3,675 research outputs found
Noncommutative Mixmaster Cosmologies
In this paper we investigate a variant of the classical mixmaster universe
model of anisotropic cosmology, where the spatial sections are noncommutative
3-tori. We consider ways in which the discrete dynamical system describing the
mixmaster dynamics can be extended to act on the noncommutative torus moduli,
and how the resulting dynamics differs from the classical one, for example, in
the appearance of exotic smooth structures. We discuss properties of the
spectral action, focussing on how the slow-roll inflation potential determined
by the spectral action affects the mixmaster dynamics. We relate the model to
other recent results on spectral action computation and we identify other
physical contexts in which this model may be relevant.Comment: 24 pages LaTe
Asymptotic safety, hypergeometric functions, and the Higgs mass in spectral action models
We study the renormalization group flow for the Higgs self coupling in the
presence of gravitational correction terms. We show that the resulting equation
is equivalent to a singular linear ODE, which has explicit solutions in terms
of hypergeometric functions. We discuss the implications of this model with
gravitational corrections on the Higgs mass estimates in particle physics
models based on the spectral action functional.Comment: 25 pages, LaTeX, 8 PDF figure
Erythrocytes from GGTA1/CMAH knockout pigs: implications for xenotransfusion and testing in non-human primates
Background
Pig erythrocytes are potentially useful to solve the worldwide shortage of human blood for transfusion. Domestic pig erythrocytes, however, express antigens that are bound by human preformed antibodies. Advances in genetic engineering have made it possible to rapidly knock out the genes of multiple xenoantigens, namely galactose α1,3 galactose (aGal) and N-glycolylneuraminic acid (Neu5Gc). We have recently targeted the GGTA1 and CMAH genes with zinc finger endonucleases resulting in double knockout pigs that no longer express aGal or Neu5Gc and attract significantly fewer human antibodies. In this study, we characterized erythrocytes from domestic and genetically modified pigs, baboons, chimpanzees, and humans for binding of human and baboon natural antibody, and complement mediated lysis.
Methods
Distribution of anti Neu5Gc IgG and IgM in pooled human AB serum was analyzed by ELISA. Erythrocytes from domestic pigs (Dom), aGal knockout pigs (GGTA1 KO), aGal and Neu5Gc double knockout pigs (GGTA1/CMAH KO), baboons, chimpanzees, and humans were analyzed by flow cytometry for aGal and Neu5Gc expression. In vitro comparative analysis of erythrocytes was conducted with pooled human AB serum and baboon serum. Total antibody binding was accessed by hemagglutination; complement-dependent lysis was measured by hemolytic assay; IgG or IgM binding to erythrocytes was characterized by flow cytometry.
Results
The pooled human AB serum contained 0.38 μg/ml anti Neu5Gc IgG and 0.085 μg/ml anti Neu5Gc IgM. Both Gal and Neu5Gc were not detectable on GGTA1/CMAH KO erythrocytes. Hemagglutinaion of GGTA1/CMAH KO erythrocytes with human serum was 3.5-fold lower compared to GGTA1 KO erythrocytes, but 1.6-fold greater when agglutinated with baboon serum. Hemolysis of GGTA1/CMAH KO erythrocytes by human serum (25%) was reduced 9-fold compared to GGTA1 KO erythrocytes, but increased 1.64-fold by baboon serum. Human IgG binding was reduced 27-fold on GGTA1/CMAH KO erythrocytes compared to GGTA1 KO erythrocytes, but markedly increased 3-fold by baboon serum IgG. Human IgM binding was decreased 227-fold on GGTA1/CMAH KO erythrocytes compared to GGTA1 KO erythrocytes, but enhanced 5-fold by baboon serum IgM.
Conclusions
Removal of aGal and Neu5Gc antigens from pig erythrocytes significantly reduced human preformed antibody-mediated cytotoxicity but may have complicated future in vivo analysis by enhancing reactivity from baboons. The creation of the GGTA1/CMAH KO pig has provided the xenotransplantion researcher with organs and cells that attract fewer human antibodies than baboon and our closest primate relative, chimpanzee. These finding suggest that while GGTA1/CMAH KO erythrocytes may be useful for human transfusions, in vivo testing in the baboon may not provide a direct transplation to the clinic
N-linked glycan profiling of GGTA1/CMAH knockout pigs identifies new potential carbohydrate xenoantigens
BACKGROUND:
The temporary or long-term xenotransplantation of pig organs into people would save thousands of lives each year if not for the robust human antibody response to pig carbohydrates. Genetically engineered pigs deficient in galactose α1,3 galactose (gene modified: GGTA1) and N-glycolylneuraminic acid (gene modified: CMAH) have significantly improved cell survival when challenged by human antibody and complement in vitro. There remains, however, a significant portion of human antibody binding.
METHODS:
To uncover additional xenoantigens, we compared the asparagine-linked (N-linked) glycome from serum proteins of humans, domestic pigs, GGTA1 knockout pigs, and GGTA1/CMAH knockout pigs using mass spectrometry. Carbohydrate structures were determined with assistance from GlycoWorkbench, Cartoonist, and SimGlycan software by comparison to existing database entries and collision-induced dissociation fragmentation data.
RESULTS:
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of reduced and solid-phase permethylated glycans resulted in the detection of high-mannose, hybrid, and complex type N-linked glycans in the 1000-4500 m/z ion range. GGTA1/CMAH knockout pig samples had increased relative amounts of high-mannose, incomplete, and xylosylated N-linked glycans. All pig samples had significantly higher amounts of core and possibly antennae fucosylation.
CONCLUSIONS:
We provide for the first time a comparison of the serum protein glycomes of the human, domestic pig, and genetically modified pigs important to xenotransplantation
Caboclos of Nazareth: Improvisation and Renovation in Maracatu de Baque Solto of Pernambuco.
This dissertation looks at an expressive musical-poetic form that has developed over the last hundred years, maracatu de baque solto of Pernambuco, but which has only recently begun to receive critical attention. Featuring poetic duels between poet-singers (or mestres) of different groups, maracatu draws on a variety of regional musical genres while also engaging creatively with mass-mediated cultural production. Maracatus organize performances in their local neighborhoods, present in neighboring towns and cities during Carnival, and participate in large festival productions. Based on three years of ethnographic and historical fieldwork in and around the town of Nazaré da Mata from 2009 to 2012, the dissertation looks at different understandings of authenticity and the dynamic relationship between modernity and tradition as articulated differently within maracatu and by its intermediaries. In exploring how the expressive genre of maracatu continues to develop, I examine how cultural identities and practices can shift, calcify, or transform over time in relation to socioeconomic change, political developments, or interaction with other social groups. Since its “discovery” by elite artists, researchers, and funding institutions, the emphasis on maracatu’s rural identity and origins on the sugar plantations has often minimized or obscured its subsequent development by generations of working-class practitioners in the urban and semi-urban peripheries since the rural exodus of the middle twentieth century. Institutional frameworks created by folklore research and elite intellectual production about popular culture have shaped the ways in which maracatu eventually achieved recognition among a broader public in Pernambuco as well as other regions of Brazil.
My research touches upon the strengths and limits of cultura popular as a form of resistance by exploring how elite interventions and popular practices have become entwined. I develop the idea of coronelismo cultural, or “cultural boss-ism,” as a way of analyzing how maracatu has developed within the persisting structures of patronage and domination that are strongly rooted in the region’s history.
As maracatu is only sparsely represented in the academic literature, it is hoped that this dissertation will contribute to our understanding of similar expressive forms elsewhere in Latin America and the Caribbean.PhDAnthropology and HistoryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111558/1/cestrad_1.pd
Viral and bacterial septicaemic infections modulate the expression of PACAP splicing variants and VIP/PACAP receptors in brown trout immune organs
Copyright © 2015. Published by Elsevier Ltd. Acknowledgements The authors thank Richard Paley, Georgina Rimmer and Tom Hill for their contribution during the brown trout infection challenges carried out in CEFAS-Weymouth biosecurity facilities. Bartolomeo Gorgoglione and Nick G. H. Taylor were supported by a DEFRA contract C3490Peer reviewedPostprin
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Population History and Gene Divergence in Native Mexicans Inferred from 76 Human Exomes.
Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico's Indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five Indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of Indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 KYA and subsequently diverging locally 6.5 and 5.7 KYA, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern Indigenous group from Oaxaca whose height is extremely low compared to other Native populations
Deposition, Accumulation, and Alteration of Cl(-), NO3(-), ClO4(-) and ClO3(-) Salts in a Hyper-Arid Polar Environment: Mass Balance and Isotopic Constraints
The salt fraction in permafrost soils/sediments of the McMurdo Dry Valleys (MDV) of Antarctica can be used as a proxy for cold desert geochemical processes and paleoclimate reconstruction. Previous analyses of the salt fraction in MDV permafrost soils have largely been conducted in coastal regions where permafrost soils are variably affected by aqueous processes and mixed inputs from marine and stratospheric sources. We expand upon this work by evaluating permafrost soil/sediments in University Valley, located in the ultraxerous zone where both liquid water transport and marine influences are minimal. We determined the abundances of Cl(-), NO3(-, ClO4(-)and ClO3(-)in dry and ice-cemented soil/sediments, snow and glacier ice, and also characterized Cl(-) and NO3(-) isotopically. The data are not consistent with salt deposition in a sublimation till, nor with nuclear weapon testing fall-out, and instead point to a dominantly stratospheric source and to varying degrees of post depositional transformation depending on the substrate, from minimal alteration in bare soils to significant alteration (photodegradation and/or volatilization) in snow and glacier ice. Ionic abundances in the dry permafrost layer indicate limited vertical transport under the current climate conditions, likely due to percolation of snowmelt. Subtle changes in ClO4(-)/NO3(-) ratios and NO3(-) isotopic composition with depth and location may reflect both transport related fractionation and depositional history. Low molar ratios of ClO3(-)/ClO4(-) in surface soils compared to deposition and other arid systems suggest significant post depositional loss of ClO3(-), possibly due to reduction by iron minerals, which may have important implications for oxy-chlorine species on Mars. Salt accumulation varies with distance along the valley and apparent accumulation times based on multiple methods range from approximately 10 to 30 kyr near the glacier to 70-200 kyr near the valley mouth. The relatively young age of the salts and relatively low and homogeneous anion concentrations in the ice-cemented sediments point to either a mechanism of recent salt removal, or to relatively modern permafrost soils (less than 1 million years). Together, our results show that near surface salts in University Valley serve as an end-member of stratospheric sources not subject to biological processes or extensive remobilization
A Naturally Narrow Positive Parity Theta^+
We present a consistent color-flavor-spin-orbital wave function for a
positive parity Theta^+ that naturally explains the observed narrowness of the
state. The wave function is totally symmetric in its flavor-spin part and
totally antisymmetric in its color-orbital part. If flavor-spin interactions
dominate, this wave function renders the positive parity Theta^+ lighter than
its negative parity counterpart. We consider decays of the Theta^+ and compute
the overlap of this state with the kinematically allowed final states. Our
results are numerically small. We note that dynamical correlations between
quarks are not necessary to obtain narrow pentaquark widths.Comment: 10 pages, 1 figure, Revtex4, two-column format, version to be
published in Phys. Rev. D, includes numerical estimates of decay width
Spitzer Space Telescope Measurements of Dust Reverberation Lags in the Seyfert 1 Galaxy NGC 6418
We present results from a fifteen-month campaign of high-cadence (~ 3 days)
mid-infrared Spitzer and optical (B and V ) monitoring of the Seyfert 1 galaxy
NGC 6418, with the objective of determining the characteristic size of the
dusty torus in this active galactic nucleus (AGN). We find that the 3.6 m
and 4.5 m flux variations lag behind those of the optical continuum by
days and days, respectively. We
report a cross-correlation time lag between the 4.5 m and 3.6 m flux
of days. The lags indicate that the dust emitting at 3.6
m and 4.5 m is located at a distance of approximately 1 light-month
(~ 0.03 pc) from the source of the AGN UV-optical continuum. The reverberation
radii are consistent with the inferred lower limit to the sublimation radius
for pure graphite grains at 1800 K, but smaller by a factor of ~ 2 than the
corresponding lower limit for silicate grains; this is similar to what has been
found for near-infrared (K-band) lags in other AGN. The 3.6 and 4.5 m
reverberation radii fall above the K-band
size-luminosity relationship by factors and ,
respectively, while the 4.5 m reverberation radius is only 27% larger than
the 3.6 m radius. This is broadly consistent with clumpy torus models, in
which individual optically thick clouds emit strongly over a broad wavelength
range.Comment: 13 pages, 9 figure
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