North Carolina Central University

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data for in vivo tests. In this review, we discuss the characteristics of 3D cell culture systems in comparison to the two-dimensional (2D) monolayer culture, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles. The innovations and development in 3D culture systems for drug discovery over the past 5 years are also reviewed in the article, emphasizing the cellular response to different classes of anticancer drugs, focusing particularly on similarities and differences between 3D and 2D models across the field. The progression and advancement in the application of 3D cell cultures in cell-based biosensors is another focal point of this review.

Packing problems, such as how densely objects can fill a volume, are among the most ancient and persistent problems in mathematics and science. For equal spheres, it has only recently been proved that the face-centered cubic lattice has the highest possible packing fraction phi=pi/18 approximately 0.74. It is also well known that certain random (amorphous) jammed packings have phi approximately 0.64. Here, we show experimentally and with a new simulation algorithm that ellipsoids can randomly pack more densely-up to phi= 0.68 to 0.71 for spheroids with an aspect ratio close to that of M&M's Candies-and even approach phi approximately 0.74 for ellipsoids with other aspect ratios. We suggest that the higher density is directly related to the higher number of degrees of freedom per particle and thus the larger number of particle contacts required to mechanically stabilize the packing. We measured the number of contacts per particle Z approximately 10 for our spheroids, as compared to Z approximately 6 for spheres. Our results have implications for a broad range of scientific disciplines, including the properties of granular media and ceramics, glass formation, and discrete geometry.

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.

We present an improved search for neutrinoless double-beta (0νββ) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>1.07×10^{26} yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.

The KamLAND experiment has determined a precise value for the neutrino oscillation parameter $\ensuremath{\Delta}{m}_{21}^{2}$ and stringent constraints on ${\ensuremath{\theta}}_{12}$. The exposure to nuclear reactor antineutrinos is increased almost fourfold over previous results to $2.44\ifmmode\times\else\texttimes\fi{}{10}^{32}\text{ }\text{ }\mathrm{proton}\text{ }\mathrm{yr}$ due to longer livetime and an enlarged fiducial volume. An undistorted reactor ${\overline{\ensuremath{\nu}}}_{e}$ energy spectrum is now rejected at $>5\ensuremath{\sigma}$. Analysis of the reactor spectrum above the inverse beta decay energy threshold, and including geoneutrinos, gives a best fit at $\ensuremath{\Delta}{m}_{21}^{2}={7.58}_{\ensuremath{-}0.13}^{+0.14}(\mathrm{stat}{)}_{\ensuremath{-}0.15}^{+0.15}(\mathrm{syst})\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}\text{ }\text{ }{\mathrm{eV}}^{2}$ and ${tan}^{2}{\ensuremath{\theta}}_{12}={0.56}_{\ensuremath{-}0.07}^{+0.10}(\mathrm{stat}{)}_{\ensuremath{-}0.06}^{+0.10}(\mathrm{syst})$. Local $\ensuremath{\Delta}{\ensuremath{\chi}}^{2}$ minima at higher and lower $\ensuremath{\Delta}{m}_{21}^{2}$ are disfavored at $>4\ensuremath{\sigma}$. Combining with solar neutrino data, we obtain $\ensuremath{\Delta}{m}_{21}^{2}={7.59}_{\ensuremath{-}0.21}^{+0.21}\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}\text{ }\text{ }{\mathrm{eV}}^{2}$ and ${tan}^{2}{\ensuremath{\theta}}_{12}={0.47}_{\ensuremath{-}0.05}^{+0.06}$.

A 14.6-kilogram sodium-doped CsI scintillator is used to detect a neutrino scattering process with a 6.7σ confidence level.

The ratio of the proton's elastic electromagnetic form factors, ${G}_{{E}_{p}}{/G}_{{M}_{p}}$, was obtained by measuring ${P}_{t}$ and ${P}_{\ensuremath{\ell}}$, the transverse and the longitudinal recoil proton polarization, respectively. For elastic $\stackrel{\ensuremath{\rightarrow}}{e}p\ensuremath{\rightarrow}e\stackrel{\ensuremath{\rightarrow}}{p}$, ${G}_{{E}_{p}}{/G}_{{M}_{p}}$ is proportional to ${P}_{t}{/P}_{\ensuremath{\ell}}$. Simultaneous measurement of ${P}_{t}$ and ${P}_{\ensuremath{\ell}}$ in a polarimeter provides good control of the systematic uncertainty. The results for the ratio ${G}_{{E}_{p}}{/G}_{{M}_{p}}$ show a systematic decrease as ${Q}^{2}$ increases from 0.5 to $3.5{\mathrm{GeV}}^{2}$, indicating for the first time a definite difference in the spatial distribution of charge and magnetization currents in the proton.

Estimating human age automatically via facial image analysis has lots of potential real-world applications, such as human computer interaction and multimedia communication. However, it is still a challenging problem for the existing computer vision systems to automatically and effectively estimate human ages. The aging process is determined by not only the person's gene, but also many external factors, such as health, living style, living location, and weather conditions. Males and females may also age differently. The current age estimation performance is still not good enough for practical use and more effort has to be put into this research direction. In this paper, we introduce the age manifold learning scheme for extracting face aging features and design a locally adjusted robust regressor for learning and prediction of human ages. The novel approach improves the age estimation accuracy significantly over all previous methods. The merit of the proposed approaches for image-based age estimation is shown by extensive experiments on a large internal age database and the public available FG-NET database.

We investigate the biologically inspired features (BIF) for human age estimation from faces. As in previous bio-inspired models, a pyramid of Gabor filters are used at all positions of the input image for the S <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> units. But unlike previous models, we find that the pre-learned prototypes for the S <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> layer and then progressing to C <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> cannot work well for age estimation. We also propose to use Gabor filters with smaller sizes and suggest to determine the number of bands and orientations in a problem-specific manner, rather than using a predefined number. More importantly, we propose a new operator “STD” to encode the aging subtlety on faces. Evaluated on the large database YGA with 8,000 face images and the public available FG-NET database, our approach achieves significant improvements in age estimation accuracy over the state-of-the-artmethods. By applying our system to some Internet face images, we show the robustness of our method and the potential of cross-race age estimation, which has not been explored by any studies before.

Abstract ZnO nanoparticles at different pH were synthesised by a sol-gel technique from zinc acetate dihydrate at a calcination temperature of 450 °C. The synthesized ZnO nanoparticles were characterised by x-ray diffraction (XDR) peak profile analysis, high-resolution scanning electron microscopy and Fourier transform infrared spectroscopy. The effects of solution pH on the crystallite size using Williamson-Hall and Debye–Scherrer were determined. The XRD analysis of the zincite phase structure of ZnO nanoparticles was obtained in the form of spheres for all the samples. The average crystallite sizes of ZnO nanoparticles decrease with increasing pH. The crystallite sizes of ZnO nanoparticles were investigated using Williamson-Hall analysis and Scherrer’s formula. The parameters such as dislocation density and lattice strain were computed for the diffraction peaks of XRD in the range of 2 θ = 10–90°. The results showed that the crystallite sizes calculated from Scherrer’s equation and Williamson-Hall analysis from XRD are not inter-correlated. Both methods give a wide deviation of crystallite size. Also, it was found that the crystallite sizes using both methods decrease with an increase in pH. Smaller crystallite sizes were estimated using the Scherrer’s formula. Thus, it is deduced that the equation fitted well for the synthesised ZnO nanoparticles.

UNLABELLED: Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students' interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training. IMPORTANCE: Engagement of undergraduate students in scientific research at early stages in their careers presents an opportunity to excite students about science, technology, engineering, and mathematics (STEM) disciplines and promote continued interests in these areas. Many excellent course-based undergraduate research experiences have been developed, but scaling these to a broader impact with larger numbers of students is challenging. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunting Advancing Genomics and Evolutionary Science (SEA-PHAGES) program takes advantage of the huge size and diversity of the bacteriophage population to engage students in discovery of new viruses, genome annotation, and comparative genomics, with strong impacts on bacteriophage research, increased persistence in STEM fields, and student self-identification with learning gains, motivation, attitude, and career aspirations.

We present a novel method for joint inversion of receiver functions and surface wave dispersion data, using a transdimensional Bayesian formulation. This class of algorithm treats the number of model parameters (e.g. number of layers) as an unknown in the problem. The dimension of the model space is variable and a Markov chain Monte Carlo (McMC) scheme is used to provide a parsimonious solution that fully quantifies the degree of knowledge one has about seismic structure (i.e constraints on the model, resolution, and trade‐offs). The level of data noise (i.e. the covariance matrix of data errors) effectively controls the information recoverable from the data and here it naturally determines the complexity of the model (i.e. the number of model parameters). However, it is often difficult to quantify the data noise appropriately, particularly in the case of seismic waveform inversion where data errors are correlated. Here we address the issue of noise estimation using an extended Hierarchical Bayesian formulation, which allows both the variance and covariance of data noise to be treated as unknowns in the inversion. In this way it is possible to let the data infer the appropriate level of data fit. In the context of joint inversions, assessment of uncertainty for different data types becomes crucial in the evaluation of the misfit function. We show that the Hierarchical Bayes procedure is a powerful tool in this situation, because it is able to evaluate the level of information brought by different data types in the misfit, thus removing the arbitrary choice of weighting factors. After illustrating the method with synthetic tests, a real data application is shown where teleseismic receiver functions and ambient noise surface wave dispersion measurements from the WOMBAT array (South‐East Australia) are jointly inverted to provide a probabilistic 1D model of shear‐wave velocity beneath a given station.

Carbon dots (CDots) have emerged to represent a highly promising new platform for visible/natural light-activated microbicidal agents. In this article, the syntheses, structures, and properties of CDots are highlighted, representative studies on their activities against bacteria, fungi, and viruses reviewed, and the related mechanistic insights discussed. Also highlighted and discussed are the excellent opportunities for potentially extremely broad applications of this new platform, including theranostics uses.

We present results from the first phase of the KamLAND-Zen double-beta decay experiment, corresponding to an exposure of 89.5 kg yr of $^{136}\mathrm{Xe}$. We obtain a lower limit for the neutrinoless double-beta decay half-life of ${T}_{1/2}^{0\ensuremath{\nu}}&gt;1.9\ifmmode\times\else\texttimes\fi{}{10}^{25}\text{ }\text{ }\mathrm{yr}$ at 90% C.L. The combined results from KamLAND-Zen and EXO-200 give ${T}_{1/2}^{0\ensuremath{\nu}}&gt;3.4\ifmmode\times\else\texttimes\fi{}{10}^{25}\text{ }\text{ }\mathrm{yr}$ at 90% C.L., which corresponds to a Majorana neutrino mass limit of $⟨{m}_{\ensuremath{\beta}\ensuremath{\beta}}⟩&lt;(120--250)\text{ }\text{ }\mathrm{meV}$ based on a representative range of available matrix element calculations. Using those calculations, this result excludes the Majorana neutrino mass range expected from the neutrinoless double-beta decay detection claim in $^{76}\mathrm{Ge}$, reported by a part of the Heidelberg-Moscow Collaboration, at more than 97.5% C.L.

The RAS oncogenes (HRAS, NRAS and KRAS) comprise the most frequently mutated class of oncogenes in human cancers (33%), thus stimulating intensive effort in developing anti-Ras inhibitors for cancer treatment. Despite intensive effort, to date, no effective anti-Ras strategies have successfully made it to the clinic. We present an overview of past and ongoing strategies to inhibit oncogenic Ras in cancer. Since approaches to directly target mutant Ras have not been successful, most efforts have focused on indirect approaches to block Ras membrane association or downstream effector signaling. While inhibitors of effector signaling are currently under clinical evaluation, genome-wide unbiased genetic screens have identified novel directions for future anti-Ras drug discovery.

The ratio of the proton elastic electromagnetic form factors, ${G}_{\mathit{Ep}}/{G}_{\mathit{Mp}}$, was obtained by measuring ${P}_{t}$ and ${P}_{\ensuremath{\ell}}$, the transverse and longitudinal recoil proton polarization components, respectively, for the elastic $\stackrel{\ensuremath{\rightarrow}}{e}p\ensuremath{\rightarrow}e\stackrel{\ensuremath{\rightarrow}}{p}$reaction in the four-momentum transfer squared range of 0.5 to $3.5\phantom{\rule{0.3em}{0ex}}\text{GeV}{}^{2}$. In the single-photon exchange approximation, ${G}_{\mathit{Ep}}/{G}_{\mathit{Mp}}$ is directly proportional to ${P}_{t}/{P}_{\ensuremath{\ell}}$. The simultaneous measurement of ${P}_{t}$ and ${P}_{\ensuremath{\ell}}$ in a polarimeter reduces systematic uncertainties. The results for ${G}_{\mathit{Ep}}/{G}_{\mathit{Mp}}$ show a systematic decrease with increasing ${Q}^{2}$, indicating for the first time a definite difference in the distribution of charge and magnetization in the proton. The data have been reanalyzed and their systematic uncertainties have become significantly smaller than those reported previously.

Increasingly, organizations and their public relations professionals are recognizing the importance of strengthening internal communication with employees. Internal communication is important for building a culture of transparency between management and employees, and it can engage employees in the organization’s priorities. This exploratory study uses findings from interviews with public relations executives to explore the growing role that internal communication plays in employee engagement. Executives employ a variety of communication methods, including face-to-face communication, to communicate with employees. The executives’ chosen communication strategies aim to build trust and engagement with employees. In doing so, public relations executives find themselves in an expanded role of fostering employee engagement.

Changes in the health and functioning of the Medicare-enrolled population aged 65+ are tracked by using the 1982-2004/2005 National Long-Term Care Surveys. We found a significant rate of decline in the prevalence of chronic disability that accelerated from 1982 to 2004. These declines are significant for both persons with less severe chronic disability, which might be compensated by modifying the built environment and providing assistive devices, and for persons with more serious disability, which may be affected by reductions in the incidence and severity of disease through biomedical interventions. Declines in chronic disability continued over the 22-year period at a rate fast enough (i.e., 1.52% per annum) to contribute significantly to the long-term fiscal stability of the Medicare (and Medicaid) programs. Changes in the rate and substance of disability declines seem consistent with the intentions of policy interventions in Medicare and Medicaid.

Mitochondria play a key role in energy production, calcium homeostasis, cell survival, and death. Adverse stimulations including neurodegenerative diseases may result in mitochondrial dynamic imbalance, free radical production, calcium accumulation, intrinsic cell death pathway activation and eventually cell death. Therefore, preserving or promoting mitochondrial function is a potential therapeutic target for the treatment of neurodegenerative disorders. Mitochondrial biogenesis is a process by which new mitochondria are produced from existing mitochondria. This biogenesis process is regulated by Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1alpha (PGC-1α). Once being activated by either phosphorylation or de-acetylation, PGC-1α activates nuclear respiratory factor 1 and 2 (NRF1 and NRF2), and subsequently mitochondrial transcription factor A (Tfam). The activation of this PGC-1α - NRF -Tfam pathway leads to synthesis of mitochondrial DNA and proteins and generation of new mitochondria. © 2017 Wiley Periodicals, Inc.