cssi/SciSciGPT-SciSciNet huggingface dataset:
The basis of the immunomodulatory activity of malaria pigment (hemozoin)

The most common and deadly form of the malaria parasite, Plasmodium falciparum, is responsible for 1.5–2.7 million deaths and 300–500 million acute illnesses annually [Bremen in J. Trop. Med. Hyg. 64:1–11 (2001); World Health Organization (2002)]. Hemozoin, the biomineral formed to detoxify the free heme produced during parasitic hemoglobin catabolism, has long been suspected of contributing to the pathological immunodeficiencies that occur during malarial infection. While there is a growing consensus in the literature that native hemozoin maintains immunosuppressive activity, there is considerable controversy over the reactivity of the synthetic form, β-hematin (BH). Given the emerging importance of hemozoin in modulating a host immune response to malarial infection, a careful examination of the effects of the constitutive components of the malaria pigment on macrophage response has been made in order to clarify the understanding of this process. Herein, we present evidence that BH alone is unable to inhibit stimulation of NADPH oxidase and inducible nitric oxide synthase, the key enzymes involved in oxidative burst, and is sensitive to the microbicidal agents of these enzymes both in vitro and in vivo. Further, by systematically examining each of the malaria pigment’s components, we were able to dissect their impact on the immune reactivity of a macrophage model cell line. Reactions between BH and red blood cell (RBC) ghosts effectively reconstituted the observed immunomodulatory reactivity of native hemozoin. Together, these results suggest that the interaction between hemozoin and the RBC lipids results in the generation of toxic products and that these products are responsible for disrupting macrophage function in vivo.
Acculturation, Enculturation, and Symptoms of Depression in Hispanic Youth: The Roles of Gender, Hispanic Cultural Values, and Family Functioning

The risk for depression increases as Hispanic youth acculturate to U.S. society. This association is stronger for Hispanic girls than boys. To better understand the influence of culture and family on depressive symptoms, we tested a process-oriented model of acculturation, cultural values, and family functioning. The data came from Project RED, which included 1,922 Hispanic students (53 % girls; 86 % were 14 years old; and 84 % were U.S. born) from Southern California. We used data from 9th to 11th grade to test the influence of acculturation-related experiences on depressive symptoms over time. Multi-group structural equation analysis suggested that both family conflict and cohesion were linked with depressive symptoms. Hispanic cultural values were associated with family cohesion and conflict but the strength and direction of these relationships varied across cultural values and gender. For girls and boys, familismo and respeto were associated with higher family cohesion and lower family conflict. Moreover, gender roles were linked with higher family cohesion in girls but not in boys. These results indicate that improving family functioning will be beneficial for boys’ and girls’ psychological well-being. This may be achieved by promoting familismo and respeto for boys and girls and by promoting traditional gender roles for girls.
Shear wave splitting beneath the central Tien Shan and tectonic implications

[1] Shear-wave splitting analyses were performed at 30 seismic stations in the central Tien Shan and its vicinity. Fast orientation at most of the stations on the Tien Shan range is ENE-WSW, parallel to the strike of the Tien Shan. It largely reflects a coherent deformation of the lithosphere in response to the NS shortening. Anisotropy with NNE-SSW fast axes is observed within adjacent basins, around the Issyk Kul and near the northwestern Tarim, where the lithosphere is presumably strong, less deformed. The NNE-SSW orientation, which coincides with the surface velocity of the central Tien Shan, can be best explained by shear between the lithosphere and asthenosphere on a regional scale rather than small-scale convection as proposed in previous studies. The dextral Talasso-Fergana fault seems to have little effect on anisotropy at its nearby stations, suggesting this fault is probably confined to the shallow part of the lithosphere.
A comparison of anionic sites in the glomerular basement membranes from different classes of fishes.

Cationized ferritin was injected into the circulatory system of teleosts, the sea raven and Atlantic eelpout, and into elasmobranchs, the spiny dogfish and the skate, to determine if the glomerular basement membranes (GBM) from these different groups of fishes possess anionic binding sites similar to those present in the GBM of mammals. The distribution of cationized ferritin was the same in all fishes listed. Cationized ferritin was localized only in the GBM and the mesangial matrix. The regular distribution of cationized ferritin within the laminae rarae (∼60 nm intervals) was taken as evidence of the presence of anionic binding sites. Cationized ferritin did not bind to the glomerular capillary endothelium, nor was any of it localized at the base of the slit diaphragms of the foot processes of the podocytes. The distribution of binding sites in the GBM of these fishes is similar to that in another teleost, the winter flounder, and in a cyclostome, the hagfish.
Rapid diffusive infiltration of sodium into partially molten peridotite

Recent seismological, geochemical and experimental observations suggest that, as mantle peridotite melts, the resulting basaltic liquid forms an interconnected network, culminating in the rapid ascent of the basalt relative to the surrounding solid matrix1,2,3. Mantle melting is therefore a polybaric process, with melts produced over a range of pressures having differing chemical characteristics4,5,6. Modelling and peridotite-melting experiments designed to simulate polybaric mantle melting generally assume that there is no interaction between melts generated at greater pressures and the overlying solid mantle at lower pressures5,7. Beneath mid-ocean ridges, melts derived from greater depth are probably channelized during ascent, so preventing direct re-equilibration with shallow peridotite8, as required by geochemical observations6,9. I show here, however, that sodium in ascending melts will quickly diffuse into the melt formed within nearby peridotite at lower pressures. This process fundamentally changes the manner by which the peridotite melts, and can account for both the creation of silica-rich glass inclusions in mantle xenoliths and the anomalous melting modes recorded by abyssal peridotites. Increased melting of lithosphere and upwelling asthenosphere could result from this process without the need to invoke higher mantle temperatures.
Control of ruthenium oxide nanorod length in reactive sputtering

Ruthenium oxide nanorods have been grown on Si wafer substrates under a variety of pre-existing surface conditions by reactive radio frequency sputtering in an electron cyclotron resonant plasma process. Nanorod formation by this method is fast relative to that observed in other processes reported in the literature, with nucleation being the rate determining step. Growth in the axial direction is limited by the availability of ruthenium precursors which competes with their consumption in the lateral growth of the nanorods. The availability of Ru precursors at the top of the nanorods can be controlled by surface diffusion and therefore substrate temperature. The ultimate length of the nanorods is determined by the mole fraction of oxygen used in the reactor ambient through the production of mobile Ru hyperoxide precursors. The results of this investigation show the way to develop a process for producing a high density field of nanorods with a specified length.
Presence of a truncated form of the vitamin D receptor (VDR) in a strain of VDR-knockout mice

As part of our studies on the membrane-initiated actions of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its localization in caveolae membrane fractions, we used a vitamin D receptor (VDR)-knockout (KO) mouse model to study the binding of [3H]-1α,25(OH)2D3 in the presumed absence of the VDR. In this mouse model, known as the Tokyo strain, the second exon of the VDR gene, which encodes the first of the two zinc fingers responsible for DNA binding, was removed, and the resulting animals have been considered to be VDR-null mice. To our surprise, several tissues in these KO mice showed significant (5–50% of that seen in wild-type animals) specific binding of [3H]-1α,25(OH)2D3 in nuclear and caveolae membrane fractions. The dissociation constants of this binding in samples from VDR-KO and wild-type mice were indistinguishable. RT-PCR analysis of intestinal mRNA from the VDR-KO animals revealed an mRNA that lacks exon 2 but contains exons 3–9 plus two 5′-untranslated exons. Western analysis of intestinal extrac...
Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha.

It is established that Yersinia pestis, the causative agent of bubonic plague, and enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica share a ca. 70-kb low-calcium response or Lcr plasmid (Lcr+). The latter is known to encode regulatory functions that restrict growth at 37 degrees C in Ca(2+)-deficient medium and virulence factors that are expressed only in vitro within this environment (e.g., certain Yops and V antigen). In this study, gamma interferon (IFN-gamma) was never detected in mice infected with 10 minimum lethal doses (MLD) of Lcr+ cells of Y. pestis, and significant levels of tumor necrosis factor alpha (TNF-alpha) arose only prior to death. Prompt and marked synthesis of these cytokines was observed upon infection with avirulent Lcr- mutants. Treatment of mice with exogenous IFN-gamma plus TNF-alpha inhibited multiplication of Lcr+ yersiniae in vivo, thereby providing protection against challenge with 10 MLD. Administration of both cytokines was required for absolute survival, suggesting a synergistic rather than cumulative interaction. This protective effect entailed cytokine priming as judged by subsequent detection of substantial levels of endogenous IFN-gamma and TNF-alpha. Monospecific anti-V-antigen, known to provide passive immunity against 10 MLD of Lcr+ Y. pestis, permitted significant synthesis of endogenous IFN-gamma and TNF-alpha. These findings demonstrate that Lcr+ yersiniae suppress synthesis of cytokines and suggest that this effect is mediated by one or more Lcr plasmid-encoded virulence factors.
(Re)Integrating Simmel in Contemporary Social Exchange: The Effect of Nonpartisans on Relational Outcomes

Despite the increased prevalence of neutral third parties in both formal and informal exchange processes, social exchange theory has yet to consider the effect of nonpartisans on important cognitive and affective outcomes of exchange. This research integrates Simmel’s conceptualization of small groups and nonpartisans with contemporary theory and research in social exchange to explore how different levels of neutral third party intervention in an exchange process affect the “relational outcomes” of exchange (perceptions of fairness of, general positive regard toward, the exchange partner and optimism about the tone of future interactions). Experimental results indicate that increased third party intervention is positively related to favorable relational outcomes. The increased likelihood of external attributions and decreased salience of conflict associated with high levels of third-party intervention partially explain this result.
DFT Study of Hg Oxidation across Vanadia-Titania SCR Catalyst under Flue Gas Conditions

The density functional theory was used to analyze the thermodynamic stability and reactivity of the vanadia-titania catalyst below monolayer regime with the purpose of having a good representation of a commercial SCR catalyst (V2O5(<2 wt %)–TiO2). The objective of this paper is to understand the reactivity of this catalyst in Hg oxidation. The SCR catalyst is modeled as a tetrahedrally coordinated divanadate unit supported on a 3-layer TiO2(001) slab to represent a catalyst with low vanadia loadings. Under flue gas conditions, the interaction of water with this surface has been studied as a function of pressure and temperature using ab initio thermodynamic calculations, showing that water coverage is temperature-dependent. Adsorbed water acts as a Lewis base, donating electrons to the TiO2(001) surface support, which increases the negative charge and reactivity of the oxygen atoms of the vanadia dimer. The reactivity of the vanadia dimer toward Hg oxidation is analyzed through the adsorption energies of H...
Muscle activation of paraspinal muscles in different types of high heels during standing

[Purpose] This study researched the effects of different types of high heels on the muscles surrounding the cervical spine, the thoracic spine, and the lumbar spine by analyzing muscle activation of the paraspinal muscles during standing while wearing high heels. The high heels were all of the same height: 8 cm. [Subjects and Methods] The 28 subjects in this experiment were females in their 20s with a foot size of 225–230 mm and a normal gait pattern. To measure the muscle activation of the paraspinal muscles, EMG electrodes were attached on the paraspinal muscles around C6, T7, and L5. The muscle activation during standing while wearing 8-cm-high wedge heels, setback heels, and French heels was then measured. The measurements were performed 3 times each, and the mean value was used for analysis. [Results] The levels of muscle activation of the paraspinal muscles induced by standing on wedge heels, setback heels, and French heels in the cervical and lumbar areas were significantly higher than those induced by standing on bare feet. But there was no significant difference according to the heel types. [Conclusion] The height of the heels presented a greater variable than the width of the heels on the muscle activation of paraspinal muscles. Therefore, wearing high heels is not recommended for those who have pain or functional problems in the cervical and/or lumbar spine.
Opportunities and Challenges for Selected Emerging Technologies in Cancer Epidemiology: Mitochondrial, Epigenomic, Metabolomic, and Telomerase Profiling

Remarkable progress has been made in the last decade in new methods for biologic measurements using sophisticated technologies that go beyond the established genome, proteome, and gene expression platforms. These methods and technologies create opportunities to enhance cancer epidemiologic studies. In this article, we describe several emerging technologies and evaluate their potential in epidemiologic studies. We review the background, assays, methods, and challenges and offer examples of the use of mitochondrial DNA and copy number assessments, epigenomic profiling (including methylation, histone modification, miRNAs, and chromatin condensation), metabolite profiling (metabolomics), and telomere measurements. We map the volume of literature referring to each one of these measurement tools and the extent to which efforts have been made at knowledge integration (e.g., systematic reviews and meta-analyses). We also clarify strengths and weaknesses of the existing platforms and the range of type of samples that can be tested with each of them. These measurement tools can be used in identifying at-risk populations and providing novel markers of survival and treatment response. Rigorous analytic and validation standards, transparent availability of massive data, and integration in large-scale evidence are essential in fulfilling the potential of these technologies. Cancer Epidemiol Biomarkers Prev; 22(2); 189–200. ©2012 AACR.
Phosphoethanolamine Substitution of Lipid A and Resistance of Neisseria gonorrhoeae to Cationic Antimicrobial Peptides and Complement-Mediated Killing by Normal Human Serum

The capacity of Neisseria gonorrhoeae to cause disseminated gonococcal infection requires that such strains resist the bactericidal action of normal human serum. The bactericidal action of normal human serum against N. gonorrhoeae is mediated by the classical complement pathway through an antibody-dependent mechanism. The mechanism(s) by which certain strains of gonococci resist normal human serum is not fully understood, but alterations in lipooligosaccharide structure can affect such resistance. During an investigation of the biological significance of phosphoethanolamine extensions from lipooligosaccharide, we found that phosphoethanolamine substitutions from the heptose II group of the lipooligosaccharide β-chain did not impact levels of gonococcal (strain FA19) resistance to normal human serum or polymyxin B. However, loss of phosphoethanolamine substitution from the lipid A component of lipooligosaccharide, due to insertional inactivation of lptA, resulted in increased gonococcal susceptibility to polymyxin B, as reported previously for Neisseria meningitidis. In contrast to previous reports with N. meningitidis, loss of phosphoethanolamine attached to lipid A rendered strain FA19 susceptible to complement killing. Serum killing of the lptA mutant occurred through the classical complement pathway. Both serum and polymyxin B resistance as well as phosphoethanolamine decoration of lipid A were restored in the lptA-null mutant by complementation with wild-type lptA. Our results support a role for lipid A phosphoethanolamine substitutions in resistance of this strict human pathogen to innate host defenses.
Building Information Modeling for Quality Management in Infrastructure Construction Projects

With the growing use of Building Information Modeling (BIM) for vertical building projects, the use of BIM in infrastructure projects steadily increases. Construction companies that build infrastructure facilities are expecting the adoption of BIM since they have observed high return on investment (ROI) resulting from BIM for vertical building projects. In this paper, the focus is placed on the utilization of BIM for quality management in highway and bridge construction. A review of the literature on quality information model and quality control process is presented. The application of BIM for quality management is described. The results of pilot study by the authors on the model-driven approach to quality assurance (QA) and quality control (QC) is reviewed. Finally the issues and obstacles to BIM implementation in the infrastructure sector are discussed. Discussions in this paper are the critical aspects of the utilization of BIM for quality management in infrastructure construction project. Based on the results of this study, great potential of using BIM for quality management in infrastructure projects has been identified. Nonetheless, only limited amount of literature on this topic is currently available. It is believed that this study will set a stepping stone to future research and practice for promoting BIM technology in horizontal construction projects.
UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development

Multi-organ animals, such as vertebrates, require the development of a closed vascular system to ensure the delivery of nutrients to, and the transport of waste from, their organs. As a result, an organized vascular network that is optimal for tissue perfusion is created through not only the generation of new blood vessels but also the remodeling and maintenance of endothelial cells via apoptotic and cell survival pathways. Here, we show that UBIAD1, a vitamin K2/menaquinone-4 biosynthetic enzyme, functions cell-autonomously to regulate endothelial cell survival and maintain vascular homeostasis. From a recent vascular transgene-assisted zebrafish forward genetic screen, we have identified a ubiad1 mutant, reddish/reh, which exhibits cardiac edema as well as cranial hemorrhages and vascular degeneration owing to defects in endothelial cell survival. These findings are further bolstered by the expression of UBIAD1 in human umbilical vein endothelial cells and human heart tissue, as well as the rescue of the reh cardiac and vascular phenotypes with either zebrafish or human UBIAD1. Furthermore, we have discovered that vitamin K2, which is synthesized by UBIAD1, can also rescue the reh vascular phenotype but not the reh cardiac phenotype. Additionally, warfarin-treated zebrafish, which have decreased active vitamin K, display similar vascular degeneration as reh mutants, but exhibit normal cardiac function. Overall, these findings reveal an essential role for UBIAD1-generated vitamin K2 to maintain endothelial cell survival and overall vascular homeostasis; however, an alternative UBIAD1/vitamin K-independent pathway may regulate cardiac function.
Neurotransmitter receptors as central regulators of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) has a near 100% mortality because it is generally detected at an advanced stage and responds poorly to existing therapeutics. This review summarizes current evidence suggesting important roles of neurotransmitter receptors in the regulation of this malignancy. Experimental evidence indicates that the alpha(7)-nicotinic acetylcholine receptor (alpha(7)nAChR) stimulates PDAC via stress neurotransmitter-mediated activation of beta-adrenergic signaling while the alpha(4)beta(2)nAChR inhibits PDAC via GABA-mediated inhibition of adenylyl cyclase activation. In analogy to molecular mechanisms that govern nicotine addiction, chronic exposure to nicotine or its nitrosated derivative nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone render the stimulatory alpha(7)nAChR hyperactive while desensitizing the inhibitory alpha(4)beta(2)nAChR. Accordingly, PDAC intervention strategies should include the diagnosis of unphysiological neurotransmitter levels and aim to restore any imbalance in stimulatory and inhibitory neurotransmitters.
The Putative Hybrid Sensor Kinase SypF Coordinates Biofilm Formation in Vibrio fischeri by Acting Upstream of Two Response Regulators, SypG and VpsR

Colonization of the Hawaiian squid Euprymna scolopes by the marine bacterium Vibrio fischeri requires the symbiosis polysaccharide (syp) gene cluster, which contributes to symbiotic initiation by promoting biofilm formation on the surface of the symbiotic organ. We previously described roles for the syp-encoded response regulator SypG and an unlinked gene encoding the sensor kinase RscS in controlling syp transcription and inducing syp-dependent cell-cell aggregation phenotypes. Here, we report the involvement of an additional syp-encoded regulator, the putative sensor kinase SypF, in promoting biofilm formation. Through the isolation of an increased activity allele, sypF1, we determined that SypF can function to induce syp transcription as well as a variety of biofilm phenotypes, including wrinkled colony formation, adherence to glass, and pellicle formation. SypF1-mediated transcription of the syp cluster was entirely dependent on SypG. However, the biofilm phenotypes were reduced, not eliminated, in the sypG mutant. These phenotypes were also reduced in a mutant deleted for sypE, another syp-encoded response regulator. However, SypF1 still induced phenotypes in a sypG sypE double mutant, suggesting that SypF1 might activate another regulator(s). Our subsequent work revealed that the residual SypF1-induced biofilm formation depended on VpsR, a putative response regulator, and cellulose biosynthesis. These data support a model in which a network of regulators and at least two polysaccharide loci contribute to biofilm formation in V. fischeri.
System dynamics—the next fifty years

Fifty years after its creation, I review the current status of the field of system dynamics and assess prospects for the next fifty. I focus on the challenges the field must face if it is to realize its potential. The first 50 years of system dynamics have established an introduction to the field. We have shown the importance of achieving a better understanding of complex systems in nature and human affairs. Now, the field is on a plateau ready to launch the next great thrust forward. We can better understand the present status of system dynamics by comparison to professions that have developed earlier. We are now at about the same state of advancement that engineering was when MIT first opened its doors in 1865, or that medicine was in the late 1800s when the Johns Hopkins School of Medicine was established. We have as much to learn yet about high-order nonlinear feedback structures around us as those earlier professions have already learned about their fields in the last 150 years. Now is the time to plan how the next 50 years can start to close this huge knowledge gap. Like those early days in more mature professions, we do not yet have universities devoted to 4-year and 6-year programs in system dynamics. Like the older professions at their beginning, we do not yet have the equivalent of programs in science and biology in kindergarten through 12th grade education to prepare students for more advanced study at the university level. Nevertheless, there has been major progress in system dynamics during the last 50 years just as there had been in those older professions before they became formalized in advanced educational programs and before they were publicly recognized. Copyright © 2007 Jay W. Forrester.
Analytical modeling of common-gate low noise amplifiers

The exponential growth of wireless portable device market has been increasing the demand for customizable power- efficient transceivers. In this paper, we present an efficient modeling methodology for common-gate low-noise amplifiers (LNAs). Leveraging our models, we designed LNAs to work for different communication standards, GSM at 900 MHz, Bluetooth at 2.4 GHz, and wireless-LAN at 5.6 GHz. Our methodology achieves about 96.45% average accuracy in predicting different figures of merit (FOM) at the center frequency, while it provides Ave orders of magnitude speedup in the design process compared to simulation-based modeling techniques.
Analytical Solutions for the Resonance Response of Goupillaud-type Elastic Media Using Z-transform Methods

Abstract The resonance frequency spectrum is first derived for an m -layered Goupillaud-type elastic medium that is subjected to a discrete sinusoidal forcing function that varies harmonically with time at one end and held fixed at the other end. Analytical stress solutions are obtained from a coupled first-order system of difference equations using z -transform methods, where the determinant of the resulting global system matrix in the z -space | A m | is a palindromic polynomial with real coefficients. The zeros of the palindromic polynomial are distinct and are proven to lie on the unit circle for 1 ≤ m ≤ 5 and for certain classes of multilayered designs identified by tridiagonal Toeplitz matrices. An important result is the physical interpretation that all the positive angles, coterminal with the angles corresponding to the zeros of | A m | on the unit circle, represent the resonance frequency spectrum for the discrete model. A sequence of resonance frequencies for the discrete model appears to be universal for all multilayered designs with an odd number of layers, as it is independent of any design parameters. The resonance frequency results for the discrete model are then extended to describe the resonance frequency spectrum for the continuous model, where the forcing function applied at one end of the strip is continuous and varies harmonically with time while the other end is held fixed. The proposed natural frequency spectrum for a free-fixed m -layered Goupillaud-type strip is confirmed by independently solving a simplified form of the frequency equation, obtained after applying a transformation of the spatial variable. Our results suggest that the natural frequency spectrum depends on the layer impedance ratios and it is inversely proportional to the equal wave travel time for each layer. The results are used to identify layered designs with a common frequency spectrum and modify an existing design to obtain a desired frequency spectrum. Other connections are made with previous stress optimization results, the Chebyshev polynomials of the first and second kind, as well as the natural frequencies of a free-fixed non-Goupillaud-type layered strip.
Simple UAV Environment (SUAVE): A viewpoint motion control evaluation

Controlling a team of Unmanned Aerial Vehicles (UAV) requires the operator to perform continuous surveillance and path planning. The operator's situation awareness is likely to degrade as an increasing number of surveillance videos must be viewed and integrated. The Picture-in-Picture display (PiP) provides one solution for integrating multiple UAV camera video by allowing the operator to view the video feed in the context of surrounding terrain. The experimental SUAVE (Simple Unmanned Aerial Vehicle Environment) display extends PiP methods by sampling imagery from the video stream to texture a 3D map of the terrain. The operator can then inspect this imagery using world in miniature (WIM) or fly-through methods. Our previous investigation of the properties and advantages of SUAVE in the context of a search mission with 11 UAVs showed a strong advantage for finding targets. We investigated the effects of constrained versus unconstrained fly through technique to evaluate the performance in such spatially immersive displays. Results indicated no difference between these two motion control techniques.
Vaccination with a MHC class II peptide in Alum and inactive pertussis strongly ameliorates clinical MG in C57BL/6 mice.

Abstract We have investigated the efficacy of immunization against peptides from predisposing MHC class II molecules in human-compatible adjuvants for ameliorating experimental autoimmune myasthenia gravis (EAMG). C57BL/6 mice were immunized three times with the peptide I-Aβ b 62–76 in Alum + killed pertussis organisms (PT) prior to two injections with t AChR. The treatment greatly reduced the occurrence and severity of clinical MG relative to controls that received saline/Alum + PT or none. It also reduced antibody and T-cell responses against t AChR. The results have important implications for the possible immunotherapy of MG by targeting disease-associated MHC.
The Scanning Of Task Environments In Hospitals: An Empirical Study

The objectives of the paper were to identify the natural taxonomy of hospitals based on their task environmental scanning activities, and to test if scanning practices had any relationship with the overall performance of these hospitals. A cluster analysis yielded for groups of hospitals each of which had distinct scanning characteristics. Results showed significantly different performances across these groups. Hospitals with the most advanced scanning function performed better than hospitals that used less advanced methods to scan the task environment.
Genome Editing in Human Pluripotent Stem Cells: Approaches, Pitfalls, and Solutions

Human pluripotent stem cells (hPSCs) with knockout or mutant alleles can be generated using custom-engineered nucleases. Transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nucleases are the most commonly employed technologies for editing hPSC genomes. In this Protocol Review, we provide a brief overview of custom-engineered nucleases in the context of gene editing in hPSCs with a focus on the application of TALENs and CRISPR/Cas9. We will highlight the advantages and disadvantages of each method and discuss theoretical and technical considerations for experimental design.
Phospha-Michael Addition as a New Click Reaction for Protein Functionalization

A new type of click reaction between an alkyl phosphine and acrylamide was developed and applied for site-specific protein labeling in vitro and in live cells. Acrylamide is a small electrophilic olefin that readily undergoes phospha-Michael addition with an alkyl phosphine. Our kinetic study indicated a second-order rate constant of 0.07 m(-1) s(-1) for the reaction between tris(2-carboxyethyl)phosphine and acrylamide at pH 7.4. To demonstrate its application in protein functionalization, we used a dansyl-phosphine conjugate to successfully label proteins that were site-specifically installed with N(ɛ) -acryloyl-l-lysine and employed a biotin-phosphine conjugate to selectively probe human proteins that were metabolically labeled with N-acryloyl-galactosamine.
Reaction rim growth on olivine in silicic melts: Implications for magma mixing

Finely crystalline amphibole or pyroxene rims that form during reaction between silicic host melt and cognate olivine xenocrysts, newly introduced during magma mixing events, can provide information about the timing between mixing and volcanic eruptions. We investigated rim growth experimentally by placing forsteritic olivine in rhyolitic and rhyodacitic melts for times between 25 and 622 h at 50 and 150 MPa, H2O-saturated, at the Ni-NiO buffer. Rims of orthopyroxene microlites formed from high-silica rhyolite and rhyodacite melts at 885 °C and 50 MPa, and in the rhyolite at 150 MPa and 885 °C. Rims of amphibole with lesser orthopyroxene formed in the rhyolite at 150 MPa and 800 °C and in the rhyodacite at 150 MPa and 885 °C. Irregular, convolute olivine edges and mass balance between olivine, melt, and rim phases show that olivine partly dissolved at all conditions. Iron-rich zones at the exteriors of olivines, which increased in width parabolically with time, show that Fe-Mg interdiffusion occurring in olivines was not outpaced by olivine dissolution. Linear increases of the square of rim widths with time suggest that diffusion within the melt is the rate-controlling process for olivine dissolution and rim growth. Rims grew one-half to one order-of-magnitude faster when melt water contents were doubled, unless conditions were far above the liquidus. Rim growth rate in rhyolite increases from 0.055 ± 0.01 μm2/h at 885 °C and 50 MPa to 0.64 ± 0.13 μm2/h at 800 °C and 150 MPa. Melt composition has a lesser effect on rim growth rates, with growth rate increasing as melt SiO2 content decreases. Pyroxene rims on olivines in andesite erupted from Arenal volcano (Costa Rica) grew at a rate of 3.0 ± 0.2 μm2/h over an eleven-year period. This rate is faster than those of the experiments due to lower melt viscosity and higher temperatures, and suggests that a magma mixing event preceded the start of the eruption by days.
Dynamics of an Isolated Population of Aedes Triseriatus (Diptera: Culicidae). I. Population size

A discrete population of Aedes triseriatus was studied in a 10.1-ha woodlot containing 108 tree holes. First, all tree holes were examined weekly and pupae were counted. In 1975, 1790 female pupae were produced. Assuming a daily survivorship rate of 0.87, 825 females were estimated to be in the population at the end of the summer. Second, adult females were captured, marked, released, and recaptured. Recovery rates of marked mosquitoes were 24–45%. Dispersal studies showed that movement within the woodlot was nearly random but that movement between woodlots did not occur; the study site was thus an ecological island. In order to make an indirect estimate of population size, 3 series of collections were made during the summer of 1975, spanning 10, 10, and 6 days. The Jolly method was the best of 3 models tested for estimating absolute numbers. At the end of the summer of 1975, we estimated that 1225 females were present. This figure matched well with the independently derived results from pupal counts. This is the first time that an independent check has been used to determine the accuracy of mark-release-recapture methods for determining size of mosquito populations.
An analysis on prognosis in 289 patients with decompensatory cirrhosis

Objective To observe the survival of cirrhotic patients and analyze the risk factors to the prognosis of cirrhotic.Methods A total of 289 patients with decompensatory cirrhosis were involved in the study.All patients were followed up by phone or mail.The clinical and laboratory variables were studied by univariate and multivariate statistical analysis.Results The survival rate during hospitalization and at 5-years was 86.6% and 25.3% respectively.Multivariate Cox's analysis showed that serum total bilirubin,albumin,creatinine,blood urea nitrogen,low density lipoprotein,prothrombin time,ascites,age were independent predictors to the prognosis of 5-years.Conclusion For decompensatory cirrhotic patients,an amount of clinical factors are significantly correlated with mortality during hospitalization or at 5-years.The liver function is the main factor to prognosis.
Refinements to the MLB-NPB Posting System: A Clear Win for Japanese Players and Loss for Japanese Teams

We theoretically and experimentally analyze recent changes in the posting system used by Japan’s Nippon Professional Baseball (NPB) organization and the U.S. Major League Baseball (MLB) organization to transfer the rights of NPB players from NPB teams to MLB teams. Under the old system—a sequential, first-price sealed-bid auction among MLB teams for player negotiation exclusivity rights—the NPB team enjoyed considerable surplus from lucrative posting fees. We predict that the revised system—an English auction with an entry fee—will transfer most of the NPB’s middleman benefits (posting fees) to the players through higher salaries. Additionally, we analyze a third, proposed but not adopted, mechanism—a weighted-average sealed-bid auction. Our experimental results confirm our theoretical predictions. Furthermore, under the new system, efficiency is greatest, MLB teams spend less on Japanese players, and the players’ salaries increase significantly.
Increased skin tumor incidence and keratinocyte hyper-proliferation in a mouse model of down syndrome

Down syndrome (DS) is a genetic disorder caused by the presence of an extra copy of human chromosome 21 (Hsa21). People with DS display multiple clinical traits as a result of the dosage imbalance of several hundred genes. While many outcomes of trisomy are deleterious, epidemiological studies have shown a significant risk reduction for most solid tumors in DS. Reduced tumor incidence has also been demonstrated in functional studies using trisomic DS mouse models. Therefore, it was interesting to find that Ts1Rhr trisomic mice developed more papillomas than did their euploid littermates in a DMBA-TPA chemical carcinogenesis paradigm. Papillomas in Ts1Rhr mice also proliferated faster. The increased proliferation was likely caused by a stronger response of trisomy to TPA induction. Treatment with TPA caused hyperkeratosis to a greater degree in Ts1Rhr mice than in euploid, reminiscent of hyperkeratosis seen in people with DS. Cultured trisomic keratinocytes also showed increased TPA-induced proliferation compared to euploid controls. These outcomes suggest that altered gene expression in trisomy could elevate a proliferation signalling pathway. Gene expression analysis of cultured keratinocytes revealed upregulation of several trisomic and disomic genes may contribute to this hyperproliferation. The contributions of these genes to hyper-proliferation were further validated in a siRNA knockdown experiment. The unexpected findings reported here add a new aspect to our understanding of tumorigenesis with clinical implications for DS and demonstrates the complexity of the tumor repression phenotype in this frequent condition.
LG-44OCCURRENCE OF BRAF V600E MUTATION IN A PEDIATRIC BRAINSTEM GANGLIOGLIOMA WITH NEAR EXCLUSIVE GLIAL COMPONENT IN THE ORIGINAL BIOPSY

LG-44. OCCURRENCE OF BRAF V600E MUTATION IN A PEDIATRIC BRAINSTEM GANGLIOGLIOMA WITH NEAR EXCLUSIVE GLIAL COMPONENT IN THE ORIGINAL BIOPSY Alex Feldman, David Kelly, Alyssa Reddy, Jeffrey Blount, and Rong Li; University of Alabama at Birmingham, Birmingham, AL, USA A five-year-old male who initially presented with apneic episodes and morbid obesity underwent imaging studies, which revealed a dorsally exophytic medullary tumor in 2014. A biopsy showed a classic pilocytic astrocytoma (PA) with no apparent neoplastic neuronal component. Following completion of chemotherapy, the patient presented again in January of 2016 with worsening symptoms; the tumor was found to have grown in size with brainstem compression. Debulking was performed. Unexpectedly, the histology of this tumor showed a ganglioglioma (GG) with many clusters of enlarged, misshapen, dysmorphic-appearing and occasionally binucleated neurons. Furthermore, BRAF V600E mutations were identified in both prior and recurrent tumors. Recent publications have found that the BRAF V600E mutation is seen in 20-58% of all GGs. In particular, pediatric brainstem GGs appear to harbor this mutation at a rate greater than 50%. Few studies have investigated the distribution of BRAF aberrations among neuronal and glial components in GGs. Pilocytic astrocytomas often possess BRAF abnormalities, though fusion genes (i.e BRAF-KIAA1549) are considerably more common (60-80%) than the BRAF V600E missense mutations (only seen in 10-12% of pediatric brainstem PAs). This case highlights the presence of the BRAF point mutation in both glial and neuronal component of a pediatric brainstem GG, supporting the hypothesis that a glioneuronal lineage precursor is initially affected by the mutation. Additionally, the presence of the BRAF point mutation in a brainstem pilocytic astrocytoma should raise the possibility of a GG in which sampling artifact highlights a near exclusive glial component. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.44 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Abstract 4083: Tumor associated macrophages mediates the oncogenic effect of FGF18 in ovarian cancer

Epithelial ovarian cancer is the fifth leading cause of cancer-related death among women and has the highest case-fatality rate among gynecologic cancers. Effective management of this deadly disease still remains scanty due to the inadequate understanding of the molecular mechanisms associated with the tumor progression and prognosis. We have previously reported the tumor-promoting role of Fibroblast growth factor 18 (FGF18), which have been identified through genomic analysis of ovarian tumors. Initial studies suggested FGF18 promotes ovarian tumor progression through NF-κB pathway mediated elevation of proinflammatory cytokines, which mediate the increased tumor burden, angiogenesis and infiltration of macrophages in FGF18 expressing xenografts. Based on these findings, the present study aims to delineate the mechanism by which FGF18 modulates the phenotype of tumor associated macrophages (TAMs) as well as the reciprocal tumor-promoting feedback from the TAMs which potentially contributes FGF18 mediated ovarian tumorigenesis. Immunohistochemical staining of a tissue array comprising 216 archived high-grade advanced stage serous ovarian tumor specimens revealed a significant correlation between the FGF18 expression and infiltration of M2-polarized macrophages (by CD163). In addition, the density of intratumoral M2 TAMs inversely associated with patients’ overall survival as a negative prognostic factor independent to age, tumor grade and debulking status. These findings suggest intratumoral TAMs may play an important role in ovarian tumorigenesis. In vitro co-culture studies further demonstrated that human monocyte cell line THP-1 or murine peritoneal macrophage cell line IC-21 could significantly activate the NF-κB pathway and increase the production of various proinflammatory cytokines in A224 ovarian cancer cells. Co-culture also increased the migratory potential of A224 cells. Addition of an IKKβ inhibitor into the co-culture system nullified the cytokine production and migration of tumor cells promoted by monocytes/macrophages, implicating the involvement of canonical NF-κB signaling in the crosstalk. Conversely, liposome clodronate mediated in vivo macrophage depletion significantly shrunk the tumor burden of the intraperitoneal xenograft derived from FGF18 overexpressing SKOV3 cells, while minimal effect was observed over the control RFP overexpressing xenograft. Besides, macrophage depletion also markedly decreased the intratumoral microvessel density induced by FGF18 overexpression. Taken together, our data potentially suggest TAMs may mediate the FGF18 related ovarian tumorigenesis by augmenting the proinflammatory status of the tumors. Citation Format: Wei Wei, Michael Birrer. Tumor associated macrophages mediates the oncogenic effect of FGF18 in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4083.
Abstract 291: Single cell analyses reveal resistance heterogeneity in EGFR mutant NSCLC

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA In EGFR mutant lung adenocarcinomas, the activating mutation to EGFR is the founder alteration, present in every cancer cell. Most patients with this genetic alteration respond to EGFR tyrosine kinase inhibitors, although the average duration of the response is only one year before the cancer develops acquired resistance. Efforts to identify the mechanisms underlying the resistance in patients have led to the identification of a resistance mechanism in the majority of cases. However, preliminary data is emerging indicating that multiple resistance mechanisms can be present within an individual patient's disease, and thus, classifying resistant disease with a single mechanism is an oversimplification. Here, utilizing single cell approaches on patient samples, we demonstrate heterogeneity within individual biopsies with respect to resistance mechanisms, epigenetic state, and sensitivity to TKI. Additionally, we observe that the fraction of T790M-positive cells is predictive of response to 3rd generation EGFR inhibitor treatment, suggesting that the degree of heterogeneity has important clinical implications. As therapies designed to target singular resistance mechanisms become more widely implemented, assessing heterogeneity will become increasingly critical in order to choose the most effective therapy for the patient. Citation Format: Matt J. Niederst, Huidan Zhang, Haichuan Hu, Naiwen Cui, Yamei Cai, Hillary Mulvey, Zofia Piotrowska, Lecia Sequist, David A. Weitz, Jeffrey A. Engelman. Single cell analyses reveal resistance heterogeneity in EGFR mutant NSCLC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 291.
Treating arrhythmias with adjunctive magnesium: identifying future research directions.

Magnesium is the fourth most abundant cation in the human body and is the second most prevalent cation in intracellular tissues. Myocardial cell action potentials are mediated by voltage-dependent Na+, K+, and Ca2+ channels which, when their function is altered, can lead to the genesis of cardiac dysrythmias. Magnesium regulates the movement of ions through these channels within myocardial tissues. The potential ability of magnesium supplementation to prevent and/or treat arrhythmias has been recognized in clinical medicine for years. This includes termination of torsade de pointes, prevention of post-operative atrial fibrillation, acute treatment of atrial fibrillation, and improving the efficacy and safety of antiarrhythmic drugs. Despite what is currently known about magnesium’s therapeutic potential, a number of limitations and gaps to the literature exist. This includes an unclear link between correction of intracellular magnesium concentrations and both mechanistic and clinical outcomes, small sample sizes, varying routes of administration and doses, as well as short follow-up periods. This review highlights these gaps and recommends areas of need for future research.