cssi/SciSciGPT-SciSciNet huggingface dataset:
Macromolecular Synthesis Shutoff Resistance by Myeloid Cells Is Critical to IRF7-Dependent Systemic Interferon Alpha/Beta Induction after Alphavirus Infection.

Alphavirus infection of fibroblastic cell types in vitro inhibits host cell translation and transcription, leading to suppression of interferon alpha/beta (IFN-α/β) production. However, the effect of infection upon myeloid cells, which are often the first cells encountered by alphaviruses in vivo, is unclear. Previous studies demonstrated an association of systemic IFN-α/β production with myeloid cell infection efficiency. Murine infection with wild-type Venezuelan equine encephalitis virus (VEEV), a highly myeloid-cell-tropic alphavirus, results in secretion of very high systemic levels of IFN-α/β, suggesting that stress responses in responding cells are active. Here, we infected myeloid cell cultures with VEEV to identify the cellular source of IFN-α/β, the timing and extent of translation and/or transcription inhibition in infected cells, and the transcription factors responsible for IFN-α/β induction. In contrast to fibroblast infection, myeloid cell cultures infected with VEEV secreted IFN-α/β that increased until cell death was observed. VEEV inhibited translation in most cells early after infection ( 6 h p.i.). Furthermore, the interferon regulatory factor 7 (IRF7), but not IRF3, transcription factor was critical for IFN-α/β induction in vitro and in sera of mice. We identified a subset of infected Raw 264.7 myeloid cells that resisted VEEV-induced translation inhibition and secreted IFN-α/β despite virus infection. However, in the absence of IFN receptor signaling, the size of this cell population was diminished. These results indicate that IFN-α/β induction in vivo is IRF7 dependent and arises in part from a subset of myeloid cells that are resistant, in an IFN-α/β-dependent manner, to VEEV-induced macromolecular synthesis inhibition.IMPORTANCE Most previous research exploring the interaction of alphaviruses with host cell antiviral responses has been conducted using fibroblast lineage cell lines. Previous studies have led to the discovery of virus-mediated activities that antagonize host cell antiviral defense pathways, such as host cell translation and transcription inhibition and suppression of STAT1 signaling. However, their relevance and impact upon myeloid lineage cell types, which are key responders during the initial stages of alphavirus infection in vivo, have not been well studied. Here, we demonstrate the different abilities of myeloid cells to resist VEEV infection compared to nonmyeloid cell types and begin to elucidate the mechanisms by which host antiviral responses are upregulated in myeloid cells despite the actions of virus-encoded antagonists.
Dynamics of space- and time-modulated metastructures

Topology has recently emerged as a principle governing unique wave transport phenomena through interface or edge modes that are impurity-immune and potentially unidirectional. In this context, this presentation illustrates the effect on dispersion topology of modulations of properties in space and time. The two modulation strategies are shown to lead to dual phenomena, which can be described by interchanging frequency and wavenumber, and that manifest themselves as gaps enabling frequency/wavenumber-selective wave manipulation. Time modulation produces narrowband tunable reflection at a frequency determined by the modulation, which is illustrated on a beam waveguide with switching negative impedance piezoelectric shunts. Adiabatic, or slow, space modulation of the stiffness properties of a plate structure drives the transition from a localized state at one boundary, to a bulk state and, finally, to another localized state at the opposite boundary. The presented investigations suggest the application of modulation strategies for single-port tunable filtering devices that may be implemented in acoustic, mechanical or photonic platforms. Moreover, the considered experimental platforms allow the exploration of various unique properties associated with time and/or space modulation, including filtering, frequency conversion, non-reciprocity, and topological pumping for wave redirection.Topology has recently emerged as a principle governing unique wave transport phenomena through interface or edge modes that are impurity-immune and potentially unidirectional. In this context, this presentation illustrates the effect on dispersion topology of modulations of properties in space and time. The two modulation strategies are shown to lead to dual phenomena, which can be described by interchanging frequency and wavenumber, and that manifest themselves as gaps enabling frequency/wavenumber-selective wave manipulation. Time modulation produces narrowband tunable reflection at a frequency determined by the modulation, which is illustrated on a beam waveguide with switching negative impedance piezoelectric shunts. Adiabatic, or slow, space modulation of the stiffness properties of a plate structure drives the transition from a localized state at one boundary, to a bulk state and, finally, to another localized state at the opposite boundary. The presented investigations suggest the application of mo...
The epigenetically-encoded memory of the innate immune system

Stimulation or infection of innate immune cells induces profound epigenetic changes, including the induction of histone modifications and alterations in DNA methylation levels. While some of these changes are rapidly reversible, others appear to be long-lasting, even in mitotic populations, with important functional consequences for the stimulus-experienced cell. Here we discuss the individual contributions of each of the plethora of known epigenetic modifications to the initial transcriptional response to immune activation, their dynamics as cells return to homeostasis, and their contribution to memory of the initial stimulus.
Navigating the complex cognitive task of classroom assessment

Abstract We investigated how a fifth-grade literacy teacher with classroom assessment expertise integrated assessment into his teaching practice. We employed a qualitative case study methodology to examine and document the processes this teacher used to make instructional decisions informed by classroom assessment events. We identified a repertoire of assessment relevant management routines and interpretation strategies that supported his assessment practice and instructional decision-making. Findings can be used to inform policy and organize content for teacher education by identifying a repertoire of potential management routines and interpretation strategies for engaging in classroom assessment and documenting how to enact these practices.
Desert island therapy.

My senior partner was an experienced and kindly clinician with an encyclopaedic medical knowledge, often spotting the zebra of an unusual diagnosis in his packed surgeries. His father had been a doctor in the Punjab and their family had been forced to leave India at partition. This had left him with a heightened awareness of the fragility of security, and a lasting dislike for sectarianism. He and his wife had also managed the difficulty of coping with a chronically unwell child for whom he spent much time trying to ensure a safe future. After he retired, a patient transferred to my list. We discussed her various struggles with anxiety, rooted in unfortunate life circumstances, and she shared with me the advice that he had given …
The Leaders’ Dilemma

The threat of a pandemic places P-20 educational leaders in the difficult position of having to make decisions with incomplete information that affect the welfare of students, employees, and the co...
Brackish Tidal Marsh Management and the Ecology of a Declining Freshwater Turtle

Water management practices in tidal marshes of the San Francisco Bay Estuary, California are often aimed at increasing suitable habitat for threatened fish species and sport fishes. However, little is known about how best to manage habitat for other sensitive status species like the semiaquatic freshwater Western Pond Turtle (Actinemys marmorata) that is declining throughout much of its range. Here, we examined the basking activity, abundance, survival, and growth of Western Pond Turtles at two brackish water study sites in Suisun Marsh, California that differed in how they were managed, with one having passive management (i.e., no active water regulation) and another having active management (i.e., water regulated for seasonal hunting). Our results revealed that basking activity was greatest when salinity, water stage, and air temperatures were low, shortwave radiation was high, and wind levels were intermediate. These preferred habitat characteristics often reflected conditions that were naturally maintained at the passively managed, muted tidal site. We also found that turtles were more abundant and had higher survival rates in the passively managed habitat compared to the actively managed habitat (201-323 turtles/km2 and 96% survival versus 11-135 turtles/km2 and 77% survival, respectively). Finally, characteristic growth constants from von Bertalanffy models showed that turtles grew more quickly in passively managed habitat compared to the actively managed habitat. Our results suggest that management strategies for this sensitive status species may be more effective if they protect passively managed muted tidal systems that limit or delay extreme cycles of salinity and water levels and conserve elevated terrestrial buffer zones adjacent to muted and full tidal systems.
Oxidative dehydrogenation of propane over transition metal sulfides using sulfur as an alternative oxidant

The use of alternative oxidants for the oxidative dehydrogenation of propane (ODHP) is a promising strategy to suppress the facile overoxidation to COx that occurs with O2. Gaseous disulfur (S2) represents a thermodynamically “softer” oxidant that has been underexplored and yet offers a potential route to more selective propylene formation. Here we describe a system for sulfur-ODHP (SODHP). We demonstrate that various metal sulfide catalysts generate unique reaction product distributions, and that propylene selectivities as high as 86% can be achieved at 450–550 °C. For a group of 6 metal sulfide catalysts, apparent activation energies for propylene formation range from 72–134 kJ mol−1 and parallel the corresponding catalyst XPS sulfur binding energies, indicating that M–S bond strength plays a key role in SODHP activity. Kinetic data over a sulfided ZrO2 catalyst indicate a rate law which is first-order in propane and zero-order in sulfur, suggesting that SODHP may occur via a mechanism analogous to the Mars van Krevelen cycle of traditional ODHP. The present results should motivate further studies of SODHP as a route to the selective and efficient oxidative production of propylene.
Cost-Effectiveness of Treatments after Closed Extraarticular Distal Radius Fractures in Older Adults from the WRIST Clinical Trial.

BACKGROUND This study performs an economic analysis of volar locking plate, external fixation, percutaneous pinning, or casting in elderly patients with closed distal radius fractures. METHODS This is a secondary analysis of the Wrist and Radius Injury Surgical Trial, a randomized, multicenter, international clinical trial with a parallel nonoperative casted group of patients older than 60 years with surgically indicated, extraarticular closed distal radius fractures. Thirty-Six-Item Short-Form Health Survey-converted utilities and total costs from Medicare were used to calculate quality-adjusted life-years and incremental cost-effectiveness ratio. RESULTS Casted patients were self-selected and older (p < 0.001) than the randomized surgical cohorts, but otherwise similar in sociodemographic characteristics. Quality-adjusted life-years for percutaneous pinning were highest at 9.17 and external fixation lowest at 8.81. Total costs expended were $16,354 for volar locking plates, $16,012 for external fixation, $11,329 for percutaneous pinning, and $6837 for casting. The incremental cost-effectiveness ratios for volar locking plates and external fixation were dominated by percutaneous pinning and casting. The ratio for percutaneous pinning compared to casting was $28,717. Probabilistic sensitivity analysis revealed a 10, 5, 53, and 32 percent chance of volar locking plate, external fixation, percutaneous pinning, and casting, respectively, being cost-effective at the willingness-to-pay threshold of $100,000 per quality-adjusted life-year. CONCLUSIONS Casting is the most cost-effective treatment modality in the elderly with closed extraarticular distal radius fractures and should be considered before surgery. In unstable closed fractures, percutaneous pinning, which is the most cost-effective surgical intervention, may be considered before volar locking plates or external fixation.
Effect of Blood Pressure Management Strategies on Outcomes in Patients with Acute Ischemic Stroke After Successful Mechanical Thrombectomy.

Background Variability, with no general consensus, exists in how patients' blood pressure should be managed after successful mechanical thrombectomy (MT) for large vessel ischemic stroke. We examined whether exceeding the systolic blood pressure (SBP) targets in patients during the first 24 hours after successful MT led to worse outcomes. Methods We retrospectively studied a consecutive sample of adult patients who had undergone MT. We collected SBP data for the first 24 hours after MT and categorized the patients into 3 groups according to cases of the SBP exceeding 140, 160, or 180 mm Hg. The primary and secondary outcomes were the modified Rankin scale score at discharge and 90 days of follow-up, the incidence of symptomatic intracranial hemorrhage, malignant cerebral edema, and hemicraniectomy, mortality within 90 days, and discharge disposition. Results A total of 117 patients were included (mean age, 65 ± 13.12 years; 53% female). The occurrence of ≥1 instance of SBP ≥180 mm Hg was significantly associated with poor functional outcomes at discharge (adjusted odds ratio [OR], 5.83; 95% confidence interval [CI], 1.41–32.9; P = 0.025) but not at 90 days of follow-up. The occurrence of SBP ≥160 mm Hg resulted in an independently increased odds of malignant cerebral edema (adjusted OR, 17.07; 95% CI, 2.56–174.4; P = 0.01), with a trend toward increased odds of symptomatic intracranial hemorrhage (adjusted OR, 4.42; 95% CI, 1.03–21.2; P = 0.0503). Conclusions These results suggest that individual instances of SBP elevation alone after successful MT, rather than a necessarily prolonged increased blood pressure as reflected by the mean or median SBP values, can significantly affect the clinical outcomes after successful MT.
Hybrid Modular Multilevel Rectifier: A New High-Efficient High-Performance Rectifier Topology for HVDC Power Delivery

This letter presents a novel three-phase rectifier topology, namely hybrid modular multilevel rectifier (HMMR) for medium or high voltage ac–dc power conversion applications. Compared with modular multilevel converter (MMC), up to 50% of the IGBTs and submodules (SMs) including capacitors can be replaced by simple high-efficient high-voltage line-frequency diode stacks. HMMR can keep the key benefits of MMC, such as modularity, reliability, and excellent harmonic performance, while significantly reducing the power losses, costs, and volume. Unlike the thyristor-based line-commutated converter (LCC) rectifier, HMMR can operate under different grid conditions and can even provide reactive power support, making it a strong candidate of rectifier unit for point-to-point MV and HV power delivery. The feasibility of proposed converter is verified by the simulation as well as experimental results.
Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC)

The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N'-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p<0.0001). We also tested the efficacy of all agents on red fibrinous clots formed in stagnant conditions. DiNAC did not lyse red clots, whereas tPA significantly lysed red clot over 48 h (p<0.01). These results lead to a novel use for DiNAC as a possible thrombolytic agent against acute arterial occlusions that could mitigate the risk of hyper-fibrinolytic bleeding.
Sudden Infant Death Syndrome

Sudden infant death syndrome (SIDS) is a cause of sudden unexpected infant death (SUID) that is unexplained and separate from death resulting from other identifiable causes of SUID. The triple-risk model is a compelling hypothesis explaining the conditions necessary for a SIDS event. Recent data suggest that brainstem 5-hydroxytryptophan or serotonin plays a pivotal role in the pathogenesis of SIDS.
Academic Library Services for First-Generation Students

Over the next decade, a growing number of first-generation students will enroll in colleges and universities, yet there are few resources on how academic libraries can support them. Library deans X...
Short-lived legacies of Prunus serotina plant–soil feedbacks

Plant–soil feedbacks (PSFs) are often involved in fundamental ecological processes such as plant succession and species coexistence. After a plant initiating PSFs dies, legacies of PSFs occurring as soil signatures that influence subsequent plants could persist for an unknown duration. Altered resource environments following plant death (especially light availability) could affect whether legacy effects manifest and persist. To evaluate PSFs and their legacies, we obtained soils from a chronosequence of Prunus serotina harvests. In a greenhouse experiment, we planted conspecific seedlings under two light levels in these soils of varying time since the influence of live Prunus serotina, and compared seed/seedling survival in soils from live trees, stumps, and surrounding forest matrix within each site and across the chronosequence. PSF legacies were measured as the difference between seedling performance in live tree and stump soils within a site. Negative PSF legacies of P. serotina were short-lived, lasting up to 0.5 years after tree removal. These effects occurred under 5% but not 30% full sun. PSFs and their legacies manifested in seed/seedling survival, but not biomass. Though restricted to low light, short-lived legacies of P. serotina PSFs could have lasting impacts on plant community dynamics during post-disturbance regeneration by disfavoring P. serotina regeneration in small tree-fall gaps.
Wireless Blind Spot Detection and Embedded Microcontroller

This paper presents the design and implementation of a blind spot detection system for installation on semitrucks to mitigate safety risks the vehicle poses due to low visibility of the surrounding area. The system is designed for easy attachment as well as operation at highway speeds. The system will have seven transmitters and a receiver with LCD display. The seven sensors attached to the vehicle will detect traffic in the vehicle’s blind spots and transmit a signal to the receiver. The receiver LCD display will alert the driver by lighting the cab image and the obstructed sensor. All eight components of the system are powered by rechargeable batteries, which are charged via a wireless charging tray connected to the 12 V power source of the vehicle. This paper describes the design, implementation, and results of each of these objectives.
Abstract W P55: Practice Diversity Among US Neurologists with Respect to the 3 to 4.5-Hour Window for Acute Stroke Thrombolysis

BACKGROUND: In 2009, the AHA/ASA endorsed extending the Acute Stroke IV tPA treatment window to 4.5 hours. Four additional exclusionary criteria were advised for treating patients in this extended window. It is unknown how the practice of stroke care has evolved since then. We developed an online survey aimed to evaluate the current practice patterns of neurologists when treating patients in the 3 to 4.5 hour therapeutic window. METHODS: We developed a survey utilizing SurveyMonkey.com. The survey included 6 questions, 1. Subspecialty, 2. Frequency of informed consent when giving IV tPA in the 3 to 4.5 hour window, 3-6. Frequency excluding patient's from treatment in the 3 to 4.5 hour window for any of the additional exclusionary criteria. Answer options for questions 2-6 included: always, often (>50% of the time), seldom(<50% of the time), and never. The publicly available AHA/ASA online member directory was utilized to identify physicians meeting criteria: Council: Stroke, Specialty: Neuro/Stroke, Count...
Developmental Cognitive Neuroscience of Adolescent Sexual Risk and Alcohol Use

Human adolescents engage in very high rates of unprotected sex. This behavior has a high potential for unintended, serious, and sustained health consequences including HIV/AIDS. Despite these serious health consequences, we know little about the neural and cognitive factors that influence adolescents' decision-making around sex, and their potential overlap with behaviorally co-occurring risk behaviors, including alcohol use. Thus, in this review, we evaluate the developmental neuroscience of sexual risk and alcohol use for human adolescents with an eye to relevant prevention and intervention implications.
Residual Dipolar Couplings: Measurements and Applications to Biomolecular Studies

Since the first successful demonstration of the tunable alignment of ubiquitin in an anisotropic liquid crystal medium only eight years ago, much progress has been made in both nuclear magnetic resonance (NMR) pulse techniques for the measurements of various residual dipolar couplings (RDCs) in both proteins and nucleic acids, and applications of RDCs to many important problems in biochemistry and structural biology. In this annual report, we first review recent developments in NMR techniques for the measurements of many types of RDCs in both proteins and nucleic acids, especially a series of novel techniques for improving spectral resolution, signal-to-noise ratio and saving experimental time. We then describe the applications of RDCs to proteins including automated resonance assignment, structure determination, ligand–protein and protein–protein dockings as well as protein folding.
17β-Hydroxysteroid Dehydrogenase from Human Red Blood Cells

Abstract 17β-Hydroxysteroid dehydrogenase has been isolated from human red cells and purified 740 times. The enzyme is sensitive to ionic strength and is most effective at sodium chloride concentrations of 0.1 m and above. 17β-Estradiol 3-sulfate reacts at a faster rate than 17β-estradiol. The Km for estradiol is 9.1 x 10-5, and for estradiol sulfate it is 3.8 x 10-4. The free compound has a pH optimum of 9.7; the sulfate reacts optimally at pH 9.0. The enzyme is specific for TPN; DPN shows one-sixth to one-tenth as much activity. The Km values for TPN are 2.7 x 10-5 with estradiol and 2.4 x 10-5 with estradiol sulfate. Acetyl-TPN is less active than TPN. Albumin inhibits the reaction, presumably by binding the steroids. Organic solvents also act inhibitorily. The enzyme appears to be of the sulfhydryl type. Enzyme activity was assayed by measurement of TPNH produced and by yield of estrone. Reduction of estrone or its sulfate occurs at slower rates than the corresponding reverse reactions. The molecular weight of the enzyme, calculated from mobility data on Sephadex gel, is approximately 75,500.
Continuous Engineering Course Improvement through Synergistic use of Multiple Assessment

During two terms of a fluid power engineering course, four formative and summative courseassessments, weekly e-mail feedback journals, midterm e-surveys, focus groups, and departmentalstudent evaluation of instruction (SEI) forms, were used to assess student perceptions of theirlearning and the instruction methods used. The weekly e-mail feedback journals and midterme-surveys enabled several course adjustments during each course term. Focus groups were used toexplore students’ perceptions of both the course and the formative assessments. The SEI providedquantitative measures of student satisfaction that correlated with the focus group discussions.Using multiple formative and summative course assessments techniques had a synergistic effect ongaining insights into the teaching-learning process.
Nano scale energetic materials: Theoretical and experimental updates

Recent advances in nanoscience are providing capabilities to fabricate materials with complex molecular patterns using various novel assembly approaches. This talk will summarize our current progress towards developing a framework of principles for design and fabrication of nano-tailored energetic materials for emerging applications. Nanoscale particles have a significantly higher surface area to volume ratio than microparticles, providing a closer contact between solid particles in a mixture.Kinetics of oxidation of metal nanoparticles acquired practical importance with rapidly developing nanoenergetic systems and materials. Nanoenergetic thermites include mixtures of Al and metal oxides in nanoscale. Our research focuses on modeling aluminum combustion in nanoscale. We consider oxidation in the spherically symmetric case, assuming that aluminum particle of radius 10 to 50 nm is covered by a thin oxide layer (1–4nm) and is surrounded by abundant amount of oxygen stored by oxidizers. The particle is rapidly heated up to ignition temperature to initiate self-sustaining oxidation reaction as a result of highly exothermic reaction. We use nonlinear Cabrera-Mott model with a self-consistent electric potential to compute oxidation reaction power (watts), as a function of temperature and oxidized metal proportion. Knowledge of such reaction power together with a self-heating model allows to predict oxidation time and reaction temperature dynamics. We compare modeling of self-heating based on matched experimentally known maximal reaction temperature with a detailed heat transfer model taking into account heat loss due to convection and radiation.
The Bastille day Shock and Merged Interaction Region at 63 au: Voyager 2 Observations

A transient flow system containing several streams and shocks associated with the Bastille Day 2000 solar event was observed by the WIND and ACE spacecraft at 1 AU. Voyager 2 (V2) at 63 AU observed this flow system after it moved through the interplanetary medium and into the distant heliosphere, where the interstellar pickup protons strongly influence the MHD structures and flow dynamics. We discuss the Voyager 2 magnetic and plasma observations of this event. Increases in the magnetic field strength B, density N, temperature T and speed V were observed at the front of a stream at V2, consistent with presence of a shock related to the Bastille Day shock at 1 AU. However, the jumps occurred in a 16.9-hour data gap, so that the shock was not observed directly, and the properties of the candidate shock cannot be determined precisely. The candidate shock was followed by a merged interaction region (MIR) that moved past V2 for at least 10 days. The first part of this MIR contains a structure that might be a magnetic cloud. Just ahead of the shock there was an abrupt increase in density associated with a decrease in temperature such that the solar wind thermal pressure was constant across it. Just behind the shock there was an abrupt decrease in density associated with a net increase in magnetic field strength. This appears to be a pressure balanced structure in which the interstellar pickup protons make a significant contribution.
Studies on busulfan (myleran) treated leukocyte cultures. I. Cytological observations.

Abstract Phytohemagglutinin-stimulated normal human leukocyte cultures were exposed to varying concentrations of Busulfan at the initiation of the cultures or after 24 h incubation. In both instances, chromosome abnormalities and reduced mitotic indices were observed in concentrations ranging from 1.0 to 20.0 μg/ml. The effects appeared proportionate to the drug concentration. Although the principal reactive site of Busulfan may be the nucleic acids, the significance of this drug's interference with other cellular processes cannot be excluded.
Low cost processes for fabricating silicon solar cells

Solar cell fabrication processes, in particular junction formation and metallization, are evaluated in terms of cell efficiencies, process yields, module packing factors, and energy cost effectiveness. It is shown that for junction formation, the diffusion processes provide a relatively low-cost approach. The costs per unit cell area can be further reduced by increased wafer area and mechanized wafer handling. The costs for a large number of metallization processes, excluding the costs of the metal, are roughly comparable. However, their varying influence on cell performance leads to a significant spread in the allowable process costs.
A note on a determinantal inequality

Abstract We estimate the difference of determinants of two square matrices in terms of the norms of their difference.
Third parties in equilibrium: comment and correction

Published in a past issue of this journal, Hug (Public Choice 82:159–180, 1995) studies political competition among three vote-maximizing parties when voters cannot know exactly which policies the parties will adopt when elected. Contrary to what is claimed in Proposition 3, in the generic case the game has no Nash equilibrium in pure strategies. In this case, only a local Nash equilibrium (LNE) may exist, but due to an incorrect second order condition, the conditions in Proposition 3 do not characterize this LNE either.
Acute Vascular Disruption by 5,6-Dimethylxanthenone-4-Acetic Acid in an Orthotopic Model of Human Head and Neck Cancer

The sustenance of most solid tumors including head and neck cancers (HNCs) is strongly dependent on the presence of a functioning vascular network. In this study, we examined the acute effects of a tumor vascular disrupting agent (VDA), 5,6-dimethylxanthenone-4-acetic acid (DMXAA; ASA404), in an orthotopic model of human HNC. Noninvasive magnetic resonance imaging (MRI) was used to monitor the vascular response of orthotopic FaDu xenografts to VDA therapy. Untreated tumors showed a marked but heterogeneous pattern of enhancement after contrast agent injection on serial T1-weighted (T1W) MR images. After VDA treatment, T2W and T1W MRI revealed evidence of hemorrhaging and lack of functioning vessels (enhancement) within the tumor. Quantitative estimates of relative vascular volume also showed a significant ( P + endothelial cells. In sharp contrast, minimal CD31 staining with irregular endothelial fragments and faint outlines of blood vessels were seen in DMXAA-treated tumor sections. CD31 immunostaining and histology also highlighted the selectivity of vascular damage and tissue necrosis after VDA therapy with no evidence of toxicity observed in normal salivary gland, heart, liver, and skeletal muscle tissues. Together, our results demonstrate a potent and selective vascular disruptive activity of DMXAA in an orthotopic HNC model. Further evaluation into its antitumor effects alone and in combination with other agents is warranted.
Microstructural interaction in the wake cohesive zone for small crack-opening displacements

This study examines the role of crack-face bridging microstructural ligaments in alumina subjected to small applied displacements. Quasistatic, monotonic loading studies have been important in the foundation of toughening mechanism characterization, where the critical features are of the order of the grain size. This work, however, reveals the more subtle role of subgrain-size features responsible for degradation of the R-curve by load-cycling in the small-displacement regime. Based on the current results, fatigue-related degradation depends upon damage to features of the order of 0.1 μm, or about 0.5% of the mean grain size. Applied displacements beyond the 0.1 μm critical displacement for this alumina resulted in nonrecoverable displacements.
Simultaneous Measurements of Intracellular [Ca2+]i and [cAMP]i in Intact Islets to Study the Mechanism Underlying Dopaminergic Inhibition of Insulin Secretion

Pancreatic islets secrete multiple hormones, including insulin, that are required to maintain euglycemia while meeting the energy demand of the body during everyday activities. We are interested in understanding the interplay between molecular mechanisms that precisely regulate these secretions. One specific paracrine modulator, dopamine, functions as a negative regulator of insulin secretion in the context of the pancreatic islet. It is secreted by the insulin-producing β-cells, activates an autocrine negative feedback that decreases the frequency of glucose-stimulated [Ca2+]i oscillations, and in turn, inhibits insulin secretion. The G-protein coupled dopamine receptors are present in islet cells, but it is not clear how activation of the these receptors results in the observed changes in [Ca2+]i in intact pancreatic islet cells. We are using an mTurquoise-Based cAMP biosensor with an improved dynamic range (Klarenbeek, J.B., et al., PLoS One, 2011), along with organic and genetically encoded Ca2+-indicator dyes. Labeled cells are studied by live imaging using perfused pancreatic islet. Spectral unmixing is used to extract the fluorescence emissions. This experimental setup allows us to monitor the effect of specific dopamine receptor agonists and antagonists on the two main cellular second messengers. Also, islets from mice with a genetic target mutation of the DRD3 (D3-KO) are used to measure how the deletion of the dopaminergic feedback changes the second messenger dynamics. With the same approach we are measuring the effects of the overexpression of dopamine receptor D3 in wild-type and D3-KO islets. The information from these experiments will help elucidate the mechanism of dopamine signaling in the pancreatic islet.
On the computation of mixed-mode stress intensity factors in functionally graded materials

A new interaction energy integral method for the computation of mixed-mode stress intensity factors at the tips of arbitrarily oriented cracks in functionally graded materials is described. In the method, interaction energy contour integrals are defined and expressed in equivalent domain form. The interaction energy integrals involve products of the actual fields, that arise from solution to the boundary value problem, with known auxiliary fields. The auxiliary stress and displacement fields are chosen to be the asymptotic near-tip fields for a crack in a homogeneous material having the same elastic constants as those found at the crack tip in the functionally graded material. The auxiliary strain fields are obtained from the auxiliary stress fields using the constitutive relation for the functionally graded material. A consequence of our choice for the auxiliary strain field is lack of compatibility which leads to extra terms in the domain integrals that need to be evaluated for the sake of accuracy. The mixed-mode stress intensity factors are obtained from the domain integrals as a post-processing step in the extended finite element method. To assess the accuracy of the method, we consider the benchmark problems of an edge-cracked plate and an angled center crack for specimens with a functional gradient in material properties. Excellent agreement is obtained between the numerical results and the analytical solutions for both stress intensity factors in all cases. All numerical results for the stress intensity factors also exhibit domain independence. The pertinent post-processing routines are provided for download via the world wide web.
Government program impacts on the selection of crop insurance in northeastern Kansas.

The impact of the government commodity program, crop insurance, disaster aid, and optional paid land diversion on net return risk for corn and soybeans is examined. Results indicate that most preferred risk management strategies include crop insurance for corn in northeast Kansas whether disaster aid is available or not. Crop insurance for soybeans is generally not preferred. Participation in the optional paid diversion program is a preferred risk management strategy for extremely risk averse producers. Willingness to pay analysis indicates that moderately and strongly risk averse producers would be willing to pay more for crop insurance when disaster aid and the optional paid land diversion for corn are not available. Risk averse corn producers would be willing to pay more for crop insurance than disaster aid as well.
Antiviral antibody reacting on the plasma membrane alters measles virus expression inside the cell

SOME viruses are known to persist despite a functional antiviral immune response by the host. For example, measles or measles-like viruses can cause persistent infection in man leading to a progressive degenerative disease, subacute sclerosing panencephalitis (SSPE), characterised by unusually high titres of measles virus antibodies in serum and cerebral spinal fluids (see refs 1, 2 for reviews). Peripheral blood lymphocytes specifically responsive to measles virus antigens are generated and lyse target cells expressing virus antigens on their surfaces3,4. Sera from SSPE patients enhance rather than block or suppress immunologically mediated killing3−5. But although this antimeasles virus immune response is vigorous, the virus infection does not terminate because one can detect virus antigens and isolate infectious virus from central nervous system and lymphoid tissues1. To explain this we postulated that antibody to measles virus modulates or strips viral antigens off surfaces of virus infected cells6–7. This contention is based on the finding that specific measles antibody added to cultured infected cells modulate viral antigens on the cells' surfaces6. These cells then express less viral antigens on their surfaces and thereby avoid the host's immune assault. Cells denuded of viral antigens on their surfaces resist antibody and complement-mediated or immune lymphocyte-mediated killing6,7 yet retain viral genetic information6. Further, during antibody modulation in vitro, the numbers of viral nucleocapsids accumulated inside the cell dramatically increase and are positioned randomly6. This in vitro picture closely resembles the distribution of nucleocapsids in cells obtained by biopsy from patients with SSPE1,8,9. Quantitatively, about 10- to 50-fold less antibody is needed on the surfaces of infected cells to modulate viral antigens than is needed to activate the complement system leading to immune lysis of infected cells5,10. To clarify the molecular events occurring during antibody-induced antigenic modulation, we have studied measles virus antibody bound to the surfaces of infected cells and ascertained what alterations occur within these cells. Here we report that measles virus antibodies added to virus infected HeLa cells decrease the content of both viral structural polypeptide haemolysin expressed on the cell surface and a structural polypeptide (measles virus phosphoprotein, P) found inside the cell. These observations indicate that antibody directed against an antigen on the cell surface can interfere with viral proteins expressed inside the cell. Because phosphoprotein seems to form complexes with the nucleocapsid, our findings may offer leads towards understanding viral regulation during persistence. We also note that three measles virus polypeptides—P, nucleocapsid (NC) and matrix protein (M)—are phosphorylated.
Perturbative corrections to the ratio Γ(B → D ρ^-)/ Γ(B → D π^-).

QCD interactions involving a heavy quark with energy much smaller than its mass can be understood in the context of an effective field theory in which the heavy quark velocity is held fixed while its mass is taken to infinity. Nonleptonic decays of hadrons containing a heavy quark further simplify when gluons exchanged carry small momenta compared to the heavy quark mass. Under these assumptions the ratio of rates for B → D ρ^- and B → D π^- is investigated. The reliability of these assumptions is tested by calculating first order, one loop QCD corrections, assuming reasonable momentum distributions for the quarks inside the light mesons.
Central Basin of Appalachian Geosyncline

This paper has for its purpose the summary and critical examination of existing information and opinion relative to the structure and stratigraphy of the central part of the Appalachian geosyncline. The Appalachian geosyncline is made up of three major basins of deposition: (1) a Northern basin with its deepest point near Altoona, Pennsylvania; (2) a Central basin with its deepest point near Elkins, West Virginia; and (3) a Southern basin with its thickest sediments centered near Birmingham, Alabama. This paper is concerned only with the Central basin. Two cross sections, showing sequence, thickness, and areal distribution of the rocks as far as known by drilling, are given. One of these is drawn transverse to the major axis of the Appalachian geosyncline and traverses the deeper part of the Central basin from northwest to southeast. The other roughly parallels the major axis of the Appalachian geosyncline and traverses the west flank of the Central basin from northeast to southwest.
An active sensor algorithm for corn nitrogen recommendations based on a chlorophyll meter algorithm.

In previous research we found active canopy sensor reflectance assessments of corn (Zea mays L.) N status have potential for directing in-season N applications, but emphasized an algorithm was needed to translate sensor readings into appropriate N application (N app ) rates. The objectives of this work were to: (i) develop an active canopy sensor algorithm based on a SPAD chlorophyll meter algorithm and (ii) validate the active canopy sensor algorithm using data collected from a companion study. We derived the sensor algorithm using a linear relationship between sensor sufficiency index (SI sensor ) and SI SPAD values established in the previous research and a published SPAD algorithm employing a quadratic equation to calculate N app as a function of SI SPAD . The resulting equation: N app = 317√0.97-SI sensor represents the function for translating SI sensor to N app . To validate the algorithm, SI sensor values collected from small plots receiving varying N amounts were converted into N app using the algorithm. Then N app was converted into crop N balance (Nb balance estimates, where N balance = applied N-N app . Negative N balance values indicate N deficiency while positive values indicate excess N. The N balance values were compared with relative yields and a quadratic-plateau model fit to the data set for both growth stages (V11 and V15), producing an R 2 of 0.66. Relative yields plateaued at an N balance near zero (-11 kg N ha -1 ), indicating the algorithm provided reasonable estimates of N app for maximizing yields. The equation provides a basis for the use of active crop canopy sensors for in-season N management of irrigated corn.
Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD).

Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes phosphatidylcholine synthesis. PEMT knockout mice have fatty livers, and it is possible that, in humans, nonalcoholic fatty liver disease (NAFLD) might be associated with PEMT gene polymorphisms. DNA samples from 59 humans without fatty liver and from 28 humans with NAFLD were genotyped for a single nucleotide polymorphism in exon 8 of PEMT which leads to a V175M substitution. V175M is a loss of function mutation, as determined by transiently transfecting McArdle-RH7777 cells with constructs of wildtype PEMT open reading frame or the V175M mutant. Met/Met at residue 175 (loss of function SNP) occurred in 67.9% of the NAFLD subjects and in only 40.7% of control subjects (p< 0.03). For the first time we report that a polymorphism of the human PEMT gene (V175M) is associated with diminished activity and may confer susceptibility to NAFLD.
Long-term C-Reactive Protein Variability and Prediction of Metabolic Risk

Abstract Objective This analysis was undertaken to determine the long-term intraindividual variability, determinants of change, and capacity of the inflammatory marker C-reactive protein (CRP) to predict metabolic traits and diabetes in a large community-based population. Methods Intraindividual CRP variability, predictors of CRP change, and metabolic events were evaluated in the Framingham Heart Study Offspring cohort using data from the same 2409 participants with CRP measured by the same methodology at each of 3 examination cycles, spanning 20 years. Results Between the first and second examinations (averaging 16 years apart), 23% to 47% of men and 27% to 49% of women remained within the same quintile of CRP values. An additional 24% to 51% of men and 24% to 50% of women occupied an adjacent quintile. Intermediate-term CRP variability (over 4 years) was similar to long-term variability. Both long- and intermediate-term variability of CRP were significantly less than that of plasma cholesterol measured in these same groups. Linear regression models for CRP at the intermediate examination demonstrated that CRP at the initial examination contributed the largest proportion of the variability (partial R-square = 0.27) seen in the overall model after adjustment for other covariates known to affect CRP concentrations. Although logistic regression models demonstrated that CRP over the intermediate term did not predict new-onset metabolic syndrome at the final examination, CRP did predict an increase in glucose and new-onset diabetes. Conclusion The results of this longitudinal analysis suggest the intraindividual, long-term variability of CRP concentrations is relatively small and predictive of new diabetes over an intermediate-term of 4 years.
The rise and fall of intracellular pH of sea urchin eggs after fertilisation.

JOHNSON et al.1 have reported an increase in the intracellular pH of sea urchin eggs, seen between 1 and 4 min after insemination, that results from the efflux of H+ ions from the cells. The rise in pH can be induced by artificial activators of metabolism such as ammonia, or organic amines such as procaine. They have postulated that this increase in cellular pH is responsible for the metabolic derepression of the eggs and the initiation of embryonic development1,2. Our interest in the control of the initiation of DNA synthesis in these synchronously dividing cells3, coupled with their method1 for estimating the intracellular pH, led us to attempt to determine if fluctuations in pH occur during the cell cycle. Here we confirm the important observation of a rise in pH at fertilisation, and we report that the rise is soon followed by a gradual drop in pH to final values lower than those of the unfertilised condition.