The strategy of any organization is based on the growth of its customer base, and one of 6 its principles is that selling a product to an existing customer is much more profitable than acquiring 7 a new customer. However, this approach has several opportunities for improvement, since it usu- 8 ally has a totally reactive approach, which does not give opportunity to the areas specialized in 9 customer experience and recovery, to give an effective response for that moment, since the customer 10 is gone at the time of the intervention. This happens because usually a diagnostic analysis of cus- 11 tomers who have stopped buying products or services in a defined period, commonly three (3) pe- 12 riods or months, is performed. This paper challenges the way to face this problem, and proposes 13 the development of a complete solution, which does not focus exclusively on the prediction of 14 churn, as is usually done in the state of the art research, but to intervene in different interactions 15 that can be carried out with customers. The above focused not only to prevent customer churn, but 16 to generate an added value of continuous improvement in sales processes, increase customer pene- 17 tration, leading to an improvement in customer experience and consequently, an increase in cus- 18 tomer loyalty.

The strategy of any organization is based on the growth of its customer base, and one of 5 its principles is that selling a product to an existing customer is much more profitable than acquiring 6 a new customer. However, this approach has several opportunities for improvement, since it usu- 7 ally has a totally reactive approach, which does not give opportunity to the areas specialized in 8 customer experience and recovery, to give an effective response for that moment, since the customer 9 is gone at the time of the intervention. This happens because usually a diagnostic analysis of cus- 10 tomers who have stopped buying products or services in a defined period, commonly three (3) pe- 11 riods or months, is performed. This paper challenges the way to face this problem, and proposes 12 the development of a complete solution, which does not focus exclusively on the prediction of 13 churn, as is usually done in the state of the art research, but to intervene in different interactions 14 that can be carried out with customers. The above focused not only to prevent customer churn, but 15 to generate an added value of continuous improvement in sales processes, increase customer pene- 16 tration, leading to an improvement in customer experience and consequently, an increase in cus- 17 tomer loyalty.

Host ribosome-associated scaffold protein Receptor for Activated C Kinase 1 (RACK1) is utilized by a diverse group of human viruses for Internal Ribosomal Entry Sites (IRES) – mediated translation of viral mRNAs. We recently reported inhibition of herpes virus by small molecules targeting the RACK1 functional site. Here, we tested these molecules against HIV-1 and HCV, as HIV-1 contains two potential IRES sites and HCV translation occurs exclusively through IRES. Compounds significantly downregulated activities of HIV-1- and HCV-related dicistronic reporter constructs in transfected HEK293T cells. The compounds also strongly downregulated production of the HIV-1 capsid protein p24 in HIV-infected cells, as well as production of HIV-1 Gag precursor p55 and p55-derived proteins p24 and p17 in cells infected with the HIV-1 virus. Hepatitis C virus (HCV) IRES activities were also significantly inhibited by RACK1 inhibitor compounds. Since a number of human and plant pathogenic viruses are reported to use IRES, the RACK1 compounds can be established as broad host-targeted antivirals.

We live in the time of profound transformations commonly labelled with the word “globalization”. The rise of one ecological-technological-social system encompassing our whole planet is an important element of these processes. Solving big global problems demands knowledge of two complementary sorts: on the one hand – going “in depth”, on the other – going “in breadth”. The present paper assumes the second (in a sense: philosophical) perspective. It tries to analyze some relations between the development of technology (IT) and the development of democracy. The notion of democracy, its various forms and axiological reasons for it are considered first. In the subsequent chapter different consequences (both positive and negative) the IT development has for contemporary democracy are discussed. In the next chapter the evolutionary nature of the technological development is debated as well as the question of (democratic) control of this process. The development of Artificial General Intelligence is presented as a challenge for democracy

Inhibition of the binding of enveloped viruses surface glycoproteins to host cell receptor(s) is a major target of vaccines and constitutes an efficient strategy to block viral entry and infection of various host cells and tissues. Cellular entry usually requires fusion of the viral envelope with host plasma membranes. Such entry mechanism is often preceded by “priming” and/or “activation” steps requiring limited proteolysis of the viral surface glycoprotein to expose a fusiogenic domain for efficient membrane juxtapositions. The 9-membered family of Proprotein Convertases related to Subtilisin/Kexin (PCSK) serine proteases (PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1/S1P and PCSK9) participate in post-translational cleavages and/or regulation of multiple secretory proteins. The type-I membrane-bound Furin and SKI-1/S1P are the major convertases responsible for the processing of surface glycoproteins of enveloped viruses. Stefan Kunz has considerably contributed to define the role of SKI-1/S1P in the activation of arenaviruses causing hemorrhagic fever. Furin was recently implicated in the activation of the spike S-protein of SARS-CoV-2 and Furin-inhibitors are being tested as antivirals in COVID-19. Other members of the PCSK-family are also implicated in some viral infections such as PCSK9 in Dengue. Herein, we summarize the various functions of the PCSKs and present arguments whereby their inhibition could represent a powerful arsenal to limit viral infections causing the present and future pandemics.

Circadian rhythms misalignment is associated with hypertension. The aim of the study was to evaluate the concentration of selected clock proteins- cryptochrome 1 (CRY1) and circadian locomotor output cycles kaput (CLOCK) and to determine their relationships with biochemical and anthropometric parameters and lifestyle elements (diet, physical activity, quality of sleep) in hypertensive patients. In 25 female with hypertension (HT) and 49 non-hypertensive women (NHT), the CRY1 and CLOCK concentrations, total antioxidant status (TAS), lipid profile and glycemia were conducted. Blood pressure and anthropometric measurements, nutritional, exercise and sleep analyses were performed. In HT the CRY1 level was 40.2% lower than in the NHT. No differences were noted in CLOCK concentration between groups. The study showed no relationship between CRY1 or CLOCK concentrations and glucose or lipids profile, amount of physical activity and sleep quality, although CRY1 was associated with some anthropometric parameters. There was a negative correlation between the CLOCK concentration and the amount of saturated fatty acids consumed (24h) in HT. That indicates the possible influence of the diet on the CLOCK level. In a detailed prognosis of the risk of hypertension, it is worth considering the measurement of the level of CRY1 in populations with abnormal anthropometric indices.

In recent years, poly (ADP-ribose) polymerase (PARP) inhibitors have heen evaluated for treating homologous recombination-deficient tumors, taking advantage of synthetic lethality. However, increasing evidence indicates that PARP proteins exert several cellular functions unrelated with their role on DNA repair, including function as a co-activators of transcription through protein-protein interaction with E2F1. Since the RB/E2F1 pathway is among the most frequently mutated in many tumours types, we investigated whether the absence of PARP activity could counteract the consequences of E2F1 hyperactivation. Our results demonstrate that genetic ablation of Parp1 extends the survival of Rb-null embryos, while genetic inactivation of Parp1 results in reduced development of pRb-dependent tumors. Our results demonstrate that PARP1 plays a key role as a transcriptional co-activator of the transcription factor E2F1, an important component of the cell cycle regulation. Furthermore, impairment of PARP results in a reduction of tumor growth, that is not depending of the activity of PARP on DNA repair. Considering that most oncogenic processes are associated with cell cycle deregulation, the disruption of this PARP1-E2F1 interaction could provide a new therapeutic target of great interest and a wide spectrum of indications.

For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. We aimed to assess whether a time trend in AAM with associated disease risk is also present in Mexico. For this, we used data of 30,826 women from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, whereas Welch-ANOVA was used to test for a time trend. AAM decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years). AAM (in years) was negatively associated with weight (β = -1.01 kg; 95 % CI -1.006, -1,004) and BMI (β = -1.01 kg/m2; -1.007, -1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

1) This study describes the good evolution of a 6-year-old girl genetically diagnosed with Rett syndrome (RTT), after having been treated with IGF-1, MT (MT), blackcurrant extracts (BC), and rehabilitation during 6 months. 2) The patient stopped her normal development from the first year of age. The patient showed low weight and height and met the main criteria for typical RTT. Curiously, there was pubic hair (Tanner II), very high plasma testosterone, despite low gonadotropins. No adrenal enzymatic deficits existed, and ultrasound abdominal studies were normal. Treatment consisted in IGF-1 (0.04 mg/kg/day, 5/week, sc) during 3-months and then 15-days resting, MT (50 mg/day, orally, uninterruptedly) and neurorehabilitation. The new blood tests were absolutely normal and the pubic hair disappeared. Then, a new treatment with IGF-1, MT, and BC started for another 3 months. After it, pubic Tanner stage increased to III, without a known cause. 3) The treatment followed led to clear improvements in most of the initial impairments, perhaps because of the effect of IGF-I, the antioxidant effects of MT and BC, and the increase in cyclic-glycine-proline (cGP) after BC administration. 4) A continuous treatment with IGF-1, MT and BC may recover most of the neurologic disabilities that occur in RTT.

This article examines illicit financial flows (IFFs) perpetuated in financial statements to develop a framework to curb IFFs. IFFs create opacity, impeding economic progress through investment deterrents and financial uncertainty. Through a comprehensive literature review and the synthesis of sets of qualitative propositions, the researchers previously developed a conceptual framework to address IFFs, and the purpose of the present article is to strengthen and validate the framework among stakeholders in the financial and audit sectors. Following a mixed inductive and deductive research approach and a qualitative methodological choice, the researchers conducted interviews among practitioners to enhance the framework, followed by a focus group to validate the framework. IFF challenges that emerged are tax evasion, for example, investments in untraceable offshore accounts, harming the economy, bitcoins not being subject to regulation everywhere in the world and being used by cryptocurrency criminals to transfer IFFs to nations with lax regulations. Internationally, IFF risks are also determined by geographical position, trade links and porous borders among countries emerged as further challenges, calling for entities to execute existing policies, improve tax enforcement methods, apply cross-border coordination, and practice financial reporting transparency aimed at combatting IFF practices. On the strength of these, the industry surveys significantly enhanced the conceptual framework.

The existence of semantic inaccuracy §2 articles by A. Einstein “On the electrodynamics of moving bodies”, illustrating the principle of the relativity of simultaneity. In a sentence “The observers co-moving with the moving rod would thus find that the two clocks do not run synchronously while the observers in the system at rest would declare them synchronous”, the preposition “not” must be moved and placed before the word “synchronous”, at the end of the sentence. The criterion for synchronism of the clocks on the rod is the time it takes for the beam to travel from clock A to clock B and back, and for observers on the rod it will be the same both when the rod is at rest and when the rod is moving. Otherwise, observers on the rod would have had at their disposal an experiment that would allow them to determine whether the rod is moving or at rest, which contradicts the first postulate of the Special Theory of Relativity. The inaccuracy is found unchanged in modern editions in English and Russian, and can become a source of difficulties when teaching the basics of the Special Theory of Relativity based on primary sources, as well as make it difficult to understand the author’s logic when studying independently. Nobel laureate R. Feynman, having expanded and modified A. Einstein's thought experiment, eliminated the inaccuracy described in the article.

The prim objective of commenced article is to determine q-sumudu transforms of a product of unified family of q-polynomials with basic (or q-) analogue of fox’s H-function and q-analog of I-functions. Specialized cases of the leading outcome are further evaluated as q-sumudu transform of general class of q-polynomials and q-sumudu transforms of the basic analogues of Fox’s H-function and I-functions.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The present standard-of-care for type 1 diabetes is exogenic insulin substitutional therapy. The most advanced stretegies in this area is the development of hybrid-closed loop system and the producing of long-acting insulins. Progresses in stem cell therapies have started to revolutionize the care of patients with type 1 diabetes; however, significant challenges remain including the limited islets availability, difficulties in maintaining the viability, the heterogeneity within a complex pathology and in patients’ responses to treatment. On the way, a considerable amount of efforts in maximizing the islet transplantation effectiveness by controlling the advantageous of different stem cell approaches. With the availability and the use of big data, the concept of precision medicine is gaining wide attention worldwide and could bring the dream of “presonlaized” therapies as a reality in the near future. Here we review the current range of treatments available as well as recent pre-clinical breakthroughs in the field of personlaized medicine for type 1 diabetes.

In this research paper, we implement the theory of the primorial function, to develop the Supremum and Infimum bounds for the sum of (log(p))². There are, however, considerable computational difficulties related to these bounds. Therefore, from a pragmatic point of view, a set of Upper and Lower bounds had been developed to bypass this issue. Despite the increased estimation error, the Upper and Lower bounds are still considered sufficiently accurate, while facilitating an easy and fast computation of the estimate of the sum.

The difficult current environmental situation, caused by construction industry residues containing ceramic materials could be improved by using these materials as recycled aggregates in mortars, with their processing causing a reduction in their use in landfill, contributing to recycling and also minimizing the consumption of virgin materials. Although some research is currently being carried out into recycled mortars, little is known about their stress-strain (σ-ε); therefore this work will provide the experimental results obtained from recycled mortars with recycled ceramic aggregates (with contents of 0, 10, 20, 30, 50 and 100%), such as: the density, the compression strength, as well as the σ-ε curves representative of their behavior. The values obtained from the analysis process of the results are those of: σ (elastic ranges and failure maximum), ε (elastic ranges and failure maximum), and Resilience and Toughness; in order to finally obtain, through numerical analysis, the equations to predict their behavior (related to their recycled content). At the end of the investigation it is established that mortars with recycled ceramic aggregate contents of up to 20% could be assimilated just like mortars with the usual aggregates, and the prediction equations produced could be used in cases of similar applications.

The center of gravity of a three-dimensional object found through an experimental method can be made easier and faster than when calculating the movement manually in order to make the movement in computer graphic images look more natural. In addition, in various sports such as skating, the score can be increased by appropriately moving the position of the center of gravity. Lastly, it is expected that it can be used even when the performance is high in the manufacturing process to increase the stability and speed of various means of transportation (eg, automobiles, airplanes, etc.).

The inability to delineate a unified physical ontology that accounts simultaneously for the laws of special relativity and the results of quantum experiments has been a defining problem in physics for more than 100 years. This analysis addresses the problem by positing an ontic, mixed ontology composed of a “discrete” 4D spacetime and a physical, ultra-high dimensional (3 x N) “Planck Space.” Together, Planck Space and the three spatial dimensions of 4D spacetime form a tightly integrated ((3 x N) + 3) hyperspace (the “Dual Ontology”). Critically, the Dual Ontology’s structure replaces 1) the continuous, differentiable manifold of 4D spacetime with a discrete 4D spacetime and 2) mathematical 3N configuration spaces with a physical (3 x N) Planck Space. Moreover, the Dual Ontology is structurally and dynamically predicated on the one-to-one mapping and identity between the discrete spatial units that simultaneously form 4D spacetime and Planck Space. The one-to-one mapping and identity of the discrete spatial units support an integrated quantum dynamics based upon the dynamic evolution of single and N-body quantum states in 4D spacetime in full compliance with the laws of special relativity and the instantaneous collapse of all quantum states in an ontic Planck Space, where special and general relativity and more generally, 4D spacetime’s laws of physics, do not apply.

In this article, the multitouch option, also called the n  touch option (or the “baseball” option when n  3 ) is analyzed and valued in closed form. This is a kind of barrier option that sets a gradual knockout / knock-in mechanism based on the number of times the underlying asset has crossed a predefined barrier in various time intervals before expiry. The higher the number of predefined time intervals during which the barrier has been touched, the lower the value of a knock-out contract at expiry, and conversely for a knock-in one. Multitouch options can be viewed as an extension of step barrier options, preserving the ability of the latter to adjust the exposure to risk over time, while eliminating the notorious danger of “sudden death” that holders of step barrier options are faced with. Unlike occupation time derivatives, the payoff at expiry does not depend on the amount of time spent outside the authorized range, but on the number of passages beyond the authorized range.

Despite huge effort has been devoted to the design of the initiators and reaction conditions, it remains challenging to synthesize high molecular weight polypeptides with conventional solution phase synthesis. In this work, surface-initiated vapor deposition polymerization (SI-VDP) was utilized to graft synthetic polypeptides poly (γ-benzyl L-glutamate) (PBLG) from polystyrene (PS) resin beads by ring-opening polymerization of N-carboxyanhydrides (NCAs). It was demonstrated for the first time that high molecular weight bulk PBLG (> 500,000) could be readily obtained within one hour via solvent-free synthetic method which paves the way for the synthesis of copolypeptides with high molecular weight.

Background Main treatment modality for spinal meningiomas (SM) is gross total resection (GTR). However, optimal timing of surgery, especially in cases with absent or mild neurological symptoms remains unclear. The aim of this study is to assess the impact of early-stage resection on neurological outcome, quality of life (QoL) and quality of care. The primary objective was a favorable neurological outcome (McCormick scale 1); Methods: We retrospectively analyzed data from patients operated on SM between 2011 and 2021. Patients with mild neurological symptoms preoperatively (McCormick scale 1 and 2) were compared to those with more severe neurological symptoms (McCormick scale 3-5). Disabilities and QoL were assessed according to validated questionnaires (SF36, ODI, NDI). Results: Age, spinal cord edema, thoracic localization, and spinal canal occupancy ratio were associated with more severe neurological symptoms (all p<.05). Patients presented with mild symptoms were associated with favorable neurological outcome (OR: 14.778 (95%CI 3.918-55.746, p<.001), which is associated with shorter hospitalization, better QoL and less disabilities (p<.05). Quality of care was comparable in both cohorts; Conclusions: Early surgical intervention of SM, before the development of severe neurological deficits, should be considered as it is associated with a favorable neurological outcome and quality of life.

Oceans cover about 70% of the Earth's surface, and about 95% remain unexplored for various reasons. Underwater wireless communication has been revolutionised with the help of Internet of Things networks. Recently, applications such as collecting marine data, marine monitoring, disaster prevention, historical exploration, oil and gas exploration, shipwreck exploration, maritime security, and monitoring of aquatic species and water pollution, and several applications have become possible. However, the problem of routing, information transfer, and resource preservation in the fluid underwater environment remains unsolved. In this research, we were looking for a solution to make routing more efficient, considering the various and practical criteria for the quality of service of the underwater IoT network. One of the outstanding features of this research is the possibility of dynamically weighing the parameters involved in routing and taking optimal and distributed decisions between network components. The proposed method has achieved acceptable results in terms of quality of service compared to recent methods.

Every subset S of a Cartesian spaces Rd, endowed with differen- tial structure C∞(S) generated by restrictions to S of functions in C∞(Rd), has a canonical partition M(S) by manifolds, which are or- bits of the family X(S) of all derivations of C∞(S) that generate local one-parameter groups of local diffeomorphisms of S. This partition satisfies the frontier condition, Whitney’s conditions A and B. If M(S) is locally finite, then it satisfies all definitions of stratification of S. This result extends to Hausdorff locally Euclidean differential spaces.

Modulation of nociception allows animals to prioritise their survival by adapting their behaviour in different contexts. In mammals, this is executed by neurons from the brain, and is referred to as the descending control of nociception. Whether insects have this control, or have the neural circuits underpinning it, has not been clarified. Here, we review evidence supporting descending control of nociception control in insects, and consider which neuronal sub-types and brain areas may be involved.

The Copenhagen interpretation of quantum mechanics and the notion of superposition of states are examined and found problematical.

The great Greek philosopher Aristotle (384–322 BCE) is almost unanimously acclaimed as the founder of zoology. There is a consensus that he was interested in attributes of animals, but whether or not he tried to develop a zoological taxonomy remains controversial. Fürst von Lieven and Humar compiled a data matrix and showed, through a parsimony analysis published in 2008, that these data produced a hierarchy that matched several taxa recognized by Aristotle. However, their analysis leaves some questions unanswered because random data can sometimes yield fairly resolved trees. In this study, we update the scores of many cells and add four new characters to the data matrix (147 taxa scored for 161 characters) and quote passages from Aristotle’s Historia animalium to justify these changes. We confirm the presence of a phylogenetic signal in these data through a test using skewness in length distribution of a million random trees, which shows that many of the characters discussed by Aristotle were systematically relevant. Our parsimony analyses on the updated matrix recover far more trees than reported by Fürst von Lieven and Humar, but their consensus includes many taxa that Aristotle recognized and apparently named for the first time, such as selachē (selachians) and dithyra (Bivalvia). This study suggests that even though taxonomy was clearly not Aristotle’s chief interest in Historia animalium, it was probably among his secondary interests. These results may pave the way for further taxonomic studies in Aristotle’s zoological writings in general. Despite being almost peripheral to Aristotle’s writings, his taxonomic contributions are clearly major achievements.

Introductions- Liveable housing environments face the menace of global climate change. In-frastructure (including buildings and houses) continuously experiences significant impacts ex-acerbated by natural variability in climate. The study addressed how climate change impacts the resilience of residential buildings, increased maintenance frequency, and the wellbeing and comfort of residents in UK residential buildings. Design/Methodology/Approach: This study used deductive reasoning and an empirical epis-temological methodology as a data-collecting basis to evaluate primary information obtained via a questionnaire. Regression analysis was ultimately employed to analyse the collected da-ta. Result/Discussions: The findings show a significant relationship between climate change and the wellbeing of the occupants of UK residential buildings. Also, the results show that social wellbeing is more important to the occupants than mental and physical wellbeing. It reveals that residential buildings in the UK suffer the cost of maintenance due to continuous reduc-tion in the building fabric's resilience to the impacts of climate change; for instance, a recent increase in rainfall/storms results in unprecedented flooding, which continues to damage the UK residential building fabrics.

As the first pilot ecological civilization zone in China, Fujian Province has an excellent ecological environment quality, and its ecological environment-related indices continue to be among the highest in the country. In order to investigate the causes of the excellent ecological quality in Fujian Province in the past 15 years, this paper selects MODIS images, land use data and provincial and municipal statistical yearbook data of Fujian province from 2005 to 2020 as data sources, evaluates the ecological system health of Fujian Province by remote-sensing ecological index (i.e. RSEI), constructs the land use intensity system of Fujian Province at the same time, and uses a coupled coordination model to analyze the coupling between RSEI and The coupled coordination model was used to analyze the coupling relationship between RSEI and land use intensity, and finally the spatial and temporal evolution of ecological health in Fujian Province from 2005 to 2020 was analyzed. The results show that the coupled coordination between land use intensity and ecosystem health in Fujian province showed a continuous increase between 2005 and 2020, especially in Ningde, where the increase was most significant, from 0.0993 to 0.963, this pattern of spatial distribution is lower in the south-eastern coastal region than in the north-western interior, higher in the south-western region than in the north-western region, and higher in the north-eastern region than in the south-eastern region. In terms of the type of role, the land use intensity of most cities in Fujian Province in 2005 played an obvious role in blocking the degree of ecosystem health, but as time changed, urban land use continued to be optimized and reached moderate or even high quality coordination with the quality of the ecological environment, but Xiamen City developed relatively slowly and its 2020 coupling degree value was 0.315, which was still in mild disorder. This study fills a gap in the research mechanism of the interaction between the degree of ecosystem health and land use intensity, and also provides a new perspective for the construction of ecological civilization and the assessment of the degree of ecosystem health in Fujian Province and the whole country.

This paper intends to examine whether a company’s policy of dividend would impact or influence the price fluctuation of respective common stock in the designated stock market particularly in Hong Kong. Hence, there are 354 companies in Hong Kong which are all listed company on the Stock Exchange of Hong Kong (HKEX), were chosen as sample data for analysis with their audited financial information ranged from 2001 to 2020. Two proxies, the yield and the ratio of pay-out of dividend were widely adopted for the measurement of the effect of dividend policy and the possible influence on the volatility of respective common stock price by employing two statistical models, which are the model of fixed and random effects to provide accurate regression coefficients. With the results from the model of fixed effects, the yield and the pay-out ratio of dividend have been found statistically associated to the price volatilization of respective common stock in Hong Kong. The statical results in this study also find the yield and the ratio of pay-out of dividend are apparently and negatively associated to the price volatilization of respective common stock in Hong Kong. The research outcomes will be a reference for further study on different variables may have effects or volatilize the price of common stock price particularly in Hong Kong capital market.

The imperfection of theoretical and methodological approaches to regulate the jump process transition when combining differentiated energy resources is a pressing issue. The goal of this paper is to develop a theory and a method to regulate the integration-balancing processes of combining diversified resources. The concept of combining integration and balancing models has been substantiated by methods of transforming multidimensional space and approximating generalized functions that represent jump-like processes. Theoretical and operational-regulatory models of economic sustainability have been developed, substantiating new concepts, patterns, properties, dependencies and indicators of the dynamics of the processes of combination; the optimality conditions for the number of approximations of generalized functions, interpreting the effects of control functions of combining resources, are determined. New methods for solving problems have been developed: the organization of the energy technology complex of facilities for enhanced resource diversification and the Center for Sustainability, improving the quality of managing dynamic processes in terms of combining and diversifying resources.

Purpose of this article is to introduce a modification of Phillips operators on the interval $\left[ \frac{1}{2},\infty \right) $ via Dunkl generalization. This type of modification enables a better error estimation on the interval $\left[ \frac{1}{2},\infty \right) $ rather than the classical Dunkl Phillips operators on $\left[ 0,\infty \right) $. We discuss the convergence results and obtain the degrees of approximations. Furthermore, we calculate the rate of convergence by means of modulus of continuity, Lipschitz type maximal functions, Peetre's $K$-functional and second order modulus of continuity.

Purpose of this article is to introduce a modification of Phillips operators on the interval $\left[ \frac{1}{2}% ,\infty \right) $ via Dunkl generalization. This type of modification enables a better error estimation on the interval $\left[ \frac{1}{2},\infty \right) $ rather than the classical Dunkl Phillips operators on $\left[ 0,\infty \right) $. We discuss the convergence results and obtain the degrees of approximations. Furthermore, we calculate the rate of convergence by means of modulus of continuity, Lipschitz type maximal functions, Peetre's $K$-functional and second order modulus of continuity.

In this paper, we study sums of finite products of Chebyshev polynomials of the first kind and Lucas polynomials and represent each of them in terms of Chebyshev polynomials of all kinds. Here the coefficients involve terminating hypergeometric functions ₂F₁ and these representations are obtained by explicit computations.

Genes and gene trees have been extensively used to study the evolutionary relationships among populations, species, families and higher systematic clades of organisms. This brought modern Biology into a sophisticated level of understanding about the evolutionary relationships and diversification patterns that happened along the entire history of organismal evolution in Earth. Genes however have not been placed in the center of questions when one aims to unravel the evolutionary history of genes themselves. Thus, we still ignore whether Insulin share a more recent common ancestor to Hexokinase or DNA polymerase. This brought modern Genetics into a very poor level of understanding about sister group relationships that happened along the entire evolutionary history of genes. Many conceptual challenges must be overcome to allow this broader comprehension about gene evolution. Here we aim to clear the intellectual path in order to provide a fertile research program that will help geneticists to understand the deep ancestry and sister group relationships among different gene families (or orthologs). We aim to propose methods to study gene formation starting from the establishment of the genetic code in pre-cellular organisms like the FUCA (First Universal Common Ancestor) until the formation of the highly complex genome of LUCA (Last UCA), that harbors hundreds of genes families working coordinated into a cellular organism. The deep understanding of ancestral relationships among orthologs will certainly inspire biotechnological and biomedical approaches and allow a deep understanding about how Darwinian molecular evolution operates inside cells and before the appearance of cellular organisms.

The biology of sexual orientations has intrigued people for generations. Many models have been providing insights to that topic, but there are still unanswered questions. In humans, sexual orientation has a learned component. Humans have to learn cues by which they identify the sex of their mates, and cues of the emotional messages that those mates broadcast. Many of those cues depend on arbitrary societal conventions. The cues are learned automatically and subconsciously during childhood, based on non-sexual experiences. When sexual orientation emerges at puberty, the youngsters cannot tell how and when they have acquired it. A model that deals with those phenomena is presented. A basic tenet of the model is that a sexual orientation is determined by the innate wirings of the brain. The model describes how the brain learns cues for identifying the sex of the mate, and cues for identifying emotional messages that the mate broadcasts. The learning mechanism is conditioning. The unconditioned stimulus is human voice. The unconditioned responses are the triggers of the physical and emotional manifestations of sexual activity. The model suggests that innate connections from auditory detectors of men’s and women’s voice onto brain centers that trigger sexual activities, such as the hypothalamus, determine the sexual orientation that emerges at puberty. Innate connections from those auditory centers to emotional centers, such as the amygdala, determine the learned emotional cues. It is also proposed that during evolution, the roles of the chemosensory system in identifying mates were taken over by the auditory system.

All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.

A simple line of reasoning, based on the most fundamental concepts of thermodynamics, yields some intriguing results for a better understanding of the processes occurring in the observable Universe. Gravitational mass must be continuously generated within an expanding thermodynamic system for this system to remain closed. The Second Law is a direct consequence of this production of mass. Simple expressions for the entropy and temperature of the Universe were obtained and the results agree well with observable values. Furthermore, it is demonstrated that the conservation laws within the Universe are independent of its energy density. Based on the solution for the quantum state of the Universe, it is conjectured that the Second Law is incomplete and must be complemented to a conservation law, which takes into account the growth of the amount of information within the Universe. Once the Second Law is complemented to a conservation law, the importance of mass generation within the Universe becomes well pronounced – not only gravitational effects play the role of an organising force, but also the amount of mass within the Universe defines both the amount of information within the Universe and the level of the Universe’s complexity.

One of the challenges of deploying Wireless Sensor Networks (WSN) at large scale is to operate for prolonged periods of time relying on the limited amounts of energy stored in its nodes. Generally, data communication is the main factor of draining energy. Consequently, reducing the amount of transmitted data by the nodes is of great interest. At the same time, reducing data to be transmitted should not decrease the quality of the deduced information. Solving this problematic is what we call in this article "Ensuring the Quality of Information Service (QoIS)". This document provides a state-of-the-art for the QoIS regarding WSNs. At first, we give a quick overview of the Internet of Things (IoT) paradigm and the WSN technologies in order to understand how data is gathered and used in these networks. Also, we introduce a novel concept: QoIS, in contrast with classic QoS. Then, it is expected a summary of criteria that asses the QoIS in WSNs plus some techniques to improve it. In this article, we will focus on data management techniques. These techniques can improve raw data, information and/or knowledge quality in energy-constrained WSNs. Finally, we give some conclusions and a glimpse about our future work.

Mathematics first is a logical system. But, the Mathematics Crisis showed that we cannot have a logical self-consistent mathematics system. Physics is a kind of applied science. It first need be valid to invent new production and understand new observation. In one theory of physics, the studied object is usually defined as an abstract concept. For example, the Sun is defined as a point particle in the Newtonian theory of gravity. In different theories of physics, the abstract concept for a same object is different. It determines that logical self-consistent is not needed for different theories of physics. Physics only can be developed from observation and experiment. But, in the past a century, physicists’ main attempt is to have a standard model, such as the Grand Unification or the Theory for Everything, from mathematics derivation. Therefore, the current attempt to develop new physics is questioned. In recent, the strong gravitational field was studied. It is found that the fundamental physical constants which are measured in the weak field shall be varied in a super strong field. For the two reasons, modern physics need be advanced greatly.

The underlying physical concept of computing out-of-time-ordered correlation (OTOC) is a significant new tool within the framework of quantum field theory, which now-a-days is treated as a measure of random fluctuations. In this paper, by following the canonical quantization technique we demonstrate a computational method to quantify the two different types of Cosmological auto-correlated OTO functions during the epoch when the non-equilibrium features dominates in Primordial Cosmology. In this formulation, two distinct dynamical time scales are involved to define the quantum mechanical operators arising from cosmological perturbation scenario. We have provided detailed explanation regarding the necessity of this new formalism to quantify any random events generated from quantum fluctuations in Primordial Cosmology. We have performed an elaborative computation for the two types of two-point and four-point auto-correlated OTO functions in terms of the cosmological perturbation field variables and its canonically conjugate momenta to quantify random auto-correlations in the non-equilibrium regime. For both the cases we found significantly distinguishable non-chaotic, but random behaviour in the OTO auto-correlations, which was not pointed before in this type of studies. Finally, we have also demonstrated the classical limiting behaviour of the mentioned two types of auto-correlated OTOC functions from the thermally weighted phase space averaged Poisson Brackets, which we found exactly matches with the large time limiting behaviour of the auto-correlations in the super-horizon regime of the cosmological scalar mode fluctuation.

Echoing the long-held JTB account of knowledge, according to which knowledge can be conceptually analyzed as justified true belief, Backes (2019) argues that our epistemic aim is to believe truly or accurately and emphasizes on that “a belief is justified iff it is highly probable”. We maintain that this line of reasoning is deficient, in terms of epistemic concerns and non-epistemic concerns of interest for both philosophy and legal theory. Specifically, in this short paper, we argue for the ineffectiveness of the aforementioned Backes’ view to meet the challenges posed by the ongoing rapid techno-scientific transformation of our contemporary societies and ways-of life.

In addition to the traditional QoS metrics of delay, delay jitter, and packet loss probability (PLP), Quality of Experience (QoE) is now widely accepted as a numerical proxy for actual user experience. The literature has reported many mathematical mappings between QoE and QoS. These QoS parameters are measured by the network providers using sampling. There are some papers studying sampling errors in QoS measurements; however there is no account of propagation of these sampling errors to QoE evaluation. In this paper, we used industrially acquired measurements of PLP and jitter to evaluate the sampling errors and correlation in measurements. Focussing on Video-on-demand (VoD) applications, we use subjective testing and regression to map QoE metrics onto PLP and jitter. The resulting mathematical functions of QoE and theory of error propagation was used to evaluate the propagated error in QoE, and this error was represented as confidence interval. Using the guidelines of UK government for sampling, our results indicate that confidence intervals around estimated QoE in a busy hour can be between MOS=1 to MOS=5 at targeted operating point of QoS parameters. These results are a new perspective on QoE evaluation, and are of great significance to all organisations that need to estimate the QoE VoD applications precisely.

The purpose of work is to quantify the changes of the organism functional reserves during the successive phases of the human health Space-Time Continuum (STC) on the basis of postulates of reliability complex systems theory. The study is devoted to the problem of age-related human involution, which is evaluated not from the causal, but from the kinetic point of view. The analysis of 10 most important basic life support systems of human body — cardiovascular (CVS), respiratory (RS), nervous (NS), digestive (DS), endocrine (ES), immune (IS), excretory (EXS), brain (BS), musculo-skeletal (MSS), hematopoietic (HS) was carried out. Based on this analysis two levels of ensuring the reliability of organism’s work were revealed: sequential and parallel. The system of logical equations for reduced sequential system is: Ys1 = CVS ∧ RS ∧ BS, where ∧ is the notation for the conjunctions of set elements. The system of logical equations for the reduced parallel system is: Ys2 = NS ∨ DS ∨ ES ∨ IS ∨ HS ∨ EXS ∨ MSS ,where ∨ is the disjunction of the scheme elements. Visualization of human STC changes the concept of the kinetics of age-related changes in the organism and the role of determinants of health as a stable factor accompanying a uniform, smooth transition from the most pronounced functions of the body to their gradual extinction. For human STC is formulated the following regularity kinetics of involutionary processes: after 30 years of age in the human body morphological changes regress in arithmetic progression, and the functions of organs in a geometric one. Assumption of health as a state redundancy of functions is suggested.

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain per-iodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tis-sue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL-cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotions of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as il-lustrated by the production of the antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the perio-dontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

Background: SARS-CoV-2 Omicron JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used RT-qPCR SGTF as the proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing for diagnosis of JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed Q229K, usually associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: The CDC should consider Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well-documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates diagnosed at Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia, between October 5, 2020, and November 5, 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD=6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25-1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38-2.19), LBW (aOR = 1.32, 95% CI: 1.06-1.66), and RDS (aOR = 1.57, 95% CI: 1.28-1.93) were significantly higher among neonates born to mothers with MDM. Types of DM were statistically significant with some neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusion: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. Early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.

Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating many physiological and pathological immune-mediated processes. Although initially described as a tumor-cytotoxic agent, over time, it has also been recognized as an essential pro-inflammatory cytokine implicated in the pathogenesis of different autoimmune diseases, such as multiple sclerosis (MS). Several studies have shown an increase in TNF expression both in acute and chronic active MS brain lesions, as well as its involvement in maintaining a chronic inflammatory intrathecal process known as “compartmentalized inflammation”, which contributes to disease progression and disability accumulation in MS, even more than acute inflammatory activity. Indeed, high TNF levels were observed in the serum and cerebrospinal fluid of subjects with MS and correlated to disease severity, promoting axonal damage and, consequently, neurodegeneration. In this review we discuss the current knowledge of TNF and its receptors involvement in MS progression, focusing on disability progression independent of relapse activity (PIRA), meant as the disability accumulation evident in relapsing MS patients not related to acute inflammatory events.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

Hyperplastic dental follicles (HDFs) represent odontogenic hamartomatous lesions originating from pericoronal tissues and are often associated with impacted or embedded teeth. These lesions may occasionally feature unique calcifying bodies, known as calcifying whorled nodules (CWN), characterized by stromal cells arranged in a whorled or spiral fashion. CWNs are typically observed in multiple calcifying hyperplastic dental follicles or regional odontodysplasia. In our study, we examined 40 cases of HDFs, including nine instances with characteristics of CWNs, which were infrequently accompanied by odontodysplasia. Histological examination was conducted on all 40 cases, with immunohistochemical analysis performed on 21 of them. Among the cases with CWN, nine affected a single embedded tooth, with one exception. CWNs exhibited diverse calcifications featuring sparse or entirely deposited psammoma bodies, and some displayed dentinoid formation. Immunohistochemically, stromal cells of HDFs were frequently positive for CD56 and nestin. In contrast, CWNs were negative for CD56 but positive for nestin and HES1, with a few DSP-positive calcified bodies. Our results revealed that hamartomatous calcifying HFDs can impact multiple and single-embedded teeth. CWNs composed of nestin and HES1-positive ectomesenchymal cells demonstrated the potential to differentiate into odontoblasts and contribute to dentin matrix formation under the influence of HES1. This study is the first report documenting odontoblastic differentiation in HDFs.

Phα1β a spider peptide, purified from the venom of Phoneutria nigriventer inhibits high voltage calcium channels and is antagonist of TRPA1 receptor two important pain transduction path-ways. In the last 15 years, we have showed, in preclinical tests with Phα1β native and recombi-nant in rodent models of pain the potential of Phα1β to become a new analgesic drug. Evaluation of new drug on human ERG channel is requirement of the regulatory agencies. For the hERG channel inhibition assay it was used the commercial kit FLIPR® Potassium Assay. It was tested the effect of Phα1β and as positive control dofetilide, a well characterized hERG block-er. Phα1β 56, 225, 450 and 900 pMol caused at a higher concentration a very weak inhibition of the hERG channel activity of about 13.47 % with channel inhibition at 50%, IC50 > 900 pMol. Dofetilide (0.0001 - 10 µM), a known hERG inhibitor, caused a well-known, concentra-tion-dependent inhibition of the hERG channel with a mean IC50 of 0.1642 µM (0.1189 – 0.2282 µM. For the cytotoxicity assay, Phα1β concentrations of 56, 225, 450 and 900 pMol incubated for 24 h with HEK293-hERG cells did not alter the viability of the HEK293-hERG cells. It is con-cluded that Phα1β even at high concentrations does not interfere with hERG channels.

Background. Waning of neutralizing and cell-mediated immune response after the primary vac-cine cycle (PVC) and the first booster dose (BD) is of concern, especially for PLWH with a CD4 count ≤200 cells/ mm3.Methods.Neutralizing antibodies (nAbs) titers by microneutralization assay against WD614G /Omicron BA.1 and IFNγ production by ELISA assay were measured in samples of PLWH at 4 time points [2 and 4 months post-PVC (T1 and T2), 2 weeks and 5 months after the BD (T3 and T4)]. Participants were stratified by CD4 count after PVC (LCD4, <200/mm3; ICD4, 201-500/mm3 and HCD4, >500/mm3). Mixed models were used to compare mean responses over T1-T4 across CD4 groups. Results. 314 PLWH on ART (LCD4=56; ICD4=120; HCD4=138) were enrolled. At T2, levels of nAbs were significantly lower in LCD4 vs ICD4/HCD4 (p=0.04). BD was crucial for increasing nAbs titres above 1:40 at T3 and up to T4 for WD614G. A positive T cell response after PVC was observed in all groups, regardless of CD4 (p=0.31). Conclusions. Waning of nAbs after PVC was more important in LCD4 group. BD managed to re-establish higher levels of nAbs against WD614G which were retained for 5 months. The level of T-cellular response was significantly higher in HCD4 and ICD4 compared to the LCD4 group although it remained above detectable levels over the entire study period regardless of CD4 count. Keywords: HIV-1 infection; SARS-CoV-2 infection;

: Ovarian cancer has a dismal prognosis. Standard treatment following surgery relies on platinum-based chemotherapy. However, sizeable percentages of patients are unresponsive. Identification of markers predicting response to chemotherapy might help select eligible patients while sparing unresponsive ones treatment-associated toxicity. Cancer/testis antigens (CTA) are expressed by healthy germ cells and malignant cells of diverse histological origin. This expression profile identifies them as attractive targets of cancer immunotherapies. We analyzed correlations between expression of MAGE-A10 and New York esophageal-1 cancer (NY-ESO-1) CTAs at protein level and effectiveness of platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). MAGE-A10 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded samples from 93 patients with advanced-stage HGSOC treated at our institutions between January 1996 and December 2013. Correlation between expression of these markers and response to platinum-based chemotherapy, evaluated according to RECIST 1.1 criteria, platinum sensitivity, measured as platinum free interval (PFI), progression free (PFS) and overall survival (OS) was explored. MAGE-A10 protein expression predicts unresponsiveness to platinum-based chemotherapy (p=0.005), poor platinum sensitivity (p<0.001), and poor PFS (p<0.001) and OS (p<0.001). Multiva-riate analysis identifies MAGE-A10 protein expression as independent predictor of poor platinum sensitivity (p=0.005) and shorter OS (p<0.001). Instead, no correlation was observed between NY-ESO-1 protein expression and response to platinum-based chemotherapy (p=0.832), platinum sensitivity (p= 0.168), PFS (p=0.126) and OS (p=0.335). MAGE-A10 protein expression reliably identifies advanced-stage HGSOC unresponsive to platinum-based chemotherapy. Targeted im-munotherapy could represent an important alternative therapeutic option in these cancers.

Tdp1 and Tdp2 are DNA repair enzymes that repair DNA damages caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reasons of resistance to such widely used drugs as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (-)-usnic acid. Both (+)- and (-)-enantiomers of compounds act equally effectively against Tdp1, and only (-)-enantiomers inhibited Tdp2. Surprisingly, the compounds protect HEK293FT wild type cells from the cytotoxic effect of etoposide but potentiate it against Tdp2 knockout cells. We assume that the sensitizing effect of the compounds in the absence of Tdp2 is associated with effective inhibition of Tdp1, which could take over the functions of Tdp2.

A patient in her early 20s presented with constant and progressive lower abdominal and back pain, mainly on the right side of the abdomen, purulent vaginal discharge and pyrexia. Radio-logical assessment revealed a possible tuboovarian abscess and incidental diagnosis of ipsilateral renal agenesis. The patient was treated for pelvic inflammatory disease (PID), however after antibiotic administration and since the symptoms were not resolving, an abdominal MRI was requested which revealed a uterus didelphys with two cervices, an obstructed haemivagina and evidence of haematocolpos. The diagnosis of OHVIRA syndrome was confirmed and the patient underwent an excision of the vaginal septum, drainage of the haematopyocolpos and laparoscopic drainage of the tuboovarian abscess. She achieved a good recovery.

Regulation (EU) No 305/2011 lays down harmonized conditions for marketing construction products in the European Union. One of its consequences has been the introduction of the product standard EN 50575 and standard EN 130501-6, concerning power, control, and communication cables permanently installed in buildings to prevent the risk of a fire and its consequences. EN 13501-6 provides the reaction to fire classifications for cables, the test methods to be performed, the requirements to meet a specific reaction to fire, and additional classifications for smoke production, flaming droplets, and acidity. EN 60754-2 is the technical standard used to assess acidity, and it defines three classes: a1, a2, and a3 (the less performant), based on pH and conductivity measurements. Due to the release of hydrogen chloride during the combustion, acidity is the weak point of PVC cables, which are not yet capable of achieving the a1 or a2 classes required in specific locations according to a fire risk assessment. EN 13501-6 does not include EN 60754-1. Both EN 60754-1 and EN 60754-2 are common standards for determining halogen gas content, acidity, and conductivity, respectively. They involve the same type of tube furnace but with different heating regimes, final temperatures, and detection methods. EN 60754-2 must be performed at temperatures between 935 – 965 °C. The paper demonstrates that, when EN 60754-2 is carried out with the thermal profile of EN 60754-1 or at 500 °C in isothermal conditions, the evolution of hydrogen chloride changes significantly if potent acid scavengers are utilized in the PVC compounds. The reason lies behind the kinetic of hydrogen chloride release during the combustion of PVC compounds: the higher the temperature or faster the heat release, the quicker hydrogen chloride evolution and the lower the probability for the acid scavenger to trap it. That further highlights the "fragility" of EN 60754-2 as a tool for assessing the risks associated with the release of hydrogen chloride in case of fire

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, South Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

The advent of immunotherapy has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), improving the prognosis of this disease and becoming a key part of the treatment, especially in the population without an oncogenic driver mutation. Two different groups of immune checkpoint inhibitors (ICIs) are used in lung cancer: Anti- Cytotoxic T-lymphocyte antigen-4 (Anti-CTLA 4) and Anti- T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti PD-L1). Here in, we review an uptodate on the use of immunotherapy for advanced NSCLC.

The human polyamines spermine and spermidine are essential for cell function, and their properties have been extensively studied. However, research results of experiments conducted without understanding the properties of polyamines have been evaluated and published by reviewers who appear to have little knowledge of the properties of polyamines. It is sad that some studies repeat what was done more than half a century ago before polyamines were characterized. First, I explain the basic properties of polyamines that researchers need to know. Then, the relationship between changes in polyamine levels in the body and age- and lifestyle-related diseases is discussed. In addition, the epigenetic mechanism of action of polyamines in relation to healthy longevity and, conversely, age- and lifestyle-related diseases and the progression of senescence are discussed. Spermine, which increases with a polyamine-rich diet, acts to suppress aberrant gene methylation and proinflammatory status associated with aging. Meanwhile, chronic inflammation associated with aging induces the enzyme activity of spermine oxidase, which breaks down spermine and produces acrolein, resulting in reduced spermine levels. Acrolein, a toxic aldehyde that increases with age- and lifestyle-related diseases, is thought to accelerate these diseases.

Tapping panel dryness (TPD) syndrome is a complex disease of Rubber tree (Hevea brasiliensis L.) which causes cessation of latex drainage upon tapping of rubber tree. Rubber tree virus (RTV1) was identified as a novel pathogen associated with rubber tree and a potential causal agent of TPD. RTV1 is a monopartite RNA virus that is linear, non-enveloped and has a single-stranded (ss) positive RNA genome of approximately 6081 nucleotides and is composed of two major open reading frames (ORFs), ORF1 (polyprotein), and ORF2 (movement protein. This study aimed to investigate the possibility of rubber genome encoded tree microRNAs (miRNAs) as novel therapeutic targets against RTV1 using in silico algorithms. Mature rubber tree miRNAs are retrieved from the miRBase database and are used for hybridization of RTV1 using five different five different computational algorithms including miRanda, RNA22, RNAhybrid and psRNATarget. A total of eleven common rubber tree miRNAs were identified based on consensus genomic positions. The consensus of four algorithms predicted the hybridization sites of hbr-miR396a and hbr-miR398 at common locus positions 6676, 1840 respectively. To validate the prediction, secondary structures of the consensual rubber tree miRNAs and free energy of duplex binding were calculated using the RNAfold and RNAcofold algorithms respectively. We created a plot between rubber tree miRNAs and RTV1 ORFs by using Circos algorithm. In this study, we predicted eleven consensual rubber tree miRNAs. Among these miRNAs, hbr-miR398 was identified as the most effectual miRNA that may target the ORF1 gene of the RTV1 genome. The predicted data will be important in the development of rubber trees resistant to RTV1.

Like 18F-FDG, 99mTc-1-thio-D-glucose (99mTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTc-TG. Twelve lym-phoma patients were injected with 729±102 MBq 99mTc-TG. Whole-body planar imaging was per-formed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTc-TG injections were well tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone mar-row, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTc-TG SPECT/CT re-vealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal le-sions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTc-TG. Potentially, 99mTc-TG SPECT can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

In the present study, we studied the effect of apolipoprotein A-1 (APOA1) on the spatial and molecular characteristics of bone marrow adipocytes, using well-characterized ApoA1 knockout mice. APOA1 is a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, and thus HDL; our recent work showed that deficiency of APOA1 increases bone marrow adiposity in mice. We found that ApoA1 deficient mice have greatly elevated adipocytes within their bone marrow compared to wild type counterparts. Morphologically, the increased adipocytes were similar to white adipocytes, and displayed proximal tibial-end localization. Marrow adipocytes from wild type mice were significantly fewer and did not display bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, Pgc1a, and the expression of leptin were greatly reduced in the ApoA1 knock-out in comparison to the wild-type mice. In the knock-out mice adiponectin was remarkably elevated. In keeping with the close ties of hematopoietic stem cells and marrow adipocytes, we found that the elevated adiposity in the ApoA1 knock out mice is associated with a significant reduction of the hematopoietic stem cells and common myeloid, but not common lymphoid, progenitors. Moreover, the “beiging”-related marker osteopontin and the angiogenic factor VEGF were also reduced in the ApoA1 knock-out mice, further supporting the notion that APOA1, and most probably HDL-C, regulate bone marrow microenvironment, favouring beige/brown adipocyte characteristics.

We study the μ-μ45-T phase diagram of the 2+1-dimensional Gross-Neveu model, where μ denotes the ordinary chemical potential, μ45 the chiral chemical potential and T the temperature. We use the mean-field approximation and two different lattice regularizations with naive chiral fermions. An inhomogeneous phase at finite lattice spacing is found for one of the two regularizations. Our results suggest that there is no inhomogeneous phase in the continuum limit. We show that a chiral chemical potential is equivalent to an isospin chemical potential. Thus, all results presented in this work can also be interpreted in the context of isospin imbalance.

The Grand Ethiopian Renaissance Dam (GERD), formerly known as the Millennium Dam, is currently under construction and has been filling at a fast rate without sufficient known analysis on possible impacts on the body of the structure. The filling of GERD not only has an impact on the Blue Nile Basin hydrology, water storages and flow but also pose massive risks in case of collapse. Rosaries Dam located in Sudan at only 116 km downstream of GERD, along with the 20 million Sudanese benefiting from that dam, would be seriously threatened in case of the collapse of GERD. In this study, through the analysis of Sentinal-1 satellite imagery we show concerning deformation patterns associated with different sections of the GERD’s Main Dam (structure RCC Dam type) and the Saddle Dam (Embankment Dam type). We processed 109 descending mode scenes from Sentinel-1 SAR imagery, from December 2016 to July 2021, using the Differential Synthetic Aperture Radar Interferometry technique to demonstrate the deformation trends of both - the GERD’s Main and Saddle Dams. The time-series generated from the analysis clearly indicates different displacement trends at various sections of the GERD as well as the Saddle Dam. Results of the multi temporal data analysis on and around the project area show inconsistent subsidence at the extremities of the GERD Main Dam, especially the west side of the dam where we recorded varying displacements in the range of 10 mm to 90 mm at the crest of the dam. We conducted the current analysis after masking the images with a coherence value of 0.9 and hence, the subsequent results are extremely reliable and accurate. Further decomposition of the subsiding rate has revealed higher vertical displacement over the west side of the GERD’s Main Dam as compared to the east side. The local geological structures consisting of weak zones under the GERD’s accompanying Saddle Dam adds further instability to its structure. We identified seven critical nodes on the Saddle Dam that match the tectonic faults lying underneath it, and which display a varying degree of vertical displacements. In fact, the nodes located next to each other displayed varying displacement trends: one or more nodes displayed subsidence since 2017 while the other node in the same section displayed uplift. The geological weak zones underneath and the weight of the Saddle Dam itself may somewhat explain this inconsistency and the non-uniform vertical displacements. For the most affected cells, we observed a total displacement value of ~90 mm during the whole study period (~20 mm/year) for the Main Dam while the value of the total displacement for the Saddle dam is ~380 mm during the same period (~85 mm/year). Analysis through CoastSat tool also suggested a non-uniformity in trends of surface water-edge at the two extremities of the Main Dam.

The aim of this study was to build a tool to analyze, using artificial intelligence, the sentiment perception of users who answered two questions from the CSQ – 8 questionnaires with raw Spanish free-text. Their responses are related to mindfulness, which is a novel technique used to control stress and anxiety caused by different factors in daily life. As such, we proposed an online course where this method was applied in order to improve the quality of life of health care professionals in COVID 19 pandemic times. We also carried out an evaluation of the satis-faction level of the participants involved, with a view to establishing strategies to improve fu-ture experiences. To automatically perform this task, we used Natural Language Processing (NLP) models such as swivel embedding, neural networks and transfer learning, so as to classify the inputs into the following 3 categories: negative, neutral and positive. Due to the lim-ited amount of data available - 86 registers for the first and 68 for the second - transfer learning techniques were required. The length of the text had no limit from the user’s standpoint, and our approach attained a maximum accuracy of 93.02 % and 90.53 % respectively based on ground truth labeled by 3 experts. Finally, we proposed a complementary analysis, using com-puter graphic text representation based on word frequency, to help researchers identify relevant information about the opinions with an objective approach to sentiment. The main conclusion drawn from this work is that the application of NLP techniques in small amounts of data using transfer learning is able to obtain enough accuracy in sentiment analysis and text classification stages

Immunotherapy has been considered for years as a viable and attractive treatment option for patients with cancer. Among immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionized the treatment of several subtypes of tumours. These approaches aimed at restoring an effective anti-tumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells, and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because in these diseases the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and will build a projection of how the field may evolve in the near future. In particular, we will analyze the current strategies being evaluated both preclinically and clinically with the aim to foster the use of immune-checkpoint inhibitors in non-Hodgkin lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.

Promoter choice is an essential consideration for transgene expression in gene therapy. The expression of multiple genes requires ribosomal entry or skip sites, or the use of multiple promoters. Promoters systems comprised of two separate, divergent promoters may significantly increase the size of genetic cassettes intended for use in gene therapy. However, an alternative approach is to use a single, compact bidirectional promoter. We identified strong and stable bidirectional activity of the RPBSA synthetic promoter comprised of a fragment of the human Rpl13a promoter, together with additional intron / exon structures. The Rpl13a-based promoter drove long-term bidirectional activity of fluorescent proteins. Similar results were obtained for the EF1-α and LMP2/TAP1 promoters. However, in a lentiviral vector, the divergent bidirectional systems failed to produce sufficient titres to translate into an expression system for dual chimeric antigen receptors (CAR) expression. Although bidirectional promoters show excellent applicability to drive short RNA in Sleeping Beauty transposon systems, their possible use in the lentiviral applications requiring longer and more complex RNA, such as dual CAR cassettes, is limited.

Neuroinflammation, defined as inflammatory reactions mediated by cytokines, chemokines, reactive oxygen species, and secondary messengers in the central nervous system (CNS) including the brain and spinal cord is the basis of many neurological disorders. Recently, erythropoietin (EPO) has been considered and studied as a modulator of neuroinflammation. On this article minireview of pathophysiology of neuroinflammation and the neuroprotective effects of EPO is discussed and a case of subacute huge subdural hematoma with double mydriasis operated urgently, treated with low daily dose (vs high dose once or twice a month in the literature) of EPO and recovered fully and discharged home with good consciousness is reported. In addition, the probable unfavorable outcome of erythropoietin administration in patients with neuroinflammation in COVID-19 is considered.

Either stereo reactants or stereo catalysis from achiral or chiral molecules are prerequisite to obtain pure enantiomeric lipid derivatives. We reviewed a few plausible organic syntheses of phospholipids under prebiotic conditions with a special attention to the starting materials as pro-chiral dihydroxyacetone and dihydroxyacetone phosphate (DHAP), which are the key molecules to break symmetry in phospholipids. The advantages of homochiral membranes compared to those of heterochiral membranes were analysed in term of specific recognition, optimal functions of enzymes, membrane fluidity and topological packing. All biological membranes contain enantiomeric lipids in modern bacteria, eukarya and archaea. The contemporary archaea, comprising of methanogens, halobacteria and thermoacidophiles are living under extreme conditions reminiscent of primitive environment and may indicate the origin of one ancient evolution path of lipid biosynthesis. The analysis of lipid metabolism reveals that all modern cells including archaea synthetize enantiomeric lipid precursors from prochiral DHAP. sn-glycerol-1-phosphate dehydrogenase (G1PDH), usually found in archaea, catalyses the formation of sn-glycerol-1-phosphate (G1P), while sn-glycerol-3-phosphate dehydrogenase (G3PDH) catalyses the formation of sn-glycerol-3-phosphate (G3P) in bacteria and eukarya. The selective enzymatic activity seems to be the main strategy that evolution retained to obtain enantiomeric pure lipids. The occurrence of two genes encoding for G1PDH and G3PDH, served to build up an evolution tree and the basis of our review focusing on the evolution of these two genes. Gene encoding for G3PDH in Eukarya may originate from G3PDH gene found in rare archaea indicating that archaea appeared earlier in the evolution tree than eukarya. Archaea and bacteria evolved probably separately, due to their distinct respective genes coding for G1PDH and G3PDH. The suggested hypothesis is that catalysis of homochiral G1P or G3P from DHAP are more efficient than those leading to racemic G1P and G3P, since there are no enzymes able to synthesize racemic G1P and G3P from DHAP. We propose that G1PDH or G3DPH, which are not “image mirror enzymes” but belonging to distinct family of proteins, emerged separately during evolution. They were probably selected for their efficient catalytic activities during evolution from large libraries of vesicles containing various biopolymers, including amino acids, carbohydrates, nucleic acids, lipids, and meteorite components to induce chemical imbalance.

Immune checkpoint inhibitors (ICIs) – anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events have been linked to these agents. However, tuberculosis (TB) reactivation during their use is increasingly reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 Immune histochemistry (IHC) strongly positive in 95% of tumor cells. The patient presented with high-grade fever and a history of productive cough for a 1-week duration. A few days later, she was diagnosed with pulmonary tuberculosis following the 6th cycle of Pembrolizumab, an anti-PD-1 monoclonal antibody. AFB smear and TB PCR from BAL were positive (rifampin resistance not detected), and she was accordingly started on Anti-TB medications. Immunotherapy was held. Of note, the patient had a history of sick contact with a patient with active TB infection ten years ago, but there was no documentation of latent TB or previous TB infection. Her HIV status is negative. Her sputum AFB smear continued to be positive after four weeks of anti-TB medications. Later, the patient was discharged after her sputum was cleared from AFB (negative x 2 sets). We assumed that our patient developed reactivation of pulmonary tuberculosis secondary to an immune checkpoint inhibitor (Pembrolizumab). She was not re-challenged with Pembrolizumab following TB diagnosis. To our knowledge, this is the first reported case from the Arab and the Middle East; it reinforces the previous observations of the association between ICIs administration and the development of MTB. Nevertheless, further studies in the clinical setting are necessary to establish the exact mechanism involved in this association. Oncologists' awareness & prompt recognition of this potential hazardous consequence are essential. Since there is no clear evidence whether LTBT prior PD-1/PD targeted immunotherapy is required, targeted LTBT before starting ICIs immunotherapy with TB chemoprophylaxis; yet to be explored, particularly in the regions where the MTB prevalence is high.

The premise regarding COVID-19 disease is that it is a spectrum which begins with infection with viral SARS-CoV-2 exposure via airborne or oral virus particles. The individual response to it depends on many factors including co-morbid conditions. An important aspect of SARS-CoV-2 virus infection is the cytokine storm that develops after the infection. The immuno-chemical chaos created in this cytokine storm is to the benefit of the virus. In this meta analysis the authors explore ways to let the cytokine storm die down by looking into the role of histamine. Histamine is a metabolic product of the essential aminoacid histidine. Histamine has 4 known receptors: H1, H2, H3 and H4. The immunoglobulines IgE and IgM are indicative for a COVID-19 infection. This immune response is related to inflammation. Inflammation, in turn, runs mainly via histamine after e.g. virus inoculation. The goal of the meta-study is to gather evidence to primarily block the H4 receptor (H4R) in gastrointestinal cells to diminish the cytokine overproduction in the $\approx$ 30\% of the patients suffering from gastrointestinal problems caused by SARS-CoV-2. Our concept is as follows. If we can strike a careful balance between hampering the gastrointestinal spreading of the virus and histamine antagonists to tackle the cytokine storm, then the natural immunity can later on come on line again and attack the virus without being led astray by cytokine chaos. We will concentrate on H4R but also look at H1R and H2R related effects. The proposed substances in our systemic approach can be balanced for an effective early treatment. The nature of our work is by its method and results theoretical. In that respect we also may note the structural chemistry indol skeleton resemblance among a number of different drugs.

Vitamin D and ω-3 fatty acids (ω-3) co-supplementation potentially improve type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation.This cohort study preliminary to a randomized control trial (RCT) is aimed to evaluate, in a series of T1D children assuming Mediterranean diet and taking cholecalciferol 1000U/day fromT1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS).Therefore, 22 new onsets of 2017 received ω-3 [eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60mg/kg/day], and were compared retrospectively vs. 37 previous onsets without ω-3 supplementation. HbA1c%, daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/dayx4 + HbA1c%) as surrogate of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As outcome, decreased insulin demand (p<0.01), particularly pre-meal boluses (p<0.01), and IDAA1c (p<0.05), were found in the ω-3 group while HbA1c% were not different in the two groups. Diet analysis, at T12 vs. T0, showed that the intake of arachidonic acid (AA) was decreased (p<0.01) in the ω-3 supplemented group while other nutrients were unchanged; at T0, the AA intake was inversely correlated with HbA1c% (p<0.05; r;.0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation and AA reduction in Mediterranean diet display benefits for T1D children and deserve further investigation.

The XChem facility at Diamond Light Source offers fragment screening by X-ray crystallography as a general access user program. The main advantage of X-ray crystallography as a primary fragment screen is that it yields directly the location and pose of the fragment hits, whether within pockets of interest or merely on surface sites: this is the key information for structure-based design and for enabling synthesis of follow-up molecules. Extensive streamlining of the screening experiment at XChem has engendered a very active user programme that is generating large amounts of data: in 2017, 36 academic and industry groups generated 35,000 datasets of uniquely soaked crystals. It has also generated a large number of learnings concerning the main remaining bottleneck, namely obtaining a suitable crystal system that will support a successful fragment screen. Here we discuss the practicalities of generating screen-ready crystals that have useful electron density maps, and how to ensure they will be successfully reproduced and usable at a facility outside the home lab.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study mRNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. Less progress has been made in the study of the differential stability of mature RNAs because the different methods have often yielded inconsistent results so that an mRNA considered to be stable can be classified as unstable by another method. Recent advances in the systematic comparison of different method variants in yeast have permitted the identification of the least invasive methodologies that reflect half-lives the most faithfully, which is expected to open the way for a consistent quantitative analysis of the determinants of mRNA stability.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.

Although evolutionary theory has yet to furnish a comprehensive rationale for the underlying mechanism of natural selection, it is pertinent to note that the phenomenon transcends the confines of biological systems, exhibiting analogous patterns in physical systems as well. Specifically, isolated and closed systems tend to evolve towards states of progressively increasing entropy. In scenarios where multiple paths for entropy increase are accessible, such systems tend to favor combinations of paths that exhibit the most rapid entropy increase rates. Among the various processes in nature, life activities constitute a salient means of achieving entropy increase. Genetic variation within organisms generates individuals that vary in their rates of entropy increase. As these organisms interact, compete and combine, they form diverse combinations of entropy-increasing pathways. Nature, in turn, selects among these combinations, favoring those that culminate in the fastest entropy increase, thereby propelling the evolution of life. Essentially, the evolution of life is an ongoing exploration of diverse combinations of pathways that maximize entropy increase across various energy pools. Amidst continuous genetic variation and the selective pressure imposed by nature for maximum entropy production rates, information accumulates, leading to a corresponding acceleration in the rate of entropy increase. This natural selection, which favors maximizing the entropy at the fastest possible rate, serves as the ultimate driving force for the origin and evolution of life.

In recent years, the economics of emotions (EoE) field, which aims to create models of the human mind, has grown quickly. EoE models work well with simulation theory (ST), which is one of the main theories of mind. EoE models show how people's behavior and emotions change based on their knowledge and perception of others. It is hoped that by developing this model, it will be possible to quantitatively analyze not only the mental states of real others, but also the subtleties of the minds of characters in novels in the future. Until now, the decision-making or the factual-reasoning mechanisms have been a black box in ST. This study analyzes how EoE models add to the understanding of ST.

System-of-systems (SoS) evolution is a complex and unpredictable process. Although various principles to facilitate collaborative SoS evolution have been proposed, there is a lack of experimental data validating their effectiveness. To address these issues, we present an Agent-Based Model (ABM) for SoS evolution in the Internet of Vehicles (IoV) , serving as a quantitative analysis tool for SoS research. By integrating multiple complex and rational behaviors of individuals, we aim to simulate real-world scenarios as accurately as possible. To simulate the SoS evolution process, our model employs multiple agents with autonomous interactions and incorporates external environmental variables. Furthermore, we propose three evaluation metrics: evolutionary time, degree of variation, and evolutionary cost, to assess the performance of SoS evolution. Our study demonstrates that enhanced information transparency significantly improves the evolutionary performance of distributed SoS. Conversely, the adoption of uniform standards only brings limited performance enhancement to distributed SoSs. Although our proposed model has limitations, it stands out from other approaches that utilize Agent-Based Modeling to analyze SoS theories. Our model focuses on realistic problem contexts and simulates realistic interaction behaviors. This study enhances the comprehension of SoS evolution processes and provides valuable insights for the formulation of effective evolutionary strategies.

Abstract Objective Variations of sex characteristics (VSC) are atypical genetic, hormonal, gonadal and anatomical sex traits that require holistic medical management. The Chicago Consensus statement 2006 introduced the requirement that multidisciplinary teams organise the transition of care from pediatric to adult services. Yet, the evidence that the transitional care is in place is scarce. The aim of this paper is to examine the implementation of transition of care for people with VSC. Method Seven focus groups were conducted with health care professionals and peer support groups in care teams in Central, Northern and Western Europe. The data from the focus groups were examined using reflexive thematic analysis. Results The participants in the study stated that the transition of care has been implemented in the last two decades. The quality of care depends on available resources and variation of sex characteristics. However, there are significant hurdles to adequate transition of care as there is lack of time and resources. Lack of adult care providers and psychosocial support leaves young adults and adults with VSC navigating the health care system often alone. Conclusion The outcome of the study shows that the transition of care is organized through the department of pediatric endocrinology. The quality of care varies due to resources and variation. Lack of adult specialists and psychosocial support represent the biggest obstacle for young adults and adults to navigate the healthcare system and for the improvement in provision of healthcare to adults, especially psychosocial support.

Morphological study of lakes defines the sensitivity of their watershed. Moreover, it plays important role in safeguarding the lake’s ecosystem services through proper planning and utilization of the lakes’ resources. In the last few decades, the morphology of lakes in Ethiopian and Kenyan Rift (EKR) valley are experiencing contradicting morphological changes. Being in the same system, some are shrinking and others are expanding beyond their natural boundaries. The objective of this review is to shed light on the trends in spatio-temporal water level fluctuation and their contributing factors for lakes to the academia and decision makers. Peer reviewed article journals, conference proceedings, thesis, and book chapters collected from online sources and supplied by authors on request formed a database of 346 documents where 226 are critically assessed. The review indicated that lakes in Ethiopian rift are shrinking and expanding, while Kenyan lakes are expanding. The en-dorheic lakes suffered the most fluctuations due to anthropogenic factors at the expense of loss of forest and woodlands in their watershed. While the lakes’ water quality related to the morphological changes are given less attention, the predicted 12 m drop of Lake Turkana due to projects in the Omo catchment did not materialize.

In 1911, A. Einstein suggested that gravity affects at the electromagnetic radiation originating from the distant sources, namely, it shifts the spectral lines in the red side of the spectrum and derived the gravitational redshift formula. A modern science claims that Einstein’s formula is mathematically immaculate. We show that this is not true: in fact, this formula is approximate. Using the law of conservation of mechanical energy, we derived two exact formulas оf the gravitational redshift.

Study Objectives: To (1) investigate the prevalence of sleep disorder symptoms in caregivers of children with autism spectrum disorder (ASD) and (2) the relationships between caregiver sleep problems and their health-related quality of life and family quality of life. Methods: Descriptive cross-sectional study of caregivers (N=62) of children ages 6 to 11 years old diagnosed with ASD receiving care at a regional autism research and resource center. Measurements and Results: Participants completed the Sleep Habits Questionnaire (SHQ), the Medical Outcomes Study (MOS) SF-12, and the Beach Center Family Quality of Life Scale (FQOL). Caregivers with longer sleep duration reported better mental health and better family quality of life. Caregivers who reported insomnia symptoms, non-restorative sleep, and insufficient sleep were more likely to report poorer mental health than caregivers who did not report these sleep disorder symptoms. Caregivers with obstructive sleep apnea and restless legs syndrome experienced worse physical quality of life. Conclusions: The physical and mental health of the primary caregiver is essential to the support of the child with ASD and to the functioning of the family. The study findings point to the importance of future research and interventions to enhance sleep health in order to improve quality of life for caregivers of children with ASD.

In the cone of positive quadratic forms C^{8 x 8}, it is shown that there exists in the neighbourhood of the quadratic form Q_{F_{22}} a large cluster of non-equivalent \Sigma_0-subcones of positive volume which are as well minimal as maximal.

On the analyzed section of 2.4 km of the national road No. 50 of the Młodzieszyn bypass, it was carried out by a consortium of OAT and SAT companies in the period April-September 2019, under constant traffic in the field of repairing the concrete pavement by replacing slabs, levelling them and sealing expansion joints, roughening and roadside reinforcements.

In the context of market relations in agriculture in the Kyzylorda region, in order to meet the needs of animal husbandry in complete feed, it is necessary to create a solid forage base. The successful solution to the tasks of increasing the number of livestock and increasing the productivity of animal husbandry in the ecological conditions of the Aral Sea region largely depends on the timely procurement of feed and the transfer of feed production to an industrial basis. It is possible to increase the production of high-quality feeds through the introduction of high-yielding varieties, the use of new resource-saving cultivation and harvesting technologies, the optimal organization of cultivation production processes, and increasing the efficiency of the use of technical means. Of all the harvested types of feeds, alfalfa has the best effect on increasing milks yield and meat gains. The green mass of alfalfa is well-eaten by all farm animals. For example, when feeding cattle, its utilization rate is 92.6%. In terms of protein richness, alfalfa hay surpasses many other feeds, so 100 kg of alfalfa hay contains 11.6 kg of digestible protein, 1.77 kg of calcium, 0.22 kg of phosphorus, and 4.5 g of carotene. In addition, in the conditions of rice crop rotation, according to its biological characteristics, alfalfa (Medicago sativa L.) is considered indispensable in agrotechnical and reclamation relations, especially in saline soils. The economic value of alfalfa lies in its wide ecological plasticity, the ability to grow back quickly after mowing, and high productivity.

While the field of personality neuroscience has extensively focused on humans and, in a few cases, primates and rodents, a wide range of research on fish personality has emerged in the last decades. This research is focused mainly on the ecological and evolutionary causes of individual differences, but also aimed less extensively at proximal mechanisms (e.g., neurochemistry or genetics). We argue that, if consistent and intentional work is made to solve some of the meta-theoretical issues of personality research both on fish and mammals, fish personality research can lead to important advances in personality neuroscience as a whole. The five dimensions of personality in fish (shyness-boldness, exploration-avoidance, activity, aggressiveness, and sociability) need to be translated into models that explicitly recognize the impacts of personality in psychopathology, synergizing research on fish as model organisms in experimental psychopathology, personality neuroscience, and ecological-ethological approaches to the evolutionary underpinnings of personality to produce a powerful framework to understand individual differences.

The emergence of Life has been a subject of intensive research for decades. Different approaches and different environmental “cradles” have been studied, from space to the deep-sea. Since the recent discovery of a natural electrical current through the deep-sea hydrothermal vent, a new energy source is considered for the transition from inorganic to organic. This energy source is used by modern microorganisms using a new trophic type, called electrotrophy. In this review, we draw the parallel between this metabolism and a new theory for the emergence of Life based on this electrical electron flow. Each step of the creation of Life is revised in the new light of this prebiotic electrochemical context, going from the evaluation of similar electrical current during the Hadean, the CO electroreduction into a prebiotic primordial soup, the production of proto-membranes, the energetic system inspired of the nitrate reduction, the proton gradient, and the transition to a planktonic proto-cell. Finally, this theory is compared to the two other theories in hydrothermal context, to assess its relevance to overcome the limitations of each one. Many critical factors that were limiting each theory can be overcome with the effect of the electrochemical reactions and the environmental changes produced.

The Sun is a frame at relative rest in which sunlight travels at the emitted speed c. Earth travels at the revolving speed v in this frame. The reflection of light as a mechanical phenomenon applies to the modified Michelson interferometer employed by Miller in his experiments with light from the Sun. Unlike the Tomaschek experiments, which use light from stars that may travel in the Universe at velocities different from that of the Sun, the fringe shifts in the Miller experiments are predictable. Based on Michelson's derivation, Miller expected in his experiments at Mount Wilson a 1.12 fringe shift and observed a fringe shift of 0.08 in 1921 and 0.088 in 1925. The reflection of light as a mechanical phenomenon predicts zero fringe shift for Miller's experiment agreeing only with his observations at the Cleveland laboratory in 1924.

Law of conservation of energy is the most well-established law of modern physics. But, inflationary cosmological model which assumes the universe to be created from a point of singularity has not been able to identify the source of energy for creation of this universe. As per uncertainty principle, a quantum vacuum fluctuation can at most create energy of ~10^-8 kg in a Planck time of ~5.4 ×10^-44 s whereas total positive energy due to matter/vacuum existing in the universe is more than ~10⁵⁴ kg. To solve this problem, we have recently published a new cosmological model (Biswaranjan Dikshit, Canadian Journal of Physics, 100, 218-225, [2022]) in which we have mathematically proved that the total energy of the universe can be zero right from the beginning of the universe to till date due to negative gravitational potential energy and thus law of conservation of energy can be satisfied during creation of the universe from nothing. In this article, starting from a simple argument, we explain why net energy of the universe can be zero only in our model, not in standard cosmological model. An interesting fact pointed out in this paper is that the factor ~10⁶² by which radius of universe has increased from its starting value of ~10^-36 m to present value of ~10²⁶ m is same as the factor by which positive energy has increased from Planck energy ~10^-8 kg to present value ~10⁵⁴ kg. This is in agreement with our new model that predicts the positive energy of universe to be proportional to the radius of universe. We also bring out to the notice that zero energy universe is possible only if smallest possible length in nature is, l_min=l_p(π/2)^1/2 = 2.0×10^-35 m. Minimum possible length is important in theory of quantum gravity and string theory.

This paper presents the results of an experimental study of the patterns of steel and lead shot transformation under the impact of environmental factors (two types of shot exposed alone and in combination with each other). The analyzed environmental factors include atmospheric precipitation of various acidity and soil solutions with a higher content of organic acids. This research demonstrated that steel shot is characterized by a high transformation rate that is an order of magnitude higher on average than the transformation rate of lead under the same conditions. The prevalence of the suspended iron form (excluding the interaction with organic acids) presents risks for such environmental components as soils and sediments and may be hazardous to the ambient air and natural waters in case of wind erosion and surface runoff from the catchment area. Furthermore, the joint presence of steel and lead shot mutually accelerates the corrosion of both metals, thus increasing the environmental risks.

This work deals with aerofoil aerodynamic features optimization, not only to improve flight features, but also to improve economy, ecology and safety of parameters of flight technique. In cruise mission, occupying the most flight time, the most important parameter is aerodynamic drag, which directly influences the aeroplane operational economy of transportation. Drag reduction is adequately reflected in the fuel consumption reduction. Consumption reduction is also adequately reflected in the flight ecology. In take-off and landing mission, the safety is priority and directly influences the aerofoil geometry. For cruise mission the new modified evolutionary algorithms (EA) are used to parameters incoming to Bezier-PARSEC 3434 parametrization. Such aerofoil is processed and evaluated by the Xfoil program. The change of model parameters results to optimal aerofoil shape. The DCAG (Direct Control Aerofoil Geometry) is unique developed mechanical device, makes possible the change of curvature of aerofoil, and also aerofoil geometry. DCAG is based on the rotary principle, which makes it possible to define the curvature of aerofoil for every roll as well as defining the geometry in the variable parts of aerofoil. For take-off and landing mission the best combination of slots and flaps is choosed. To improve of laminarity and reduce turbulent flow the DCAG is used. The work results to optimization, which is 50 times faster in comparison to ordinary optimization, with minimum of input parameters (flight speed, chord length, range of angles of attack and fitness function). The optimized aerofoil can achieve savings in fuel consumption up to 44% in comparison with unoptimized aerofoil, the aerodynamic drag reduction up to 44%. The output was checked by ANSYS Fluent simulation.

AbstractThis work deals with aerofoil aerodynamic features optimization, not only to improve flight features, but also to improve economy, ecology and safety of parameters of flight technique.In cruise mission, occupying the most flight time, the most important parameter is aerodynamic drag, which directly influences the aeroplane operational economy of transportation. Drag reduction is adequately reflected in the fuel consumption reduction. Consumption reduction is also adequately reflected in the flight ecology. In take-off and landing mission, the safety is priority and directly influences the aerofoil geometry.For cruise mission the new modified evolutionary algorithms (EA) are used to parameters incoming to Bezier-PARSEC 3434 parametrization. Such aerofoil is processed and evaluated by the Xfoil program. The change of model parameters results to optimal aerofoil shape.The DCAG (Direct Control Aerofoil Geometry) is unique developed mechanical device, makes possible the change of curvature of aerofoil, and also aerofoil geometry. DCAG is based on the rotary principle, which makes it possible to define the curvature of aerofoil for every roll as well as defining the geometry in the variable parts of aerofoil.For take-off and landing mission the best combination of slots and flaps is choosed. To improve of laminarity and reduce turbulent flow the DCAG is used.The work results to optimization, which is 50 times faster in comparison to ordinary optimization, with minimum of input parameters (flight speed, chord length, range of angles of attack and fitness function).The optimized aerofoil can achieve savings in fuel consumption up to 44% in comparison with unoptimized aerofoil, the aerodynamic drag reduction up to 44%.The output was checked by ANSYS Fluent simulation.

The police occupy a very important position in the entire criminal justice system in Nigeria. The nature of police relationship with the people and the manner in which the public were handled at the station and on the street daily within the community affects the way the people perceive them and the level of cooperation they get from the people in curbing crime in the society. The study took place in Zaria, Kaduna state, Northern Nigeria .The study population was the police in Zaria. Three police stations (Zaria City, Sabon Gari and Samaru police stations) were purposively selected reflecting the socio-cultural and demographic backgrounds of Zaria residence and population. The Divisional Police officers and police officers in-charge of crime were interviewed. The police crime and incidence records were examined while the general conduct and social atmosphere of the police and police stations were observed. Using in- depth interview, observational method and police records, it was discovered that the socio economic status of suspects affected how they were treated by the police in the police stations studied. Also the environment a suspect lives affected how they were treated too by the police. It was recommended that the police make the rule of law their guide in the handling of suspects in the police stations irrespective of socio-demographic variable or area of habitation of the suspects. Police brutality and violations of citizen’s rights should be checked by senior police officers while community-policing style should be implemented across communities in Nigeria.

This paper aims to investigate the airflow that can transport emission sources of PM2.5 from neighboring countries to contribute to air pollution in northern Thailand. We applied the coupled atmospheric and air pollution model which is based on the Weather Research and Forecasting Model (WRF) and a Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT). The model output was compared to the ground-based measurement from the Pollution Control Department (PCD) to examine model performance. As a result of model evaluation, the meteorological variables fairly agreed well compared to observation with Index of Agreement (IOA) in ranges of 0.57 to 0.79 for temperature and 0.32 to 0.54 for wind speed, while the fractional bias of temperature and wind speed were 1.3 to 2.5 °C and 1.2 to 2.1 m/s. Burma was a country that contributed much of hotpot locations by 37% of the entire hotspot locations of Southeast Asia in March. The influence of the Asian Monsoon can bring pollutants from neighboring countries such as Burma and Laos toward northern Thailand in March that likely contribute to high concentrations of PM2.5 in northern Thailand.

We address the need for a model by considering two competing theories regarding the origin of life: (i) the Metabolism First theory and (ii) the RNA World theory. We discuss two inter-related points. (I) Models are valuable tools in understanding both the processes and intricacies of the origin of life issues. (II) Insights from models also help us to evaluate the core objection to origin of life theories called “the inefficiency objection” commonly raised by proponents of both the Metabolism First theory and the RNA World theory against each other. We use Simpson’s paradox as a tool for challenging this objection. We will use models in various senses ranging from taking them as representations of reality to treating them as theories/accounts that provide heuristics for probing reality. In this paper, we will frequently use models and theories interchangeably. Additionally, we investigate Conway’s Game of Life and contrast it with our Simpson’s Paradox (SP)-based approach to emergence of life issues. Finally, we discuss some of the consequences of our view. A scientific model is testable in three senses: (i) a logical sense, (ii) a nomological sense, and (iii) a current technological sense. The SP-based model is testable in the logical sense. It is also testable nomologically. However, it is not currently feasible to test it.

There are many pollution and environment problem in the human ecosystem. There are different methods are used to removal of sulfur from sour gases for example Basic Claus process and Modified Claus process . There are different chemical software are used for simulation and optimization of Claus process for example Aspen Plus and Chemcad ECT. The Gibbs free energy method is introduced and model of Claus process. There are new parameter are introduced in reaction furnace to reduce the error from 33% to 7 %. The waste heat boiler is installed at the reaction furnace in which high pressure stream is produced and study the decomposition the hydrogen sulphide. The new rate of reaction is introduced of the enhancement of H2 production in chemical process. The simulation of reaction furnace in Aspen plus software is the maximum utilization of process. Due to suitable operating condition of reaction furnace is caused the maximum destruction of ammonia gas in the reactor. When we are increasing the oxygen concentration and temperature of feed is causing decreasing the ammonia production in reaction furnace. It is below than acceptance value of ammonia is 150 ppm in the reaction furnace. The presence of oxygen components, Sulfur oxide, hydroxide components are effect on decreasing the amount of ammonia in furnace and temperature is about at 1350⁰C. It is noted that when the production of sulfur recovery is decrease in Claus process and the production of carbon monoxide is increase in the thermal section at the existence. Now we are work on parametric studies of furnace that could be causes the production of ammonia destruction and CO emission in the Claus process. Due to optimize the reaction furnace parameter are help to get large of sulfur production, ammonia gas destruction, increased the catalyst life and decreased of dangerous gases.

Preparing high school students for engineering disciplines is crucial for sustainable scientific and technological developments in the USA. This paper discusses a pre-college program, which not only exposes students to various engineering disciplines but also enables them to consider engineering as the profession. The four-week long “Engineering Innovation (EI)” course is offered every year to high school students by the center of outreach, Johns Hopkins University. EI program is designed to develop problem-solving skills through extensive hands-on engineering experiments. A team consisting of an instructor, generally a PhD in Engineering, and a teaching fellow, generally a high school science teacher, closely work with students to pedagogically inculcate basics of core engineering disciplines such as civil, mechanical, electrical, materials, and chemical engineering. EI values independent problem-solving skills and simultaneously promote the team spirit among students. A number of crucial engineering aspects such as professional ethics, communications, technical writing, and understanding of common engineering principles are inculcated among high school students via well-designed individual and group activities. This paper discusses the model of EI program and its impact on students learning and their preparation for the engineering career.

An idea expressed in the paper [Entropy 2017, 19, 345] about the deductive formulation of a physical theory resting on explicitly- and universally-introduced basic concepts is developed. An entropic measure of time with a number of properties leading to an analog of the Galilei–Einstein relativity principle is considered. Using the introduced measure and a simple model, a kinematic law relating the size, time, and number of particles of a system is obtained. Corollaries of this law are examined. In particular, accelerated increase of the system size and, if the system size remains unchanged, decrease of the number of particles are found. An interesting corollary is the emergence of repulsive and attractive forces inversely proportional to the square of the system size for relatively dense systems and constant for sufficiently rarefied systems.