Deformation and Breakup of Finite-sized Bubbles in Intense Turbulence

From rain droplets in clouds to entrained gas bubbles in oceans, the majority of fluid mechanics problems in nature and industry are turbulent and consist of multiple phases. In such flows, bubbles and droplets experience complex deformation. Though this deformation occurs at small-scale interfaces, it plays important roles in many large-scale processes e.g. the overall heat and mass transfer in two-phase energy systems. To understand the fundamental physics behind the interaction between turbulence and deformable bubbles, simultaneous 3D measurements of both phases are essential. However, obtaining such measurements is a very challenging task. To address this problem, a unique vertical water tunnel (V-ONSET) capable of generating energetic turbulence is designed. V-ONSET is equipped with six high-speed cameras uniformly distributed around its test section to obtain high-resolution images of both bubbles and the turbulent carrier phase simultaneously. To reconstruct the 3D shapes of bubbles, a new algorithm addressing the limited-angle reconstruction problem by using the physical constraint of minimum surface energy is developed. Moreover, to quantify turbulence, tracer particles in the surrounding flow are tracked with an in-house OpenLPT code. Leveraging such unique simultaneous measurements of bubbles and their surrounding turbulent flow, we investigate the mechanisms in turbulence responsible for the deformation and breakup of bubbles. We identify and evaluate two key mechanisms namely, the coarse-grained turbulent strains and the slip velocity between the two phases. Interestingly, two Weber numbers based on these two mechanisms show that in strong turbulence, the rather ignored mechanism of the slip velocity has a comparable magnitude to the other mechanism of turbulent strains. The distributions of these two Weber numbers are modeled based on turbulent flow characteristics. This also helps to estimate bubble breakup probability in turbulence. Furthermore, we investigate the orientation dynamics of bubbles with respect to the aforementioned deformation mechanisms. It elucidates that bubbles exhibit the strongest alignment with the slip velocity direction indicating the dominant role played by the compression induced by the slip velocity. Finally, a Lagrangian model including both deformation mechanisms is proposed to predict bubble deformation and orientation in turbulence

Bioequivalence evaluation of two capsule formulations of amoxicillin in healthy adult male bangladeshi volunteers: A single-dose, randomized, open-label, two-period crossover study

AbstractBackground: Amoxicillin, a semisynthetic penicillin antibiotic, is widely prescribed in Bangladesh due to its extended spectrum and its rapid and extensive oral absorption with good tolerability. Although a number of generic oral formulations of amoxicillin are available in Bangladesh, a study of the bioequivalence and pharmacokinetic properties of these formulations has not yet been conducted in a Bangladeshi population.Objective: The aim of this study was to assess the pharmacokinetic properties and bioequivalence of 2 formulations of amoxicillin 500-mg capsules (test, SK-mox®; reference, Amoxil-Bencard®) using serum data.Methods: This single-dose, randomized, open-label, 2-period crossover study was conducted in healthy male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were assigned to receive the test or the reference drug as a single-dose, 500-mg capsule under fasting conditions after a 1-week washout period. After oral administration, blood samples were collected and analyzed for amoxicillin concentration using a validated high-performance liquid chromatography method. The pharmacokinetic parameters were determined using a noncompartmental method. The formulations were considered bioequivalent if the natural log-transformed ratios of pharmacokinetic parameters were within the predetermined equivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement.Results: Twenty-four healthy adult male Bangladeshi volunteers (mean [SD] age, 26.92 [3.37] years; age range, 23–34 years; mean [SD] body mass index, 23.O9 [1.58] kg/m2) participated in the study. Using serum data, the values obtained for the test and reference formulations, respectively, were as follows: Cmax, 9.85 (2.73) and 10.63 (2.12) μg/mL; Tmax, 1.29 (0.58) and 1.33 (0.49) hours; and AUC0–12, 27.09 (7.62) and 28.56 (6.30) μg/mL · h−1. No period, sequence, or formulation effects were observed; however, significant variation was found among subjects with regard to AUC0–12 (P < 0.001), AUC0−∞ (P = 0.002), area under the moment curve (AUMC) from 0 to 12 hours (P < 0.001), and AUMC0−∞ (P = 0.017). All CIs for the parameters measured were within the FDA-accepted limits of 80% to 125%.Conclusion: The present study suggests that the test 500-mg amoxicillin capsule was bioequivalent to the reference 500-mg capsule according to the FDA regulatory definition, in this population of healthy adult male Bangladeshi volunteers

Genetic Revelation of the Potentially Malignant Disorders in the Oral and Maxillofacial Region

The oral and maxillofacial region is the site of numerous cancer forms. The most frequent cancer, which accounts for more than 90% of these tumors, is squamous cell carcinoma. Genetic changes caused by malignant transformation later result in phenotypic changes in cells. Potentially malignant disorders and circumstances can lead to the development of some malignancies, such as oral squamous cell carcinomas (OSCCs). Because OSCC and precursor lesions cannot be detected early, the 5-year survival rate for OSCC is still only about 50%. Early detection of oral cancer, particularly in the premalignant stage, can greatly reduce death and morbidity. The clinical, histological revelations and etiopathogenesis of a few potentially malignant disorders of the oral and maxillofacial region are reviewed in this chapter

Respiratory Syncytial Virus infection promotes necroptosis and HMGB1 release by airway epithelial cells

Rationale: Respiratory syncytial virus (RSV) bronchiolitis causes significant infant mortality. Bronchiolitis is characterized by airway epithelial cell (AEC) death; however, the mode of death remains unknown. Objectives: To determine whether necroptosis contributes to RSV b r onchiolitis pathogenesis via HMGB1 (high mobility group box 1) release. Methods: Nasopharyngeal samples were collected from children presenting to the hospital with acute respiratory infection. Primary human AECs and neonatal mice were inoculated with RSV and murine Pneumovirus, respectively. Necroptosis was determined via viability assays and immunohistochemistry for RIPK1 (receptor-interacting protein kinase-1), MLKL (mixed lineage kinase domain-like pseudokinase) protein, and caspase-3. Necroptosis was blocked using pharmacological inhibitors and RIPK1 kinase-dead knockin mice. Measurements and Main Results: HMGB1 levels were elevated in nasopharyngeal samples of children with acute RSV infection. RSV-induced epithelial cell death was associated with increased phosphorylated RIPK1 and phosphorylated MLKL but not active caspase-3 expression. Inhibition of RIPK1 or MLKL attenuated RSV-induced HMGBI translocation and release, and lowered viral load. MLKL inhibition increased active caspase-3 expression in a caspase-8/9-dependent manner. In susceptible mice, Pneumovirus infection upregulated RIPK1 and MLKL expression in the airway epithelium at 8 to 10 days after infection, coinciding with AEC sloughing, HMGB1 release, and neutrophilic inflammation. Genetic or pharmacological inhibition of RIPK1 or MLKL attenuated these pathologies, lowered viral load, and prevented type 2 inflammation and airway remodeling. Necroptosis inhibition in early life ameliorated asthma progression induced by viral or allergen challenge in later life. Conclusions: Pneumovirus infection induces AEC necroptosis. Inhibition of necroptosis may be a viable strategy to limit the severity of viral bronchiolitis and break its nexus with asthma

Novel mechanisms of airway inflammation in mouse models of allergen and virus-induced asthma

Asthma is a heterogeneous disorder encompassing distinct clinical phenotypes thought to be mediated by distinct mechanisms. The Receptor for Advanced Glycation End products (RAGE) is a pattern-recognition receptor capable of ‘sensing’ exogenous and endogenous molecules; and there is evidence that ligand-RAGE axis is activated in asthma. We investigated the role of RAGE and its ligand high-mobility group box-1 (HMGB1) in the inception and progression of allergen and virus-induced asthma using mouse models. We demonstrate that RAGE is a critical mediator of allergic airway sensitization induced by house dust mite (HDM) and cockroach (CR) allergens. Our studies suggest that RAGE is engaged secondary to the release of HMGB1 by airway epithelial cells; and that HMGB1-RAGE signalling drives type 2 immunity and airway inflammation. RAGE is also required for anti-viral immunity to pneumonia virus of mice (PVM) (equivalent to human respiratory syncytial virus). PVM infection in RAGE-deficient mice led to increased HMGB1 expression in the airways; this contributed to the development of an asthma-like pathology characterised by airway smooth muscle remodelling, airways hyperresponsiveness and the absence of granulocytic inflammation, representing a pauci-granulocytic phenotype of human asthma. In separate studies we investigated whether an anti-IL-6 receptor (IL-6R) antibody protects against allergic airway inflammation. Intriguingly, anti-IL-6R protected against CR-induced airway inflammation but exacerbated the airway inflammatory response to HDM. This differential response was related to differential activation of IL-6 signalling mechanisms in response to CR and HDM. The studies herein expose novel molecular mechanisms that may explain the development of specific phenotypes of human asthma in response to viral or allergic triggers. Selective targeting of these pathways in appropriate patient sub-groups may lead to better outcomes in asthma management

Deformation and Breakup of Finite-sized Bubbles in Intense Turbulence

From rain droplets in clouds to entrained gas bubbles in oceans, the majority of fluid mechanics problems in nature and industry are turbulent and consist of multiple phases. In such flows, bubbles and droplets experience complex deformation. Though this deformation occurs at small-scale interfaces, it plays important roles in many large-scale processes e.g. the overall heat and mass transfer in two-phase energy systems. To understand the fundamental physics behind the interaction between turbulence and deformable bubbles, simultaneous 3D measurements of both phases are essential. However, obtaining such measurements is a very challenging task. To address this problem, a unique vertical water tunnel (V-ONSET) capable of generating energetic turbulence is designed. V-ONSET is equipped with six high-speed cameras uniformly distributed around its test section to obtain high-resolution images of both bubbles and the turbulent carrier phase simultaneously. To reconstruct the 3D shapes of bubbles, a new algorithm addressing the limited-angle reconstruction problem by using the physical constraint of minimum surface energy is developed. Moreover, to quantify turbulence, tracer particles in the surrounding flow are tracked with an in-house OpenLPT code. Leveraging such unique simultaneous measurements of bubbles and their surrounding turbulent flow, we investigate the mechanisms in turbulence responsible for the deformation and breakup of bubbles. We identify and evaluate two key mechanisms namely, the coarse-grained turbulent strains and the slip velocity between the two phases. Interestingly, two Weber numbers based on these two mechanisms show that in strong turbulence, the rather ignored mechanism of the slip velocity has a comparable magnitude to the other mechanism of turbulent strains. The distributions of these two Weber numbers are modeled based on turbulent flow characteristics. This also helps to estimate bubble breakup probability in turbulence. Furthermore, we investigate the orientation dynamics of bubbles with respect to the aforementioned deformation mechanisms. It elucidates that bubbles exhibit the strongest alignment with the slip velocity direction indicating the dominant role played by the compression induced by the slip velocity. Finally, a Lagrangian model including both deformation mechanisms is proposed to predict bubble deformation and orientation in turbulence

Functional reconstitution of natural killer cells in allogeneic hematopoietic stem cell transplantation

Natural killer (NK) cells are the first lymphocyte population to reconstitute following allogeneic hematopoietic stem cell transplantation (HSCT) and are important in mediating immunity against both leukemia and pathogens. Although NK cell numbers generally reconstitute within a month, the acquisition of mature NK cell phenotype and full functional competency can take 6 months or more, and is influenced by graft composition, concurrent pharmacologic immunosuppression, graft-versus-host disease, and other clinical factors. In addition, cytomegalovirus infection and reactivation have a dominant effect on NK cell memory imprinting following allogeneic HSCT just as it does in healthy individuals. Our understanding of NK cell education and licensing has evolved in the years since the "missing self" hypothesis for NK-mediated graft-versus-leukemia effect was first put forward. For example, we now know that NK cell "re-education" can occur, and that unlicensed NK cells can be more protective than licensed NK cells in certain settings, thus raising new questions about how best to harness graft-versus-leukemia effect. Here, we review current understanding of the functional reconstitution of NK cells and NK cell education following allogeneic HSCT, highlighting a conceptual framework for future researc

Leveraging graph theory approach for managing design principles for sustainable manufacturing of industry 4.0: A case study of electrical equipment manufacturing industry

Analyzing design principles and supply chain sustainability are critical for organizational success in today's competitive marketplace. The process of evaluating an organization's supply chain design principles and manufacturing sustainability entails incorporating various sources of information, which are typically uncertain, incomplete, and subjective in nature. Particularly when various organizations are confronted with significant principles such as a lack of interoperability, decentralization, virtualization, real-time and capabilities, service orientation, and so on. Using graph theory and a matrix approach (GTMA), this article attempts to analyze the interaction between design principles-related factors with a focus on operational excellence, growth and sustainability in supply chains by considering the business of Industry 4.0. We have considered electrical equipment manufacturing Industry 4.0 as test ground. Based on a literature review and expert opinions, we identified several key principles, and then explored the most significant one using graph theory and a matrix approach. The findings indicate that autonomy has been evaluated as the most significant challenge to manage design principles most effectively for sustainable manufacturing in the Industry 4.0 context. Therefore, organizations must enhance autonomous systems capable of operating and making decisions alone, without relying on external instructions or support, in order to achieve sustainability. This and the other identified principles to achieving corporate supply chain sustainability are ranked in this paper. These findings will be useful for managers and policymakers managing the interaction between people and processes, as well as corporate sustainability management in Industry 4.0-based supply chain organizations. The unique contributions of this paper can aid in the improvement of design principles and the sustainability of emerging economies' Industry 4.0 perspectives