cssi/SciSciGPT-SciSciNet huggingface dataset:
Isolated boost circuit for power factor correction

To provide a 48 volt DC bus for distributed power systems, AC-DC power converters with high power factor and isolation are required. Instead of using a conventional two stage scheme which has a boost front end followed by a DC-DC converter, a boost derived topology is chosen to achieve high power factor, isolation, and voltage step down. A newly proposed technology of soft switched insulated gate bipolar transistors (IGBTs) is used for this application to reduce the IGBT switching loss and achieve low conduction loss. The design considerations of the power stage and the control circuit are provided. A prototype converter is built to show the feasibility of the single stage scheme. >
The Impact of Blood Conservation on Outcomes in Cardiac Surgery: Is It Safe and Effective?

Background Increasing evidence shows that perioperative blood transfusion in cardiac surgery is associated with increased postoperative morbidity and mortality and decreased long-term survival. Tolerance of "permissive anemia" is an important element of perioperative blood conservation strategy. The safety of tolerating perioperative anemia has been a significant deterrent for widespread application of blood conservation. This study examines whether blood conservation is equally safe or superior to the common practice of transfusion in cardiac surgery. Methods The total study population consisted of 32,449 patients who underwent isolated coronary artery bypass surgery from June 2000 until December 2004 with complete data from 17 institutions in the State of New Jersey. Englewood Hospital and Medical Center (EH) has a well-established blood conservation program. Five hundred eighty-six EH patients (blood conservation cohort) were compared with a propensity score–matched cohort of 586 patients from the other New Jersey institutions (OH-M) representing the common practice of transfusion. Outcomes were classified as very serious complications, serious complications, or neither (no very serious complication or serious complication). Analysis consisted of McNemar tests and multiple logistic regression. Results Fewer patients were transfused at EH compared with OH-M (10.6% versus 42.5%; p p = 0.02). Of the EH patients, 11.1% experienced a very serious complication or serious complication versus 18.7% in the OH-M cohort ( p = 0.0002). Transfusion was associated with an increased risk of an adverse outcome in both cohorts (EH: odds ratio, 7.3; 95% confidence interval, 3.7 to 14.4 versus OH-M: odds ratio, 4.6; 95% confidence interval, 2.8 to 7.7). Conclusions Blood conservation is safe and effective in reducing transfusions. Tolerance of perioperative anemia, which is one of the main components of blood conservation, does not increase the risk of complications or death in cardiac surgery. Avoidance of transfusion reduces the risk of complications. This study further solidifies the relationship between transfusion and adverse outcome in cardiac surgery.
Prime–boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu+ metastatic breast cancer in mice

Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu+ cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models. The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines. Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime–boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime–boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNγ. We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime–boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime–boost protocol, is justified.
Volatiles in High-K Magmas from the Western Trans-Mexican Volcanic Belt: Evidence for Fluid Fluxing and Extreme Enrichment of the Mantle Wedge by Subduction Processes

Primitive, high-K minettes and basanites erupted during the Pleistocene from cinder cones on the flanks of the Colima Volcanic Complex in the western Trans-Mexican Volcanic Belt. Melt inclusions in olivine (Fo89^92) from tephra at these cones reveal that both magma types are oxidized and volatile rich, with high H2 O( � 6� 2 wt%), CO2 (� 5300 ppm), S (� 6700 ppm), Cl (� 2300 ppm), and F (� 8100 ppm) contents. A nearby calc-alkaline basaltic andesite cinder cone with more evolved composition (Fo78^80 olivine) has melt inclusions with similarly high H2O (� 5� 5 wt%) but much lower CO2, S, and Cl compared with the potassic magmas. Melt inclusions from each cone have highly variable H2O and CO2, corresponding to crystallization pressures of5100 bars to � 7 kbar. This indicates that olivine crystallized from variably degassed melts over a wide range of depths extending from the lower crust (4 25 km depth) to very shallow levels. The H2O and CO2 variations cannot be explained by simple degassing models but instead requiring more complex, open-system processes or possibly reflect disequilibrium degassing.Trace element variations in the melt inclusions suggest that phlogopite and garnet were residual minerals during melting in the mantle source, and the presence of garnet suggests an origin in asthenospheric rather than lithospheric mantle. Decompression melting of phlogopite^garnet peridotite cannot produce the high H2O contents of the potassic magmas, and thus the presence of fluids during melting is required. Trace element modeling of a mantle source (intermediate in composition between enriched mid-ocean ridge basalt and ocean island basalt sources) that is fluxed with an H2O-rich fluid or hydrous melt from the subducting slab can reproduce most of the trace element characteristics of the potassic melts, demonstrating that they are clearly linked with subduction processes. Formation ofthe potassic magmasprobably involved slab rollback, trenchward migration of the arc into the region above metasomatically enriched forearc mantle, and heating of this veined and fluid-fluxed mantle as a result of upwelling of hot mantle through a tear between the subducted Cocos and Rivera plates.
Bacteria respond to host cell lysophospholipids

Evaluation of: Subramanian N, Qadri A.: Lysophospholipid sensing triggers secretion of flagellin from pathogenic Salmonella. Nat. Immunol. 7(6), 583–589 (2006). The ability of host cells to detect pathogen-specific molecules has now become readily appreciated. Toll-like receptors can detect conserved structures on pathogens and once recognized can trigger an innate immune response. In this report, Subramanian and Qadri present evidence that the host does not simply respond to the presence of bacteria or bacterial factors, but can also trick pathogens into revealing themselves by inducing the secretion of one of these pathogen-associated molecules.
2,3,7,8-Tetrachlorodibenzo-p-dioxin affects the number and function of murine splenic dendritic cells and their expression of accessory molecules.

Primary T cell-mediated immune responses are highly susceptible to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, yet direct effects of TCDD on T cells have been difficult to demonstrate. Since the activation of naive T cells has been shown to be initiated primarily by dendritic cells (DC), these cells represent a potential target for TCDD immunotoxicity. In this report, we have examined the influence of TCDD exposure on splenic DC phenotype and function in the absence of antigenic stimulation. Results showed that DC from TCDD-treated mice expressed higher levels of several accessory molecules including ICAM-1, CD24, B7-2, and CD40, whereas the expression of LFA-1 was significantly reduced. These effects were dose-dependent and persisted for at least 14 days after exposure. The effects were also dependent upon the aryl hydrocarbon receptor (AhR), as similar effects were observed in AhR+/+ C57Bl/6 and Balb/c mice but not in AhR-/- mice. When DC from TCDD-treated mice were cultured with allogeneic T cells, the proliferative response and production of IL-2 and IFN-gamma by the T cells were increased. Production of IL-12 by the DC was likewise enhanced in comparison to cells from vehicle-treated mice. Interestingly, however, the number of DC recovered from TCDD-treated mice was significantly decreased. Taken together, these results suggest that, in the absence of antigen, TCDD provides an activation stimulus to DC that may lead to their premature deletion. Since the survival of DC has been shown to influence the strength and duration of the immune response, these results suggest a possible novel mechanism for TCDD-induced immune suppression.
Phosphoinositide specificity determines which cytohesins regulate β1 integrin recycling

Summary Recycling of internalized integrins is a crucial step in adhesion remodeling and cell movement. Recently, we determined that the ADP-ribosylation factor–guanine nucleotide exchange factors (ARF-GEFs) cytohesin 2/ARNO and cytohesin 3/GRP1 have opposing effects on adhesion and stimulated β1 integrin recycling even though they are very closely related proteins (80% sequence identity). We have now determined the sequence differences underlying the differential actions of cytohesin 2/ARNO and cytohesin 3/GRP1. We found that the ability of cytohesins to promote β1 integrin recycling and adhesion depends upon the presence or absence of a key glycine residue in their pleckstrin homology (PH) domains. This glycine residue determines the phosphoinositide specificity and affinity of cytohesin PH domains. Switching the number of glycines in the PH domains of cytohesin 2 and cytohesin 3 is sufficient to reverse their effects on adhesion and spreading and to reverse their subcellular locations. Importantly, we also find that a mutant form of cytohesin 3/GRP1 that has three rather than two glycines in its PH domain rescues β1 integrin recycling in cytohesin 2/ARNO knockdown cells. Conversely, a mutant form of cytohesin 2/ARNO with two glycines in its PH domain fails to rescue β1 integrin recycling. Therefore, we conclude that phosphoinositide specificity is the sole functional difference that determines which cytohesin can promote integrin recycling.
Elliptic Analogues of the Macdonald and Koornwinder Polynomials

Perhaps the nicest multivariate orthogonal polynomials are the Macdonald and Koornwinder polynomials, respectively 2-parameter deformations of Schur functions and 6-parameter deformations of orthogonal and symplectic characters, satisfying a trio of nice properties known as the Macdonald “conjectures”. In recent work, the author has constructed elliptic analogues: a family of multivariate functions on an elliptic curve satisfying analogues of the Macdonald conjectures, and degenerating to Macdonald and Koornwinder polynomials under suitable limits. This article will discuss the two main constructions for these functions, focusing on the more algebraic/combinatorial of the two approaches.
Labor market structure and fertility differences among Puerto Rican women: The effects of economic and social policies on opportunity costs

The oft-observed inverse relationship between economic activity in the formal or informal sector and levels of fertility is attributed to the opportunity costs of reproduction. The economic and social policies that initiate and maintain the substantial flow of federal transfer payments to the Puerto Rican population is likely to reduce the opportunity costs among women participating in the informal economy; therefore, informal labor market participants will have fertility levels more like women who have never worked than like women active in the formal labor market. Using data from the 1982 Puerto Rican Fertility and Family Planning Assessment, this paper compares fertility differentials among ever-married women who have never worked, who have ever worked in the informal economy, and who have only worked in the formal economy. Contrary to expectations, the fertility levels of informal labor market participants are more like those of formal labor market participants; economic activity in either sector is associated with bearing fewer children. Federal transfer payments do not appear to reduce the opportunity costs of reproduction among women employed in the informal economy. An earlier version of this paper was presented at the 1989 meeting of the Population Association of America.
Idea Generation, Creativity, and Incentives

Idea generation (ideation) is critical to the design and marketing of new products, to marketing strategy, and to the creation of effective advertising copy. However, there has been relatively little formal research on the underlying incentives with which to encourage participants to focus their energies on relevant and novel ideas. Several problems have been identified with traditional ideation methods. For example, participants often free ride on other participants' efforts because rewards are typically based on the group-level output of ideation sessions. This paper examines whether carefully tailored ideation incentives can improve creative output. I begin by studying the influence of incentives on idea generation using a formal model of the ideation process. This model illustrates the effect of rewarding participants for their impact on the group and identifies a parameter that mediates this effect. I then develop a practical, web-based asynchronous “ideation game,” which allows the implementation and test of various incentive schemes. Using this system, I run two experiments that demonstrate that incentives do have the capability to improve idea generation, confirm the predictions from the theoretical analysis, and provide additional insight on the mechanisms of ideation.
Controversy and the development of reproductive sciences.

Under what conditions does an entire line of scientific work become controversial, and with what consequences? Nuclear physics, environmental studies, and sociobiology are familiar examples of controversial sciences. The case examined here is the development of American reproductive sciences over the past century, shaped by four domains of controversy: (1) association with sexuality and reproduction; (2) association with clinical quackery and hotly debated treatments; (3) association with controversial social movements; and (4) the capacity of reproductive sciences to create “Brave New Worlds.” Scientists' strategies for managing controversy are delineated.The framework used is arena analysis, and the paper concludes with rudiments of a conditional theory of status as a controversial “boundary world.”
Efficient distributed processor level fault diagnosis of multiple processor systems

A distributed processor level fault diagnosis algorithm is proposed where every processor will come up with its own conclusion about the status of other processors and also the links connecting it to its neighboring processors. Performance is improved by considering a dynamic testing strategy where each processor is assigned a small number of processors to test it, ideally two. Then, when some processors or links fail, a new testing assignment is made among the processors. Simulation results are presented to show that the proposed algorithm is effective in reducing the testing overhead. >
Stability of Tl-Ba-Ca-Cu-O superconducting thin films

We report the stability of TlBa{sub 2}CaCu{sub 2}O{sub 7} (Tl-1212) and Tl{sub 2}Ba{sub 2}CaCu{sub 2}O{sub 8} (T1-2212) thin films and by inference, the stability of TlBa{sub 2}Ca{sub 2}Cu{sub 3}O{sub 9} (Tl-1223) and Tl{sub 2}Ba{sub 2}Ca{sub 2}Cu{sub 3}O{sub 10} (Tl-2223) thin films, under a variety of conditions. In general, we observe that the stability behavior of the single Tl-O layer materials (Tl-1212 and Tl-1223)are similar and the double Tl-O layer materials (Tl-2212 and Tl-2223) are similar. All films are stable with repeated thermal cycling to cryogenic temperatures. Films are also stable in acetone and methanol. Moisture degrades film quality rapidly, especially in the form of vapor. Tl-1212 is more sensitive to vapor than Tl-2212. These materials are stable to high temperatures in either N{sub 2}, similar to vacuum for the cuprates, and O{sub 2} ambients. While total degradation of properties (superconducting and structural) occur at the same temperatures for all phases, 600 C in N{sub 2} and 700 C in O{sub 2}, the onset of degradation occurs at somewhat lower temperatures for Tl-1212 than for Tl-2212 films. In all cases, sample degradation is associated with Tl depletion from the films.
The University Lost: The Meaning of the University

This essay examines the current state of the University in terms of lost meaning and value, especially from the perspective of scholarship. The author specifically points to three works of literature and writers on the subject, and how these works have significantly contributed to our understanding of what is taking place within the modern University, and how the University has transitioned and specifically, radically changed from its originary purpose to the “modern” University as an institution narrower in scope and depth, role, and even responsibility. The author examines the writings of John Henry Newman, Bill Readings, and John Milton, and comments on several of their ideas and demonstrates how these ideas are relevant in understanding and improving the modern University which has shifted from academic to managerial orientation; faculty to administrators—hence its decline. Finally, the author provides several examples of challenges in the modern University and how these have created the gaps in perceived and real purpose and philosophy of the ideal university versus current “all-administrative” university and its perceived status and role.
Evidence for Weak-Form Market Efficiency in Hotel Real Estate Markets

The purpose of this study is to test for evidence of weak-form market efficiency in hotel real estate markets by measuring how rapidly price changes diffuse in geographically proximal areas. Using autocorrelation and cross-correlation analysis, we found that there is little evidence that past hotel prices predict future hotel prices in the same city as well as neigh- boring cities. In addition, buy-and-sell trading strategies based on the information in past hotel prices did not earn higher returns than buy-and-hold strategies. The results of this study are supportive of the existence of weak-form market efficiency in the pricing of hotel real estate.
Descriptive statistics: where they sit and how they fall

This column continues a series on topics in research methodology, statistics, and data analysis techniques for the library and information sciences. It discusses the basics of descriptive statistics (mean, median, mode, range, standard deviation), how to use them, and when they are and are not appropriate.
Power-Aware Design via Micro-architectural Link to Implementation

Micro-architectural power macro-models dictate the power budget of a new chip design. Based on the early feasibility studies, power specification of new features are defined and then verified all through the design cycle. In this paper, we introduce a novel power-aware design paradigm that aligns power macro-models by mapping power-significant events at all levels of design hierarchy. We apply this paradigm on a state-of-the-art 65nm high-performance micro-processor and demonstrate significant benefits in power optimization at RTL implementation.Moreover, this approach facilitates a feedback loop from the design implementation to higher level (micro-architectural) power models and thus has built-in potential for more accurate power models.
Simplified procedure for determination of estrogen in pregnancy urine.

Determination of total estrogen in pregnancy urine has involved hydrolysis, extraction of estrogen, development of color, and extraction of chromogen prior to absorbance measurements. The necessity for each of these steps was evaluated and a more simple procedure was developed which requires only extraction of estrogen and development of color. The new procedure should be useful for prenatal screening and monitoring of high-risk pregnancies.
Muir-Torre syndrome (MTS): An update and approach to diagnosis and management

Muir-Torre syndrome (MTS) is a rare genetic condition that predisposes individuals to skin tumors and visceral malignancies. Because of the potentially aggressive nature of internal malignancies and sebaceous carcinoma, and the tendency to have multiple low-grade visceral cancers, close cancer surveillance is required in individuals and their families with this usually autosomal dominant disorder. Although the majority of MTS is caused by mutations in DNA mismatch repair genes resulting in microsatellite instability, a newly described subtype of MTS does not demonstrate microsatellite instability and may be inherited in an autosomal recessive pattern. In addition, MTS may be unmasked in transplant recipients taking specific immunosuppressant drugs or other immunosuppressed patients. Neoplasms may be subject to immunohistochemistry or both immunohistochemistry and genetic testing to confirm the diagnosis of MTS. Here, we offer an update and an approach to the diagnosis and management of MTS with a particular emphasis on the role of immunohistochemistry and genetic testing.
New Experimental Data of STBLI at DNS/LES Accessible Reynolds Numbers

An experimental investigation was conducted to study four shock/turbulent boundary layer interactions. In Mach 2.9 flow, a 24o compression corner and a 12o reflected shock interaction were studied at Reθ = 2400. In a Mach 8 flow, an 8o compression corner and a 10o sharp fin were studied at Reθ = 3500. These low Reynolds number flows were chosen to coincide with DNS accessible Reynolds numbers in order to make direct comparisons. Measurements included mean flow surveys, surface pressure distributions, surface flow visualizations and Filtered Rayleigh Scattering (FRS). FRS was used to make twodimensional images of the flow in the streamwise direction giving a qualitative picture of the nature of the interaction. Statistical data of the boundary layer characteristics was also obtained from the FRS images. The results show the incoming boundary layer at both Mach numbers to be fully turbulent. The interactions in Mach 2.9 flow produced large areas of separation. The compression ramp in the Mach 8 flow was found to remain attached throughout the interaction, while the 10o sharp fin produced a large threedimensional separated region. The preliminary results indicate good agreement between experiment and DNS computations.
Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity

Idelalisib is a small-molecule inhibitor of PI3Kδ with demonstrated efficacy for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as front-line therapy, we enrolled 24 subjects in a phase 2 study consisting of 2 months of idelalisib monotherapy followed by 6 months of combination therapy with idelalisib and the anti-CD20 antibody ofatumumab. After a median follow-up period of 14.7 months, hepatotoxicity was found to be a frequent and often severe adverse event. A total of 19 subjects (79%) experienced either grade ≥1 ALT or AST elevation during the study, and 13 subjects (54%) experienced grade ≥3 transaminitis. The median time to development of transaminitis was 28 days, occurring before ofatumumab introduction. Younger age and mutated immunoglobulin heavy chain status were significant risk factors for the development of hepatotoxicity. Multiple lines of evidence suggest that this hepatotoxicity was immune mediated. A lymphocytic infiltrate was seen on liver biopsy specimens taken from 2 subjects with transaminitis, and levels of the proinflammatory cytokines CCL-3 and CCL-4 were higher in subjects experiencing hepatotoxicity. All cases of transaminitis resolved either by holding the drug, initiating immunosuppressants, or both, and rates of recurrent toxicity were lower in patients taking steroids when idelalisib was reinitiated. A decrease in peripheral blood regulatory T cells was seen in patients experiencing toxicity on therapy, which is consistent with an immune-mediated mechanism. These results suggest that caution should be taken as drugs within this class are developed for CLL, particularly in younger patients who have not received prior disease-specific therapy. This study was registered at www.clinicaltrials.gov as #NCT02135133.
Introduction: London's Importance

Between 1550 and 1750, London became Europe's largest city, a world-bestriding economic and cultural center, and the crucible for many of the hallmarks of modern life. This book presents London's history during the period when it rose to global prominence and came to dominate the economic, political, social, and cultural life of the British Isles as never before, nor, it will be argued, since. London: A Social and Cultural History, 1550–1750 synthesizes recent work in urban history, testimony by contemporary Londoners and tourists, and fictional works in which the city plays a part to trace London's rise, its role as a harbinger of modernity, and the ways in which its inhabitants coped with those achievements. One of those inhabitants, Samuel Johnson (1709–1784), famously said “there is in London all that life can afford.” Indeed, to evoke the full range of Londoners’ experience, it is necessary to traverse the whole of the metropolis, from the splendid galleries of Whitehall and St. James's to the damp and sooty alleys and courts of the City outparishes, along the way braving the dangers of plague and fire; witnessing the spectacles of the lord mayor's pageant and the hangings at Tyburn; and taking refreshment in the city's pleasure gardens, coffeehouses, and taverns. Having spent some years making this trek ourselves, the authors trust confidently that, at its end, readers will find themselves, to echo Johnson again, no more tired of London than they are tired of life. L ondon's I mportance In 1550, as this book opens London was already the most prominent city in England, containing its principal harbor; its largest concentration of population, wealth, and culture; and its capital, in suburban Westminster. But England, sitting on the periphery of Europe, the military equivalent of Denmark, the economic inferior of Flanders, was not a terribly important country. In fact, it could be argued that London's greatest significance in 1550 was as the funnel through which the ideas and products of other, more powerful European states passed into England. Two centuries later, much had changed. London was still the seat of government and greatest city in England, but England was now the dominant country in the British Isles, a leading player in Europe, and the proprietor of a worldwide empire. Indeed, by the end of the Seven Years’ War in 1763, the Union Jack flew from Canada to India, and from Gibralter to Tahiti.
Cardiovascular-renal complications and the possible role of plasminogen activator inhibitor: a review

Since angiotensin increases the expression of plasminogen activator inhibitor (PAI), mechanisms associated with an actively functioning renin-angiotensin-aldosterone system can be expected to be associated with increased PAI-1 expression. These mechanisms are present not only in common conditions resulting in glomerulosclerosis associated with aging, diabetes or genetic mutations, but also in autoimmune disease (like scleroderma and lupus), radiation injury, cyclosporine toxicity, allograft nephropathy and ureteral obstruction. While the renin-angiotensin-aldosterone system and growth factors, such as transforming growth factor-beta (TGF-β), are almost always part of the process, there are rare experimental observations of PAI-1 expression without their interaction. Here we review the literature on PAI-1 and its role in vascular, fibrotic and oxidative injury as well as work suggesting potential areas of intervention in the pathogenesis of multiple disorders.
Interaction of the Complexin Accessory Helix with Synaptobrevin Regulates Spontaneous Fusion

Neuronal transmitters are released from nerve terminals via the fusion of synaptic vesicles with the plasma membrane. Vesicles attach to membranes via a specialized protein machinery composed of membrane-attached (t-SNARE) and vesicle-attached (v-SNARE) proteins that zipper together to form a coiled-coil SNARE bundle that brings the two fusing membranes into close proximity. Neurotransmitter release may occur either in response to an action potential or through spontaneous fusion. A cytosolic protein, Complexin (Cpx), binds the SNARE complex and restricts spontaneous exocytosis by acting as a fusion clamp. We previously proposed a model in which the interaction between Cpx and the v-SNARE serves as a spring to prevent premature zippering of the SNARE complex, thereby reducing the likelihood of fusion. To test this model, we combined molecular-dynamics (MD) simulations and site-directed mutagenesis of Cpx and SNAREs in Drosophila. MD simulations of the Drosophila Cpx-SNARE complex demonstrated that Cpx's interaction with the v-SNARE promotes unraveling of the v-SNARE off the core SNARE bundle. We investigated clamping properties in the syx3-69 paralytic mutant, which has a single-point mutation in the t-SNARE and displays enhanced spontaneous release. MD simulations demonstrated an altered interaction of Cpx with the SNARE bundle that hindered v-SNARE unraveling by Cpx, thus compromising clamping. We used our model to predict mutations that should enhance the ability of Cpx to prevent full assembly of the SNARE complex. MD simulations predicted that a weakened interaction between the Cpx accessory helix and the v-SNARE would enhance Cpx flexibility and thus promote separation of SNAREs, reducing spontaneous fusion. We generated transgenic Drosophila with mutations in Cpx and the v-SNARE that disrupted a salt bridge between these two proteins. As predicted, both lines demonstrated a selective inhibition in spontaneous release, suggesting that Cpx acts as a fusion clamp that restricts full SNARE zippering.
Lenalidomide Decreases PD-1 Expression, Depletes Regulatory T-Cells and Improves Cellular Response to a Multiple Myeloma/Dendritic Cell Fusion Vaccine In Vitro

Abstract 492 Introduction: We have developed a cancer vaccine for multiple myeloma in which patient derived tumor cells are fused with dendritic cells (DCs) such that a broad array of tumor antigens are presented in the context of DC mediated costimulation. In clinical studies, we have demonstrated that vaccination results in the induction of anti-tumor immunity and disease response in a subset of patients. A fundamental challenge limiting the efficacy of cellular immunotherapy is the immunosuppressive milieu that characterizes patients with myeloma. We have previously reported that the PD-1/PDL-1 pathway plays an important role in suppressing T cell immunity in patients with myeloma, PD-1 expression is upregulated on T cells isolated from patients with multiple myeloma, and PD-1 blockade is associated with enhancement of T-cell response to the vaccine. Lenalidomide is a potent anti-myeloma agent whose activity may be linked, in part, to its immunomodulatory properties. We hypothesized that lenalidomide would augment the capacity to elicit anti-myeloma immunity. In our current study, we examined the effect of lenalidomide on T-cell activation and polarization, PD-1 signaling, and vaccine-induced responses in vitro. Methods and results: Peripheral blood mononuclear cells were cultured in media containing IL-2 with and without 1μM lenalidomide. The expression of cell surface molecules and intracellular cytokines was assessed using flow cytometry. Exposure of unstimulated T cells to lenalidomide resulted in a decrease in the percentage of CD4+ T cells expressing PD-1 (from 8.0% to 5.6%, p=0.04) and a 2 fold increase in T-cell proliferation as measured by incorporation of tritiated thymidine. We then examined the effect of lenalidomide on T cell activation by ligation of the costimulatory complex using antibodies directed against CD3 and anti CD28. Most notably, the upregulation of PD-1 by CD3/CD28 ligation was markedly decreased in the presence of lenalidomide as measured in CD4+ cells (from 26% to 15%, p Conclusions: In vitro exposure to lenalidomide results in enhanced T-cell activation in response to direct ligation of the co-stimulatory complex and stimulation by the DC/myeloma fusion vaccine. Exposure to lenalidomide suppresses T cell expression of PD-1 and expansion of regulatory T cells, 2 critical pathways responsible for tumor mediated immune suppression. To our knowledge, this is the first demonstration of an interaction between lenalidomide and the PD-1/PDL-1 pathway. These findings support the development of cellular immunotherapy in conjunction with lenalidomide, including its use with the DC/myeloma fusion vaccine. Disclosures: No relevant conflicts of interest to declare.
Science among the Ottomans: The Cultural Creation & Exchange of Knowledge. By Miri Shefer-Mossensohn. (Austin, TX: University of Texas Press, 2015. Pp. xvi, 246, $55.00.)

This book was first conceived as a Hebrew textbook for a survey course on Ottoman history and was later expanded and rewritten as a monograph responding to the “acute” need for an English book on t...
DFT Investigation of Ligand Photodissociation in [RuII(tpy)(bpy)(py)]2+ and [RuII(tpy)(Me2bpy)(py)]2+ Complexes.

Photoinduced ligand dissociation of pyridine occurs much more readily in [Ru(tpy)(Me2bpy)(py)]2+ than in [Ru(tpy)(bpy)(py)]2+ (tpy = 2,2′:6′,2″-terpyridine; bpy = 2,2′-bipyridine, Me2bpy = 6,6′-dimethyl-2,2′-bipyridine; py = pyridine). The S0 ground state and the 3MLCT and 3MC excited states of these complexes have been studied using BP86 density functional theory with the SDD basis set and effective core potential on Ru and the 6-31G(d) basis set for the rest of the atoms. In both complexes, excitation by visible light and intersystem crossing leads to a 3MLCT state in which an electron from a Ru d orbital has been promoted to a π* orbital of terpyridine, followed by pyridine release after internal conversion to a dissociative 3MC state. Interaction between the methyl groups and the other ligands causes significantly more strain in [Ru(tpy)(Me2bpy)(py)]2+ than in [Ru(tpy)(bpy)(py)]2+, in both the S0 and 3MLCT states. Transition to the dissociative 3MC states releases this strain, resulting in lower barri...
Feature Tracking Cardiac MRI Reveals Abnormalities in Ventricular Function in Patients With Bicuspid Aortic Valve and Preserved Ejection Fraction

Subclinical systolic and diastolic left ventricular (LV) dysfunction has been reported in previous echocardiographic studies on congenital bicuspid aortic valve (BAV). Patients with BAV commonly undergo evaluation with magnetic resonance imaging, and feature-tracking cardiovascular magnetic resonance (CMR-FT) is an emerging technique that assesses myocardial strain using standard cine sequences. This study investigated differences in myocardial strain between patients with BAV with preserved ejection fraction (EF) and controls using CMR-FT. Patients with isolated BAV and preserved EF, who had previously undergone CMR (n = 42; mean age, 41.2 ± 13.9) were compared with controls (n = 19; 36.6 ± 9.8; P = .2). Investigational CMR-FT strain analysis software was used to measure circumferential systolic and diastolic strain values, as well as standard LV volumetric and functional parameters. The majority of patients with BAV had mild or no valve dysfunction, and LV myocardial mass end-diastolic volume indices were similar between groups. Peak diastolic circumferential strain rate was lower in patients with BAV than in controls (0.89 ± 0.27 vs 1.21 ± 0.21 s−1, P = .003). After adjusting for covariates, only myocardial mass index was independently associated with peak circumferential systolic strain and diastolic strain rate. Feature-tracking CMR can identify abnormalities of LV strain in a clinical cohort of asymptomatic patients with BAV with preserved EF. Decreases in circumferential diastolic strain rate in patients with BAV suggest evidence of early diastolic dysfunction.
Prediction of magnetospheric parameters using artificial neural networks

Artificial neural network models have been developed that provide the magnetospheric parameters Dst, polar cap potential and the midnight equatorward boundary of diffuse aurora. Layered feedforward neural networks have successfully learned the relationship between the solar wind and the magnetospheric parameters using supervised back-propagation training. All models have achieved a higher prediction accuracy than the existing empirical or statistical models. These models are applied to the prediction of the parameters, which will then be used by the Rice Magnetospheric Specification and Forecast Model (MSFM). The neural network models are able to forecast the magnetospheric parameters 30 to 60 minutes ahead using the information from a solar wind monitor spacecraft. With the forecast values, the MSFM will be able to forecast particle fluxes in the inner magnetosphere. The MSFM is applied to the April 1988 magnetic storm for the forecast capability test. The neural network modeling, the comparison of the prediction accuracy with other methods and the result of the MSFM forecast capability test are presented.
PGHS-2 Dependent Formation of 8-Epi PGF2α by Human Monocytes

Arachidonic acid is converted enzymatically into different prostaglandins (PG) by the activity of a key enzyme, PG-endoperoxide synthase (PGHS), which exhibits both bisoxygenase and peroxidase activity (1). Cell-specific isomerization or reduction of PGH2 by various synthases (isomerases) or reductases leads to the formation of different prostanoids (2). It has been demonstrated that mammalian cells contain two isoforms of PGHS referred to as PGHS-1 and PGHS-2, encoded by separated genes (3). PGHS-1 is constitutively expressed in most tissue including platelets, endothelial cells and monocytes. However, it is recognized that expresion of PGHS-1 may be regualted. For example, androgens upregulate PGHS-1 in seminiferous tubules (4), as do cytokines in bone marrow derived mast cells (5). PGHS-2 expression is readily induced by serum, growth factors, cytokines in wide variety of cell types (6,7). Conventionally, this has implied the predominant importance of this isoform in regulating the inflammatory response. Data consistent with this view of the roles of the two enzymes have been obtained from “knock out” mice (8–10). Thus, while the PGHS-1 knock out exhibits a normal phenotype (8), inflammatory responses were modified following disruption of the PGHS-2 gene (9).
Trumping Obamacare: How the Use of Exercise of Executive Power can Undermine Women's Healthcare Without Repealing the Affordable Care Act

The enactment of the “Patient Protection and Affordable Care Act” in March 2010 beget the most significant alteration to the nation’s health care system since the establishment of Medicaid and Medicare. For women, healthcare reform contained several landmark gender inclusive provisions including: dismantling barriers to access women’s preventive health services, eliminating cost-sharing in the delivery of those services in addition to jettisoning the discriminatory health insurance practice of gender rating. However, from the moment of its legislative conception to enactment and implementation, healthcare reform has fomented controversy and women’s reproductive health, in particular, has constituted one of the principal foci of partisan contention and oppositional interest group competition. Arguably, one of the more vulnerable features of healthcare reform that is subject to administrative reversal are the rules, regulations and/or directives concerning access to women’s health services. And while “PPACA may be the most important measure ever passed to expand access to evidence-based reproductive health services in the United States” (Sonfield and Pollak, 2012), Obama’s signature legislative accomplishment may be short lived given the current occupant of the White House. To determine the degree to which this preliminary appraisal of the contentious political milieu of healthcare reform may be accurate, we examine how and to what degree the Trump administration has sought to rescind and/or modify regulatory provisions involving women’s (reproductive) health services.
A Digital Laser Speckle Technique for Generating Slope Contours of Bent Plate

A digital method is proposed whereby spatial speckles created when an optically rough surface is illuminated by a diffuse coherent laser beam are used to generate slope contour fringes. This is done by photographing the speckles contained in a parallel plane in front of the plate before and after deformation. The resulting photographs are then Fast Fourier Transformed twice with the digital image correlation software CASI to produce slope contours.
The Impact of LTA Volunteerism on Leadership and Management Development: An Autoethnographic Reflection

Many language teacher association (LTA) volunteers bring leadership and management (L & M) skills from their careers and see such volunteerism as a means of developing these skills further. This has been my case although I have never taken the opportunity to fully reflect on how volunteering has impacted my professional life. This exploratory study, informed by autoethnographic and pragmatic principles, provides insights into the extent of this impact by reflecting on emergent themes emanating from the qualitative analysis of introspective reflective narratives. These themes are: knowledge; responsibility; skills and attributes; feedback; and finally, challenges. Findings provide subjective pointers to the elements of L & M development that are most likely to be positively impacted by LTA volunteerism, which may act as a stimulus for reflection for current volunteers or those considering volunteering for career advancement.
Rescue Sedation When Treating Acute Agitation in the Emergency Department With Intramuscular Antipsychotics.

Background Rapid treatment of agitation in the emergency department (ED) is critical to avoid injury to patients and providers. Treatment with intramuscular antipsychotics is often utilized, but there is a paucity of comparative effectiveness evidence available. Objective The purpose of this investigation was to compare the effectiveness of droperidol, olanzapine, and haloperidol for treating agitation in the ED. Methods This was a retrospective observational study of adult patients who received intramuscular medication to treat agitation. Patients were classified based on the initial antipsychotic they received. The primary effectiveness outcome was the rate of additional sedation administered (rescue medication) within 1 h. Secondary outcomes included rescue sedation for the entire encounter and adverse events. Results There were 15,918 patients included (median age 37 years, 75% male). Rescue rates at 1 h were: 547/4947 for droperidol (11%, 95% confidence interval [CI] 10-12%), 988/8825 olanzapine (11%, 95% CI 10-12%), and 390/2146 for haloperidol (18%, 95% CI 17-20%). Rescue rates for the entire ED encounter were: 832/4947 for droperidol (17%, 95% CI 16-18%), 1665/8825 for olanzapine (19%, 95% CI 18-20%), and 560/2146 for haloperidol (26%, 95% CI 24-28%). Adverse events were uncommon: intubation (49, 0.3%), akathisia (7, 0.04%), dystonia (5, 0.03%), respiratory arrest (1, 0.006%), and torsades de pointes (0), with no significant differences between drugs. Conclusions Olanzapine and droperidol lead to lower rates of rescue sedation at 1 h and overall, compared with haloperidol. There were no significant differences in major adverse events.
Continual Learning via Neural Pruning

We introduce Continual Learning via Neural Pruning (CLNP), a new method aimed at lifelong learning in fixed capacity models based on neuronal model sparsification. In this method, subsequent tasks are trained using the inactive neurons and filters of the sparsified network and cause zero deterioration to the performance of previous tasks. In order to deal with the possible compromise between model sparsity and performance, we formalize and incorporate the concept of graceful forgetting: the idea that it is preferable to suffer a small amount of forgetting in a controlled manner if it helps regain network capacity and prevents uncontrolled loss of performance during the training of future tasks. CLNP also provides simple continual learning diagnostic tools in terms of the number of free neurons left for the training of future tasks as well as the number of neurons that are being reused. In particular, we see in experiments that CLNP verifies and automatically takes advantage of the fact that the features of earlier layers are more transferable. We show empirically that CLNP leads to significantly improved results over current weight elasticity based methods.
Outdoor Experimentation on a Polycrystalline Photovoltaic Module in Algiers

Publisher Summary This chapter discusses the performances of a 18 peak-watt double glass polycrystalline photovoltaic (PV) module obtained from outdoor experimentations in the location of Dar El Beida (Algiers) during 1996. The measurements made on the PV module are I–V curves, open circuit voltage, short circuit current, maximum conversion power, fill factor, conversion efficiency, and cell temperature. The experimentation consists in submitting the polycrystalline module to the climatic conditions prevailing in Algiers, traduced by high temperature variations, strong solar radiation flux and dust, especially in summer. Slight degradations of fill factor and conversion efficiency are then observed during the period of experimentation, which are similar to those found for a monocrystalline PV module. Such degradations are mainly influenced by temperature, moisture, and wind.