Study of the K_{L}→π

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Professor Serara Kupe-Mogwe's contribution to development of the nursing profession in Botswana.

BACKGROUND: The aim of this communication is to pay tribute to a nursing pioneer of our time, Professor Serara Kupe-Mogwe, for her outstanding contribution to development of the nursing profession in Botswana. I pay this tribute in response to the World Health Organization's declaration of 2020 as the Year of the Nurse and the Midwife. METHODS: Data supporting this manuscript were obtained through Internet searches, local newspapers, and interviews with those who knew her. RESULTS: Kupe-Mogwe's contributions to nursing in Botswana are presented. CONCLUSION: The legacy she has left is celebrated and should be remembered. IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY: The findings have implications for nursing education, nursing leadership, and acknowledgment of women and their contribution.

Search for K_{L}→π

A search for the rare decay K_{L}→π^{0}νν[over ¯] was performed. With the data collected in 2015, corresponding to 2.2×10^{19} protons on target, a single event sensitivity of (1.30±0.01_{stat}±0.14_{syst})×10^{-9} was achieved and no candidate events were observed. We set an upper limit of 3.0×10^{-9} for the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K_{L}→π^{0}X^{0} was also set as 2.4×10^{-9} at the 90% C.L., where X^{0} is an invisible boson with a mass of 135 MeV/c^{2}.

Realization by impedance discontinuity of a unidirectional wave in a duct with harmonically perturbed uniform mean flow.

This paper presents a study of intentionally induced acoustic mode complexity in rigid-walled ducts of separable geometry and with uniform mean flow. An intermediately located perforated plate conceptualized as an impedance discontinuity is employed to maximize the acoustic mode complexity, in turn producing a unidirectional traveling wave from the source to the impedance discontinuity. The impedance of the perforated plate for realization of a unidirectional traveling wave is derived analytically and is found to be a function of the modal wavenumbers, the Mach number of the mean flow, the position of the perforated plate, and the termination impedance. The conditions derived analytically are verified computationally by finite element analysis. A measure of acoustic mode complexity is defined and also evaluated from the finite element analysis. It is found that the realization of a unidirectional traveling wave is robust at low Mach number mean flows, except at the occurrence of resonances. The method presented in this work provides a strategy to control the transmission of acoustic energy in rigid-walled ducts of separable geometry in the presence of uniform mean flow.

Inducing a nonreflective airborne discontinuity in a circular duct by using a nonresonant side branch to create mode complexity.

A nonreflective airborne discontinuity is created in a one-dimensional rigid-walled duct when the mode complexity introduced by a nonresonant side branch reaches a maximum, so that a sound wave can be spatially separated into physical regions of traveling and standing waves. The nonresonance of the side branch is demonstrated, the mode complexity is quantified, and a computational method to optimize side-branch parameters to maximize mode complexity in the duct in the presence of three-dimensional effects is presented. The optimal side-branch parameters that maximize the mode complexity and thus minimize reflection are found using finite element analysis and a derivative-free optimization routine. Sensitivity of mode complexity near the optimum with respect to side-branch parameters is then examined. The results show reflection from the impedance discontinuity in the duct can be reduced nearly to zero, providing a practical means of achieving a nonreflective discontinuity for a plane wave propagating in a duct of finite length.

Targeted energy transfer and modal energy redistribution in automotive drivetrains.

The new generations of compact high output power-to-weight ratio internal combustion engines generate broadband torsional oscillations, transmitted to lightly damped drivetrain systems. A novel approach to mitigate these untoward vibrations can be the use of nonlinear absorbers. These act as Nonlinear Energy Sinks (NESs). The NES is coupled to the primary (drivetrain) structure, inducing passive irreversible targeted energy transfer (TET) from the drivetrain system to the NES. During this process, the vibration energy is directed from the lower-frequency modes of the structure to the higher ones. Thereafter, vibrations can be either dissipated through structural damping or consumed by the NES. This paper uses a lumped parameter model of an automotive driveline to simulate the effect of TET and the assumed modal energy redistribution. Significant redistribution of vibratory energy is observed through TET. Furthermore, the integrated optimization process highlights the most effective configuration and parametric evaluation for use of NES.

Utilizing intentional internal resonance to achieve multi-harmonic atomic force microscopy.

During dynamic atomic force microscopy (AFM), the deflection of a scanning cantilever generates multiple frequency terms due to the nonlinear nature of AFM tip-sample interactions. Even though each frequency term is reasonably expected to encode information about the sample, only the fundamental frequency term is typically decoded to provide topographic mapping of the measured surface. One of main reasons for discarding higher harmonic signals is their low signal-to-noise ratio. Here, we introduce a new design concept for multi-harmonic AFM, exploiting intentional nonlinear internal resonance for the enhancement of higher harmonics. The nonlinear internal resonance, triggered by the non-smooth tip-sample dynamic interactions, results in nonlinear energy transfers from the directly excited fundamental bending mode to the higher-frequency mode and, hence, enhancement of the higher harmonic of the measured response. It is verified through detailed theoretical and experimental study that this AFM design can robustly incorporate the required internal resonance and enable high-frequency AFM measurements. Measurements on an inhomogeneous polymer specimen demonstrate the efficacy of the proposed design, namely that the higher harmonic of the measured response is capable of enhanced simultaneous topography imaging and compositional mapping, exhibiting less crosstalk with an abrupt height change.

Complex nonlinear dynamics in the limit of weak coupling of a system of microcantilevers connected by a geometrically nonlinear tunable nanomembrane.

Intentional utilization of geometric nonlinearity in micro/nanomechanical resonators provides a breakthrough to overcome the narrow bandwidth limitation of linear dynamic systems. In past works, implementation of intentional geometric nonlinearity to an otherwise linear nano/micromechanical resonator has been successfully achieved by local modification of the system through nonlinear attachments of nanoscale size, such as nanotubes and nanowires. However, the conventional fabrication method involving manual integration of nanoscale components produced a low yield rate in these systems. In the present work, we employed a transfer-printing assembly technique to reliably integrate a silicon nanomembrane as a nonlinear coupling component onto a linear dynamic system with two discrete microcantilevers. The dynamics of the developed system was modeled analytically and investigated experimentally as the coupling strength was finely tuned via FIB post-processing. The transition from the linear to the nonlinear dynamic regime with gradual change in the coupling strength was experimentally studied. In addition, we observed for the weakly coupled system that oscillation was asynchronous in the vicinity of the resonance, thus exhibiting a nonlinear complex mode. We conjectured that the emergence of this nonlinear complex mode could be attributed to the nonlinear damping arising from the attached nanomembrane.

The effect of nutritional status and muscle fiber type on myogenic satellite cell fate and apoptosis.

Satellite cells (SC) are multipotential stem cells that can be induced by nutrition to alter their cellular developmental fate, which may vary depending on their fiber type origin. The objective of the current study was to determine the effect of restricting protein synthesis on inducing adipogenic transdifferentiation and apoptosis of SC originating from fibers of the fast glycolytic pectoralis major (p. major) and fast oxidative and glycolytic biceps femoris (b. femoris) muscles of the chicken. The availability of the essential sulfur amino acids Met and Cys was restricted to regulate protein synthesis during SC proliferation and differentiation. The SC were cultured and treated with 1 of 6 Met/Cys concentrations: 60/192, 30/96 (control), 7.5/24, 3/9.6, 1/3.2, or 0/0 mg/L. Reductions in Met/Cys concentrations from the control level resulted in increased lipid staining and expression of the adipogenic marker genes peroxisome proliferator-activated receptor gamma and stearoyl-CoA desaturase during differentiation in the p. major SC. Although b. femoris SC had increased lipid staining at lower Met/Cys concentrations, there was no increase in expression of either adipogenic gene. For both muscle types, SC Met/Cys, concentration above the control increased the expression of peroxisome proliferator-activated receptor gamma and stearoyl-CoA desaturase during differentiation. As Met/Cys concentration was decreased during proliferation, a dose-dependent decline in all apoptotic cells occurred except for early apoptotic cells in the p. major, which had no treatment effect (P < 0.05). During differentiation, decreasing Met/Cys concentration caused an increase in early apoptotic cells in both fiber types and no effect on late apoptotic cells except for an increase in the p. major 7.5/24 mg/L of Met/Cys treatment. In general, the viability of the SC was unaffected by the Met/Cys concentration except during proliferation in the p. major 0/0 mg/L of Met/Cys treatment, which increased SC viability. These data demonstrate the effect of nutrition on SC transdifferentiation to an adipogenic lineage and apoptosis, and the effect of fiber type on this response in an in vitro context.

The effect of nutritional status on myogenic gene expression of satellite cells derived from different muscle types.

Satellite cells (SC) are a multipotential stem cell population responsible for facilitating posthatch muscle fiber hypertrophy. The proliferation and differentiation of SC is sensitive to nutritional regimen, and the SC response to nutrition varies depending upon their muscle type of origin. The objective of the current study was to determine the effect of altering protein synthesis on the expression of several key genes regulating SC activity and the effect of muscle type. Satellite cells isolated from the fast glycolytic pectoralis major and the fast oxidative and glycolytic biceps femoris were studied. These genes included the myogenic regulatory factors myogenic determination factor 1 (MyoD) and myogenin, the cell-membrane associated proteoglycans syndecan-4 and glypican-1, the extracellular matrix proteoglycan decorin, and the transcription factor paired box 7. Protein synthesis potential varied by the concentration of the sulfur amino acids Met and Cys during SC proliferation and differentiation. The SC were cultured and treated with 1 of 6 Met/Cys concentrations: 60/192, 30/96 (control), 7.5/24, 3.0/9.6, 1.0/3.2, or 0/0 mg/L. A consistent pattern of gene expression emerged following Met/Cys manipulation as increasing reductions in mRNA expression for all genes were observed as Met/Cys concentration decreased, whereas increased Met/Cys concentration caused either no change or had a small negative effect on mRNA expression. Reduced paired box 7 expression would limit myogenic specification of SC, whereas decreased myogenic regulatory factor expression would affect subsequent myogenic development of the SC. Decreased levels of decorin affect SC response to growth factors like myostatin and transforming growth factor ß, and extracellular matrix organization. These data highlight the importance of nutrition on the expression of genes critical for satellite cell activation, proliferation and differentiation, and growth factor signal transduction.

Modulation of turkey myogenic satellite cell differentiation through the shedding of glypican-1.

Glypican-1 is a cell membrane heparan sulfate proteoglycan. It is composed of a core protein with covalently attached glycosaminoglycan, and N-linked glycosylated (N-glycosylated) chains, and is attached to the cell membrane by a glycosylphosphatidylinositol (GPI) linkage. Glypican-1 plays a key role in the growth and development of muscle by regulating fibroblast growth factor 2 (FGF2). The GPI anchor of glypican-1 can be cleaved, resulting in glypican-1 being secreted or shed into the extracellular matrix environment. The objective of the current study was to investigate the role of glypican-1 shedding and the glycosaminoglycan and N-glycosylated chains in regulating the differentiation of turkey myogenic satellite cells. A glypican-1 construct without the GPI anchor was cloned into the mammalian expression vector pCMS-EGFP, and glypican-1 without the GPI anchor and glycosaminoglycan and N-glycosylated chains were also cloned. These constructs were co-transfected into turkey myogenic satellite cells with a small interference RNA targeting the GPI anchor of endogenous glypican-1. The soluble glypican-1 mutants were not detected in the satellite cells but in the cell medium, suggesting the secretion of the soluble glypican-1 mutants. Soluble glypican-1 increased satellite cell differentiation and enhanced myotube formation in the presence of exogenous FGF2. The increase in differentiation was supported by the elevated expression of myogenin. In conclusion, the shedding of glypican-1 from the satellite cell surface acts as a positive regulator of satellite cell differentiation and sequesters FGF2, permitting further differentiation.

Adenovirus-mediated interference of FABP4 regulates mRNA expression of ADIPOQ, LEP and LEPR in bovine adipocytes.

Fatty acid binding protein 4 (FABP4) is an important adipocyte gene, with roles in fatty acid transport and fat deposition in animals as well as human metabolic syndrome. However, little is known about the functional regulation of FABP4 at the cellular level in bovine. We designed and selected an effective shRNA (small hairpin RNA) against bovine FABP4, constructed a corresponding adenovirus (AD-FABP4), and then detected its influence on mRNA expression of four differentiation-related genes (PPAR(y), CEBPA, CEBPB, and SREBF1) and three lipid metabolism-related genes (ADIPOQ, LEP and LEPR) of adipocytes. The FABP4 mRNA content, derived from bovine adipocytes, decreased by 41% (P < 0.01) after 24 h and 66% (P < 0.01) after 72 h of AD-FABP4 infection. However, lower mRNA content of FABP4 did not significantly alter levels of differentiation-related gene expression at 24 h following AD-FABP4 treatment of bovine-derived preadipocytes (P = 0.54, 0.78, 0.89, and 0.94, respectively). Meanwhile, knocking down (partially silencing) FABP4 significantly decreased ADIPOQ (P < 0.05) and LEP (P < 0.01) gene expression after 24 h of AD-FABP4 treatment, decreased ADIPOQ (P < 0.01) and LEP (P < 0.01) gene expression, but increased LEPR mRNA expression (P < 0.01) after a 72-h treatment of bovine preadipocytes. We conclude that FABP4 plays a role in fat deposition and metabolic syndrome by regulating lipid metabolism-related genes (such as ADIPOQ, LEP and LEPR), without affecting the ability of preadipocytes to differentiate into adipocytes.

The effect of nutritional status on myogenic satellite cell proliferation and differentiation.

Early posthatch satellite cell (SC) mitotic activity is a critical component of muscle development and growth. Satellite cells are stem cells that can be induced by nutrition to follow other cellular developmental pathways. The objective of the current study was to determine the effect of restricting protein synthesis on the proliferation and differentiation of SC, using variable concentrations of Met and Cys to modulate protein synthesis. Broiler pectoralis major SC were cultured and treated with 1 of 6 different Met/Cys concentrations: 60/192, 30/96 (control), 7.5/24, 3/9.6, 1/3.2, or 0/0 mg/L. The effect of Met/Cys concentration on SC proliferation and differentiation was measured, and myonuclear accretion was measured by counting the number of nuclei per myotube during differentiation. The 30/96 mg/L Met/Cys treatment resulted in the highest rate of proliferation compared with all other treatments by 72 h of proliferation (P < 0.05). Differentiation was measured with Met/Cys treatments only during proliferation and the cultures receiving normal differentiation medium (R/N), normal proliferation medium and differentiation medium with variable Met/Cys (N/R), or both proliferation and differentiation receiving variable Met/Cys treatments (R/R). Differentiation responded in a dose-dependent manner to Met/Cys concentration under all 3 of these treatment regimens, with a degree of recovery in the R/N regimen cells following reinstatement of the control medium. Reductions in both proliferation and differentiation were more pronounced as Met/Cys concentrations were further reduced, whereas increased differentiation was observed under the increased Met/Cys concentration treatment when applied during differentiation in the N/R and R/R regimens. The number of nuclei per myotube was significantly decreased in the severely Met/Cys restricted treatments (P < 0.05). These data demonstrate the sensitivity of pectoralis major SC to nutritional availability and the importance of optimal nutrition during both proliferation and differentiation for maximizing SC activity, which will affect subsequent muscle mass accretion.

Heparan sulfate proteoglycans, syndecan-4 and glypican-1, differentially regulate myogenic regulatory transcription factors and paired box 7 expression during turkey satellite cell myogenesis: implications for muscle growth.

The heparan sulfate proteoglycans have been shown to play essential roles in the proliferation and differentiation of myogenic satellite cells. Myogenic regulatory factors (MRF) and paired box 7 (Pax7) are essential transcription factors for satellite cell myogenesis. The objective of the current study was to investigate whether the expression of the MRF and Pax7 is, in part, regulated by the heparan sulfate proteoglycans, syndecan-4, and glypican-1, whose expression has been shown to differentially affect satellite cell proliferation and differentiation. To test this objective, small interfering RNA was used to knockdown the gene expression of glypican-1 and syndecan-4. The effect on the expression of MRF and Pax7 was measured at the mRNA level by real-time quantitative PCR. The knockdown of the glypican-1 gene decreased mRNA expression of MyoD, myogenin, MRF4, and Pax7 expression during proliferation and differentiation of turkey satellite cells; whereas knockdown of the syndecan-4 gene increased mRNA expression of MyoD and MRF4 expression during cell proliferation but not during differentiation and had no effect on myogenin and Pax7 expression. These data suggested that the precise expression of the MRF are dependent upon the appropriate expression of glypican-1 and syndecan-4 during satellite cell proliferation and differentiation, and Pax7 expression is influenced by glypican-1.

Cost-effectiveness of triple drug administration (TDA) with praziquantel, ivermectin and albendazole for the prevention of neglected tropical diseases in Nigeria.

Onchocerciasis, lymphatic filariasis (LF), schistosomiasis and soil transmitted, helminthiasis (STH) are all co-endemic in Nigeria. Annual mass drug administration (MDA) with ivermectin (for onchocerciasis), albendazole (for STH and with ivermectin for LF) and praziquantel (for schistosomiasis) is the WHO-recommended treatment strategy for preventive chemotherapy. Separate delivery rounds for distribution of these drugs have been the usual approach to MDA. All three drugs, however, have now been shown to be clinically and programmatically safe for co-administration with what has come to be known as triple drug administration (TDA). We examined the cost savings of converting from separate delivery rounds to TDA in two states in Nigeria. In 2008, eight local government areas received a single round of ivermectin with albendazole followed at least 1 week later by a single round of praziquantel to school-aged children. The following year, a single round was administered with TDA. The number of treated individuals was essentially unchanged during both years (1,301,864 in 2008 and 1,297,509 in 2009) and no change in adverse events was reported. The total programmatic costs for the MDA, not including drug and overhead costs, reduced by 41% from $123,624 to $72,870. Cost savings were limited in larger populations due to economies of scale. TDA is recommended for mature MDA.

Tunable, broadband nonlinear nanomechanical resonator.

A nanomechanical resonator incorporating intrinsically geometric nonlinearity and operated in a highly nonlinear regime is modeled and developed. The nanoresonator is capable of extreme broadband resonance, with tunable resonance bandwidth up to many times its natural frequency. Its resonance bandwidth and drop frequency (the upper jump-down frequency) are found to be very sensitive to added mass and energy dissipation due to damping. We demonstrate a prototype nonlinear mechanical nanoresonator integrating a doubly clamped carbon nanotube and show its broadband resonance over tens of MHz (over 3 times its natural resonance frequency) and its sensitivity to femtogram added mass at room temperature.

Perspectives on the formation of an interdisciplinary research team.

As research funding becomes more competitive, it will be imperative for researchers to break the mentality of a single laboratory/single research focus and develop an interdisciplinary research team aimed at addressing real world challenges. Members of this team may be at the same institution, may be found regionally, or may be international. However, all must share the same passion for a topic that is bigger than any individual's research focus. Moreover, special consideration should be given to the professional development issues of junior faculty participating in interdisciplinary research teams. While participation may be "humbling" at times, the sheer volume of research progress that may be achieved through interdisciplinary collaboration, even in light of a short supply of grant dollars, is remarkable.

Effect of glypican-1 covalently attached chains on turkey myogenic satellite cell proliferation, differentiation, and fibroblast growth factor 2 responsiveness.

Glypican-1 is a cell membrane heparan sulfate proteoglycan that is composed of a core protein and covalently attached glycosaminoglycan (GAG) chains and N-linked glycosylated (N-glycosylated) chains. The glypican-1 GAG chains are required for cell differentiation and responsiveness to fibroblast growth factor 2 (FGF2). The role of glypican-1 N-glycosylated chains in regulating cell activities has not been reported. The objective of the current study was to investigate the role of glypican-1 N-glycosylated chains and the interaction between N-glycosylated and GAG chains in turkey myogenic satellite cell proliferation, differentiation, and FGF2 responsiveness. The wild-type turkey glypican-1 and turkey glypican-1 with mutated GAG chain attachment sites were cloned into the pCMS-EGFP mammalian expression vector and were used as templates to generate glypican-1 N-glycosylated 1-chain and no-chain mutants with or without GAG chains by site-directed mutagenesis. The wild-type glypican-1 and all glypican-1 N-glycosylated 1-chain and no-chain mutants with or without GAG chains were transfected into turkey myogenic satellite cells. Cell proliferation, differentiation, and FGF2 responsiveness were measured. The overexpression of glypican-1 N-glycosylated 1-chain and no-chain mutants without GAG chains increased cell proliferation and differentiation compared with the wild-type glypican-1 but not the glypican-1 N-glycosylated mutants with GAG chains attached. Cells overexpressing glypican-1 N-glycosylated mutants with or without GAG chains increased cell responsiveness to FGF2 compared with wild-type glypican-1. These data suggest that glypican-1 N-glycosylated chains and GAG chains are critical in regulating turkey myogenic satellite cell proliferation, differentiation, and responsivness to FGF2.

Changes in satellite cell proliferation and differentiation during turkey muscle development.

Posthatch muscle growth is determined by the activation, differentiation, and fusion of satellite cells. Satellite cells composing an individual muscle are heterogeneous, which will differentially affect muscle growth. The proliferation and differentiation of turkey primary pectoralis major muscle cells were investigated in vitro at 1 d of age and at 4, 8, 16, 26, 35, 45, and 54 wk of age. The turkey was selected for these studies because turkey skeletal muscle fibroblasts do not grow in primary muscle cell cultures. Results from the proliferation analysis showed a decrease in proliferation by 8 wk of age. Differentiation into myotubes was significantly decreased by 4 wk of age and myotube diameter was decreased. The changes in muscle weight relative to total BW were measured for the anterior latissimus dorsi, biceps brachii, pectoralis major, sartorius, biceps femoris, and gastrocnemius muscles to compare the relative growth of different muscles. The age at which the muscles reached their maximum relative weight was muscle-dependent, with the biceps brachii plateauing the earliest at 4 wk and the sartorius the latest at 45 wk of age. These data suggested that changes in myogenic cells begin to occur early in muscle development and the activity of the satellite cells during these initial stages of posthatch growth is critical in overall muscle mass accumulation.

The journey through Pick's Disease with a loved one: a personal account.

BACKGROUND: The aim of this short communication is to share my personal experience of caring for a terminally ill family member who was afflicted with Pick's disease. I tell my story in the hope of increasing society's awareness on this little known but devastating disease and assisting those who might be facing a similar situation. Pick's disease is a rare and incurable type of dementia that is associated with atrophy of the frontal and temporal lobes of the brain over time as a result of accumulation of tau protein fibres known as Pick's bodies. The exact cause is not known, but genetic predisposition is implicated in some disease cases. Pick's disease tends to affect men and women alike. It affects thinking, language and problem solving. METHODS: Data supporting this document were obtained from a thorough review of the literature and Internet search on Pick's disease, as well as from a personal experience with Pick's disease as it was unfolding. RESULTS: Clinical features, diagnosis and treatment, and stages of the disease are presented. CONCLUSION: Very little is known about Pick's disease. Additional research is needed to inform practice about tau protein dementias.