bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity
Authors: Neeland Melanie R. , Elhay Martin J. , Nathanielsz Jackie , Meeusen Els N. T. , de Veer Michael J. 
Published: March 2014

Abstract
Liposomal vaccine formulations incorporating stimulants that target innate immune receptors have been shown to significantly increase vaccine immunity. Following vaccination, innate cell populations respond to immune stimuli, phagocytose and process Ag, and migrate from the injection site, via the afferent lymphatic vessels, into the local lymph node. In this study, the signals received in the periphery promote and sculpt the adaptive immune response. Effector lymphocytes then leave the lymph node via the efferent lymphatic vessel to perform their systemic function. We have directly cannulated the ovine lymphatic vessels to detail the in vivo innate and adaptive immune responses occurring in the local draining lymphatic network following vaccination with a liposome-based delivery system incorporating CpG. We show that CpG induces the rapid recruitment of neutrophils, enhances dendritic cell–associated Ag transport, and influences the maturation of innate cells entering the afferent lymph. This translated into an extended period of lymph node shutdown, the induction of IFN-γ–positive T cells, and enhanced production of Ag-specific Abs. Taken together, the results of this study quantify the real-time in vivo kinetics of the immune response in a large animal model after vaccination of a dose comparable to that administered to humans. This study details enhancement of numerous immune mechanisms that provide an explanation for the immunogenic function of CpG when employed as an adjuvant within vaccines.
Myeloid-Derived Suppressor Cells Contribute to Staphylococcus aureus Orthopedic Biofilm Infection
Authors: Heim Cortney E. , Vidlak Debbie , Scherr Tyler D. , Kozel Jessica A. , Holzapfel Melissa , Muirhead David E. , Kielian Tammy 
Published: March 2014

Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes that are potent inhibitors of T cell activation. A role for MDSCs in bacterial infections has only recently emerged, and nothing is known about MDSC function in the context of Staphylococcus aureus infection. Because S. aureus biofilms are capable of subverting immune-mediated clearance, we examined whether MDSCs could play a role in this process. CD11b+Gr-1+ MDSCs represented the main cellular infiltrate during S. aureus orthopedic biofilm infection, accounting for &gt;75% of the CD45+ population. Biofilm-associated MDSCs inhibited T cell proliferation and cytokine production, which correlated with a paucity of T cell infiltrates at the infection site. Analysis of FACS-purified MDSCs recovered from S. aureus biofilms revealed increased arginase-1, inducible NO synthase, and IL-10 expression, key mediators of MDSC suppressive activity. Targeted depletion of MDSCs and neutrophils using the mAb 1A8 (anti-Ly6G) improved bacterial clearance by enhancing the intrinsic proinflammatory attributes of infiltrating monocytes and macrophages. Furthermore, the ability of monocytes/macrophages to promote biofilm clearance in the absence of MDSC action was revealed with RB6-C85 (anti–Gr-1 or anti-Ly6G/Ly6C) administration, which resulted in significantly increased S. aureus burdens both locally and in the periphery, because effector Ly 6C monocytes and, by extension, mature macrophages were also depleted. Collectively, these results demonstrate that MDSCs are key contributors to the chronicity of S. aureus biofilm infection, as their immunosuppressive function prevents monocyte/macrophage proinflammatory activity, which facilitates biofilm persistence.
Polymicrobial Sepsis Alters Antigen-Dependent and -Independent Memory CD8 T Cell Functions
Authors: Duong Sean , Condotta Stephanie A. , Rai Deepa , Martin Matthew D. , Griffith Thomas S. , Badovinac Vladimir P. 
Published: March 2014

Abstract
Mortality from sepsis frequently results from secondary infections, and the extent to which sepsis affects pathogen-specific memory CD8 T cell responses remains unknown. Using the cecal ligation and puncture model of polymicrobial sepsis, we observed rapid apoptosis of pre-existing memory CD8 T cells after sepsis induction that led to a loss in CD8 T cell–mediated protection. Ag sensitivity (functional avidity) and Ag-driven secondary expansion of memory CD8 T cells were decreased after sepsis, further contributing to the observed loss in CD8 T cell–mediated immunity. Moreover, Ag-independent bystander activation of memory CD8 T cells in response to heterologous infection was also significantly impaired early after sepsis induction. The reduced sensitivity of pre-existing memory CD8 T cells to sense inflammation and respond to heterologous infection by IFN-γ production was observed in inbred and outbred hosts and controlled by extrinsic (but not cell-intrinsic) factors, suggesting that sepsis-induced changes in the environment regulate innate functions of memory CD8 T cells. Taken together, the data in this study revealed a previously unappreciated role of sepsis in shaping the quantity and functionality of infection- or vaccine-induced memory CD8 T cells and will help further define the decline in T cell–mediated immunity during the sepsis-induced phase of immunosuppression.
Multimarginal Optimal Transport Maps for One–dimensional Repulsive Costs
Authors: Colombo Maria , De Pascale Luigi , Di Marino Simone 
Published: March 2014

AbstractWe study a multimarginal optimal transportation problem in one dimension. For a symmetric, repulsive cost function, we show that, given a minimizing transport plan, its symmetrization is induced by a cyclical map, and that the symmetric optimal plan is unique. The class of costs that we consider includes, in particular, the Coulomb cost, whose optimal transport problem is strictly related to the strong interaction limit of Density Functional Theory. In this last setting, our result justifies some qualitative properties of the potentials observed in numerical experiments.
Understanding Resident Learning Preferences Within an Internal Medicine Noon Conference Lecture Series: A Qualitative Study
Authors: Sawatsky Adam P. , Zickmund Susan L. , Berlacher Kathryn , Lesky Dan , Granieri Rosanne 
Published: March 2014

Abstract

Background
The lecture remains the most common approach for didactic offerings in residency programs despite conflicting evidence about the effectiveness of this format.

Objective
The purpose of this study was to explore the perspectives of internal medicine residents toward conferences held in the lecture format.

Methods
The investigators invited internal medicine residents (N  =  144) to participate in focus groups discussing their perspectives about noon conference lectures. The investigators used a semistructured guide to ask about motivations for attendance and effectiveness of noon conferences, transcribed the recordings, coded the discussions, and analyzed the results.

Results
Seven focus groups with a total of 41 residents were held. This identified 4 major domains: (1) motivations for attendance; (2) appropriate content; (3) effective teaching methods; and (4) perspectives on active participation. Residents' motivations were categorized into external factors, including desire for a break and balance to their workload, and intrinsic attributes, including the learning opportunity, topic, and speaker. Appropriate content was described as clinically relevant, practical, and presenting a balance of evidence. Identified effective teaching methods included shorter teaching sessions focused on high-yield learning points structured around cases and questions. While active participation increases residents' perceived level of stress, the benefits of this format include increased attention and learning.

Conclusions
This study furthers our knowledge of the learning preferences of internal medicine residents within the changing environment of residency education and can be used in conjunction with principles of adult learning to reform how we deliver core medical knowledge.
Effects of Potential Federal Funding Cuts on Graduate Medical Education: Results of a Survey of Designated Institutional Officials
Authors: Holt Kathleen D. , Miller Rebecca S. , Philibert Ingrid , Nasca Thomas J. 
Published: March 2014

Abstract

Background
Proposed reductions in federal funding for physician education may affect the United States' ability to produce the number of physicians needed to provide care.

Objective
Using a survey similar to that used by the ACGME in 2011, we assessed designated institutional officials' (DIOs) perceptions of the impact of potential GME funding reductions.

Method
In August 2013, we sent a survey link to all DIOs of ACGME-accredited institutions (N  =  678). A 9-item survey asked how future federal funding would affect the number of residency programs in their institutions under 4 different funding scenarios: stable funding, and reductions of 10%, 33%, and 50%. We also asked about changes in the number of residency positions during the last 2 years.

Results
The response rate was 47.9% (325 of 678 DIOs); respondents represent 58.9% of accredited institutions with more than 1 program. Most respondents reported no change or an increase under the stable funding scenario. Under a 33% funding reduction, an estimated 17 379 (14.8% of all current) positions would be lost, and a 50% reduction would result in a loss of 33 562 positions (28.6%). Primary care specialties (eg, family medicine, internal medicine) would be most affected under the greatest funding reductions.

Conclusions
The findings of the 2013 survey are consistent with 2011 data, with DIOs projecting significant reductions in programs and positions under more severe budget cuts. DIO comments highlighted reduced optimism (compared to data obtained in 2011) about the effect of funding cuts and concerns about the impact of reductions on patient care and health care personnel at teaching institutions.
Concise Review: Pluripotent Stem Cell-Based Regenerative Applications for Failing β-Cell Function
Authors: Holditch Sara J. , Terzic Andre , Ikeda Yasuhiro 
Published: March 2014

Abstract
Diabetes engenders the loss of pancreatic β-cell mass and/or function, resulting in insulin deficiency relative to the metabolic needs of the body. Diabetic care has traditionally relied on pharmacotherapy, exemplified by insulin replacement to target peripheral actions of the hormone. With growing understanding of the pathogenesis of diabetic disease, alternative approaches aiming at repair and restoration of failing β-cell function are increasingly considered as complements to current diabetes therapy regimens. To this end, emphasis is placed on transplantation of exogenous pancreas/islets or artificial islets, enhanced proliferation and maturation of endogenous β cells, prevention of β-cell loss, or fortified renewal of β-like-cell populations from stem cell pools and non-β-cell sources. In light of emerging clinical experiences with human embryonic stem cells and approval of the first in-human trial with induced pluripotent stem cells, in this study we highlight advances in β-cell regeneration strategies with a focus on pluripotent stem cell platforms in the context of translational applications.
Human Finger-Prick Induced Pluripotent Stem Cells Facilitate the Development of Stem Cell Banking
Authors: Tan Hong-Kee , Toh Cheng-Xu Delon , Ma Dongrui , Yang Binxia , Liu Tong Ming , Lu Jun , Wong Chee-Wai , Tan Tze-Kai , Li Hu , Syn Christopher , Tan Eng-Lee , Lim Bing , Lim Yoon-Pin , Cook Stuart A. , Loh Yuin-Han 
Published: March 2014

Abstract
Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a “do-it-yourself” basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide.
E region radar echoes from low‐latitude field‐aligned irregularities due to gravity waves and tides: A case study using radar, lidar, and radiosonde observations and simulations
Authors: Sridharan S. , Sandhya M. 
Published: March 2014

AbstractOn the night of 5 February 2011, the height‐time plot of echo from E region field‐aligned irregularities (FAI) received by the Indian mesosphere‐stratosphere‐troposphere radar at Gadanki (13.5°N, 79.2°E) shows a slow‐descending layered structures separated by nearly 8 km in the height region 80–100 km and vertically elongated structures with quasiperiodic variations at higher heights. The stratospheric thermal structure also shows similar slowly descending structures with nearly 8 km separation. Hodograph of 7–9 km band‐pass filtered radiosonde zonal and meridional winds over Gadanki form clearly an ellipse, and the dominant period obtained from the ratio of major to minor axes of the ellipse is nearly 24 h indicating the presence of a nonmigrating diurnal tide with vertical wavelength of 8 km. The two‐dimensional spectrum of temperature perturbations, which are assumed to be due to gravity waves, shows dominant periods near 1 h and 1.5 h. The spectrum of FAI echo also shows similar dominant periods. Altitude‐time cross section of vertical ion velocity is computed using winds composed of observed gravity wave and tidal parameters. As the diurnal tide over Tirunelveli (8.7°N, 77.8°E) shows weaker amplitudes above 90 km, the removal of tidal contribution clearly reveals the observed FAI echo structure of vertically slanting plasma blob structures at higher heights and slowly descending continuous structures separated by 8 km at lower heights. The present study clearly demonstrates the role of tides and gravity waves in the formation of descending echo structures and quasiperiodic echoes respectively.
Direct calculation of the ring current distribution and magnetic structure seen by Cluster during geomagnetic storms
Authors: Shen C. , Yang Y. Y. , Rong Z. J. , Li X. , Dunlop M. , Carr C. M. , Liu Z. X. , Baker D. N. , Chen Z. Q. , Ji Y. , Zeng G. 
Published: March 2014

AbstractMagnetic disturbances caused by the Earth's ring current, particularly during storm time activity, have a dominant effect on the geomagnetic field. Strong currents and large kinetic and magnetic energies can change considerably local field geometry and depress the ground geomagnetic field. The multispacecraft magnetic measurements of Cluster allow extensive in situ coverage of the ring current. We select 48 storm time Cluster crossing events to investigate the variation of the local current density distribution and magnetic configuration of the ring current. We find direct evidence for the existence of an inner, eastward flowing current in addition to the dominant westward current, in the ring plane. The radius of curvature of the magnetic field lines (MFLs) is found to be increasingly reduced at all local times during increasing storm activity, changing the resulting ring current magnetic geometry considerably, where the MFL configuration and the azimuthal current density distribution are asymmetric with the local time. During similar storm activity the radius of curvature of the local MFLs, Rc, is smallest on the nightside to duskside, medium on the dawnside, and largest on the dayside. This change in geometry may have significant influence on the spatial distribution of the particles with various energies in the plasmasphere, ring current, and radiation belts.
The location of magnetic reconnection at Saturn's magnetopause: A comparison with Earth
Authors: Fuselier S. A. , Frahm R. , Lewis W. S. , Masters A. , Mukherjee J. , Petrinec S. M. , Sillanpaa I. J. 
Published: March 2014

AbstractData from the Cassini Electron Spectrometer are used to investigate the location of magnetic reconnection at Saturn's magnetopause. Heated, streaming electron distributions in the boundary layer on the magnetosheath side of the magnetopause are evidence of reconnection and an open magnetopause. A model for the location of reconnection is used to compare the modeled and observed streaming direction of the heated electron distributions. Magnetic reconnection at Saturn's magnetopause is predicted and observed to occur at locations similar to those at Earth's magnetopause. Although not conclusive, the results here are consistent with the expected importance of X‐line drifts in suppressing low‐shear reconnection. Because of different conditions at Saturn's magnetopause, this suppression is predicted to be more severe at Saturn than at Earth.
Pn anisotropy in Mesozoic western Pacific lithosphere
Authors: Shintaku Natsumi , Forsyth Donald W. , Hajewski Christina J. , Weeraratne Dayanthie S. 
Published: March 2014

AbstractPn is the high‐frequency, scattered P phase guided for great distances within the old oceanic lithosphere. Two arrays of ocean bottom seismometers were deployed on old (150–160 Ma) seafloor in the northwestern Pacific south of Shatsky Rise for the Pacific Lithosphere Anisotropy and Thickness Experiment. We use Pn phases from 403 earthquakes during the 1 year of deployment to measure apparent velocities across the arrays. Each array was deployed on a separate limb of a magnetic bight, formed near a fast‐spreading, ridge‐ridge‐ridge triple junction. Using high‐frequency waves (5–10 Hz), we look at variations of Pn velocities as a function of azimuth. In the western array, we find Pn anisotropy with velocities ranging from ~8.7 km/s in the back azimuth (θ) direction of 310° to ~7.7 km/s at ~350°. In the eastern array, the velocity ranges from ~8.5 km/s in back azimuth direction of ~210° to ~7.7 km/s at 260° and ~310°. We observe rapid velocity changes with azimuth in the both arrays requiring sinusoidal variations of roughly equal amplitude as a function of both 2θ and 4θ, which is not expected for the orthorhombic symmetry of olivine or orthopyroxene. The fastest directions on the two limbs are roughly orthogonal to each other suggesting the dominance of fossil anisotropy, but the fast directions of the 2θ components are skewed counterclockwise from the spreading directions. We speculate that the rapid azimuthal variations may be caused by vertical stratification with changing anisotropy with depth in the oceanic lithosphere.
Active tectonics and earthquake potential of the Myanmar region
Authors: Wang Yu , Sieh Kerry , Tun Soe Thura , Lai Kuang‐Yin , Myint Than 
Published: March 2014

AbstractThis paper describes geomorphologic evidence for the principal neotectonic features of Myanmar and its immediate surroundings. We combine this evidence with published structural, geodetic, and seismic data to present an overview of the active tectonic architecture of the region and its seismic potential. Three tectonic systems accommodate oblique collision of the Indian plate with Southeast Asia and extrusion of Asian territory around the eastern syntaxis of the Himalayan mountain range. Subduction and collision associated with the Sunda megathrust beneath and within the Indoburman range and Naga Hills accommodate most of the shortening across the transpressional plate boundary. The Sagaing fault system is the predominant locus of dextral motion associated with the northward translation of India. Left‐lateral faults of the northern Shan Plateau, northern Laos, Thailand, and southern China facilitate extrusion of rocks around the eastern syntaxis of the Himalaya. All of these systems have produced major earthquakes within recorded history and continue to present major seismic hazards in the region.
Postseismic pressure solution creep: Evidence and time‐dependent change from dynamic indenting experiments
Authors: Gratier Jean Pierre , Renard François , Vial Benjamin 
Published: March 2014

AbstractActive faults in the Earth's upper crust can slide either steadily by aseismic creep or abruptly causing earthquakes. Seismic and aseismic processes are closely related: earthquakes are often followed by transient afterslip creep. Postseismic displacement rates progressively decrease with time over a period of years or decades. So seismic fracturing activates the creep rate, and various healing processes progressively reduce it. This article presents pressure solution indenter experiments on halite, calcite, and plaster that show how fracturing and comminution processes induced by dynamic stress loading (applied by dropping steel balls) drastically accelerate the displacement rates accommodated by pressure solution creep by decreasing the dissolution contact area and the diffusive mass transfer distance along this contact. However, as fractures progressively heal and dissolution contacts flatten, these effects disappear, and the displacement rates slow down. The time‐dependent change in indenter displacement after dynamic stress loading has been measured and is best fitted by power laws with exponents that change with time from 0.3 to 1 when healing is achieved. Natural postseismic (afterslip) displacement/time relationships have been analyzed and also show a power law change with a power law exponent in the range of 0.25–0.4. It is proposed that the variation in power law exponent with time is related to the change in morphology of the dissolution contact that is fractured or comminuted during the dynamic event and is then progressively healed and smoothed. In natural faults, monitoring the power law parameters could give access to the characteristic healing time in the fault.
Equations of state in the Fe‐FeSi system at high pressures and temperatures
Authors: Fischer Rebecca A. , Campbell Andrew J. , Caracas Razvan , Reaman Daniel M. , Heinz Dion L. , Dera Przemyslaw , Prakapenka Vitali B. 
Published: March 2014

AbstractEarth's core is an iron‐rich alloy containing several weight percent of light element(s), possibly including silicon. Therefore, the high pressure‐temperature equations of state of iron‐silicon alloys can provide understanding of the properties of Earth's core. We performed X‐ray diffraction experiments using laser‐heated diamond anvil cells to achieve simultaneous high pressures and temperatures, up to ~200 GPa for Fe–9 wt % Si alloy and ~145 GPa for stoichiometric FeSi. We determined equations of state of the D03, hcp + B2, and hcp phases of Fe–9Si, and the B20 and B2 phases of FeSi. We also calculated equations of state of Fe, Fe11Si, Fe5Si, Fe3Si, and FeSi using ab initio methods, finding that iron and silicon atoms have similar volumes at high pressures. By comparing our experimentally determined equations of state to the observed core density deficit, we find that the maximum amount of silicon in the outer core is ~11 wt %, while the maximum amount in the inner core is 6–8 wt %, for a purely Fe‐Si‐Ni core. Bulk sound speeds predicted from our equations of state also match those of the inner and outer core for similar ranges of compositions. We find a compositional contrast between the inner and outer core of 3.5–5.6 wt % silicon, depending on the seismological model used. Theoretical and experimental equations of state agree at high pressures. We find a good match to the observed density, density profile, and sound speed of the Earth's core, suggesting that silicon is a viable candidate for the dominant light element.