Effect of a modulated acoustic field on the dynamics of a vibrating charged bubble.

We investigate the effect of amplitude-modulated acoustic irradiation on the dynamics of a charged bubble vibrating in a liquid. We show that the potential V(x) of the bubble, and the number and stability of its equilibria, depend on the magnitude of the charge it carries. Under high-frequency amplitude-modulation, a modulation threshold, Gth, was found for the onset of increased bubble amplitude oscillations. For some pressure field values, charge can facilitate the control of chaotic dynamics via reversed period-doubling bifurcation sequences. There is evidence for peak-shouldering and shock waves. The Mach number increases rapidly with the drive amplitude G. In the supersonic regime, for G>1.90Pa, the high-frequency modulation raises both Blake's and the transient cavitation thresholds. We found a decrease in the bubble's maximum charge threshold, and threshold modulation amplitude for the occurrence Vibrational resonance (VR). VR occurs due to the modulated oscillatory pressure field, and the influence on VR of the electrostatic charge, and other parameters of the system are investigated. In contrast to the cases of VR reported earlier, where the amplitude G of the high-frequency driving is typically much higher than the amplitude of the low-frequency driving (Ps), the VR resonance peaks occur here at relatively low G values (0

Pathways to health outcomes after cancer diagnosis: A systematic review of cancer survivorship in Nigeria.

OBJECTIVE: With advancements in medicine and technology, more people are surviving cancers. However, cancer mortality in Nigeria remains high. The yearly estimate is 72,000 cancer-related deaths, making cancer one of the leading causes of death in Nigeria. The current study aimed to identify and synthesize factors that facilitate or hinder cancer survivorship in Nigeria and add to our understanding of the patterns of cancer survivorship in LMICs, such as Nigeria. METHOD: Following preferred reporting items for systematic reviews and meta-analyses guidelines, a systematic review was conducted across PubMed, Cochrane, and Scopus databases. We identified 31 peer-reviewed studies that examined cancer treatment, management, care, and survivorship in Nigeria. RESULTS: Eight themes emerged from 31 peer-reviewed studies that examined the factors that facilitate or hinder cancer survivorship among Nigerians. They include themes such as self-care and management, treatment options, availability of pseudo-doctors/pharmacists, and the desire to live. The themes were further grouped into three overarching themes: psychosocial, economic, and health care. CONCLUSION: Cancer survivors in Nigeria face many unique experiences that impact their health outcomes and chances of survivorship. Therefore, understanding cancer survivorship in Nigeria must involve studies on diagnosis, treatment, remission, surveillance, after-cancer care, and end-of-life. With enhanced support, cancer survivors will have improved health, thereby reducing the cancer mortality rate in Nigeria.

H3.3 contributes to chromatin accessibility and transcription factor binding at promoter-proximal regulatory elements in embryonic stem cells.

BACKGROUND: The histone variant H3.3 is enriched at active regulatory elements such as promoters and enhancers in mammalian genomes. These regions are highly accessible, creating an environment that is permissive to transcription factor binding and the recruitment of transcriptional coactivators that establish a unique chromatin post-translational landscape. How H3.3 contributes to the establishment and function of chromatin states at these regions is poorly understood. RESULTS: We perform genomic analyses of features associated with active promoter chromatin in mouse embryonic stem cells (ESCs) and find evidence of subtle yet widespread promoter dysregulation in the absence of H3.3. Loss of H3.3 results in reduced chromatin accessibility and transcription factor (TF) binding at promoters of expressed genes in ESCs. Likewise, enrichment of the transcriptional coactivator p300 and downstream histone H3 acetylation at lysine 27 (H3K27ac) is reduced at promoters in the absence of H3.3, along with reduced enrichment of the acetyl lysine reader BRD4. Despite the observed chromatin dysregulation, H3.3 KO ESCs maintain transcription from ESC-specific genes. However, upon undirected differentiation, H3.3 KO cells retain footprinting of ESC-specific TF motifs and fail to generate footprints of lineage-specific TF motifs, in line with their diminished capacity to differentiate. CONCLUSIONS: H3.3 facilitates DNA accessibility, transcription factor binding, and histone post-translational modification at active promoters. While H3.3 is not required for maintaining transcription in ESCs, it does promote de novo transcription factor binding which may contribute to the dysregulation of cellular differentiation in the absence of H3.3.

Theoretic measure and thermal properties of a standard Morse potential model.

Since the proposition of the standard form of Morse potential [Formula: see text] model over the years, there has not been much attention on the potential. Its application to different studies such as the thermodynamic properties and information theory are yet to be reported to the best of our understanding. In this study, the solutions of the radial Schrödinger equation for the standard Morse potential is obtained using supersymmetric approach. The effect of the quantum number on the energy eigenvalue for the standard Morse potential is examined numerically for the hydrogen molecule (H2), lithium molecule (Li2), and potassium molecule (K2). Using the energy equation and the wave function obtained, the theoretic measures and thermodynamic properties of hydrogen, lithium, and potassium molecules are calculated via maple program. It has been shown that the energy of the standard Morse potential is fully bounded for the three molecules studied. A higher concentration of electron density corresponds to a strongly localized distribution in the position configuration. The Beckner, Bialynicki-Birula, and Mycieslki (BBM) inequality is satisfied for both the ground state and the first excited state. Finally, the product of uncertainty obtained obeyed the Heisenberg uncertainty relation.

Non-relativistic molecular modified shifted Morse potential system.

A shifted Morse potential model is modified to fit the study of the vibrational energies of some molecules. Using a traditional technique/methodology, the vibrational energy and the un-normalized radial wave functions were calculated for the modified shifted Morse potential model. The condition that fits the modified potential for molecular description were deduced together with the expression for the screening parameter. The vibrational energies of SiC, NbO, CP, PH, SiF, NH and Cs2 molecules were computed by inserting their respective spectroscopic constants into the calculated energy equation. It was shown that the calculated results for all the molecules agreement perfectly with the experimental RKR values. The present potential performs better than Improved Morse and Morse potentials for cesium dimer. Finally, the real Morse potential model was obtained as a special case of the modified shifted potential.

CRLF2 overexpression results in reduced B-cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome.

Children with Down syndrome (DS) are 10-fold more likely to develop B-cell acute lymphoblastic leukemia (B-ALL), with a higher frequency of rearrangements resulting in overexpression of cytokine receptor-like factor 2 (CRLF2). Here, we investigated the impact of CRLF2 overexpression on B-cell progenitor proliferation, immunophenotype, and gene expression profile in the Dp(16)1Yey (Dp16) mouse model of DS compared with wild-type (WT) mice. CRLF2 overexpression enhanced immature B-lymphoid colony development and increased the proportion of less differentiated pre-pro-B cells, with a greater effect in Dp16 versus WT. In CRLF2-rearranged (CRLF2-R) B-ALL patient samples, cells with higher CRLF2 expression exhibited a less differentiated B-cell immunophenotype. CRLF2 overexpression resulted in a gene expression signature associated with E2F signaling both in Dp16 B-progenitors and in DS-ALL patient samples, and PI3K/mTOR and pan-CDK inhibitors, which reduce E2F-mediated signaling, exhibited cytotoxicity in CRLF2-R B-ALL cell lines and patient samples. CRLF2 overexpression alone in Dp16 stem and progenitor cells did not result in leukemic transformation in recipient mice. Thus, CRLF2 overexpression results in reduced B-cell differentiation and enhanced E2F signaling in Dp16 B-progenitor cells and DS-ALL patient samples. These findings suggest a functional basis for the high frequency of CRLF2-R in DS-ALL as well as a potential therapeutically targetable pathway.

Nonlinear growth and mathematical modelling of COVID-19 in some African countries with the Atangana-Baleanu fractional derivative.

We analyse the time-series evolution of the cumulative number of confirmed cases of COVID-19, the novel coronavirus disease, for some African countries. We propose a mathematical model, incorporating non-pharmaceutical interventions to unravel the disease transmission dynamics. Analysis of the stability of the model's steady states was carried out, and the reproduction number R 0 , a vital key for flattening the time-evolution of COVID-19 cases, was obtained by means of the next generation matrix technique. By dividing the time evolution of the pandemic for the cumulative number of confirmed infected cases into different regimes or intervals, hereafter referred to as phases, numerical simulations were performed to fit the proposed model to the cumulative number of confirmed infections for different phases of COVID-19 during its first wave. The estimated R 0 declined from 2.452-9.179 during the first phase of the infection to 1.374-2.417 in the last phase. Using the Atangana-Baleanu fractional derivative, a fractional COVID-19 model is proposed and numerical simulations performed to establish the dependence of the disease dynamics on the order of the fractional derivatives. An elasticity and sensitivity analysis of R 0 was carried out to determine the most significant parameters for combating the disease outbreak. These were found to be the effective disease transmission rate, the disease diagnosis or case detection rate, the proportion of susceptible individuals taking precautions, and the disease infection rate. Our results show that if the disease infection rate is less than 0.082/day, then R 0 is always less than 1; and if at least 55.29% of the susceptible population take precautions such as regular hand washing with soap, use of sanitizers, and the wearing of face masks, then the reproduction number R 0 remains below unity irrespective of the disease infection rate. Keeping R 0 values below unity leads to a decrease in COVID-19 prevalence.

Defining the transcriptional control of pediatric AML highlights RARA as a superenhancer-regulated druggable dependency.

Somatic mutations are rare in pediatric acute myeloid leukemia (pAML), indicating that alternate strategies are needed to identify targetable dependencies. We performed the first enhancer mapping of pAML in 22 patient samples. Generally, pAML samples were distinct from adult AML samples, and MLL (KMT2A)-rearranged samples were also distinct from non-KMT2A-rearranged samples. Focusing specifically on superenhancers (SEs), we identified SEs associated with many known leukemia regulators. The retinoic acid receptor alpha (RARA) gene was differentially regulated in our cohort, and a RARA-associated SE was detected in 64% of the study cohort across all cytogenetic and molecular subtypes tested. RARA SE+ pAML cell lines and samples exhibited high RARA messenger RNA levels. These samples were specifically sensitive to the synthetic RARA agonist tamibarotene in vitro, with slowed proliferation, apoptosis induction, differentiation, and upregulated retinoid target gene expression, compared with RARA SE- samples. Tamibarotene prolonged survival and suppressed the leukemia burden of an RARA SE+ pAML patient-derived xenograft mouse model compared with a RARA SE- patient-derived xenograft. Our work shows that examining chromatin regulation can identify new, druggable dependencies in pAML and provides a rationale for a pediatric tamibarotene trial in children with RARA-high AML.

ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress.

ATRX is a tumor suppressor that has been associated with protection from DNA replication stress, purportedly through resolution of difficult-to-replicate G-quadruplex (G4) DNA structures. While several studies demonstrate that loss of ATRX sensitizes cells to chemical stabilizers of G4 structures, the molecular function of ATRX at G4 regions during replication remains unknown. Here, we demonstrate that ATRX associates with a number of the MCM replication complex subunits and that loss of ATRX leads to G4 structure accumulation at newly synthesized DNA. We show that both the helicase domain of ATRX and its H3.3 chaperone function are required to protect cells from G4-induced replicative stress. Furthermore, these activities are upstream of heterochromatin formation mediated by the histone methyltransferase, ESET, which is the critical molecular event that protects cells from G4-mediated stress. In support, tumors carrying mutations in either ATRX or ESET show increased mutation burden at G4-enriched DNA sequences. Overall, our study provides new insights into mechanisms by which ATRX promotes genome stability with important implications for understanding impacts of its loss on human disease.

Vibrational and stochastic resonances in driven nonlinear systems: part 2.

Nonlinearity is ubiquitous in both natural and engineering systems. The resultant dynamics has emerged as a multidisciplinary field that has been very extensively investigated, due partly to the potential occurrence of nonlinear phenomena in all branches of sciences, engineering and medicine. Driving nonlinear systems with external excitations can yield a plethora of intriguing and important phenomena-one of the most prominent being that of resonance. In the presence of additional harmonic or stochastic excitation, two exotic forms of resonance can arise: vibrational resonance or stochastic resonance, respectively. Several promising state-of-the-art technologies that were not covered in part 2 of this theme issue are discussed here. They include inter alia the improvement of image quality, the design of machines and devices that exert vibrations on materials, the harvesting of energy from various forms of ambient vibration and control of aerodynamic instabilities. They form an important part of the theme issue as a whole, which is dedicated to an overview of vibrational and stochastic resonances in driven nonlinear systems. This article is part of the theme issue 'Vibrational and stochastic resonance in driven nonlinear systems (part 2)'.

Anxiogenic and memory impairment effect of food color exposure: upregulation of oxido-neuroinflammatory markers and acetyl-cholinestrase activity in the prefrontal cortex and hippocampus.

Erythrosine and tartrazine are one of the synthetic azo dye mostly consumed in food, drugs and other industrial compounds. This study was designed to investigate the adverse effect of combine erythrosine and tartrazine on cognitive and neurobehavioral functions, pro-oxidants, endogenous antioxidants, cholinergic system and pro-inflammatory cytokines in rats. Erythrosine and tartrazine (2 mg/kg, 6 mg/kg, and 10 mg/kg, b.w., p.o, 50:50) was administered to rats (n = 6) for 6 weeks. Memory and neurobehavioral assessment using Novel object recognition test (NORT) and Elevated plus maze (EPM) and biochemical (pro-oxidants and anti-oxidant enzymes) and pro-inflammatory cytokine measurement from the brain sub regions namely, hippocampus and prefrontal cortex were done at the end of treatment. The results showed (p < 0.05) significant decreased memory and neurobehavioral function, increased acetyl-cholinesterase and pro-oxidants activity (Malonaldehyde level and Nitrite), decreased endogenous anti-oxidants (Glutathione and Catalase) and increased pro-inflammatory cytokines (Tumor necrosis factor-alpha, TNF-α). We suggested that the mechanism by which this oxidative and neuro-inflammatory damage and cholinergic system alteration occur might be related to the release of metabolite in fission of the azo dyes of the combined erythrosine and tartrazine administration in the animals. However, we concluded on these findings that erythrosine and tartrazine dyes significantly provoke the release of oxido-nitrergic and neuroinflammatory stress markers and also may incite acetyl-cholinesterase activities in different brain regions leading to memory and neurobehavioral impairment.

The Burden of Emergency Abdominal Surgery Heavily Outweighs Elective Procedures in KwaZulu-Natal Province, South Africa.

BACKGROUND: South Africa is a middle-income country with major discrepancies in wealth and access to care. There is a significant burden of surgical disease and limited access to quality health care for a large proportion of the population. This article quantifies the burden of abdominal surgery over a 6-month period in KwaZulu-Natal (KZN) province and quantifies the emergency to elective (Ee) ratio for these operations. METHODS: This study describes the abdominal operations conducted at all regional and tertiary hospitals in the public health sector of KZN province for the period of 1 July to December 31, 2015. Operations performed were tabulated in a spreadsheet and categorized as elective, emergency, and trauma. They were further subdivided by anatomical region and by specific predetermined procedures. Uncertain criteria were clarified using a modified Delphi discussion. The Ee ratio was determined using the recently described technique. RESULTS: Between June, 1st and December 31, 2015, of 13,282 operations, there were 4580 (34.5%) elective operations, 7777 (58.6%) emergency operations, and 925 (6.9%) trauma-related operations. A total of 5630 abdominal operations were performed of which 2949 were emergency procedures. There were 660 trauma-related abdominal procedures and 2021 elective procedures. There was a heavy weighting toward emergency surgeries with an Ee ratio of 145 for abdominal surgery. The previous sub-Saharan African ratio was estimated to be 62.6. CONCLUSIONS: An overview of abdominal surgery in KZN reveals a high ratio of emergency to elective surgery. This suggests that the current primary health care program is failing to detect and treat acute surgical disease timeously.

Vibrational resonances in driven oscillators with position-dependent mass.

The vibrational resonance (VR) phenomenon has received a great deal of research attention over the two decades since its introduction. The wide range of theoretical and experimental results obtained has, however, been confined to VR in systems with constant mass. We now extend the VR formalism to encompass systems with position-dependent mass (PDM). We consider a generalized classical counterpart of the quantum mechanical nonlinear oscillator with PDM. By developing a theoretical framework for determining the response amplitude of PDM systems, we examine and analyse their VR phenomenona, obtain conditions for the occurrence of resonances, show that the role played by PDM can be both inductive and contributory, and suggest that PDM effects could usefully be explored to maximize the efficiency of devices being operated in VR modes. Our analysis suggests new directions for the investigation of VR in a general class of PDM systems. This article is part of the theme issue 'Vibrational and stochastic resonance in driven nonlinear systems (part 1)'.

Vibrational and stochastic resonances in driven nonlinear systems.

Nonlinear systems are abundant in nature. Their dynamics have been investigated very extensively, motivated partly by their multidisciplinary applicability, ranging from all branches of physical and mathematical sciences through engineering to the life sciences and medicine. When driven by external forces, nonlinear systems can exhibit a plethora of interesting and important properties-one of the most prominent being that of resonance. In the presence of a second, higher frequency, driving force, whether stochastic or deterministic/periodic, a resonance phenomenon arises that can generally be termed stochastic resonance or vibrational resonance. Operating a system in or out of resonance promises applications in several advanced technologies, such as the creation of novel materials at the nano, micro and macroscales including, but not limited to, materials having photonic band gaps, quantum control of atoms and molecules as well as miniature condensed matter systems. Motivated in part by these potential applications, this 2-part Theme Issue provides a concrete up-to-date overview of vibrational and stochastic resonances in driven nonlinear systems. It assembles state-of-the-art, original contributions on such induced resonances-addressing their analysis, occurrence and applications from either the theoretical, numerical or experimental perspectives, or through combinations of these. This article is part of the theme issue 'Vibrational and stochastic resonance in driven nonlinear systems (part 1)'.

Enhancer polymorphisms at the IKZF1 susceptibility locus for acute lymphoblastic leukemia impact B-cell proliferation and differentiation in both Down syndrome and non-Down syndrome genetic backgrounds.

Children with Down syndrome have an approximately 10-fold increased risk of developing acute lymphoblastic leukemia and this risk is influenced by inherited genetic variation. Genome-wide association studies have identified IKZF1 as a strong acute lymphoblastic leukemia susceptibility locus in children both with and without Down syndrome, with association signals reported at rs4132601 in non-Down syndrome and rs58923657 in individuals with Down syndrome (r2 = 0.98 for these two loci). Expression quantitative trait locus analysis in non-Down syndrome lymphoblastoid cell lines has demonstrated an association between the rs4132601 risk allele and decreased IKZF1 mRNA levels. In this study, we provide further mechanistic evidence linking the region encompassing IKZF1-associated polymorphisms to pro-leukemogenic effects in both human lymphoblastoid cell lines and murine hematopoietic stem cells. CRISPR/Cas9-mediated deletion of the region encompassing the rs17133807 major allele (r2 with rs58923657 = 0.97) resulted in significant reduction of IKZF1 mRNA levels in lymphoblastoid cell lines, with a greater effect in Down syndrome versus non-Down syndrome cells. Since rs17133807 is highly conserved in mammals, we also evaluated the orthologous murine locus at rs263378223, in hematopoietic stem cells from the Dp16(1)Yey mouse model of Down syndrome as well as non-Down syndrome control mice. Homozygous deletion of the region encompassing rs263378223 resulted in significantly reduced Ikzf1 mRNA, confirming that this polymorphism maps to a strong murine Ikzf1 enhancer, and resulted in increased B-lymphoid colony growth and decreased B-lineage differentiation. Our results suggest that both the region encompassing rs17133807 and its conserved orthologous mouse locus have functional effects that may mediate increased leukemia susceptibility in both the Down syndrome and non-Down syndrome genetic backgrounds.

Acoustic vibrational resonance in a Rayleigh-Plesset bubble oscillator.

The phenomenon of vibrational resonance (VR) has been investigated in a Rayleigh-Plesset oscillator for a gas bubble oscillating in an incompressible liquid while driven by a dual-frequency force consisting of high-frequency, amplitude-modulated, weak, acoustic waves. The complex equation of the Rayleigh-Plesset bubble oscillator model was expressed as the dynamics of a classical particle in a potential well of the Liénard type, thus allowing us to use both numerical and analytic approaches to investigate the occurrence of VR. We provide clear evidence that an acoustically-driven bubble oscillates in a time-dependent single or double-well potential whose properties are determined by the density of the liquid and its surface tension. We show both theoretically and numerically that, besides the VR effect facilitated by the variation of the parameters on which the high-frequency depends, amplitude modulation, the properties of the liquid in which the gas bubble oscillates contribute significantly to the occurrence of VR. In addition, we discuss the observation of multiple resonances and their origin for the double-well case, as well as their connection to the low frequency, weak, acoustic force field.

Quantum vibrational resonance in a dual-frequency-driven Tietz-Hua quantum well.

We investigate the response of a quantum particle in the Tietz-Hua quantum potential driven by biharmonic fields: a low-frequency force and a very high frequency force. The response is characterized by the occurrence of a maximum in the first-order transition probability amplitude |s|^{2} under the influence of the applied fields. It is shown that in the absence of the high-frequency component of the applied fields, |s|^{2} shows a distinct sequence of resonances, whereas an increase in the amplitude of the high-frequency field induces minima in |s|^{2}. However, the |s|^{2} maximum occurs in the low-frequency regime where it may be considered otherwise weak in the presence of a single harmonic force.

Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome.

Children with Down syndrome (DS) have a 20-fold increased risk of acute lymphoblastic leukemia (ALL) and distinct somatic features, including CRLF2 rearrangement in ∼50% of cases; however, the role of inherited genetic variation in DS-ALL susceptibility is unknown. We report the first genome-wide association study of DS-ALL, comprising a meta-analysis of 4 independent studies, with 542 DS-ALL cases and 1192 DS controls. We identified 4 susceptibility loci at genome-wide significance: rs58923657 near IKZF1 (odds ratio [OR], 2.02; Pmeta = 5.32 × 10-15), rs3731249 in CDKN2A (OR, 3.63; Pmeta = 3.91 × 10-10), rs7090445 in ARID5B (OR, 1.60; Pmeta = 8.44 × 10-9), and rs3781093 in GATA3 (OR, 1.73; Pmeta = 2.89 × 10-8). We performed DS-ALL vs non-DS ALL case-case analyses, comparing risk allele frequencies at these and other established susceptibility loci (BMI1, PIP4K2A, and CEBPE) and found significant association with DS status for CDKN2A (OR, 1.58; Pmeta = 4.1 × 10-4). This association was maintained in separate regression models, both adjusting for and stratifying on CRLF2 overexpression and other molecular subgroups, indicating an increased penetrance of CDKN2A risk alleles in children with DS. Finally, we investigated functional significance of the IKZF1 risk locus, and demonstrated mapping to a B-cell super-enhancer, and risk allele association with decreased enhancer activity and differential protein binding. IKZF1 knockdown resulted in significantly higher proliferation in DS than non-DS lymphoblastoid cell lines. Our findings demonstrate a higher penetrance of the CDKN2A risk locus in DS and serve as a basis for further biological insights into DS-ALL etiology.