Factors of Success: A Study of Select Ohio School Districts’ Achievement

From segregation, integration by bussing, and near-bankruptcy, the Cleveland Metropolitan School District’s history is embattled to say the least. The district has struggled to properly educate students for decades. Large metropolitan school districts, like Cleveland, have always faced difficulties in educating its students. The Ohio Department of Education rated the Cleveland Metropolitan School District in “Academic Emergency” for the 2011-2012 academic year; the worst of six academic rankings. Of the largest districts in Ohio, including Columbus, Cincinnati, Akron, Dayton, and Toledo, Cleveland has had the lowest four-year graduation rate every year since 2000, averaging only a 50.97% graduation rate over the eleven-year period. Drawing from some of the recent research on public education, this study will present a model that predicts student achievement on state standardized tests in the Cleveland Metropolitan School District. After developing a well-specified model, the model and explanatory factors will be evaluated for potential contributions to the literature. It is the purpose of this paper to aid researchers and district policy makers to better understand what factors significantly contribute to student achievement, and, possibly, how to improve the quality of education Cleveland students receive

WITHAFERIN A: A NOVEL THERAPEUTIC APPROACH FOR MALIGANT BRAIN TUMORS

High-grade gliomas, including the astrocytoma glioblastoma multiforme (GBM), are the most common adult primary malignant brain tumor. The mean post-diagnosis survival time of patients with GBM is approximately 14 months and has improved only minimally over the last several decades given a lack of novel and effective therapeutic strategies or interventions. Similar issues persist for other forms of brain cancer, notably medulloblastomas (MB) in the pediatric patient population. Given our inability to extend survival and enhance quality of life adequately in these brain tumor patients, there is a critical need for novel chemotherapeutic agents in the treatment of GBM and MB that may work as monotherapy agents or in synergistic combinations with current interventions. In this work, the role of the natural product withaferin A (WA), a steroidal lactone with intriguing cytotoxic properties, was studied alone or in combination with currently approved anti-cancer agents (temozolomide, radiation therapy, and proteosome inhibitors) against GBM and MB brain tumors. It was shown that WA could produce G2/M cell cycle arrest and apoptosis with inhibitory modulation of the Akt/mammalian target of rapamycin (mTOR) pathway in GBM. Similarly, WA inhibited Wnt/β-catenin signaling through degradation of transcription factor (TCF)/lymphoid enhancer-binding factor (LEF) family members in MB. Overall, exposure to WA was associated with generalized N-acetyl-L-cysteine-repressible cellular oxidation, thiol reactivity, and alterations in the heat shock protein (HSP) 90 chaperone axis. WA failed to alter intrinsic HSP90 activity but reduced the association between HSP90 and co-chaperone Cdc37. These findings were expanded to demonstrate WA-mediated potentiation of cytotoxicity with concurrent proteasomal inhibition through an accumulation of aberrant proteins. WA also increased tumor cell radiosensitivity through disruption of normal DNA damage recognition and repair. While WA failed to significantly enhance the cytotoxicity of temozolomide (TMZ), it demonstrated the ability to re-sensitize TMZ-resistant GBM through reduction in O6-methylguanine-DNA methyltransferase (MGMT). This study identifies novel utility for the cytotoxic steroid lactone WA in the treatment of the malignant brain tumors GBM and MB through its alterations of oncogenic cellular signaling pathways, protein homeostasis, and the DNA-damage response mechanism. As such, WA represents a promising experimental therapeutic that warrants further translational exploration

Assessing Criterion Validity of Using Internet Searches as a Measure of Public Attention

We examine the criterion validity of using internet searches as a measure of public attention to United States Supreme Court (USSC) cases. First, we construct a measure of public attention to three cases by comparing relevant search terms in Google Trends to one top search terms of the year, then sum the measure week by week during the period of the research design. To test the measure’s criterion validity, we replicate Scott and Saunders’ (2006) models using their dataset (created by conducting phone interviews of a national sample using random digit dialing) that was designed to assess awareness of USSC decisions. We fnd that public attention as measured by Google Trends data is predictive of public awareness of USSC decisions for two of their three models. We conclude that using free, publicly available big data to measure public attention to USSC cases has criterion validity, and is a valuable tool for researchers studying public policy and process. Our fndings contribute to the body of research by demonstrating the validity of internet searches as a measure of public attention beyond its validity in elections and public policy, as Swearingen and Ripberger (2014) and Ripberger (2011) have done

Mapping Clearances in Tropical Dry Forests Using Breakpoints, Trend, and Seasonal Components from MODIS Time Series:Does Forest Type Matter?

Tropical environments present a unique challenge for optical time series analysis, primarily owing to fragmented data availability, persistent cloud cover and atmospheric aerosols. Additionally, little is known of whether the performance of time series change detection is affected by diverse forest types found in tropical dry regions. In this paper, we develop a methodology for mapping forest clearing in Southeast Asia using a study region characterised by heterogeneous forest types. Moderate Resolution Imaging Spectroradiometer (MODIS) time series are decomposed using Breaks For Additive Season and Trend (BFAST) and breakpoints, trend, and seasonal components are combined in a binomial probability model to distinguish between cleared and stable forest. We found that the addition of seasonality and trend information improves the change model performance compared to using breakpoints alone. We also demonstrate the value of considering forest type in disturbance mapping in comparison to the more common approach that combines all forest types into a single generalised forest class. By taking a generalised forest approach, there is less control over the error distribution in each forest type. Dry-deciduous and evergreen forests are especially sensitive to error imbalances using a generalised forest model i.e., clearances were underestimated in evergreen forest, and overestimated in dry-deciduous forest. This suggests that forest type needs to be considered in time series change mapping, especially in heterogeneous forest regions. Our approach builds towards improving large-area monitoring of forest-diverse regions such as Southeast Asia. The findings of this study should also be transferable across optical sensors and are therefore relevant for the future availability of dense time series for the tropics at higher spatial resolutions

Visual histological grading system for the evaluation of in vitro-generated neocartilage

Here we present the development of a visual evaluation system for routine assessment of in vitro-engineered cartilaginous tissue. Neocartilage was produced by culturing human articular chondrocytes in pellet culture systems or in a scaffold-free bioreactor system. All engineered tissues were embedded in paraffin and were sectioned and stained with Safranin O-fast green. The evaluation of each sample was broken into 3 categories (uniformity and intensity of Safranin O stain, distance between cells/amount of matrix produced, and cell morphology), and each category had 4 components with a score ranging from 0 to 3. Three observers evaluated each sample, and the new system was independently tested against an objective computer-based histomorphometry system. Pellets were also assessed biochemically for glycosaminoglycan (GAG) content. Pellet histology scores correlated significantly with GAG contents and were in agreement with the computer-based histomorphometry system. This system allows a valid and rapid assessment of in vitro-generated cartilaginous tissue that has a relevant association with objective parameters indicative of cartilage quality

Oxidative cytotoxic agent withaferin A resensitizes temozolomide-resistant glioblastomas via MGMT depletion and induces apoptosis through Akt/mTOR pathway inhibitory modulation

Temozolomide (TMZ) has remained the chemotherapy of choice in patients with glioblastoma multiforme (GBM) primarily due to the lack of more effective drugs. Tumors, however, quickly develop resistance to this line of treatment creating a critical need for alternative approaches and strategies to resensitize the cells. Withaferin A (WA), a steroidal lactone derived from several genera of the Solanaceae plant family has previously demonstrated potent anti-cancer activity in multiple tumor models. Here, we examine the effects of WA against TMZ-resistant GBM cells as a monotherapy and in combination with TMZ. WA prevented GBM cell proliferation by dose-dependent G2/M cell cycle arrest and cell death through both intrinsic and extrinsic apoptotic pathways. This effect correlated with depletion of principle proteins of the Akt/mTOR and MAPK survival and proliferation pathways with diminished phosphorylation of Akt, mTOR, and p70 S6K but compensatory activation of ERK1/2. Depletion of tyrosine kinase cell surface receptors c-Met, EGFR, and Her2 was also observed. WA demonstrated induction of N-acetyl-L-cysteine-repressible oxidative stress as measured directly and through a subsequent heat shock response with HSP32 and HSP70 upregulation and decreased HSF1. Finally, pretreatment of TMZ-resistant GBM cells with WA was associated with O6-methylguanine-DNA methyltransferase (MGMT) depletion which potentiated TMZ-mediated MGMT degradation. Combination treatment with both WA and TMZ resulted in resensitization of MGMT-mediated TMZ-resistance but not resistance through mismatch repair mutations. These studies suggest great clinical potential for the utilization of WA in TMZ-resistant GBM as both a monotherapy and a resensitizer in combination with the standard chemotherapeutic agent TMZ

Novel natural withanolides induce apoptosis and inhibit migration of neuroblastoma cells through down regulation of N-myc and suppression of Akt/mTOR/NF-κB activation

Despite recent advances in intensive chemotherapy treatments, long-term success is achieved in less than 30% of children with high-risk neuroblastoma (NB). Key regulatory pathways including the PI3K/Akt, mTOR and NF-κB are implicated in the pathogenesis of NB. Although drugs targeting these individual pathways are in clinical trials, they are not effective due to the activation of compensatory mechanisms. We have previously reported that natural novel withanolides from Physalis longifolia can potently inhibit these key regulatory pathways simultaneously. In the present study, we examined the efficacy and mechanisms through which novel withanolides and their acetate derivatives (WGA-TA and WGB-DA) from P.longifolia kill NB cells. The results from the study demonstrated that our novel acetate derivatives are highly effective in inhibiting the proliferation, shifting the cell cycle and inducing apoptosis in a dose dependent manner. Analysis of oncogenic pathway proteins targeted by withanolides indicated induction of heat shock response due to oxidative stress. Dose dependent decrease in clients of HSP90 chaperone function due to suppression of Akt, mTOR, and NF-κB pathways led to decrease in the expressions of target genes such as cyclin D1, N-myc and Survivin. Additionally, there was a dose dependent attenuation of the migration and invasion of NB cells. Furthermore, the lead compound WGA-TA showed significant reduction in tumor growth of NB xenografts. Taken together, these results suggest that withanolides are an effective therapeutic option against NBs

Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways

Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was found to inhibit proliferation by inducing a dose-dependent G2/M cell cycle arrest and promoting cell death through both intrinsic and extrinsic apoptotic pathways. This was accompanied by an inhibitory shift in the Akt/mTOR signaling pathway which included diminished expression and/or phosphorylation of Akt, mTOR, p70 S6K, and p85 S6K with increased activation of AMPKα and the tumor suppressor tuberin/TSC2. Alterations in proteins of the MAPK pathway and cell surface receptors like EGFR, Her2/ErbB2, and c-Met were also observed. WA induced an N-acetyl-L-cysteinerepressible enhancement in cellular oxidative potential/stress with subsequent induction of a heat shock stress response primarily through HSP70, HSP32, and HSP27 upregulation and HSF1 downregulation. Taken together, we suggest that WA may represent a promising chemotherapeutic candidate in glioblastoma therapy warranting further translational evaluation

Coordination and control – limits in standard representations of multi-reservoir operations in hydrological modeling

Major multi-reservoir cascades represent a primary mechanism for dealing with hydrologic variability and extremes within institutionally complex river basins worldwide. These coordinated management processes fundamentally reshape water balance dynamics. Yet, multi-reservoir coordination processes have been largely ignored in the increasingly sophisticated representations of reservoir operations within large-scale hydrological models. The aim of this paper is twofold, namely (i) to provide evidence that the common modeling practice of parameterizing each reservoir in a cascade independently from the others is a significant approximation and (ii) to demonstrate potential unintended consequences of this independence approximation when simulating the dynamics of hydrological extremes in complex reservoir cascades. We explore these questions using the Water Balance Model, which features detailed representations of the human infrastructure coupled to the natural processes that shape water balance dynamics. It is applied to the Upper Snake River basin in the western US and its heavily regulated multi-reservoir cascade. We employ a time-varying sensitivity analysis that utilizes the method of Morris factor screening to explicitly track how the dominant release rule parameters evolve both along the cascade and in time according to seasonal high- and low-flow events. This enables us to address aim (i) by demonstrating how the progressive and cumulative dominance of upstream releases significantly dampens the ability of downstream reservoir rules\u27 parameters to influence flow conditions. We address aim (ii) by comparing simulation results with observed reservoir operations during critical low-flow and high-flow events in the basin. Our time-varying parameter sensitivity analysis with the method of Morris clarifies how independent single-reservoir parameterizations and their tacit assumption of independence leads to reservoir release behaviors that generate artificial water shortages and flooding, whereas the observed coordinated cascade operations avoided these outcomes for the same events. To further explore the role of (non-)coordination in the large deviations from the observed operations, we use an offline multi-reservoir water balance model in which adding basic coordination mechanisms drawn from the observed emergency operations is sufficient to correct the deficiencies of the independently parameterized reservoir rules from the hydrological model. These results demonstrate the importance of understanding the state–space context in which reservoir releases occur and where operational coordination plays a crucial role in avoiding or mitigating water-related extremes. Understanding how major infrastructure is coordinated and controlled in major river basins is essential for properly assessing future flood and drought hazards in a changing world