1,099 research outputs found
Chasing the elusive "in-between" state of the copper-amyloid ÎČ complex by X-ray absorption through partial thermal relaxation after photoreduction
The redox activity of Cu ions bound to the amyloid-ÎČ (AÎČ) peptide is implicated as a source of oxidative stress in the context of Alzheimer's disease. In order to explain the efficient redox cycling between CuII -AÎČ (distorted square-pyramidal) and CuI -AÎČ (digonal) resting states, the existence of a low-populated "in-between" state, prone to bind Cu in both oxidation states, has been postulated. Here, we exploited the partial X-ray induced photoreduction at 10â
K, followed by a thermal relaxation at 200â
K, to trap and characterize by X-ray Absorption Spectroscopy (XAS) a partially reduced Cu-AÎČ1-16 species different from the resting states. Remarkably, the XAS spectrum is well-fitted by a previously proposed model of the "in-between" state, hence providing the first direct spectroscopic characterization of an intermediate state. The present approach could be used to explore and identify the catalytic intermediates of other relevant metal complexes
A Novel Technique for Region and Linguistic Specific nTMS-based DTI Fiber Tracking of Language Pathways in Brain Tumor Patients
Navigated transcranial magnetic stimulation (nTMS) has recently been
introduced as a non-invasive tool for functional mapping of cortical language
areas prior to surgery. It correlates well with intraoperative
neurophysiological monitoring (IONM) findings, allowing defining the best
surgical strategy to preserve cortical language areas during surgery for
language-eloquent tumors. Nevertheless, nTMS allows only for cortical mapping
and postoperative language deficits are often caused by injury to subcortical
language pathways. Nowadays, the only way to preoperatively visualize language
subcortical white matter tracts consists in DTI fiber tracking (DTI-FT).
However, standard DTI-FT is based on anatomical landmarks that vary
interindividually and can be obscured by the presence of the tumor itself. It
has been demonstrated that combining nTMS with DTI-FT allows for a more
reliable visualization of the motor pathway in brain tumor patients.
Nevertheless, no description about such a combination has been reported for
the language network. The aim of the present study is to describe and assess
the feasibility and reliability of using cortical seeding areas defined by
error type-specific nTMS language mapping (nTMS-positive spots) to perform
DTI-FT in patients affected by language-eloquent brain tumors. We describe a
novel technique for a nTMS-based DTI-FT to visualize the complex cortico-
subcortical connections of the language network. We analyzed quantitative
findings, such as fractional anisotropy values and ratios, and the number of
visualized connections of nTMS-positive spots with subcortical pathways, and
we compared them with results obtained by using the standard DTI-FT technique.
We also analyzed the functional concordance between connected cortical nTMS-
positive spots and subcortical pathways, and the likelihood of connection for
nTMS-positive vs. nTMS-negative cortical spots. We demonstrated, that the
nTMS-based approach, especially what we call the âsingle-spotâ strategy, is
able to provide a reliable and more detailed reconstruction of the complex
cortico-subcortical language network as compared to the standard DTI-FT. We
believe this technique represents a beneficial new strategy for customized
preoperative planning in patients affected by tumors in presumed language
eloquent location, providing anatomo-functional information to plan language-
preserving surgery
Decision Making in Patients With Metastatic Spine. The Role of Minimally Invasive Treatment Modalities
Spine metastases affect more than 70% of terminal cancer patients that eventually suffer from severe pain and neurological symptoms. Nevertheless, in the overwhelming majority of the cases, a spinal metastasis represents just one location of a diffuse systemic disease. Therefore, the best practice for treatment of spinal metastases depends on many different aspects of an oncological disease, including the assessment of neurological status, pain, location, and dissemination of the disease as well as the ability to predict the risk of disease progression with neurological worsening, benefits and risks associated to treatment and, eventually, expected survival. To address this need for a framework and algorithm that takes all aspects of care into consideration, we reviewed available evidence on the multidisciplinary management of spinal metastases. According to the latest evidence, the use of stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) for spinal metastatic disease is rapidly increasing. Indeed, aggressive surgical resection may provide the best results in terms of local control, but carries a significant rate of post-surgical morbidity whose incidence and severity appears to be correlated to the extent of resection. The multidisciplinary management represents, according to current evidence, the best option for the treatment of spinal metastases. Noteworthy, according to the recent literature evidence, cases that once required radical surgical resection followed by low-dose conventional radiotherapy, can now be more effectively treated by minimally invasive spinal surgery (MISS) followed by spine SRS with decreased morbidity, improved local control, and more durable pain control. This combination allows also extending this standard of care to patients that would be too sick for an aggressive surgical treatment
Vaccination with Flt3L-induced CD8α+ dendritic cells prevents CD4+ T helper cell-mediated experimental autoimmune myocarditis
Experimental autoimmune myocarditis (EAM) represents a CD4(+) T helper (Th) cell-mediated mouse model of inflammatory heart disease. Interferon (IFN)-γ, typically produced by Th1 cells, reduces EAM severity in myosin heavy-chain-(MyHC)-α peptide/Complete Freund adjuvant-immunized mice. Thus, developing a vaccination strategy that promotes differentiation of Th1 cells may be beneficial in EAM. FMS-like tyrosine kinase 3 ligand (Flt3L)-induced splenic CD8α(+) dendritic cells (DC), which produce interleukin (IL)-12p35, were identified to selectively induce biased differentiation towards Th1. Mice vaccinated with MyHC-α-loaded Flt3L-induced splenic CD8α(+) DC were protected from EAM. In contrast, when Flt3L-induced splenic CD8α(+) DC were pre-stimulated and over-activated with LPS and αCD40 antibodies or loaded with unspecific OVA(323-339) peptide instead of MyHC-α peptide, mice developed similar disease scores as non-vaccinated controls. Vaccination efficacy depended on IFN-γ, since CD8α(+)-vaccinated IFN-γR(-/-) mice were not protected. Importantly, splenic CD8α(+) vaccination was independent of regulatory T cells. Taken together, Flt3L-induced dendritic cell-based antigen-specific vaccination limits expansion of auto-reactive Th cells and protects mice from autoimmune heart inflammation
A year in review in Minerva Anestesiologica 2014
Year in revie
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
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