78 research outputs found
6D Dyonic String With Active Hyperscalars
We derive the necessary and sufficient conditions for the existence of a
Killing spinor in N=(1,0) gauge supergravity in six dimensions coupled to a
single tensor multiplet, vector multiplets and hypermultiplets. These are shown
to imply most of the field equations and the remaining ones are determined. In
this framework, we find a novel 1/8 supersymmetric dyonic string solution with
nonvanishing hypermultiplet scalars. The activated scalars parametrize a 4
dimensional submanifold of a quaternionic hyperbolic ball. We employ an
identity map between this submanifold and the internal space transverse to the
string worldsheet. The internal space forms a 4 dimensional analog of the
Gell-Mann-Zwiebach tear-drop which is noncompact with finite volume. While the
electric charge carried by the dyonic string is arbitrary, the magnetic charge
is fixed in Planckian units, and hence necessarily non-vanishing. The source
term needed to balance a delta function type singularity at the origin is
determined. The solution is also shown to have 1/4 supersymmetric AdS_3 x S^3
near horizon limit where the radii are proportional to the electric charge.Comment: 28 pages, latex, minor corrections mad
Ianus: an Adpative FPGA Computer
Dedicated machines designed for specific computational algorithms can
outperform conventional computers by several orders of magnitude. In this note
we describe {\it Ianus}, a new generation FPGA based machine and its basic
features: hardware integration and wide reprogrammability. Our goal is to build
a machine that can fully exploit the performance potential of new generation
FPGA devices. We also plan a software platform which simplifies its
programming, in order to extend its intended range of application to a wide
class of interesting and computationally demanding problems. The decision to
develop a dedicated processor is a complex one, involving careful assessment of
its performance lead, during its expected lifetime, over traditional computers,
taking into account their performance increase, as predicted by Moore's law. We
discuss this point in detail
Reasons for hospitalizations in patients with type 2 diabetes mellitus in the CANVAS Program:a secondary analysis
AIMS: To determine the reasons for hospitalizations in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program and the effects of the sodium glucose co-transporter 2 inhibitor canagliflozin on hospitalization. MATERIALS AND METHODS: A secondary analysis was performed on the CANVAS Program that included 10,142 participants with type 2 diabetes mellitus randomized to canagliflozin or placebo. The primary outcome was total (first plus all recurrent) all-cause hospitalization (ACH). Secondary outcomes were total hospitalizations categorized by the Medical Dictionary for Regulatory Activities hierarchy at the system organ class level, reported by investigators at each center. Outcomes were assessed using negative binomial models. RESULTS: Of the 7115 hospitalizations reported, the most common reasons were cardiac disorders (23.7%), infections and infestations (15.0%), and nervous system disorders (9.0%). The rate of total ACH was lower in the canagliflozin group (n=5795) compared to the placebo group (n=4347): 197.9 versus 215.8 participants per 1000 patient-years, respectively (rate ratio [RR] 0.92; 95% confidence interval [CI] 0.86, 0.98). Canagliflozin reduced the rate of total hospitalizations due to cardiac disorders (RR 0.81; 95% CI 0.75, 0.88). There was no significant difference between the canagliflozin and placebo groups in the rates of total hospitalizations due to infections and infestations (RR 0.96; 95% CI 0.86, 1.02) or nervous system disorders (RR 0.96; 95% CI 0.88, 1.05). CONCLUSIONS: In the CANVAS Program, the most common reasons for hospitalization were cardiac disorders, infections and infestations, and nervous system disorders. Canagliflozin, compared with placebo, reduced the rate of total ACH. This article is protected by copyright. All rights reserved
Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?
Objective: Conventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging,NODDI), to demonstrate the strong potential of the new marker. Methods: We related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion. Results: We report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI-derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates. Interpretation: Neurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices
Feasibility of data-driven, model-free quantitative MRI protocol design: application to brain and prostate diffusion-relaxation imaging
Purpose: We investigate the feasibility of data-driven, model-free quantitative MRI (qMRI) protocol design on in vivo brain and prostate diffusion-relaxation imaging (DRI).
Methods: We select subsets of measurements within lengthy pilot scans, without identifying tissue parameters for which to optimise for. We use the “select and retrieve via direct upsampling” (SARDU-Net) algorithm, made of a selector, identifying measurement subsets, and a predictor, estimating fully-sampled signals from the subsets. We implement both using artificial neural networks, which are trained jointly end-to-end. We deploy the algorithm on brain (32 diffusion-/T1-weightings) and prostate (16 diffusion-/T2-weightings) DRI scans acquired on three healthy volunteers on two separate 3T Philips systems each. We used SARDU-Net to identify sub-protocols of fixed size, assessing reproducibility and testing sub-protocols for their potential to inform multi-contrast analyses via the T1-weighted spherical mean diffusion tensor (T1-SMDT, brain) and hybrid multi-dimensional MRI (HM-MRI, prostate) models, for which sub-protocol selection was not optimised explicitly.
Results: In both brain and prostate, SARDU-Net identifies sub-protocols that maximise information content in a reproducible manner across training instantiations using a small number of pilot scans. The sub-protocols support T1-SMDT and HM-MRI multi-contrast modelling for which they were not optimised explicitly, providing signal quality-of-fit in the top 5% against extensive sub-protocol comparisons.
Conclusions: Identifying economical but informative qMRI protocols from subsets of rich pilot scans is feasible and potentially useful in acquisition-time-sensitive applications in which there is not a qMRI model of choice. SARDU-Net is demonstrated to be a robust algorithm for data-driven, model-free protocol design
Noninvasive diffusion magnetic resonance imaging of brain tumour cell size for the early detection of therapeutic response
Cancer cells differ in size from those of their host tissue and are known to change in size during the processes of cell death. A noninvasive method for monitoring cell size would be highly advantageous as a potential biomarker of malignancy and early therapeutic response. This need is particularly acute in brain tumours where biopsy is a highly invasive procedure. Here, diffusion MRI data were acquired in a GL261 glioma mouse model before and during treatment with Temozolomide. The biophysical model VERDICT (Vascular Extracellular and Restricted Diffusion for Cytometry in Tumours) was applied to the MRI data to quantify multi-compartmental parameters connected to the underlying tissue microstructure, which could potentially be useful clinical biomarkers. These parameters were compared to ADC and kurtosis diffusion models, and, measures from histology and optical projection tomography. MRI data was also acquired in patients to assess the feasibility of applying VERDICT in a range of different glioma subtypes. In the GL261 gliomas, cellular changes were detected according to the VERDICT model in advance of gross tumour volume changes as well as ADC and kurtosis models. VERDICT parameters in glioblastoma patients were most consistent with the GL261 mouse model, whilst displaying additional regions of localised tissue heterogeneity. The present VERDICT model was less appropriate for modelling more diffuse astrocytomas and oligodendrogliomas, but could be tuned to improve the representation of these tumour types. Biophysical modelling of the diffusion MRI signal permits monitoring of brain tumours without invasive intervention. VERDICT responds to microstructural changes induced by chemotherapy, is feasible within clinical scan times and could provide useful biomarkers of treatment response
Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes
Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons(1,2). Several groups have attributed this apparent plasticity to 'transdifferentiation'(3-5). Others, however, have suggested that cell fusion could explain these results(6-9). Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of multinucleated cells. No evidence of transdifferentiation without fusion was observed in these tissues. These observations provide the first in vivo evidence for cell fusion of BMDCs with neurons and cardiomyocytes, raising the possibility that cell fusion may contribute to the development or maintenance of these key cell types.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62789/1/nature02069.pd
Expression of the "stem cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas
<p>Abstract</p> <p>Background</p> <p>It has been suggested that a small population of cells with unique self-renewal properties and malignant potential exists in solid tumors. Such "cancer stem cells" have been isolated by flow cytometry, followed by xenograft studies of their tumor-initiating properties. A frequently used sorting marker in these experiments is the cell surface protein CD133 (prominin-1). The aim of this work was to examine the distribution of CD133 in pancreatic exocrine cancer.</p> <p>Methods</p> <p>Fifty-one cases of pancreatic ductal adenocarcinomas were clinically and histopathologically evaluated, and immunohistochemically investigated for expression of CD133, cytokeratin 19 and chromogranin A. The results were interpreted on the background of CD133 expression in normal pancreas and other normal and malignant human tissues.</p> <p>Results</p> <p>CD133 positivity could not be related to a specific embryonic layer of organ origin and was seen mainly at the apical/endoluminal surface of non-squamous, glandular epithelia and of malignant cells in ductal arrangement. Cytoplasmic CD133 staining was observed in some non-epithelial malignancies. In the pancreas, we found CD133 expressed on the apical membrane of ductal cells. In a small subset of ductal cells and in cells in centroacinar position, we also observed expression in the cytoplasm. Pancreatic ductal adenocarcinomas showed a varying degree of apical cell surface CD133 expression, and cytoplasmic staining in a few tumor cells was noted. There was no correlation between the level of CD133 expression and patient survival.</p> <p>Conclusion</p> <p>Neither in the pancreas nor in the other investigated organs can CD133 membrane expression alone be a criterion for "stemness". However, there was an interesting difference in subcellular localization with a minor cell population in normal and malignant pancreatic tissue showing cytoplasmic expression. Moreover, since CD133 was expressed in shed ductal cells of pancreatic tumors and was found on the surface of tumor cells in vessels, this molecule may have a potential as clinical marker in patients suffering from pancreatic cancer.</p
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