Generalized Box-Cox method to estimate sample mean and standard deviation for Meta-analysis

Meta-analysis is the aggregation of data from multiple studies to find patterns across a broad range relating to a particular subject. It is becoming increasingly useful to apply meta-analysis to summarize these studies being done across various fields. In meta-analysis, it is common to use the mean and standard deviation from each study to compare for analysis. While many studies reported mean and standard deviation for their summary statistics, some report other values including the minimum, maximum, median, and first and third quantiles. Often, the quantiles and median are reported when the data is skewed and does not follow a normal distribution. In order to correctly summarize the data and draw conclusions from multiple studies, it is necessary to estimate the mean and standard deviation from each study, considering variation and skewness within each study. In past literature, methods have been proposed to estimate the mean and standard deviation, but do not consider negative values. Data that include negative values are common and would increase the accuracy and impact of the me-ta-analysis. We propose a method that implements a generalized Box-Cox transformation to estimate the mean and standard deviation accounting for such negative values while maintaining similar accuracy.Comment: 9 pages, 6 figure

Loss of the chromatin regulator MRG15 limits neural stem/progenitor cell proliferation via increased expression of the p21 Cdk inhibitor

AbstractChromatin regulation is crucial for many biological processes such as transcriptional regulation, DNA replication, and DNA damage repair. We have found that it is also important for neural stem/progenitor cell (NSC) function and neurogenesis. Here, we demonstrate that expression of the cyclin-dependent kinase inhibitor p21 is specifically up-regulated in Mrg15 deficient NSCs. Knockdown of p21 expression by p21 shRNA results in restoration of cell proliferation. This indicates that p21 is directly involved in the growth defects observed in Mrg15 deficient NSCs. Activated p53 accumulates in Mrg15 deficient NSCs and this most likely accounts for the up-regulation of p21 expression in the cells. We observed decreased p53 and p21 levels and a concomitant increase in the percentage of BrdU positive cells in Mrg15 null cultures following expression of p53 shRNA. DNA damage foci, as indicated by immunostaining for γH2AX and 53BP1, are detectable in a sub-population of Mrg15 deficient NSC cultures under normal growing conditions and the majority of p21-positive cells are also positive for 53BP1 foci. Furthermore, Mrg15 deficient NSCs exhibit severe defects in DNA damage response following ionizing radiation. Our observations highlight the importance of chromatin regulation and DNA damage response in NSC function and maintenance

CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation

Receptor tyrosine kinases, such as VEGFR, PDGFR and EGFR, play important roles in renal cancer. In this study, we investigated EGFR knockout as a therapeutic approach in renal cell carcinoma (RCC). We showed that a renal cell carcinoma cell line (RC21) has higher expression of EGFR as compared to other frequently used cell lines such as HEK293, A549, Hela and DLD1. Ablation of EGFR by CRISPR/Cas9 significantly restrained tumor cell growth and activated the MAPK (pERK1/2) pathway. The VEGFR and PDGFR inhibitor, sunitinib, attenuated the expression of MAPK (pERK1/2) and pAKT induced by EGFR loss and further inhibited EGFR(-/-) cell proliferation. We showed that loss of EGFR eventually leads to resistance to SAHA and cisplatin. Furthermore, EGFR loss induced G2/M phase arrest and resulted in an increased resistance to TNF-related apoptosis-inducing ligand (TRAIL) in renal cell carcinoma. Thus, ablation of overexpressed EGFR by CRISPR/Cas9 alone or in combination with sunitinib may be a new treatment option for renal cell carcinoma

A Model for Spheroid Versus Monolayer Response of SK-N-SH Neuroblastoma Cells to Treatment with 15-Deoxy-\u3cem\u3ePGJ\u3c/em\u3e\u3csub\u3e2\u3c/sub\u3e

Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, as in vitro spheroids or in vivo. This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy-PGJ2 and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-PGJ2. The monolayer model is extended to a five-dimensional nonlinear model of in vitro tumor spheroid growth and treatment that includes compartments of the cell cycle (G1,S,G2/M) as well as quiescent (Q) and necrotic (N) cells. Monolayer treatment data for 15-deoxy-PGJ2 is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment

Antimony nanobelt asymmetric membranes for sodium ion battery

In this study, composite asymmetric membranes containing antimony (Sb) nanobelts are prepared via a straightforward phase inversion method in combination with post-pyrolysis treatment. Sb nanobelt asymmetric membranes demonstrate improved cyclability and specific capacity as the alloy anode of sodium ion battery compared to Sb nanobelt thin films without asymmetric porous structure. The unique structure can effectively accommodate the large volume expansion of Sb-based alloy anodes, prohibit the loss of fractured active materials, and aid in the formation of stable artificial solid electrolyte interphases as evidenced by an outstanding capacity retention of ∼98% in 130 cycles at 60 mA g−1. A specific capacity of ∼600 mAh g−1 is obtained at 15 mA g−1 (1/40C). When the current density is increased to 240 mA g−1, ∼80% capacity can be maintained (∼480 mAh g−1). The relations among phase inversion conditions, structures, compositions, and resultant electrochemical properties are revealed through comprehensive characterization

Nanomedicine strategies for central nervous system (CNS) diseases

The blood-brain barrier (BBB) is a crucial part of brain anatomy as it is a specialized, protective barrier that ensures proper nutrient transport to the brain, ultimately leading to regulating proper brain function. However, it presents a major challenge in delivering pharmaceuticals to treat central nervous system (CNS) diseases due to this selectivity. A variety of different vehicles have been designed to deliver drugs across this barrier to treat neurodegenerative diseases, greatly impacting the patient’s quality of life. The two main types of vehicles used to cross the BBB are polymers and liposomes, which both encapsulate pharmaceuticals to allow them to transcytose the cells of the BBB. For Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and glioblastoma brain cancer, there are a variety of different nanoparticle treatments in development that increase the bioavailability and targeting ability of existing drugs or new drug targets to decrease symptoms of these diseases. Through these systems, nanomedicine offers a new way to target specific tissues, especially for the CNS, and treat diseases without the systemic toxicity that often comes with medications used currently

A Life-Cycle Energy and Inventory Analysis of Adiabatic Quantum-Flux-Parametron Circuits

The production process of superconductive integrated circuits is complex and consumes significant amounts of resources and energy. Therefore, it is crucial to evaluate the environmental impact of this emerging technology. An attractive option for the next generation of superconductive technology is Adiabatic Quantum-Flux-Parametron (AQFP) devices. This study is the first to present a comprehensive process-based life-cycle assessment (LCA) and inventory analysis of AQFP integrated circuits. To generate relevant outcomes, we conduct a comparative LCA that included the bulk CMOS technology. The inventory analysis considered the manufacturing, assembly, and use phases of the circuits. To ensure a fair assessment, we choose the 32-bit AQFP RISC-V single-core processor as the reference functional unit and compare its performance with that of a CMOS counterpart. Our findings reveal that the AQFP processor consumes several orders of magnitude less energy during the use phase than its CMOS counterpart. Consequently, the total life cycle energy (which encompasses manufacturing and assembly energies) of AQFP integrated circuits improves at least by two orders of magnitude

3D printed architected hollow sphere foams with low-frequency phononic band gaps

We experimentally and numerically investigate elastic wave propagation in a class of lightweight architected materials composed of hollow spheres and binders. Elastic wave transmission tests demonstrate the existence of vibration mitigation capability in the proposed architected foams, which is validated against the numerically predicted phononic band gap. We further describe that the phononic band gap properties can be significantly altered through changing hollow sphere thickness and binder size in the architected foams. Importantly, our results indicate that by increasing the stiffness contrast between hollow spheres and binders, the phononic band gaps are broadened and shifted toward a low-frequency range. At the threshold stiffness contrast of 50, the proposed architected foam requires only a volume fraction of 10.8% while exhibiting an omnidirectional band gap size exceeding 130%. The proposed design paradigm and physical mechanisms are robust and applicable to architected foams with other topologies, thus providing new opportunities to design phononic metamaterials for low-frequency vibration control