1,343 research outputs found
A Comparison of Different Corneal Iontophoresis Protocols for Promoting Transepithelial Riboflavin Penetration.
Wide-field fluorescence lifetime imaging with optical sectioning and spectral resolution applied to biological samples
Seeing Tree Structure from Vibration
Humans recognize object structure from both their appearance and motion;
often, motion helps to resolve ambiguities in object structure that arise when
we observe object appearance only. There are particular scenarios, however,
where neither appearance nor spatial-temporal motion signals are informative:
occluding twigs may look connected and have almost identical movements, though
they belong to different, possibly disconnected branches. We propose to tackle
this problem through spectrum analysis of motion signals, because vibrations of
disconnected branches, though visually similar, often have distinctive natural
frequencies. We propose a novel formulation of tree structure based on a
physics-based link model, and validate its effectiveness by theoretical
analysis, numerical simulation, and empirical experiments. With this
formulation, we use nonparametric Bayesian inference to reconstruct tree
structure from both spectral vibration signals and appearance cues. Our model
performs well in recognizing hierarchical tree structure from real-world videos
of trees and vessels.Comment: ECCV 2018. The first two authors contributed equally to this work.
Project page: http://tree.csail.mit.edu
Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)
Peer reviewedPublisher PD
Mechanistic model of natural killer cell proliferative response to IL-15 receptor stimulation
Natural killer (NK) cells are innate lymphocytes that provide early host defense against intracellular pathogens, such as viruses. Although NK cell development, homeostasis, and proliferation are regulated by IL-15, the influence of IL-15 receptor (IL-15R)-mediated signaling at the cellular level has not been quantitatively characterized. We developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Our computational results demonstrated that IL-15/IL-15R complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. Ligand binding and receptor internalization modulated IL-15R occupancy. Our work supports the hypothesis that the total number and duration of IL-15/IL-15R complexes on the cell surface crosses a quantitative threshold prior to the initiation of NK cell division. Furthermore, our model predicted that the upregulation of IL-15Rα on NK cells substantially increased IL-15R complex formation and accelerated the expansion of dividing NK cells with the greatest impact at low IL-15 concentrations. Model predictions of the threshold requirement for NK cell recruitment to the cell cycle and the subsequent exponential proliferation correlated well with experimental data. In summary, our modeling analysis provides quantitative insight into the regulation of NK cell proliferation at the receptor level and provides a framework for the development of IL-15 based immunotherapies to modulate NK cell proliferation
Theoretical study of the insulating oxides and nitrides: SiO2, GeO2, Al2O3, Si3N4, and Ge3N4
An extensive theoretical study is performed for wide bandgap crystalline
oxides and nitrides, namely, SiO_{2}, GeO_{2}, Al_{2}O_{3}, Si_{3}N_{4}, and
Ge_{3}N_{4}. Their important polymorphs are considered which are for SiO_{2}:
-quartz, - and -cristobalite and stishovite, for
GeO_{2}: -quartz, and rutile, for Al_{2}O_{3}: -phase, for
Si_{3}N_{4} and Ge_{3}N_{4}: - and -phases. This work
constitutes a comprehensive account of both electronic structure and the
elastic properties of these important insulating oxides and nitrides obtained
with high accuracy based on density functional theory within the local density
approximation. Two different norm-conserving \textit{ab initio}
pseudopotentials have been tested which agree in all respects with the only
exception arising for the elastic properties of rutile GeO_{2}. The agreement
with experimental values, when available, are seen to be highly satisfactory.
The uniformity and the well convergence of this approach enables an unbiased
assessment of important physical parameters within each material and among
different insulating oxide and nitrides. The computed static electric
susceptibilities are observed to display a strong correlation with their mass
densities. There is a marked discrepancy between the considered oxides and
nitrides with the latter having sudden increase of density of states away from
the respective band edges. This is expected to give rise to excessive carrier
scattering which can practically preclude bulk impact ionization process in
Si_{3}N_{4} and Ge_{3}N_{4}.Comment: Published version, 10 pages, 8 figure
Severe leukoencephalopathy with fulminant cerebral edema reflecting immune reconstitution inflammatory syndrome during HIV infection: a case report
<p>Abstract</p> <p>Introduction</p> <p>Immune reconstitution inflammatory syndrome is a well-known complication in HIV-infected patients after initiation of highly active antiretroviral therapy resulting in rapid CD4<sup>+ </sup>cell count recovery and suppression of viral load. Generally, immune reconstitution inflammatory syndrome is based on opportunistic infections, but rare cases of immune reconstitution inflammatory syndrome inducing demyelinization of the nervous system have also been observed.</p> <p>Case presentation</p> <p>A 37-year-old African woman with HIV infection diagnosed at 13 years of age was admitted to the emergency department after experiencing backache, severe headache, acute aphasia and psychomotor slowing for one week. Nine weeks earlier, highly active antiretroviral therapy in this patient had been changed because of loss of efficacy, and a rapid increase in CD4<sup>+ </sup>cell count and decrease of HIV viral load were observed. Magnetic resonance imaging of the brain showed extensive white matter lesions, and analysis of cerebrospinal fluid revealed an immunoreactive syndrome. Intensive investigations detected no opportunistic infections. A salvage therapy, including osmotherapy, corticosteroids and treatment of epileptic seizures, was performed, but the patient died from brainstem herniation 48 hours after admission. Neuropathologic examination of the brain revealed diffuse swelling, leptomeningeal infiltration by CD8 cells and enhancement of perivascular spaces by CD8+ cells.</p> <p>Conclusion</p> <p>Immune reconstitution inflammatory syndrome in this form seems to represent a severe autoimmunologic disease of the brain with specific histopathologic findings. This form of immune reconstitution inflammatory syndrome did not respond to therapy, and extremely rapid deterioration led to death within two days. Immune reconstitution inflammatory syndrome may also occur as severe leukoencephalopathy with fulminant cerebral edema during HIV infection with rapid immune reconstitution.</p
Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome
Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency
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