cssi/SciSciGPT-SciSciNet huggingface dataset:
GGA1-mediated endocytic traffic of LR11/SorLA alters APP intracellular distribution and amyloid-β production

Proteolytic processing of the amyloid-β precursor protein (APP) and generation of amyloid-β peptide (Aβ) are key events in Alzheimer's disease (AD) pathogenesis. Cell biological and genetic evidence has implicated the low-density lipoprotein and sorting receptor LR11/SorLA in AD through mechanisms related to APP and Aβ production. Defining the cellular pathway(s) by which LR11 modulates Aβ production is critical to understanding how changes in LR11 expression affect the development of Aβ pathology in AD progression. We report that the LR11 ectodomain is required for LR11-mediated reduction of Aβ and that mutagenesis of the LR11 Golgi-localizing, γ-adaptin ear homology domain, ADP-ribosylation factor (GGA)-binding motif affects the endosomal distribution of LR11, as well as LR11's effects on APP traffic and Aβ production. Targeted small interfering RNA (siRNA) knockdown studies of GGA1, GGA2, and GGA3 indicate a surprising degree of specificity toward GGA1, suggesting that GGA1 is a candidate regulator of LR11 traffic. Additional siRNA knockdown experiments reveal that GGA1 is necessary for both LR11 and β-site APP-cleaving enzyme-1 (BACE1) modulation of APP processing to Aβ. Mutagenesis of BACE1 serine 498 to alanine enhances BACE1 targeting to LR11-positive compartments and nullifies LR11-mediated reduction of Aβ. On basis of these results, we propose that GGA1 facilitates LR11 endocytic traffic and that LR11 modulates Aβ levels by promoting APP traffic to the endocytic recycling compartment.
Tyrosine Phosphorylation of the CD3-ε Subunit of the T Cell Antigen Receptor Mediates Enhanced Association with Phosphatidylinositol 3-Kinase in Jurkat T Cells

T cell receptor signaling results both in T cell proliferation and apoptosis. A key enzyme at the intersection of these downstream pathways is phosphatidylinositol 3'-kinase (PI 3-kinase). In a previous report, we showed that the p85alpha subunit of the PI 3-kinase preferentially associated with the CD3-zeta membrane-proximal immunoreceptor tyrosine-based activation motif of the zeta chain (zetaA-ITAM) (Exley, M., Varticovski, L., Peter, M., Sancho, J., and Terhorst, C. (1994) J. Biol. Chem. 269, 15140-15146). Here, we demonstrate that tyrosine phosphorylation of CD3-epsilon can recruit the PI 3-kinase enzyme in a T cell activation-dependent manner. In vivo studies with Jurkat cells stably transfected with a CD8-CD3-epsilon chimera (termed CD8-epsilon) shows that ligation of endogenous CD3-epsilon or CD8-epsilon by specific antibodies induces tyrosine phosphorylation of CD3-epsilon or CD8-epsilon, respectively. Increased tyrosine phosphorylation correlates with increased binding of p85alpha PI 3-kinase and recruitment of PI 3-kinase enzymatic activity to CD3-epsilon or CD8-epsilon proteins. Mutagenesis studies in COS-7 cells, transiently transfected with CD8-epsilon, p85alpha, and Fyn cDNAs in various combinations, show that both Tyr170 and Tyr181 within the CD3-epsilon-ITAM are required for efficient binding of p85alpha PI 3-kinase. Thus, replacement of Tyr170 by Phe (Y170F), or Tyr181 by Phe (Y181F) significantly reduces binding of p85alpha PI 3-kinase, whereas it does not affect binding of Fyn. Further in vitro experiments suggest that a direct binding of the tandem SH2 domains of p85alpha PI 3-kinase to the two phosphorylated tyrosines in a single CD3-epsilon-ITAM may occur. The data also support a model in which a single CD3 subunit can recruit distinct effector molecules by means of TCR-mediated differential ITAM phosphorylation.
C. Elegans Genetic Strategies to Identify Novel Parkinson's Disease-associated Therapeutic Targets and Leads

Publisher Summary This chapter presents C. elegans genetic strategies to identify novel Parkinson's disease (PD)-associated therapeutic targets and leads. C. elegans is a powerful tool for genetic analysis and determination of molecular mechanisms involved PD-associated DA neuron cell death. C. elegans is also a powerful and facile system for drug discovery and target validation. The worm is sensitive to a number of human neuroreactive compounds including acetylcholine receptor agonist, anesthetics, cholinesterase inhibitors, immunosupressants, and serotonin, GABA, and dopamine-related compounds, and these drugs appear to interact with the worm homologs and at the orthologous active sites. A C. elegans toxin-based therapeutic lead screen provides opportunities to select compounds that protect against different steps of the neurodegeneration process. The identiﬁcation of the D2 agonist quinpirole (QPR), bromocriptine (BMC), and the mixed D1/D2 agonist dihydrexidine as neuroprotective compounds is analyzed. It is suggested that C. elegans will play an integral role in the identification in the future of novel human therapeutic targets and leads.
Theories and Techniques of Marital and Family Therapy

Histories of the intertwined fields of marriage and family therapy have appeared during the past 2 decades (e.g., Broderick & Schrader, 1991; Guerin, 1976; F. Kaslow, 1982, 1987; Thomas, 1992). Elaborating upon an earlier version of this material (F. Kaslow, 1987), this chapter concentrates on developments in the past decade, a time during which the convergence of the marital and family therapy fields has been accepted.
THE SQUALIFORMS OF THE LIGURIAN SEA: A REVISED LIST WITH NOTES

ABSTRACT A revised list of the Squaliforms of the Ligarian Sea is presented with notes added from recent observations.
Factors predicting health behaviors among Army Reserve, active duty Army, and civilian hospital employees.

ABSTRACT This study identified health-risk and health-promoting behaviors in military and civilian personnel employed in hospitals. Intrinsic self-motivation and extrinsic organizational workplace factors were examined as predictors of health behaviors. Because reservists represent a blend of military and civilian lifestyles, descriptive analyses focused on comparing Army Reserve personnel (n = 199) with active duty Army (n = 218) and civilian employees (n = 193), for a total sample of 610. Self-motivation and social support were significant factors contributing to the adoption of health-promoting behaviors; however, organizational workplace cultures were inconsistent predictors of health among the three groups. Only the active Army subgroup identified a hierarchical culture as having an influence on health promotion, possibly because of the Army's mandatory physical fitness and weight control standards. Social support and self-motivation are essential to promoting health among employees, thus hospital co...
1-PHENOXYPHOSPHOLENE 1-OXIDES

Abstract Isomerically pure samples of the two isomers of 1-phenoxyphospholene 1-oxide were prepared and exhaustively characterized by 1H, 31P and 13C nmr, IR and mass spectrometry.
Al 65 Cu 20 Fe 15 in amorphous, crystalline and quasicrystalline states

Three structurally distinct states (amorphous, crystalline, and quasicrystalline) of Al65Cu20Fe15 and neighboring compositions, have been observed. A new metastable state. Intermediate between the amorphous and the quasicrystalline states, has been found. Mossbauer-effect measurements on these samples Al65Cu20xFe15+x (−10≤x≤ 10, at.%) In the three different states show that the differences in the effective isomer shifts and quadrupole splittings among the three states are small despile diametrically different structures.
Superposition effect is a “local” phenomenon when we investigate the processes behind release of photo electrons

The “locality” of superposition effect becomes evident when one explicitly models the light-matter stimulation and energy exchange processes using basic QM recipe of taking square modulus of simultaneous dipolar stimulations of the detecting molecules by all waves.
Trends in Male and Female Genital Warts Among Adolescents in a Safety-Net Health Care System 2004-2013: Correlation With Introduction of Female and Male Human Papillomavirus Vaccination.

BackgroundHuman papillomavirus (HPV) vaccination remains underused in the United States, and few population-level studies on effectiveness exist.MethodsWe examined trends in rates of genital warts diagnoses and HPV vaccination rates (defined as receipt of 1 or more vaccine doses) among low-income an
Analog decoding of product codes

A method is presented for analog soft-decision decoding of block product codes (block turbo codes). Extrinsic information is exchanged as analog signals between component row and column decoders. The component MAP decoders use low-power analog computation in subthreshold CMOS circuits to implement the sum-product algorithm. An example decoder design is presented for a (16, 11)/sup 2/ Hamming code.
Dynamic simulation of LNG loading, BOG generation, and BOG recovery at LNG exporting terminals

Abstract Liquefied natural gas (LNG) is a prominent clean energy source available in abundance. LNG has high calorific value, while lower price and emissions. Vapors generated from LNG due to heat leak and operating-condition-changes are called boil-off gas (BOG). Because of the very dynamic in nature, the rate of BOG generation during LNG loading (jetty BOG, or JBOG) changes significantly with the loading time, which has not been well studied yet. In this work, the LNG vessel loading process is dynamically simulated to obtain JBOG generation profiles. The effect of various parameters including holding-mode heat leak, initial-temperature of LNG ship-tank, JBOG compressor capacity, and maximum cooling-rate for ship-tank, on JBOG profile is studied. Understanding JBOG generation would help in designing and retrofitting BOG recovery facilities in an efficient way. Also, several JBOG utilization strategies are discussed in this work. The study would help proper handling of BOG problems in terms of minimizing flaring at LNG exporting terminals, and thus reducing waste, saving energy, and protecting surrounding environments.
Mentoring and Informal Learning as Continuing Professional Education

This chapter examines the role of mentoring in continuing professional education from a critical perspective, addressing informal and formal mentoring relationships while highlighting their potential to encourage critical reflection, learning, and coconstruction of knowledge.
Thinking Outside the Ledger: A Visual Representation Project for Accounting Students

“Thinking Outside the Ledger – a Visual Representation Project for Accounting Students” discusses a learning experience that provides practice in reflective thinking and communication skills. The project, called VRep, asks students to address an accounting issue and communicate it visually with their own independent creation, interpretation or modification – such as a diagram, concept map, picture, flow chart, acronym, drawing or model. This paper presents the theoretical arguments for such a project. It then details the dissemination of the project. Finally, it summarizes students’ results and experiences with the project and provides examples of their work. Students’ perceptions of VRep indicate that they perceive it as more useful to them than most homework assignments. They further believe that with VRep, they will retain more learning as compared to most homework assignments. In addition, 74% of students recommend VRep be assigned in future audit classes. Unexpected bright spots of the student results include engaged scholarship and opportunities for instructors to praise and reward normally “C” students with “A” grades. This paper begins a conversation among accounting educators as to how students can learn to communicate accounting matters visually, as well as how the creation of visual representations enhances learning.
CHANGES IN RENAL PERFUSION PRESSURE DURING HEMODYNAMICALLY GUIDED THERAPY IS ASSOCIATED WITH WORSENING RENAL FUNCTION

Background: Patients in acute decompensated heart failure (ADHF) undergoing diuretic therapy are vulnerable to worsening renal function (WRF). We hypothesized that decreases in renal perfusion pressure (RPP), the difference between mean arterial pressure and central venous pressure, would provide a
Abdominal obesity and white matter microstructure in midlife.

The aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion-tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40-62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full-tensor, high-dimension normalization, and tract-based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL-cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp 38:3337-3344, 2017. © 2017 Wiley Periodicals, Inc.
Who experiences growth in news media literacy and why does it matter? Examining education, individual differences, and democratic outcomes

Developing news media literacy skills is recognized as an important part of becoming an informed citizen, but not enough research examines how growth in media literacy differs by individual characteristics. Using a panel study of undergraduate students, we examine which predispositions predict growth in news media literacy beliefs over the semester. We then test whether growth in news media literacy leads individuals to more highly value and engage in heterogeneous political discussion, a critical part of a functioning democracy. Our results suggest some individuals experience more growth in news media literacy, and that growth contributes to democratic attitudes and behaviors.
Deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B-cell development.

Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B-cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B-cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the Ig heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3Δ/- bone marrow. For Hdac3Δ/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment use. Although transcriptional effects within these loci were modest, Hdac3Δ/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Reintroduction of wild-type Hdac3 restored normal B-cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells.
Effect of intermediate layers on atomic layer deposition-aluminum oxide protected silver mirrors

This work investigates intermediate materials deposited between silver (Ag) thin-film mirrors and an aluminum oxide (AlOx) barrier overlayer and compares the effects on mirror durability to environmental stresses. Physical vapor deposition of various fluorides, oxides, and nitrides in combination with AlOx by atomic layer deposition (ALD) is used to develop several coating recipes. Ag-AlOx samples with different intermediate materials undergo aggressive high-temperature (80°C), high-humidity (80%) (HTHH) testing for 10 days. Reflectivity of mirror samples is measured before and after HTHH testing, and image processing techniques are used to analyze the specular surface of the samples after HTHH testing. Among the seven intermediate materials used in this work, TiN, MgAl2O4, NiO, and Al2O3 intermediate layers offer more robust protection against chemical corrosion and moisture when compared with samples with no intermediate layer. In addition, results show that the performance of the ALD-AlOx barrier overlayer depends significantly on the ALD-growth process temperature. Because higher durability is observed in samples with less transparent TiN and NiO layers, we propose a figure of merit based on post-HTHH testing reflectivity change and specular reflective mirror surface area remaining after HTHH testing to judge overall barrier performance.
Near-infrared used in process chemistry

Dr. Gary Heiftje has written a text book on Analytical Chemistry which some consider to be a classic. That textbook contains one sentence on near-infrared spectroscopy which states that “The NIR is generally a useless region for an analytical chemist.” While this statement is indeed correct for classical studies for functional group assignment, laboratory technicians and process engineers out-perform conventional spectroscopy time and time again by using near-infrared (NIR) spectroscopy for routine analysis. NIR analysis, or NIRA as it is called by some, relates NIR diffuse reflectance or transmission spectra to analyte concentrations. It is, therefore, primarily a quantitative technique, although it can be used for qualitative purposes as well.
A Hybrid Nodal Diffusion/SP3 Method Using One-Node Coarse-Mesh Finite Difference Formulation

A hybrid nodal diffusion/simplified P{sub 3} (SP{sub 3}) method was implemented within the framework of a one-node coarse-mesh finite difference formulation. The one-node formulation enables the use of various combinations of space, energy, and angular approximations within the framework of the one-node global/local solution approach. Spatial approximations include advanced nodal methods and fine-mesh finite difference methods. Energy approximations involve conventional two-group and multiple energy groups. Angular approximations contain both the diffusion and SP{sub 3} methods. Partial-moment boundary conditions are used to solve the one-node problems since they simplify the formulation of consistent interface conditions for the various methods. All directional moments are determined simultaneously to stabilize convergence of the one-node global/local solution approach. Results for a light water reactor mixed-oxide benchmark problem indicate that the hybrid application of the one-node-based nodal SP{sub 3} method developed here can provide substantial reductions in the computational time without compromising the accuracy of the solution.
Pursuit Games: A Survey

A survey of results on pursuit games in finite-dimensional spaces is presented, with emphasis on computable methods of winning. Two proto-principles are treated: neutralisation of effect of opponent’s control, and maintanance of constant observation vector. The appendices illustrate their application.
The truss-beam and space technology

A method is presented herein to determine the dynamic characteristics of truss-beam systems for both planar and space structures. Results from this approach are compared with those of the finite element method and test results. The truss-beam model is based on the assumptions of negligible web contribution, i.e., very large flexible structures. Future experimental evaluation of the plane truss-system is planned at North Carolina Agricultural and Technical State University and this experimental program is described.
Abstract 3735: Somatostatin receptor-based imaging and treatment of murine pancreatic neuroendocrine tumors induced by MEN1-loss

Background: Somatostatin receptor ligands are used for the detection and treatment of neuroendocrine tumors. Mutations of MEN1 are frequently observed in human pancreatic neuroendocrine tumors (PanNETs). We utilized a previously described murine model of PanNET that harbors a floxed Men1 allele to study the feasibility of somatostatin receptor type 2 (SSTR2) imaging and therapy in mice. Methods: Mice with pancreatic-specific expression of Cre recombinase and floxed Men1 (Pdx1-cre, Men1f/f) were aged to 9-12 months to allow for the development of PanNETs. Mice were injected with either the SSTR2 agonist 68Ga-DOTA-TATE or antagonist 177Lu-DOTA-JR11 via tail vein. Imaging with 68Ga-DOTA-TATE was performed using PET/CT. Percent uptake of injected activity was calculated for visualized tumors. 177Lu-DOTA-JR11 binding was visualized with autoradiography. Immunofluorescence (IF) detected SSTR2 expression and a marker of DNA damage (γ-H2AX). Results: IF staining for SSTR2 showed membranous localization of the receptor limited to areas of neoplasia with high and low levels of SSTR2 expression variable by individual animal and tumor. Tumors were successfully detected in mice injected with 68Ga-DOTA-TATE using PET/CT. The mean maximum percent uptake of injected activity for visualized tumors was 2.8% +/- 0.34. Injection of 177Lu-DOTA-JR11 and subsequent autoradiography confirmed localization of radionuclide to areas of histology-confirmed neoplasia. Treatment effect (DNA damage) was observed with co-localization of γ-H2AX and SSTR2 staining in neoplastic areas as compared to hyperplastic islets and normal pancreatic parenchyma that were both SSTR2 and γ-H2AX negative. Conclusion: PanNETs from Pdx1-cre, Men1f/f mice can be successfully imaged and treated using somatostatin-based radionuclides. This genetically accurate model can be employed to study peptide receptor radionuclide therapy efficacy and toxicity either alone or in combination with other treatment strategies. Citation Format: Janet W. Li, Hanwen Zhang, Sean D. Carlin, Nitya Raj, David S. Klimstra, Steven K. Libutti, Wolfgang A. Weber, Diane Reidy-Lagunes, Brian R. Untch. Somatostatin receptor-based imaging and treatment of murine pancreatic neuroendocrine tumors induced by MEN1-loss [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3735.
Research on agricultural product price forecasting model based on improved BP neural network

BP neural network algorithm and genetic algorithm are the core algorithms in machine learning algorithms. Major mainstream internet companies and financial institutions have begun to use machine learning algorithms to fit the data, which directly stimulates the development of domestic machine learning algorithms. The research of this paper shows that the algorithm optimization has strong advantages in modeling real estate data, but the current neural network training process cannot be explained. With the development of technology and artificial intelligence, more progress will be made in the area of GA optimization of BP neural networks.
US Criminal Justice Policy and Practice in the Twenty-First Century: Toward the End of Mass Incarceration?

Although the wisdom of mass incarceration is now widely questioned, incarceration rates have fallen far less than what would be predicted on the basis of crime trends. Informed by institutional studies of path dependence, sociolegal scholarship on legal discretion, and research suggesting that “late mass incarceration” is characterized by a moderated response to nonviolent crime but even stronger penalties for violent offenses, this article analyzes recent sentencing‐related reforms and case processing outcomes. Although the legislative findings reveal widespread willingness to moderate penalties for nonviolent crimes, the results also reveal a notably heightened system response to both violent and nonviolent crimes at the level of case processing. These findings help explain why the decline in incarceration rates has been notably smaller than the drop in crime rates and are consistent with the literature on path dependence, which emphasizes that massive institutional developments enhance the capacity and motivation of institutional actors to preserve jobs, resources, and authorities. The findings also underscore the importance of analyzing on‐the‐ground case processing outcomes as well as formal law when assessing the state and fate of complex institutional developments such as mass incarceration.
The Shifting Landscape of the Homeschooling Continuum.

In 1988, Van Galen proposed two distinct categories to describe homeschooling parents – ideologues and pedagogues. Her model has been widely cited in the homeschooling literature. In the 30 years s...
Utilization of Mixed Municipal Solid Waste Compost as a Soilless Potting Component in Greenhouse Production of Four Floricultural Crops

Abstract Mixed municipal solid waste compost (MSWC) was evaluated as a soilless potting mix component for greenhouse production using four floricultural crops: dusty miller (Senecio cineraria), hybrid petunia (Petunia × hybrida), Japanese holly fern (Cyrtomium falcatum), and begonia (Begonia × semperflorens-cultorum). Dusty miller and petunia plugs were transplanted into 36-cell trays filled with MSWC based substrates and grown for two months. Petunia only grew well in the blend with the lowest MSWC ratio (33%), while dusty miller grew well in all MSWC blends. Japanese holly fern and begonia liners were transplanted into 15 cm (6 in) azalea pots and grown for 12 weeks in five substrates: 100% pine bark (PB), 3: 1 PB: MSWC, 1: 1 PB: MSWC, 1: 3 PB: MSWC, and commercially available Fafard 3B Mix. In addition to substrate, a controlled-release fertilizer was applied at two rates to form a two-way factorial completely randomized design. Replacement of PB with MSWC resulted at least equal plant quality and grow...
The Effects of Method and Comprehensiveness of Training on the Reliability and Validity of Ratings of Counselor Empathy.

Type and comprehensiveness of training were experimentally manipulated to study their effects on the reliability and validity of rated counselor empathy. Implications for observer training are disc...
Initiation of a Delayed Cord Clamping Protocol in Preterm Infants with a Focus on Interdisciplinary Communication

Background: Delayed Cord Clamping (DCC) has been recommended by multiple medical bodies, including the American Congress of Obstetricians and Gynecologists, especially due to its benefits in preterm neonates, however it has only been minimally adopted in many practices. Studies in protocol initiation of DCC have demonstrated stepwise initiation of a protocol for preterm infants in the delivery room with variable compliance. This study evaluated if a DCC protocol can be successfully initiated with minimal education, primarily through clear communication between interdisciplinary providers at all levels. …
Impact of Simulation Training on Diagnostic Arthroscopy Performance: A Randomized Controlled Trial.

Purpose To determine the impact of training on a virtual reality arthroscopy simulator on both simulator and cadaveric performance in novice trainees. Methods A randomized controlled trial of 28 participants without prior arthroscopic experience was conducted. All participants received a demonstration of how to use the ArthroVision Virtual Reality Simulator and were then randomized to receive either no training (control group, n = 14) or a fixed protocol of simulation training (n = 14). All participants took a pretest on the simulator, completing 9 tasks ranging from camera-steadying tasks to probing structures. The training group then trained on the simulator (1 time per week for 3 weeks). At week 4, all participants completed a 2-part post-test, including (1) performing all tasks on the simulator and (2) performing a diagnostic arthroscopy on a cadaveric knee and shoulder. An independent, blinded observer assessed the performance on diagnostic arthroscopy using the Arthroscopic Surgical Skill Evaluation Tool scale. To compare differences between non–normally distributed groups, the Mann-Whitney U test was used. An independent-samples t test was used for normally distributed groups. The Friedman test with pair-wise comparisons using Bonferroni correction was used to compare scores within groups at multiple time points. Bonferroni adjustment was applied as a multiplier to the P value; thus, the α level remained consistent. Significance was defined as P Results In both groups, all tasks except task 5 (in which completion time was relatively fixed) showed a significant degree of correlation between task completion time and other task-specific metrics. A significant difference between the trained and control groups was found for post-test task completion time scores for all tasks. Qualitative analysis of box plots showed minimal change after 3 trials for most tasks in the training group. There was no statistical correlation between the performance on diagnostic arthroscopy on either the knee or shoulder and simulation training, with no difference in Arthroscopic Surgical Skill Evaluation Tool scores in the training group compared with controls. Conclusions Our study suggests that an early ceiling effect is shown on the evaluated arthroscopic simulator model and that additional training past the point of proficiency on modern arthroscopic simulator models does not provide additional transferable benefits on a cadaveric model. Level of Evidence Level I, randomized controlled trial.
A multi-dimensional dataset for two-phase instability in low pressure natural circulation based on direct transient local measurement

Abstract Thermal hydraulic instability can challenge the control and the safety of nuclear reactors. This experimental research captures and investigates the instability in a low-pressure (1–10 atmospheres) natural circulation loop with an adiabatic chimney installed above the heated section. Direct transient local measurement of two-phase flow is performed at multiple axial locations along the flow channel with thermocouples and conductivity probes traversed by customized high-precision mechanisms. Based on the periodicity of oscillations, a post-processing method is proposed to align the data captured non-simultaneously to reconstruct the instability behavior in one representative period. The averaging operation over multiple oscillation cycles is performed to reduce the random errors. Cyclic phenomena are clearly demonstrated by the post-processed data, and rapid void fraction change induced by the flashing is observed to be significant in the driving mechanism for low pressure oscillations. Parametric effects of inlet subcooling, heat flux, inlet flow restriction and system pressure are studied within the experiment range, and qualitative results are explained and compared with existing literature. The ratio between the oscillation period and the travelling time of the fluid particle through the test section is compared with the theoretical value for the density wave oscillation. The new dataset contains directly measured transient multi-dimensional two-phase data along the flow channel for natural circulation under density wave oscillations. The generated dataset is valuable for the validation of system analysis codes and CFD codes in the simulation of natural circulation phenomena and dynamic two-phase flow.
Why (a Theory of) Opportunity Matters: Refining the Austrian View of Entrepreneurial Discovery

The concept of entrepreneurial opportunity has undergone a period of useful critique and refinement since Venkataraman (1997) and Shane and Venkataraman (2000) employed the term as one of the defining features of entrepreneurship studies. This paper presents a novel Austrian reinterpretation of this concept as an intersubjective phenomenon that emerges from the dual entrepreneurial process of discovery and judgment. Just as markets can be described as price discovery procedures for existing goods, services, and resources, entrepreneurship can be usefully described as a price discovery procedure for future goods, services, and resources. This view retains the essential elements of Kirzner’s (1973) approach while also refining the opportunity discovery concept within an evolutionary realist framework for understanding entrepreneurial motivation and action.
Tailoring Lithium Polysulfide Coordination and Clustering Behavior through Cationic Electrostatic Competition

The materials chemistry underlying lithium-sulfur (Li-S) batteries is uniquely dependent on the behavior of soluble lithium polysulfide intermediates, which form during operation and mediate the charge-transfer process in solution. The manner by which lithium polysulfides are solvated by surrounding solvent and salt compounds is a critical factor with regards to electrochemical utilization and reversibility of the sulfur active material. Particularly at low-temperature and lean electrolyte conditions, lithium polysulfides tend to coordinate with other polysulfide units in solution, forming large, aggregated clusters that stymie the electrochemical conversion process. However, the tendency to cluster is known to be influenced by the presence of strongly binding anionic species in solution, which present electrostatic competing interactions with Li+. The heightened electrostatic competition in turn can dissuade the formation of clustered Li+-Sx2- bond networks. Here, we extend that understanding to the influence of distinct cationic species in solution, which can present analogous competing interactions with Sx2- dianions to stymie polysulfide cluster formation. We find that introducing NH4+ cations into solution through an ammonium trifluoroacetate additive positively tailors the polysulfide coordination shell. This improves the electrochemical conversion kinetics at challenging lean electrolyte and subzero low-temperature conditions, and provides a more holistic understanding of polysulfide coordination behavior.
Does Inequality Stay in the Shadow? The Cross-national Effects of Educational Equity on Private Tutoring and Student Achievement

Abstract By using multiple regression and hierarchical linear modeling, this study investigates shadow education across and within national educational systems in order to estimate the effect of educational equity on the relationship between private tutoring and student achievement. Data are from the Programme for International Student Assessment (PISA) 2012 and supplemented by World Bank data. Results indicate students’ participation in three types of private tutoring (commercial company, personal, and family tutoring) are negatively related to student achievement in the cross-national sample. Evidence suggests, however, that private tutoring may differently associate with student achievement depending on student- and nation-level educational equity factors and contexts. Finally, the validity of private tutoring as a measure of shadow education is deconstructed given these results.
Cores that don't count

We are accustomed to thinking of computers as fail-stop, especially the cores that execute instructions, and most system software implicitly relies on that assumption. During most of the VLSI era, processors that passed manufacturing tests and were operated within specifications have insulated us from this fiction. As fabrication pushes towards smaller feature sizes and more elaborate computational structures, and as increasingly specialized instruction-silicon pairings are introduced to improve performance, we have observed ephemeral computational errors that were not detected during manufacturing tests. These defects cannot always be mitigated by techniques such as microcode updates, and may be correlated to specific components within the processor, allowing small code changes to effect large shifts in reliability. Worse, these failures are often "silent" - the only symptom is an erroneous computation. We refer to a core that develops such behavior as "mercurial." Mercurial cores are extremely rare, but in a large fleet of servers we can observe the disruption they cause, often enough to see them as a distinct problem - one that will require collaboration between hardware designers, processor vendors, and systems software architects. This paper is a call-to-action for a new focus in systems research; we speculate about several software-based approaches to mercurial cores, ranging from better detection and isolating mechanisms, to methods for tolerating the silent data corruption they cause.
A 70-Year-Old Woman With Refractory Hypoxemia.

Case Presentation A 70-year-old woman was transferred to our ED from an outside ED for hypoxemia. Three weeks earlier, an inpatient evaluation for syncope revealed a right intraventricular filling defect, multiple pulmonary nodules, pulmonary emboli, and a left breast mass. She underwent breast biopsy, was started on rivaroxaban, and was discharged with outpatient follow-up. She experienced progressively worsening dyspnea, prompting a return to the outside ED, where she was found to be severely hypoxemic and was intubated. Her medical history included diabetes, hypertension, hyperlipidemia, COPD, hypothyroidism, diastolic heart failure, and a 40+ pack-year smoking history.
Environmental and Economic Sustainability

Introduction The Exponential Era Crisis-Which Crisis? True Sustainability for This Century Objectives and Structure of the Book Notes Sustainability in the Twenty-first Century A Short History of Sustainability The Challenges of the Twenty-first Century An Overview of Global Trends Why Sustainability Has Not Worked The Twentieth-Century Prosperity Explosion Twentieth-Century Engineering Twenty-First Century Economics for the Twenty-First Century Conclusion Notes Quantifying Sustainability for Improved Decision Making Balancing Environment, Society, and Economy The Environmental and Economic Sustainability Assessment: Embedding Sustainability in Decision Making Socioenvironmental Economic Analysis Full Social Cost-Benefit Analysis Valuing the Environment and Society Applying the Environmental and Economic Sustainability Assessment Examples Notes Water Introduction Water Management in Industry: Overview Water Use and Protection in Oilfield Development in North Africa Produced Water Management in Oilfield Operations Water Management in Mine Development Example: Determining a Sustainable Wastewater Treatment and Discharge Strategy Summary Notes Greenhouse Gases and Climate Change Introduction Carbon Mitigation Risk Adaptation Risks Example: GHG Management in Heavy Oil Production Summary Notes Energy Introduction Example: Commercial-Scale Solar Thermal Power in Australia Example: Comparing Renewable Energy Options Summary Notes Contaminated Sites and Waste Introduction Conceptual Framework The Economics of Remediation Economic Sustainability Analysis for Contaminated Land The Social Cost of Waste Management Using Landfill Case History: Brownfield Redevelopment in Canada Case History: Groundwater Remediation at a Refinery in Europe Remediating NAPLs in Fractured Aquifers Example: DNAPL in a Fractured Carbonate Aquifer, United States Example: NAPL in a Fractured Carbonate Aquifer, United Kingdom Discussion Notes Best Practice for the Twenty-first Century Summary Technology Management and Decision Making Into the Future Notes Index
DNA Polymerase III of B.subtilis: Characterization of the Binding Site for Arylhydrazinopyrimidine Inhibitors

A distinct class of 6-substituted pyrimidines, exemplified by the 6-(arylazo)pyrimidine, 6-(p-hydroxyphenylazo)uracil (HPUra)) selectively inhibits the replicative synthesis of DNA of Gram-positive bacteria (1). The site of drug action is the replication-specific enzyme, DNA polymerase III (2,3,4) (Pol III). The mechanism of pol III inhibition by HPUra and analogous 6-substituted uracils — a mechanism which has been studied in detail in our laboratory and that of Cozzarelli (3,4,5,6,7,8,9) — involves the following three processes:- (1) reduction of the drug to an active, hydrazino (H2) form (i.e.,\(-N=N-\to -\begin{matrix} N \\ H \\ \end{matrix}-\begin{matrix} N \\ H \\ \end{matrix}-\), (2) hydrogen bonding, in competition with dGTP, to an unpaired cytosine residue in the template strand immediately distal to the 3’ hydroxyl primer terminus, i.e. 3’OH and, (3) reversible reaction of the template-bound drug with enzyme, sequestering the latter from productive activity as a component of a relatively stable, ternary complex. The novel mechanism by which H2·HPUra pairs with cytosine (4) and our current concept of the drug:DNA:enzyme complex (8) are depicted, respectively, in parts A and B of Fig. 1.
The Role of Equity Theory in Knowledge Sharing

Determining which factors promote or impede the sharing of knowledge within organizations constitutes an important area of research. This paper examines knowledge sharing through the lens of equity theory. The study will explore the impact of three types of justice – distributional, procedural and interactional – on knowledge sharing. Hypotheses regarding the influence of distributional, procedural, and interactional justice on knowledge sharing processes are presented. These hypotheses will be tested based on the survey.
C57BL/6 Mice Genetically Deficient in IL-12/IL-23 and IFN-γ Are Susceptible to Experimental Autoimmune Myasthenia Gravis, Suggesting a Pathogenic Role of Non-Th1 Cells

Immunization with Torpedo acetylcholine receptor (TAChR) induces experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 (B6) mice. EAMG development needs IL-12, which drives differentiation of Th1 cells. The role of IFN-γ, an important Th1 effector, is not clear and that of IL-17, a proinflammatory cytokine produced by Th17 cells, is unknown. In this study, we examined the effect of simultaneous absence of IL-12 and IFN-γ on EAMG susceptibility, using null mutant B6 mice for the genes of both the IL-12/IL-23 p40 subunit and IFN-γ (dKO mice). Wild-type (WT) B6 mice served as control for EAMG induction. All mice were immunized with TAChR in Freund’s adjuvant. dKO mice developed weaker anti-TAChR CD4+T cells and Ab responses than WT mice. Yet, they developed EAMG symptoms, anti-mouse acetylcholine receptor (AChR) Ab, and CD4+ T cell responses against mouse AChR sequences similar to those of WT mice. dKO and WT mice had similarly reduced AChR content in their muscles, and IgG and complement at the neuromuscular junction. Naive dKO mice had significantly fewer NK, NKT, and CD4+CD25+Foxp3+ T regulatory (Treg) cells than naive WT mice. Treg cells from TAChR-immunized dKO mice had significantly less suppressive activity in vitro than Treg cells from TAChR-immunized WT mice. In contrast, TAChR-specific CD4+ T cells from TAChR-immunized dKO and WT mice secreted comparable amounts of IL-17 after stimulation in vitro with TAChR. The susceptibility of dKO mice to EAMG may be due to reduced Treg function, in the presence of a normal function of pathogenic Th17 cells.
Role of Clinical Pharmacist in a Heart Failure Clinic

Purpose: To determine if the inclusion of a clinical pharmacist (CP) in a heart failure (HF) multidisciplinary team could lead to a reduction in the number of hospital admissions and additionally decrease the clinical signs and symptoms of HF patients with either Medicaid or no medical insurance. Methods: Longitudinal study to determine the impact of a pharmaceutical-care service program to HF patients by comparing the 9-month period before (pre-intervention) and the 9-month period after (post-intervention) implementation of the program. The intervention of the CP was directed in two complementary functions. The first was direct patient contact and the second was to provide drug information to the medical clinicians. Results: Twenty-nine outpatients completed the study. Over 9 months, the CP made a total of 216 interventions and had three in-person, follow-up contacts and three telephone contacts per patient. At post-intervention, there was a statistically significant reduction in the total number of hospitalizations (50 vs 23; P < 0.018) and length of stay (LOS) (263 days vs 108 days; P < 0.03). However, there was an insignificant reduction in HF hospitalizations, LOS, and total number of HF signs and symptoms. Conclusions: Addition of a CP to an outpatient HF clinic can lead to fewer hospital admissions and a reduction in the LOS in patients with either Medicaid or no medical insurance.
NetworkPreserving BCU Method and Its Theoretical Foundation

This chapter contains sections titled: Introduction Reduced-State Model Static and Dynamic Properties Analytical Results Overall Static and Dynamic Relationships Dynamic Property (D3) Conceptual Network-Preserving BCU Method Concluding Remarks
EFFECT OF FREQUENCY-DEPENDENT ASPHALT CONCRETE LAYER MODULI ON PAVEMENT RESPONSE

The viscoelastic nature of asphalt concrete (AC) renders its properties to be frequency dependent. Static backcalculation of layer moduli from falling weight deflectometer (FWD) testing does not take into account their frequency dependence. This paper shows the effect of frequency dependent AC properties on the horizontal strain and vertical deflection using the computer program SAPSI-M and field results. The analysis shows that the decrease in horizontal strain with increasing truck speed can be duplicated only by using frequency dependent properties for the asphalt concrete layer.
Differential regulation in the heart of mitochondrial carnitine palmitoyltransferase-I muscle and liver isoforms

Carnitine palmitoyltransferase-I (CPT-I) plays a crucial role in regulating cardiac fatty acid oxidation which provides the primary source of energy for cardiac muscle contraction. CPT-I catalyzes the transfer of long chain fatty acids into mitochondria and is recognized as the primary rate controlling step in fatty acid oxidation. Molecular cloning techniques have demonstrated that two CPT-I isoforms exist as genes encoding the 'muscle' and 'liver' enzymes. Regulation of fatty acid oxidation rates depends on both short-term regulation of enzyme activity and long-term regulation of enzyme synthesis. Most early investigations into metabolic control of fatty acid oxidation at the CPT-I step concentrated on the hepatic enzyme which can be inhibited by malonyl-CoA and can undergo dramatic amplification or reduction of its sensitivity to inhibition by malonyl-CoA. The muscle CPT-I is inherently more sensitive to malonyl-CoA inhibition but has not been found to undergo any alteration of its sensitivity. Short-term control of activity of muscle CPT-I is apparently regulated by malonyl-CoA concentration in response to fuel supply (glucose, lactate, pyruvate and ketone bodies). The liver isoform is the only CPT-I enzyme present in the mitochondria of liver, kidney, brain and most other tissues while muscle CPT-I is the sole isoform expressed in skeletal muscle as well as white and brown adipocytes. The heart is unique in that it contains both muscle and liver isoforms. Liver CPT-I is highly expressed in the fetal heart, but at birth its activity begins to decline whereas the muscle isoform, which is very low at birth, becomes the predominant enzyme during postnatal development. In this paper, the differential regulation of the two CPT-I isoforms at the protein and the gene level will be discussed.
Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis.

Objective In lupus nephritis (LuN), severe tubulointerstitial inflammation (TII) predicts progression to renal failure. Severe TII is associated with tertiary lymphoid neogenesis and in situ antigen-driven clonal B cell selection. The autoantigen(s) driving in situ B-cell selection in TII are not known. This study aimed to identify the dominant driving autoantigen(s).