Rapidly changing dynamics of globalization and increasing market competition are causing the companies all around the world confronting several new challenges and opportunities. To be competitive and successful apart from relative importance of physical resources, companies must adapt modern strategies and policies regarding market flexibility and development. The purpose of this study is to empirically investigate the relationship between intellectual capital and firm value. Furthermore, the moderating role of managerial ownership has been evaluated with the help of regression analysis. The sample included the panel data taken from non-financial firms listed on Pakistan stock exchange (PSX) covering the period 2010-2015. A sample of 79 firms out of 384 firms have been selected with the help of systematic sampling technique. VAIC (Value Added Intellectual Coefficient) model has been used for the calculation of intellectual capital. Tobin's Q has been taken as a measure of firm value. Managerial ownership has been tested as moderator. Based on data analysis, it is concluded that the relationship between intellectual capital and firm value is positively significant. It is also concluded that managerial ownership moderates the relationship between intellectual capital and firm value negatively.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

An active power dispatch method for a microgrid (MG) with multi-type loads, renewable energy sources (RESs) and distributed energy storage devices (DESDs) is the focus of this paper. The MG operates in a grid-connected model, and distributed power sources contribute to the service for load demands. The outputs of multiple DESDs are controlled to optimize the active power dispatch. Our goal with optimization is to reduce the economic cost under time-of-use (TOU) price, and to adjust the excessively high or low load rate of distributed transformers (DTs) caused by the peak-valley demand and load uncertainties. To simulate a practical environment, the stochastic characteristics of multi-type loads are formulated. The transition matrix of system state is provided. Then, a finite-horizon Markov decision process (FHMDP) model is established to describe the dispatch optimization problem. A learning-based technique is adopted to search the optimal joint control policy of multiple DESDs. Finally, simulation experiments are performed to validate the effectiveness of the proposed method, and the fuzzification analysis of the method is presented.

Background and objectives: The correlation of cardiac troponin I with early in-hospital outcomes in acute myocardial infarction is not well established. This study aims to assess the role of troponin I in predicting in-hospital outcomes and early left ventricular systolic dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods: In a prospective study, 116 patients (74males and 42 females), with STEMI who had been admitted to the Coronary CareUnit from March 2015 to September 2015 were enrolled. Patients were divided according to the level of troponin I on admission into 3 groups (low, medium and high elevation). Results: The mean age (+ SD) of the patients was 60+11.4 years. The troponin level of 66.2% of males was high compared with 52.4% of females (p=0.002). The incidence of acute pulmonary edema (21.1%), cardiogenic shock (7%) and early left ventricular systolic dysfunction (49.3%) was significantly higher among patients with high troponin level compared with (0%, 0% and 16%, respectively) among patients with low troponin level. All deaths and cardiac arrest were of high troponin level. Conclusions: High admission troponin I in STEMI permits early identification of patients at increased risk of major cardiac complications and death.

A literature review was conducted to summarize the frequency of the D-allele of the angiotensin-converting enzyme-1 in all countries with available data. Using an ecological study design limited to high income countries, we found that the country-level frequency of the D-allele was associated with increased COVID-19 incidence and mortality.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

Fourteen (14) rack-mounted polycrystalline modules installed on the concrete roof of the solar energy applications laboratory at the Kwame Nkrumah University of Science and Technology (KNUST) in Ghana, a hot humid environment were assessed after 19 years of continuous outdoor expodure. The physical state of the modules was documented using a visual inspection checklist. They were further assessed by current-voltage (I-V) characterization and thermal imaging. The modules were found to be in good physical state, except some bubbles on front side and minor discolouration/corrosion at edge of the cells. Compared with reference values, the performance decline of the modules observed over the exposure period was: nominal power (P_nom), 21% to 35%; short circuit current (I_sc), 5.8% to 11.7%; open circuit voltage (V_oc) 3.6% to 5.6% and 11.9% to 25.7% for fill factor (FF). It is hoped that this study will provide some helpful information to project developers, manufacturers and the research community on the long-term performance of PV modules in Ghana.

The seeds of red clover are heteromorphic and two color morphs can be visually recognized, light purple and yellow, resulting from heterozygosity and recessive homozygosity at two loci. Here, we report the responses of seed imbibition, seed germination, and early seedling growth of the two morphs to distilled water, sodium chloride, and complete nutrient solution. The sensitivity of red clover seeds to treatments increased with the stage of development in what seems to be a cumulative process. No differences were found in seed imbibition between morphs or between treatments. In seedling growth, on the contrary, treatments were always effective, but differences between morphs were only observed in seeds that were treated with nutrient solution, whereas in the intermediate stage of seed germination, the effects by treatments were observed together with the appearance of differences between morphs in distilled water and in the treatment by sodium chloride solution. Simultaneously, the superior performance of the yellow morph that was found in germination, which appears to be a trait stable across cultivars of red clover seeds, turned into a superior performance of the light purple morph in seedling growth.

A gold(I) complex with a triphenylphosphine and a monodentate N,N-dimethyldithiocarbamate ligand was synthesized and characterized by Raman spectroscopy and single crystal X-ray diffraction. DFT calculations (Gaussian 09, PBE1PBE/Lanl2dz) were undertaken for a single complex in the gas-phase. The DFT-optimized structure is in good agreement with the crystal structure and the DFT-calculated Raman spectrum also is in excellent agreement with the experimental spectrum. Assignments of the Raman peaks are based on these DFT calculations. Frontier molecular orbitals were calculated and their nature is discussed.

Rhenium Disulfide (ReS2) has evolved as a novel 2D transition-metal dichalcogenide (TMD) material which has promising applications in optoelectronics and photonics because of its distinctive anisotropic attributes. In this review, we emphasize on formulating saturable absorbers (SAs) based on ReS2 to produce Q-switched and mode-locked pulsed lasers of diverse operation wavelengths like 1 μm, 1.5 μm, 2 μm, and 3 μm. We outline ReS2 synthesis techniques and integration platforms concerning solid-state and fiber-type lasers. We discuss the laser performance based on SAs attributes. Lastly, we draw conclusions and outlook by recommending additional improvements for SA devices so as to advance the domain of ultrafast photonic technology.

This paper includes some new investigations and results for post quantum calculus, denoted by (p,q)-calculus. A chain rule for (p,q)-derivative is developed. Also, a new (p,q)-analogue of the exponential function is introduced and some its properties including the addition property for (p,q)-exponential functions are investigated. Several useful results involving (p,q)-binomial coefficients and (p,q)-antiderivative are discovered. At the final part of this paper, (p,q)-analogue of some elementary functions including trigonometric functions and hyperbolic functions are considered and some properties and relations among them are analyzed extensively.

Assuming a two component, positive and negative mass, superfluid/supersolid for space (the Winterberg model), we model the Higgs field as a condensate made up of a positive and a negative mass, planckion pair. The connection is shown to be consistent (compatible) with the underlying field equations for each field, and the continuity equation is satisfied for both species of planckions, as well as for the Higgs field. An inherent length scale for space (the vacuum) emerges, which we estimate from previous work to be of the order of,

Integrated ultra-low-loss waveguides are highly desired for integrated photonics to enable applications that require long delay lines, high-Q resonators, narrow filters, etc. Here we present an ultra-low-loss silicon waveguide on 500 nm thick SOI platform. Meter-scale delay lines, million-Q resonators and tens of picometer bandwidth grating filters are experimentally demonstrated. We design a low-loss low-reflection taper to seamlessly integrate the ultra-low-loss waveguide with standard heterogeneous Si/III-V integrated photonics platform to allow realization of high-performance photonic devices such as ultra-low-noise lasers and optical gyroscopes.

In this paper, we introduce a new generalization of the r-Stirling numbers of the second kind based on the q-numbers via an exponential generating function. We investigate their some properties and derive several relations among q-Bernoulli numbers and polynomials, and newly de…ned (q, r, w)-Stirling numbers of the second kind. We also obtain q-Bernstein polynomials as a linear combination of (q, r, w)-Stirling numbers of the second kind and q-Bernoulli polynomials in w.

For evaluating probabilities of arbitrary random events with respect to a given multivariate probability distribution, specific techniques are of great interest. An important two-dimensional high risk limit law is the Gauss-exponential distribution whose probabilities can be dealt with based upon the Gauss-Laplace law. The latter will be considered here as an element of the newly introduced family of (p,q)-spherical distributions. Based upon a suitably defined non-Euclidean arc-length measure on (p,q)-circles we prove geometric and stochastic representations of these distributions and correspondingly distributed random vectors, respectively. These representations allow dealing with the new probability measures similarly like with elliptically contoured distributions and more general homogeneous star-shaped ones. This is demonstrated at hand of a generalization of the Box-Muller simulation method. En passant, we prove an extension of the sector and circle number functions.

Motivated by Kurt's work [Filomat 30 (4) 921-927, 2016], we first consider a class of a new generating function for (p, q)-analog of Apostol type polynomials of order a including Apostol-Bernoulli, Apostol-Euler and Apostol-Genocchi polynomials of order a. By making use of their generating function, we derive some useful identities. We also introduce (p, q)-analog of Stirling numbers of second kind of order v by which we construct a relation including aforementioned polynomials.

We consider the problem of coordinating the charging of an entire fleet of electric vehicles (EV), using a model-free approach, i.e. purely data-driven reinforcement learning (RL). The objective of the RL-based control is to optimize charging actions, while fulfilling all EV charging constraints (e.g. timely completion of the charging). In particular, we focus on batch-mode learning and adopt fitted Q-iteration (FQI). A core component in FQI is approximating the Q-function using a regression technique, from which the policy is derived. Recently, a dueling neural networks architecture was proposed and shown to lead to better policy evaluation in the presence of many similar-valued actions, as applied in a computer game context. The main research contributions of the current paper are that (i)we develop a dueling neural networks approach for the setting of joint coordination of an entire EV fleet, and (ii)we evaluate its performance and compare it to an all-knowing benchmark and an FQI approach using EXTRA trees regression technique, a popular approach currently discussed in EV related works. We present a case study where RL agents are trained with an epsilon-greedy approach for different objectives, (a)cost minimization, and (b)maximization of self-consumption of local renewable energy sources. Our results indicate that RL agents achieve significant cost reductions (70--80%) compared to a business-as-usual scenario without smart charging. Comparing the dueling neural networks regression to EXTRA trees indicates that for our case study's EV fleet parameters and training scenario, the EXTRA trees-based agents achieve higher performance in terms of both lower costs (or higher self-consumption) and stronger robustness, i.e. less variation among trained agents. This suggests that adopting dueling neural networks in this EV setting is not particularly beneficial as opposed to the Atari game context from where this idea originated.

This article aims to identify the generating function of modi…ed Apostol type q-Bernoulli polynomials. With the aid of this generating function, some properties of modi…ed Apostol type q-Bernoulli polynomials are given. It is shown that aforementioned polynomials are q-Appell. Hence, we make use of these polynomials to have applications on q-Umbral calculus. From those applications, we derive some theorems in order to get Apostol type modi…ed q-Bernoulli polynomials as a linear combination of some known polynomials which we stated in the paper.

New q-series in the spirit of Jacobi have been found in a publication rst published in 1884 written in Russian and translated into English in 1928. This work was found by chance and appears to be almost totally unknown. From these entirely new q-series, fresh lattice sums have been discovered and are presented here.

In the present paper, we introduce (p, q)-extension of Apostol type Frobenius-Euler polynomials and numbers and investigate some basic identities and properties for these polynomials and numbers, including addition theorems, difference equations, derivative properties, recurrence relations and so on. Then, we provide integral representations, explicit formulas and relations for these polynomials and numbers. Moreover, we discover (p, q)-extensions of Carlitz's result [L. Carlitz, Mat. Mag., 32 (1959), 247–260] and Srivastava and Pintér addition theorems in [H. M. Srivastava, A. Pinter, Appl. Math. Lett., 17 (2004), 375–380].

In this paper, we introduce a new generalization of the Hermite polynomials via (p, q)-exponential generating function and investigate several properties and relations for mentioned polynomials including derivative property, explicit formula, recurrence relation, integral representation. We also de…ne a (p, q)-analogue of the Bernstein polynomials and acquire their some formulas. We then provide some (p, q)-hyperbolic representations of the (p, q)-Bernstein polynomials. In addition, we obtain a correlation between (p, q)-Hermite polynomials and (p, q)-Bernstein polynomials.

The prevalence of differential equations as a mathematical technique has refined the fields of control theory and constrained optimization due to the newfound ability to accurately model chaotic, unbalanced systems. However, in recent research, systems are increasingly more nonlinear and difficult to model using Differential Equations only. Thus, a newer technique is to use policy iteration and Reinforcement Learning, techniques that center around an action and reward sequence for a controller. Reinforcement Learning (RL) can be applied to control theory problems since a system can robustly apply RL in a dynamic environment such as the cartpole system (an inverted pendulum). This solution successfully avoids use of PID or other dynamics optimization systems, in favor of a more robust, reward-based control mechanism. This paper applies RL and Q-Learning to the classic cartpole problem, while also discussing the mathematical background and differential equations which are used to model the aforementioned system.

Human Perrault syndrome (PRLTS) is defined by autosomal recessive inheritance with primary ovarian insufficiency and early hearing loss. Most PRLTS disease proteins modulate mitochondrial transcription or translation. Among the genetic causes are ClpP mutations, which trigger also complete azoospermia, whose cellular and molecular underpinnings are unknown. Here, the ClpP-null mouse model was studied by global transcriptomics, proteomics, RT-qPCR, immunoblots, tissue fractionation, testis histology, and was crossed with STING/IFNAR mutants. Spermatogenesis showed accumulated early spermatocytes, versus deficits of desynapsis and kinetochore factors; excess Dazl/Stra8 and acetylSMC3, versus deficient SHCBP1L, were molecular correlates. Spermiogenesis showed few round spermatids, tsHMG/TFAM in elongated spermatids was absent; transcripts for tail/acrosome factors were downregulated from start. Nuclear anomalies included a failed Rec8 induction, early BRDT deficiency, histone H3 cleavage, and cGAMP increase, among antiviral responses typical of ClpP-mutants. However, deletion of downstream innate immune signals STING/IFNAR failed to reestablish fertility. As mitochondrial triggers, we observed accumulation of ClpX, with PTCD1, POLDIP2, GRSF1, ALKBH7, DNAJA3, AURKAIP1, VWA8, and Perrault proteins ERAL1, PEO1, HARS2, partially showing nuclear redistribution. ClpP-depletion is known to cause extra-mitochondrial release of mispacked mtDNA/mtRNA/protein complexes. Now we define nuclear inflammatory responses and meiotic arrest as consequences, similar to observations in mito-mice and mutator-mice.

The main goal of the present paper is to construct some families of the Carlitz’s q-Bernoulli polynomials and numbers. We firstly introduce the modified Carlitz’s q-Bernoulli polynomials and numbers with weight (α, β) and investigate their some explicit properties and identities arising from the bosonic q-Volkenborn integral on ℤ_p. We then define the modified degenerate Carlitz’s q-Bernoulli polynomials and numbers with weight (α, β) and obtain some recurrence relations and other identities. Moreover, we derive some correlations with the modified Carlitz’s q-Bernoulli polynomials with weight (α, β), the modified degenerate Carlitz’s q-Bernoulli polynomials with weight (α, β), the Stirling numbers of the first kind and second kind.

This review describes the positive effects of growth hormone on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease inducing the generation of new collateral vessels able to bypass a major artery occlusion. We include some preliminary data from a trial in which GH or placebo is given to elder people suffering from critical limb ischemia, showing the effects of the hormone on plasma markers of inflammation, and stating that the administration of GH in short periods of time is safe and effective even in diabetic patients. We also analyze how Klotho may have strong relationships with GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. In summary, we postulate that short-time GH administration is useful for treating cardiovascular diseases.

Amid to the COVID-19 pandemic, digital health literacy (DHL) has become a significant public health concern. This research aims to assess information seeking behavior, as well as the ability to find relevant information and deal with DHL among university students in Pakistan. An online-based cross-sectional survey, using a web-based interviewing technique, was conducted to collect data on DHL. Simple bivariate and multivariate linear regression was performed to assess the association of key characteristics with DHL. The results show a high DHL related to COVID-19 in 54.3% of students. Most of the Pakistani students demonstrated ~50% DHL in all dimensions, except of reliability. Multivariate findings showed that gender, sense of coherence and importance of information were found to be significantly associated with DHL. However, a negative association was observed with students’ satisfaction with information. This led to the conclusion that critical operational and navigations skills are essential to achieve COVID-19 DHL and cope with stress, particularly to promote both personal and community health. Focused interventions and strategies should be designed to enhance DHL amongst university students to combat the pandemic.

As shown in former papers, the nonadiabatic Heisenberg model presents a novel mechanism of Cooper pair formation generated by the strongly correlated atomic-like motion of the electrons in narrow, roughly half-filled "superconducting bands". These are energy bands represented by optimally localized spin-dependent Wannier functions adapted to the symmetry of the material under consideration. The formation of Cooper pairs is not the result of an attractive electron-electron interaction but can be described in terms of quantum mechanical constraining forces constraining the electrons to form Cooper pairs. There is theoretical and experimental evidence that only this nonadiabatic mechanism operating in superconducting bands may produce eigenstates in which the electrons form Cooper pairs. These constraining forces stabilize the Cooper pairs in any superconductor, whether conventional or unconventional. Here we report evidence that also the experimentally found superconducting state in bismuth at ambient as well as at high pressure is connected with a narrow, roughly half-filled superconducting band in the respective band structure. This observation corroborates once more the significance of constraining forces in the theory of superconductivity.

One third of a person’s life is spent on sleep, therefore the quality and habit of sleep affects health. A single case study indicated that perspiration could serve as a prognostic marker. Diagnosing nocturnal perspiration is common clinical practice, since this serves as a major symptom in many pathologies. Till this day no specific evidence-based approach for diagnosing nocturnal perspiration exists. By introducing the Q-strip, a device which quantitatively measures nocturnal perspiration, this could be acquired. The Q-strip could serve a purpose in diagnosing nocturnal perspiration more efficient without being intrusive. In addition to its health sensing potentials, the Q-strip makes it possible to visualise perspiration patterns. This introduces the possibility to examine the quality of sleep. Future research is recommended to investigate this.

In this paper we present experimental results concerning Acoustic Emission (AE) recorded during cyclic compression tests on two different kinds of brittle building materials, namely concrete and basalt. The AE inter-event times were investigated through a non-extensive statistical mechanics analysis which shows that their decumulative probability distributions follow q-exponential laws. The entropic index q and the relaxation parameter q  1=Tq, obtained by fitting the experimental data, exhibit systematic changes during the various stages of the failure process, namely (q; Tq) linearly align. The Tq = 0 point corresponds to the macroscopic breakdown of the material. The slope, including its sign, of the linear alignment appears to depend on the chemical and mechanical properties of the sample. These results provide an insight on the warning signs of the incipient failure of building materials and could therefore be used in monitoring the health of existing structures such as buildings and bridges.

Abstract: Targeted ubiquitination and proteasomal degradation regulates various cellular pathways, and the discovery that CPT induced rapid proteasomal degradation of topoI is the primary mechanism of CPT resistance was novel and compelling. CPTs are used extensively to treat various solid tumors like colorectal, gastric, pancreatic, ovarian and small cell lung cancer. The response rate is low and the classical mechanisms of drug resistance are yet to be validated. Remarkably, CPT resistant cells degrade topoI rapidly by UPP and recently we’ve published the molecular determinants of this pathway. To further understand the UPP mediated CPT resistance mechanism we used targeted proteasome prohibition by ixazomib (MLN9708) to stabilize topoI and determine its impact on CPT resistance. CPT resistant and sensitive cancer lines were both treated with ixazomib in combination with CPT. The CPT induced rate of topoI degradation, and its stabilization by ixazomib, was visualized and estimated by immunohistochemistry, immunofluorescence and immunoblotting assays, MTT and subG1 assays provided the drug sensitivity. Our results demonstrate that cells that degrade topoI rapidly are very resistant to CPT, and ixazomib significantly inhibits CPT induced topoI degradation. Notably, inhibition of proteasomal degradation by ixazomib overcomes the drug resistance and sensitizes the cells for CPTs.

In this paper, we investigate p-adic q-integral (q-Volkenborn integral) on Z_p of p-adic gamma function via their Mahler expansions. We also derived two q-Volkenborn integrals of p-adic gamma function in terms of q-Daehee polynomials and numbers and q-Daehee polynomials and numbers of the second kind. Moreover, we discover q-Volkenborn integral of the derivative of p-adic gamma function. We acquire the relationship between the p-adic gamma function and Stirling numbers of the first kind. We finally develop a novel and interesting representation for the p-adic Euler constant by means of the q-Daehee polynomials and numbers.

Rapid diagnosis of acute myocardial infarction is critical for intervention and treatment to decrease morbidity and mortality. For this reasons, this study aimed to design a sensitive biosensor for cardiac troponin I (cTnI) for early prediction and intervention. The sensor was designed from golden plate immobilized with anti- cTnI antibody conjugated with horseradish peroxidase (HRP) enzyme. The rate of degradation of H2O2 is directly related to serum cTnI level. Serum cTnI level was quantified from 3 studied groups including; healthy subjects and patients with ischemic heart (IHD) diseases and myocardial infarction (MI) by ELISA and biosensor techniques to achieve the improved sensitivity of the biosensor. It was found that cTnI levels in healthy subjects ranged from 8-13 ng/dl and in patients with IHD ranged from 20 - 41 ng/dl and MI range from 57- 180 ng/dl. The sensitivity of biosensor was ranged from 85-95% compared with ELISA technique. The developed biosensor is promising in ICU hospitals for early diagnosis and prevent complications of the stroke. It is recommended to apply this biosensor in the large scale of patients with different stages of the cardiac disease.

A series of precise data consisting of zircon U–Pb ages, whole-rock geochemistry and Sr–Nd–Hf isotope compositions from the Huhetaoergai granitic pluton was collected in this study and combined with data from the western Huhetaoergai, Zhuxiaogubuhe and Yagan granitic plutons to constrain the petrogenesis and tectonic setting of granitic plutons in the northern Ya-Gan fault zone, North Alxa, China. The Huhetaoergai pluton is composed of hornblende diorite, medium- to coarse-grained biotite adamellite and coarse-grained biotite adamellite with K-feldspar megacrysts. The U–Pb zircon ages of biotite adamellite are 220.5 ± 1.9 Ma and 226.5 ± 2.4 Ma. These granitoids are I-type granites with highly radiogenic initial ⁸⁷Sr/⁸⁶Sr of 0.708085–0.735470, negative eNd(t) average values of −2.98–3.23 and high eHf(t) of 9–11.05. These features indicate the granitoids were formed from magmas generated from juvenile crust. We speculate that the granitoids of the Huhetaoergai pluton were emplaced during an episode of intense intraplate orogenic movement evolution in an extrusional setting after a period of extensional postcollisional intraplate evolution.

In this paper we introduce the hypo-q-norms on a Cartesian product of inner product spaces. A representation of these norms in terms of inner products, the equivalence with the q-norms on a Cartesian product and some reverse inequalities obtained via the scalar Shisha-Mond, Birnacki et al., Grüss type inequalities, Boas-Bellman and Bombieri type inequalities are also given.

There is high confidence that climate change has increased the probability of concurrent temperature-precipitation extremes, changed their spatial-temporal variations, and affected the relationships between drivers of such natural hazards. However, the extent of such changes has been less investigated in Australia. Daily weather data (131 years, 1889-2019) at 700 grid cells (1◦ × 1◦) across Australia was obtained to calculate annual and seasonal mean daily maximum temperature (MMT) and total precipitation (TPR). A nonparametric multivariate copula framework was adopted to estimate the return period of compound hot-dry (CHD) events based on an ‘And’ hazard scenario (hotter than a threshold ‘And’ drier than a threshold). CHD extremes were defined as years with joint return periods of larger than 25 years. Mann-Kendall nonparametric tests was used to analyse trends in MMT and TPR as well as in the frequency of univariate and CHD extremes. A general cooling-wetting trend was observed over 1889-1989. Significant increasing trends were detected over 1990-2019 in the frequency and severity of hot extremes across the country while trends in dry extremes were mostly insignificant (and decreasing). Results showed a significant increase in the association between temperature and precipitation at various temporal scales. The frequency of CHD extremes was mostly stable over 1889-1989, but significantly increased between 1990 and 2019 at 44% of studied grid cells, mostly located in the north, south-east and south-west. Spatial homogeneity (i.e. connectedness) and propagation of extreme events from one grid cell to its neighbouring cells was investigated across Australia. It can be concluded that this connectedness has not significantly changed since 1889.

The main purpose of this paper is to introduce a new class of $q$-Hermite-Fubini numbers and polynomials by combining the $q$-Hermite polynomials and $q$-Fubini polynomials. By using generating functions for these numbers and polynomials, we derive some alternative summation formulas including powers of consecutive $q$-integers. Also, we establish some relationships for $q$-Hermite-Fubini polynomials associated with $q$-Bernoulli polynomials, $q$-Euler polynomials and $q$-Genocchi polynomials and $q$-Stirling numbers of the second kind.

Nucleoli are emerging as key sensors of cellular stress and regulators of the downstream consequences on proliferation, metabolism, senescence and apoptosis. NF-kB signalling is activated in response to a similar plethora of stresses, which leads to modulation of cell growth and death programs. Although these pathways are distinct, it is increasingly apparent that they converge at multiple levels. Exposure of cells to certain insults causes a specific type of nucleolar stress that is characterised by degradation of the PolI complex component, TIF-IA, and increased nucleolar size. Recent studies have shown that this atypical nucleolar stress lies upstream of cytosolic IkB degradation and NF-kB nuclear translocation. Under these stress conditions, the RelA component of NF-kB accumulates within functionally altered nucleoli to trigger a nucleophosmin dependent, apoptotic pathway. In this review, we will discuss these points of crosstalk and their relevance to the anti-tumour mechanism of aspirin and small molecule CDK4 inhibitors. We will also briefly discuss how NF-kB-nucleoli crosstalk may be more broadly relevant to the regulation of cellular homeostasis and how it may be exploited for therapeutic purpose.

Reinforcement learning (RL) is an extensively applied control method for the purpose of designing intelligent control systems to achieve high accuracy as well as better performance. In the present article, the PID controller is considered as the main control strategy for brushless DC (BLDC) motor speed control. For better performance, the fuzzy Q-learning (FQL) method as a reinforcement learning approach is proposed to adjust the PID coefficients. A comparison with the adaptive PID (APID) controller is also performed for the superiority of the proposed method, and the findings demonstrate the reduction of the error of the proposed method and elimination of the overshoot for controlling the motor speed. MATLAB/SIMULINK has been used for modeling, simulation, and control design of the BLDC motor.

We present an overview over eight brightly luminescent Cu(I) dimers of the type Cu2X2(PN)3 with X = Cl, Br, I and P^N = 2-diphenylphosphino-pyridine (Ph2Ppy), 2-diphenylphosphino-pyrimidine (Ph2Ppym), 1-diphenylphosphino-isoquinoline (Ph2Piqn) including three new crystal structures (Cu2Br2(Ph2Ppy)3, 1-Br, Cu2I2(Ph2Ppym)3, 2-I, and Cu2I2(Ph2Piqn)3, 3-I). However, we mainly focus on their photo-luminescence properties. All compounds exhibit combined thermally activated delayed fluorescence (TADF) and phosphorescence at ambient temperature. Emission color, decay time, and quantum yield varies over large ranges. For deeper characterization, we select Cu2I2(Ph2Ppy)3, 1-I, showing a quantum yield of 81 %. DFT and SOC-TDDFT calculations provide insight into the electronic structures of the singlet S1 and triplet T1 states. Both stem from metal+iodide-to-ligand charge transfer transitions. Evaluation of the emission decay dynamics, measured from 1.2 ≤ T ≤ 300 K, gives ∆E(S1-T1) = 380 cm-1 (47 meV), a transition rate of k(S1→S0) = 2.25×106 s-1 (445 ns), T1 zero-field splittings, transition rates from the triplet substates, and spin-lattice relaxation times. We also discuss the interplay of S1-TADF and T1-phosphorescence. The combined emission paths shorten the overall decay time. For OLED applications, utilization of both singlet and triplet harvesting can be highly favorable for improvement of the device performance.

In this paper, we introduce a new class of $(p,q)$-analogue type of Fubini numbers and polynomials and investigate some properties of these polynomials. We establish summation formulas of these polynomials by summation techniques series. Furthermore, we consider some relationships for $(p,q)$-Fubini polynomials associated with $(p,q)$-Bernoulli polynomials, $(p,q)$-Euler polynomials and $(p,q)$-Genocchi polynomials and $(p,q)$-Stirling numbers of the second kind.

A study of Bianchi Type I cosmological model is undertaken in the framework of creation of particles. To accommodate the creation of new particles, the universe is regarded as an Open thermodynamical system. The energy conservation equation is modified with the incorporation of a creation pressure in the energy momentum tensor. Exact solutions of the field equations are obtained (i) for a particular choice of the particle creation function and (ii) by considering the deceleration parameter to be constant. In the first model the behavior of the solution at late times is investigated. The physical aspects of the model have also been discussed. In the case of the second model we have restricted our analysis to the power law behaviour for the average scale factor. This leads to a particular form for the particle creation function. The behavior of the solution is investigated and the physical aspects of the model have also been discussed for the matter dominated era.

A series of dinuclear copper(I) N,C,N- and P,C,P-carbodiphosphorane (CDP) complexes using multidentate ligands CDP(Py)2 (1) and (CDP(CH2PPh2)2 (13) have been isolated and characterized. Detailed structural information was gained by single crystal XRD analyses of nine representative examples. The common structural motive is the central double ylidic carbon atom with its characteristic two lone-pairs involved into binding of two geminal L-Cu(I) fragments at Cu-Cu distances in the range 2.55 – 2.67 Å. In order to enhance conformational rigidity within the characteristic Cu-C-Cu triangle, two types of chelating side arms were symmetrically attached to each phosphorus atom: two 2-pyridyl functions in ligand CDP(Py)2 (1) and its dinuclear copper complexes 2-9 and 11, as well as two diphenylphosphinomethylene functions in ligand CDP(CH2PPh2)2 (13) and its di- and mononuclear complexes 14-18. Neutral complexes were typically obtained via reaction of 1 with Cu(I) species CuCl, CuI, and CuSPh or via salt elimination reaction of [(CuCl)2(CDP(Py)2] (2) with sodium carbazolate. Cationic Cu(I) complexes were prepared upon treating 1 with two equivalents of [Cu(NCMe)4]PF6, followed by the addition of either two equivalent of an aryl phosphine (PPh3, P(C6H4OMe)3) or one equivalent of a bisphosphine ligands DPEPhos, XantPhos or dppf. For the first time carbodiphosphorane CDP(CH2PPh2)2 (13) could be isolated upon treating its precursor [CH(dppm)2]Cl (12) with NaNH2 in liquid NH3. A protonated and a deprotonated derivative of ligand 13 were prepared and their coordination was compared to neutral CDP ligand 13. NMR analysis and DFT calculations reveal, that the most stable tautomer of 13 does not show a CDP (or carbone) structure in its uncoordinated base form. For most of the prepared complexes, photoluminescence upon irradiation with UV light at room temperature was observed. Quantum yields (PL) were determined to 36% for dicationic [(CuPPh3)2(CDP(Py)2)](PF6)2 (4) and to 60% for neutral [(CuSPh)2(CDP(CH2PPh2)2] (16).

ntroduction: Respiratory tract Infections are the greatest cause of death worldwide. Since its outbreak in 2019, the coronavirus pandemic (COVID-19) has been a challenge to humans in terms of treatment and prevention of this respiratory viral infection. The re-emergence of respiratory viral infections like influenza, pose a serious hazard to global public health because they occur seasonally. Creating broad-spectrum antiviral compounds for rapid action in the case of an outbreak crisis, as well as bioweapon defences, is critical. Human galectin-3 is found in high concentrations in activated T lymphocytes, epithelial and endothelial cells, and fibroblasts. ProLectin -I and ProLectin -M are both galectin antagonists. Blocking viral entry with a complex polysaccharide component "ProLectin-M" has downstream effects on viral reproduction enabling it to be used as a therapeutic tool and a safe alternative to conventional anti-viral medicines. Methods: In total, 3 cell based assays have been conducted to evaluate antiviral efficacy of ProLectin–I and ProLectin-M against SARS-CoV-2 virus, Influenza-A (H1N1), and human respiratory syncytial virus (hRSV) strain A2. ProLectin-M and ProLectin-I were evaluated for their anti-viral potency using SARS-CoV2 virus strain by viral RNA Extraction and qRT-PCR assays. The plaque assays were carried out to determine the antiviral activity of the test products (ProLectin-I and ProLectin-M) against ‘Influenza-A (H1N1)-A/PR/8/34 (TC adapted)’ and ‘Human respiratory syncytial virus (hRSV) strain A2’ in a cell based in vitro setting. As eference standard, "Oseltamivir Phosphate" and "Remdesivir" were used to determine antiviral activity of test products against H1N1 and hRSV strains respectively.Results: The IC_{50 of} ProLectin-M and ProLectin-I against SARS-CoV-2 virus was found to be 6248 ng/ml (6.2µg/ml) and 4207 ng/ml (4.2μg/ml) respectively. The CC₅₀ value was similar in both the test products i.e. >100 µg/ml. Against Influenza A (H1N1) strain, ProLectin-M exhibited 95 % reduction in the viral load at the test concentration of 21.8 µg/mL with an IC₅₀ value of 5.4 µg/mL whereas, ProLectin-I did not show any cytotoxicity till 250 µg/mL concentration. Against 'human respiratory syncytial virus (hRSV) strain A2, ProLectin-M exhibited 65 % reduction in the viral load at the test concentration of 43.75 µg/mL with an IC₅₀ value of 27.41 µg/mL whereas, ProLectin- I did not show any cytotoxicity till 250 µg/mL concentration. Conclusion: Both ProLectin-I and ProLectin-M have been reported to exhibit broad-spectrum antiviral activity in ‘in-vitro’ setting. ProLectin-M reducing influenza-A virus by 95% and hRSC strain A2 by 65%. To better understand broad spectrum antiviral activity of ProLectin-I and ProLectin-M, further pre-clinical research is warranted.

In this paper, we introduce and study the notion of rough I₂-lacunary statistical convergence of double sequences in normed linear spaces. We also introduce the notion of rough I₂-lacunary statistical limit set of a double sequence and discuss about some properties of this set.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

In this paper, we introduce the (ρ,q)-analogue of the p-adic factorial function. By utilizing some properties of (ρ,q)-numbers, we obtain several new and interesting identities and formulas. We then construct the p-adic (ρ,q)-gamma function by means of the mentioned factorial function. We investigate several properties and relationships belonging to the foregoing gamma function, some of which are given for the case p = 2. We also derive more representations of the p-adic (ρ,q)-gamma function in general case. Moreover, we consider the p-adic (ρ,q)-Euler constant derived from the derivation of p-adic (ρ,q)-gamma function at x = 1. Furthermore, we provide a limit representation of aforementioned Euler constant based on (ρ,q)-numbers. Finally, we consider (ρ,q)-extension of the p-adic beta function via the p-adic (ρ,q)-gamma function and we then investigate various formulas and identities.

Read-Across Structure-Activity Relationship (RASAR) is an emerging cheminformatic approach that combines the usefulness of a QSAR model and similarity-based Read-Across predictions. In this work, we have generated a simple, interpretable, and transferable quantitative-RASAR (q-RASAR) model which can efficiently predict the cytotoxicity of TiO2-based multi-component nanomaterials. The data set involves 29 TiO2-based nanomaterials which contain specific amounts of noble metal precursors in the form of Ag, Au, Pd, and Pt. The data set was rationally divided into training and test sets and the Read-Across-based predictions for the test set were generated using the tool Read-Across-v4.1 available from https://sites.google.com/jadavpuruniversity.in/dtc-lab-software/home. The hyperparameters were optimized based on the training set data and using this optimized setting, the Read-Across-based predictions for the test set were obtained. The optimized hyperparameters and the similarity approach, which yields the best predictions, were used to calculate the similarity and error-based RASAR descriptors using the tool RASAR-Desc-Calc-v2.0 available from https://sites.google.com/jadavpuruniversity.in/dtc-lab-software/home. These RASAR descriptors were then clubbed with the physicochemical descriptors and were subjected to features selection using the tool Best Subset Selection v2.1 available from https://dtclab.webs.com/software-tools. The final set of selected descriptors was used to develop multiple linear regression based q-RASAR models, which were validated using stringent criteria as per the OECD guidelines. Finally, a random forest model was also developed with the selected descriptors. The final machine learning model can efficiently predict the cytotoxicity of TiO2-based multi-component nanomaterials superseding previously reported models in the prediction quality.

Matiyasevich's theorem states that there is no algorithm to decide whether or not a given Diophantine equation has a solution in non-negative integers. Smorynski's theorem states that the set of all Diophantine equations which have at most finitely many solutions in non-negative integers is not recursively enumerable. We prove: (1) Smorynski's theorem easily follows from Matiyasevich's theorem, (2 ) Hilbert's Tenth Problem for Q has a negative solution if and only if the set of all Diophantine equations with a finite number of rational solutions is not recursively enumerable.

Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

Japanese encephalitis (JE) is a vaccine preventable disease caused by the Japanese encephalitis virus (JEV), which is primarily prevalent in Asia. JEV is a Flavivirus, classified into a single serotype with five genetically distinct genotypes (I, II, III, IV, and V). JEV genotype III (GIII) had been the most dominant strain and caused numerous out breaks in the JEV endemic countries until 1990. However, recent data shows the emergence of genotype I (GI) as a dominant genotype and it is gradually displacing GIII. The exact mechanism of this genotype displacement is still unclear. The virus can replicate in mosquito vectors and vertebrate hosts to maintain its zoonotic life cycle; pigs and aquatic wading birds act as an amplifying/reservoir hosts, and humans and equines are the dead end hosts. The important role of pigs as an amplifying host for JEV is well known. However, the influence of other domestic animals especially birds that live in high abundance and close proximity to human is not well studied. Here, we strive to briefly highlight the role of birds in JEV zoonotic transmission, discovery of birds as a natural reservoirs and amplifying host for JEV, species of birds susceptible to JEV infection, and the proposed effect of JEV on poultry industry in future perspective which have been neglected for a long times. We also discussed the recent in vitro and in vivo studies which show that the newly emerged GI viruses replicated more efficiently in bird-derived cells and ducklings/chicks than GIII, and an important role of birds in the JEV genotype shift from GIII to GI.

Increasing the quality factor (Q) of an optical resonator device has been a research focus to be utilized in various applications. Higher Q-factor means light is confined in a longer time which will produce a shaper peak and higher transmission. In this paper, we introduce a novel technique to increase further the Q-factor of a one-dimensional photonic crystal (1D PhC) cavity device by using an end loop-mirror (ELM). The technique utilizes and recycles the light transmission from the conventional 1D PhC cavity design. The design has been proved to work by using the 2.5D FDTD simulation with Lumerical FDTD and MODE softwares. By using the ELM technique, the Q- factor of a 1D PhC design has been shown to have increased up to 79.53 % from the initial Q value without the ELM. This novel design technique can be combined with any high Q-factor and very high Q-factor designs to increase more the Q-factor value of a photonic crystal cavity devices or any other suitable optical resonator devices. The experimental result shows that the device is measurable by adding a Y-branch component to the one-port structure and able to get the high-Q result.

In this paper, we investigate several relations for p-adic gamma function by means of their Mahler expansion and fermionic p-adic q-integral on ℤ_{p}. We also derive two fermionic p-adic q-integrals of p-adic gamma function in terms of q-Boole polynomials and numbers. Moreover, we discover fermionic p-adic q-integral of the derivative of p-adic gamma function. We acquire a representation for the p-adic Euler constant by means of the q-Boole polynomials. We finally develop a novel, explicit and interesting representation for the p-adic Euler constant including Stirling numbers of the first kind.

The micropaleontological study (radiolarians and foraminifera) of the sediment core AMK-340, Reykjanes Ridge, North Atlantic, combined with the radiocarbon dating and Oxygen/Carbon isotopic record, provided data for the reconstruction of the summer paleotemperature on the water depth of 100 m, and paleoenvironments during the Termination I in the age interval of 14.5–8 ka. The response of the main microfossil species on the paleoceanographic changes within the Bølling-Allerød (BA) warming, the Younger Dryas (YD) cold event, and final transition to the warm Holocene was different. The BA warming was well reflected in the radiolarian and benthic but not planktic foraminiferal record. The high abundances of the cold-water radiolarian species Amphimelissa setosa as the Greenland/Iceland Sea indicator marked a cooling at the end of the BA and within the start of the YD at 13.2–12.3 ka. The micropaleontological and isotopic data together with the paleotemperature estimates for the Reykjanes Ridge at 60° N document that, after the warm BA, the middle YD ca. 12.5–12.2 ka was the next significant step toward the Holocene warming. Start of the Holocene interglacial conditions was reflected in abundant occurrence of the microfossils being indicators of the open boreal North Atlantic environments and lower oxygen isotope values indicating increasing warmth.

RNA editing involves the insertion, deletion or substitution of single nucleotides within a RNA molecule, without altering the DNA sequence. Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. Initially, the A-to-I RNA editing phenomenon was discovered and studied in messenger RNAs (mRNAs), where it can influence RNA splicing and cause the recoding of codon sequences. The employment of more powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

The aim of this work is to introduce new ways to model the I-V characteristic of a PV cell or PV module using straight lines and Bézier curves. This is a complete novel approach, Bézier curves being previously used mainly for computer graphics. The I-V characteristic is divided in three sections, modeled with lines and a quadratic Bézier curve in the first case and with three cubic Bézier curves in the second case. The result proves to be accurate and relies on the fundamental points usually present in the PV cell datasheets: Voc (the open circuit voltage), Isc (the short circuit current), Vmp (the maximum power corresponding voltage) and Imp (the maximum power corresponding current) and the parasitic resistances Rsh0 (shunt resistance at Isc) and Rs0 (series resistance at Voc). The proposed algorithm completely defines all the implied control points and the error is analyzed. The temperature and irradiance influence is also analyzed. The model is also compared using the least squares fitting method. The final validation shows how to use Bézier cubic curves to accurately represent the I-V curves of an extensive range of PV cells and arrays.

The role of innate immunity in neutralization of viral infections (including COVID-19) and forming long-lasting and specific immune memory is considered. It is assumed that antiviral protection is generated by the mechanism of RNA interference (RNAi) and is based on the presence of specific viral patterns in the DNA library of the host cells.

In this paper, a study of modeling PV cell (solar cell), PV module (solar modules) and PV array solar array) using Matlab/Simulink software is presented. This study is focused on the study to design photovoltaic cell, photovoltaic modules, photovoltaic panels and PV array (solar array) and to analyze the change in PV performance according to changes in different parameters such temperature, solar irradiation, reverse saturation current, series resistance and shunt resistance. This study shows the PV and IV characteristics curve for each model from which MPP (maximum power point) is determined. In this study, different PV and IV characteristic curves are gained for varying temperatures with specified solar irradiation conditions,s and then the MPP is tracked. The highest power output is also compared between the designed PV module and the selected PV module (MX Solar USA MX60-245)

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance due to an increased knowledge of its underlying molecular mechanisms and its modulation by the tumor microenvironment and immune cell repertoire. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 pathologically classified human papilloma virus (HPV)-negative OSCC lesions and correlated to the intra-tumoral immune cell response, IFN- signaling and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was found in OSCC sections when compared to non-neoplastic cells. Tumoral HLA-I APM component expression was further categorized into the three major phenotypes HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh. In the HLA-Ihigh/APMhigh group, the highest frequency of intra-tumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3+ cells was found. Patients within this group presented the most unfavorable survival, which was significantly evident in stage T2 tumors. Despite a correlation with the number of intra-tumoral CD8+ T cells, tumoral JAK1 expression as a surrogate marker for IFN- signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

Dysregulation of the angiotensin-II Type-I receptor (AT1R) and its pathway was reported to associate with poor-prognosis in several malignancies, including colorectal-cancer (CRC). We have explored the therapeutic-potential of targeting AT1R using valsartan, and its pharmacological-interaction with Fluorouracil (5-FU) in CRC. Anti-proliferative function was evaluated in 2-/3-dimensional cells and in vivo models. Anti-proliferative, anti-migratory, apoptotic function and effect on cell-cycle was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing test, and Fluorescence-activated cell sorting (FACS), respectively, while gene-expression was determined at mRNA/protein levels. By histogical analysis and measuring of oxidative/antioxidant markers, we evaluated the anti-inflammatory properties of valsartan. Valsartan suppressed cell-growth and impacted the anti-tumor-activities of 5-FU by apoptosis-induction. Valsartan inhibited the cells migration by perturbation of Matrix metalloproteinase (MMP1). Furthermore, valsartan inhibited tumor-growth and metastasis, and this was more notable in valsartan/5-FU combination-treated-group. The mechanism was plausible to be via the induction of Reactive-oxygen-species (ROS) and down-regulation of Superoxide-dismutase (SOD), thiol/catalase (CAT) as well as Vascular endothelial growth factor (VEGF) and Transforming growth factor beta (TGF-β). Valsartan may protect cells against intestinal fibrosis by modulation of pro-fibrotic and pro-inflammatory components include fibronectin, Interleukin) IL-1β (, Tumor necrosis factor alpha) TNF-α (, Interferon gamma) INF-γ (, and Monocyte Chemotactic Protein 1 (MCP-1). Our findings demonstrated that targeting the AT1R receptor may inhibit tumor-growth and ameliorate fibrosis and inflammation associated with CRC via modulation of AT1 and TGF-β pathways.

Background: This literature review investigates qualitative and quantitative uses of indocyanine green (ICG) in surgical treatment, as this novel technique has become increasingly popular in ORs (operating rooms) worldwide due to its many advantages. Method: An extensive literature review was performed by searching for relevant terms in 5 international databases (www.pubmed.gov, www.sciencedirect.com, www.scopus.com, www.Oxfordjournals.com, www.reaxys.com). The results of this search were summarized into the main advantages of employing ICG in colorectal surgery as follows: a) intraoperative fluorescence angiography capability; b) fluorescence-guided identification of lymph node involvement in colorectal cancer and the sentinel lymph node method; c) positive fluorescence flagging of a liver tumour as small as "only" 200 tumour cells; d) facilitation of fistula diagnosis; and e) tumour tattooing. Moreover, in addition to qualitative intraoperative ICG use, this technique can be combined with quantitative methods and parameters, such as maximum intensity, relative maximum intensity, and different inflow parameters (time-to-peak, slope, and t1/2max). The conclusion of this article is that fluorescence surgery with ICG aided by near-infrared (NIR) light is a relatively recent technology, an advantage of which is improving the specific anatomic and functional information provided, thus allowing more comprehensive and safer tumour removal as well as preservation of important structures.

In this paper, we investigate p-adic q-integral (q-Volkenborn integral) on ℤ_{p} of p-adic gamma function via their Mahler expansions. We also derived two q-Volkenborn integrals of p-adic gamma function in terms of q-Daehee polynomials and numbers and q-Daehee polynomials and numbers of the second kind. Moreover, we discover q-Volkenborn integral of the derivative of p-adic gamma function. We acquire the relationship between the p-adic gamma function and Stirling numbers of the first kind. We finally develop a novel and interesting representation for the p-adic Euler constant by means of the q-Daehee polynomials and numbers.

Based on the geochemical analysis of the volcanic material from the sediment core AMK-340, central zone of the Reykjanes Ridge, we could detect two ash-bearing sediment units accumulated during the Termination I. They correlate to the Ash Zone I in the North Atlantic Late Quaternary sediments having an age of 12170-12840, within the Younger Dryas cold chronozone, and 13600-14540 years, within and Bølling-Allerød warm chronozone. The ash of the Younger Dryas unit is presented mostly by the mafic and persilicic material originated from the Icelandic volcanoes; Vedde Ash is presented in one sediment sample from this unit. The ash of the Bølling-Allerød unit is presented mostly by the mafic shards which are related to the basalts of the rift zone on the Reykjanes Ridge, having presumably the local origin. A detection of Vedde Ash helped to specify the timing of the previously reconstructed paleoceanographic changes for the Termination I in the point of study: a significant warming in the area could occur as early as 300 years prior to the end of the conventional Younger Dryas cold chronozone.

36 years after the publication of the important article by Busa and Nuccitelli on the variability of intracellular pH (pH_i) and the interdependence of pH_i and intracellular Ca²⁺ concentration ([Ca²⁺]_i), little research has been carried out on pH_i and calcium signaling. Moreover, the results appear to be contradictory. Some authors claim that the increase in [Ca²⁺]_i is due to a reduction in pH_i, others that it is caused by an increase in pH_i. The reasons for these conflicting results have not yet been discussed and clarified in an exhaustive manner. Variations in pH_i have a significant impact on the increase in [Ca²⁺]_i and hence on some of the basic biochemical mechanisms of calcium signaling. This paper focuses on the possible triggering role of protons, highlighting the mechanisms potentially involved and the open issues that could be clarified by research.

Geopolymer cement has been popularly studied nowadays compared to ordinary Portland cement because it demonstrated superior environmental advantages due to its lower carbon emissions and waste material utilization. This paper focuses on the formulation of geopolymer cement from nickel-laterite mine waste (NMW) and coal fly ash (CFA) as geopolymer precursors, and sodium hydroxide (SH) and sodium silicate (SS) as alkali activators. Different mix formulations of raw materials are synthesized to produce a geopolymer based from an I-optimal design and obtained different compressive strengths. A mixed formulation of 50% NMW and 50% CFA, SH-to-SS ratio of 0.5, and an activator-to-precursor ratio of 0.429 yielded the highest 28-day unconfined compressive strength (UCS) of 22.10 ± 5.40 MPa. Furthermore, using an optimized formulation of 50.12% NMW, SH-to-SS ratio of 0.516, and an activator-to-precursor ratio of 0.428, a UCS value of 36.30 ± 3.60 MPa was obtained. The result implies that the synthesized geopolymer material can be potentially used for concrete structures and pavers, pedestrian pavers, light traffic pavers, and plain concrete.

Mitochondria play key roles in cellular energy metabolism in eukaryotes. Mitochondria of most organisms contain their own genome and specific transcription and translation machineries. The expression of angiosperm mtDNA involves extensive RNA-processing steps, such as RNA trimming, editing, and the splicing of numerous group II-type introns. Pentatricopeptide repeat (PPR) proteins are key players of plant organelle gene expression and RNA metabolism. In the present analysis, we reveal the function of the MITOCHONDRIAL SPLICING FACTOR 2 gene (MISF2, AT3G22670) and show that it encodes a mitochondria-localized PPR protein that is crucial for early embryo-development in Arabidopsis. Molecular characterization of embryo-rescued misf2 plantlets indicates that the splicing of nad2 intron 1 and thus respiratory complex I biogenesis are strongly compromised. Moreover, the molecular function seems conserved between MISF2 protein in Arabidopsis and its orthologous gene (EMP10) in maize, suggesting that the ancestor of MISF2/EMP10 was recruited to function in nad2 processing before the monocot-dicot divergence, ~200 million years ago. These data provide new insights into the function of nuclear-encoded factors in mitochondrial gene expression and respiratory chain biogenesis during plant embryo development.

In the present paper, the (p,q)-Hermite based Apostol type Frobenius-Euler polynomials and numbers are firstly considered and then diverse basic identities and properties for the mentioned polynomials and numbers, including addition theorems, difference equations, integral representations, derivative properties, recurrence relations. Moreover, we provide summation formulas and relations associated with the Stirling numbers of the second kind.

Soft-Core architecture for Analogue to Digital Converter (ADC) sampling is useful for mixed signal applications. Soft-core architecture for cutting edge odd or even ADC sampling with interface to block RAM memory has not been found. Soft-core architecture as a concept has become popular due to the advantage of customization for different applications as compared to general-core architecture suited for single application. The latest generation of piece wise sampling is odd sampling and was introduced in the second decade of the 20th century. Odd and even order sampling techniques are analogue in nature driven by a tuned (tuned for odd or even) mixer. This paper proposes a third-generation piece wise sampling with soft-core architecture that enables an option to select both odd and even while interfacing to memory mapping. The proposed odd/even has superior SNR performance of 6 dB as compared to existing architecture such as Mod-∆ which recorded worst performance of 18 dB. Advances in soft-core technology have allowed a niche odd/even switching field to be identified and studied, the study has also been extended to include memory architecture.

ND1 subunit possesses the majority of the inhibitor binding domain of the human MRC-I. This is an attractive target for the search for new inhibitors that seek mitochondrial dysfunction. It is known, from in vitro experiments, some metabolites from Annona muricata called acetogenins have important biological activities such as anticancer, antiparasitic, and insecticide. Previous studies propose an inhibitory activity of bovine MRC-I by bis-THF acetogenins such as annocatacin B, however, there are few studies on its inhibitory effect on human MRC-I. In this work, we evaluate the molecular and energetic affinity of the annocatacin B molecule with the human ND1 subunit in order to elucidate its potential capacity to be a good inhibitor of this subunit. For this purpose, QM optimizations, MD simulations and MM/PBSA analysis were performed. As a control to compare our outcomes, the molecule rotenone, which is a known MRC-I inhibitor, was chosen. Our results show that annocatacin B has a greater affinity for the ND1 structure, its size and folding were probably the main characteristics that contributed to stabilize the molecular complex. Furthermore, the MM/PBSA calculations showed a 35% stronger BFE compared to the rotenone complex. Detailed analysis of the BFE shows that the aliphatic chains of annocatacin B play a key role in molecular coupling by distributing favorable interactions throughout the major part of the ND1 structure. These results are consistent with experimental studies that mention that acetogenins may be good inhibitors of MRC-I.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

Soybean is a highly nutritious legume grown globally as a food and feed crop. An examination of a collection of 10 cultivated and 6 wild Korean soybean varieties showed that there is phenotypic variability notable in different soybeans. Therefore, to develop a list of biomarker candidates useful for growing soybeans of better quality and quantity, the genes of 16 Korean soybean varieties were compared with those of the reference Glycine max var. Williams 82. The comparison was made through gene sequencing to facilitate selection of nsSNPs. The objective of the study was to find out the structural and functional variations caused by nsSNPs and discuss whether the collection of Korean soybean varieties qualifies as biomarkers based on their phenotypic traits. Analysis of the data collected was done using four software: SIFT, Polyphen, PANTHER, and I-mutant 2.0, which are designed to detect the rate of functional and structural variations caused by the nsSNPs in cultivated and wild soybean varieties. Genotypic information obtained in the analysis was used to develop a core collection of biomarkers based on whether nsSNP content was found in more than half of the 16 samples. Therefore, the list of biomarker candidates developed from this study showed that Korean soybean could provide valuable information needed in both future crop genetic research and identification of biomarkers.

In this paper, we derive multifarious relationships among the two types of higher order q-Daehee polynomials and p-adic gamma function via Mahler theorem. Also, we compute some weighted p-adic q-integrals of the derivative of p-adic gamma function related to the Stirling numbers of the both kinds and the q-Bernoulli polynomials of order k.

In this paper, a new class of q-Hermite based Frobenius type Eulerian polynomials is introduced by means of generating function and series representation. Several fundamental formulas and recurrence relations for these polynomials are derived via different generating methods. Furthermore, diverse correlations including the q-Apostol-Bernoulli polynomials, the q-Apostol-Euler poynoomials, the q-Apostol-Genocchi polynomials and the q-Stirling numbers of the second kind are also established by means of the their generating functions.

Curcumin, a natural polyphenolic compound isolated from the plant Curcuma longa, is known to induce autophagy in various cancer cells, including lung cancer. In the present study, we also confirmed by LC3 immunofluorescence and immunoblotting analyses that curcumin triggers autophagy in human lung adenocarcinoma A549 cell line. In parallel with autophagy induction, gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis was markedly elevated in response to curcumin in A549 cells. To investigate transcriptional activation of hST8Sia I associated with autophagy formation in curcumin-treated A549 cells, functional characterization of the 5’-flanking region of the hST8Sia I gene was carried out using luciferase reporter assay system. Deletion analysis demonstrated that the -1146 to -646 region, which includes putative c-Ets-1, CREB, AP-1 and NF-κB binding sites, functions as the curcumin-responsive promoter of hST8Sia I in A549 cells. Site-directed mutagenesis and chromatin immunoprecipitation assay demonstrated that the NF-κB binding site at -731 to -722 was indispensable for the curcumin-induced hST8Sia I gene expression in A549 cells. Moreover, the transcriptional activation of hST8Sia I by curcumin A549 cells was strongly inhibited by compound C, an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that curcumin controls hST8Sia I gene expression via AMPK signal pathway in A549 cells.

A good management of diabetes requires at the same time self-regulation behaviour and a balanced involvement of family components. This study’s aims were: understanding fear of injections and perceptions of family conflicts in preadolescents and adolescents with type 1 diabetes mellitus and their mothers, comparing their perceptions, and identifying the risk factors impacting patients’ quality of life. Participants were one hundred and two patients (Mean age = 14.63, SD = 2.43; age range = 10-19 years; Females = 52) and their mothers (Mean age = 46.94, SD = 6.2, age range = 27-63 years), who filled in self and proxy-report questionnaires. Twenty % of patients and 14.7% of their mothers reported clinical score for fear of self-injection and blood testing. Mothers reported higher fear of injecting and family conflicts compared with the patients. Age, fear of injecting and family conflicts impacted significantly on patients’ quality of life perceptions. Clinical consideration and recommendations are given basing on the empirical results.

Looking at different operating climatic conditions, the electrical behavior predicting photovoltaic modules gets very important. For the estimation of output power from photovoltaic (PV) plants this is a very essential and basic aspect. In this paper, the relationship between the I-V curve and the irradiation spectrum is discussed by combining the single diode model. An explicit elementary analytical model with two defined shape parameters is discussed and improved with three approximations and second order Taylor expansion. Then, the explicit elementary analytical model is investigated under varying conditions leveraging the four parameters I_ph, I₀, R_s and R_sh from the single diode model. The relationship between the physical parameters and the condition parameters are discussed and applied to extract the shape parameters at different scenarios. Considering the aging effect, the process of calculation to predict the I-V curve under different splitting spectra is simplified as follow: (1) two shape parameters are gotten from the I-V data at measurement reference conditions (MRC); (2) the short circuit current, open circuit voltage and shape parameters under any splitting spectrum can be calculated based on the relationship provided in article; (3) the performance of PV panel can be predicted with parameters. The validation of this model was experimentally proven leveraging monocrystalline silicon photovoltaic module with different splitting films. Results showed that the model accurately predicts the I-V characteristics for the examined PV modules at different irradiance spectra and cell temperatures. Moreover, the presented model performs superior compared to other investigated models when looking at accuracy and simplicity.

The activity of prioritizing software requirements should be done as efficiently as possible. Selecting the most stable requirements for the most important customers for the development company can be a positive factor when we consider that the available resource does not always encompass the implementation of all requirements. Quantitative methods for reaching software prioritization in releases are many in the field of Search-Based Software Engineering (SBSE). However, we show that it is possible to use qualitative Verbal Decision Analysis (VDA) methods to solve this same type of problem. Moreover, we will use the ZAPROS III-i methods to prioritize requirements considering the opinion of the decision-maker, who will participate in this process. Finally, the results obtained in the VDA structured methods were quite satisfactory when compared to the methods using SBSE. A comparison of results between quantitative and qualitative methods will be made and discussed later.

We propose the Hamiltonian formalism of Bianchi type 1 cosmological model for perfect fluid. We have considered both the equation of state parameter ω and the cosmological constant Λ as the function of volume V(t) which is defined by the product of three scale factors of the Bianchi type 1 line element. We propose a Lagrangian for the anisotropic Bianchi type-1 model in view of a variable mass moving in a variable potential . We can decompose the anisotropic expansion in terms of expansion and shearing motion by Lagrangian mechanism. We have considered a canonical transformation from expanding scale factor to scalar field ø which helps us to give the proper classical definition of that scalar field in terms of scale factors of the mentioned model. This definition helps us to explain the cosmological inflation. We have used large anisotropy(as in the cases of Bianchi models) and proved that cosmic inflation is not possible in such large anisotropy. Therefore we can conclude that the extent of anisotropy is less in case of our universe. Otherwise the inflation theory which explained the limitations of Big Bang cannot be resolved.Part II is contained with some analysis of the lagrangian ; derived in Part I ; on the quintessence model.

A linear Cauchy problem with polynomial coefficients wich combines q-difference operators for q>1 and differential operators of irregular type is examined. A finite set of sectorial holomorphic solutions w.r.t the complex time is constructed by means of classical Laplace transforms. These functions share a common asymptotic expansion in the time variable which turns out to carry a double layers structure which couples q-Gevrey and Gevrey bounds. In the last part of the work, the problem of confluence of these solutions as q tends to 1 is investigated.

The extended finite element method (XFEM) is now widely used in crack simulations and the direction of propagation of the XFEM crack in SS-304 has been quite interesting. This paper discusses the direction,θ(+ve in anti-clockwise direction), of the XFEM crack (under mode-I) propagation based on the von Mises stress-field around the crack-tip for static loading under the light water reactors (LWRs) conditions. The Mises core region from the crack-tip is chosen for β=〖90〗^o, the angle between the load and the initial crack. Experimental data for LWRs’environment is obtained and the simulations have been carried out applying three different static loads and results for the direction of the crack are calculated by measuring the stress-field around the crack-tip. It has been found that the direction of the XFEM varies inversely as the stress-field around the crack tip is increased. The computational results have been compared with the numerical results based on the minimum strain energy density criterion[S-criterion].

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance with growing evidence of its underlying molecular mechanisms and its interaction with the immune cell control. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 consecutive human papilloma virus (HPV)-negative OSCC lesions and correlated to tumor specific parameters, the intratumoral immune cell response and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was seen in OSCC sections when compared to non-neoplastic cells. Based on the expression levels of HLA-I APM components three main OSCC subgroups were detected and categorized into HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh phenotypes. In the HLA-Ihigh/APMhigh group, the highest frequency of intratumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3 cells was found. Despite being associated with the highest T cell infiltration, patients within this group presented the most unfavorable survival, which was most evident in stage T2 tumors. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

Tuning fork gyroscopes (TFGs) are promising for potential high-precision applications. This work proposes and experimentally demonstrates a novel high-Q dual mass tuning fork microelectro-mechanical system (MEMS) gyroscope utilizing three-dimensional (3D) packaging techniques. Except for two symmetrically-decoupled proof masses (PM) with synchronization structures, a symmetrically-decoupled lever structure is designed to force the antiparallel, antiphase drive-mode motion and basically eliminate the low-frequency spurious modes. The thermoelastic damping (TED) and anchor loss are greatly reduced by the linearly-coupled, momentum- and torque-balanced antiphase sense mode. Besides, a novel 3D packaging technique is used to realize high Q-factors. A composite substrate encapsulation cap, fabricated by through-silicon-via (TSV) and glass-in-silicon (GIS) reflow processes, is anodically bonded to the sensing structures at wafer scales. A self-developed control circuit is adopted to realize loop control and characterize gyro-scope performances. It is shown that a high-reliability electrical connection together with a high-air-impermeability package can be fulfilled with this 3D packaging technique. Furthermore, the Q-factors of the drive and sense modes reach up to 51947 and 49249, respectively. This TFG realizes a wide measurement range of ±1800° /s and a high resolution of 0.1° /s with a scale-factor nonlinearity 720 ppm after automatic mode-matching. Besides, the long-term zero-rate output (ZRO) drift can be effectively suppressed by temperature compensation, inducing a small angle random walk (ARW) of 0.923°/√h and a low bias instability (BI) of 9.270°/h.

Glutamate excitotoxicity is implicated in the pathogenesis of many disorders, including stroke, traumatic brain injury, and Alzheimer’s disease, for which central insulin resistance is a comorbid condition. Massive glutamate release primarily through ionotropic N-methyl-D-aspartate receptors (NMDARs) causes a sustained rise in [Ca2+]i, followed by mitochondrial depolarization and an increase in intracellular O2• (superoxide) production. Recently, we found that insulin protected neurons against excitotoxicity by diminishing the delayed calcium deregulation (DCD), However, a role of insulin in superoxide production in excitotoxicity still needs to be clarified. The present study is aimed to investigate the effects of insulin on glutamate-evoked superoxide generation and DCD using the fluorescent indicators dihydroethidium, MitoSOX Red, and Fura-FF in rats cultured cortical neurons. We found that insulin significantly diminished both the intracellular and mitochondrial superoxide production in neurons exposed to glutamate and there was a strong linear correlation between [Ca2+]i and intracellular superoxide. MK 801, an inhibitor of NMDAR-gated Ca2+ influx, completely abrogated the glutamate effects in both the presence and absence of insulin. In experiments on sister cultures, insulin diminishes neuronal death. Thus, collectively, data obtained suggest that insulin diminishes glutamate-induced superoxide production in neurons via fall of [Ca2+]i increased and thereby improves viability of neurons

In this paper, we investigate a new $q$-analogue of the higher order degenerate Changhee polynomials and numbers, which are called the Witt-type formula for the $q$-analogue of degenerate Changhee polynomials of order $r$. We can derive some new interesting identities related to the degenerate $(h,q)$-Changhee polynomials and numbers.

In this article, a new class of $q$-Hermite based unified Apostol type polynomials is introduced by means of generating function and series representation. Several important formulas and recurrence relations for these polynomials are derived via different generating methods. We also introduce $q$-analog of Stirling numbers of second kind of order $\nu$ by which we construct a relation including aforementioned polynomials.

Coxiella burnetii (Derrick) Philip, the causative agent of Q fever, is mainly transmitted by aerosols, but ticks can also be a source of infection. Transstadial and transovarical transmission of C. burnetii by Hyalomma lusitanicum (Koch) has been suggested. There is a close relationship between this tick species, wild animals and C. burnetii but the transmission in a natural environment has not been demonstrated. In this study, we collected 80 engorged nymphs of H. lusitanicum from red deer and wild rabbits. They molt to adults under laboratory conditions and we feed them artificially through silicone membranes after a preconditioning period. C. burnetii DNA was tested in ticks, blood and feces samples using real-time PCR. The pathogen was found in 36.25% of fed adults demonstrating that transstadial transmission from nymph to adult occurs in nature. The presence of DNA in the 60% of blood samples confirms that adults transmit the bacteria during feeding. Further studied are needed about co-feeding and other possible transmission routes to define the role of this tick species in the cycle of C. burnetii.

Global financial investments in energy production and consumption are significant since all aspects of a country's economic activity, and development require energy resources. In this paper, we assess the investment trends in the global energy sector during, before and after financial crises of 2008 using two data sources: (1) Dealogic database providing cross‐border mergers and acquisitions (M&As), and (2) fDi Intelligence fDi Markets database providing greenfield (GF) foreign direct investments (FDIs). We highlight the changing role of China and compare its M&A and GF FDI activities to those of the United States, Germany, UK, Japan and others during this period. We analyze the investments along each segment of the energy supply chain of these countries to highlight the geographical origin and destination, sectoral distribution, and cross‐border M&As and GF FDI activities. Our paper shows that while energy accounts for nearly 25% of all GF FDI, it only accounts for 4.82% of total M&A FDI activity in the period 1996-2016. China's outbound FDI in the energy sector started its ascent around the time of the global recession and had accelerated in the post-recession phase. In the energy sector, the development of China's outbound cross‐border M&As is similar to USA or UK, located mostly in the developed countries in the west, while their outbound GF investments are spread across many countries around the world. Also, China's outbound energy M&As are concentrated in certain segments (extraction, and electricity generation) while their GF covers all segments of the energy supply chain.

The practice of quantified-self sleep tracking is increasingly common nowadays among healthy individuals as well as patients with sleep problems. However, existing sleep-tracking technologies only support simple data collection and visualization, and are incapable of providing actionable recommendations that are tailored to users' physical, behavioral and environmental context. Here we coined the term context-aware sleep health recommender system (CASHRS) as an emerging multidisciplinary research field that bridges ubiquitous sleep computing and context-aware recommender systems. In this paper, we presented a narrative review to analyze the type of contextual information, the recommendation algorithms, the context filtering techniques, the behavior change techniques, the system evaluation, and the challenges in peer-reviewed publications that meet the characteristics of CASHRS. Analysis results identified current research trends, the knowledge gap, and future research opportunities in CASHRS.

In the last two decades, variably doped strontium barium niobate (SBN) has attracted a lot of scientific interest mainly due to its specific non-linear optical response. Comparably, the parental compound, i.e., undoped SBN, appears to be less studied so far. Here, two different cuts of single-crystalline nominally pure strontium barium niobate in the composition Sr0.61Ba0.39Nb2O6 (SBN61) are comprehensively studied and analyzed with regard to their photoconductive responses. We present conductivity measurements under systematically varied illumination conditions along either the polar z-axis or perpendicular to it (x-cut). Apart from a pronounced photoconductivity (PC) already under daylight and a large effect upon super-bandgap illumination in general, we observe (i) distinct spectral features when sweeping the excitation wavelength over the sub-bandgap region as then discussed in the context of deep and shallow trap states, (ii) extremely slow long-term relaxation for both light-on and light-off transients in the range of hours and days, (iii) a critical dependence of the photoresponse on the pre-illumination history of the sample, and (iv) a current-voltage hysteresis depending on both the illumination and the electrical-measurement conditions in a complex manner.

Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen the immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors such as cGAS/STING in combination with immunotherapies. In this review, we present a case for targeting nucleic acid sensing pathways within the tumor vasculature to invigorate tumor immune responses. We introduce two specific nucleic acid sensors, the DNA sensor TREX1 and the RNA sensor RIG-I and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment.

In this paper, we have used magnetron sputtering to grow the high-quality GeSn layer on Ge (100) with Sn compositin up to 7%. The crystallinity of the GeSn layer is pretty good, and the strain relaxation degree of the GeSn layer is evaluated to be approximately 50%. The root mean square (RMS) value is 0.8 nm, and the averaged TDDs in the GeSn layer is 8.7×109 cm-2, which is obtained from the rocking curve of GeSn layer along (004) plane. PL measurement result shows the significant optical emission from the deposited high-quality GeSn layer, which also means that magnetron sputtering is an optional way to achieve the higher Sn composition GeSn luminescent material. To verify whether our deposited GeSn can used for optoelectronic devices, we fabricate the simple vertical p-i-n diode, and the room temperature current-voltage (I-V) characteristic was obtained. This result paves the way for future sputtered-GeSn optimization, which is critical for the optoelectronic application.

In this paper, by using the q-integer, we introduce a new generalization of Fibonacci and Lucas sedenions called q-Fibonacci and q-Lucas sedenions. We present some fundamental properties of these type of sedenions such as Binet formulas, exponential generating fuctions, summation formulas, Catalan's identity, Cassini's identity and d'Ocagne's identity.

β-Ga2O3 crystal have attracted great attentions in the fields of photonics and photoelectronics because of its ultra wide-band gap and high thermal conductivity. Here, pure β-Ga2O3 crystal was successfully grown by optical floating zone (OFZ) method, and used as saturable absorbers to realize a passively Q-switched all-solid-state 1μm laser for the first time. By placing the as-grown β-Ga2O3 crystal into the resonator of Nd:GYAP solid-state laser, a Q-switched pulses at the center wavelength of 1080.4 nm are generated under a output coupling of 10%. The maximum output power is 191.5 mW while the shortest pulse width is 606.54 ns, and the maximum repetition frequency is 344.06 kHz. The maximum pulse energy and peak power are 0.567 μJ and 0.93 W, respectively. Our experimental results show that β-Ga2O3 crystal has great potential in the development of all-solid-state 1μm pulsed laser.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

The II law of thermodynamics is most often given in three supposedly equivalent formulations: two Clausius (I and II) and one Kelvin. The most general and indisputable entropy formulation belong to Clausius (II). The earlier Clausius I principle determines the natural direction heat flow between bodies at different temperatures. On the other hand, the Kelvin principle states that it is impossible to completely convert heat into work. The author argues that the Kelvin principle is a weaker statement (or more strictly non-equivalent) than Clausius I principle, and the latter is a weaker statement than Carnot principle, which is equivalent to Clausius II principle. As a result, the Kelvin principle and the Clausius I principle are not exhaustive formulations of the II law of thermodynamics. At the same time, it turns out that the Carnot principle becomes such a formulation. Apart from providing a complete set of proof and disproof, the author, indicates where the methodological errors were made in the alleged proof of the equivalence of the Kelvin principle and both Clausius principles.

The compound, C27H23N3 (1), crystallizes in the triclinic system of the P-1 space group. The unit cell comprises a dimer of 1, in which the monomers are linked by two complementary hydrogen bonds between N1 and H1-C1 of another molecule. The dimers form chains along the a-axis through intermolecular interactions between the N2 acceptor atoms and C17 donors from molecules in the nearest neighbouring dimer. These interactions form extended sheets of the dimers of 1, along the ab plane. The quinolinylmeth-2-yl groups of 1 lie in almost orthogonal planes and their N1/2(q) donor atoms being away from the apical amino N3 atom.

Type 2 diabetes has been linked to the expression of Human Leukocyte Antigens, principally to the major Histocompatibility Complex Class II and only scarce reports to Major Histocompatibility Complex class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC class I related to Type 2 diabetes in the Mexican population using the GWAS SIGMA database. This database contains information of 3,848 Mexican individuals with type 2 diabetes and 4,366 control individuals from the same population without clinical or hereditary history of the disease. The searching criteria considered a P value < 0.005 and odds ratio, OR > 1.0. Ten novel statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01), and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related with the development of Type 2 diabetes complications.

Chinese divination of I Ching has a history of thousands of years. The six lines changes in 64 hexagrams have exceeded one billion scenarios, and the inherent laws among them have not been well revealed to this day. By using big data's technology and coin toss method, this paper simulates the change of 64 hexagrams, and explores the probability and proportion of each hexagram during the change from the perspective of quantification, as well as the maximum and minimum conversion rate of hexagram change. This paper summarizes the basic characteristics and the basic law of hexagram change, and accordingly constructs the spatial form of hexagram change, and reveals the hidden secrets of the ancient Book of changes (I Ching). To achieve this goal, we randomly toss three coins 600 million times to generate 100 million hexagrams. According to the basic rules of hexagram divination, we calculate the hexagram changes. The results showed that: (1) Changes of things are mostly simple changes. The probability of 1 billion randomly generated hexagrams from one to three dynamic lines is close to 80%. (2) About 17% of the 64 hexagrams have no dynamic lines, which means that a significant proportion of the 64 hexagrams are invariant. (3) Small probability changing hexagram certainty and large probability changing hexagram uncertainty. (4) After generating one billion hexagrams at random, the topographic map with the probability of changing hexagrams has axial symmetry and fractal geometric characteristics, and the fractal characteristics are mainly manifested in that the changes on both sides of the symmetry are presented based on the triangle background. These results reflect the obvious characteristics and internal regularity of the changes in the 64 hexagrams of the I Ching. This article provides new ideas for scientific exploration of the internal laws of the 64 hexagrams in the I Ching.

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5’ region that in normal, healthy individuals contains 20-44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55-199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMPK activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here we report an enlarged and extended study of mitochondrial function and associated cellular stress-signalling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction of reactive O2 species (ROS) levels in premutation cells and revealed for the first time that TORC1 activities are reduced. Extensive correlation, multiple regression and Principal Components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most “proximal” regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signalling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK activation and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration and ATP steady state levels. In addition the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells, but may presage the previously reported activation of TORC1 in FXS cells.