376 research outputs found
Statistischer Uberblick uber die innerhalb der letzten neun Jahre in der dermato-urologischen Universitats-Klinik zu Okayama beobachteten urologischen Falle
Es sind, kurz gefasst, 4911 verschiedene urologische Falle, im Laufe der letzten Jahre zur Beobachtung kamen, statistisch bearbeitet worden. Darunter befinden sich 4291 Fa1le, also 87.4%, mannlichen und 620, d .h 12.6%, weiblichen Geschlechts. Diese samtlichen Fallen sind in sieben Kategorien und ferner je nach den befallenen Organen wieder in verschiedene Unterabteilungen zusammengestellt worden. Hier sei nochmals betont, dass bei kombinierter Krankheit nur die Haupterkrankung angefdhrt wurde. </p
Dark Radiation and Dark Matter in Large Volume Compactifications
We argue that dark radiation is naturally generated from the decay of the
overall volume modulus in the LARGE volume scenario. We consider both
sequestered and non-sequestered cases, and find that the axionic superpartner
of the modulus is produced by the modulus decay and it can account for the dark
radiation suggested by observations, while the modulus decay through the
Giudice-Masiero term gives the dominant contribution to the total decay rate.
In the sequestered case, the lightest supersymmetric particles produced by the
modulus decay can naturally account for the observed dark matter density. In
the non-sequestered case, on the other hand, the supersymmetric particles are
not produced by the modulus decay, since the soft masses are of order the heavy
gravitino mass. The QCD axion will then be a plausible dark matter candidate.Comment: 27 pages, 4 figures; version 3: version published in JHE
Probing the Inhibitor versus Chaperone Properties of sp2-Iminosugars towards Human β-Glucocerebrosidase: A Picomolar Chaperone for Gaucher Disease
A series of sp2-iminosugar glycomimetics differing in the reducing or nonreducing character, the configurational pattern (d-gluco or l-ido), the architecture of the glycone skeleton, and the nature of the nonglycone substituent has been synthesized and assayed for their inhibition properties towards commercial glycosidases. On the basis of their affinity and selectivity towards GH1 β-glucosidases, reducing and nonreducing bicyclic derivatives having a hydroxylation profile of structural complementarity with d-glucose and incorporating an N′-octyl-isourea or -isothiourea segment were selected for further evaluation of their inhibitory/chaperoning potential against human glucocerebrosidase (GCase). The 1-deoxynojirimycin (DNJ)-related nonreducing conjugates behaved as stronger GCase inhibitors than the reducing counterparts and exhibited potent chaperoning capabilities in Gaucher fibroblasts hosting the neuronopathic G188S/G183W mutation, the isothiourea derivative being indeed one of the most efficient chaperone candidates reported up to date (70% activity enhancement at 20 pM). At their optimal concentration, the four selected compounds promoted mutant GCase activity enhancements over 3-fold; yet, the inhibitor/chaperoning balance became unfavorable at much lower concentration for nonreducing as compared to reducing derivatives.España Ministerio de EconomĂa y Competitividad (contract numbers CTQ2015-64425-C2-1-R and SAF2016-76083-R)Junta de AndalucĂa contract number FQM2012-146
Probing the Inhibitor versus Chaperone Properties of sp2-Iminosugars towards Human -Glucocerebrosidase: A Picomolar Chaperone for Gaucher Disease
A series of sp2-iminosugar glycomimetics differing in the reducing or nonreducing character, the configurational pattern (d-gluco or l-ido), the architecture of the glycone skeleton, and the nature of the nonglycone substituent has been synthesized and assayed for their inhibition properties towards commercial glycosidases. On the basis of their affinity and selectivity towards GH1 β-glucosidases, reducing and nonreducing bicyclic derivatives having a hydroxylation profile of structural complementarity with d-glucose and incorporating an N′-octyl-isourea or -isothiourea segment were selected for further evaluation of their inhibitory/chaperoning potential against human glucocerebrosidase (GCase). The 1-deoxynojirimycin (DNJ)-related nonreducing conjugates behaved as stronger GCase inhibitors than the reducing counterparts and exhibited potent chaperoning capabilities in Gaucher fibroblasts hosting the neuronopathic G188S/G183W mutation, the isothiourea derivative being indeed one of the most efficient chaperone candidates reported up to date (70% activity enhancement at 20 pM). At their optimal concentration, the four selected compounds promoted mutant GCase activity enhancements over 3-fold; yet, the inhibitor/chaperoning balance became unfavorable at much lower concentration for nonreducing as compared to reducing derivatives.Ministerio de EconomĂa y Competitividad CTQ2015-64425-C2-1-R , SAF2016-76083-RJunta de AndalucĂa FQM2012-1467Japan Society for the Promotion of Science JSPS KAKENHI 17K1005
Transplanckian axions !?
We discuss quantum gravitational effects in Einstein theory coupled to
periodic axion scalars to analyze the viability of several proposals to achieve
superplanckian axion periods (aka decay constants) and their possible
application to large field inflation models. The effects we study correspond to
the nucleation of euclidean gravitational instantons charged under the axion,
and our results are essentially compatible with (but independent of) the Weak
Gravity Conjecture, as follows: Single axion theories with superplanckian
periods contain gravitational instantons inducing sizable higher harmonics in
the axion potential, which spoil superplanckian inflaton field range. A similar
result holds for multi-axion models with lattice alignment (like the
Kim-Nilles-Peloso model). Finally, theories with axions can still achieve a
moderately superplanckian periodicity (by a factor) with no higher
harmonics in the axion potential. The Weak Gravity Conjecture fails to hold in
this case due to the absence of some instantons, which are forbidden by a
discrete gauge symmetry. Finally we discuss the realization of
these instantons as euclidean D-branes in string compactifications.Comment: 46 pages, 6 figures. Added references, clarifications, and missing
factor of 1/2 to instanton action. Conclusions unchange
Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves
peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine.
Results
There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups.
Conclusion
Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak
Goldstones in Diphotons
We study the conditions for a new scalar resonance to be observed first in
diphotons at the LHC Run-2. We focus on scenarios where the scalar arises
either from an internal or spacetime symmetry broken spontaneously, for which
the mass is naturally below the cutoff and the low-energy interactions are
fixed by the couplings to the broken currents, UV anomalies, and selection
rules. We discuss the recent excess in diphoton resonance searches observed by
ATLAS and CMS at 750 GeV, and explore its compatibility with other searches at
Run-1 and its interpretation as Goldstone bosons in supersymmetry and composite
Higgs models. We show that two candidates naturally emerge: a Goldstone boson
from an internal symmetry with electromagnetic anomalies, and the scalar
partner of the Goldstone of supersymmetry breaking: the sgoldstino. The dilaton
from conformal symmetry breaking is instead disfavoured by present data, in its
minimal natural realization.Comment: 18 pages + refs, 2 figures. v2: typos corrected, references added,
discussions extended and three new plots. Conclusion unchanged. v3: published
versio
Explicit de Sitter Flux Vacua for Global String Models with Chiral Matter
We address the open question of performing an explicit stabilisation of all
closed string moduli (including dilaton, complex structure and Kaehler moduli)
in fluxed type IIB Calabi-Yau compactifications with chiral matter. Using toric
geometry we construct Calabi-Yau manifolds with del Pezzo singularities.
D-branes located at such singularities can support the Standard Model gauge
group and matter content. In order to control complex structure moduli
stabilisation we consider Calabi-Yau manifolds which exhibit a discrete
symmetry that reduces the effective number of complex structure moduli. We
calculate the corresponding periods in the symplectic basis of invariant
three-cycles and find explicit flux vacua for concrete examples. We compute the
values of the flux superpotential and the string coupling at these vacua.
Starting from these explicit complex structure solutions, we obtain AdS and dS
minima where the Kaehler moduli are stabilised by a mixture of D-terms,
non-perturbative and perturbative alpha'-corrections as in the LARGE Volume
Scenario. In the considered example the visible sector lives at a dP_6
singularity which can be higgsed to the phenomenologically interesting class of
models at the dP_3 singularity.Comment: 49 pages, 5 figures; v2: references adde
Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann–Pick Disease Type C
Niemann–Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation–tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509
String theoretic QCD axions in the light of PLANCK and BICEP2
The QCD axion solving the strong CP problem may originate from antisymmetric
tensor gauge fields in compactified string theory, with a decay constant around
the GUT scale. Such possibility appears to be ruled out now by the detection of
tensor modes by BICEP2 and the PLANCK constraints on isocurvature density
perturbations. A more interesting and still viable possibility is that the
string theoretic QCD axion is charged under an anomalous U(1)_A gauge symmetry.
In such case, the axion decay constant can be much lower than the GUT scale if
moduli are stabilized near the point of vanishing Fayet-Illiopoulos term, and
U(1)_A-charged matter fields get a vacuum value far below the GUT scale due to
a tachyonic SUSY breaking scalar mass. We examine the symmetry breaking pattern
of such models during the inflationary epoch with the Hubble expansion rate
10^{14} GeV, and identify the range of the QCD axion decay constant, as well as
the corresponding relic axion abundance, consistent with known cosmological
constraints. In addition to the case that the PQ symmetry is restored during
inflation, there are other viable scenarios, including that the PQ symmetry is
broken during inflation at high scales around 10^{16}-10^{17} GeV due to a
large Hubble-induced tachyonic scalar mass from the U(1)_A D-term, while the
present axion scale is in the range 10^{9}-5\times 10^{13} GeV, where the
present value larger than 10^{12} GeV requires a fine-tuning of the axion
misalignment angle. We also discuss the implications of our results for the
size of SUSY breaking soft masses.Comment: 29 pages, 1 figure; v3: analysis updated including the full
anharmonic effects, references added, version accepted for publication in
JHE
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