L15 medium. Booster vaccination with the same vaccines was given 3-weeks later, and mating took place 1 week thereafter. Broodstock blood sera, fertilized eggs and larvae were collected from 6-14 weeks post-primary vaccination for measurement of TiLV-specific antibody (anti-TiLV IgM) levels. In parallel, passive immunization using sera from the immunized female broodstock was administered to naïve tilapia juveniles to assess if antibodies induced in immunized broodstock were protective. The results showed that anti-TiLV IgM was produced in the majority of both male and female broodstock vaccinated with either the HKV or FKV and that and that these antibodies could be detected in the fertilized eggs and larvae from vaccinated broodstock. Higher levels of maternal antibody were observed in fertilized eggs from broodstock vaccinated with HKV than those vaccinated with FKV. Low levels of TiLV-IgM were detected in some of the 1-3-day old larvae but were undetectable in 7-14-day old larvae from the vaccinated broodstock, indicating a short persistence of TiLV-IgM in larvae. Moreover, passive immunization proved that antibodies elicited by TiLV vaccination were able to confer 85% to 90% protection against TiLV challenge in naïve juvenile tilapia. In conclusion, immunization of tilapia broodstock with TiLV vaccines could be a potential strategy for the prevention of TiLV in tilapia fertilized eggs and larvae, with HKV appearing to be more promising than FKV for maternal vaccination.

We report the first correction by Prime editing of a mutation in the RYR1 gene, paving the way to gene therapies for RYR1-related myopathies. The RYR1 gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which degenerates into motor disabilities. Currently, there are no effective treatments for these diseases, which are mainly caused by point mutations. Prime editing allows the modification of precise nucleotides in the DNA. Our results showed a 59% correction rate of the T4709M mutation in the RYR1 gene in human myoblasts by RNA delivery of the Prime editing components. It is to be noted that the T4709M is recessive, and thus, persons having a heterozygous mutation are healthy. These results are the first demonstration that it is possible to correct mutations in the RYR1 gene.

Prime number-related issues can be viewed from drastically different perspectives by examining the close connections between prime numbers and composite numbers. We think that multiple perspectives are the pillars on the path to solutions so we have created this study. As a result of the study, we proposed two new formulas by presenting three theorems and one proof for each theorem, a total of three proofs. We proved that the formula p · n + p returns a composite number in the first of the theorems, which is the preliminary theorem. Our first theorem except the preliminary theorem is that the formula p · n + p returns all composite numbers, and we proved that too. Finally, we created Theorem II using Theorem I to use in our other work and proved that the formula 2 · n · p + p returns all odd composite numbers, which is Theorem II. Afterward, we presented the similarities of the 2 · n · p + p formula we put forth with another known formula.

This paper proposes an approach to estimate the parameters of an AC-DC boost power factor corrector converter which includes an EMI filter. To this end, once the topology is known, measurements at the input and output terminals of the converter are done to identify the values of the passive elements. The proposed methodology is based on the trust-region nonlinear least squares algorithm to identify the parameters of the converter. The steady-state and the transient signals of the converter at the input/output terminals are acquired non-intrusively without any internal modification of the circuitry. The accuracy of the parameter identification carried out is determined by comparing the estimated values with the actual values provided by the manufacturer, and by contrasting the measured signals with the ones obtained with a simulation model with the estimated values of the parameters. The results presented in this paper prove the accuracy of the proposed approach, which can be extended to other power converters and filters.

Data from the WHO and UNICEF Estimates of National Immunization Coverage (WUENIC) 2022 revision were analyzed to assess the status of routine immunization in the WHO African Region, disrupted by the COVID-19 pandemic. In 2022, the coverage with the first and third dose of diphtheria-tetanus-pertussis containing vaccine (DTP1 and DTP3 respectively) and with the first dose of measles-containing vaccine (MCV1), in the region, was estimated at 80%, 72% and 69%, respectively (all below the 2019 level). Only 13 of the 47 countries (28%) achieved the global target coverage of 90% or above with DTP3 in 2022. From 2019 to 2022, 28.7 million zero-dose were recorded (19.0% of target population). Ten countries of the region accounted for 80.3% of all zero-dose children including the four most populous countries (Nigeria, Ethiopia, Democratic Republic of the Congo, United Republic of Tanzania). Reported administrative coverage greater than WUENIC was found in 19 countries, highlighting routine immunization data quality issues. The WHO African region has not yet recovered from COVID-19 disruptions to routine immunization. It is critical for Governments to ensure that processes are in place to prioritize investments for restoring immunization services, catching-up on vaccination of zero-dose and un-der-vaccinated children and improving data quality.

Phytoalexins are naturally-occurring molecules with antimicrobial activity deriving from the secondary metabolism of plants, which are synthesized in response to physical agents or stresses, phytopathogenic agents (fungi, bacteria and viruses) as well as numerous chemical compounds and biological control agents. Among these, grapevine phytoalexins, which belong to the chem-ical group of stilbenes, exhibit biocidal activity against a large number and a variety of plant pathogens. An important issue in research on these compounds is to be able to stimulate their synthesis in planta and to determine whether the induction of their production can serve as a basis for protecting that plant against its pathogens. Quite a few chemical compounds, derivatives of phytohormones bio-elicitors as well as biocontrol agents have been used to induce the synthesis of stilbene phytoalexins with the aim of conferring protection to grapevine against its main dis-eases (gray mold, downy mildew, powdery mildew and esca). This article reviews the experi-ments that have been carried out in this direction during the last thirty years and shows that the observed protective effects towards pathogens are generally linked to induction and priming of the grapevine phytoalexin response, confirming the interest of using, in a more general way, stimulation of the production of phytoalexins in plants as a basis for crop protection.

In this paper, the distribution of prime numbers is expressed based on proving the Riemann hypothesis. The relationship between three numbers, three, six, and nine, and the modality to the distribution of prime numbers, is one of the results of Riemann's zeta function. Prime numbers are classified into six groups of single-digit numbers. There are no prime numbers in groups of three, six, and nine. The groups are made based on the sum of the internal digits. And for each set, there is an angle in the complex plane. The distance between the prime numbers in each group has a regular pattern. This pattern is a multiple of the numbers three, six, and nine. According to Euler's number, for an angle of 60 degrees, the real part of the cosine is 1/2. Accordingly, all prime numbers are related to angles greater than 60 degrees to 90 degrees. As a result, based on the relationship between the golden spiral and the complex conjugate of the zeta function, the function in The 1/2 point becomes zero based on the prime numbers.

This study investigated live animal performance and carcass characteristics of Australian prime lambs fed oil based polyunsaturated fatty acid (PUFA) enriched pellets in a feedlot system. The tested hypothesis was that supplementation of lambs with a variety of dietary oil based PUFA enriched pellets would enhance growth and carcass characteristics compared with the control lambs on lucerne only. Seventy-two, 6 months old White Suffolk x Corriedale first-cross prime lambs with an average liveweight (LWT) of 35.7 ± 0.9 kg were allocated to six treatment groups in a completely randomised experimental design. The treatments were: (1) control: lucerne hay only; or lucerne hay plus wheat-based pellets infused with 50 ml/kg DM of oils from (2) rice bran (RBO); (3) canola (CO); (4) rumen protected (RPO); (5) flaxseed (FO) and (6) safflower (SO) dietary sources. All lambs had ad libitum access to lucerne hay and clean fresh water. Supplemented lambs were fed 1kg of pellet/head/day for 10 weeks. Feed intake, final LWT, average daily gain (ADG), body conformation and carcass characteristics of lambs in the supplemented groups were all greater than for the control group. SO lambs had the lowest ADG of 190.3 g/day. RBO and CO treatments had the lowest feed cost per unit gain of AU$ 3.0/kg. Supplemented lambs had similar over the hooks (OTH) incomes that were all higher than that of the control group. This empirical evidence-based data demonstrated that supplementation of lambs with RBO and CO had comparatively lower feed costs without compromising ADG, carcass characteristics and OTH income.

Background: Relatively little is known and inconclusive about social inequality in human papillomavirus (HPV) vaccination among teenagers in the United States. This study aims to investigate whether there is a social disparity in HPV vaccination among teenagers and if so, whether it can differ by the source of teen vaccination information (parental reports and provider records). 
Methods: We used the data from the 2019 National Immunization Survey-Teen (NIS-Teen; 42,668 teenagers, aged 13-17) including parental reported vaccination status. Among them, 18,877 teenagers had adequate provider reported vaccination records. Two socioeconomic status (SES) measures were used: mother’s education and annual family income. Multivariate logistic analyses were conducted. 
Results: False negatives of parental reports against provider records were more than two times higher (p < 0.001) in low SES teens than in high SES teens. In both SES measures, the proportion of HPV unvaccinated teenagers were lowest in the highest SES level in analyses with parental reports. However, it was the opposite in analyses with provider records. Interestingly, regardless of vaccination information source, the HPV unvaccinated rate was highest in the middle SES teens (>12 years, non-college graduates; and above poverty level, but not > $75K). 
Conclusion: A significant social inequality in HPV vaccination among teenagers exists in the United States. The pattern of social inequality in HPV vaccination can be distorted when only parent reported vaccination information is used.

ATP and other nucleoside phosphates have specific receptors named purinergic receptors. Purinergic receptors and ectonucleotidases regulate various signaling pathways that play a role in physiological and pathological processes. Extracellular ATP in the tumor microenvironment (TME) has a higher level than in normal tissues and plays a role in cancer cell growth, survival, angiogenesis, metastasis, and drug resistance. In this review, we investigated the role of purinergic receptors in the development of resistance to therapy through changes in tumor cell metabolism. When a cell transforms to neoplasia, its metabolic processes change. The metabolic reprogramming modified metabolic feature of the TME, that can cause impeding immune surveillance and promote cancer growth. The purinergic receptors contribute to therapy resistance by modifying cancer cells' glucose, lipid, and amino acid metabolism. Limiting the energy supply of cancer cells is one approach to overcoming resistance. Glycolysis inhibitors which reduce intracellular ATP levels, may make cancer cells more susceptible to anti-cancer therapies. The loss of the P2X7R through glucose intolerance and decreased fatty acid metabolism reduces therapeutic resistance. Potential metabolic blockers that can be employed in combination with other therapies will aid in the discovery of new anti-cancer immunotherapy to overcome therapy resistance. Therefore, therapeutic interventions that are considered to inhibit cancer cell metabolism and purinergic receptors simultaneously can potentially reduce resistance to treatment.

This article investigates if public investments in rural basic infrastructure represent the best strategy for boosting the local economy of rural communities from Romania. The article focuses on one specific program implemented under the Cohesion policy in the framework of the National Plan for Rural Development called Measure 322. Geographically, the research included a sample of rural communes from the North-Western Region of Romania. Moreover, the study also looks at other determinants of local economic development (LED) than infrastructure investments, with a focus on certain feature characterizing Romanian rural communities such as population size, isolation from urban centers, connection with European and national roads networks, educational stock, etc. The research included three steps, namely the construction of the LED Index, a cvasi-experimental research, and a regression model. Our main findings seem to suggest that while investments in infrastructure help the development gap between beneficiaries and non-beneficiaries remains relatively the same. In terms of determinants of LED, percentage of population with a university degree and connection to a European road are the most significant in the Romanian rural context.

The concepts of fractional calculus and the related techniques have been gaining momentum in circuit system fields, and an increasing body of evidence suggests that fractional-order characteristics are widely distributed in electronic components. In this paper, we consider the fractional characteristics of non-solid aluminum electrolytic capacitors and focus on the nonlinear dynamic characteristics of peak-current-mode controlled (PCMC) dc-dc boost converters with such components. In the work, we establish a piecewise smooth non-commensurate fractional-order model to describe the converter, in which the fractional-order equivalent impedance model of capacitors is adopted and the detailed control loop is considered. In order to analyze the converter, we use the fractional Adams-Bashforth-Moulton typed method (F-ABM) and stroboscopic map technique to obtain the time-domain solutions and the bifurcation diagram. The results of bifurcation diagrams indicate that, with the change of different parameters, the converter enters chaotic state through period doubling bifurcation. In order to provide empirical evidence for the nonlinear dynamic analysis, we consider both circuit-level simulation and experiments in the work, the results of which further confirm the results of theoretical analysis.

Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T cell response, but far from all patients elicit a sufficient immunological response. This witnesses a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic healthy human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy showing E1-specific T cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors, and preferably in patient samples.