cssi/SciSciGPT-SciSciNet huggingface dataset:
Use of In Vitro Morphogenesis of Mouse Embryoid Bodies to Assess Developmental Toxicity of Therapeutic Drugs Contraindicated in Pregnancy

In utero exposure to certain chemicals can impair embryo development, causing embryonic death, growth retardation, or severe birth defects. Establishment of effective in vitro tests is crucial for identifying developmental toxicants and for reducing the financial and ethical burden of animal-based tests. Previously, we created an in vitro morphogenesis model using pluripotent P19C5 mouse embryonal carcinoma stem cells that mimics the process of gastrulation and axial body elongation of embryos. Because many birth defects are caused by dysregulation of cellular behaviors during embryogenesis, the morphogenesis model may serve as a unique tool to investigate the impacts of developmental toxicants. The aim of this study is to evaluate the applicability and limitations of the model using 20 therapeutic drugs, 16 of which are contraindicated in pregnancy and 4 are considered safe. P19C5 embryoid bodies (EBs) were exposed to different concentrations of drugs during 4 days of 3-dimensional culture. The treatment effects on growth and morphogenesis were analyzed using morphometric measurements of EB size and shape, respectively. Viability assays of P19C5 cells and NIH/3T3 fibroblasts were used to determine the drug concentrations that caused general cytotoxicity and those that selectively diminished P19C5 proliferation relative to NIH/3T3 proliferation. Thirteen contraindicated drugs diminished P19C5 cell proliferation, reduced EB growth, or altered morphogenesis at concentrations below generally cytotoxic levels. Two safe drugs also exhibited these impacts at the highest concentration tested. Although additional validation studies are required, this study introduces morphogenesis-based stem cell models as potentially effective in vitro tools for developmental toxicity research.
In Search of Balance: A Conceptual and Empirical Integration of Multiple Meanings of Work–Family Balance

This paper provides a framework that elaborates on four conceptualizations of work-family balance: additive spillover (unique effects of bi-directional conflict and enrichment), multiplicative spillover (interactive effects of lower conflict with higher enrichment), balance satisfaction (one's attitude toward resource allocation across work and family roles) and balance effectiveness (one's interdependent self-evaluation of meeting shared expectations across work and family roles). We describe the conceptual differences among these approaches and hypothesize how they operate differently in predicting work and family attitudes and performance. Relative weights analyses showed that additive spillover was the most important predictor of work attitudes (organizational commitment, job satisfaction, and turnover intent), followed by balance satisfaction and effectiveness. However, balance satisfaction and effectiveness together were the most important predictors of family satisfaction and job and family performance. Mediation tests revealed that unique and interactive effects of bidirectional conflict and enrichment related to work and family attitudes and performance indirectly through balance satisfaction and effectiveness. We discuss implications of these findings and offer suggestions to guide future research and theory on work-family balance.
A compact planar self-affine sierpinski carpet fractal monopole antenna with band notch characteristics for ultra wideband communications

This paper presents a novel compact planar self-affine sierpinski carpet fractal monopole coplanar waveguide (CPW) fed ultra-wideband (UWB) antenna with improved gain, radiation efficiency and a sharp band-notched characteristics for the rejection of interfering WLAN (5.15---5.825 GHz) assigned for IEEE 802.11a narrow band communication system. The significant improvements in gain and radiation efficiency are achieved by the introduction of carpet fractals in the radiating circular patch. The antenna covers the entire UWB frequency band (3.1---10.6 GHz) with voltage standing wave ratio (VSWR) ≤ 2 which depicts optimum impedance matching of the proposed antenna structure. The antenna occupies a compact size of 36 × 41 mm2 and band rejection is achieved by embedding compact C--shaped slots with folded arms on the ground planes of the CPW feed lines which yield a very sharp notch for WLAN band. The band rejection is demonstrated by a high value of VSWR around notch frequency. Compact self-affine sierpinski carpet fractals are introduced in the radiating circular patch to improve performance of the UWB antenna. The proposed fractal antenna exhibits improved gain that varies from 2 to 6 dBi and optimum radiation efficiency which varies from 85 to 99.9 % over the UWB frequency range. The gain and radiation efficiency are suppressed with strong dips at the desired rejection WLAN band. Omnidirectional radiation characteristic is achieved over UWB frequency range which supports the uniform transmission of signal irrespective of the orientation of the antenna direction.
Criteria for the Diagnosis of Melanoma

Despite the introduction of molecular techniques, the diagnosis of melanoma is still mainly achieved through the recognition of particular histological details (criteria) that, when taken together, should allow us to reach the correct diagnosis. Unfortunately, this procedure is hampered by the low specificity and sensitivity of many criteria, by personal bias, and the presence of conflicting criteria in the same lesion.
"It was my fault": bullied students' causal and controllable attributions in bullying blogs

Student bullying is a growing and damaging social problem. The devastating outcomes bullied individuals often experience due to such treatment make understanding this phenomenon imperative. Utilizing Heider's (1958) attribution theory, this study explores how bullied students (n = 100) attribute locus of causality and controllability for their victimization in 5 bullying blogs. Findings from this investigation reveal that (a) male and female bloggers' causal and controllable attributions do not differ; (b) bloggers most often attribute blame to bullies, although a noteworthy portion also attribute internal causation; and (c) bloggers often attribute bullying as uncontrollable for several reasons. This study also identifies factors that influence shifts in negative attributions about bullying. These findings inform bullying programs with the hope of reducing destructive attribution formations that potentially lead to prolonged victimization and detrimental consequences.
Abstract 2710: Aggressive Blood Pressure Lowering in Acute Intracerebral Hemorrhage is Associated with Perihematomal Hypoperfusion and Ischemia

Introduction Optimal blood pressure control following acute ICH remains controversial. Blood pressure reduction may limit hematoma expansion, but may also cause hypoperfusion and further damage in the perihematomal region. We examined the relationship between the extent and speed of systolic blood pressure (SBP) lowering and perihematomal perfusion and ischemia. Methods Consecutive prospectively enrolled ICH patients with an MRI within 24 hours of symptom onset were included. Hourly SBPs were recorded from hospital presentation to MRI acquisition. Aggressive BP lowering was defined as: ≥30% reduction from baseline and at least one BP drop of ≥35mmHg/h. Hematoma volume was considered large if ≥30cc. FLAIR, GRE and perfusion weighted images were co-registered. T max maps were generated using RApid processing of PerfusIon and Diffusion (RAPID) software. The perihematomal region was defined by outlining the perihematomal edema on FLAIR images and subtracting the inner surface of blood products on the GRE generating a perihematomal rim. Statistical analyses were done using MATLAB. Results Twenty-seven patients were included (age: 62.7±17.9years; ICH volume: 26±26cc). Six of 27 (22%) patients experienced aggressive SBP lowering. Numbers reported: mean(IQR). The aggressiveness of SBP reduction was similar in large versus small hematomas: the percentage drop in SBP was 26% (10-33) vs. 21% (13-28), and the highest SBP drop was 43mmHg/h (29-56) versus 46mmHg/h (31-51), p=0.61 and p=0.92, respectively. Patients with SBP drops ≥35mmHg/h tended to have delayed bolus arrival (high T max ), 6.1s (4.8-7.7) versus 5.3s (3.5-5.6) (p=0.06), as did patients with SBP drops ≥30%,T max values 7.3s (6.2-8.6) versus 5.3s (3.6-6.2) (p=0.014). The effect was magnified in patients with a large (≥30%) and fast (≥35mmHg/h) drop in SBP, despite hematoma volumes being equivalent (p=0.01, Figure1). Five of 6 patients with aggressive SBP lowering had a T max >6s. Conversely, 7 out of 8 patients with modest SBP reduction had a T max ≤6s (Figure2). Out of 11 patients with T max >6s, 8 had DWI lesions (73%) versus 4 of 16 (25%) with T max ≤6s (p=0.02). Conclusions: Aggressive SBP lowering in acute ICH is associated with high T max values in the perihematomal region irrespective of hematoma volume. High T max values in turn are associated with DWI lesions.
Real Estate Portfolio Risk Reduction through Intracity Diversification

Executive Summary. This study examines gains in real estate portfolio efficiency obtainable through intracity diversification. Employing a unique, ten-and-a-half year, Seattle, Washington, apartmen...
Rapid Process Optimization: A Novel Process Improvement Methodology to Innovate Health Care Delivery

Health care systems have utilized various process redesign methodologies to improve care delivery. This article describes the creation of a novel process improvement methodology, Rapid Process Optimization (RPO). This system was used to redesign emergency care delivery within a large academic health care system, which resulted in a decrease: (1) door-to-physician time (Department A: 54 minutes pre vs 12 minutes 1 year post; Department B: 20 minutes pre vs 8 minutes 3 months post), (2) overall length of stay (Department A: 228 vs 184; Department B: 202 vs 192), (3) discharge length of stay (Department A: 216 vs 140; Department B: 179 vs 169), and (4) left without being seen rates (Department A: 5.5% vs 0.0%; Department B: 4.1% vs 0.5%) despite a 47% increased census at Department A (34 391 vs 50 691) and a 4% increase at Department B (8404 vs 8753). The novel RPO process improvement methodology can inform and guide successful care redesign.
Seismic study of crustal structure in Pennsylvania and New York

Abstract Blasts at two quarries in northern New York and central Pennsylvania have been recorded to a distance of 309 km. The data indicate an essentially homogeneous, unlayered crust, with elastic wave velocities possibly increasing with depth. An average crustal thickness for the region is 34.4 km., with no indication of significant difference in thickness between the two areas. Observed compressional wave velocities for the crust are 6.39 and 6.31 km/sec. for New York, and 6.04 km/sec. for Pennsylvania. The corresponding shear wave velocities are 3.62 and 3.60 km/sec., and 3.61 km/sec. Average upper mantle velocities are 8.14 km/sec. for P n and 4.69 km/sec. for S n . The compressional wave velocity of anorthosite near Tahawus, N.Y., is 6.63 km/sec. No near-vertical reflections from the Mohorovicic discontinuity were observed.
Energy States of Ligand Capped Ag Nanoparticles: Relating Surface Plasmon Resonance to Work Function

The work function (WF) and surface plasmon resonance (SPR) of organic ligand capped Ag nanoparticles (NPs) have been studied experimentally and computationally. Experimental observations reveal a significant increase in WF as the size of ligand-capped Ag NPs increases, a trend contrary to that previously observed for bare Ag NPs. Computational results confirm the effect on the WF from simplified ligand molecules and relate it to charge transfer between the Ag core and surrounding ligands. We also observe a possible coupling between increases in WF and decreases in SPR transition energy, supported by computational results and attributed to the interplay between the 4d and 5s electron states of the system. These results, along with our observations of WF dependence on ligand choice, indicate the ability to strongly engineer the electronic structure of metal NPs through size and ligand control.
Effect of intravenously injected radioisotopes on metastatic tumor cells in organs of the mouse.

Summary and Conclusion1. Intraperitoneal inoculation of liver brei from sarcoma-37 (i.p. growth, 5-day-old) induced tumor growth in nearly all of mice. This was attributed to the presence in the liver of metastatic cells spread from the primary tumor. Similar results were obtained only in rare instances with liver brei from the mice of the same series injected intravenously with colloidal Au198 on the date of primary tumor inoculation (graft) or 2 days earlier or later. Analogous difference in results was recorded in experiments with i.p. inoculation of lung brei from tumor-bearing mice untreated and treated intravenously with radioactive chromic phosphate. It was concluded that injected radioisotopes reduced the number and the viability of metastatic tumor cells in the liver or in the lung. 2. Tumor growth from the organs which retain only small amounts of particulate isotopes (spleen) or none was but slightly inhibited or not at all. It was concluded that retention of radioisotopes by the organ was a pr...
Examination of moderators of expressive writing in patients with renal cell carcinoma: the role of depression and social support.

Objective To identify groups most likely to benefit from an Expressive Writing (EW) intervention, we examined psychosocial variables as intervention moderators. We hypothesized that EW would be particularly effective for participants with high levels of depressive symptoms and social support at study entry. Methods Patients (n = 277; 60.6% male) with kidney cancer were randomly assigned to either an expressive (EW) or neutral writing (NW) condition. Intervention outcomes included measures of depressive symptoms (CESD), cancer-related symptoms (MDASI), fatigue (BFI), and sleep disturbances (PSQI) assessed at baseline, 1, 4, and 10 months later. Moderators were measured at baseline. Results As hypothesized, depressive symptoms and social support moderated intervention efficacy. When examining both moderators simultaneously, EW appeared to be most effective in terms of cancer-related symptoms (p < 0.05) and depressive symptoms (p < 0.01) for participants with elevated depressive symptoms who received high levels of social support at baseline relative to their counterparts in the NW condition. Moreover, participants in EW with high levels of social support at baseline reported lower levels sleep disturbances (p = 0.005) than their counterparts in NW. Conclusions Recognition of baseline depressive symptoms and social support as intervention moderators may lead to improved patient selection for EW interventions, as EW may be particularly beneficial regarding QOL outcomes for patients that have social support available including participants with depressive symptoms. EW may not be beneficial, or potentially even contraindicated, for participants lacking social support. Copyright © 2016 John Wiley & Sons, Ltd.
Epidemiological Investigation on 306 Cases with Japanese Encephalitis in Kaijiang County

ObjectiveTo study epidemic and clinical features of Japanese encephalitis(JE) and to provide scientific basis for JE prevention and control.MethodsThe data of 306 cases with JE from 1985 to 2005 were carried out epidemiological case investigation and analysis.Blood of JE cases from 2002 to 2005 was taken to detect the IgM antibody by the reverse passive hemagglutination inbibition(RPHI).ResultsThree hundred and six cases with JE were distributed in 168 villages and residents' committees of 20 towns in Kaijiang County.The incidence in rural area was 37.25 times of that in cities and towns with the fatality rate of 3.27%(10/306).The onset peak concentrated on August,accounting for 63.73%(195/306).Childen of 2 to 6 years old occupied 78.43%(240/306).The ratio between male and female was 1.41∶1.The cases appeared mostly in children living scattered,accounted for 57.19%(175/306).The body temperature ≥39℃ occupied 88.56%(271/306).The patients were most of medium and severe types,accuounting for 71.90%(220/306).There was an increase tendency of severe and critically severe along with the age growth.There were 10.46%(32/306) with inoculation of vaccinum encephalitidis epidemicae,and 52.81%(47/89) with mosquito contolling measures in family.The clinical serodiagnosed rate of JE cases was 63.33%(19/30).ConclusionsThe prevention tactics of JE epidemic should be focused on children of 2 to 6 years old living scattered.And mosquito controlling and killing are the keys to controlling prevalence of JE.
The surface analysis and surface treatment of PBO fiber

A series of study were carried out on the coating composition and content on the PBO fiber surface through thermal gravitation analysis(TGA) and infrared spectroscopy(IR).The relationship between the concentration of coupling agent and the pull-out strength was investigated through the pull-out test.The results show that the coating on fiber surface consists of several organic compounds,and the treatment of surface through coupling agent can increase interface bonding strength.The coupling agents include KH560,KH550,KH570,KH590.The efficiency of treatment with KH560 is upto 59% of strength increase and better than that with other agents.
Predicting ventilator-induced lung injury using a lung injury cost function.

This article describes a new computational model of lung mechanics that includes mechanisms for predicting the development of ventilator-induced lung injury (VILI) via the mechanisms of both volutr...
Chemical Composition of Living Cells

Abstract: Most all diseases in animals are manifestations of abnormalities in biomolecules, chemical reactions, or biochemical pathways, so understanding the macromolecules within cells is critical. Hydrogen, oxygen, nitrogen, carbon, sulfur and phosphorus normally make up more than 99% of the mass of living cells. This chapter aims to give an overview of critical macromolecules, while going into more detail for the general structure and important details about intra and extracellular proteins; homogenous from heterogenous polymers; compound, simple and derived lipids. It also aims to allow readers to articulate how and why the inorganic elements are essential to life, as well as understand a basic understanding of physiological chemistry is fundamental to a clinical understanding of disease processes.
Tolerancing, alignment and test of the Transiting Exoplanet Survey Satellite (TESS) optical assembly

The Transiting Exoplanet Survey Satellite (TESS) will carry four visible waveband seven-element refractive f/1.4 lenses, each with a 34 degree diagonal field of view. This paper describes the tolerancing, assembly and alignment methods developed during the build of the TESS Risk Reduction Unit optical system. Lens assembly tolerances were derived from a sensitivity analysis using an image quality metric customized for mission performance. The optomechanical design consists of a two-stage lens housing that provides access for active alignment of each lens using a Trioptics OptiCentric measurement system. Thermal stresses and alignment shifts are mitigated by mounting the optics with cast RTV silicone spacers into individually aligned bezels, and custom fixtures were developed to aid in RTV bonding with reduced alignment error. The lens assembly was tested interferometrically over the field of view at room temperature and results were used to successfully predict lens performance and compensator adjustments and detector shim thickness for the -75C operational temperature and pressure.
Insights into the Mechanism of Tandem Alkene Hydroformylation over a Nanostructured Catalyst with Multiple Interfaces.

The concept of tandem catalysis, where sequential reactions catalyzed by different interfaces in single nanostructure give desirable product selectively, has previously been applied effectively in the production of propanal from methanol (via carbon monoxide and hydrogen) and ethylene via tandem hydroformylation. However, the underlying mechanism leading to enhanced product selectivity has remained elusive due to the lack of stable, well-defined catalyst suitable for in-depth comprehensive study. Accordingly, we present the design and synthesis of a three-dimensional (3D) catalyst CeO2–Pt@mSiO2 with well-defined metal–oxide interfaces and stable architecture and investigate the selective conversion of ethylene to propanal via tandem hydroformylation. The effective production of aldehyde through the tandem hydroformylation was also observed on propylene and 1-butene. A thorough study of the CeO2–Pt@mSiO2 under different reaction and control conditions reveals that the ethylene present for the hydroformylat...
Density Segregation of Corn and Wheat Naturally Contaminated with Aflatoxin, Deoxynivalenol and Zearalenone

Density segregation was used to reduce mycotoxin levels of corn samples naturally contaminated with aflatoxin or deoxynivalenol, and wheat samples naturally contaminated with deoxynivalenol or zearalenone. Corn kernels which were buoyant in saturated sodium chloride represented 3% of the total sample, yet contained 74% of the aflatoxin. Corn buoyant in water contained 51 and 14% of the total deoxynivalenol present in two naturally contaminated corn samples. Subsequent segregation of corn non-buoyant in water with 30% sucrose removed additional deoxynivalenol-contaminated kernels, resulting in the combined removal of 59 and 79% of the deoxynivalenol. Removal of deoxynivalenol-contaminated corn kernels with both water and 30% sucrose reduced the concentration of deoxynivalenol by 53 and 77%. Removing wheat buoyant in water and 30% sucrose decreased the deoxynivalenol present by 96 and 68%, and reduced the deoxynivalenol concentration by 96 and 67%. Removing wheat naturally contaminated with zearalenone buoyant in water and 30% sucrose combined resulted in no detectable zearalenone remaining in the non-buoyant fraction of the samples.
Simplification by elimination

The Petroleum and Chemical industry continues to test the boundaries of project and system size to deliver bigger facilities, at less cost, and in a shorter timeframe. The effect is an increased pressure on systems, engineering capabilities, and disciplines that are dependent on others for information to deliver on a reduced schedule. This paper will present two key ideas for electrical system design to increase execution certainty and remove dependencies. The first will be the concept of elimination: removing or rearranging components specifically for control and management of power systems to simplify interfaces and reduce cable. The second will be simplification: understanding how the integration of instrument control and safety systems with smart motor control centers increases design certainty to reduce schedule and dependencies.
Rhabdomyolysis After Coadministration of Atorvastatin and Sacubitril/Valsartan (Entresto™) in a 63-Year-Old Woman

A 63-year-old woman previously stable on a regimen of atorvastatin 40 mg daily, carvedilol 25 mg twice daily, digoxin 0.125 mg daily, furosemide 40 mg daily, spironolactone 25 mg daily, rivaroxaban 15 mg daily, and enalapril 20 mg twice daily for heart failure developed rhabdomyolysis 26 days after enalapril was stopped and sacubitril/valsartan (Entresto™) started. The patient received sacubitril/valsartan at 24/26 mg twice daily for heart failure; however, after 26 days she developed muscle and skin pain. Investigations revealed elevated creatine kinase and liver function tests, and rhabdomyolysis with raised transaminases was diagnosed. Sacubitril/valsartan and atorvastatin were discontinued and the patient was hydrated. She returned to baseline in 23 days and has not had any reoccurrence of rhabdomyolysis and elevated transaminases for 46 days. A Naranjo assessment score of 5 was obtained, indicating a probable relationship between the patient’s rhabdomyolysis and her use of sacubitril/valsartan. The Drug Interaction Probability Scale score was 3, consistent with a possible interaction as a cause for the reaction, with sacubitril/valsartan as the precipitant drug and atorvastatin as the object drug.
Fractional In Situ Pad Conditioning in Chemical Mechanical Planarization

Material removal rate, shear force and variance of shear force during copper polishing are studied as a function of pad conditioning scheme: 0% in situ conditioning (i.e., basically the equivalent of ex situ conditioning) and fractional in situ conditioning variants (i.e., conditioning during the first 25, 50, 75 or 100% of the total polish time). Spectral analysis of raw shear force data is employed to help elucidate the fundamental physical phenomena during copper chemical mechanical planarization. Fast Fourier transform is performed to convert the shear force data from time domain into frequency domain. The energy distribution of copper polishing is quantified which sheds light on the effect of fractional in situ pad conditioning. Variance of shear force and spectral analysis indicate that pad micro-texture evolution ceases after 50% fractional conditioning, thereby indicating that in situ conditioning time can be reduced during a given polishing process thus extending pad life. This study shows that a combination of unique spectral fingerprinting and analysis of force variance can be used to monitor the effect of pad conditioning in real time. This work also underscores the importance of real-time detection and non-destructive method to extend pad life and consumable usage during CMP by optimizing the pad conditioning time.
Investigation of Many-Body Correlation in Biexcitonic Systems Using Electron–Hole Multicomponent Coupled-Cluster Theory

Generation of biexcitons in semiconductor nanoparticles has important technological applications in designing efficient light-harvesting materials. Like excitons, the attractive electron–hole interaction terms are responsible for binding in biexcitonic systems. However, unlike excitons, electron–electron and hole–hole repulsive components also contribute to the overall interaction in a biexcitonic system. Consequently, a balanced treatment of many-body correlation associated with electron–electron, hole–hole, and electron–hole interactions is needed for understanding quaisparticle binding in biexcitons. This work presents a theoretical investigation of the effect of size and chemical composition on biexciton binding energies in semiconductor nanoparticles using the electron–hole multicomponent coupled-cluster theory (eh-mcCC). Exciton and biexciton binding energies for quantum dots with diameters 1–20 nm for four semiconductor materials (CdSe, CdS, CdTe, and PbS) were calculated using the eh-mcCC method. ...
Compositional effects in Ag2ZnSnSe4 thin films and photovoltaic devices

Abstract Ag2ZnSnSe4 (AZTSe) is a relatively new n-type photovoltaic (PV) absorber material which has recently demonstrated a conversion efficiency of ∼5% in a Schottky device architecture. To date, little is known about how the influence of composition on AZTSe material properties and the resulting PV performance. In this study, the Ag/Sn ratio is shown to be critical in the controlling grain growth, non-radiative recombination, and the bulk defect structure of the absorber. Insufficient Ag (relative to Zn and Sn) results in small grains, low photoluminescence intensities, and band gap narrowing, possibly due to an increase in the bulk defect density. Additionally, etching the AZTSe films in KCN prior to junction formation is found to be important for achieving reproducible efficiencies. Surface analysis using Auger Nanoprobe Microscopy analysis reveals that a KCN etch can selectively remove potentially harmful Ag-rich secondary phases, therefore improving the MoO3/AZTSe junction quality. Moreover, grain boundaries in AZTSe are found to be enriched in Sn and O following KCN; the role this oxide plays in surface passivation and junction formation has yet to be determined.
‘Angry Mab with Blisters Plague’: The Pre-Modern Science of Contagion in Romeo and Juliet

Critics have often struggled with reconciling Mercutio’s Queen Mab speech with the rest of Romeo and Juliet. As Harold C. Goddard observes, ‘The famous description of her has been widely held to be . . . an outburst of poetry from the author put arbitrarily in Mercutio’s mouth.’1 E. Pearlman maintains that ‘There is no overlap between the realist, materialist Mercutio and the Mercutio who celebrates Queen Mab in elaborate, imaginative, and romantic terms.’2 But scholars interested in finding traces of the history of science in early modern literature suggest that Mercutio offers a vision that ‘anticipates the worlds which early microscopists glimpse through the lens some thirty years later.’3 As Jennifer Ailles imaginatively puts it, ‘By figuring the originator of dreams as an external creature that is small, almost at the ‘atomi[c]’ level of germs and bacteria, and which invades the larger corpus without impunity, Shakespeare provides a pseudo-medical discourse of infection that is closer to what medical scientists now know and postulate about the spread of disease.’4 Although Romeo and Juliet is one of the few plays of the period to stage, however obliquely, the actual presence of plague in the community, few early modern medical writers conceived of diseases as individual entities, much less as substances operating on the ‘atomic level’ of germs or microbes. And yet Mercutio’s story of Queen Mab does provide us with an early modern narrative of how infection spreads. In a culture that understood the plague in supernatural terms, as a punishment sent by God, many writers suggested that demonic invisible spirits were the agents of an epidemic.
Reflections on the First Man versus Machine No-Limit Texas Hold ‘em Competition

The first human versus computer no-limit Texas hold ‘em competition took place from April 24–May 8, 2015 at River’s Casino in Pittsburgh, PA. In this article I present my thoughts on the competition design, agent architecture, and lessons learned. Several problematic hands from the competition are highlighted that reveal the most glaring weaknesses of the agent. The research underlying the agent is placed within a broader context in the AI research community, and several avenues for future study are mapped out.
Abstract TP413: How Good Is That "doc In The Box"?

A Comprehensive Stroke Center with a telestroke program is a hub for 14 partner hospitals. It has been providing expert stroke neurology consultation using telemedicine for 3 years. Accuracy of the physician assessment of a potential stroke patient using telemedicine is not widely reviewed. Utilizing real time audio/video encounters and the ability to visualize radiology images, it is expected that the physician would be able to make an accurate consult impression of acute ischemic stroke (AIS) and recommend safe treatment options. All patients that were consulted and subsequently transferred to the hub were analyzed for variances between consult impression for AIS and a final discharge diagnosis of AIS. In the first year of the telemedicine program, the stroke neurologists accurately diagnosed 79% of AIS patients transferred to the hub facility. In the second and third year, the accuracy decreased to 76% (p value > 0.05). The consult volume has greatly increased over the three years without impacting the level of care the stroke neurologists have be able to provide. In addition to an average of 77% accuracy in determining AIS, the use of tissue plasminogen activator (tPA) is dramatic when compared to the institutional treatment rate of 18%. The tPA treatment rate for patients consulted using telemedicine with an AIS impression transferred to the hub was compared to the true treatment rate based on discharge diagnosis (Table 1). Table 1 demonstrates a high rate of tPA administration using telemedicine. When the rates are adjusted to recognize the final diagnosis, the rate does not significantly change. Patients that were accepted from a partner hospital post-tPA infusion without a final stoke diagnosis did not experience any adverse sequela related to tPA administration. In conclusion, the Comprehensive Stroke Center Telestroke Program has demonstrated an average of 77% accuracy for evaluating the AIS patient and safe thrombolysis treatment recommendations.
The Role of Sphingosine-1-Phosphate and Ceramide-1-Phosphate in Inflammation and Cancer.

Inflammation is part of our body’s response to tissue injury and pathogens. It helps to recruit various immune cells to the site of inflammation and activates the production of mediators to mobilize systemic protective processes. However, chronic inflammation can increase the risk of diseases like cancer. Apart from cytokines and chemokines, lipid mediators, particularly sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), contribute to inflammation and cancer. S1P is an important player in inflammation-associated colon cancer progression. On the other hand, C1P has been recognized to be involved in cancer cell growth, migration, survival, and inflammation. However, whether C1P is involved in inflammation-associated cancer is not yet established. In contrast, few studies have also suggested that S1P and C1P are involved in anti-inflammatory pathways regulated in certain cell types. Ceramide is the substrate for ceramide kinase (CERK) to yield C1P, and sphingosine is phosphorylated to S1P by sphingosine kinases (SphKs). Biological functions of sphingolipid metabolites have been studied extensively. Ceramide is associated with cell growth inhibition and enhancement of apoptosis while S1P and C1P are associated with enhancement of cell growth and survival. Altogether, S1P and C1P are important regulators of ceramide level and cell fate. This review focuses on S1P and C1P involvement in inflammation and cancer with emphasis on recent progress in the field.
Regulatory policy for the development of targeted therapies for low-frequency molecular subtypes of disease.

Numerous challenges arise when developing targeted therapies for diseases comprising low-frequency molecular subtypes. In this article, we describe a pragmatic, science-based regulatory policy for the development and approval of targeted therapies in such cases. Numerous challenges arise when developing targeted therapies for diseases comprising low-frequency molecular subtypes. In this article, we describe a pragmatic, science-based regulatory policy for the development and approval of targeted therapies in such cases.
Investigating Lock Delay on the Upper Mississippi River: a Spatial Panel Analysis

A set of 28 lock and dam sites on the upper Mississippi River is essential to transporting US agricultural commodities to the world market. Currently, increasing delay of tows and vessels at this aging lock and dam system have generated great concerns about the navigational efficiency of this inland waterway. However, limited studies have focused on the statistical analysis of the relationship between lock delay and lock characteristics. In addition, previous research on the association between lock delay and lock traffic, or other characteristics, have neglected the spatial dependence among locks although the departures (arrival distributions) at a given lock could affect (be affected by) the arrivals (departures) at the adjacent locks. The objective of this study is to examine the impact of selected factors on delay at the lock and dam system using a spatial panel analysis incorporating spatial interdependence among locks. Results suggest that a 1% increase in lockage processing time result in a 2.3% increase in lock delay considering both direct and spillover effects on the upper Mississippi River. Numbers of lockage for commercial vessels at a given lock also contribute to its own delay and delay at other locks. Our findings confirm the importance of incorporating spatial spillover effect in the analysis of delay issue on inland waterway given the interdependence among locks.
Appraising cervical mucus: a new approach to evaluating contraceptives.

Purpose: Timing of sample collection represents a major source of variability in studies evaluating the effects of administered agents on cervical mucus in naturally-cycling women. We sought to cre...
Stability and Change in Kelp Forest Habitats at San Nicolas Island

Kelp forest communities are highly variable over space and time. Despite this complexity it has been suggested that kelp forest communities can be classified into one of 2 states: kelp dominated or sea urchin dominated. It has been further hypothesized that these represent “alternate stable states” because a site can remain in either of these states for decades before some perturbation causes a rapid shift to the other state. Our research group has maintained a subtidal community monitoring program for 38 years at San Nicolas Island consisting of twice-annual scuba-based surveys at 6 sites distributed within 4 regions around the island. Three types of perturbations are thought to be relevant to subtidal community dynamics at San Nicolas: (1) physical disturbances in the form of major storm and El Nino/ Southern Oscillation (ENSO) events; (2) invertebrate diseases, which periodically decimate urchin populations; and (3) the reintroduction and subsequent increase of sea otters (Enhydra lutris nereis). These 3 perturbations differ in spatial and temporal specificity; physical disturbances and disease outbreaks occur periodically and could affect all 4 regions, while sea otter predation has been concentrated primarily at the West End sites over the last 15 years. The different types of perturbations and the duration of the time series at the kelp forests at San Nicolas make the data set ideal for testing the “alternate stable state” hypothesis. We use nonmetric multidimensional scaling (NMDS) to examine spatial and temporal patterns of community similarity at the 4 regions. In particular, we evaluate support for the existence of stable states, which are represented on NMDS plots as distinct spatial clusters. Community dynamics at each site approximated a biased random walk in NMDS space, with one or more basins of attraction and occasional jumps between basins. We found evidence for alternative stable states at some sites, and we show that transitions from one stable state to another may be influenced by interactions between multiple perturbations.
Mechanisms of rapid cancer cell reprogramming initiated by targeted receptor tyrosine kinase inhibitors and inherent therapeutic vulnerabilities

Receptor tyrosine kinase (RTK) pathways serve as frequent oncogene drivers in solid cancers and small molecule and antibody-based inhibitors have been developed as targeted therapeutics for many of these oncogenic RTKs. In general, these drugs, when delivered as single agents in a manner consistent with the principles of precision medicine, induce tumor shrinkage but rarely complete tumor elimination. Moreover, acquired resistance of treated tumors is nearly invariant such that monotherapy strategies with targeted RTK drugs fail to provide long-term control or cures. The mechanisms mediating acquired resistance in tumors at progression treated with RTK inhibitors are relatively well defined compared to the molecular and cellular understanding of the cancer cells that persist early on therapy. We and others propose that these persisting cancer cells, termed “residual disease”, provide the reservoir from which acquired resistance eventually emerges. Herein, we will review the literature that describes rapid reprogramming induced upon inhibition of oncogenic RTKs in cancer cells as a mechanism by which cancer cells persist to yield residual disease and consider strategies for disrupting these intrinsic responses for future therapeutic gain.
Density Functional Theory Investigation of the Role of Cocatalytic Water in the Water Gas Shift Reaction over Anatase TiO2 (101)

The water gas shift reaction (WGS) mechanism on the anatase TiO2 (101) surface has been investigated using periodic density functional theory. Reaction energies and activation energy barriers for direct CO oxidation and associative pathways with carboxyl and formate intermediates were calculated and compared. Unassisted by water, the formation of formate was infeasible due to the difficulty in transferring hydrogen from the anatase surface to hydrogenate CO, while the carboxyl mechanism had the lowest apparent activation energy barrier among the three. Coadsorbed water species were found to be effective hydrogen transfer cocatalysts, with molecularly physisorbed water acting as a hydrogen donor and dissociatively chemisorbed water acting as a hydrogen acceptor. Using water as the hydrogen donor, CO hydrogenation became competitive with the carboxyl mechanism, indicating that the reactivity of water could change the relative competitiveness of different WGS pathways. These results suggest that adsorbed wat...
The C-Test: A Viable Alternative to the Use of the Cloze Procedure in Testing?

A few years ago, two German researchers, Christine Klein-Braley and Ulrich Raatz, developed a test procedure which they believe maintains the virtues of the cloze test procedure while exhibiting none of its defects — the C-Test. The C-Test consists of a number of texts or passages in which, beginning in the second or third sentence in each passage, the second half of every other word has been deleted, leaving the first part of each mutilated word as a cue for the test taker.
Multivariate probabilistic approximation in wavelet structure

Let $$\varphi _0 (x,y): = \{ _{0,}^{1,} {\text{ }}_{otherwise}^{{\text{x,y}} \geqslant {\text{0}}} $$ and F(x,y) be a continuous distribution function on R2.
UPLC-MS/MS analysis of dextromethorphan-O-demethylation kinetics in rat brain microsomes.

Abstract Formation of dextrorphan (DXT) from dextromethorphan (DXM) has been widely used to assess cytochrome P450 2D (CYP2D) activity. Additionally, the kinetics of CYP2D activity have been well characterized in the liver microsomes. However, studies in brain microsomes are limited due to the lower microsomal content and abundance of CYP2D in the brain relative to the liver. In the present study, we developed a micro-scale enzymatic incubation method, coupled with a sensitive UPLC-MS/MS assay for the quantitation of the rate of DXT formation from DXM in brain microsomes. Rat brain microsomes were incubated with different concentrations of DXM for various times. The reaction was stopped, and the proteins were precipitated by the addition of acetonitrile, containing internal standard (d3-DXT). After centrifugation, supernatant (2 μL) was injected onto a UPLC, C18 column with gradient elution. Analytes were quantitated using triple-quadrupole MS/MS with electrospray ionization in positive ion mode. The assay, which was validated for accuracy and precision in the linear range of 0.25 nM to 100 nM DXT, has a lower limit of quantitation of 0.125 fmol on the column. Using our optimized incubation and quantitation methods, we were able to reduce the incubation volume (25 μL), microsomal protein amount (5 μg), and incubation time (20 min), compared with reported methods. The method was successfully applied to estimation of the Michaelis-Menten (MM) kinetic parameters of dextromethorphan-O-demethylase activity in the rat brain microsomes (mean ± SD, n = 4), which showed a maximum velocity of 2.24 ± 0.42 pmol/min/mg and a MM constant of 282 ± 62 μM. It is concluded that by requiring far less biological material and time, our method represents a significant improvement over the existing techniques for investigation of CYP2D activity in rat brain microsomes.
Utterance-Wise Recurrent Dropout and Iterative Speaker Adaptation for Robust Monaural Speech Recognition

This study addresses monaural (single-microphone) automatic speech recognition (ASR) in adverse acoustic conditions. Our study builds on a state-of-the-art monaural robust ASR method that uses a wide residual network with bidirectional long short-term memory (BLSTM). We propose a novel utterance-wise dropout method for training LSTM networks and an iterative speaker adaptation technique. When evaluated on the monaural speech recognition task of the CHiME-4 corpus, our model yields a word error rate (WER) of 8.28% using the baseline language model, outperforming the previous best monaural ASR by 16.19% relatively.
Impact of Open Access to Physician Notes on Radiation Oncology Patients: Results from an Exploratory Survey

Abstract Purpose There is an increasing effort to allow patients open access to their physician notes through electronic medical record portals. However, limited data exist on the impact of such access on oncology patients, and concerns remain regarding potential harms. Therefore, we determined the baseline perceptions and impact of open access to oncology notes on radiation oncology patients. Methods and materials Patients receiving radiation therapy were provided instructional materials on accessing oncology notes at the time of their initial evaluation. Patients were prospectively surveyed to evaluate baseline interest and expectations before access and to determine the actual usage and impact at the end of their radiation treatment course. Results A total of 220 patients were surveyed; 136 (62%) completed the baseline survey, of which 88 (40%) completed the final survey. The majority of participants were age >60 years (n = 83; 61%), and 70 were male (51%). Before accessing the notes, the majority of patients agreed that open access to oncology notes would improve understanding of diagnosis (99%), understanding of treatment side effects (98%), reassurance about treatment goals (96%), and communication with family (99%). All patients who accessed the notes found them to be useful. After accessing the notes, approximately 96%, 94%, and 96% of patients reported an improved understanding of their diagnosis, an improved understanding of treatment side effects, and feeling more reassured about their treatment, respectively. Approximately 11%, 6%, and 4% of patients noted increased worry, increased confusion, and finding information they now regret reading, respectively. Patient age, sex, and specific cancer diagnoses were not predictive of experiencing negative effects from accessing the notes. Conclusions Radiation oncology patients have a strong interest in open access to their physician notes, and the majority of patients expect and actually report meaningful benefits. These data support strategies to allow more patients with cancer access to their physicians’ notes.
Clustering Blockchain Data

Blockchain datasets, such as those generated by popular cryptocurrencies Bitcoin, Ethereum, and others, are intriguing examples of big data. Analysis of these datasets has diverse applications, such as detecting fraud and illegal transactions, characterizing major services, identifying financial hotspots, and characterizing usage and performance characteristics of large peer-to-peer consensus-based systems. Unsupervised learning methods in general, and clustering methods in particular, hold the potential to discover unanticipated patterns leading to valuable insights. However, the volume, velocity, and variety of blockchain data, as well as the difficulties in evaluating results, pose significant challenges to the efficient and effective application of clustering methods to blockchain data. Nevertheless, recent and ongoing work has adapted classic methods, as well as developed new methods tailored to the characteristics of such data. This chapter motivates the study of clustering methods for blockchain data, and introduces the key blockchain concepts from a data-centric perspective. It presents different models and methods used for clustering blockchain data, and describes the challenges and some solutions to the problem of evaluating such methods.