5,688 research outputs found
Home Telemonitoring of COVID Patients by Medical Students at the Christiana Care Virtual Practice
SARS-Cov2 arrived in Delaware on March 11, 2020. By March 22, 2020, stay at home orders were in place1. During this time, CareVio, a subsidiary of ChristianaCare, was tasked with developing a strategy to monitor the Delaware community. CareVio repurposed Twistle – a telemonitoring application utilized to distribute symptom related surveys and conduct text message conversations for follow up. This service had the capability to act as a virtual information desk and triage patients to be seen by virtual practice providers or the emergency department. Patient monitoring via Twistle was initiated on March 18, 2020 and medical students from Sidney Kimmel Medical College and Philadelphia College of Osteopathic Medicine assumed the role 7 days later
Lentiviral-Mediated Transcriptional Targeting of Dendritic Cells for Induction of T Cell Tolerance In Vivo
Abstract
Dendritic cells (DCs) are important APCs able to induce both tolerance and immunity. Therefore, DCs are attractive targets for immune intervention. However, the ex vivo generation and manipulation of DCs at sufficient numbers and without changing their original phenotypic and functional characteristics are major obstacles. To manipulate DCs in vivo, we developed a novel DC-specific self-inactivating lentiviral vector system using the 5′ untranslated region from the DC-STAMP gene as a putative promoter region. We show that a gene therapy approach with these DC-STAMP-lentiviral vectors yields long-term and cell-selective transgene expression in vivo. Furthermore, transcriptionally targeted DCs induced functional, Ag-specific CD4 and CD8 T cell tolerance in vivo, which could not be broken by viral immunization. Tolerized CTL were unable to induce autoimmune diabetes in a murine autoimmune model system. Therefore, delivering transgenes specifically to DCs by using viral vectors might be a promising tool in gene therapy
Transcriptional Targeting of B Cells for Induction of Peripheral CD8 T Cell Tolerance
Abstract
Several mechanisms are in place to neutralize autoimmune CD8 T cells by tolerance induction. Developing self-specific CD8 T cells are eliminated in the thymus by Ag-presenting epithelial and dendritic cells (DCs). However, CD8 T cells escaping thymic central tolerance can also be inactivated by tolerance mechanisms in peripheral organs. In contrast to DCs, the role of B cells in generating CD8 T cell tolerance is not well-characterized. To investigate this question in more detail, we transcriptionally targeted Ag to B cells using B cell-specific retroviral vectors in vivo. Although Ag expression could be detected in B cells of thymus, lymph nodes, and spleen, B cells were unable to induce central tolerance of CD8 thymocytes. In contrast, in peripheral organs, we could identify clonal deletion and functional inhibition (anergy) of CD8 T cells as tolerance-inducing mechanisms. Although Ag expressed by B cells was acquired and cross-presented by DCs, B cells were also sufficient to tolerize CD8 T cells directly. These findings suggest exploitation of B cells for Ag-specific immunotherapy of CD8 T cell-mediated autoimmune diseases
First detection of the RGB-bump in the Sagittarius dSph
We present V, I photometry of the Sagittarius Dwarf Spheroidal galaxy (Sgr)
for a region of ~ 1^{circ} times 1^{circ}, centered on the globular cluster M
54. This catalog is the largest database of stars (~500,000) ever obtained for
this galaxy. The wide area covered allows us to measure for the first time the
position of the RGB-bump, a feature that has been identified in most Galactic
globular clusters and only recently in a few galaxies of the Local Group. The
presence of a single-peaked bump in the RGB differential Luminosity Function
confirms that there is a dominant population in Sgr (Pop A).
The photometric properties of the Pop A RGB and the position of the RGB bump
have been used to constrain the range of possible ages and metallicities of
this population. The most likely solution lies in the range -0.6 < [M/H] <=
-0.4 and 4 Gyr <= age <= 8 Gyr.Comment: 14 pages, 4 figures, accepted by ApJ Letter
The quasar M_bh - M_host relation through Cosmic Time II - Evidence for evolution from z=3 to the present age
We study the dependence of the M_bh - M_host relation on the redshift up to
z=3 for a sample of 96 quasars the host galaxy luminosities of which are known.
Black hole masses were estimated assuming virial equilibrium in the broad line
regions (Paper I), while the host galaxy masses were inferred from their
luminosities. With this data we are able to pin down the redshift dependence of
the M_bh - M_host relation along 85 per cent of the Universe age. We show that,
in the sampled redshift range, the M_bh - L_host relation remains nearly
unchanged. Once we take into account the aging of the stellar population, we
find that the M_bh / M_host ratio (Gamma) increases by a factor ~7 from z=0 to
z=3. We show that Gamma evolves with z regardless of the radio loudness and of
the quasar luminosity. We propose that most massive black holes, living their
quasar phase at high-redshift, become extremely rare objects in host galaxies
of similar mass in the Local Universe.Comment: 10 pages, 8 figures, 2 tables. Accepted for publication in MNRA
Active percolation analysis of pyramidal neurons of somatosensory cortex: A comparison of wildtype and p21H-Ras<Sup>Val12 transgenic mice
This article describes the investigation of morphological variations among two sets of neuronal cells, namely a control group of wild type rat cells and a group of cells of a trangenic line. Special attention is given to singular points in the neuronal structure, namely the branching points and extremities of the dendritic processes. The characterization of the spatial distribution of such points is obtained by using a recently reported morphological technique based on forced percolation and window-size compensation, which is particularly suited to the analysis of scattered points, presenting several coexisting densities. Different dispersions were identified in our statistical analysis, suggesting that the transgenic line of neurons is characterized by a more pronounced morphological variation. A classification scheme based on a canonical discriminant function was also considered in order to identify the morphological differences
Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia
Mmutations in paraplegin, a putative mitochondrial metallopeptidase of the AAA family, cause an autosomal recessive form of hereditary spastic paraplegia (HSP). Here, we analyze the function of paraplegin at the cellular level and characterize the phenotypic defects of HSP patients' cells lacking this protein. We demonstrate that paraplegin coassembles with a homologous protein, AFG3L2, in the mitochondrial inner membrane. These two proteins form a high molecular mass complex, which we show to be aberrant in HSP fibroblasts. The loss of this complex causes a reduced complex I activity in mitochondria and an increased sensitivity to oxidant stress, which can both be rescued by exogenous expression of wild-type paraplegin. Furthermore, complementation studies in yeast demonstrate functional conservation of the human paraplegin–AFG3L2 complex with the yeast m-AAA protease and assign proteolytic activity to this structure. These results shed new light on the molecular pathogenesis of HSP and functionally link AFG3L2 to this neurodegenerative disease
Directed polymers and interfaces in random media : free-energy optimization via confinement in a wandering tube
We analyze, via Imry-Ma scaling arguments, the strong disorder phases that
exist in low dimensions at all temperatures for directed polymers and
interfaces in random media. For the uncorrelated Gaussian disorder, we obtain
that the optimal strategy for the polymer in dimension with
involves at the same time (i) a confinement in a favorable tube of radius with (ii) a superdiffusive behavior with for the wandering of the best favorable
tube available. The corresponding free-energy then scales as with and the left tail of the probability
distribution involves a stretched exponential of exponent .
These results generalize the well known exact exponents ,
and in , where the subleading transverse length is known as the typical distance between two replicas in the Bethe
Ansatz wave function. We then extend our approach to correlated disorder in
transverse directions with exponent and/or to manifolds in dimension
with . The strategy of being both confined and
superdiffusive is still optimal for decaying correlations (), whereas
it is not for growing correlations (). In particular, for an
interface of dimension in a space of total dimension with
random-bond disorder, our approach yields the confinement exponent . Finally, we study the exponents in the presence of an
algebraic tail in the disorder distribution, and obtain various
regimes in the plane.Comment: 19 page
Targeted therapy for metastatic renal cell carcinoma
Peer reviewedPublisher PD
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