192 research outputs found
Resonant states in an attractive one dimensional cusp potential
We solve the two-component Dirac equation in the presence of a spatially one
dimensional symmetric attractive cusp potential. The components of the spinor
solution are expressed in terms of Whittaker functions. We compute the bound
states solutions and show that, as the potential amplitude increases, the
lowest energy state sinks into the Dirac sea becoming a resonance. We
characterize and compute the lifetime of the resonant state with the help of
the phase shift and the Breit-Wigner relation. We discuss the limit when the
cusp potential reduces to a delta point interaction.Comment: 11 pages. To appear in Physica Script
Hilbert space of wormholes
Wormhole boundary conditions for the Wheeler--DeWitt equation can be derived
from the path integral formulation. It is proposed that the wormhole wave
function must be square integrable in the maximal analytic extension of
minisuperspace. Quantum wormholes can be invested with a Hilbert space
structure, the inner product being naturally induced by the minisuperspace
metric, in which the Wheeler--DeWitt operator is essentially self--adjoint.
This provides us with a kind of probabilistic interpretation. In particular,
giant wormholes will give extremely small contributions to any wormhole state.
We also study the whole spectrum of the Wheeler--DeWitt operator and its role
in the calculation of Green's functions and effective low energy interactions.Comment: 23 pages, 2 figures available upon request, REVTE
Circular strings, wormholes and minimum size
The quantization of circular strings in an anti-de Sitter background
spacetime is performed, obtaining a discrete spectrum for the string mass. A
comparison with a four-dimensional homogeneous and isotropic spacetime coupled
to a conformal scalar field shows that the string radius and the scale factor
have the same classical solutions and that the quantum theories of these two
models are formally equivalent. However, the physically relevant observables of
these two systems have different spectra, although they are related to each
other by a specific one-to-one transformation. We finally obtain a discrete
spectrum for the spacetime size of both systems, which presents a nonvanishing
lower bound.Comment: 11 pages, LaTeX2e, minor change
A multimodal spectroscopy system for real-time disease diagnosis
The combination of reflectance, fluorescence, and Raman spectroscopy—termed multimodal spectroscopy (MMS)—provides complementary and depth-sensitive information about tissue composition. As such, MMS is a promising tool for disease diagnosis, particularly in atherosclerosis and breast cancer. We have developed an integrated MMS instrument and optical fiber spectral probe for simultaneous collection of all three modalities in a clinical setting. The MMS instrument multiplexes three excitation sources, a xenon flash lamp (370–740 nm), a nitrogen laser (337 nm), and a diode laser (830 nm), through the MMS probe to excite tissue and collect the spectra. The spectra are recorded on two spectrograph/charge-coupled device modules, one optimized for visible wavelengths (reflectance and fluorescence) and the other for the near-infrared (Raman), and processed to provide diagnostic parameters. We also describe the design and calibration of a unitary MMS optical fiber probe 2 mm in outer diameter, containing a single appropriately filtered excitation fiber and a ring of 15 collection fibers, with separate groups of appropriately filtered fibers for efficiently collecting reflectance, fluorescence, and Raman spectra from the same tissue location. A probe with this excitation/collection geometry has not been used previously to collect reflectance and fluorescence spectra, and thus physical tissue models (“phantoms”) are used to characterize the probe’s spectroscopic response. This calibration provides probe-specific modeling parameters that enable accurate extraction of spectral parameters. This clinical MMS system has been used recently to analyze artery and breast tissue in vivo and ex vivo.National Institutes of Health (U.S) ( Grant No. P41-RR-02594
Self-isospectrality, special supersymmetry, and their effect on the band structure
We study a planar model of a non-relativistic electron in periodic magnetic
and electric fields that produce a 1D crystal for two spin components separated
by a half-period spacing. We fit the fields to create a self-isospectral pair
of finite-gap associated Lame equations shifted for a half-period, and show
that the system obtained is characterized by a new type of supersymmetry. It is
a special nonlinear supersymmetry generated by three commuting integrals of
motion, related to the parity-odd operator of the associated Lax pair, that
coherently reflects the band structure and all its peculiarities. In the
infinite period limit it provides an unusual picture of supersymmetry breaking.Comment: Title changed by the Editor of Phys. Rev. Lett., published versio
Huntington's disease-specific mis-splicing unveils key effector genes and altered splicing factors
Correction of mis-splicing events is a growing therapeutic approach for neurological diseases such as spinal muscular atrophy or neuronal ceroid lipofuscinosis 7, which are caused by splicing-affecting mutations. Mis-spliced effector genes that do not harbour mutations are also good candidate therapeutic targets in diseases with more complex aetiologies such as cancer, autism, muscular dystrophies or neurodegenerative diseases. Next-generation RNA sequencing (RNA-seq) has boosted investigation of global mis-splicing in diseased tissue to identify such key pathogenic mis-spliced genes. Nevertheless, while analysis of tumour or dystrophic muscle biopsies can be informative on early stage pathogenic mis-splicing, for neurodegenerative diseases, these analyses are intrinsically hampered by neuronal loss and neuroinflammation in post-mortem brains. To infer splicing alterations relevant to Huntington's disease pathogenesis, here we performed intersect-RNA-seq analyses of human post-mortem striatal tissue and of an early symptomatic mouse model in which neuronal loss and gliosis are not yet present. Together with a human/mouse parallel motif scan analysis, this approach allowed us to identify the shared mis-splicing signature triggered by the Huntington's disease-causing mutation in both species and to infer upstream deregulated splicing factors. Moreover, we identified a plethora of downstream neurodegeneration-linked mis-spliced effector genes that-together with the deregulated splicing factors-become new possible therapeutic targets. In summary, here we report pathogenic global mis-splicing in Huntington's disease striatum captured by our new intersect-RNA-seq approach that can be readily applied to other neurodegenerative diseases for which bona fide animal models are available.Extremadura Research Centre for Advanced Technologies (CETA-CIEMAT), funded by the European Regional Development Fund (ERDF). CETA-CIEMAT belongs to CIEMAT and the Government of Spai
CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington's disease
Huntington’s disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins 1 to 4 (CPEB1 to CPEB4) are RNA binding proteins that repress or activate translation of CPE-containing transcripts by shortening or elongating their poly(A) tail. Here, we found increased CPEB1 and decreased CPEB4 protein in the striatum of patients and mouse models with HD. This correlated with a reprogramming of polyadenylation in 17.3% of the transcriptome, markedly affecting neurodegeneration-associated genes including PSEN1, MAPT, SNCA, LRRK2, PINK1, DJ1, SOD1, TARDBP, FUS, and HTT and suggesting a new molecular mechanism in neurodegenerative disease etiology. We found decreased protein content of top deadenylated transcripts, including striatal atrophy–linked genes not previously related to HD, such as KTN1 and the easily druggable SLC19A3 (the ThTr2 thiamine transporter). Mutations in SLC19A3 cause biotin-thiamine–responsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD
The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: A call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, st jude global, UICC and WHPCA
The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.Fil: Pritchard Jones, Kathy. University College London; Estados UnidosFil: de Abib, Simone C.V.. International Society Of Paediatric Surgical Oncology; Surinam. Universidade Federal de Sao Paulo; BrasilFil: Esiashvili, Natia. University of Emory; Estados UnidosFil: Kaspers, Gertjan J.L.. Princess Máxima Center for Pediatric Oncology; PaĂses BajosFil: Rosser, Jon. No especifĂca;Fil: van Doorninck, John A.. Rocky Mountain Hospital for Children; Estados UnidosFil: Braganca, JoĂŁo M.L.. No especifĂca;Fil: Hoffman, Ruth I.. No especifĂca;Fil: Rodriguez Galindo, Carlos. St Jude Children’s Research Hospital; Estados UnidosFil: Adams, Cary. Union for International Cancer Control; SuizaFil: Connor, Stephen R.. Worldwide Hospice Palliative Care Alliance; Estados UnidosFil: Abdelhafeez, Abdelhafeez H.. International Society of Paediatric Surgical Oncology; Suiza. St. Jude Children’s Research Hospital; Estados UnidosFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Howard, Scott C.. International Society of Paediatric Surgical Oncology; Suiza. University of Tennessee; Estados UnidosFil: Challinor, Julia M.. International Society of Paediatric Surgical Oncology; Suiza. University of California; Estados UnidosFil: Hessissen, Laila. Children Hospital of Rabat; Marruecos. International Society of Paediatric Surgical Oncology; SuizaFil: Dalvi, Rashmi B.. Bombay Hospital Institute of Medical Sciences; India. International Society of Paediatric Surgical Oncology; SuizaFil: Kearns, Pamela. International Society of Paediatric Surgical Oncology; SuizaFil: Chantada, Guillermo Luis. International Society of Paediatric Surgical Oncology; Suiza. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Frazier, Lindsay A.. International Society of Paediatric Surgical Oncology; Suiza. Dana-Farber Cancer Institute; Estados UnidosFil: Sullivan, Michael J.. University of Melbourne; Australia. International Society of Paediatric Surgical Oncology; SuizaFil: Schulte, Fiona S.M.. University of Calgary; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Morrissey, Lisa K.. Boston Children’s Hospital; Estados Unidos. International Society of Paediatric Surgical Oncology; SuizaFil: Kozhaeva, Olga. European Society for Paediatric Oncology; BĂ©lgicaFil: Luna Fineman, Sandra. Children’s Hospital Colorado; Estados Unidos. International Society of Paediatric Oncology; SuizaFil: Khan, Muhammad S.. Tawam Hospital; Emiratos Arabes Unido
The Aguablanca Ni–(Cu) sulfide deposit, SW Spain: geologic and geochemical controls and the relationship with a midcrustal layered mafic complex
The Aguablanca Ni–(Cu) sulfide deposit is
hosted by a breccia pipe within a gabbro–diorite pluton.
The deposit probably formed due to the disruption of a
partially crystallized layered mafic complex at about 12–
19 km depth and the subsequent emplacement of melts and
breccias at shallow levels (<2 km). The ore-hosting breccias
are interpreted as fragments of an ultramafic cumulate,
which were transported to the near surface along with a
molten sulfide melt. Phlogopite Ar–Ar ages are 341–
332 Ma in the breccia pipe, and 338–334 Ma in the layered
mafic complex, and are similar to recently reported U–Pb
ages of the host Aguablanca Stock and other nearby calcalkaline
metaluminous intrusions (ca. 350–330 Ma). Ore
deposition resulted from the combination of two critical
factors, the emplacement of a layered mafic complex deep
in the continental crust and the development of small
dilational structures along transcrustal strike-slip faults that
triggered the forceful intrusion of magmas to shallow
levels. The emplacement of basaltic magmas in the lower
middle crust was accompanied by major interaction with
the host rocks, immiscibility of a sulfide melt, and the
formation of a magma chamber with ultramafic cumulates
and sulfide melt at the bottom and a vertically zoned mafic
to intermediate magmas above. Dismembered bodies of
mafic/ultramafic rocks thought to be parts of the complex
crop out about 50 km southwest of the deposit in a
tectonically uplifted block (Cortegana Igneous Complex,
Aracena Massif). Reactivation of Variscan structures that
merged at the depth of the mafic complex led to sequential
extraction of melts, cumulates, and sulfide magma. Lithogeochemistry
and Sr and Nd isotope data of the Aguablanca
Stock reflect the mixing from two distinct reservoirs, i.e.,
an evolved siliciclastic middle-upper continental crust and a
primitive tholeiitic melt. Crustal contamination in the deep
magma chamber was so intense that orthopyroxene
replaced olivine as the main mineral phase controlling the early fractional crystallization of the melt. Geochemical
evidence includes enrichment in SiO2 and incompatible
elements, and Sr and Nd isotope compositions (87Sr/86Sri
0.708–0.710; 143Nd/144Ndi 0.512–0.513). However, rocks
of the Cortegana Igneous Complex have low initial
87Sr/86Sr and high initial 143Nd/144Nd values suggesting
contamination by lower crustal rocks. Comparison of the
geochemical and geological features of igneous rocks in the
Aguablanca deposit and the Cortegana Igneous Complex
indicates that, although probably part of the same magmatic
system, they are rather different and the rocks of the
Cortegana Igneous Complex were not the direct source of
the Aguablanca deposit. Crust–magma interaction was a
complex process, and the generation of orebodies was
controlled by local but highly variable factors. The model
for the formation of the Aguablanca deposit presented in
this study implies that dense sulfide melts can effectively
travel long distances through the continental crust and that
dilational zones within compressional belts can effectively
focus such melt transport into shallow environments
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