cssi/SciSciGPT-SciSciNet huggingface dataset:
Paediatric Germ Cell Tumours in the West Midlands Health Authority Region (WMHAR): Increasing Incidence and Pattern of Geographical Distribution

Publisher Summary This chapter discusses a study investigating increasing incidence and pattern of geographical distribution for pediatric germ cell tumors (GCTs) in the West Midlands Health Authority Region (WMHAR). As it had been reported that malignant germ cell tumors (MGCT) were increasing in incidence in the North West Region of the U.K., the investigation started to examine the rates in the WMHAR. At the same time, the geographical distribution of the cases was analyzed to gain possible further insights into any changes in incidence rates. A total of 216 cases of childhood GCT during 1957–92 were identified, of which 103 were malignant. When the cases were mapped, higher rates were seen at health district level in the urban/industrial regions of the West Midlands, with a noticeable increase in the urban areas between the two time periods. This suggests the possibility that industrial/urban carcinogens may be implicated in the observed increase in childhood GCTs. To further investigate the observations found in this study, there is a need for case-control studies, particularly of occupational and environmental exposures.
MPBSD: A Moving Target Defense Approach for Base Station Security in Wireless Sensor Networks

This paper addresses one major concern on how to secure the location information of a base station in a compromised Wireless Sensor Network (WSN). In this concern, disrupting or damaging the wireless base station can be catastrophic for a WSN. To aid in the mitigation of this challenge, we present Moving Proximity Base Station Defense (MPBSD), a Moving Target Defense (MTD) approach to concealing the location of a base station within a WSN. In this approach, we employ multiple base stations to serve a WSN where one of the multiple base stations is elected to serve the WSN in a specific period of time. Specifically, our approach periodically changes the designation over a period of time to provide obscurity in the location information of the base station. We further evaluate MPBSD using a real-world testbed environment utilizing Wi-Fi frequencies. Our results show that MPBSD is an effective MTD approach to securing base stations for a WSN in term of sensory performance such as end-to-end delay.
Teaching the internist to see: effectiveness of a 1-day workshop in bedside ultrasound for internal medicine residents

A growing body of evidence supports the use of bedside ultrasound for core Internal Medicine procedures and increasingly as augmentation of the physical exam. The literature also supports that trainees, both medical students and residents, can acquire these skills. However, there is no consensus on training approach. To implement and study the effectiveness of a high-yield and expedited curriculum to train internal medicine interns to use bedside ultrasound for physical examination and procedures. The study was conducted at a metropolitan, academic medical center and included 33 Internal Medicine interns. This was a prospective cohort study of a new educational intervention consisting of a single-day intensive bedside ultrasound workshop followed by two optional hour-long workshops later in the year. The investigation was conducted at Oregon Health & Science University in Portland, Oregon. The intensive day consisted of alternating didactic sessions with small group hands-on ultrasound practice sessions and ultrasound simulations. A 30-question assessment was used to assess ultrasound interpretation knowledge prior to, immediately post, and 6 months post intervention. Thirty-three interns served as their own historical controls. Assessment performance significantly increased after the intervention from a mean pre-test score of 18.3 (60.9 % correct) to a mean post-test score 25.5 (85.0 % correct), P value of <0.0001. This performance remained significantly better at 6 months with a mean score of 23.8 (79.3 % correct), P value <0.0001. There was significant knowledge attrition compared to the immediate post-assessment, P value 0.0099. A single-day ultrasound training session followed by two optional noon conference sessions yielded significantly improved ultrasound interpretation skills in internal medicine interns.
QoS Management on Heterogeneous Architecture for Multiprogrammed, Parallel, and Domain-Specific Applications

Quality-of-service (QoS) management is widely employed to provide differentiable performance to programs with distinctive priorities on conventional chip-multiprocessor (CMP) platforms. Recently, heterogeneous architecture integrating diverse processor cores on the same silicon has been proposed to better serve various application domains, and it is expected to be an important design paradigm of future processors. Therefore, the QoS management on emerging heterogeneous systems will be of great significance. Workloads on heterogeneous architectures can be multiprogrammed, heterogeneous, and/or domain specific depending on the form factor and device of interest. Considering the diverse characteristics of these three classes of workloads is important when managing QoS on heterogeneous architectures. For example, for parallel applications, considering the diverse characteristics of thread synchronization, data sharing, and parallelization pattern of representative parallel applications, governing the execution of multiple parallel programs with different performance requirements becomes a complicated yet significant problem. In this paper, we study QoS management for multiprogrammed, parallel, and domain-specific applications running on heterogeneous CMP systems. We comprehensively assess a series of task-to-core mapping policies on a real heterogeneous hardware (QuickIA) by characterizing their impacts on performance of individual applications. Our evaluation results show that the proposed QoS policies are effective to improve the performance of programs with highest priority while striking good tradeoff with system fairness.
Transforming Enterprises through Mobile Applications: A Multi-Phase Framework

Mobile applications have become an important strategic imperative to many leading enterprises. While the potential value and impact of enterprise mobility is understood, only little is known about the transformational capabilities of mobile applications. This research develops a conceptual multi-phase framework of mobile transformations by integrating the emerging literature on mobile business and enterprise transformation with best practice approaches employed in industry. The framework provides a basis for future mobile enterprise oriented studies, enhances our understanding of mobile application opportunities, and facilitates the development of appropriate mobility strategies.
A Framework for Community Detection in Large Networks Using Game-Theoretic Modeling

Community detection is a fundamental component of large network analysis. In both academia and industry, progressive research has been made on problems related to community network analysis. Community detection is gaining significant attention and importance in the area of network science. Regular and synthetic complex networks have motivated intense interest in studying the fundamental unifying principles of various complex networks. This paper presents a new game-theoretic approach towards community detection in large-scale complex networks based on modified modularity; this method was developed based on modified adjacency, modified Laplacian matrices and neighborhood similarity. This approach was used to partition a given network into dense communities. It is based on determining a Nash stable partition, which is a pure strategy Nash equilibrium of an appropriately defined strategic game in which the nodes of the network were the players and the strategy of a node was to decide to which community it ought to belong. Players chose to belong to a community according to a maximized fitness/payoff. Quality of the community networks was assessed using modified modularity along with a new fitness function. Community partitioning was performed using Normalized Mutual Information and a ‘modularity measure’, which involved comparing the new game-theoretic community detection algorithm (NGTCDA) with well-studied and well-known algorithms, such as Fast Newman, Fast Modularity Detection, and Louvain Community. The quality of a network partition in communities was evaluated by looking at the contribution of each node and its neighbors against the strength of its community.
Methylnaltrexone Versus Naloxone for Opioid-Induced Constipation in the Medical Intensive Care Unit:

Background: Opioid-induced constipation (OIC) is common in critically ill patients; it leads to complications that can increase hospital stay and, rarely, bowel perforation. Opioid antagonists are considered a logical approach to treat OIC; however, the agent of choice has yet to be determined. Objective: To assess the effectiveness and safety of enteral naloxone (NTX) versus subcutaneous methylnaltrexone (MNTX) for the treatment of OIC in the medical intensive care unit. Methods: This retrospective review evaluated patients who received fentanyl continuous infusions for at least 72 hours and were initiated on NTX or MNTX. Active colitis, mechanical gastrointestinal obstruction, and inability to receive NTX orally were exclusion criteria. The primary outcome was time to first bowel movement (BM). Secondary outcomes included total number of BMs within 48 hours, opioid requirements after NTX or MNTX, and change in any of the following after the opioid antagonist: heart rates, mean arterial pressures, and le...
Factors Affecting Whites' and Blacks' Attitudes Toward Race Concordance With Doctors

This paper assesses whether 2 dimensions of whites' and blacks' attitudes toward race concordance with doctors are associated with past unfair treatment in health care and general racial attitudes, and whether the association varies by race. Using telephone survey data, we find that among blacks, but not whites, more positive attitudes toward race-concordant doctors are associated with past unfair treatment in health care related to doctor race. In addition, we find that among whites, but not blacks, more positive attitudes toward race concordance are associated with negative attitudes toward interracial contact in general. We conclude that these dimensions of blacks' and whites' attitudes toward health care are associated with distinct factors. The findings encourage research on how attitudes formed outside health care, as well as how health care experiences influence attitudes toward health care and how these factors may vary by location in the system of racial inequality.
PlanIt and DQ-N for Low-Power Wide-Area Networks: Demo Abstract

Low-Power Wide-Area networks promise to deliver limited IoT payloads reliably at distances in excess of 10 km raising the possibility of thousands of IoT devices connected to a single base station. PlanIt is a web application able to visualize connectivity in these large-scale deployments prior to deploying hardware or even making a single signal-strength measurement. DQ-N is an adaptation of distributed queuing, a hybrid MAC protocol, compatible with current LoRa packet radios that significantly increases the number of nodes that can be supported from a signal base station. This demo will allow users to visualize LoRa coverage for the entire USA and demonstrate DQ-N using several sensor nodes.
Distributed Intelligence: Trends in the Management of Complex Systems

The ability to incorporate intelligence in even small devices and to make use of contextual information from widely deployed sensors has already begun to change management paradigms. As edge computing and IoT become more prevalent, systems will increasingly consist of cooperating, heterogeneous, distributed, autonomous elements. Architectures for cognitive, collaborative systems are evolving to deal with such complex environments. Concepts from multi-agent systems and autonomic computing are being applied to cope with the scope and breadth of large collections of interacting devices and services. Technologies for security and access control must evolve as well. Policy-based mechanisms are widely used and have been very successful in protecting information and controlling access to systems and services. They tend to rely, however, on a centralized infrastructure and on the automated enforcement of directives. Newer paradigms are being investigated that allow policy structures to be more dynamic and contextual, while still preserving the desired levels of control. We will present trends in the evolution of architectures for distributed, federated systems, and the technologies for managing them.
Roles of Free Electrons and H2O2 in the Optical Breakdown-Induced Photochemical Reduction of Aqueous [AuCl4]−

Free electrons and H2O2 formed in an optical breakdown plasma are found to directly control the kinetics of [AuCl4]− reduction to form Au nanoparticles (AuNPs) during femtosecond laser-assisted synthesis of AuNPs. The formation rates of both free electrons and H2O2 strongly depend on the energy and duration of the 800 nm laser pulses over the ranges of 10–2400 μJ and 30–1500 fs. By monitoring the conversion of [AuCl4]− to AuNPs using in situ UV–vis spectroscopy during laser irradiation, the first- and second-order rate constants in the autocatalytic rate law, k1 and k2, were extracted and compared to the computed free electron densities and experimentally measured H2O2 formation rates. For laser pulse energies of 600 μJ and lower at all pulse durations, the first-order rate constant, k1, was found to be directly proportional to the theoretically calculated plasma volume, in which the electron density exceeds the threshold value of 1.8 × 1020 cm–3. The second-order rate constant, k2, was found to correlate...
Role of platinum-based chemotherapy for Merkel cell tumor in adjuvant and metastatic settings.

9049 Background: Merkel Cell Carcinoma (MCC) is a rare, highly aggressive primary neuroendocrine carcinoma of skin. The tumor always stains positive for CK20. Chemotherapy for metastatic disease ha...
Fundamentals of Magnetic Bearings

Active magnetic bearings (AMBs) are non-contact bearings for rotating machines. A pair of electromagnets acting at opposite sides of the rotor balance the attractive magnetic forces in order to center the rotor in the control axis. Some fundamental concepts and terminologies that are needed for describing the operation and modeling of active magnetic bearings are introduced in this chapter. A simplified model of the AMB force is derived to study the interaction between the electromagnetic actuators and the rotor target. A linear variation of this model is commonly used in the design of rotor levitation controllers, and it is also presented in this chapter. Additionally, we discuss common AMB losses, such as flux leakage, eddy current, and hysteresis, which limit the maximum performance of the bearings. We conclude the chapter with a review of the different AMB levitation control methods that are found in the literature, including both classical and modern control methods.
The Historical Decrease of Soil Erosion in the Eastern United States – The Role of Geography and Engineering

The severity of historical soil erosion in the eastern U.S. is largely a function of the excessive rainfall there as compared to Europe where most early U.S. agricultural practices originated. Amelioration of this excessive erosion came only in the mid-20th centuries with new soil conservation techniques developed by agricultural engineers with widespread regional experimentation. In addition, greatly enhanced productivity allowed U.S. agriculture to use only the better soils, allowing vast areas of poorer soils to revert to forest. Not only has soil erosion been reduced, but significant amounts of carbon have been sequestered, wildlife habitat has been improved, and the nation has much larger forest reserves. The downside of enhanced agriculture has been excessive use of nutrients with the movement into natural waters.
Selection, System and Historiography

This paper is contentious, assertive and programmatic. It attempts to assay certain characteristics of a chronological history of science as practiced. It presents a model based on evolutionary theory that shows how to do that job better. After a brief excursion into the ontological assumptions of history writing, it goes on to sketch a different, systemic model. This systemic model is compatible with the traditional model, but will allow science better to be seen in its complex relation to other human and social aspects. As a leitmotif it is argued that intentionality and the mental or their teleological analogues, as an essential part of selectivity, are an ineliminable part of the history of science, however done.
Three-Dimensional Reconstruction

The value of projection images is restricted if one wants to comprehend the architecture of an unknown structure. In 1968, the first three-dimensional (3D) reconstruction of a biological object was published, a phage tail with a helical symmetry. Soon after that, an article that sketches out the strategy for reconstruction of a single macromolecule lacking order and symmetry was published. Since then, the methodologies dealing with the two types of objects have developed more or less separately, although the existence of the same mathematical thread has often been emphasized. This chapter discusses some basic mathematical principles underlying reconstruction: the different data collection schemes and reconstruction strategies that answer the questions of how to maximize information, minimize radiation damage, or determine the directions of projections, while leaving open the choice of reconstruction algorithm and the main algorithmic approaches that include weighted back-projection, Fourier interpolation methods, and iterative algebraic methods.
Developing Guidance for Delimiting the Assessment Areas or Stream Reaches

Abstract Describing precisely the part of a wetland or stream that an assessment is based on is essential to correctly interpret the results of a RAM application. This can be particularly challenging for small wetlands that are part of a wetland-upland complex, for streams that change their flow duration or condition in short distances, and for wetlands or stream reaches that are so large that only a small portion can be observed in one day. This chapter describes options for setting the assessment area boundaries in these and other situations.
Single Crystalline 4H-SiC Membrane Resonators

We report the first wafer-scale fabrication of semi-insulating, single-crystalline 4H-SiC membrane resonators by timed deep reactive ion etch (DRIE). Trenches were etched $184 \mu\mathrm{m}$ deep with 84.7° sidewall angle to form $16 \mu\mathrm{m}$ thick suspended membranes. Sidewall angle, DRIE footing, and surface roughness are characterized. Measured resonance frequencies match with COMSOL simulation within 4%. The modes have quality factors of 500 to 1000 at ambient condition.
Chapter 28 – CR1

CR1 is a type I transmembrane, N-linked glycoprotein, expressed predominantly on blood cells and involved in innate immunity. The gene encoding CR1 is member of the RCA (regulators of complement activation) group located on chromosome 1. The extracellular domain of CR1 contains the binding site for all nascent complement fragments C3b, C4d, C1q and mannan-binding lectin, and Epstein–Barr virus. CR1, both as a membrane-bound, as well as soluble, protein helps regulating the activation of the complement system. On circulating nucleated cells, CR1 is involved in phagocytosis of complement-opsonised particles and immune complexes. The expression levels on circulating red blood cells (RBCs) are genetically determined and varies between 90, 500 or 1200 CR1 copies/cell. In humans, there are no known innate deficiencies of CR1. Acquired low expression levels of CR1 on circulating RBCs are seen in pregnancy and a wide spectrum of chronic and acute inflammatory conditions. Mice do not express CR1, but an alternatively spliced variant of CR2.
Can texture analysis of pre-immunotherapy CT imaging predict clinical outcomes for patients with advanced NSCLC treated with Nivolumab?

e20720Background: Targeted therapies are ineffective in most NSCLC patients and response rates remain < 20% for patients with advanced NSCLC on immuno-monotherapy. Predictive models that distinguis...
Insights into the dynamic hydrogenation of mayenite [Ca24Al28O64]4+(O2−)2: Mixed ionic and electronic conduction within the sub-nanometer cages

Abstract Novel structures with mixed ionic and electronic conduction (MIEC) are very attractive for their versatility in energy and sustainable technologies. Sub-nanoporous mayenite (12CaO·7Al2O3, C12A7) presents a unique cage structure, which can accommodate a series of anions, including O2−, O−, OH−, H− and even e− (electride). Conduction behavior of C12A7 in reducing conditions (H2) is interesting due to the coexistence of various cage species. Herein, to get in-depth insights into the H− incorporation, dynamic C12A7 hydrogenation was studied by in-situ electrical conductivity tests up to 800 °C, concerning the mixed conduction of O2−, H−, and e− within the sub-nano cages. It was found H− injection was accompanied by the production of electronic conduction, which can be retained even by slow cooling. MIEC was further confirmed by an electromotive force (emf) tests over the range of 500–800 °C. Systematic studies indicated that bulk injection of H− probably proceeded via an indirect approach, the simultaneous transport of e− and H+. Conductive competition between O2− and H+ within the cages was also suggested by ± switching of the open-circuit voltage (OCV) at different temperature zones. Furthermore, based on the high sensitivity of the MIEC equilibrium in hydrogenated C12A7 to the environment, the prototype of high-temperature ceramic sensors for H2 and O2 were also presented.
Looking Again at Findings: Secondary Analysis

Secondary analysis of the findings of over two dozen research projects by this author addressing a variety of types of information policy and/or journalism questions over almost three dozen years yields a great deal of analytical value for those studying contemporary governance issues raised by uses of algorithms in the news, whether undertaken by public or private sector entities. Details of this case demonstrate the value of this type of secondary analysis as a research method in its own right, particularly useful when addressing what is being experienced as the “new” new technology, and particularly useful early on in such research projects.
KS0 and Λ production in charged particle jets in p–Pb collisions at sNN=5.02TeV with ALICE

Abstract We study the production of K S 0 mesons and Λ baryons in jets in p–Pb collisions at s NN = 5.02 TeV with ALICE at the LHC. The p T -differential density of the particles produced in jets is compared to the inclusive distributions and the Λ / K S 0 ratio is reported in bins of multiplicity of the collisions. The hard scatterings are selected on an event-by-event basis using the anti- k T clustering algorithm with resolution parameter R = 0.2, 0.3 and 0.4, reconstructed from charged particles with a minimum p T,jet of 10 (or 20) GeV / c .
Baicalein, an enteric microbial metabolite, suppresses gut inflammation and cancer progression in ApcMin/+ mice.

Chronic inflammation is recognized as a risk factor for colorectal cancer (CRC) development. Baicalin (BI), a major constituent in an anti-inflammatory herb Scutellaria baicalensis, can be biotransformed into baicalein (BE) by the intestinal microbiota. We evaluated the anti-inflammation and anti-CRC effects of the metabolite BE. The in vitro biotransformation by human intestinal microbiota from BI into BE has been determined with HPLC. Using a gut-specific ApcMin/+ mouse model, the effects of oral BE on the life span, organ index, and tumor multiplicity were evaluated. The expressions of inflammatory cytokines were determined using ELISA. To verify the in vivo data, the anti-inflammatory and antiproliferative effects of BE were determined with an in vitro cell model. HPLC analysis showed that BI was quickly transformed into BE by the intestinal microbiota. Oral BE (30 mg/kg/day) significantly increased the life span, from 125.2 to 218.4 days (P < 0.01%). BE treatment also decreased intestine index and increased spleen index. Compared with the model group, following BE treatment, tumor numbers were significantly reduced in the small intestine and colon (P < 0.01, P < 0.05, respectively). In the gut tissues, BE treatment significantly reduced inflammatory cytokine levels such as IL-1β, IL-2, IL-6, IL-10, G-CSF, and GM-CSF. In vitro data supported our in vivo results that the anti-CRC effects of BE were via the inhibition of gut inflammation and induction of cancer cell death. Our results suggest that the parent compound BI can be quickly converted into its microbial metabolite BE, which has stronger bioactive effects than BI. Baicalein is an active chemopreventive metabolite for inflammatory associated CRC.
Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma

Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12-213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (> 5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP > 5.5 was associated with the presence of cirrhosis (P =0.001), coexisting non-alcoholic steatohepatitis (NASH) (P = 0.035), and GT 1 (P = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis (P = 0.003), Child-Pugh score < 6 (P = 0.015), and baseline AFP < 10 (P = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child-Pugh score < 6, and baseline AFP < 10.
Functional Dart Thrower’s Motion (DTM) of the wrist and the injured scapholunate interosseous ligament: a scoping review

Date Presented 04/05/19 Primary Author and Speaker: Jamie Bergner Contributing Authors: Jennifer Farrar, Rogelio Coronado
Measuring eye movements during locomotion: filtering techniques for obtaining velocity signals from a video-based eye monitor

Video-based eye-tracking systems are especially suited to studying eye movements during naturally occurring activities such as locomotion, but eye velocity records suffer from broad band noise that is not amenable to conventional filtering methods. We evaluated the effectiveness of combined median and moving-average filters by comparing prefiltered and postfiltered records made synchronously with a video eye-tracker and the magnetic search coil technique, which is relatively noise free. Root-mean-square noise was reduced by half, without distorting the eye velocity signal. To illustrate the practical use of this technique, we studied normal subjects and patients with deficient labyrinthine function and compared their ability to hold gaze on a visual target that moved with their heads (cancellation of the vestibulo-ocular reflex). Patients and normal subjects performed similarly during active head rotation but, during locomotion, patients held their eyes more steadily on the visual target than did subjects.
CXL146, a Novel 4H-Chromene Derivative, Targets GRP78 to Selectively Eliminate Multidrug-Resistant Cancer Cells

The 78-kDa glucose-regulated protein (GRP78), an endoplasmic reticulum (ER) chaperone, is a master regulator of the ER stress. A number of studies revealed that high levels of GRP78 protein in cancer cells confer multidrug resistance (MDR) to therapeutic treatment. Therefore, drug candidate that reduces GRP78 may represent a novel approach to eliminate MDR cancer cells. Our earlier studies showed that a set of 4H-chromene derivatives induced selective cytotoxicity in MDR cancer cells. In the present study, we elucidated its selective mechanism in four MDR cancer cell lines with one lead candidate (CXL146). Cytotoxicity results confirmed the selective cytotoxicity of CXL146 toward the MDR cancer cell lines. We noted significant overexpression of GRP78 in all four MDR cell lines compared with the parental cell lines. Unexpectedly, CXL146 treatment rapidly and dose-dependently reduced GRP78 protein in MDR cancer cell lines. Using human leukemia (HL) 60/mitoxantrone (MX) 2 cell line as the model, we demonstrated that CXL146 treatment activated the unfolded protein response (UPR); as evidenced by the activation of inositol-requiring enzyme 1α, protein kinase R-like ER kinase, and activating transcription factor 6. CXL146-induced UPR activation led to a series of downstream events, including extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase activation, which contributed to CXL146-induced apoptosis. Targeted reduction in GRP78 resulted in reduced sensitivity of HL60/MX2 toward CXL146. Long-term sublethal CXL146 exposure also led to reduction in GRP78 in HL60/MX2. These data collectively support GRP78 as the target of CXL146 in MDR treatment. Interestingly, HL60/MX2 upon long-term sublethal CXL146 exposure regained sensitivity to mitoxantrone treatment. Therefore, further exploration of CXL146 as a novel therapy in treating MDR cancer cells is warranted. SIGNIFICANCE STATEMENT: Multidrug resistance is one major challenge to cancer treatment. This study provides evidence that cancer cells overexpress 78-kDa glucose-regulated protein (GRP78) as a mechanism to acquire resistance to standard cancer therapies. A chromene-based small molecule, CXL146, selectively eliminates cancer cells with GRP78 overexpression via activating unfolded protein response-mediated apoptosis. Further characterization indicates that CXL146 and standard therapies complementarily target different populations of cancer cells, supporting the potential of CXL146 to overcome multidrug resistance in cancer treatment.
XenoNet: Inference and Likelihood of Intermediate Metabolite Formation.

Drug metabolism is a common cause of adverse drug reactions. Drug molecules can be metabolized into reactive metabolites, which can conjugate to biomolecules, like protein and DNA, in a process termed bioactivation. To mitigate adverse reactions caused by bioactivation, both experimental and computational screening assays are utilized. Experimental assays for assessing the formation of reactive metabolites are low throughput and expensive to perform, so they are often reserved until later stages of the drug development pipeline when the drug candidate pools are already significantly narrowed. In contrast, computational methods are high throughput and cheap to perform to screen thousands to millions of compounds for potentially toxic molecules during the early stages of the drug development pipeline. Commonly used computational methods focus on detecting and structurally characterizing reactive metabolite-biomolecule adducts or predicting sites on a drug molecule that are liable to form reactive metabolites. However, such methods are often only concerned with the structure of the initial drug molecule or of the adduct formed when a biomolecule conjugates to a reactive metabolite. Thus, these methods are likely to miss intermediate metabolites that may lead to subsequent reactive metabolite formation. To address these shortcomings, we create XenoNet, a metabolic network predictor, that can take a pair of a substrate and a target product as input and (1) enumerate pathways, or sequences of intermediate metabolite structures, between the pair, and (2) compute the likelihood of those pathways and intermediate metabolites. We validate XenoNet on a large, chemically diverse data set of 17 054 metabolic networks built from a literature-derived reaction database. Each metabolic network has a defined substrate molecule that has been experimentally observed to undergo metabolism into a defined product metabolite. XenoNet can predict experimentally observed pathways and intermediate metabolites linking the input substrate and product pair with a recall of 88 and 46%, respectively. Using likelihood scoring, XenoNet also achieves a top-one pathway and intermediate metabolite accuracy of 93.6 and 51.9%, respectively. We further validate XenoNet against prior methods for metabolite prediction. XenoNet significantly outperforms all prior methods across multiple metrics. XenoNet is available at https://swami.wustl.edu/xenonet.
Fostering Culturally Proactive Pedagogies: Designing Learning Events for Elementary Literacy Methods Courses

This design-based study explored what happens when literacy educators from across the country intentionally create learning events that engage preservice teachers in exploring culturally proactive ...
Benchmarking OECD countries’ sustainable development performance: A goal-specific principal component analysis approach

Abstract This paper proposes a framework to assess the status of sustainable development performance of OECD countries towards reaching the 2030 agenda based on the 17 Sustainable Development Goals (SDGs). Each SDG addresses a critical area of sustainable development and is represented with several social, economic, or environmental indicators. As a result of data collection efforts, 17 SDGs are represented with total of over 90 variables following the guidance of United Nation’s (UN) recent reports. Using such a high number of variables to create a benchmark score for each of the 35 OECD countries is a challenging and complex task due to the degree of correlation among the indicators and unit of measurement differences. To cope with these challenges, we proposed a Goal-Specific Principal Component Analysis (GS-PCA) approach and compared statistically with the UN reports for experimental validation purpose. It was found that SDG1 No Poverty, SDG7 Affordable and Clean Energy, SDG11 Sustainable Cities and Communities, SDG17 Partnerships to Achieve the Goal and the group mean of 17 SDGs were found to be improving. On the other hand, SDG4 Quality Education and SDG8 Decent Work and Economic Growth were in decline. The highest performance was observed in SDG 8 Decent Work and Economic Growth (78.06) and the lowest performance was observed in SDG 17 Partnerships to Achieve the Goal (29.93). In addition, substantial differences were observed in the scores and ranks of mediocre and poor performing countries compared to the benchmark reports, while both the results of this study and benchmark reports were found to be strongly positively correlated.
Engaging in Interactive Book Reading: Experiences of Refugee Mother–Child Dyads

Interactive book reading is an active practice that aims to stimulate children’s language and literacy development. The interactions that take place during book reading are essential to understand; however, there is limited research on the practice of interactive book reading within refugee families. This qualitative study utilized observation and focus group data to capture the interactions taking place between six refugee mothers and their preschool aged children (3–5 years). The two broad aims of the study were first, to explore interactive book reading experiences of refugee mother–child dyads with the goal of understanding the strategies mothers used during book reading. The second aim was to identify how dual language books benefited families during and beyond interactive book reading. Results demonstrated that mothers incorporated multiple interactive reading strategies while navigating interesting language dynamics. Findings further highlighted the need for continued research on the reading practices of refugee families with preschool-aged children to develop culturally relevant literacy programming and support for these families.
Membrane bending by protein phase separation

Membrane bending is a ubiquitous cellular process that is required for membrane traffic, cell motility, organelle biogenesis, and cell division. Proteins that bind to membranes using specific structural features, such as wedge-like amphipathic helices and crescent-shaped scaffolds, are thought to be the primary drivers of membrane bending. However, many membrane-binding proteins have substantial regions of intrinsic disorder which lack a stable three-dimensional structure. Interestingly, many of these disordered domains have recently been found to form networks stabilized by weak, multivalent contacts, leading to assembly of protein liquid phases on membrane surfaces. Here we ask how membrane-associated protein liquids impact membrane curvature. We find that protein phase separation on the surfaces of synthetic and cell-derived membrane vesicles creates a substantial compressive stress in the plane of the membrane. This stress drives the membrane to bend inward, creating protein-lined membrane tubules. A simple mechanical model of this process accurately predicts the experimentally measured relationship between the rigidity of the membrane and the diameter of the membrane tubules. Discovery of this mechanism, which may be relevant to a broad range of cellular protrusions, illustrates that membrane remodeling is not exclusive to structured scaffolds but can also be driven by the rapidly emerging class of liquid-like protein networks that assemble at membranes.
A Combinatorial Approach to Testing Deep Neural Network-based Autonomous Driving Systems

Recent advancements in the field of deep learning have enabled its application in Autonomous Driving Systems (ADS). A Deep Neural Network (DNN) model is often used to perform tasks such as pedestrian detection, object detection, and steering control in ADS. Unfortunately, DNN models could exhibit incorrect or unexpected behavior in real-world scenarios. There is a need to rigorously test these models with real-world driving scenarios so that safety-critical bugs can be detected before their deployment in the real world.In this paper, we propose a combinatorial approach to testing DNN models. Our approach generates test images by applying a set of combinations of some basic image transformation operations to a seed image. First, we identify a set of valid transformation operations or simply transformations. Next, we design an input parameter model based on the valid transformations and generate a t-way (t=2) combinatorial test set. Each test represents a combination of transformations, and can be used to produce a test image. We execute the test images on a DNN model and distinguish between consistent and inconsistent behavior using a relation. We conducted an experimental evaluation of our approach on three DNN models that are used in the Udacity challenge. Our results suggest that test images generated by our approach can effectively identify inconsistent behaviors and can significantly increase neuron coverage. To the best of our knowledge, our work is the first effort to use a combinatorial testing approach to generating test images based on image transformations for testing DNNs used in ADS.
Population variability of Neotropical rodents: influence of body size, habitat, and food habits

Population variability of Neotropical rodents is examined with respect to taxon, body mass, habitat association, and trophic category. The coefficient of variation of reported density estimates of local populations is used as a measure of variability. The Cricetid rodents exhibit the greatest range of variability. Larger species are less variable than smaller ones. Populations of rodents from temperate forests and tropical savannas are more variable than those from tropical wet forests. No clear relation between trophic category and population variability is discernible.
A Student's Guide to Entropy

Striving to explore the subject in as simple a manner as possible, this book helps readers understand the elusive concept of entropy. Innovative aspects of the book include the construction of statistical entropy from desired properties, the derivation of the entropy of classical systems from purely classical assumptions, and a statistical thermodynamics approach to the ideal Fermi and ideal Bose gases. Derivations are worked through step-by-step and important applications are highlighted in over 20 worked examples. Around 50 end-of-chapter exercises test readers' understanding. The book also features a glossary giving definitions for all essential terms, a time line showing important developments, and list of books for further study. It is an ideal supplement to undergraduate courses in physics, engineering, chemistry and mathematics.
The Impact of Foreign Direct Investment (FDI) on Women’s Entrepreneurship

Women entrepreneurs around the world have increasingly contributed to innovation, employment, and wealth creation (Brush & Cooper, 2012; Brush, de Bruin, & Welter, 2009). Studies suggest that foreign direct investment can be an important determinant of entrepreneurship in general. However, the link between foreign ventures and women entrepreneurs remains under-researched. Therefore, we suggest that the presence of foreign ventures affects women's entrepreneurship. We develop and test our model on cross-sectional data encompassing 36 countries in 2006. The results show that foreign direct investment and women's entrepreneurship have an inverted u-shaped relationship. Implications for further research and public policy are discussed.
Relaxation oscillation suppression in Nd:YAG lasers using intra resonator harmonic generation

Relaxation oscillations can be suppressed through proper resonator design and second harmonic generation internal to the resonator. Experimental results are in substantial agreement with a rate equation model.
Imaging Science in Astronomy

The vast majority of information about the universe is collected via electromagnetic radiation. This radiation is emitted by matter distributed across tremendous ranges in temperature, density, and chemical composition. Thus, more than any other science, astronomy depends on innovative methods to extend image taking to new, unexplored regions of the electromagnetic spectrum. To bring sufficient breadth and depth to their studies, astronomers also require imaging capability across a vast range in spatial resolution and sensitivity, with emphasis on achieving the highest possible resolution and signal gain in a given wavelength regime. This simultaneous quest for better wavelength coverage and ever higher spatial resolution and sensitivity represents the driving force for innovation and discovery in astronomical imaging. Classical astronomy—for example, the search for new solar system objects and the classification of stars—is still largely conducted in the optical wavelength regime (400–700 nm). This has been the case, of course, since humans first imagined the constellations, noted the appearance of “wandering stars” (planets), and recorded the appearance of transient phenomena such as comets and novae. During the latter half of the twentieth century, however, a revolution in astronomical imaging took place. This relatively brief period in recorded history saw the development and rapid refinement of techniques for collecting and detecting electromagnetic radiation across a far broader wavelength range, from the radio through γ rays. Just as these techniques have reached maturation, astronomers have also developed the means to surmount apparently fundamental physical barriers placed on image quality, such as the distorting effects of refraction by Earth's atmosphere and diffraction by a single telescope of finite aperture. The accelerating pace of these innovations has resulted in deeper understanding of, and heightened appreciation for, both the rich diversity of astrophysical phenomena and the fundamental, unsolved mysteries of the cosmos. Keywords: multiwavelength imaging; requirements; limitations; space infrared telescope facility; obstacles
Evaluating SFI for a CISC architecture

Executing untrusted code while preserving security requires that the code be prevented from modifying memory or executing instructions except as explicitly allowed. Software-based fault isolation (SFI) or "sandboxing" enforces such a policy by rewriting the untrusted code at the instruction level. However, the original sandboxing technique of Wahbe et al. is applicable only to RISC architectures, and most other previous work is either insecure, or has been not described in enough detail to give confidence in its security properties. We present a new sandboxing technique that can be applied to a CISC architecture like the IA-32, and whose application can be checked at load-time to minimize the TCB. We describe an implementation which provides a robust security guarantee and has low runtime overheads (an average of 21% on the SPECint2000 benchmarks). We evaluate the utility of the technique by applying it to untrusted decompression modules in an archive tool, and its safety by constructing a machine-checked proof that any program approved by the verification algorithm will respect the desired safety property.
Immunotherapy for Recurrent Spontaneous Abortion

Recurrent spontaneous abortion (RSA) is a significant health problem affecting 2%–5% of reproducing couples (1). Although genetic, anatomic, and hormonal factors have been implicated in the etiology of RSA, a sizable proportion remains unexplained (2). An immunologic cause has been suggested for more than 80% of otherwise unexplained RSAs (3). Immunotherapy in various forms has been proposed as a treatment for these couples (4–12).
Programmed cell death during endosperm development

The endosperm of cereals functions as a storage tissue in which the majority of starch and seed storage proteins are synthesized. During its development, cereal endosperm initiates a cell death program that eventually affects the entire tissue with the exception of the outermost cells, which differentiate into the aleurone layer and remain living in the mature seed. To date, the cell death program has been described for maize and wheat endosperm, which exhibits common and unique elements for each species. The progression of endosperm programmed cell death (PCD) in both species is accompanied by an increase in nuclease activity and the internucleosomal degradation of nuclear DNA, hallmarks of apoptosis in animals. Moreover, ethylene and abscisic acid are key to mediating PCD in cereal endosperm. The progression of the cell death program in developing maize endosperm follows a highly organized pattern whereas in wheat endosperm, PCD initiates stochastically. Although the essential characteristics of cereal endosperm PCD are now known, the molecular mechanisms responsible for its execution remain to be identified.
Gamma-Ray Lines from Supernova 1987A

We review the observations of γ-ray lines from SN 1987A and place them in the context of theoretical expectations and related observations, including the optical light curve and hard X-ray detections.