The physiological mechanism of membrane potential generation relies on the passage of mobile ions across the plasma membrane, which is selectively permeable to mobile ions. The existence of a membrane and the transport of ions across it are essential for the generation of membrane potential. However, a long-forgotten theory, Association-Induction hypothesis, asserts that the heterogeneous distribution of charges in space, due to ion adsorption, is the true cause of membrane potential generation. Using an artificial living cell model consisting of a viscous aqueous solution, the mechanism of membrane potential generation is restudied in this work. The results indicate that membrane potential can be generated even in the absence of a plasma membrane and that ion adsorption leading to a heterogeneous spatial charge distribution is an essential factor for membrane potential generation. Consequently, the authors invites people to reconsider the Association-Induction hypothesis as a genuine mechanism for generating membrane potential.

In the current era of ‘big data’, scientists are able to quickly amass enormous amount of data in a limited number of experiments. The investigators then try to hypothesize about the root cause based on the observed trends for the predictors and the response variable. This involves identifying the discriminatory predictors that are most responsible for explaining variation in the response variable. In the current work, we investigated three related multivariate techniques: Principal Component Regression (PCR), Partial Least Squares or Projections to Latent Structures (PLS), and Orthogonal Partial Least Squares (OPLS). To perform a comparative analysis, we used a publicly available dataset for Parkinson’ disease patien ts. We first performed the analysis using a cross-validated number of principal components for the aforementioned techniques. Our results demonstrated that PLS and OPLS were better suited than PCR for identifying the discriminatory predictors. Since the X data did not exhibit a strong correlation, we also performed Multiple Linear Regression (MLR) on the dataset. A comparison of the top five discriminatory predictors identified by the four techniques showed a substantial overlap between the results obtained by PLS, OPLS, and MLR, and the three techniques exhibited a significant divergence from the variables identified by PCR. A further investigation of the data revealed that PCR could be used to identify the discriminatory variables successfully if the number of principal components in the regression model were increased. In summary, we recommend using PLS or OPLS for hypothesis generation and systemizing the selection process for principal components when using PCR.rewordexplain later why MLR can be used on a dataset with no correlation

Ethnobotany has been, for too long, a descriptive discipline. However, ethnobotanists are increasingly calling for a paradigm shift towards the formulation of unifying theories and hypothesis-driven research in ethnobotany. Here, we formulated a theory, termed time-since-introduction theory, to explain the integration of alien plants into local pharmacopoeias in their recipient environment. This theory suggests that the factor time is paramount in determining which alien plants are more likely to be included in the medicinal flora of the areas they are introduced in. The theory relies on three hypotheses, the availability and versatility hypotheses alongside the residence time hypothesis newly proposed in the present study. We tested this theory by fitting a structural equation model to ethnobotanical data collected on South Africa’s alien woody flora. Although residence time is a direct predictor of medicinal status of alien plants, it is a better predictor when mediated through plant versatility. These findings are in support of the theory, and we consequently proposed a framework with which to understand different paths linking all three hypotheses. Collectively, our study shows the value of time in the development of ethnobotanical knowledge and fully responds to the pressing call for paradigm shift in ethnobotany.

This work discusses the relationship between foreign direct investment (FDI) and pollution in Spain using an autoregressive distributed lag regression model (ARDL) from 1961 to 2018. The authors apply the theoretical context of pollution haven/halo and conclude that FDI in Spain does not contribute to the transfer of green technologies for cleaner production, despite being included within the European environmental regulatory framework. The authors also verify the adequacy of the environmental Kuznets curve (EKC) and the Load Capacity Curve hypothesis (LCC) in the Spanish environmental context and find that income per capita has a positive effect on environmental sustainability and quality. In this sense, the further development of an efficient renewable energy infrastructure could efficiently drive to a better standards all pollution indexes in Spain, including nuclear energy production, contributing the emissions neutrality aimed by the EU by 2050.

A wide range of research has been developed in the empirical literature regarding income and price elasticities of health care expenditure (HCE). The results are mixed, as researchers employ different methodologies and data sources. The benefits of the panel data method, such as greater data variation, less collinearity, and more degrees of freedom, made it attractive among economists. However, the pooled mean group (PMG) method provides robust estimates compared to conventional methods, such as the mean group estimator and dynamic fixed-effects estimator. As such, this paper applies the PMG method to scrutinize the effect of income and price on U.S. health care consumption using a panel of 46 states. The income and price elasticities were found to be 0.85 and -0.48, respectively, which partially describes the recessionary decline in health care consumption following the Great Recession. In addition, the model reveals that the short-run income elasticity is smaller than the long-run. This confirms that U.S. health care consumption follows the permanent income hypothesis. Consequently, the short-run efficacy of public policies targeting HCE remains limited. The results of this paper suggest reconsidering and adjusting health care policies during a recession so as to avoid probable long-run adverse effects on HCE.

We find that the overnight returns of Korean exchange-traded index funds (ETFs) are significantly positive, whereas the subsequent intraday returns are negative. These intraday return reversals are caused by relatively higher opening prices than the closing prices. In the Korean ETF market, where institutional investors are dominant participants, the return reversals are not explained by the attention hypothesis as in Berkman et al. [1]. Hence, we investigate whether the disagreement hypothesis can explain return reversals. Under the disagreement situations between positive and negative traders at the open, positive traders can have a positive influence on the ETF prices by increasing their investments. However, negative traders, who give up investments due to limited short selling opportunities in the ETF market, have no effects on the prices. Comparing ETF markets with KOSPI 200 Futures where there are no restrictions on short selling, we find that short selling constraints are significant factors for the return reversals. This implies that disagreement among the investors can cause return reversals even in the markets without noise traders. Using unique Korean market data, we conclude that return reversals cannot be completely explained by the attention hypothesis, and that disagreement among investors is also a significant factor for the return reversals. This study contributes to the existing literature by showing that the attention hypothesis does not explain return reversals in the ETF market completely, and suggesting the disagreement hypothesis as an alternative.

The origin of life has not been solved as yet, in spit of the time passage more than thirty years from publication of RNA world hypothesis by W. Gilbert (1986), which is based on the “gene/replicator--first” theory. On the contrary, I have proposed [GADV]-protein world hypothesis (GADV hypothesis), assuming that life emerged from [GADV]-protein world, which is grounded on the “protein/metabolism-first” theory. However, two weak points of protein world hypothesis, (i) protein cannot be produced without gene, and (ii) protein cannot be self-replicated, have been frequently pointed out by supporters of RNA world hypothesis. Then, I examined whether the two weak points could be overcome by GADV hypothesis or not. From the results, it was confirmed that (i) [GADV]-protein could be pseudo-replicated in the absence of gene owing to protein 0^th-order structure or [GADV]-amino acids, and (ii) the replication ability is not always required from the beginning but it is sufficient to acquire it at some time point until the emergence of life. Thus, it was concluded that life emerged as [GADV]-protein world hypothesis, which is grounded on the “protein/metabolism-first” theory, expects.

Ayurveda as a healthcare system has survived for thousands of years but continues to be dogged by reported lack of efficacy of the treatments in clinical trials. The reported lack of efficacy could be due to a real lack of efficacy (which then contradicts the survival of Ayurveda as a functional medical system enjoying considerable public patronage) or could be attributed to inadequacies in the efforts towards evidence generation or in a larger context the overall scientific conduct of research in Ayurveda. In an effort towards better evidence generation, there is an immediate need for standardizing the design, conduct and reporting of clinical trials of Ayurveda but it is a daunting task. For this effort to benefit the scientific endeavors of Ayurveda researchers, it should allow the researchers to be able to apply Ayurveda’s multi-component, individualized and inherently holistic approach. Statistical principles can benefit this effort. Statistical hypothesis testing (SHT) is central to these statistical principles and also aligns well with conventional scientific principles of evidence generation. Although there are challenges with SHT, good practitioners engaged in it do much more than just apply the mathematical theory behind it. As a particular example, lot of time in clinical trial designing is spent in addressing biases and designing trials prudently by minimizing the effect of such biases. SHT can benefit such an effort objectively. There is a need for Ayurveda researchers to engage deeply and mindfully about biases in study design in order to gain scientific validity and acceptability. The article highlights issues that arise in Ayurveda research, and discusses few ways of dealing with these issues using statistical principles.

Theoretical physics addresses the fundamental principles of nature and the mysteries of the universe. In the last century, the theory of relativity challenged people's understanding of time and space, while quantum mechanics revealed various forms of energy. However, the concept of gravity remains elusive. All matter in the universe is composed of energy that can be converted into other forms, yet it is always conserved. However, achieving a state of equilibrium, represented by the equal sign, can be challenging to achieve on both macro and quantum scales. A phenomenon that can transition from one state to infinity is called collision and is essential for understanding natural phenomena and physical processes throughout the universe. In the study of general relativity cannot be three-dimensional problems to gain mathematical inspiration, understand the application of new dimensions. Here, we elucidate the nature of gravity, which inspires the solution of the Riemann hypothesis. Our results show that the conduction mode of dimensional energy is defined by Euler's formula.

The Hamiltonian of a quantum mechanical system has an affiliated spectrum. If this spectrum is the sequence of prime numbers, a connection between quantum mechanics and the nontrivial zeros of the Riemann zeta function can be made. In this case, the Riemann zeta function is analogous to chaotic quantum systems, as the harmonic oscillator is for integrable quantum systems. Such quantum Riemann zeta function analogies have led to the Bender-Brody-Müller (BBM) conjecture, which involves a non-Hermitian Hamiltonian that maps to the zeros of the Riemann zeta function. If the BBM Hamiltonian can be shown to be Hermitian, then the Riemann Hypothesis follows. As such, herein we perform a symmetrization procedure of the BBM Hamiltonian to obtain a unique Hermitian Hamiltonian that maps to the zeros of the analytic continuation of the Riemann zeta function, and provide an analytical expression for the eigenvalues of the results. The holomorphicity of the resulting eigenvalues is examined. Moreover, a second quantization of the resulting Schrödinger equation is performed, and a convergent solution for the nontrivial zeros of the analytic continuation of the Riemann zeta function is obtained. Finally, from the holomorphicity of the eigenvalues it is shown that the real part of every nontrivial zero of the Riemann zeta function converges at σ = 1/2.

1. Darwin’s naturalization hypothesis predicts that alien species closely related to native species are less likely to naturalize because of strong competition due to niche overlap. Closely related species are likely to attract similar herbivores and to release similar plant volatiles following herbivore attack, thus could attract the same predators. However, the importance of phylogenetic relatedness on the interaction between alien and native plants has never been tested in a multitrophic context. 2. In a mesocosm experiment we grew six alien target plant species alone and in competition with nine native plant species of varying phylogenetic relatedness. To test the effects of multitrophic interactions on the performance of alien target species, we used enclosure cages to expose plants to the presence and absence of herbivorous arthropods, predatory arthropods and nematodes. 3. Surprisingly, biomass and number of flowering structures increased with presence of competitors for some of the alien species, but overall there was no consistent competition effect. Similarly, we found that none of the multitrophic-interaction treatments affected survival, biomass or number of flowering structures of the alien species. 4. We conclude there was no significant relationship between performance measures of the alien species and their phylogenetic relatedness to the native competitors.

In this article, it is demonstrated that if the zeta function does not have a sequence of zeros whose real part converges to 1, then it cannot have any zeros in the critical strip, showing that the Riemann Hypothesis is false.

Based on the foundations of thermodynamics and the equilibrium conditions for the coexistence of two phases in a magnetic Ising-like system, we show, first, that there is a critical point where the isothermal susceptibility diverges and the specific heat may remain finite, and second, that near the critical point the entropy of the system, and therefore all free energies, do obey scaling. Although we limit ourselves to such a system, we elaborate about the possibilities of finding universality, as well as the precise values of the critical exponents using thermodynamics only.

In this paper, the elemental construct of an I-shaped fin cooling a heat generating volume is studied through the entropy production perspective. Using the constructal design method framework with entropy production minimization as an objective leads to different optimal shape ratio, different from the ones obtained using the excess of temperature. Moreover, the optimal shape ratio evolution is not necessary the same for local entropy production minimization (excess of entropy production) and global entropy production (entropy produced in the whole area). Finally, an analysis on a possible dimensionless number is introduced for the study of constructal plates.

Conventional models do not fully explain composition of the solar system – for example, the presence of p-nuclei and post-post-Fe-nuclei remains not yet understood (and is one of the great unresolved puzzles of nuclear astrophysics in general); other puzzles exist. We offer a hypothesis which can explain the appearance of non-native elements in the solar system, and a feasible scenario for its implementation. The hypothesis suggests that a nuclear-fission "event" occurred in the inner part of the solar system at the time currently defined as the birth of the system. Conventional models have never considered fission as a contributing nuclei-production mechanism. Upon examination of the existing models and factual data (presented in volumes of publications but never combined into an aggregate), we identified one plausible scenario by which a fission event (not demolishing the entire solar system) could occur: an encounter with a compact super-dense stellar "fragment" (with specific properties) and its "explosion" in fission-cascades. Such scenario also helps resolve other long-standing puzzles of the solar system. For example, it provides that the fission-produced nuclei subsequently transformed into the material that (eventually) accreted into the "rocky" objects in the system (terrestrial planets, asteroids, etc.) and enriched the pre-existed hydrogen-helium objects (the Sun and the gaseous giants) – this offers an explanation for the planets’ inner position and compositional differences within the predominantly hydrogen-helium rest of the solar system. Other implications also follow.

The basic idea is to expand the completed zeta function $\xi(s)$ in MacLaurin series (infinite polynomial), which can be further expressed as infinite product (Hadamard product) by conjugate complex roots. Finally, the functional equation $\xi(s)=\xi(1-s)$ leads to $(s-\alpha_i)^2 = (1-s-\alpha_i)^2, i \in \mathbb{N}$ with solution $\alpha_i= \frac{1}{2}, i \in \mathbb{N}$, where $\alpha_i$ are the real parts of the zeros of $\xi(s)$, i.e., $s_i =\alpha_i\pm j\beta_i, i\in \mathbb{N}$. Therefore, a proof of the Riemann Hypothesis is achieved.

Aim: This study aimed to carrying out a prospective survey on socio-demographics and lifestyle factors among a population of Caribbean immigrants living in the US. Materials and Methods: The data were processed and analysed using the SPSS software and Excel. Crosstabulations were done. The Chi-square test was use to evaluate different hypotheses in this study. Statistical significance was defined as p<0.05.Results: Gender was found statistically significant difference with the country of birth of the Caribbean immigrants (p=0.038), and in the cleanness of their neighbourhoods (p=0.045). There were differences in occupations between males and females (p=0.001). Males were less unemployed than females (p=0.011). Gender also showed statistically significant difference in how easy the immigrants balanced their work and personal life (p=0.044). Age groups depicted differences in the physical health of the immigrants (p=0.001). The use of alcohol and tobacco was not an important risk factor among participants (p=0.529).Conclusions: These facts suggest that socio-demographics among a population of Caribbean immigrants were significantly different among genders. However the use of tobacco and alcohol showed not significant differences among the immigrants.

In this paper, we derive Von Koch's inequality without using the Riemann Hypothesis. As well known, Von Koch's inequality is equivalent to the Riemann Hypothesis. Namely, we show that the Riemann Hypothesis is true. Furthermore, we show that the upper limit of its can be lowered.

Serendipity favors the prepared mind, but how does the brain make that lucky find? Analyzing the cerebral mechanisms behind an exceptional (albeit trivial) discovery, the author suggests that a combination of ‘concept cells’ and the Global Neuronal Workspace Hypothesis could explain how we make great discoveries.

This two-part series describes how to test hypotheses on molecular mechanisms that underlie biological phenomena, using preclinical drug testing as a simplified example. While pursuing drug testing in preclinical research, it is important for students to understand the limitations of descriptive as well as mechanistic studies. The former does not identify any causal links between two or more variables; it identifies the presence or absence of correlations. The latter has caveats presented in Parts I and II of this series. Part II also describes how to test for a causal link between drug-induced activation of biological targets and therapeutic outcomes. Here, the mechanism of action of the drug is identified with pharmacological or genetic approaches that modify the expression/activity of the drug targets. Without interference with the proposed mechanism of action, a causal link between activation (or inhibition) of the target P and the therapeutic outcomes of drug D cannot be established. Using pharmacological agonists and antagonists, gene knockout and overexpression, or protein knockdown tools, designing a full-factorial three-way ANOVA forces the investigator to include the appropriate control groups, mitigating the risk of false positive or false negative conclusions. Upon completion of this series, the educator and student will have some of the tools in hand to design mechanistic studies and interpret various experimental outcomes, with knowledge of strengths and limitations of preclinical research.

Many discoveries in the biological sciences have emerged from observational studies, but student researchers also need to learn how to design experiments that distinguish correlation from causation. For example, identifying the physiological mechanism of action of drugs with therapeutic potential requires the establishment of causal links. Only by specifically interfering with the purported mechanisms of action of a drug can the researcher determine how the drug “causes” its physiological effects. Typically, pharmacological or genetic approaches are employed to modify the expression and/or activity of the biological drug target or downstream pathways, to test if the salutary properties of the drug are thereby abolished. However, experimental techniques have caveats that tend to be underappreciated, particularly for the newer methods. In this two-part series, the caveats and strengths of mechanistic preclinical research are described, using the intuitive example of pharmaceutical drug testing in experimental models of human diseases. This series is not intended to tackle the perpetual clash between the frequentist approach to statistics and other schools of thought. Rather, Part I focuses on technical practicalities and common pitfalls of cellular and animal models designed for drug testing, and Part II describes in simple terms how to leverage a full-factorial three-way ANOVA, to test for causality in the link between drug-induced activation (or inhibition) of a biological target and therapeutic outcomes. Upon completion of this series, the student is expected to appreciate the strengths as well as limitations of mechanistic research and to avoid some of its pitfalls.

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.

The association between mental illness and violent crimes such as homicide is complex. In 1939, Lionel Penrose hypothesized that the availability of psychiatric hospital beds was inversely related to the prison population, presumably due to the hospitalization of potential offenders with a mental illness. Subsequent studies have found evidence for this association, but questions remain about the contributions of confounding factors. Moreover, there has been a move towards deinstitutionalization and community care of the mentally ill over the past six decades. In this study, the association between national homicide rates and three measures of the availability of psychiatric care – the numbers of psychiatrists, general hospital psychiatric beds, and psychiatric hospital beds per 100,000 population – was examined using a time-lagged correlation analysis. Associations between homicide rates and socioeconomic factors associated with crime were also examined. It was found that the availability of psychiatrists and of general hospital psychiatric beds were both negatively correlated with homicide rates, and that the association with general hospital psychiatric beds remained significant even after correction for confounding factors. These results suggest the need for a more nuanced interpretation of Penrose’s original formulation, involving the interplay of social, economic factors and psychological factors rather than linear causality.

The provenance of the aminoacyl-tRNA synthetases (aaRS) poses challenging questions because of their role in the emergence and evolution of genetic coding. We investigate evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—residue-by-residue conservation, its variance, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from distinct, successive genetic sources. These data are especially significant in light of: (i) experimental fragmentations of the Class I scaffold into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that two of these partitions arose from an ancestral Class I aaRS gene encoding a Class II ancestor in frame on the opposite strand. Phylogenetic metrics of different modules vary in accordance with their presumed functionality. A 46-residue Class I “protozyme” roots the Class I molecular tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting is consistent with near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved long after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.

Let's define $\delta(x) = (\sum_{{q\leq x}}{\frac{1}{q}}-\log \log x-B)$, where $B \approx 0.2614972128$ is the Meissel-Mertens constant. The Robin theorem states that $\delta(x)$ changes sign infinitely often. Let's also define $S(x) = \theta(x) - x$, where $\theta(x)$ is the Chebyshev function. It is known that $S(x)$ changes sign infinitely often. We define the another function $\varpi(x) = \left(\sum_{{q\leq x}}{\frac{1}{q}}-\log \log \theta(x)-B \right)$. We prove that when the inequality $\varpi(x) \leq 0$ is satisfied for some number $x \geq 3$, then the Riemann hypothesis should be false. The Riemann hypothesis is also false when the inequalities $\delta(x) \leq 0$ and $S(x)\geq 0$ are satisfied for some number $x \geq 3$ or when $\frac{3 \times \log x + 5}{8 \times \pi \times \sqrt{x} + 1.2 \times \log x + 2} + \frac{\log x}{\log \theta(x)} \leq 1$ is satisfied for some number $x \geq 13.1$.

Robin criterion states that the Riemann Hypothesis is true if and only if the inequality $\sigma(n) < e^{\gamma } \times n \times \log \log n$ holds for all natural numbers $n > 5040$, where $\sigma(n)$ is the sum-of-divisors function and $\gamma \approx 0.57721$ is the Euler-Mascheroni constant. Let $q_{1} = 2, q_{2} = 3, \ldots, q_{m}$ denote the first $m$ consecutive primes, then an integer of the form $\prod_{i=1}^{m} q_{i}^{a_{i}}$ with $a_{1} \geq a_{2} \geq \cdots \geq a_{m} \geq 0$ is called an Hardy-Ramanujan integer. If the Riemann Hypothesis is false, then there are infinitely many Hardy-Ramanujan integers $n > 5040$ such that Robin inequality does not hold and $n < (4.48311)^{m} \times N_{m}$, where $N_{m} = \prod_{i = 1}^{m} q_{i}$ is the primorial number of order $m$.

The origin of cancer remains one of the most important enigmas in modern biology. The prevailing paradigm has failed to grasp a comprehensive view of the disease. Naturally, therapies developed under the current assumptions are inadequate and cancer is practically an incurable disease. Meanwhile, descriptive studies continuously extend the molecular complexity of cancer without an equivalent advancement in its understanding. Furthermore, they tend to accumulate inconsistencies inexplicable under the classical view. This paper presents a compelling theory of the origin of carcinomas. By hypothesis, a series of generic events in epithelial tissues promoted by cellular aging and inflammation enables the reactivation of developmental programs. The origin of carcinomas in vivo is described as the time-ordered cell state transitions undergone by epithelial cells in the hyperplasia due to replicative senescence and inflammation towards a mesenchymal undifferentiated endogenous cell state with cancerous behavior. In support of the theory, the molecular, cellular, and histopathological evidence is critically reviewed. A plausible model for the origin of carcinomas is presented to explain the mechanism underlying carcinogenesis from an evolutive and developmental perspective. The implications of the hypothesis in the current strategies for cancer prevention and treatment are discussed along with rational alternatives and some predictions for possible experimental validation.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. However, emerging research from detailed studies of comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language suggest that language and social cognition are two deeply interrelated capacities of the human species. For instance, recent developmental studies on the acquisition of language in infants and young children, draw attention to the important crucial benefits associated with several different aspects of social stimulation for youngsters, including the quantity and quality of linguistic input, dyadic infant/child-to-parent verbal and non-verbal social interactions, and other important social cues integral for facilitating language learning and social bonding. Studies of the adult human brain further suggest a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting the function of these regions may link language with social cognition and social bonding. In effect, the social brain and social complexity hypotheses may jointly help to explain how neurotypical children and adults learn language, why autistic adults and children exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other animals with significant computational abilities do not acquire the capacity for language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain, while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain.

The primary purpose of this article is to deduce specific order estimates for the \textit{Mertens Function} $M(n)$, which facilitates us to analyze the location of zeros of the \textit{Riemann Zeta function} $\zeta(s)$. The paper also provides a brief overview about the notion of the \textit{Mertens Function} $M(n)$ and \textit{Redheffer Matrices} $\mathbb{A}_{n}$. In addition to learning about various \textit{spectral properties} of $ \mathbb{A}_{n}$, we shall also deduce the relation between these two, which, eventually would lead us to establish a necessary and sufficient condition for the \textit{Riemann Hypothesis} to hold true, as justified by \textit{Redheffer} himself. We shall also observe several numerical evidence as well as theoretical justification behind the falsity of the famous \textit{Mertens Hypothesis}, along with how researchers over the years have approached towards deriving an estimate of the smallest possible natural number $n$ for which the first such violation of the theorem occurs, utilizing numerous conjectures annotating about the order of $M(n)$. Readers who are highly motivated in pursuing research in any of the topics relevent to the contents of this paper will surely find the \texttt{References} section to be extremely resourceful.

In this paper we investigate some properties of square-free numbers. In particular, we study a function that counts the number of square-free numbers no larger than the given number n. We show that this function has asymptotics consistent with the predictions of the Riemann hypothesis and use this to obtain new and better estimates of the density of square-free numbers. Finally, we present a well-known generalization of the concept of a square-free number to monoids and research on square-free factorizations.

Prime numbers are the atoms of mathematics and mathematics is needed to make sense of the real world. Finding the Prime number structure and eventually being able to crack their code is the ultimate goal in what is called Number Theory. From the evolution of species to cryptography, Nature finds help in Prime numbers. One of the most important advances in the study of Prime numbers was the paper by Bernhard Riemann in November 1859 called “Ueber die Anzahl der Primzahlen unter einer gegebenen Grösse” (On the number of primes less than a given quantity). In that paper, Riemann gave a formula for the number of primes less than x in terms the integral of 1/log(x) and the roots (zeros) of the zeta function defined by: Where ζ(z) is a function of a complex variable z that analytically continues the Dirichlet series. Riemann also formulated a conjecture about the location of the zeros of RZF, which fall into two classes: the "trivial zeros" -2, -4, -6, etc., and those whose real part lies between 0 and 1. Riemann's conjecture Riemann hypothesis [RH] was formulated as this: [RH] The real part of every nontrivial zero z* of the RZF is 1/2. Proving the RH is, as of today, one of the most important problems in mathematics. In this paper we will provide a proof of the RH. The proof of the RH will be built following these five parts: PART 1: Description of the RZF PART 2: The C-transformation PART 3: Application of the C-transformation to in Re(z) 0 to obtain ζ(z)=X(z)-Y(z) PART 4: Analysis of the values of z such that X(z)=Y(z), and |X(z)|=|Y(z)|, that equates to ζ(z)=0 Proof that |X(z)|=|Y(z)| only if Re(z)=1/2 Conclude that ζ(z)=0 only if Re(z)=1/2 for Re(z) 0 PART 5: We will also prove that all non-trivial zeros of ζ(z) in the critical line of the form are not distributed randomly. There is a relationship between the values of those zeros and the Harmonic function that leads to an algebraic relationship between any two zeros.

In this study, a simple approach to solving the Riemann Hypothesis, one of the most prominent unsolved problems in the field of Number Theory in mathematics and one of the “Millenium Prize Problems”, is presented. The Riemann Hypothesis, a conjecture about distribution of prime numbers, has remained unsolved since it was first proposed by German mathematician, Bernhard Riemann in 1859. This paper introduces an analytic continuation of the Zeta Function as well as symmetric approach through integration by parts to address this hypothesis. The proposed solution is obtained through analytical continuation in the critical strip 0<Re(s)<1 to establish that Re(s)=1/2.

World Health Organization (WHO) provides the guideline for managing the Particulate Matter (PM) level because when the PM level is higher, it threats the human health. For managing PM level, the procedure for measuring PM value is needed firstly. We use Tapered Element Oscillating Microbalance (TEOM)-based PM measuring sensors because it shows higher cost-effectiveness than Beta Attenuation Monitor (BAM)-based sensor. However, TEOM-based sensor has higher probability of malfunctioning than BAM-based sensor. In this paper, we call the overall malfunction as an anomaly, and we aim to detect anomalies for the maintenance of PM measuring sensors. We propose a novel architecture for solving the above aim that named as Hypothesis Pruning Generative Adversarial Network (HP-GAN). We experimentally compare the several anomaly detection architectures to certify ours performing better.

Time irreversibility, i.e. the lack of invariance of the statistical properties of a system under time reversal, is a fundamental property of all systems operating out of equilibrium. Time reversal symmetry is associated with important statistical and physical properties and is related to the predictability of the system generating the time series. Over the past fifteen years, various methods to quantify time irreversibility in time series have been proposed, but these can be computationally expensive. Here we propose a new method, based on permutation entropy, which is essentially parameter-free, temporally local, yields straightforward statistical tests, and has fast convergence properties. We apply this method to the study of financial time series, showing that stocks and indices present a rich irreversibility dynamics. We illustrate the comparative methodological advantages of our method with respect to a recently proposed method based on visibility graphs, and discuss the implications of our results for financial data analysis and interpretation.

This work uses a new approach to investigate the Riemann hypothesis, drawing conclusions about its trueness. It is based on the more general method presented in a very recent publication, by the same author, showing in detail how to approach that very well-known and interesting problem. This is achieved by means of the theory of dynamical systems (Poincaré index associated to equilibria of 2-dimensional systems) and the study of the zeros of the Dirichlet eta function, defined by a Dirichlet series. By using the well-known fact that the zeros of the eta function include all zeros of the Riemann zeta function in the (open) critical strip, excluded the critical line, ((0,1/2) ∪ (1/2,1)) × (−∞,∞), the development proceeds using only the eta function. In addition, the open and simply connected region (1/2,1) × (0,∞) is used along the text, taking into account the symmetries of zeros of the functions under analysis in the critical strip. The basic line of proof is to find the mathematical expression for the Poincaré index of the vector field associated to the eta function, assuming the existence of a zero of the eta function outside the critical line (in (1/2,1) × (0,∞)), and investigating the resulting unfoldings. Eventually, an inconsistency occurs and the proof ends by contradiction.

: Aim: The aim in this study was to conduct a prospective survey regarding the sociodemographics and lifestyle risk factors for cancer of a population of Caribbean immigrants living in the U.S. Materials and Methods: The data were processed and analysed using SPSS software 27 and Excel. Crosstabulations were performed. The chi-square test was used to evaluate different hypotheses. Statistical significance was defined as p &lt; 0.05. Results: Statistically significant differences in the country of birth of the Caribbean immigrants were found for sex (p = 0.038) and the cleanness of their neighbourhoods (p = 0.045). We found differences in occupations between men and women (p = 0.001). Men were less unemployed than women (p = 0.011). Sex also showed statistically significant differences in how easily the immigrants balanced their work and personal life (p = 0.044). Age groups depicted differences in the physical health of the immigrants (p = 0.001). The use of alcohol and tobacco was not an important risk factor among participants (p = 0.529). Conclusions: These findings suggest that the sociodemographics risk factors for cancer among a population of Caribbean immigrants were significantly different between the sexes. However, the use of tobacco and alcohol showed insignificant differences among the immigrants.

The etiological agent of various viral diseases has been identified, and clinical characteristics and complications of each disease are well known. In general, a viral disease appears as acute systemic inflammatory disease, but after acute infection, some patients remain asymptomatic carriers or suffer chronic viral diseases, suggesting that the phenomena are unavoidable processes for viruses’ coexistence with their hosts as virome in microbiota of human species. Although each viral disease has been described as having different pathophysiology, the host's control systems, including immune systems, against the insults from any viral infections, have the same components in previously healthy hosts. Therefore, considering the characteristics of the life cycle of viruses being dependent on the host cell and the same immune components of the host, it is reasonable assumption that there is a common immune mechanism to respond to the insults from all viral diseases. The authors discuss on the characteristics of virus infection and unresolved issues in viral diseases and propose a rationale of early immune modulators for acute insults from viral diseases based on our clinical experiences and the protein-homeostasis-system hypothesis.

Hashimoto’s thyroiditis (HT) is a gender autoimmune disease that is manifested by chronic inflammation of thyroid. Clinical trial studies (CTSs) use molecular biotechnologies (MB) to approach HT appearance. Aims of this study was to analyze the applications of MB in CTSs carried out in HT populations (HT-CTSs). Further, to evaluate the role of MB in the context of hygiene hypothesis (HH). From 75 HT-CTSs found at https://beta.clinicaltrials.gov/ web place, forty-five were considered for this investigation. Finally, six HT-CTSs were reported as molecular HT-CTSs (mHT-CTSs) because of these were planning to utilize MB. Two of mHT-CTSs were settled on French population to isolate DNA viral sequences. Blood, urine, and thyroid tissues biospecimens were analyzed to pick out parvo and polyoma viruses. Two mHT-CTSs carried out in China, were aimed to identify oral and fecal microbiotas by measuring PCR sequencing of 16S rRNA gene. Two mHT-CTSs were programmed in USA and Greece, respectively, for interception of DNA polymorphisms to associate with genetic susceptibility to HT. In conclusion, MB are mainly employed in HT-CTSs for infective pathogenesis and genetic fingerprinting of HT. Besides, MB don't prove the evidence of HH; however, they are useful for direct evidence of the presence of viruses.

A paradigm shift away from null hypothesis significance testing seems in progress. Based on simulations, we illustrate some of the underlying motivations. First, P-values vary strongly from study to study, hence dichotomous inference using significance thresholds is usually unjustified. Second, statistically significant results have overestimated effect sizes, a bias declining with increasing statistical power. Third, statistically non-significant results have underestimated effect sizes, and this bias gets stronger with higher statistical power. Fourth, the tested statistical hypotheses usually lack biological justification and are often uninformative. Despite these problems, a screen of 48 papers from the 2020 volume of the Journal of Evolutionary Biology exemplifies that significance testing is still used almost universally in evolutionary biology. All screened studies tested default null hypotheses of zero effect with the default significance threshold of p = 0.05, none presented a pre-specified alternative hypothesis, pre-study power calculation, and the probability of ‘false negatives’(beta error). The results sections of the papers presented 49 significance tests on average (median 23, range 0–390). Of 41 studies that contained verbal descriptions of a ‘statistically non-significant’ result, 26 (63%) falsely claimed the absence of an effect. We conclude that studies in ecology and evolutionary biology are mostly exploratory and descriptive. We should thus shift from claiming to ‘test’ specific hypotheses statistically to describing and discussing many hypotheses (possible true effect sizes) that are most compatible with our data, given our statistical model. We already have the means for doing so, because we routinely present compatibility (‘confidence’) intervals covering these hypotheses.

While immutability is Blockchain's* much celebrated covenant, change is the rule of life. The paradox has seriously limited real-world deployability of Smart Contracts (SC), faltering its mainstream adoption and sustainability. Once implemented, SC remains unstoppable even if its execution makes losses, as evident in the recently exploded $50+B DeFi industry. How do we reconcile the two and make DeFI/Blockchain profitable and sustainable? A DISC (Dynamic Immutable Smart Contract) hypothesis was proposed to resolve the paradox. Using an existing decentralized IoT device framework we test the DISC hypothesis, by designing/implementing a DISC protocol that delivers an algorithmically controlled dynamic off-chain data feed into a self-executing SC. The experiment successfully introduced limited dynamism into SC without compromising its immutability or undermining user control over their SC terms. If consistently reproduced in diverse settings, the DISC protocol could earn an important milestone in the evolution of Blockchain's decentralized economy of the future.

During the current COVID-19 pandemic caused by SARS-CoV-2, clinicians and scientists are working assiduously to unravel its pathophysiology and find effective treatments. An impressive number of papers has been published on SARS-CoV-2, exposing the complexity of the disease, the tendency of scientists to form hypotheses within their area of expertise, and the lack of orchestration of research. Hypotheses and research findings mainly complement each other, though sometimes controversies can be discerned among various theories and study results. Our overview aims to portray the ‘big picture’ of COVID-19, visualising the interwovenness of different pathophysiological pathways, with a focus on cytokine-induced pathology, the sequelae of ACE2 downregulation, and thrombosis associated with microvascular injury. It aids in overseeing the effects of repurposed drugs on intended targets, but also alerts to the (adverse) effects on interacting pathways. The overview shows how comorbidities probably increase susceptibility to (severe) COVID-19 and provides the possible pathophysiological origin of signs, symptoms, and biochemical abnormalities.

The reliability analysis allows to estimate the system's probability of detecting and identifying outlier. Failure to identify an outlier can jeopardise the reliability level of a system. Due to its importance, outliers must be appropriately treated to ensure the normal operation of a system. The system models are usually developed from certain constraints. Constraints play a central role in model precision and validity. In this work, we present a detailed optical investigation of the effects of the hard and soft constraints on the reliability of a measurement system model. Hard constraints represent a case in which there exist known functional relations between the unknown model parameters, whereas the soft constraints are employed for the case where such functional relations can slightly be violated depending on their uncertainty. The results highlighted that the success rate of identifying an outlier for the case of hard constraints is larger than soft constraints. This suggested that hard constraints should be used in the stage of pre-processing data for the purpose of identifying and removing possible outlying measurements. After identifying and removing possible outliers, one should set up the soft constraints to propagate the uncertainties of the constraints during the data processing. This recommendation is valid for outlier detection and identification purpose.

In this paper we evaluate the effects of hard and soft constraints on the Iterative Data Snooping (IDS), an iterative outlier elimination procedure. Here, the measurements of a levelling geodetic network were classified according to the local redundancy and maximum absolute correlation between the outlier test statistics, referred to as clusters. We highlight that the larger the relaxation of the constraints, the higher the sensitivity indicators MDB (Minimal Detectable Bias) and MIB (Minimal Identifiable Bias) for both the clustering of measurements and the clustering of constraints. There are circumstances that increase the family-wise error rate (FWE) of the test statistics, increase the performance of the IDS. Under a scenario of soft constraints, one should set out at least three soft constraints in order to identify an outlier in the constraints. In general, hard constraints should be used in the stage of pre-processing data for the purpose of identifying and removing possible outlying measurements. In that process, one should opt to set out the redundant hard constraints. After identifying and removing possible outliers, the soft constraints should be employed to propagate their uncertainties to the model parameters during the process of least-squares estimation.

Studies on the structure of economic systems are, most frequently, carried out by the methods of informational statistics. These methods, often accompanied by a wide range of indicators (Shannon entropy, Balassa coefficient, Herfindahl specialty index, Gini coefficient, Theil index etc.) around which a wide literature has been created over time, have a major disadvantage. Such weakness is related to the imposition of the system condition, therefore the need to know all the components of the system (as absolute values or as weights). This restriction is difficult to accomplish in some situations, and in others, this knowledge may be irrelevant, especially when there is an interest in structural changes only in some of the components of the economic system (either we refer to the typology of economic activities - NACE or of territorial units – NUTS). This article presents a procedure for characterizing the structure of a system and for comparing its evolution over time, in the case of incomplete information, thus eliminating the restriction existent in the classical methods. The proposed methodological alternative uses a parametric distribution, with subunit values for the variable. The application refers to Gross Domestic Product values for five of the 28 European Union countries, with annual values of over 1,000 billion Euros (Germany, Spain, France, Italy and United Kingdom) for the years 2003 and 2015. A form of the Wald sequential test is applied to measure changes in the structure of this group of countries, between the years compared. The results of this application validate the proposed method.

Understanding the mechanism, how entirely new (EntNew) gene/protein or the first ancestral gene/protein of a family was created, should be one of the most important issues in the biological sciences. However, the mechanism is totally unknown still now. On the other hand, it is well known that mature protein is generally rigid and one catalytic center exists on the protein. Creation of such a mature EntNew gene/protein should be, of course, carried out through random process, because it cannot be designed in advance. However, the EntNew gene/protein never be created by random polymerization of the respective monomeric units, because of the extraordinary large sequence diversities of ~10¹⁸⁰ and ~10¹³⁰, respectively. Protein 0^th-order structure or a specific amino acid composition, in which immature but water-soluble protein can be produced even through random process, holds the key for solving the difficult problem. As it was fragmentally described in the previous papers how and where EntNew gene/protein was created, I describe in detail in this review three processes generating EntNew gene/protein with some flexibility under three genetic codes, the universal genetic code, SNS primitive code and GNC primeval code, and discuss why the mature gene/protein could be created through the processes.

Modern gastroenterology, which occupies the pages of scientific journals without alternative, began as an initiative of manufacturers of diagnostic equipment. For widespread advertising, they selected practical doctors who were not familiar with the methodology of science and superficial knowledge of physiology. This is how a group led by DeMeester arose, which in 1976 published the DeMeester score, i.e., the normal limit for esophageal pH monitoring. pH <4, less than 4% of the time per day was considered normal, i.e., it was unreasonably claimed that such reflux is physiological. This article proves that this study was carried out with numerous methodological errors, which led to an erroneous conclusion. For a long time, pH monitoring was considered the gold standard and with its help hypotheses were proposed that form the basis of modern gastroenterology. The article proves the fallacy of 13 hypotheses, which are presented as theories. Numerous articles using pH monitoring have publicized this method. Practitioners became "great scientists", equipment manufacturers became successful businessmen. Over time, they found other groups of practitioners to promote devices for impedance ph monitoring, high-resolution manometry, and many others. At the same time, a network of reviewers who believe in the infallibility of the luminaries do not allow studies that contradict their faith to be published. Thus, fundamental science was destroyed, which alone could assess the harm of false research both for science and for patients. Conclusion This study provides a list of hypotheses, that were previously considered theories, but since scientific evidence has proven these assumptions to be false, they should be excluded from subsequent use and citation.

In the first part of this article, we discuss and generalize the complete convergence introduced by Hsu and Robbins (1947) to the r-complete convergence introduced by Tartakovsky (1998). We also establish its relation to the r-quick convergence first introduced by Strassen (1967) and extensively studied by Lai (1976). Our work is motivated by various statistical problems, mostly in sequential analysis. As we show in the second part, generalizing and studying these convergence modes is important not only in probability theory but also to solve challenging statistical problems in hypothesis testing and changepoint detection for general stochastic non-i.i.d. models.

This essay is a personal insight based on my own experience in the Iberian Pyrenees, which addresses three situations common in paleoecological research, such as the verification of previously devised hypotheses (anticipation), the finding on unknown events in unstudied sites (discovery) and the finding of unexpected outputs in already known areas (serendipity). The account is concentrated on the value of the coring sites by themselves as generators of paleoecological knowledge, rather than on the actual findings, which are presented and discussed in the corresponding data papers. The main aim is to show that there is still much room for new findings, even in areas that have been surveyed for long time and are supposed to be well known, from a paleoecological perspective. Finally, some general lessons are derived and conceptualized.

A generalization of the sum of divisors function involves a recursive definition. This leads to variants of superabundant numbers, colossally abundant numbers, and Gronwall's theorem (relevant to the Riemann hypothesis).

Accurate prediction of the membrane potential by membrane theory is possible on the basis that the plasma membrane is selectively permeable to ions and that permeability determines the characteristics of the membrane potential. However, an experimental and artificial cell system with an impermeable membrane serving as a model plasma membrane has a non-zero membrane potential, and this potential generated across the membrane is somehow consistent with the potential characteristics predicted by the membrane theory, despite the impermeability of the membrane to ions. A long-forgotten theory, called the association-induction hypothesis (AIH), has emerged as a more plausible mechanism for generating the membrane potential than the membrane theory to explain this unexpected behavior. The AIH asserts that ion-selective membrane permeability is not necessary for the generation of the membrane potential, which is contrary to the membrane theory. Although such an idea is not easy to accept, the experimental results clearly suggest the correctness of the AIH.

This paper investigates whether optimisation methods with the population made up of one solution can suffer from structural bias just like their multisolution variants. Following recent results highlighting the importance of choice of strategy for handling solutions generated outside the domain, a selection of single solution methods are considered in conjunction with several such strategies. Obtained results are tested for the presence of structural bias by means of a traditional approach from literature and a newly proposed here statistical approach. These two tests are demonstrated to be not fully consistent. All tested methods are found to be structurally biased with at least one of the tested strategies. Confirming results for multisolution methods, it is such strategy that is shown to control the emergence of structural bias in single solution methods. Some of the tested methods exhibit a kind of structural bias that has not been observed before.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

High-dimensional measurement error data are becoming more prevalent across various fields. Research on measurement error regression models has gained increasing attention due to the risk of drawing inaccurate conclusions if measurement errors are ignored. When the dimension p is larger than the sample size n, it is challenging to develop statistical inference methods for high-dimensional measurement error regression models due to the existence of bias, nonconvexity of objective function, high computational cost and many other difficulties. Over the past few years, some works have overcome the aforementioned difficulties and proposed several statistical inference methods. This paper mainly reviews the current development on estimation, hypothesis testing and variable screening methods for high-dimensional measurement error regression models and shows the theoretical results of these methods with some directions worthy of exploring for future research.

This research article provides criticism and arguments why the canonical framework for derivatives pricing is incomplete and why the delta-hedging approach is not appropriate. An argument is put forward, based on the efficient market hypothesis, why a proper risk-adjusted discount rate should enter into the Black-Scholes model instead of the risk-free rate. The resulting pricing equation for derivatives and in particular the formula for European call options is then shown to depend explicitly on the drift of the underlying asset, which is following a geometric Brownian motion. It is conjectured that with the generalized model, the predicted results by the model could be closer to real data. The adjusted pricing model could partly also explain the mystery of volatility smile. The present model also provides answers to many finance professionals and academics who have been intrigued by the risk-neutral features of the original Black-Scholes pricing framework. The model provides generally different fair values for financial derivatives compared to the Black-Scholes model. In particular, the present model predicts that the original Black-Scholes model tends to undervalue for example European call options.

A concise proof of the Riemann Hypothesis is presented by clarifying the Hadamard product expansion over the zeta zeros, demonstrating that the Riemann Hypothesis is true.

Different cohort studies documented a lower glomerular filtration rate (GFR) in former extremely low birth weight (ELBW, <1000 g) neonates throughout childhood when compared to term controls. The current aim is to pool these studies to describe the GFR pattern over the pediatric age range. To do so, we conducted a systematic review on studies reporting on GFR measurements in former ELBW cases while GFR data of healthy age-matched controls included in these studies were co-collected. Based on 248 hits, 6 case-control and 3 cohort studies were identified, with 444 GFR measurements in 380 former ELBW cases (median age 5.3-20.7 years). The majority were small (17-78 cases) single center studies, with heterogeneity in GFR measurement (inulin, Cystatin C or creatinine estimated GFR formulae) tools. Despite this, the median GFR (ml/kg/1.73m²) within case-control studies was consistently lower (-13, range -8 to -25%) in cases, so that a relevant minority (15-30%) has a eGFR<90 mgl/kg/1.73m²). Consequently, this pooled analysis describes a consistent pattern of reduced eGFR in former ELBW cases throughout childhood. Research should focus on perinatal risk factors for impaired GFR and long-term outcome, but is hampered by single center cohorts, study size, and heterogeneity of GFR assessment tools.

Human cytomegalovirus (HCMV) is a β-herpes virus that is a significant pathogen within immune compromised populations. HCMV morbidity is induced through viral dissemination and inflammation. Typically, viral dissemination is thought to follow Fenner’s hypothesis where virus replicates at the site of infection, followed by replication in the draining lymph nodes, and eventually replicating within blood filtering organs. Although CMVs somewhat follow Fenner’s hypothesis, they deviate from it by spreading primarily through innate immune cells as opposed to cell free virus. Also, in vivo CMVs infect new cells via cell to cell spread and disseminate directly to secondary organs through novel mechanisms. We review the historic and recent literature pointing to CMV’s direct dissemination to secondary organs and the genes that it has evolved for increasing its ability to disseminate. We also highlight aspects of CMV infection for studying viral dissemination when using in vivo animal models.

To date, no scientific study has found evidence of an afterlife, and the mechanism of consciousness is two of the most challenging questions. Here, I show a hypothesis for consciousness and the probability of an afterlife through three simple thought experiments and theoretical evidence. More studies are needed to understand the mechanism precisely. I found that consciousness can be discussed based on a new theory. Here, I hypothesize that when a person or animal dies, the selection of a new nervous system's characteristic of a new life might depend on the characteristics of the final evolved yet unknown particle. Here, I suggest that the positive or adverse evolution of the said particle depends on the natural evolution of the materialistic brain's cognition, including intelligence. The fittest intellectuals, those who have a higher potential scan mind virus, may survive happier and help more for others to improve psychological well-being. Here, I suggest that when a brain dies, the two microparticles might emit at infinite speed from the dead brain and simultaneously bond with a naturally select suitable zygote or early nervous system somewhere in the universe/s, forming a new life with the impact of new nurture.

Hsp70.1 has dual functions as chaperone protein and lysosomal stabilizer. Previously, we reported that calpain-mediated cleavage of carbonylated Hsp70.1 causes ischemic neuronal death by inducing lysosomal rupture. Recently, we found that the consecutive injections of vegetable oil-peroxidation product ‘hydroxynonenal’ induces hepatocyte death via the similar cascade. As Hsp70.1 is related also to fatty acid β-oxidation in the liver, its deficiency is known to cause accumulation of fat. Genetic deletion of betaine-homocysteine S-methyltransferase (BHMT) was reported to perturb choline metabolism, inducing decrease of phosphatidylcholine with the resultant hepatic steatosis. Here, focusing on disorders of Hsp70.1 and BHMT, we studied the mechanism of hepatocyte degeneration and steatosis, using monkeys after the consecutive injections of synthetic hydroxynonenal. As these monkeys showed a significant impairment of liver functions, the liver tissues without and with hydroxynonenal injections were compared by proteomics, immunoblotting, immunohisto-chemical and electron microscopic analyses. Western blotting showed upregulation of neither Hsp70.1 nor BHMT, but an increased cleavage of both proteins. Proteomics showed downregulation of Hsp70.1, while 2-fold increments of carbonylated BHMT. Hsp70.1 carbonylation was negligible, showing a marked contrast to ischemic neurons which were associated with ~10-fold increments. The control liver histologically showed lipid droplets in Ito cells, but lipid depositions within hepatocytes were very little. In contrast, after hydroxynonenal injections, widespread fatty degeneration and focal coagulation necrosis were observed with accumulation of numerous tiny lipid droplets within and around the degenerating/dying hepatocytes. Electron microscopy showed lysosomal membrane permeabilization/rupture, remarkable dissolution of mitochondria and rough ER membrane, and proliferation of abnormal peroxisomes. It is probable that disruptions of rough ER caused impaired synthesis of Hsp70.1 and BHMT proteins, while impairments of mitochondria and peroxisomes presumably contributed to the sustained generation of reactive oxygen species. Since both Hsp70.1 and BHMT are vulnerable to the long-standing oxidative stressor, hydroxynonenal-induced disorders facilitated degeneration and steatosis of hepatocytes, respectively.

Severe COVID-19 is associated with viraemia and multiple organ disease. Similar clinicopathological features have been previously seen in SARS and MERS. Clinically, the severity of SARS, MERS and COVID-19 has been associated with the presence of SARS-CoV, MERS-CoV or SARS-CoV2 viraemia in affected patients. In vitro work has looked at the pattern of viral entry and release from polarised epithelial cells infected by coronaviruses. This work has demonstrated a correlation between the severity of a coronavirus infection and the ability of the virus to reach and infect the basal surface of host cells. It has been postulated that this ability helps the virus invade the bloodstream of the host, resulting in a systemic infection with multiple organ involvement. Here we propose that basal surface release and entry of COVID-19 into and out of cells at epithelial-endothelial interface plays a key pathogenic role in severe COVID-19 disease.

Whether and how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus regarding behavioral, molecular, and electrical recording parameters remains unclear. Following the experimental protocols of a rat hemorrhage CPSP model, the VBC of the thalamus of wild-type and P2X7 receptor KO mice was injected with 10 mU/0.2 μl type IV collagenase to produce an animal model of stroke-like thalamic hemorrhage. Behavioral data showed that the CPSP group induced thermal and mechanical pain, while the P2X7 receptor KO group showed reduced thermal and mechanical pain behaviors. Molecular assessments revealed that the CPSP group had lower expression of NeuN and KCC2 and higher expression of GFAP, IBA1, and BDNF. The P2X7 KO group showed lower expression of GFAP, IBA1, and BDNF and higher expression of KCC2 than the CPSP group. The expression of NKCC1, GABAa receptor, and TrkB did not differ significantly between the control, CPSP, and P2X7 receptor KO groups. Muscimol application increased multiunit numbers and [Cl-] influx in the membrane in the CPSP group, while P2X7 receptor KO reduced multiunit activity and [Cl-] outflux. P2X4 receptor expression was significantly decreased in the 100 kb but not the 50 kb site in the P2X7 receptor KO group. Altogether, the P2X7 hypothesis of CPSP was proposed, wherein P2X7 receptor KO changed the CPSP pain behavior, numbers of astrocytes and microglia, CSD amplitude of the anterior cingulate cortex and the medial dorsal thalamus, BDNF and KCC2 expression, [Cl-], and P2X4 activation in 100 kb with P2X7 receptors. The present findings have implications for the clinical treatment of CPSP symptoms.

This review delves into the significance of chemical communication in mammals, with an emphasis on the role of the vomeronasal system in sensing pheromone-mediated interactions. The vomeronasal system shapes a variety of social and sexual behaviors, including reproduction, hierarchy formation, maternal bonding, and species recognition. Intriguingly, this system presents a vast degree of evolutionary variability, more so than variations observed in the olfactory system. This adaptive diversity underscores the challenges in studying the vomeronasal system, emphasizing the need for detailed research into its neuroanatomy and functional morphology. This review traverses an array of topics central to our understanding of chemical communication in mammals. We begin with the foundational role and basic concepts of chemocommunication. This is followed by an in-depth exploration of the olfactory systems. Subsequently, the neuroanatomical underpinnings of the vomeronasal system are juxtaposed against those of the olfactory system. Our focus then shifts to an exhaustive study of the sensory element of the vomeronasal system, the vomeronasal organ, and the integrating center of this information, the accessory olfactory bulb. The discussion extends to secondary projections of both the olfactory and vomeronasal systems in the light of the dual olfactory hypothesis. The review culminates with a detailed look at four specific models of vomeronasal system organization belonging to four evolutionarily distinct mammalian families: rodents, marsupials, herpestids, and bovids. These have been meticulously analyzed by the authors, aiming to spotlight the significant morphofunctional differences stemming from the adaptive changes imprinted on the system.

Climate change has become a major concern for developing countries given the risk that it posses on energy and food independence, and on general productivity. Despite having an energy system with low carbon intensity when compared to other Latin American countries, Colombia is already facing climate change impacts and requires urgent efforts to mitigate them. As a developing country, the challenge is bigger as policies for economic growth should be in line with the global commitment of reducing greenhouse gas emissions. With the aim of contributing to the design of climate policies, this study assesses the impact of economic development on the environment by examining the validity of the Environmental Kuznets Curve hypothesis for Colombia. Statistically validated and stable autoregressive distributed lag models are estimated for three different environmental indicators: carbon dioxide emissions, methane emissions, and ecological footprint. Moreover, the effects of other variables such as urbanization, foreign direct investment, value added of agricultural and industrial sectors, and energy use are analyzed with dynamic simulations. Empirical evidence supports a long-run equilibrium relationship among investigated variables and the existence of an inverted U-shaped EKC relationship between Gross Domestic Product (GDP) and methane emissions, and GDP and ecological footprint. Shifting to renewable energy sources and leveraging the use of cleaner technologies in agricultural and industrial sectors are found to be key for economic growth without harming the environment.

This study estimates the effects of double long memory and structural breaks on the persistence level of six major cryptocurrency markets. We apply the Bai and Perron’s structural break test, Inclán and Tiao’s iterated cumulative sum of squares (ICSS) algorithm, and the fractionally integrated generalized autoregressive conditional heteroscedasticity (FIGARCH) model with different distributions. The results show that long memory and structural breaks characterize the conditional volatility of cryptocurrency markets and confirm our hypothesis that ignoring structural breaks leads to an underestimation of the persistence of volatility modelling. The ARFIMA-FIGARCH model with structural breaks and a skewed Student–t distribution fits the cryptocurrency market’s price dynamics well.

In this paper, we suggest an expansion of the Planck distribution function derived from the Boltzmann principle. Thereby, we consider expanding Planck's law with a new distribution function, and discuss fine structure constant. Furthermore, using ideas applied to the expansion of the Planck distribution function, we show that Von Koch's inequality can be derived without using the Riemann Hypothesis, that is, the Riemann Hypothesis is true, and that the abc conjecture is not true. Furthermore, we define a generalization of Entropy and discuss that Entropy is relevant to dynamical systems described by logistic function models, such as the growth of bacteria and populations.

Nitrogen and phosphorous support the ecosystem by supplying nutrients to algae and aquatic plants. Having them in excess results in the eutrophication of waters creating quality problems. In the past, nitrogen has been widely investigated for wells in the context of groundwater flow. However, a national-scale nitrogen assessment in rivers and streams has not received enough attention. In this research, the Wilcoxon rank sum test, as a non-parametric hypothesis testing method, has been applied to nitrogen concentration in the form of nitrate-nitrogen and nitrite-nitrogen in rivers and streams of the Contiguous United States. This approach was particularly selected because of the non-normal and positively skewed nitrogen levels occurring in the surface flow. This method was able to identify the impaired body of waters as well as quantify the confidence, significance, and errors involved. The Northern Appalachians (NAP), Northern Plains (NPL), and Xeric (XER) ecoregions were worsening in the nitrogen-nitrate condition with NAP, and XER needed immediate actions. The nitrite-nitrogen condition did not pose an immediate threat, so mitigation plans should focus more on nitrate-nitrogen remediation. It was shown that the method was superior to the two-sample t-test by yielding lower type II errors.

Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, microbial and helminthic probiotic therapies have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, that contributes to a range of age-related diseases, including cardiovascular disease, dementia and cancer. Interestingly, Crowe et al. (2020) recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?

A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthesis system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remains largely unknown thus far. Based on ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.

Recent observations of the dark energy density have demonstrated the fine-tuning problem, and the challenges faced by theoretical modeling. In this study, we apply the self-similar symmetry (SSS) model, describing the hierarchical structure of the universe based on the Dirac large numbers hypothesis, to Einstein's cosmological term. We introduce a new similarity dimension, D_B, in the SSS model. Using the D_B SSS model, the cosmological constant Λ is simply expressed as a function of the cosmic microwave background (CMB) temperature. The result shows that both the gravitational constant G and Λ are coupled with the CMB temperature, which simplifies the solution of Einstein's field equations for the variable Λ-G model.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

It has not been reasonably explained still now, how the “chicken and egg relationship” between gene and protein was formed, although RNA world hypothesis was proposed to aim at explaining formation process of the relationship about 40 years ago. On the other hand, GADV hypothesis advocates that life emerged after five members of the fundamental life system; cell structure, metabolism, tRNA, genetic code and gene, were piled up one by one onto immature [GADV]-proteins, which were produced by random joining of [GADV]-amino acids on the primitive Earth. Furthermore, formation process of the first (GNC)n RNA gene encoding a mature [GADV]-protein can be also reasonably explained according to the hypothesis as follows. Double-stranded (ds)-(GNC)n RNA could be produced by complementary strand synthesis of a single-stranded (ss)-(GNC)n RNA, which was formed by random joining of GNC anticodons carried by four types of AntiC-SL tRNAs. Successively, the first (GNC)n RNA gene was generated upon maturation of an immature [GADV]-protein, which was produced through expression of codon sequence on one strand of ds-(GNC)n RNA, as accumulating necessary base substitutions and raising a weak catalytic activity of the immature protein to a more active state. It is considered that, consequently, a gene encoding a mature protein, which has the “chicken and egg relationship”, was generated for the first time. Therefore, it can be concluded that the “chicken and egg relationship” was built not by formation of either one, gene or protein, but by maturation of an immature gene, which was lead by improvement of catalytic activity of an immature protein. That is, it can be concluded that the reason, why it was unable to give an answer to the question on the formation process of the “chicken-egg relationship” thus far, is because it was an unanswered question.

This paper shows that by applying the Nyquist-Shannon sampling theorem, the spatial and temporal resolution of a simulation can be no more than half the resolution of the simulating reality. This has significant implications for not only the values of the observables in the simulation but also its physical laws. This progressive halving of nested simulations coupled with the minimum resolution compatible with the production of a simulation also sets a limit to the nestedness of a lineage of simulations (it is by no means infinite). The limit of nestedness is then used to calculate the probability that we are living in a simulation assuming a single base reality. This will be shown to be significantly lower than popular expectation. A Kardashev-like scale, with three variants, is also developed to gauge the technological advancement of a civilization in relation to the extent to which it can extract information from space and time.

In light of the self-simulation hypothesis, a simple form implementation of the principle of efficient language is discussed in a self-referential geometric quasicrystalline state sum model in three dimensions. Emergence is discussed in context of geometric state sum models.

In the case of vascular plants the process of water loss by leafs and water absorption by the root is well known. There is agreement on the passive nature of long-distance moisture movement in the dead cells of the xylem; however, controversy exists focusing on the long-distance water transport principle. Hales (1726) founded a view of bulk flow based on water suction after experiments with cut twigs. The previous doctrine of long-distance water transport within vessel elements and tracheid of the xylem of intact plants – the relevant cohesion theory in text books – was developed mainly by Boehm (1893), Renner (1911) and Dixon (1914) with plant artefacts. Water movement according to this theory is based on an assumed hydrodynamic bulk fluid flow in xylem in continuous water columns (free of water vapour space), under tension, according to the law of Poiseuille (see e.g. Dixon 1914). Physically hydrodynamics is part of fluid mechanics, as a result Poiseuille’s law is usually valid only for hydrodynamic bulk flow in ideal capillaries (Sutera & Skalak, 1993). Besides the basic requirement for transport, according to cohesion theory, the existence of ideal capillaries is not compatible with either: “Because vessel elements and tracheid do not stand as ideal capillaries. …” (Bresinsky et al. 2008, translated from German). Unlike ideal capillaries, the walls of vessel elements and tracheid interact with the transported water. These walls are able to function as a source or as a sink for the transported water because of interaction with the cell walls. With the interaction, vessel elements and tracheid, part of the xylem, can shrink and swell, unlike ideal capillaries. Because the xylem (in woody plants part of the wood) is inconsistent with the basic law of fluid flow, the equation of mass balance (Zimmermann et al. 2004) and cohesion theory are not strictly followed.Many plant physiologists view the cohesion theory as appropriate, however, this theory remains controver­sial, i.e. by Eisenhut (1988), Laschimke (1990) and Hahn (1993). Nultsch (1996) gives doubts referring to the present doctrine of plant water transport. Zimmermann et al. (2004) reject the cohesion theory and conclude: “... that the arguments of the proponents of the Cohesion Theory are completely misleading” (Zimmermann et al. 2004). Hence cohesion theory can be treated as inapplicable and the question arises: how does water transport in fact function? In the following, it is gone into in more detail. A sorption hypothesis of actual water transport, based on empirical fact, shall be addressed in this paper.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (DChol.) from consumption of saturated fat (DS), polyunsaturated fat (DP), and cholesterol (DZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

The precise mathematical description of gaze patterns is still an unsettled matter of debate. This can, consequently, affect the analysis of this type of data in its practical applications. In this scope, we show evidence that a Lévy-flight description of eye-gaze trajectories is not only appropriate but its scale invariant properties are remarkably useful to assist in diagnosing children with Attention Deficit and Hyperactivity Disorder (ADHD), alongside with the usual cognitive tests. Using this picture, we find that the distribution of the characteristic exponent of Lévy-flights statistically is different in children with ADHD. Furthermore, we observe that these children deviate from a strategy that is considered optimal for searching processes, in contrast to non-ADHD children. We focus on the case where both eye-tracking data and data from a cognitive test are present and show that the study of gaze patterns in children with ADHD can help in identifying this condition. Since eye-tracking data can be gathered during cognitive tests without needing extra time-consuming specific tasks, we argue that it is in prime position to provide assistance in the arduous task of ADHD diagnosing.

Ad- and desorption forces move water in living xylem/wood from the root to the leaf thermodynamically. The doctrine of plant water transport, the so-called cohesion- or cohesion-tension theory, postulates however that the process is physically based on a hydraulic fluid flow with negative pressure in water conducting tubes originating from the leaves. Lower pressure (suction) driven volume flow is physically a branch of mechanics. Moisture absorbed from the soil via the root is thought to be pulled up the stem by the leaves in continuous and tensioned threads of water. It is assumed that the hydraulic Hagen/Poiseuille flow law, derived for tubes, applies in the xylem. In a textbook of botany you can find the opinion: "Just as the pipes of a water pipe supply necessary water to each household, leaf nerves supply water and nutrient salts to each individual cell.” (Translated from German). Many plant physiologists consider this hydraulic principle to be correct, but it does not remain unchallenged. Doubts are repeatedly expressed. The question arises: How does water transport actually take place? It is shown how the diffusive/adsorption transport principle works. The partial dehydration (desorption) of the plant, driven by the diffusive process of transpiration, forms a combined concentration and adsorption-site gradient for water in the xylem matrix. Especially with open stomata the lowest moisture concentration and the highest number of adsorption-sites for water (sites with free van der Waals forces), can be found in the mesophyll cell walls at the liquid/vapor boundary in the leaf. The water taken up by the root moves spontaneously in the direction of this boundary and can thus partially or completely compensate for the existing concentration- and adsorption-site- differences for water. Thus, a thermodynamic overlapping diffusive/adsorptive movement of moisture along the stationary xylem/wood takes place. After the introduction and a review of some controversies with cohesion theory, the physiology of the processes associated with long-distance water displacement is mentioned below. A thermodynamic adsorption hypothesis of the natural water transport in plants, based on known facts, is presented.

In ethnobotany, the availability hypothesis predicts that plants that are abundant and easily accessible to people are more likely to be medicinal than not. By protecting species diversity away from people, protected areas (PAs) may act as a limiting factor to a sustainable development of traditional knowledge concerning medicinal uses, and in so doing, PAs provide opportunity to prioritize ex-situ conservation for species that are PAs restricted. In this scenario, ex-situ conservation becomes the only chance for people to develop traditional knowledge on plants which otherwise wouldn’t be documented as traditionally useful to people. To test these expectations, we used data collected for almost 20 years of fieldworks on plant medicinal uses and their abundance inside and outside the Kruger National Park (KNP), South Africa. We fitted four different scenarios of structural equation models (SEMs) to the data collected. We found that total plant abundance (abundance outside + inside KNP) is a significant positive predictor of medicinal status, and so is abundance outside KNP, thus supporting the availability hypothesis. However, not only abundance inside KNP is not a direct significant correlate of medicinal status, but also the relationship between both is negative. The lack of predictive power of inside-abundance is most likely because some species are exclusively found inside KNP, and local communities do not have access to them. It also shows that the positive and direct correlation of total abundance with medicinal status is driven by outside-abundance. In addition, the negative relationships between inside abundance and medicinal status implies that abundant plants inside KNP tend to be not-medicinal, further providing evidence that PAs hinder the development of medicinal knowledge. Furthermore, when inside and outside abundance were included simultaneously in a model as two distinct variables, inside abundance was never a direct significant predictor of medicinal status, but it was so, via an indirect path mediated by outside abundance. This suggests that outside abundance is the key variable driving the development of medicinal plant knowledge. Cumulatively, our findings suggest that anything that promotes the growth of PA-restricted plants beyond the natural realized niches of these plants (ex-situ conservation) such as in botanical gardens, private gardens, in agroforestry systems, etc., is to be promoted so that people-plant interactions may continue for the benefits of ethnobotanical knowledge development.

Alzheimer’s and Parkinson's diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in medi-ating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

In this paper we address some variants for the products of Hadamard and Patterson. We prove that all zeros of the Riemann $\Xi$--function are real. We also prove that the Riemann hypothesis is true. The equivalence theorems associated with the Riemann zeta--function are obtained in detail.

An iterative outlier elimination procedure based on hypothesis testing, commonly known as Iterative Data Snooping (IDS) among geodesists, is often used for the quality control of the modern measurement systems in geodesy and surveying. The test statistic associated with IDS is the extreme normalised least-squares residual. It is well-known in the literature that critical values (quantile values) of such a test statistic cannot be derived from well-known test distributions, but must be computed numerically by means of Monte Carlo. This paper provides the first results about Monte Carlo-based critical value inserted to different scenarios of correlation between the outlier statistics. From the Monte Carlo evaluation, we compute the probabilities of correct identification, missed detection, wrong exclusion, overidentifications and statistical overlap associated with IDS in the presence of a single outlier. Based on such probability levels we obtain the Minimal Detectable Bias (MDB) and Minimal Identifiable Bias (MIB) for the case where IDS is in play. MDB and MIB are sensitivity indicators for outlier detection and identification, respectively. The results show that there are circumstances that the larger the Type I decision error (smaller critical value), the higher the rates of outlier detection, but the lower the rates of outlier identification. For that case, the larger the Type I Error, the larger the ratio between MIB and MDB. We also highlight that an outlier becomes identifiable when the contribution of the measures to the wrong exclusion rate decline simultaneously. In that case, we verify that the effect of the correlation between the outlier statistics on the wrong exclusion rates becomes insignificant from a certain outlier magnitude, which increases the probability of identification.

Environmental DNA (eDNA) is an increasingly used non-invasive molecular tool for detecting species presence and monitoring populations. In this article, we review the current state of non-avian reptile eDNA work in aquatic systems, as well as present a field experiment on detecting the presence of painted turtle (Chrysemys picta) eDNA. Thus far, turtle and snake eDNA studies have been successful mostly in detecting the presence of these animals in field conditions. However, some instances of low detection rates and non-detection occur for these non-avian reptiles, especially for squamates. We explored this matter by sampling lentic ponds with different densities (0 kg/ha, 6 kg/ha, 9 kg/ha, and 13 kg/ha) of painted turtles over three months, attempting to detect differences in eDNA accumulation using a qPCR assay. Only one sample of the highest density pond readily amplified eDNA. Yet, estimates of eDNA concentration from pond eDNA were rank-order correlated with turtle density. We present a “shedding hypothesis”–the possibility that animals with hard, keratinized integument do not shed as much DNA as mucus-covered organisms–as a potential challenge for turtle eDNA studies. Despite challenges with eDNA inhibition and availability in water samples, we remain hopeful that eDNA can be used to detect freshwater turtles in the field. We provide key recommendations for biologists wishing to use eDNA methods for detecting non-avian reptiles.

Contact with nature is suggested to be as an important resource for human health and well-being. Stress alleviation and reduction of mental fatigue are main instances of improvement of human health and well-being in contact with nature. Although the term restoration experience in contact with nature has been used repeatedly for concepts of stress alleviation and reduction of mental fatigue, these refer to different sets of theories and research studies. In this paper, by reviewing the nature-health related theories of Biophilia, Stress Recovery Theory, Attention Restoration Theory and Supportive Environment Theory (SET), the similarities and differences between these two concepts have been discussed. Moreover, the measurement approach instruments based on different study methodologies and aims are provided. This paper could provide information for future studies with focus on factors to be of benefit for restoration experience in design and planning of natural landscape environments with the aim of health and well-being development.

This study aimed to compare procedural learning skills between Spanish-speaking preschool children (ages 4 years to 4 years, 11 months) with Developmental Language Disorder (DLD) and their typically developing (TD) peers. Using the Serial Reaction Time task, participants (30 DLD and 30 TD children) respond to visual stimuli in a sequenced manner over four blocks, followed by a random order block. The task assessed reaction time (RT) and accuracy. Results showed a significant interaction between group and block for reaction time (RT) and accuracy, with children with DLD exhibiting longer RTs and accuracy deficits across blocks. In contrast, the TD group showed higher RT efficiency and accuracy in the sequential blocks and as expected, decreased performance in the random block according to the experimental manipulation. Overall, the results of this investigation suggest that there was no implicit learning in the DLD group, as indicated by the SRT task paradigms of procedural memory. These findings align with the Procedural Deficit Hypothesis (PDH), suggesting that linguistic deficits in the TD population may derive from a general dysfunction of the procedural memory system domain in the Spanish context.

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.

Whether the universe is a computer simulation, or whether we wish to efficiently model our universe in a computer simulation, there would be benefits to modeling it in a fashion analogous to computer spreadsheet, each lattice cell can be conceived as containing all the mathematical formula necessary to continuously compute its state relative to changes in all its neighboring cells, and by progression, in relation to all the cells of entire space-time lattice. Alternatively, the “real” universe may itself be built on a space cell lattice, an irregular foam of space cells, in which each cell may be conceived as a multidimensional cell of distortable space, the shape of which fully describes (a) the four basic forces (gravity, electromagnetic, strong, weak) observed at that cell of space, and (b) the probability (or weight distribution) of any quantum states overlapping the cell and its neighbors. At an appropriate scale, it would appear that this conceptual model would resolve apparent conflicts between general relativity and quantum physics. It would also provide a new interpretation of Planck’s constant as description of the number of space cell events associated with any set of observable events. If formulae operating at a lattice cell level can be improve our ability to understand and model larger scale phenomena, this would be strong evidence in favor of the theory that mathematics is not just a human invention but rather an inherent feature of space-time itself.

Globally, anthropogenic sound and artificial light pollution have increased to alarming levels. Evidence suggests that these can disrupt critical processes that impact ecosystems and human health. However, limited focus has been given to the potential effects of sound and artificial light pollution on microbiomes. Microbial communities are the foundations of our ecosystems. They are essential for human health and provide myriad ecosystem services. Therefore, disruption to microbiomes by anthropogenic sound and artificial light could have important ecological and human health implications. In this mini-review, we provide a critical appraisal of available scientific literature on the effects of anthropogenic sound and light exposure on microorganisms and discuss the potential ecological and human health implications. Our mini-review shows that a limited number of studies have been carried out to investigate the effects of anthropogenic sound and light pollution on microbiomes. However, based on these studies, it is evident that anthropogenic sound and light pollution have the potential to significantly influence ecosystems and human health via microbial interactions. Many of the studies suffered from modest sample sizes, suboptimal experiments designs, and some of the bioinformatics approaches used are now outdated. These factors should be improved in future studies. This is an emerging and severely underexplored area of research that could have important implications for global ecosystems and public health. Finally, we also propose the photo-sonic restoration hypothesis: does restoring natural levels of light and sound help to restore microbiomes and ecosystem stability?

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

Abstract The relationship between cancer and neurodegeneration has spurred extensive scientific discourse, challenging their historical classification as distinct disorders. While cancer signifies uncontrolled cellular proliferation and neurodegeneration marks progressive neuronal loss, recent insights highlight intriguing interconnections between these seemingly disparate conditions. Cancer entails perpetual signaling for growth, evasion of growth inhibitors, resistance to cell death, acquisition of replicative immortality, stimulation of blood vessel growth (angiogenesis), and initiation of invasion and metastasis. Conversely, investigations emphasize disrupted cellular energy regulation and evasion of immune surveillance as key traits arising from genome instability, mutations, and inflammation driving tumorigenesis. Neurodegeneration involves neuronal malfunction and depletion, synaptic impairment, and protein abnormalities aggregations contributing to muscle atrophy and cognitive deficits. Varied clinical studies underscore contrasting correlations between cancer and neurodegeneration, hinting at mirrored molecular pathways that foster cell resilience or vulnerability. Research explores cellular signaling in tumorigenesis, shared with neurodegenerative disorders. Aberrant expression or mutations in crucial genes implicated in neurodegeneration also surface in cancer contexts. Debates persist on the nature of the relationship between cancer and neurodegeneration, contemplating inverse associations or shared pathways. Understanding their complex interplay, encompassing genetics, cellular mechanisms, and environmental influences, remains pivotal in unraveling their connections. This review explores the intriguing perspective that neurodegeneration and cancer might share fundamental genetic links, delving into potential implications for their onset and progression.

A recent research has identified an inverse amplitude link between obliquity damping and short eccentricity amplification during Mid-Late Pleistocene based on LR04 δ18O and equatorial Pacific Site 846 sea surface temperature records, which is associated with the Earth's long-term cooling. In the present study, new evidence of this anticorrelation is presented from Antarctic D-CO2-CH4 records, global benthic-planktic δ18O, and regional (Atlantic, Pacific, Mediterranean, and Indian) climate-related proxies. Based on a critical review of theoretical constrains (Earth's oblateness changes and ice-volume phase lag in the obliquity band <5.0 kyr), this widespread and symmetric (bipolar) obliquity response damping has been interpreted as an effect of the obliquity-oblateness feedback, which could be the latent physical mechanism at the origin of the Mid-Pleistocene Transition (MPT). Indeed, results and considerations of the present work suggest that fast and positive/negative net variation of the Earth's oblateness in the obliquity band was controlled by dominant glacio-eustatic water mass component and, assuming a rapid response of the ice-volume to surface temperature changes, the mean obliquity lag response is estimated to be <5.0 kyr over the past 800 kyr. These elements may explain the interglacial/glacial damping observed in the obliquity response. The consolidation of the Earth's long-term icy-state in the subtrend IV, culminated with the post-MPT obliquity damping, might have contributed to the strengthening of the short eccentricity response by mitigating the obliquity ‘ice-killing’ during obliquity maxima (interglacials), favouring the obliquity-cycle skipping and a feedback amplified ice-growth in the short eccentricity band (obliquity damping hypothesis). This could suggest a different impact of the climate friction than what is generally believed, which is presumably the latent physical mechanism that triggers transient ‘competitive’ interaction between obliquity and short eccentricity started early during the Piacenzian.

Ecologists use the net biotic interactions among plants to predict fundamental ecosystem features. Following this approach, ecologists have built a giant body of theory founded on observational evidence. However, due to the limitations that a phenomenological approach raises both in empirical and theoretical studies, an increasing number of scientists claim the need for a mechanistic understanding of plant interaction outcomes, and a few studies have taken such a mechanistic approach. In this synthesis, we propose a modeling framework to study the plant interaction mechanistically. We first establish a conceptual ground to frame plant-plant interactions, and then, we propose to formalize this research line theoretically developing a family of individual-based, spatially-explicit models in which biotic interactions are an emergent property mediated by the interaction between plants’ functional traits and the environment. These models allow researchers to evaluate the strength and sign of biotic interactions under different environmental scenarios and thus constitute a powerful tool to investigate the mechanisms underlying facilitation, species coexistence, or the formation of vegetation spatial patterns.

While the COVID-19 outbreak was reported to first originate from Wuhan, China, it has been declared as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 by WHO, and it has spread to over 180 countries by the time of this paper was being composed. As the disease spreads around the globe, it has evolved into a worldwide pandemic, endangering the state of global public health and becoming a serious threat to the global community. To combat and prevent the spread of the disease, all individuals should be well-informed of the rapidly changing state of COVID-19. In the endeavor of accomplishing this objective, a COVID-19 real-time analytical tracker has been built to provide the latest status of the disease and relevant analytical insights. The real-time tracker is designed to cater to the general audience without advanced statistical aptitude. It aims to communicate insights through various straightforward and concise data visualizations that are supported by sound statistical foundations and reliable data sources. This paper aims to discuss the major methodologies which are utilized to generate the insights displayed on the real-time tracker, which include real-time data retrieval, normalization techniques, ARIMA time-series forecasting, and logistic regression models. In addition to introducing the details and motivations of the utilized methodologies, the paper additionally features some key discoveries that have been derived in regard to COVID-19 using the methodologies.

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

In this study, we consider a Lambert series whose coefficients are the sum of divisors function. Utilizing the Lambert series in the sequel we introduce a normalized linear operator JR_(α,β) (z) by applying the convolution with Rabotnov function. We then, acquire sufficient conditions for JR_(α,β) (z) to be Univalent, Starlike and Convex respectively. In each component of this study, we expand the derived results by applying two Robin's inequalities, one of which is equivalent to the Riemann hypothesis.

Foundational and state-of-the-art anomaly detection methods through power system state estimation are reviewed. The traditional components for bad data detection such as chi-square testing, residual-based methods, and hypothesis testing are discussed to explain the motivations for recent anomaly detection methods given the increasing complexity of power grids, energy management systems, and cyber-threats. In particular, state estimation anomaly detection based on data-driven quickest change detection and artificial intelligence are discussed and directions for research are suggested with particular emphasis on considerations of the future smart grid.

Alzheimer's Disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD) - whose causes are not completely understood - and familial (FAD) - with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits of amyloid-beta (Ab) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein (P-tau). An ever-growing body of research supports the infectious hypothesis of sporadic forms of AD. Indeed, it has been documented that some pathogens, such as herpesviruses and certain bacterial species, are commonly present in AD patients, prompting recent clinical research to focus on the characterization of Antimicrobial Peptides (AMPs) in this pathology. Literature also demonstrates that Ab can be considered itself as an AMP thus representing a type of innate immune defense peptide that protect the host against a variety of pathogens. Beyond Ab, other proteins with antimicrobial activity, such as lactoferrin, defensins, cystatins, thymosin β4, LL37, histatin 1 and statherin have been shown to be involved in AD. Here we have summarized and discussed these findings and explored the diagnostic and therapeutic potential of AMPs in AD.

This research paper aims to explicate the complex issue of the Riemann's Hypothesis and ultimately presents its elementary proof. The method implements one of the binomial coefficients, to demonstrate the maximal prime gaps bound. Maximal prime gaps bound constitutes a comprehensive improvement over the Bertrand's result, and becomes one of the key elements of the theory. Subsequently, implementing the theory of the primorial function and its error bounds, an improved version of the Gauss' offset logarithmic integral is developed. This integral serves as a Supremum bound of the prime counting function Pi(n). Due to its very high precision, it permits to verify the relationship between the prime counting function Pi(n) and the offset logarithmic integral of Carl Gauss. The collective mathematical theory, via the Niels F. Helge von Koch equation, enables to prove the RIemann's Hypothesis conclusively.

Understanding how the coronaviruses invade our body is an essential point, and the expression profile of coronaviruses receptor may help us to find where the coronavirus infects our body. We found that the coronavirus receptors, including angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-Cov-2, are digestion-related enzymes in human enterocytes. Coronaviruses are continually altering the binding receptor and binding modes during their evolution, but the potential target cell in the small intestine is constant when in the lung is inconstant. Enterocytes may act as a conserved cell reservoir for coronaviruses, which may be partially explained by the Red Queen hypothesis. We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies.

1. Heterospecific pollen interference has recently been proposed as a mechanism contributing to the success of alien invaders, as heterospecific pollen of alien plants interferes with the reproduction of natives by reducing fruit and seed set. However, no study has looked at the opposite interaction. Moreover, few studies have considered the roles of phylogenetic and trait distances between pollen donors and recipients. 2. We did a large multi-species experiment in which we used alien and native species both as pollen recipients and as pollen donors, and included phylogenetic as well as trait distance as explanatory variables. 3. We found that both alien and native recipients suffered from heterospecific pollen from donors of the opposite status in terms of seed and fruit set. Phylogenetic distance and trait distance both affected heterospecific pollen interference, but the effect depended on recipient and donor statuses. 4. We conclude that heterospecific pollen interference affects both native and alien recipients, thus indirectly altering community composition and increasing biotic resistance against invaders.