cssi/SciSciGPT-SciSciNet huggingface dataset:
Morphology development during phase inversion in isothermal, model experiments : steady simple-shear and quiescent flow fields

Abstract The effect of component viscosities on phase inversion was examined under two idealized flow fields: steady simple-shear and quiescent. In both cases, disk samples with a specific initial morphology — major-component pellets in a minor-component matrix — were prepared. For the steady simple-shear flow experiments, the evolution of morphology with strain was determined. The same stages of morphology development were observed in all blends; however, the rate of morphology development decreased with increasing effective viscosity ratio. The quiescent experiments tested whether phase inversion occurred in samples that were annealed for a set time. Blends with lower absolute viscosities phase inverted faster. Lattice-Boltzmann simulations demonstrated a functional dependence of t c ∗ ∝Z −0.36 λ 0 −0.73 based on the dimensionless time to phase inversion t c ∗ , Ohnesorge number Z , and viscosity ratio λ 0 . This dependence, when extrapolated to the experimental processing window, agrees with the experimental results and indicates that the dimensional time to phase inversion under quiescent conditions depends on η minor 0.37 η major 0.27 . Data from both flow fields indicate that phase inversion occurs when the minor component reaches a critical film thickness. This thickness under steady, simple-shear flow was 0.2–0.3 μm at low strain rates. The results from the two flow fields differ in the driving force behind film thinning: shear deformation of the major component drives film thinning under steady, simple-shear flow; interfacial-tension drives it under quiescent conditions.
Control of a large scale solar thermal energy storage system

Dynamic simulation results for a thermal energy storage (TES) unit used in a parabolic trough concentrated solar power (CSP) system are presented. A two-tank-direct method is used for the thermal energy storage. The heat transfer fluid flow rate through the solar collector maintains a constant outlet temperature and the flow rate through the boiler regulates power output. The use of storage greatly improves the system's ability to provide power at a constant rate despite significant disturbances in the amount of solar radiation available. It can also shift times of power generation to better match times of consumer demand. By contrast, a CSP system without storage undergoes large fluctuations in power output, particularly during intermittent cloud cover. Adding a storage system increases the solar share of the power plant by over 80%, reducing the requirement for supplementary fossil energy by as much as 8.4 MWh daily.
Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes.

Background Methylmalonic acidemia (MMA), a common organic aciduria, is caused by deficiency of the mitochondrial localized, 5'deoxyadenosylcobalamin dependent enzyme, methylmalonyl-CoA mutase (MUT). Liver transplantation in the absence of gross hepatic dysfunction provides supportive therapy and metabolic stability in severely affected patients, which invites the concept of using cell and gene delivery as future treatments for this condition.
Conservatism and British Foreign Policy, 1820–1920: The Derbys and their World. Edited by Geoffrey Hicks . (Farnham, England: Ashgate, 2011. Pp. xii, 234. $124.95.)

This compilation of essays was inspired by Angus Hawkins and Geoffrey Hicks. In the course of the twentieth century, every nineteenth‐century British prime minister received at least one modern, fu...
Geochemical characteristics of land and its effect on human heart and cancer death rates in the United States and China

Abstract The diverse geochemistry of different soil areas by city, county, state or province-wide localities, or in international comparisons, caused variations in age-adjusted annual heart death rate (HDR) and cancer death rate (CDR) per 100 000 persons (10−5 yr−1), despite a commonly held view that food transportation and human migration would preclude such variation. The HDR increases exponentially with age, but many risk factors (diet, smoking, etc.) shift the exponential durves representing different longevity. With increasing blood Se levels from 17, 47, 157 and 230 ng cm−3, an HDR of 250 10−5 yr−1 occurs at a median age of 5, 18, 48 and 52 yr, respectively. At HDR of 1000 10−5 yr−1, the median age is 28, 34, 62 and 68 yr, respectively. A 60% increase in HDR occurs inversely between 157 and 230 ng cm−3 Se, almost uniformly at ages 40, 50, 60 and 70. Only 5–10 yr of longevity correspond directly with these two blood Se means. Blood Se levels of 68–70 ng cm−3 that occur in Finland and New Zealand are intermediate to the above data sets, the first two from China and the second two from the U.S.A. All essential trace elements (Mo, Zn, etc.) appear to play analogous quantitative metabolic roles in critical steps in CDR and other health-risks built into human genetics. More trace element data are needed for rural and urban human populations for more detailed interpretations of the geochemical weathering and agricultural roles of the trace elements in relation to human health.
Layered Depth Panoramas

Representations for interactive photorealistic visualization of scenes range from compact 2D panoramas to data-intensive 4D light fields. In this paper, we propose a technique for creating a layered representation from a sparse set of images taken with a hand-held camera. This representation, which we call a layered depth panorama (LDP), allows the user to experience 3D by off-axis panning. It combines the compelling experience of panoramas with limited 3D navigation. Our choice of representation is motivated by ease of capture and compactness. We formulate the problem of constructing the LDP as the recovery of color and geometry in a multi-perspective cylindrical disparity space. We leverage a graph cut approach to sequentially determine the disparity and color of each layer using multi-view stereo. Geometry visible through the cracks at depth discontinuities in a frontmost layer is determined and assigned to layers behind the frontmost layer. All layers are then used to render novel panoramic views with parallax. We demonstrate our approach on a variety of complex outdoor and indoor scenes.
Control with random communication delays via a discrete-time jump system approach

Digital control systems with random but bounded delays in the feedback loop can be modeled as finite-dimensional, discrete-time jump linear systems, with the transition jumps being modeled as finite-state Markov chains. This type of system can be called a "stochastic hybrid system". Due to the structure of the augmented state-space model, control of such a system is an output feedback problem, even if a state feedback law is intended for the original system. We present a V-K iteration algorithm to design switching and non-switching controllers for such systems. This algorithm uses an outer iteration loop to perturb the transition probability matrix. Inside this loop, one or more steps of V-K iteration is used to do controller synthesis, which requires the solution of two convex optimization problems constrained by LMIs.
A PERSONAL VIEW OF MUSCLE AND MOTILITY MECHANISMS

This is a personal account of some of the successive steps in our understanding of the structural mechanism of muscle contraction during the last 45 years. It describes how I. as an ex-physicist, came to be studying muscle by X-ray diffraction in 1949; how the concepts of the double array of actin and myosin filaments and, later, the overlapping fiament model and the sliding fiament mechanism were developed; and how further electron microscope fiidings of the structural polarity of muscle filaments led to the suggestion that analogous structures and mechanisms might be involved in cellular motility. The article describes briefly how synchrotron radiation has made it possible to obtain detailed structural information about contracting muscle with millisecond time resolution and discusses some of the recent major advances in the field and the prospects of reaching a full understanding of the contraction mechanism.
Whose Power? Whose and Which Duties? Pension Fund Investments and Fiduciary-Related Duties in the United States and India

This paper is set within the context of the challenges (and opportunities) posed by significant demographic changes; an associated heightened concern for the well-being of older generations of people especially as they make a transition from being among the workforce; the corresponding need for an economy which enables younger generations to create wealth to sustain themselves sufficiently well while providing the goods and services required to support those older generations over and after that transition; and the need for institutions, policies, and practices – overall what we refer to as the “retirement system” – commensurate with the foregoing which on an ongoing basis enable individuals over their working lifetime to accumulate claims for those goods and services as they leave the workforce in their later years. A retirement system typically encompasses several different clusters of institutions, policies, and practices which we refer to as “retirement plans”. The more specific context for this paper is that of retirement plans which involve members in deriving claims directly or indirectly from financial investments made by them or by others on their behalf. In conventional terminology such plans might be referred to as “funded” ones as contrasted with, for example, “pay-as-you-go” plans.Almost by definition, central to the efficacy of funded plans are the roles and responsibilities of those individuals with ultimate authority to make the required investment-related decisions and effective fulfillment of them. (Here, we will refer to such individuals as “investment decision-makers”.) Central to the reference to “efficacy,” of course, is whether and how decisions are calculated in appropriate ways to enable realization of the sought-for claims. Practically speaking that might mean claims to an income stream in retirement – what is often referred to as a “pension” – or claims to the availability at various times of an amount of accumulated financial assets which can be a source of income or which can be withdrawn (“cashed out” so to say) to meet certain retirement-related needs and expectations. However, whatever individuals’ worries about financial security in general or as it relates to retirement, they may well have other concerns which beyond that – for example the import or impact of the behavior of the enterprises in which investments are made – which bear upon their investment decisions or how others acting on their behalf invest in their name. Moreover, as implied above, retirement plans and the retirement system as a whole are nested in the larger economy and society. Especially when the scale of funded plans of the system is great relative to the size of the economy, the economic and other implications of plan-related investment decisions overall – and perhaps in some cases on an individual basis – may loom large. If so, that poses issues as to the interplay of those implications with the roles and responsibilities of investment decision makers.
Design of a low-profile barrier for curved alignments using finite element impact simulation

Publisher Summary This chapter presents a new low-profile portable concrete barrier intended for use in roadside work zone environments through the use of nonlinear-finite-element-impact simulation. Design decisions are based on virtual testing of the barrier system done through impact simulation rather than costly iterative crash testing. A single set of crash tests can validate compliance with pertinent crash worthiness standards. The primary innovation in the barrier design is the ability to accommodate both horizontal and vertical roadway curvatures while still maintaining a low profile and preserving the ability to redirect errant vehicles. Work zones represent a type of roadside environment, in which special attention must be given to barrier height if adequate safety is to be provided both to the traveling people and to work zone personnel. While tall profile barriers provide excellent redirection and traffic separation capabilities, they can also obscure a driver's field of view and lead to accidents.
The reviews are in: Resources for undergraduate neuroscience education

There is great satisfaction for an Editor in Chief to be found in the moment an issue has been finalized for publication, and the time comes for preparing a suitable editorial for the issue. And then there are those moments when time for that simply doesn’t exist—such as when conference travel conflicts with a publication date. Such is the case as we finalize this Fall 2014 issue, and I must rush to the airport to attend the IASP World Congress on Pain in Buenos Aires. So it is with great satisfaction but little editorializing that I say this issue of the Journal of Undergraduate Neuroscience (JUNE) continues an expanded focus in our media review section. Our editorial board and review board members, along with others, have responded to the development of our cooperative agreements with publishers, and in this issue examine a wide range of neuroscience-relevant writing for its potential use in enriching undergraduate neuroscience education. I remind interested readers of JUNE that they, too, can be a part of JUNE’s media review team by contacting JUNE at moc.liamg@LANRUOJNUFENUJ to inquire about available titles. In this issue, we have six reviews contributed by Cecala (Glickstein’s Neuroscience: A Historical Introduction), Grisham (Wallisch et al.’s MATLAB for Neuroscientists), Kalat (Frazzetto’s Joy, Guilt, Anger, Love), Krishnan (Meneses’s Identification of Neural Markers Accompanying Memory), Lom (Schoonover’s Portraits of the Mind), Strickland (Carter and Shieh’s Guide to Research Techniques in Neuroscience), and seven laboratory experiences and instruction technique articles sure to enrich the neuroscience curriculum. Deal et al. discuss the use of a K-12 outreach program as a way to educate neuroscience students; while Kasuga and Ushiba detail their development of a new experimental system for teaching theories of visuomotor learning to undergraduates in the laboratory. Kover, lead author of a group of coauthors, gives details on an exercise using the writing of grant proposals in a first-year neuroscience course to foster students’ scientific thinking skills. Martins and Mello-Carpos provide us with an examination of the use of Brain Awareness Week activities to promote student interest in their curricular neuroscience components, and Monesson-Olson, Troconis, and Trapani detail an exercise recording field potentials from zebrafish larvae during escape responses. In the classroom, Walters et al. explore the claims of a variety of commercial products to impact favorably on cognitive function, as a way to drive home lessons in research methods. Yates and Stavnezer complete this issue, discussing the use of regional neuroscience network to engage students involved in summer research programs. As we all move into the rhythms of a new academic year, these authors provide us with a wealth of suggestions for opportunities to pursue new approaches to our own courses and laboratory experiences. From the conference and dance floors in Argentina, best wishes for a productive school year.
Magnetic Resonance Elastography of the Mouse Brain In Vivo

In the current study we apply the magnetic resonance elastography (MRE) technique to estimate the dynamic shear modulus of mouse brain tissue in vivo. The frequency used (1200 Hz) is well above those reported previously [1]. Estimates of dynamic shear modulus range from 12,600–14,800 N/m2 at 1200 Hz. These data are strictly relevant only to small oscillations at this specific frequency, but these values are obtained at high frequencies (and thus high deformation rates) and non-invasively throughout the brain. These data complement measurements of nonlinear viscoelastic properties obtained by others at slower rates, either ex vivo or invasively.Copyright © 2007 by ASME
Novel hydroxyapatite-based consolidant and the acceleration of hydrolysis of silicate-based consolidants

This paper discusses the effectiveness of hydroxyapatite (HAP) as an inorganic consolidant for physically weathered Indiana Limestone, and as a coupling agent between limestone and a silicate consolidant. A double application is investigated, in which samples are coated with HAP followed by a commercially available silicate-based consolidant (Conservare ® OH-100). To artificially weather limestone, a thermal degradation technique was utilized. Diammonium hydrogen phosphate (DAP) salt was reacted with limestone, alone and with cationic precursors, to produce HAP films. The dynamic elastic modulus, water sorptivity and tensile strength of the treated stones were evaluated. HAP was found to be an effective consolidant for weathered Indiana Limestone, and its performance was enhanced by addition of millimolar quantities of calcium chloride. However, HAP was not useful as a coupling agent; a double treatment with DAP is more effective than sequential treatment with DAP and Conservare ® .
MAINTENANCE OF INFLATED STRUCTURE SHAPE USING ELECTRON GUN CONTROLLED PIEZOELECTRIC MATERIALS

This paper examines one method for actively controlling the shape of an aerospace inflated structure. The basic concept is to fabricate the structure from a piezoelectric thin film, and then use an electron gun as a charge source for shape control. In the electron gun control method the need for separate electrodes and wire leads is eliminated by depositing the control charges directly on the surface of the piezoelectric material. Since piezoelectric materials are dielectrics the charges remain where deposited by the electron gun. The spatial resolution of this control method is as small as the spot size of the electron beam, which in a focused beam can be as small as tens of microns. Large areas can be covered by a single electron gun simply by scanning the beam using deflection plates. Some practical aspects of electron gun control are presented in this paper. A description of an experimental test bed assembled to evaluate electron gun control of PZT-5H is presented, as are results and conceptual models of system behavior.
PAF and PDGF increase cytosolic [Ca2+] and phospholipase activity in mesangial cells

Platelet-activating factor (PAF) and platelet-derived growth factor (PDGF) likely play important roles in glomerular processes. To identify mechanisms of PAF- and PDGF-induced mesangial cell activation, we characterized effects of both agents on cytosolic free [Ca2+] ([Ca2+]f) and phospholipase activation. When cultured rat renal mesangial cells were stimulated by PAF, [Ca2+]f increased (within 10 s) from 110 +/- 6 to 209 +/- 14 nM, due to release of Ca2+ from intracellular storage sites, as well as entry of Ca2+ from external milieu. PAF also rapidly increased free arachidonate, diacylglycerol, and inositol trisphosphate (IP3) levels. PDGF increased [Ca2+]f from 78 +/- 12 to 192 +/- 22 nM, but the time response was different from that seen with PAF. Peak [Ca2+]f increase occurred at approximately 1 min subsequent to stimulation. Like PAF, increased [Ca2+]f was due to release of Ca2+ from intracellular stores and entry from extracellular media. PDGF increased levels of free arachidonate prior to an increa...
A Memorial Laissez-Passer? Church Exhibitions and National Victimhood in Germany

Church exhibitions on the Second World War are a common facet of German memorial culture. Overlooked by scholarship — perhaps for lacking the aesthetic sophistication and curatorial self-awareness ofmany contemporarymemorials and museums — these exhibitions are still part of a public realm of discourses on memory demanding critical examination.1 Church exhibitions are heterogeneous in form, content, and tone; they are unified by the use of Christian imagery and values. The explicit presence of religious symbolism inflects the representation of Nazism, the war, and reconstruction by evoking ideas of sin, punishment, and redemption. These themes are potentially problematic in narratives of the German past, decontextualizing German victimhood and suggesting the possibility of historical expiation and normalization.2 Some exhibitions avoid these pitfalls by presenting a broader historical background; others emphasize German suffering without mentioning the war origins, aggressions perpetrated by Germany, or the complicity of some civilians and clerics with the Nazi regime.
An automated method for determining glycosylation and site diversity in glycoproteins

The determination of glycosylation sites and oligosaccharide heterogeneity is key toward understanding the biological roles of glycoproteins. There are no previous methods that can reliably detetermine the site of glycosylation and the glycan heterogeneity at specific sites. We have developed a procedure for the determination of glycosylation sites and oligosaccharide heterogeneity in glycoproteins. The method is based on a combination of nonspecific proteolysis, deglycosylation, and high mass accuracy mass spectrometry analysis. The glycoprotein was proteolytically degraded using a nonspecific protease into glycopeptide fragments. The exact peptide mass was calculated by subtracting the glycan mass from the observed glycopeptide mass. The amino acid sequence of a matched peptide mass was identified from the protein database. A computer program, GlycoX, was developed in MATLAB to aid in the determination of the glycosylation sites and oligosaccharide heterogeneity in glycoproteins.
Optimal Taxation When Children's Abilities Depend on Parents' Resources

Empirical research suggests that parents, and therefore the tax policy that affects them, can have a significant effect on their children's future earnings abilities. We take a first step toward ch...
Hypoxia induces activity of both efflux and influx transporters in retinal epithelial cells

Introduction: Hypoxia mediated signalingcauses a number of vascular retinal diseases. Their treatmentsremain challenging. To date, the effect of hypoxia onexpression of drug transporters (efflux and influx) in retinal cells has not been studied. Therefore, we have investigated molecular and functional expression of membrane transporters in human retinal pigmented epithelial (RPE) cells cultured under normoxic and hypoxic conditions.
Everyday Multitasking Abilities in Older HIV+ Adults: Neurobehavioral Correlates and the Mediating Role of Metacognition

Author(s): Fazeli, PL; Casaletto, KB; Woods, SP; Umlauf, A; Scott, JC; Moore, DJ; HNRP Group | Abstract: ObjectiveThe prevalence of older adults living with HIV is rising, as is their risk for everyday functioning problems associated with neurocognitive dysfunction. Multitasking, the ability to maintain and carry out subgoals in support of a larger goal, is a multidimensional skill ubiquitous during most real-life tasks and associated with prefrontal networks that are vulnerable in HIV. Understanding factors associated with multitasking will improve characterization of HIV-associated neurocognitive disorders. Metacognition is also associated with frontal systems, is impaired among individuals with HIV, and may contribute to multitasking.MethodNinety-nine older (≥50 years) adults with HIV completed: the Everyday Multitasking Test (MT), a performance-based measure during which participants concurrently attempt four everyday tasks (e.g., medication management) within a time limit; a comprehensive neuropsychological battery; measures of metacognition regarding their MT performance (e.g., metacognitive knowledge and online awareness).ResultsBetter global neuropsychological performance (i.e., average T-score across all domains) was associated with better Everyday MT total scores (rho = 0.34; p l .001), as was global metacognition (rho = 0.37, p l .01). Bootstrapping mediation analysis revealed global metacognition was a significant partial mediator between neurocognition and Everyday MT (b = 0.09, 95% confidence interval [CI] = 0.01, 0.25). Specifically, metacognitive knowledge (but not online awareness) drove this mediation (b = 0.13, 95% CI = 0.03, 0.27).ConclusionsConsistent with findings among younger persons with HIV, neuropsychological performance is strongly associated with a complex, laboratory-based test of everyday multitasking, and metacognition of task performance was a pathway through which successful multitasking occurred. Interventions aimed at modifying metacognition to improve daily functioning may be warranted among older adults with HIV.
The machine in the market: Computers and the infrastructure of price at the New York Stock Exchange, 1965–1975:

This article traces the development and expansion of early computer systems for managing and disseminating 'real-time' market data at the most influential stock market in the United States, the New York Stock Exchange (NYSE). It follows electronic media at the NYSE over a roughly ten-year period, from the time of the deployment of a computer called the Market Data System (MDS) through debates surrounding the National Market System and the passage of the 1975 Securities Acts Amendments. Building on research at the archives of the NYSE and the Securities and Exchange Commission (SEC), this history emphasizes the regulatory and managerial contexts in which market data became computerized. The SEC viewed market automation as both necessary for the viability of the securities industry and a mechanism for expanding regulatory oversight over the venues of stock trading. Moving from the MDS to later technical projects in the late 1960s and early 1970s, this article charts the changing meaning of electronic governance in a market increasingly conceptualized as a technical object. Adding to recent work in the social studies of finance and financial technologies, this history sites early NYSE computerization programs within managerial efforts to consolidate control over the clerical labor of financial markets, and in contests between regulatory and market institutions. It concludes by exploring the differing forms of electronic governance activated in these efforts to bring computers into the market.
Patient navigation for lung cancer screening among current smokers in community health centers a randomized controlled trial.

Annual chest computed tomography (CT) can decrease lung cancer mortality in high-risk individuals. Patient navigation improves cancer screening rates in underserved populations. Randomized controlled trial was conducted from February 2016 to January 2017 to evaluate the impact of a patient navigation program on lung cancer screening (LCS) among current smokers in five community health centers (CHCs) affiliated with an academic primary care network. We randomized 1200 smokers aged 55-77 years to intervention (n = 400) or usual care (n = 800). Navigators contacted patients to determine LCS eligibility, introduce shared decision making about screening, schedule appointments with primary care physicians (PCPs), and help overcome barriers to obtaining screening and follow-up. Control patients received usual care. The main outcome was the proportion of patients who had any chest CT. Secondary outcomes were the proportion of patients contacted, proportion receiving LCS CTs, screening results and number of lung cancers diagnosed. Of the 400 intervention patients, 335 were contacted and 76 refused participation. Of the 259 participants, 124 (48%) were ineligible for screening; 119 had smoked <30 pack-years, and five had competing comorbidities. Among the 135 eligible participants in the intervention group, 124 (92%) had any chest CT performed. In intention-to-treat analyses, 124 intervention patients (31%) had any chest CT versus 138 control patients (17.3%, P < 0.001). LCS CTs were performed in 94 intervention patients (23.5%) versus 69 controls (8.6%, P < 0.001). A total of 20% of screened patients required follow-up. Lung cancer was diagnosed in eight intervention (2%) and four control (0.5%) patients. A patient navigation program implemented in CHCs significantly increased LCS among high-risk current smokers.
Blood Relatives: Splicing Mechanisms underlying Erythropoiesis in Health and Disease.

During erythropoiesis, hematopoietic stem and progenitor cells transition to erythroblasts en route to terminal differentiation into enucleated red blood cells. Transcriptome-wide changes underlie distinct morphological and functional characteristics at each cell division during this process. Many studies of gene expression have historically been carried out in erythroblasts, and the biogenesis of β-globin mRNA—the most highly expressed transcript in erythroblasts—was the focus of many seminal studies on the mechanisms of pre-mRNA splicing. We now understand that pre-mRNA splicing plays an important role in shaping the transcriptome of developing erythroblasts. Recent advances have provided insight into the role of alternative splicing and intron retention as important regulatory mechanisms of erythropoiesis. However, dysregulation of splicing during erythropoiesis is also a cause of several hematological diseases, including β-thalassemia and myelodysplastic syndromes. With a growing understanding of the role that splicing plays in these diseases, we are well poised to develop gene-editing treatments. In this review, we focus on changes in the developing erythroblast transcriptome caused by alternative splicing, the molecular basis of splicing-related blood diseases, and therapeutic advances in disease treatment using CRISPR/Cas9 gene editing.
A novel approach to discrete truss design problems using mixed integer neighborhood search

Discrete truss sizing problems are very challenging to solve due to their combinatorial, nonlinear, non-convex nature. Consequently, truss sizing problems become unsolvable as the size of the truss grows. To address this issue, we consider various mathematical formulations for the truss design problem with the objective of minimizing weight, while the cross-sectional areas of the bars take only discrete values. Euler buckling constraints, Hooke’s law, and bounds for stress and displacements are also considered. We propose mixed integer linear optimization (MILO) reformulations of the non-convex mixed integer models. The resulting MILO models are not solvable with existing MILO solvers as the size of the problem grows. Our novel methodology provides high-quality solutions for large-scale real truss sizing problems, as demonstrated through extensive numerical experiments.
Preoperative factors predictive of pathologic upstaging in clinical stage I gastric cancer patients.

39Background: In patients with stage 1 gastric cancer, surgical resection without neoadjuvant therapy is offered as the first line treatment. However, some of these patients are found to have highe...
Female sex and brain-selective estrogen benefit α-synuclein tetramerization and the PD-like motor syndrome in 3K transgenic mice

Many studies report a higher risk for Parkinson's disease (PD) and younger age of onset in men. This, and the fact that the neuropathological process underlying PD symptoms may begin before menopause, suggests that estrogen-based hormone therapy could modify this higher risk in males. However, the effects of female sex or estrogen on α-synuclein (αS) homeostasis and related PD neuropathology remain unknown. Here, we used an αS tetramer-abrogating mouse model of PD (3K) that amplifies the familial E46K PD mutation to investigate the effects of female sex and brain-selective estrogen treatment on αS tetramerization and solubility, formation of vesicle-rich αS+ aggregates, dopaminergic and cortical fiber integrity, and associated motor deficits. In male 3K mice, the motor phenotype became apparent at ∼10 weeks and increased to age 6 months, paralleled by PD-like neuropathology, whereas 3K females showed a significant delay in onset. At 6 months, this beneficial phenotypic effect in 3K females was associated with a higher αS tetramer-to-monomer ratio and less decrease in dopaminergic and cortical fiber length and quantity. Brain-selective estrogen treatment in symptomatic 3K mice significantly increased the tetramer-to-monomer ratio, turnover by autophagy of aggregate-prone monomers, and neurite complexity of surviving DAergic and cortical neurons, in parallel with benefits in motor performance. Our findings support an upstream role for αS tetramer loss in PD phenotypes and a role for estrogen in mitigating PD-like neuropathology in vivo Brain-selective estrogen therapy may be useful in delaying or reducing PD symptoms in men and postmenopausal women.SIGNIFICANCE STATEMENT The mechanisms responsible for the male-to-female preponderance in Parkinson's disease (PD) are not well understood yet important for treatment efficacy. We previously showed that abrogating native α-synuclein (αS) tetramers produces a close PD model, including dopaminergic and cortical fiber loss and a progressive motor disorder responsive to l-DOPA. Here, we analyzed sex and use 10b-17β-dihydroxyestra-1,4-dien-3-one treatment of symptomatic 3K males, and demonstrate that the beneficial effects of female sex on PD-like neuropathology can be reinstated by elevating estrogen in the male brain. The study provides evidence that 17β-estradiol restores the tetramer-to-monomer ratio by autophagy turnover of excess αS monomers, vesicle and fiber integrity in brain regions critically involved in motor behavior. These data provide the basis for understanding sex differences in αS homeostasis and the development of therapeutic approaches to treating men and postmenopausal women with PD.
A survey of world language cooperating teachers: Implications for teacher development

In an era of long‐standing world language teacher shortages, the preservice mentoring process has become even more critical. Using data from a national survey, this study provides a profile of PreK–12 world language cooperating teachers (CTs) and shares their beliefs about and perspectives on the teacher candidates with whom they work, their interactions with postsecondary stakeholders, their reasons for serving as CTs, and the challenges that inhibit the smooth and meaningful induction of new colleagues into the profession. Implications highlight opportunities for reform in world language teacher development.
Comparing Board Examination Scores Between Pediatric Residents in Continuity Clinics at Different Sites.

Objective Determine if there is a difference in medical knowledge between pediatric residents attending continuity clinic at a community-based center versus those attending an academic center, as measured by the American Board of Pediatrics In-Training Exam (in-training exam) and the American Board of Pediatrics Certification Exam (certification exam). Methods A retrospective evaluation of in-training and certification exam scores of pediatric residents enrolled at the Medical College of Wisconsin and Children's Hospital of Wisconsin was performed. Test scores of the group of residents participating in a community-based continuity clinic were compared to those residents attending an academic center continuity clinic. Results There were no statistically significant differences in mean test scores for each of the 3 years of residency training on the in-training exam or board certifying exam after graduation. In-training exam scores significantly predicted certification exam scores, and there were significant increases in the in-training exam scores throughout residency, irrespective of clinic location. Conclusion This study shows no difference between residents participating in a communitybased continuity clinic and those participating in an academic center continuity clinic in objective outcomes as measured by scores on the American Board of Pediatrics In-Training Exam and the American Board of Pediatrics Certifying Exam.
Shellfish Tropomyosin IgE Cross-Reactivity Differs Among Edible Insect Species.

Scope Insects are a potentially environmentally friendly alternative dietary protein source to supplement mammalian and fish sources, but potential allergenic risks are a concern. Consumption of insects may result in anaphylaxis and has been implicated in cross-reactivity with shellfish. Many allergenic proteins may be involved in cross-reactivity, including tropomyosin (TM). The uniformity of TM cross-reactivity among edible insects is unknown. Candidate edible insects for variability in shellfish IgE cross-reactivity are investigated. Methods and results Selected insects and known related sources of allergens are extracted and probed by immunoblot with sera/plasma from patients sensitized to insects or shellfish. Quantification of TM in these extracts is performed using mass spectrometry. A comparison of the quantity of TM and the IgE reactivity of TM from these insects is performed. Distinct patterns of IgE cross-reactivity are observed with three insect species showing diminished reactivity. This pattern is not consistent with the amount of TM present in these insects, or with overall sequence homology. Conclusion Insects display a diversity of TM-associated IgE reactivity. It is likely that minor sequence features and/or structural effects are primarily responsible. Additionally, it is demonstrated that some insect species may present significantly less IgE cross-reactivity to shrimp than do others.
Endogenous CCN family member WISP1 inhibits trauma-induced heterotopic ossification

Heterotopic ossification (HO) is defined as abnormal differentiation of local stromal cells of mesenchymal origin, resulting in pathologic cartilage and bone matrix deposition. Cyr61, CTGF, Nov (CCN) family members are matricellular proteins that have diverse regulatory functions on cell proliferation and differentiation, including the regulation of chondrogenesis. However, little is known regarding CCN family member expression or function in HO. Here, a combination of bulk and single-cell RNA sequencing defined the dynamic temporospatial pattern of CCN family member induction within a mouse model of trauma-induced HO. Among CCN family proteins, Wisp1 (also known as Ccn4) was most upregulated during the evolution of HO, and Wisp1 expression corresponded with chondrogenic gene profile. Immunohistochemistry confirmed WISP1 expression across traumatic and genetic HO mouse models as well as in human HO samples. Transgenic Wisp1LacZ/LacZ knockin animals showed an increase in endochondral ossification in HO after trauma. Finally, the transcriptome of Wisp1-null tenocytes revealed enrichment in signaling pathways, such as the STAT3 and PCP signaling pathways, that may explain increased HO in the context of Wisp1 deficiency. In sum, CCN family members, and in particular Wisp1, are spatiotemporally associated with and negatively regulate trauma-induced HO formation.
Seawater-based one-pot ionic liquid pretreatment of sorghum for jet fuel production

Most solvent-based lignocellulosic pretreatment technologies require large amounts of freshwater, which competes with municipal/agricultural uses and can significantly influence the operating cost of a biorefinery. Seawater and other brackish water are abundant and have no competitive human uses, therefore are potentially a better water source to use in a biorefinery than freshwater. We found that performing pretreatment and saccharification using the biocompatible ionic liquid (IL) cholinium lysinate diluted in seawater in a consolidated single unit operation or “one-pot” process configuration results in comparable glucose and xylose yields relative to freshwater. Next, the sugars in seawater hydrolysates were converted into the potential jet fuel molecule prespatane by an engineered strain of Rhodosporidium toruloides. This study illustrates that seawater can effectively displace freshwater when used in a one-pot biomass pretreatment, deconstruction, and conversion process using a biocompatible IL and a salt-tolerant microorganism.
Singlet oxygen-dependent chloroplast degradation is independent of macroautophagy in the Arabidopsis ferrochelatase two mutant

Abstract Background Chloroplasts respond to stress and changes in the environment by producing reactive oxygen species (ROS) that have specific signaling abilities. The ROS singlet oxygen (1O2) is unique in that it can signal to initiate selective degradation of damaged chloroplasts and then cell death. This chloroplast quality control pathway can be monitored in the Arabidopsis mutant plastid ferrochelatase two (fc2) that conditionally accumulates chloroplast 1O2 under diurnal light cycling conditions leading to rapid chloroplast degradation and eventual cell death. The cellular machinery involved in such degradation, however, remains unknown. Recently it has been demonstrated that whole damaged chloroplasts can be transported to the central vacuole via a process requiring autophagosomes and core components of the autophagy machinery. The relationship between this process, referred to as chlorophagy, and the degradation of 1O2-stressed chloroplasts and cells has remained unexplored. Results To further understand 1O2-induced cellular degradation and determine what role autophagy may play, the expression of autophagy-related genes were monitored in 1O2-stressed fc2 seedlings and found to be induced. Although autophagosomes were present in fc2 cells, they did not associate with chloroplasts during 1O2 stress. Mutations blocking the core autophagy machinery (atg5, atg7, and atg10) were unable to suppress 1O2-induced chloroplast degradation or cell death in the fc2 mutant, suggesting autophagosome formation and macroautophagy are dispensable for 1O2–mediated cellular degradation. However, both atg5 and atg7 led to specific defects in chloroplast ultrastructure and photosynthetic efficiencies, suggesting macroautophagy may be involved in protecting chloroplasts from photo-oxidative damage. Finally, genes predicted to be involved in microautophagy were shown to be induced in stressed fc2 seedlings, indicating a possible role for an alternate form of autophagy in the dismantling of 1O2-damaged chloroplasts. Conclusions Our results support the hypothesis that 1O2-dependent chloroplast degradation is independent from autophagosome formation, canonical macroautophagy, and chlorophagy. Instead, ATG-independent microautophagy may be involved in such degradation. However, canonical macroautophagy may still play a role in protecting chloroplasts from 1O2-induced photo-oxidative stress. Together, this suggests chloroplast function and degradation is a complex process that utilizes multiple autophagy and degradation machineries, possibly depending on the type of stress or damage incurred.
Probabilistic semantics for epistemic modals: Normality assumptions, conditional epistemic spaces and the strength of must and might

The epistemic modal auxiliaries must and might are vehicles for expressing the force with which a proposition follows from some body of evidence or information. Standard approaches model these operators using quantificational modal logic, but probabilistic approaches are becoming increasingly influential. According to a traditional view, must is a maximally strong epistemic operator and might is a bare possibility one. A competing account—popular amongst proponents of a probabilisitic turn—says that, given a body of evidence, must $$\phi $$ entails that $$Pr(\phi )$$ is high but non-maximal and might $$\phi $$ that $$Pr(\phi )$$ is significantly greater than 0. Drawing on several observations concerning the behavior of must, might and similar epistemic operators in evidential contexts, deductive inferences, downplaying and retractions scenarios, and expressions of epistemic tension, I argue that those two influential accounts have systematic descriptive shortcomings. To better make sense of their complex behavior, I propose instead a broadly Kratzerian account according to which must $$\phi $$ entails that $$Pr(\phi ) = 1$$ and might $$\phi $$ that $$Pr(\phi ) > 0$$ , given a body of evidence and a set of normality assumptions about the world. From this perspective, must and might are vehicles for expressing a common mode of reasoning whereby we draw inferences from specific bits of evidence against a rich set of background assumptions—some of which we represent as defeasible—which capture our general expectations about the world. I will show that the predictions of this Kratzerian account can be substantially refined once it is combined with a specific yet independently motivated ‘grammatical’ approach to the computation of scalar implicatures. Finally, I discuss some implications of these results for more general discussions concerning the empirical and theoretical motivation to adopt a probabilisitic semantic framework.
Short Pulse Scattering from Wires and Chaff Clouds

The scattering from a conducting wire of an ultra-wide band pulse with one-cycle-sine waveform has been investigated. There exists a similarity between the spectrum of the one-cycle-sine waveform and the characteristic spectrum of the wire, which is calculated based on Einarsson’s second order formula. This similarity in the spectra entails a possible resonant response of the wire to a pulse of this kind. Scattered pulses are obtained by the Fourier transform algorithm; and by appropriate choice of the duration of the one-cycle-sine waveform, resonances in backscattering, bistatic scattering, and specular scattering are observed. It is found that the resonant scattering is directly associated with the excitation of a very strong traveling wave on the wire.
Reader's Response: Motivating Graduate Students.

A response to “Applying Graduate Student Perceptions of Task Engagement to Enhance Learning Conditions“ Jay Caulfield, Volume 4, Number 1 ( January 2010).
Sorption, Diffusion, and Catalytic Reaction in Zeolites

Publisher Summary This chapter discusses the quantitative aspects of catalytic reaction rates in zeolites. The chapter examines possible models representing equilibrium and rate phenomena in gas-zeolite systems to obtain an understanding of the kinetics of chemical reactions in zeolites. Sorption equilibria and rates of sorption/desorption, exchange, and catalytic reaction are closely related and are represented in terms of the same model. In the case of sorption by zeolites, the sorbed amount is found to be proportional to the mass of the solid sorbent, independent of crystallite size or extent of phase boundary; sorption in the bulk volume is generally large compared with adsorption on the crystal faces. Sorption in zeolites is regarded as adsorption on an “internal surface,” the lattice being considered as an analog of a macroporous solid. This description is useful to characterize the sorption properties and sorption capacities of zeolites. However, the “internal surface” does not constitute a phase boundary and the theories of surface thermodynamics and capillarity cannot be applied to the internal surface and pore structure.
Electronic cigarettes and nicotine dependence: evolving products, evolving problems

Electronic cigarettes (ECIGs) use an electric heater to aerosolize a liquid that usually contains propylene glycol, vegetable glycerin, flavorants, and the dependence-producing drug nicotine. ECIG-induced nicotine dependence has become an important concern, as some ECIGs deliver very little nicotine while some may exceed the nicotine delivery profile of a tobacco cigarette. This variability is relevant to tobacco cigarette smokers who try to switch to ECIGs. Products with very low nicotine delivery may not substitute for tobacco cigarettes, so that ECIG use is accompanied by little reduced risk of cigarette-caused disease. Products with very high nicotine delivery may make quitting ECIGs particularly difficult should users decide to try. For non-smokers, the wide variability of ECIGs on the market is especially troublesome: low nicotine products may lead them to initiate nicotine self-administration and progress to higher dosing ECIGs or other products, and those that deliver more nicotine may produce nicotine dependence where it was not otherwise present. External regulatory action, guided by strong science, may be required to ensure that population-level nicotine dependence does not rise.