Developing and Advancing a Cyberinfrastructure to Gain Insights into Research Investments: An Organizing Research Framework

Developing and Advancing a Cyberinfrastructure to Gain Insights into Research Investments: An Organizing Research Framework Although the National Science Foundation (NSF) funds approximately 24% of basic research conducted in America’s colleges and universities (NSF), there is little we know about how NSF-­‐funding decisions have resulted in the current research landscape. This gap was the impetus for a project –Deep Insights Anytime, Anywhere (DIA2)— that begins to address this problem by focusing on NSF investments in undergraduate STEM education research, and how education innovations make an impact and diffuse throughout the STEM education community. The project team has designed an information portal (http://www.dia2.org) to allow researchers and scientists to browse and search public data from NSF to understand what research has taken place in specific areas and to find collaborators. There are many challenges in developing and using such a cyberinfrastructure, but also many potential advantages for practitioners and researchers. In this paper we will specifically discuss the research opportunities provided by DIA2 and present the research framework guiding the DIA2 project—a description of the three major themes/areas of research for the study. It summarizes the research questions and research activities corresponding to each of the themes, presents next steps, and based on our findings, highlights the value of DIA2 to members of the STEM education community. These concentrated efforts can help us better understand the domain of STEM research. Reference NSF. About the National Science Foundation. Retrieved October 14, 2014, from http://nsf.gov/about

Development and Airworthiness Certification of the Ti6Al4V Inlet Casing Inner Forging

The inlet casing inner has manufactured using Ti-6Al-4V alloy through a closed die-forging route. It undergoes cyclic loads in addition to operating in extreme conditions in high-temperature environments. The demanding mission requirement of these engines necessitates the inlet casing inner to be flawless throughout its life cycle while retaining its structural integrity. It makes the qualification for airworthiness of the casing, a daunting task. In addition, the qualification tests also help to evaluate the design and manufacturing processes (closed die forging) of the inlet casing inner. The tests also provide data for further improvement of the inlet casing inner in terms of strength and fatigue life. It helps to ensure that the inlet casing inner will be able to perform as expected throughout its operational life. All the batch and consolidated test results comply with the relevant ASTM, MIL standards, and test schedule requirements

Unification of Radio Galaxies and Their Accretion/Jet Properties

We investigate the relation between black hole mass, M_bh, and jet power, Q_jet, for a sample of BL Lacs and radio quasars. We find that BL Lacs are separated from radio quasars by the FR I/II dividing line in M_bh-Q_jet plane, which strongly supports the unification scheme of FR I/BL Lac and FR II/radio quasar. The Eddington ratio distribution of BL Lacs and radio quasars exhibits a bimodal nature with a rough division at L_bol/L_Edd~0.01, which imply that they may have different accretion modes. We calculate the jet power extracted from advection dominated accretion flow (ADAF), and find that it require dimensionless angular momentum of black hole j~0.9-0.99 to reproduce the dividing line between FR I/II or BL Lac/radio quasar if dimensionless accretion rate mdot=0.01 is adopted, which is required by above bimodal distribution of Eddington ratios. Our results suggest that black holes in radio galaxies are rapidly spinning.Comment: To appear JAA in Jun

Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma

Uveal melanoma (UM) is a rare aggressive intraocular tumour with a propensity for liver metastases, occurring in ∼50% of patients. The tumour suppressor BAP1 is considered to be key in UM progression. Herein, we present the largest study to date investigating cellular expression patterns of BAP1 protein in 165 UMs, correlating these patterns to prognosis. Full clinical, histological, genetic, and follow‐up data were available for all patients. BAP1 gene sequencing was performed on a subset of 26 cases. An independent cohort of 14 UMs was examined for comparison. Loss of nuclear BAP1 (nBAP1) protein expression was observed in 54% (88/165) UMs. nBAP1 expression proved to be a significant independent prognostic parameter: it identified two subgroups within monosomy 3 (M3) UM, which are known to have a high risk of metastasis. Strikingly, nBAP1‐positiveM3 UMs were associated with prolonged survival compared to nBAP1‐negative M3 UMs (Log rank, p = 0.014). nBAP1 protein loss did not correlate with a BAP1 mutation in 23% (6/26) of the UMs analysed. Cytoplasmic BAP1 protein (cBAP1) expression was also observed in UM: although appearing ‘predominantly diffuse’ in most nBAP1‐negative UM, a distinct ‘focal perinuclear’ expression pattern – localized immediately adjacent to the cis Golgi – was seen in 31% (18/59). These tumours tended to carry loss‐of‐function BAP1 mutations. Our study demonstrates loss of nBAP1 expression to be the strongest prognostic marker in UM, confirming its importance in UM progression. Our data suggest that non‐genetic mechanisms account for nBAP1 loss in a small number of UMs. In addition, we describe a subset of nBAP1‐negative UM, in which BAP1 is sequestered in perinuclear bodies, most likely within Golgi, warranting further mechanistic investigation

Scaled testing for COVID-19 needs community involvement.

With limited vaccine coverage and in the absence of specific therapeutics, the options to curb the COVID-19 pandemic today are mostly infection prevention measures and diagnostic tests to identify infected individuals rapidly, followed by isolation and contact tracing. The past months have seen significant worldwide scale-up of testing through quantitative PCR (qPCR) detecting nucleic acid of SARS-CoV-2. However, with the current resurgence of cases in Europe and elsewhere, qPCR demand far exceeds capacity. Moreover, qPCR is expensive, requires sophisticated laboratories, well-trained staff, and extensive logistics. Capacity deficits are aggravated in LMICs (Lower and Middle-Income Countries) with rampant shortages of tests kits, qualified staff, and laboratories, compromising clinical utility. Africa CDC reports 23 countries with proxy PCR coverage of <5000 tests/million population [1]. Alternative novel molecular diagnostics such as LAMP, DNAnudge and LAMPore remain widely unscalable. Moreover, even qPCR has its limitations in detecting non-infectious traces of viral RNA [2] and false negativity issues [3]. We conclude that molecular testing for COVID-19 is unfit for reaching scale at the community level

Selective Inhibition of Plasmodium falciparum ATPase 6 by Artemisinins and Identification of New Classes of Inhibitors after Expression in Yeast

Treatment failures with artemisinin combination therapies (ACTs) threaten global efforts to eradicate malaria. They highlight the importance of identifying drug targets and new inhibitors and of studying how existing antimalarial classes work. Here, we report the successful development of a heterologous expression-based compound-screening tool. The validated drug target Plasmodium falciparum ATPase 6 (PfATP6) and a mammalian orthologue (sarco/endoplasmic reticulum calcium ATPase 1a [SERCA1a]) were functionally expressed in Saccharomyces cerevisiae, providing a robust, sensitive, and specific screening tool. Whole-cell and in vitro assays consistently demonstrated inhibition and labeling of PfATP6 by artemisinins. Mutations in PfATP6 resulted in fitness costs that were ameliorated in the presence of artemisinin derivatives when studied in the yeast model. As previously hypothesized, PfATP6 is a target of artemisinins. Mammalian SERCA1a can be mutated to become more susceptible to artemisinins. The inexpensive, low-technology yeast screening platform has identified unrelated classes of druggable PfATP6 inhibitors. Resistance to artemisinins may depend on mechanisms that can concomitantly address multitargeting by artemisinins and fitness costs of mutations that reduce artemisinin susceptibility

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas

Non-invasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

Background and Aims: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. Approach and Results: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. Conclusions: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage

A New Classification System for the Actions of IRS Chemicals Traditionally Used For Malaria Control

Knowledge of how mosquitoes respond to insecticides is of paramount importance in understanding how an insecticide functions to prevent disease transmission. A suite of laboratory assays was used to quantitatively characterize mosquito responses to toxic, contact irritant, and non-contact spatial repellent actions of standard insecticides. Highly replicated tests of these compounds over a range of concentrations proved that all were toxic, some were contact irritants, and even fewer were non-contact repellents. Of many chemicals tested, three were selected for testing in experimental huts to confirm that chemical actions documented in laboratory tests are also expressed in the field. The laboratory tests showed the primary action of DDT is repellent, alphacypermethrin is irritant, and dieldrin is only toxic. These tests were followed with hut studies in Thailand against marked-released populations. DDT exhibited a highly protective level of repellency that kept mosquitoes outside of huts. Alphacypermethrin did not keep mosquitoes out, but its strong irritant action caused them to prematurely exit the treated house. Dieldrin was highly toxic but showed no irritant or repellent action. Based on the combination of laboratory and confirmatory field data, we propose a new paradigm for classifying chemicals used for vector control according to how the chemicals actually function to prevent disease transmission inside houses. The new classification scheme will characterize chemicals on the basis of spatial repellent, contact irritant and toxic actions

Flexible Systems in HR

Editorial special issueThe final publication is available at Springer via http://dx.doi.org/10.1007/s40171-016-0125-5Research on the concept of ‘flexibility’ has produced a substantive scholarly in recent decades and has evolved as a focal area of management research (Mønsted 1991; Sushil 1994; Skipper et al. 2014; Krishna et al. 2015). According to Sushil (2001) ‘Flexibility offers freedom of choice and is highly context specific’. Here, ‘context specific’ refers to the role of contingencies within flexibility which might render it as a form of a firm’s dynamic capability. The dynamic capability scholarship argues that in order to achieve excellence, organizations should develop capabilities complementary to their competencies (Teece et al. 1997; Helfat and Peteraf 2009). Thus, flexible HR practices can help organizations in achieving sustainable competitiveness through creating, integrating, reconfiguring, and building on its human resource base. For example, organizations can achieve competitive edge by customizing training and development programs