Kosambi-Cartan-Chern perspective on chaos: Unveiling hidden attractors in nonlinear autonomous systems.

This article confronts the formidable task of exploring chaos within hidden attractors in nonlinear three-dimensional autonomous systems, highlighting the lack of established analytical and numerical methodologies for such investigations. As the basin of attraction does not touch the unstable manifold, there are no straightforward numerical processes to detect those attractors and one has to implement special numerical and analytical strategies. In this article we present an alternative approach that allows us to predict the basin of attraction associated with hidden attractors, overcoming the existing limitations. The method discussed here is based on the Kosambi-Cartan-Chern theory which enables us to conduct a comprehensive theoretical analysis by means of evaluating geometric invariants and instability exponents, thereby delineating the regions encompassing chaotic and periodic zones. Our analytical predictions are thoroughly validated by numerical results.

The impact of entrepreneurship research on other academic fields.

The remarkable ascent of entrepreneurship witnessed as a scientific field over the last 4 decades has been made possible by entrepreneurship's ability to absorb theories, paradigms, and methods from other fields such as economics, psychology, sociology, geography, and even biology. The respectability of entrepreneurship as an academic discipline is now evidenced by many other fields starting to borrow from the entrepreneurship view. In the present paper, seven examples are given from this "pay back" development. These examples were first presented during a seminar at the Erasmus Entrepreneurship Event called what has the entrepreneurship view to offer to other academic fields? This article elaborates on the core ideas of these presentations and focuses on the overarching question of how entrepreneurship research impacts the development of other academic fields. We found that entrepreneurship research questions the core assumptions of other academic fields and provides new insights into the antecedents, mechanisms, and consequences of their respective core phenomena. Moreover, entrepreneurship research helps to legitimize other academic fields both practically and academically.

Entrepreneurship research questions the core assumptions of other academic fields and legitimizes them both practically and academically. Since the 1980s, entrepreneurship research has seen tremendous growth and development, establishing itself as an academic field. Entrepreneurship is also taught extensively in leading business schools around the world. Indeed, few business schools do not address entrepreneurship in their curriculum. This represents a sea change: although entrepreneurs and new ventures had a remarkable impact on society, academia barely noticed it in the 1980s. Simply put: economics and business students rarely, if ever, encountered any mention of entrepreneurship during their studies. While entrepreneurship research has now developed its own methodological toolbox, it has extensively borrowed perspectives, theories, and methods from other fields. In the 2020s, we now find that entrepreneurship scholars are sharing its toolbox with other academic fields, questioning the core assumptions of other academic fields and providing new insights into the antecedents, mechanisms, and consequences of their respective core phenomena. Moreover, entrepreneurship research helps to legitimize other academic fields both practically and academically. Hence, entrepreneurship research now plays not just an important role in entrepreneurship education, practice, and policy but also throughout many other research fields.

Efficacy and Safety of Fixed Combination of Hydroxychloroquine with Azithromycin Versus Hydroxychloroquine and Placebo in Patients with Mild COVID-19: Randomized, double blind, Placebo controlled trial

To determine the efficacy and safety of fixed combination of hydroxychloroquine/azithromycin (HCQ+AZT) compared to hydroxychloroquine (HCQ) alone or placebo in mild COVID-19 outpatients to avoid hospitalization. Materials and methodsThis randomized, parallel, double-blind clinical trial included male and female patients aged 18 and 76 years non COVID vaccinated, who were diagnosed with mild COVID-19 infection. All patients underwent liver and kidney profile test, as well as a health questionnaire and clinical revision to document that they did not have uncontrolled comorbidities. They were randomly assigned to one of the three treatment arms: 1) hydroxychloroquine with azithromycin 200 mg/250 mg every 12 hours for five days followed by hydroxychloroquine 200 mg every 12 hours for 5 days; 2) hydroxychloroquine 200 mg every 12 hours for ten days; or 3) placebo every 12 hours for ten days. The primary outcome of the study was hospitalization, while the secondary outcomes were disease progression, pneumonia, use of supplemental oxygen, and adverse events. This study was registered in clinicaltrials.gov with the NCT number of 04964583. ResultsA total of 92 participants were randomized. Of whom, 30 received HCQ+AZT, 31 received HCQ, and 31 received placebo. The median age was 37 years, 27.2% of the participants had comorbidities, and the global incidence of hospitalization was 2.2%. The incidence of hospitalization was 6.7% (2/30) in the HCQ+AZT group compared to the HCQ or placebo groups, in which there were no hospitalizations. Progression of disease was higher in the HCQ group [RR=3.25 (95% CI, 1.19-8.87)] compared with placebo group. There was no statistical difference between the HCQ+AZT group and the placebo group in progression of disease. The incidence of pneumonia was 30% in the HCQ+AZT group, 32.2% in the HCQ group, and 9.6% in the placebo group (HCQ + AZT vs Placebo; p=0.06). There was a significant risk of pneumonia versus placebo only in the HCQ group [RR=3.33 (95% CI, 1.01-10.9)]. Supplemental oxygen was required by 20% (6/30) of the patients in the HCQ+AZT group, 6.4 (2/31) of the patients in the HCQ group, and 3.2% (1/31) of the patients in the placebo group,[(HCQ + AZT vs Placebo; p=0.100), (HCQ vs Placebo, p=0.610)]. There was no statistical difference between groups for negative test (PCR) on day 11. The most frequent adverse events were gastrointestinal symptoms. No lengthening of the QT interval was observed in patients receiving HCQ+AZT or HCQ. ConclusionThe use of HCQ+AZT does not decrease the risk of hospitalization in patients with mild COVID-19. The use of HCQ increases the risk of progression and pneumonia.

Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).

Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum's group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case -controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of 110,241 cases and 122,525 controls derived from the current literature. We strongly suggest that while we may take argument concerning many of these so-called controls (e.g. blood donors) it is quite remarkable that there are a plethora of case -control studies indicating selective association of these risk alleles ( measured in GARS) for the most part indicating a hypodopaminergia. The paper presents the detailed methodology of the GARS. Data collection procedures, instrumentation, and the analytical approach used to obtain GARS and subsequent research objectives are described. Can we combat SUD through early genetic risk screening in the addiction field enabling early intervention by the induction of dopamine homeostasis? It is envisaged that GARS type of screening will provide a novel opportunity to help identify causal pathways and associated mechanisms of genetic factors, psychological characteristics, and addictions awaiting additional scientific evidence including a future meta- analysis of all available data -a work in progress.

Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies.

Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called 'missing heritability'. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51-62% in the number of genome-wide significant loci and a relative loss in polygenic score R2 of 36-38%). Hence, cross-study heterogeneity contributes to the missing heritability.

Mitochondrial stress-induced p53 attenuates HIF-1α activity by physical association and enhanced ubiquitination.

Retrograde signaling is a mechanism by which mitochondrial dysfunction is communicated to the nucleus for inducing a metabolic shift essential for cell survival. Previously, we showed that partial mitochondrial DNA (mtDNA) depletion in different cell types induced mitochondrial retrograde signaling pathway (MtRS) involving Ca+2-sensitive Calcineurin (Cn) activation as an immediate upstream event of stress response. In multiple cell types, this stress signaling was shown to induce tumorigenic phenotypes in immortalized cells. In this study we show that MtRS also induces p53 expression, which was abrogated by Ca2+ chelators and short hairpin RNA-mediated knockdown of CnAß mRNA. Mitochondrial dysfunction induced by mitochondrial ionophore, carbonyl cyanide m-chlorophenyl hydrazone and other respiratory inhibitors, which perturb the transmembrane potential, were equally efficient in inducing the expression of p53 and downregulation of MDM2. Stress-induced p53 physically interacted with hypoxia-inducible factor-1α (HIF-1α) and attenuated the latter's binding to promoter DNA motifs. In addition, p53 promoted ubiquitination and degradation of HIF-1α in partial mtDNA-depleted cells. The mtDNA depleted cells, with inhibited HIF-1α, showed upregulation of glycolytic pathway genes, glucose transporter 1-4 (Glut1-4), phosphoglycerate kinase 1 and Glucokinase but not of prolyl hydroxylase isoforms. For the first time we show that p53 is induced as part of MtRS and it renders HIF-1α inactive by physical interaction. In this respect, our results show that MtRS induces tumor growth independent of the HIF-1α pathway.

Consequence of neo-adjuvant chemotherapy on morphology of breast carcinoma: A systematic evaluation.

BACKGROUND: Neo-adjuvant chemotherapy (NAC) in locally advanced breast cancer is the present trend. Following NAC, a considerable alteration of morphology occurs in the tumor. AIMS: To study effects of NAC on morphology of breast carcinoma and to evaluate the pathologic response (PR). MATERIALS AND METHODS: A total of 39 surgically resected mastectomy specimens of patients of invasive locally advanced breast carcinoma who received NAC were evaluated for macroscopic and microscopic (by routine stains and immunohistochemistry) alteration of morphology. RESULTS: Macroscopically well-defined tumor noted in 25 cases (64.1%) and in the rest (14 cases, 35.9%), only fibrotic areas identified. Microscopic examination identified malignant cells in 29 (74.4%), significant chronic inflammation in 24 (61.5%), hyalinized fibrosed stroma in 25 (64.1%) and necrosis in 11 (28.2%) cases. Immunohistochemistry assisted in differentiating malignant cells from histiocytes. In 15 cases (38.5%), axillary lymph nodes isolated where fibrosis seen in 12 (30.8%) and malignant cell in 8 (20.5%) cases. In 34 cases where the pre-treatment biopsy were available, complete pathologic response (pCR) and partial pathologic response (pPR) were achieved in 7 (20.6%) and 23 (67.4%) cases respectively. DISCUSSION: Protocol of systematic evaluation of morphological changes is different in cases of a patient treated by NAC. Nature of malignancy was difficult to categorize as morphology of typical breast carcinomas were altered. Sometimes, immunohistochemistry is advantageous as routine H and E stains are not sufficient to isolate malignant cells in fibrotic and necrotic areas. Appropriate morphological evaluation of the mastectomy specimen is absolutely crucial for assessment of PR and subsequent management.

Self-Employment and Health: Barriers or Benefits?

The self-employed are often reported to be healthier than wageworkers; however, the cause of this health difference is largely unknown. The longitudinal nature of the US Health and Retirement Study allows us to gauge the plausibility of two competing explanations for this difference: a contextual effect of self-employment on health (benefit effect), or a health-related selection of individuals into self-employment (barrier effect). Our main finding is that the selection of comparatively healthier individuals into self-employment accounts for the positive cross-sectional difference. The results rule out a positive contextual effect of self-employment on health, and we present tentative evidence that, if anything, engaging in self-employment is bad for one's health. Given the importance of the self-employed in the economy, these findings contribute to our understanding of the vitality of the labor force. Copyright © 2014 John Wiley & Sons, Ltd.

Internal consistency of event-related potentials associated with cognitive control: N2/P3 and ERN/Pe.

Recent studies in psychophysiology show an increased attention for examining the reliability of Event-Related Potentials (ERPs), which are measures of cognitive control (e.g., Go/No-Go tasks). An important index of reliability is the internal consistency (e.g., Cronbach's alpha) of a measure. In this study, we examine the internal consistency of the N2 and P3 in a Go/No-Go task. Furthermore, we attempt to replicate the previously found internal consistency of the Error-Related Negativity (ERN) and Positive-Error (Pe) in an Eriksen Flanker task. Healthy participants performed a Go/No-Go task and an Eriksen Flanker task, whereby the amplitudes of the correct No-Go N2/P3, and error trials for ERN/Pe were the variables of interest. This study provides evidence that the N2 and P3 in a Go/No-Go task are internally consistent after 20 and 14 trials are included in the average, respectively. Moreover, the ERN and Pe become internally consistent after approximately 8 trials are included in the average. In addition guidelines and suggestions for future research are discussed.

Serum testosterone levels in males are not associated with entrepreneurial behavior in two independent observational studies.

Previous research has suggested a positive association between testosterone (T) and entrepreneurial behavior in males. However, this evidence was found in a study with a small sample size and has not been replicated. In the present study, we aimed to verify this association using two large, independent, population-based samples of males. We tested the association of T with entrepreneurial behavior, operationalized as self-employment, using data from the Rotterdam Study (N=587) and the Study of Health in Pomerania (N=1697). Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured in the serum. Free testosterone (FT), non-SHBG-bound T (non-SHBG-T), and the TT/SHBG ratio were calculated and used as measures of bioactive serum T, in addition to TT adjusted for SHBG. Using logistic regression models, we found no significant associations between any of the serum T measures and self-employment in either of the samples. To our knowledge, this is the first large-scale study on the relationship between serum T and entrepreneurial behavior.

Cationic-vacancy-induced room-temperature ferromagnetism in transparent, conducting anatase Ti1-xTaxO2 (x~0.05) thin films.

We report room-temperature ferromagnetism (FM) in highly conducting, transparent anatase Ti(1-x)Ta(x)O(2) (x∼0.05) thin films grown by pulsed laser deposition on LaAlO(3) substrates. Rutherford backscattering spectrometry (RBS), X-ray diffraction, proton-induced X-ray emission, X-ray absorption spectroscopy (XAS) and time-of-flight secondary-ion mass spectrometry indicated negligible magnetic contaminants in the films. The presence of FM with concomitant large carrier densities was determined by a combination of superconducting quantum interference device magnetometry, electrical transport measurements, soft X-ray magnetic circular dichroism (SXMCD), XAS and optical magnetic circular dichroism, and was supported by first-principles calculations. SXMCD and XAS measurements revealed a 90 per cent contribution to FM from the Ti ions, and a 10 per cent contribution from the O ions. RBS/channelling measurements show complete Ta substitution in the Ti sites, though carrier activation was only 50 per cent at 5 per cent Ta concentration, implying compensation by cationic defects. The role of the Ti vacancy (V(Ti)) and Ti(3+) was studied via XAS and X-ray photoemission spectroscopy, respectively. It was found that, in films with strong FM, the V(Ti) signal was strong while the Ti(3+) signal was absent. We propose (in the absence of any obvious exchange mechanisms) that the localized magnetic moments, V(Ti) sites, are ferromagnetically ordered by itinerant carriers. Cationic-defect-induced magnetism is an alternative route to FM in wide-band-gap semiconducting oxides without any magnetic elements.

On graphical representation of trans-membrane proteins.

In the first part of this paper, we present a novel graphical representation of proteins, which starts with constructing a map of a protein that is obtained from a matrix, the elements of which record the adjacencies of pairs of amino acids in the primary structure of a protein. Starting with the novel protein map, one interprets its matrix elements as vertices of a graph, which are labelled in sequential order as in the protein sequence. The nearest vertices are connected to the nearest neighbour which has a smaller label. In the second part of this paper, we describe the construction of protein binary codes that can serve as protein descriptors. This novel graphical representation of proteins is illustrated on segments of trans-membrane proteins, which are embedded in the membrane.

Black tea (Camellia sinensis) decoction shows immunomodulatory properties on an experimental animal model and in human peripheral mononuclear cells.

BACKGROUND: Black tea (Camellia sinensis) has been used as a daily beverage for time immemorial. Immunomodulatory effects of tea are recognized as it stimulates the proliferation of cultured human peripheral blood mononuclear cells. Anti-inflammatory effects of tea have also been depicted in the available literature. Therefore, we designed this study to examine the potential immunemodulatory and anti-inflammatory activities of black tea in a rat model and in human peripheral mononuclear cells. AIMS: The purpose of the study was to determine (1) evaluation of anti-inflammatory effects of black tea on rats, (2) evaluation of immunemodulator effects of black tea on rats, and (3) evaluation of immunemodulator effects of black tea on human peripheral mononuclear cells. MATERIALS AND METHODS: Black tea decoction (10% and 20%) was prepared. Acute anti-inflammatory activity of tea decoction was evaluated using carrageenan and dextran whereas chronic anti-inflammatory (Immunomodulatory) effects were evaluated in a complete Freunds' adjuvant-induced arthritis model. Immunostimulatory role was evaluated in cultured human (in vitro) peripheral mononuclear cells (T-lymphocytes) by using methyl thioazolyl tetrazolium (MTT) and Trypan blue assay. STUDY DESIGN: An experimental study was designed. RESULTS: Black tea decoction (10% and 20%) strength has shown significant anti-inflammatory effects (64.8% and 77% reduction, respectively), on carrageenan-induced acute inflammatory models (rat paw edema) which can be comparable with the standard drug indomethacin (89.1%). In a chronic anti-inflammatory model, black tea decoction (10% and 20%) has shown significant suppressive effects on rat paw edema (38.56% and 69.53%) observed on 21(st) day. Lymphoproliferative action of tea was evaluated on human peripheral mononuclear cells using an MTT assay where the number of living cells were expressed in terms of optical density at 570 nm. An experiment has shown that black tea increases the maximum number of T-lymphocytes at 72 h with a maximum strength of 20%. Maximum number of viable cells (T-lymphocytes) was observed with black tea at 20% strength at 72 h. The results were expressed as mean ± SD, and the significance was evaluated by Student's t-test versus control, with P < 0.05 implying significance. CONCLUSIONS: Taken together, our data indicate that black tea has potential anti-inflammatory and immunomodulatory action and this corroborates with the current trend of tea being promoted as a 'health drink'.

Electronic phase separation at the LaAlO3/SrTiO3 interface.

There are many electronic and magnetic properties exhibited by complex oxides. Electronic phase separation (EPS) is one of those, the presence of which can be linked to exotic behaviours, such as colossal magnetoresistance, metal-insulator transition and high-temperature superconductivity. A variety of new and unusual electronic phases at the interfaces between complex oxides, in particular between two non-magnetic insulators LaAlO(3) and SrTiO(3), have stimulated the oxide community. However, no EPS has been observed in this system despite a theoretical prediction. Here, we report an EPS state at the LaAlO(3)/SrTiO(3) interface, where the interface charges are separated into regions of a quasi-two-dimensional electron gas, a ferromagnetic phase, which persists above room temperature, and a (superconductor like) diamagnetic/paramagnetic phase below 60 K. The EPS is due to the selective occupancy (in the form of 2D-nanoscopic metallic droplets) of interface sub-bands of the nearly degenerate Ti orbital in the SrTiO(3). The observation of this EPS demonstrates the electronic and magnetic phenomena that can emerge at the interface between complex oxides mediated by the Ti orbital.

Finite element analysis of a TMJ implant.

To determine the causes of failure of an artificial temporomandibular joint implant, one must study the magnitude and location of the maximum stresses under physiological loading. In this study, we analyzed the stresses in a commercially available TMJ implant, the bone (i.e., mandible), and the bone-implant interface using a finite element software package. Both titanium and Co-Cr-Mo/Vitallium metals as well as bones with various degrees of osteoporosis were studied. The results of the analysis showed that the maximum stresses occurred at the location of the first screw hole (closest to the condyle) of the implant. In addition, the highest microstrains were observed in the bone adjacent to the first screw hole. The results of our study have potential clinical benefit in terms of improved implant design and hence better performance.

Nonparaxial effects on the propagation and scattering of a polarized optical pulse.

Propagation characteristics of a polarized optical solitary pulse are analyzed by taking into account the effect of nonparaxiality and mutual interaction. To start with, a pair of generalized nonlinear Schrodinger equations is deduced through an operator approach. Stationary solutions of such a system are then analyzed numerically through a boundary value problem in two stages, with and without the nonparaxial effect. In the second stage, the propagating form of the corresponding spatial soliton is studied by an extended split step algorithm ETDRK. The initial profile is considered to be both a one- and two-soliton solution, to visualize the event of scattering and fusion. From this data, we have computed the intensity, root mean square spectral width, and chirp of a single soliton as it propagates. In the case of the two-soliton solution, we observe that for source parameter values, the fusion is more favored than scattering. It is observed that nonparaxiality and the interaction between A(x) and A(y) tends to destroy the periodic behaviors of these parameters. Lastly, we have investigated the modulational instability of the system as function of frequency detuning and nonparaxiality. The form of the gain is discussed as a function of nonparaxiality.

The dynamics of size-at-age variability.

In this paper, we propose a theoretical framework within which a unified treatment of the key sources of size-at-age variability-size dependence of growth rate, stochastic growth rate variations and individual-to-individual variability in growth performance-is possible. We use this framework to develop a general criterion for growth depensation in cohorts, which we define as the increase of the coefficient of variation of size-at-age, with increasing age. We use this criterion to show that size dependence of growth rate, acting alone, is depensatory only if the growth rate increases faster than linearly with size (that is, if growth is faster than exponential), while stochastic growth rate variation is invariably depensatory. Many species exhibit growth rates that scale less than linearly with size; indeed the commonly used von Bertalanffy model shows growth rates which actually decrease with size. In such a species, the size dependence of growth rate acts compensatorily, while stochastic growth rate variability is depensatory. We show that the tension between these two mechanisms leads to quasi-stationary size-at-age variability, which we can calculate analytically in some special cases and obtain by a simple numerical procedure where analysis is impractical.