cssi/SciSciGPT-SciSciNet huggingface dataset:
Neuroinflammation and white matter pathology in schizophrenia: systematic review.

Abstract Background Neuroinflammation and white matter pathology have each been independently associated with schizophrenia, and experimental studies have revealed mechanisms by which the two can interact in vitro, but whether these abnormalities simultaneously co-occur in people with schizophrenia remains unclear. Method We searched MEDLINE, EMBASE, PsycINFO and Web of Science from inception through 12 January 2014 for studies reporting human data on the relationship between microglial or astroglial activation, or cytokines and white matter pathology in schizophrenia. Results Fifteen studies totaling 792 subjects (350 with schizophrenia, 346 controls, 49 with bipolar disorder, 37 with major depressive disorder and 10 with Alzheimer's disease) met all eligibility criteria. Five neuropathological and two neuroimaging studies collectively yielded consistent evidence of an association between schizophrenia and microglial activation, particularly in white rather than gray matter regions. Ultrastructural analysis revealed activated microglia near dystrophic and apoptotic oligodendroglia, demyelinating and dysmyelinating axons and swollen and vacuolated astroglia in subjects with schizophrenia but not controls. Two neuroimaging studies found an association between carrier status for a functional single nucleotide polymorphism in the interleukin-1β gene and abnormal white as well as gray matter volumes in schizophrenia but not controls. A neuropathological study found that orbitofrontal white matter neuronal density was increased in schizophrenia cases exhibiting high transcription levels of pro-inflammatory cytokines relative to those exhibiting low transcription levels and to controls. Schizophrenia was associated with decreased astroglial density specifically in subgenual cingulate white matter and anterior corpus callosum, but not other gray or white matter areas. Astrogliosis was consistently absent. Data on astroglial gene expression, mRNA expression and protein concentration were inconsistent. Conclusion Neuroinflammation is associated with white matter pathology in people with schizophrenia, and may contribute to structural and functional disconnectivity, even at the first episode of psychosis.
Extending the Behavioral Immune System to Political Psychology: Are Political Conservatism and Disgust Sensitivity Really Related?:

Previous research suggests that several individual and cultural level attitudes, cognitions, and societal structures may have evolved to mitigate the pathogen threats posed by intergroup interactions. It has been suggested that these anti-pathogen defenses are at the root of conservative political ideology. Here, we test a hypothesis that political conservatism functions as a pathogen-avoidance strategy. Across three studies, we consistently find no relationship between sensitivity to pathogen disgust and multiple measures of political conservatism. These results are contrasted with theoretical perspectives suggesting a relationship between conservatism and pathogen avoidance, and with previous findings of a relationship between conservatism and disgust sensitivity.
Expressive Probability Models in Science

The paper is a brief summary of an invited talk given at the Discovery Science conference. The principal points are as follows: first, that probability theory forms the basis for connecting hypotheses and data; second, that the expressive power of the probability models used in scientific theory formation has expanded significantly; and finally, that still further expansion is required to tackle many problems of interest. This further expansion should combine probability theory with the expressive power of first-order logical languages. The paper sketches an approximate inference method for representation systems of this kind.
Determination of right ventricular wall stress in mitral regurgitation using computer-based model

To assess the influence of work load on both LV and RV performance in chronic severe mitral regurgitation (MR), our model for estimating LV wall stress was extended to include the RV modeled as a bi-axially truncated prolate ellipsoid. Pressure and echocardiographic chamber dimensions were entered into the model. Estimated RV circumferential(cir), meridional(mer) and radial(rad) stress in MR were 124/spl plusmn/13, 97/spl plusmn/13 and 16/spl plusmn/2, and LV cir, mer and rad stress estimates were 300/spl plusmn/31, 123/spl plusmn/14 and 68/spl plusmn/5 (/spl times/10/sup 3/ Dynes/cm/sup 2/), respectively. The RV-cir and rad and LV-cir, mer and rad stresses were significantly higher than control (p<.05). These preliminary results indicate that RV wall stress estimation appears feasible and may provide important pathophysiologic understanding of processes affecting both RV and LV performance.
Composite analysis for Escherichia coli at coastal beaches.

At some coastal beaches, concentrations of fecal-indicator bacteria can differ substantially between multiple points at the same beach at the same time. Because of this spatial variability, the recreational water quality at beaches is sometimes determined by stratifying a beach into several areas and collecting a sample from each area to analyze for the concentration of fecal-indicator bacteria. The average concentration of bacteria from those points is often used to compare to the recreational standard for advisory postings. Alternatively, if funds are limited, a single sample is collected to represent the beach. Compositing the samples collected from each section of the beach may yield equally accurate data as averaging concentrations from multiple points, at a reduced cost. In the study described herein, water samples were collected at multiple points from three Lake Erie beaches and analyzed for Escherichia coli on modified mTEC agar (EPA Method 1603). From the multiple-point samples, a composite sample (n =116) was formed at each beach by combining equal aliquots of well-mixed water from each point. Results from this study indicate that E. coli concentrations from the arithmetic average of multiple-point samples and from composited samples are not significantly different (t = 1.59, p = 0.1139) and yield similar measures of recreational water quality; additionally, composite samples could result in a significant cost savings.
BAKING CHARACTERISTICS AND PROTEIN QUALITY OF SOY‐WHOLE EGG SOY‐EGG YOLK AND SOY‐EGG WHITE SUPPLEMENTED BREADS

Full-fat soy (S), and other full-fat soy-whole egg (SE), soy-egg yolk (SEY) and soy-egg white (SEW) flours were produced and utilized as 12% supplements for patent wheat flour in breads. Addition of 0.5% sodium stearoyl-2-lactylate (SSL) improved loaf volumes of all bread types except SEY. Generally, 30 or 45 ppm bromate supplementation also resulted in increased loaf volumes. Organoleptic evaluations of bread types indicate that 100% wheat flour and SEY supplemented loaves scored well in most quality characteristics. Protein efficiency ratio analyses showed that all S and soy-egg fortified breads produced better growth than 100% wheat flour bread. The results indicate that supplementation of breads with SEY flour produces breads of good quality without the need for SSL or bromate.
Fluxes of ammonia and sulfate over maize using relaxed eddy accumulation

The dry deposition of fine aerosol sulfate and ammonia was measured over maize using the relaxed eddy accumulation method (REA). This micrometeorological method determines the flux by sampling the concentrations in the ‘‘updraft’’ and ‘‘downdraft’’ eddy motions, with the flux being proportional to the difference in concentration between the ‘‘up’’ and ‘‘down’’ concentrations. The fine aerosol fraction and gas phase components were separated using annular denuders followed by filterpacks using Teflon filters. Measurements were made when the leaf area index was low (� 1) and later when the canopy was fully developed (LAI � 4) to evaluate the role of LAI on the aerosol deposition velocity. The deposition measurements of sulfate aerosol yielded daytime deposition velocities larger than expected (� 2c m s � 1 ) from short crops but consistent with other field measurements over forests. Over a young fertilized stand of maize with a leaf area index of � 1, large emissions of ammonia were observed for several days following the surface application of urea containing fertilizer. Measurements overa fully developed canopy with a leaf area indexof about 4, showed both deposition and emission events. # 2005 Elsevier B.V. All rights reserved.
SAT-based synthesis of clock gating functions using 3-valued abstraction

Clock gating is a power reduction technique for digital circuits that works by eliminating unnecessary switching of parts of the clock network, a power-hungry component in hardware designs. An effective approach to clock gating synthesis is based on a functional analysis of the design using BDDs. Algorithms of this type attempt to build a BDD for a clock gating circuit and then reduce its size with an approximation. If the BDD of a particular latch grows too large the attempt to gate that latch is aborted. We replace BDDs with a SAT-based technique combined with 3-valued abstraction. Our technique generates the approximation directly from the circuit, and thus avoids the explosion. Furthermore, our technique is incremental in the sense that it produces a partial result (a weaker approximation) if time or memory limits are exceeded. Our experimentation shows that more than 70% of latches that could not be gated using the BDD-based approach were gated by the SAT-based method.
Advances in atypical antipsychotics for the treatment of schizophrenia: new formulations and new agents.

Innovation in atypical antipsychotic agents continues with new preparations of available drugs as well as novel agents. In this article, we provide an update on these novel products by reviewing information from a computerised literature search, recent abstracts and discussions with industry representatives.
Inverter loss estimation method for real time applications

This paper proposes a polynomial based inverter loss estimation method. From the I-V characteristics of the inverter switching event, different sets of polynomial functions that can accurately describe the switching behaviors are determined first and then it is used in the inverter loss estimation. The proposed method is simple and computationally effective. Simulation results indicate that this method shows improved accuracy in inverter loss estimation compared to a steady state power based lookup table models over drive cycle.
Work in progress - improving self-efficacy with a freshman mentor program

Transitioning from high school to a university setting is difficult, and when combined with the academic stresses of an engineering program, low undergraduate retention rates are a common problem. A solution is to produce a curriculum that can instruct students about engineering basics while improving self-efficacy. Most current methods to increase self efficacy are mentorship programs, addressing different learning pedagogies, and creating separate learning communities. Execution of these methods is prohibitive when educating large numbers of students. Preliminary self efficacy survey results show an improvement in our students as a response to both our Freshman Mentor program and Platform for Learning, TekBots.
Proper and unit bitolerance orders and graphs

Abstract We say any order ≺ is a tolerance order on a set of vertices if we may assign to each vertex x an interval I x of real numbers and a real number t x called a tolerance in such a way that x ≺ y if and only if the overlap of I x and I y is less than the minimum of t x and t y and the center of I x is less than the center of I y . An order is a bitolerance order if and only if there are intervals I x and real numbers t 1 ( x ) and t r ( x ) assigned to each vertex x in such a way that x ≺ y if and only if the overlap of I x and I y , is less than both t r ( x ) and t 1 ( y ) and the center of I x is less than the center of I y . A tolerance or bitolerance order is said to be bounded if no tolerance is larger than the length of the corresponding interval. A bounded tolerance graph or bitolerance graph (also known as a trapezoid graph ) is the incomparability graph of a bounded tolerance order or bitolerance order. Such a graph or order is called proper if it has a representation using intervals no one of which is a proper subset of another, and it is called unit if it has a representation using only unit intervals. In a recent paper, Bogart, Fishburn, Isaak and Langley (1995) gave an example of proper tolerance graphs that are not unit tolerance graphs. In this paper we show that a bitolerance graph or order is proper if and only if it is unit. For contrast, we give a new view of the construction of Bogart et al. (1995) from an order theoretic point of view, showing how linear programming may be used to help construct proper but not unit tolerance orders.
Interleaved, multisite electrical stimulation of cat sciatic nerve produces fatigue-resistant, ripple-free motor responses

We studied the use of physiologically based, multisite, intrafascicular electrical stimulation of the sciatic nerve to achieve ripple-free contractions and sustained, fatigue-resistant forces over a physiological range of forces in cat gastrocnemius muscle. Electrode arrays containing 100, 0.5-1.5-mm-long penetrating microelectrodes were inserted into the sciatic nerves of cats, and forces generated by gastrocnemius muscles in response to stimulation of the nerves were monitored via a force transducer attached to the tendons. In single-electrode stimulation, responses evoked by low-frequency [15 pulses/second, (p/s)] stimulation exhibited greater fatigue resistance than did responses evoked by higher frequency stimulation (30 and 60 p/s), but showed far more ripple within each response. We compared interleaved 15 p/s stimulation of four electrodes (100 /spl mu/s biphasic pulses, 750-ms pulse trains) that produced a net stimulation frequency of 60 p/s with multielectrode 60 p/s quasi-simultaneous stimulation protocols. Across a broad range of forces (10% to 80% of maximum), responses evoked by multielectrode 15 p/s interleaved stimulation exhibited substantially less fatigue than did responses evoked by 60 p/s quasi-simultaneous stimulation, and less ripple than responses evoked by single-electrode 15 p/s stimulation. The effectiveness of this physiologically based stimulation paradigm encourages its application in the field of motor neuroprosthetics.
The Nonlinear Dynamics of a Jet Shear Layer with Swirl

The present computational study concerns the three-dimensional evolution of a nominally axisymmetric jet with swirl subject to axisymmetric and azimuthal perturbations. We employ an inviscid vortex filament technique to gain insight into the vorticity dynamics of the flow. As a first step, we consider the effect of streamwise vorticity in the jet shear layer only. For the case of an axisymmetric perturbation, we observe the formation of weakly swirling vortex rings connected by braids in which the effect of the swirl is relatively more important. The streamwise vorticity forming in the braid is of the same sign everywhere, however, due to the axisymmmetry, concentrated structures do not formn in the braid. By introducing an additional periodic perturbation in the azimuthal direction, the axisymmetry is broken and the emergence of concentrated streamwise braid vortices all of the same sign is observed. A Kelvin-Helmholtz-like instability of the curved braid vorticity layer plays a significant role in their generation.
Platelet inhibition strategies in percutaneous coronary intervention: competition or coopetition?

Over the past two and a half decades, a remarkable series of tools, technologies, and techniques have been created, developed, and refined for the performance of percutaneous coronary intervention (PCI). A constant over time, however, has been the therapeutic framework of enlargement of the luminal
INFLUENCE OF OPIUM AVAILABILITY ON ADDICTION RATES IN LAOS

Crude rates of opium addiction were determined in 1972-1974 in ten communities of Laos, representing eight different ethnic groups and three provinces. In six rural communities, data were obtained by a house-to-house survey, and in four urban communities by opium den registration. Communities raising opium poppy as a cash crop had highest crude rates of addiction (7.0-9.8 addicts per 100 people). Thos involved in opium commerce had intermediate rates (4.1-5.5). Where neither opium production nor commerce was present, the communities had the lowest rates of addiction (1.8-2.3).
Using 3D Modeling Techniques to Enhance Teaching of Difficult Anatomical Concepts.

Rationale and Objectives Anatomy is an essential component of medical education as it is critical for the accurate diagnosis in organs and human systems. The mental representation of the shape and organization of different anatomical structures is a crucial step in the learning process. The purpose of this pilot study is to demonstrate the feasibility and benefits of developing innovative teaching modules for anatomy education of first-year medical students based on three-dimensional (3D) reconstructions from actual patient data. Materials and Methods A total of 196 models of anatomical structures from 16 anonymized computed tomography datasets were generated using the 3D Slicer open-source software platform. The models focused on three anatomical areas: the mediastinum, the upper abdomen, and the pelvis. Online optional quizzes were offered to first-year medical students to assess their comprehension in the areas of interest. Specific tasks were designed for students to complete using the 3D models. Results Scores of the quizzes confirmed a lack of understanding of 3D spatial relationships of anatomical structures despite standard instruction including dissection. Written task material and qualitative review by students suggested that interaction with 3D models led to a better understanding of the shape and spatial relationships among structures, and helped illustrate anatomical variations from one body to another. Conclusions The study demonstrates the feasibility of one possible approach to the generation of 3D models of the anatomy from actual patient data. The educational materials developed have the potential to supplement the teaching of complex anatomical regions and help demonstrate the anatomical variation among patients.
The Influence of Feed Texture on Broiler Performance

Abstract Three broiler feeding experiments involving a total of 15,750 broilers were conducted to compare the effects of feed texture especially unsifted versus sifted pellets on broiler performance (weight and feed efficiency). Broiler chicks fed crumbles through the first four weeks of age were significantly heavier and required significantly less feed to produce a unit of body weight than those fed the all-mash diet. From 4 to 8 weeks of age the birds started on crumbles were fed: 1) pellets unsifted, 2) pellets sifted, 3) crumbles, and 4) one-half pellets and one-half crumbles. A detailed comparison between the broilers fed unsifted and sifted pellets revealed that their performances were almost identical. Therefore, the use of unsifted pellets would appear to be more economical for commercial broiler production than the more costly sifted pellets.
Effects of Planting Date and Soil Water on Infestation of Sunflower by Larvae of Cylindrocopturus adspersus

Plant population had no significant effect on the infesation level of Cylindrocopturus adspersus (LeConte) larvae infesting the stalks of cultivated sunflower under dryland conditions. However, the mean number of larvae per plant was significantly (5% level) reduced by both delayed planting dates and reduced preplant soil water. Delayed planting dates also significantly reduced the avg number of larvae per plant and percentage infestation in irrigated sunflower. Application of insecticide to control adults reduced the number of larvae infesting stalks of irrigated sunflower, reduced plant lodging, and resulted in significant (5% level) increases in both the quantity and the quality of seeds produced in plants that did not lodge.
Involuntary Heroes: Hurricane Katrina's Impact on Civil Liberties

We are taught that the Constitution guarantees us certain civil liberties, such as the freedoms of religion and assembly and the right to bear arms. We are not taught that none of these rights are absolute and that the government can regulate these rights. We are also not taught that the government has the power to infringe on people’s civil liberties, subject to varying levels of judicial review. The protection of civil liberties is especially important when there is an emergency or crisis, raising the question of whether or not we need an emergency constitution. While this question has been raised when there is a national disaster, it is also a significant issue when there is a regional or state-based emergency, such as the one that resulted from Hurricane Katrina.Following an increasing number of emergencies throughout the country, including Hurricane Sandy, the Ferguson, Missouri, unrest, and the Ebola outbreak, there is a need to assess whether our civil liberties are protected in these circumstances. On the tenth anniversary of Hurricane Katrina, this book explores how state emergency laws impact constitutional civil liberties by examining the experiences of Hurricane Katrina’s “involuntary heroes,” those whose civil liberties were infringed upon by the government and who ultimately received little to no redress in the judicial system for their suffering. It is essential reading for constitutional scholars and for members of the general public who truly want to understand constitutional rights within the context of this historic crisis.
Evaluating Choquet Integrals Whose Arguments are Probability Distributions

We describe the use of the Choquet integral for finding a mean-like aggregated value of a collection of arguments with respect to a fuzzy measure. We observe the need for ordering the arguments in using this integral. We consider the case where the arguments being aggregated are random variables, probability distributions. In this case, we are faced with the problem of having to order probability distributions. Given the difficulty of obtaining a linear ordering over a collection of probability distributions, we must search for other methods for obtaining a Choquet type aggregation of a collection of probability distributions that does not require a linear ordering; we refer to these as surrogates. Here, we provide one surrogate for calculating the Choquet integral in the case where the objects being aggregated are probability distributions called the probabilistic exceedance method.
Stitching Together Creativity and Responsibility: Interpreting Frankenstein Across Disciplines

This article explores Mary Shelley’s Frankenstein as an “object of care” for use in examining the relationship between creativity and responsibility in the sciences and beyond. Through three short ...
Survey on occupational hazards of dimethylformamide in a tannery

[Objective]To understand the existence of occupational hazards of dimethylformamide(DMF)in an artificial leather factory,and provide evidence for workplace improvement,physical and mental health of workers.[Methods]Through the field occupational health survey,the distribution of DMF and its exposure mode and chance to workers were identified.Sampling and detection were based on GBZ 159-2004 and GBZ/T 160.62-2004.Occupational health examination was performed on workers exposed to DMF according to GBZ 188-2007 "Occupational Health Surveillance Technical Specification".Results of the testing and health check were analyzed.[Results] DMF was detected in workplace air of 88 points,concentration ranged from 6.8-106.6 mg/m,with average of 61.8 mg/m3.Unqualified DMF was detected on 57 points,with unqualified rate of 64.8%.The abnormal rates of neural levy and liver function in exposure group were higher than those of control group,with significantly differences(χ2=9.55、19.45,all P0.01).The concentration of NMF in urine of shift end of exposure group ranged from 3.2-78.20 mg/g·Cr,with average of 16.60 mg/g·Cr;no NMF was detected in control group.The concentration of NMF in urine of shift end was positively related with air DMF concentration and abnormal rate of liver function(r=0.937,0.613,P0.01).[Conclusion]DMF hazard is serious in this tannery.It is suggested to strengthen ventilation detoxification and to configure personal protection equipment and other measures to reduce air DMF concentration,to decrease the inhaled amount of DMF through the skin and respiratory tract.The reducing amount of DMF generated is the key for occupational hazard prevention of NMF.
Alzheimer's disease: a novel hypothesis for the development and the subsequent role of beta amyloid

Spirochetes, biofilms, innate immune system activity have all been recently found in the brains of Alzheimer's disease patients. The mechanism and actions of those entities in producing the disease were postulated in those studies. The production and role of beta amyloid were not included in the discussion; we hypothesize herein how the development of that molecule occurs as a result of the Toll-like receptor 2 activation leading not only to TNFα, but also NFκB which themselves have been previously shown to induce the secretases necessary to cleave the amyloid precursor protein. This leads directly to beta amyloid. The beta amyloid (Aβ) has been shown to be antimicrobial, and its presence on and around the hippocampal plaques (the pathological hallmark of Alzheimer's disease) has been demonstrated. It becomes apparent that the Aβ tries to kill the spirochetes but cannot penetrate the biofilm. Its buildup then interrupts and destroys the neurocircuitry of the brains.
Strategies and Practicalities in the Production and Use of Gas Isotope Standard Materials

Publisher Summary This chapter provides a practical guide to the production and use of gas isotope reference materials (RMs) at the National Institute of Standards and Technology. These RMs are developed by the International Atomic Energy Agency in accordance with guidelines of the International Organization for Standardization. The strategies and practicalities used in the production and use of gas isotope standard materials are assessment of needs, gas selection criteria, safety considerations, measurement strategy, data normalization, and a web-based interactive data reduction algorithm. Use of gas isotope RMs as a part of a total quality assurance system results in improved measurement reproducibility among laboratories. An example is presented using the carbon dioxide materials RM 8562, RM 8563, and RM 8564, where normalization of data improved interlaboratory reproducibility by a factor of three or more. By utilizing gas isotope RMs and associated tools as a part of a total quality assurance system, improvements in reproducibility of measurement can be realized across laboratories.
Trade-Offs in Sustainable Development

I first went to Laos in 1987. As I drove the streets of Vientiane on my way to meet government officials, every child under 10 would turn to stare at my rented car, a rare and unusual sight on streets used primarily by bicyclists and bullock carts, with perhaps the odd motorcycle or rickshaw. Laos was just opening up to the rest of the world. Its communist leadership rarely met Westerners. It was a poor, landlocked, rural country with the highest concentration of unexploded ordinance on earth. Today it has joined the ranks of middle-income countries, thanks to the development of its hydropower and other minerals.
Hope, Change, Pragmatism

This chapter focuses on the months from late spring to mid-autumn 2009, when Obama’s administration began to proactively implement its foreign policy agenda. The period ends with Obama’s final decision regarding a possible Afghanistan “surge.” The chapter itself first reviews early debates about how to characterize and explain Obama’s grand strategy before turning to its substantive core: how Obama articulated grand strategy and, in turn, how his administration implemented grand strategy. Brief analysis and findings at the end suggest that officials were responsive to early, perceived failures and were willing to make limited adjustments to their grand strategic approach. This grand strategy itself was a mix of liberal internationalist ambitions and pragmatic realism.
The [4Fe-4S] clusters of Rpo3 are key determinants in the post Rpo3/Rpo11 heterodimer formation of RNA polymerase in Methanosarcina acetivorans.

Subunits Rpo3 and Rpb3/AC40 of RNA polymerase (RNAP) from many archaea and some eukaryotes, respectively, contain a ferredoxin-like domain (FLD) predicted to bind one or two [4Fe-4S] clusters postulated to play a role in regulating the assembly of RNAP. To test this hypothesis, the two [4Fe-4S] cluster Rpo3 from Methanosarcina acetivorans was modified to generate variants that lack the FLD or each [4Fe-4S] cluster. Viability of gene replacement mutants revealed that neither the FLD nor the ability of the FLD to bind either [4Fe-4S] cluster is essential. Nevertheless, each mutant demonstrated impaired growth due to significantly lower RNAP activity when compared to wild type. Affinity purification of tagged Rpo3 variants from M. acetivorans strains revealed that neither the FLD nor each [4Fe-4S] cluster is required for the formation of a Rpo3/11 heterodimer, the first step in the assembly of RNAP. However, the association of the Rpo3/11 heterodimer with catalytic subunits Rpo2′ and Rpo1″ was diminished by the removal of the FLD and each cluster, with the loss of cluster 1 having a more substantial effect than the loss of cluster 2. These results reveal that the FLD and [4Fe-4S] clusters, particularly cluster 1, are key determinants in the post Rpo3/11 heterodimer assembly of RNAP in M. acetivorans.
Who gets to play? Access, popular media and participatory literacies

AbstractEarly literacy is often over-simplified as a set of skills for beginning reading, an approach which overlooks the ways that children play their way into cultures, using play as a literacy that accesses popular media as rich literary repertoires of characters and storylines. This article examines how children’s play reveals their participatory literacies in preschool classrooms where teachers provide play-based media literacy curricula. Participatory literacies are ways of interpreting, making, sharing and belonging in increasingly globally and digitally mediated cultures. Data are excerpted from a five-year study of literacy play in classrooms that provide a space for children to draw upon popular media repertoires as cultural capital and resources for literacy development. Mediated discourse analysis of classroom video located and analyzed children’s play for use of creative and collaborative dimensions of participatory literacies. Results showed that young children drew on their media knowledge ...
The process of drug discovery and the Yin/Yang of small-molecule/biotech option

Abstract Until the mid 90ties of last century, talking about drug discovery and development was essentially referred to the process of discovery and development of small-molecule chemical entities. All the language, common procedures and technicalities were inherent to this setting; concepts such as drug design, hit and lead compounds, high-throughput screening were referring to the typical mode of investigating and selecting small-molecule candidates through pre-clinical development. At that time, the arrival of the first biotech drugs has markedly changed the landscape, requiring a completely new approach to pre-clinical development. Issues related to drug-receptor interaction or to the selection from a huge number of candidates were obviously simplified to a minimum compared to the small-molecule setting. Conversely, the pharmaceutical development of biotech drugs showed far higher complexity, and the overall high complexity of industrial production initially represented a major issue to justify the high costs of biotech drugs. Besides, the technical impossibility to make ‘generics’ of biotech drugs was another strong reason driving Pharma companies toward the development of biotech drugs. Thus, in the beginning the early development phases of small-molecules or biotech drugs really stood as two distant planets. However, by the time such initial distances have been progressively reduced. From the biotech site, the technique of phage-display library scanning and similar approaches made the selection of biotech lead compounds resembling more closely what happens with small molecules; also the complexities and high costs of pharmaceutical production have progressively reduced their impact. On the other site, the impressive progresses of basic knowledge on the human kinome and other relevant fields of molecular and cellular biology made possible that today we have small-molecule drugs targeting the same pathologies once specifically targeted by biotech drugs, MoAbs in particular. Another factor (albeit not related to drug development) with an important role in reducing distances between small-molecule and biotech drugs has been the novel approach to estimate the value of drugs, and therefore their prices. Since nowadays the major drive fixing the value (and costs) of new drugs is the added value for human health, any difference related to the costs of production has been greatly reduced, and we have today several high-cost small molecules along with their sibling biotech drugs. Last but not least, biotech drugs can be ‘copied’ as well, since we now have biosimilar drugs, although the pathway to develop copies of biotech drugs remains steeper compared to that leading to the equivalents of small-molecule drugs.
The Future of Eudaimonic Well-Being: Subjectivism, Objectivism and the Lump Under the Carpet

Persistent and heated terminological disputes (such as the one over the concept of eudaimonia) often hide something more fundamental and, when this is the case, agreeing on terms just moves the battle somewhere else: the lump under the carpet is pushed to a different quadrant, but it doesn’t go away. I want to explore one possible interpretation of the real lump under the carpet, namely, a very deep disagreement about the nature of a good human life. This disagreement is between those who think that what justifies our taking something to be good is our subjective attitude toward it (liking it, wanting it and so forth) and those who think that what justifies our taking something to be good is some good-making feature of the thing that is independent of how we feel about it. I consider some obstacles to understanding this disagreement and explore briefly why it matters.
Transposon Tagging in Setaria viridis

Transposon tagging populations are important resources for characterizing gene function in model plant systems. In Setaria viridis, a transposon tagging population utilizing the miniature Ping (mPing) element was generated by introducing a construct containing mPing and the transposase Ping into accession A10.1. Transformants were screened for the presence of the transgene and mPing insertions were identified using nested inverse-PCR coupled with Illumina sequencing. Here we describe step-by-step protocols for generating the Setaria viridis mPing population, introduce methods for genotyping mPing insertion alleles, and discuss future implementations of the system.
Remote site-selective C–H activation directed by a catalytic bifunctional template

In chemical syntheses, the activation of carbon-hydrogen (C-H) bonds converts them directly into carbon-carbon or carbon-heteroatom bonds without requiring any prior functionalization. C-H activation can thus substantially reduce the number of steps involved in a synthesis. A single specific C-H bond in a substrate can be activated by using a 'directing' (usually a functional) group to obtain the desired product selectively. The applicability of such a C-H activation reaction can be severely curtailed by the distance of the C-H bond in question from the directing group, and by the shape of the substrate, but several approaches have been developed to overcome these limitations. In one such approach, an understanding of the distal and geometric relationships between the functional groups and C-H bonds of a substrate has been exploited to achieve meta-selective C-H activation by using a covalently attached, U-shaped template. However, stoichiometric installation of this template has not been feasible in the absence of an appropriate functional group on which to attach it. Here we report the design of a catalytic, bifunctional nitrile template that binds a heterocyclic substrate via a reversible coordination instead of a covalent linkage. The two metal centres coordinated to this template have different roles: one reversibly anchors substrates near the catalyst, and the other cleaves remote C-H bonds. Using this strategy, we demonstrate remote, site-selective C-H olefination of heterocyclic substrates that do not have the necessary functional groups for covalently attaching templates.
Wilson’s disease

Wilson s disease (WD) is a genetically determined, autosomal recessive disorder of copper metabolism. The gene ATP7B encodes a copper carrier that both transports copper from hepatocyte to bile and ceruloplasmin copper incorporation. WD may present with almost any variety of liver disease at an age ranging from 4–12 years, or with neurological and psychiatric symptoms in adolescence. Less commonly, haemolysis and/or fulminant hepatic failure may be an initial presentation. Low plasma ceruloplasmin, a positive penicillamine challenge test, and a high hepatic copper content suggest the diagnosis. Molecular methods help in diagnosing WD. If diagnosed early, it is treatable with chelators and/or zinc, and has a good prognosis. Fulminant hepatic disease has a poor outcome without transplantation.
Impact of Procalcitonin (PCT)-Guided Antibiotic Therapy on Mortality in Critically Ill Patients: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials

AbstractBackgroundProcalcitonin (PCT)-guided antibiotic therapy has been shown to reduce antibiotic use in critically ill patients with suspected or proven infection, but its impact on mortality remains uncertain. Our meta-analysis examines the effect of PCT-guided antibiotic therapy on survival in critically ill patients.MethodsWe searched PubMed, the Cochrane Library, Scopus, Web of Science, EMBASE and clinicaltrials.gov electronic databases up to October 2016. The meta-analysis was restricted to randomized controlled trials (RCTs) of critically ill patients receiving PCT-guided antibiotic treatment and reporting survival or antibiotic duration. Study quality was assessed using the Cochrane risk of bias tool. Two reviewers conducted all review stages independently, and a third reviewer adjudicated any differences. Data was pooled using random-effects meta-analysis.ResultsOf the 18 RCTs selected (n = 5,183 patients; Table), 17 assessed mortality and 11 assessed antibiotic duration; 8 scored ≥3 and 10 scored ≤2 out of 6 on the risk of bias assessment. Compared with controls, PCT-guided antibiotic treatment was associated with a significant reduction in mortality (20.7% vs. 23.0%; risk ratio [RR] 0.90[95% CI, 0.81–0.99], I2=0%; Figure 1). Survival benefit was retained in the RCT subset with a lower risk of bias (score ≥ 3; RR 0.87 [95% CI, 0.77,0.98], I2=0%; Figure 2) but not with higher risk (score ≤ 2; RR 0.98 [95% CI, 0.80–1.20], I2=0%). Our analysis of the effect of PCT-guided antibiotic therapy on antibiotic duration displayed significant heterogeneity (I2=61.2%, P = 0.004), which precluded reporting on aggregate effect. Important limitations were: single center RCT (n = 9), lack of double blinding (all studies) and variable protocol non-adherence and timeframes examined for mortality.ConclusionIn a meta-analysis of RCTs of critically ill patients with suspected or proven infection, PCT-guided antibiotic treatment was associated with a significant reduction in mortality. The observed survival benefit was weighted towards RCTs of relatively higher quality. However, the plausibility of this finding, as well as the impact of protocol non-adherence on outcome needs further study.Funded by Intramural NIH and NCI Contract# HHSN261200800001EDisclosures All authors: No reported disclosures.
On the Accurate Calculation of Effective Wake/Application to Ducted Propellers

A hybrid method that couples a potential flow solver with a Reynolds-Averaged Navier-Stokes (RANS) solver for calculating the effective wake of a propeller is proposed. Two improvements are addressed in this method: 1) a conservative interpolation scheme that conserves the total forces when passing information from the potential flow solver to the RANS solver; and 2) a novel option that evaluates the effective wake at the control points in the blade zone. The proposed method is first assessed in the case of an open propeller subject to uniform inflow and then applied to predict the performance of the ducted propellers under uniform inflow. The results of the numerical simulation are correlated with available experimental measurements.
Planning for City Sustainability: GreenWorks Orlando Case Study

In this chapter, we examine GreenWorks Orlando. GreenWorks Orlando is an overarching planning and organizational framework established by the City of Orlando, Florida. The two specific plans developed under the GreenWorks umbrella that are the focus of this case study—the GreenWorks Orlando Community Action Plan and the Orlando Municipal Operations Sustainability Plan—were developed to serve as the foundation for community sustainability. This chapter describes the processes of translating Orlando’s goal of becoming the greenest city in America into these planning initiatives and the implications of these plans on city programmatic efforts that advance the city’s primary sustainability objectives—advancing economic growth in green industries and protecting the environment and curbing greenhouse gas emissions.
Nondeterministic Online Automata

We saw in Section 3.1 that one can view OAs as abstract representations of actual circuits or machines or programs. In contrast, the generalization of OAs that we present now is a mathematical abstraction that cannot be realized directly from conventional hardware or software elements. It is best to view this model either as a pure mathematical convenience—whose utility we shall see imminently—or as a “computational strategy” that we shall try to realize via sophisticated transformation of a program.
Acetylation of Sphingosine by PAF-Dependent Transacetylase

Sphingosine induces many protein kinase C-dependent and -independent effects on biological systems. In parallel, C2-ceramide used by investigators as an unnatural, cell permeable analog of long-chain acyl-ceramides, possesses biological activities similar with natural ceramides. We have recently characterized a membrane-associated, CoA-independent transacetylase that can transfer the acetate group from PAF to sphingosine and form C2-ceramide. This enzyme has a strict stereochemical configuration requirement for sphingosine; only the naturally-occurring D-erythro-isomers of sphingosine accepts the acetate from PAF. Also, it has a rigid substrate specificity for sphingolipid-related analogues. Dipalmitoyl-glycerophosphocholine (-GPC) or hexadecylarachidonoyl-GPC can not transfer their long-chain acyl groups directly to sphingosine and sphingosine can not be acetylated by acetyl-CoA:lyso-PAF acetyltransferase. Results obtained from studies on pH optima, subcellular distribution, temperature sensitivities, inhibitors, tissue distributions, and expression of enzyme activities in Xenopus oocytes suggest that PAF:sphingosine transacetylase is similar, but not identical to the PAF:lysophospholipid transacetylase we have previously identified. The transacetylases function to diversify the biological responses of PAF.
Specific nonsurgical therapy in male infertility.

SUMMARY Although the objective of this article was to discuss the specific medically treatable causes of male infertility, the reader will be impressed by the fact that many of the treatments seem less than “specific.” The need to treat infections to improve fertility is ill defined. The utilization of a scrotal cooling device as “specific” nonsurgical treatment for varicocele is yet to be defined. Immunologic suppression is indeed a specific form of therapy for a measurable phenomenon; unfortunately, the significance of that phenomenon as well as the best means and location of its assessment are undergoing significant reevaluation. An exciting frontier is the prospect of preventing infertility in the patient undergoing therapy for cancer, thus obviating the need for treatment of the ensuing infertility. Before specific therapies can be anticipated to have a predictable beneficial effect, these areas require active investigation to define the problem more clearly.
Facilitating compliance with antipsychotic medication.

Noncompliance with medication is common among patients who have schizophrenia and is a leading cause of rehospitalization in this population. Both standard and subjective risk-factor assessments have been used to identify patients who are likely to refuse or discontinue treatment. Noncompliant patients who have schizophrenia commonly have been treated with potent D2 dopamine-receptor antagonists and therefore may have experienced extrapyramidal side effects. The newer antipsychotics (i.e., serotonin-dopamine antagonists) are efficacious in reducing the symptoms of schizophrenia without associated dysphoria and motor side effects. Clozapine and other newer antipsychotics may improve certain aspects of cognition. The improved psychiatric state and cognitive function may facilitate "involved compliance" as a result of increased insight, awareness, and judgment. These cognitive faculties allow patients to appreciate their improved state and take steps to maintain it. The periodic visits for blood monitoring mandated for clozapine therapy also facilitate the formation of a therapeutic alliance that allows the clinician to monitor compliance. Facilitating involved compliance this way among patients who have schizophrenia may reduce the cost of this disorder to society.
Rapid dissolution of surrogate nuclear debris using ammonium bifluoride fusion and indirect sonication dissolution methods

Prompt analysis of elemental and isotopic information from post-detonation nuclear debris is critical for rapid attribution analysis. In this work, the capabilities of dissolution methods that use ammonium bifluoride (ABF, NH4HF2) and pressurized microwave digestion with HF acid are reported for NIST Surrogate Post-detonation Urban Debris (SPUD). Elemental concentration and isotope ratios were measured using inductively coupled plasma mass spectrometry. The SPUD material was also analyzed for U concentration using instrumental neutron activation analysis. The ABF dissolution method with a 10:1 ABF to sample ratio and the pressurized microwave digestion methods resulted in comparable results.
Differential Equations & Differential Invariants

This chapter leaves the realm of cyber-physical systems whose differential equations are solvable in closed form.Without closed-form solvable differential equations, the continuous dynamics of cyber-physical systems becomes much more challenging. The change is as noticeable and significant as the change from singleshot control systems to systems with an unbounded number of interactions in a control loop. All of a sudden, we can no longer pretend each differential equation could be replaced by an explicit representation of a function that describes the resulting state at time t along with a quantifier for t. Instead, differential equations have to be handled implicitly based on their actual dynamics as opposed to their solution. This leads to a remarkable shift in perspective opening up a new world of fascination in the continuous dynamical aspects of cyber-physical systems, and it begins by ascribing an entirely new meaning to primes in cyber-physical system models.