Optomechanical cooling of levitated spheres with doubly-resonant fields

Optomechanical cooling of levitated dielectric particles represents a promising new approach in the quest to cool small mechanical resonators towards their quantum ground state. We investigate two-mode cooling of levitated nanospheres in a self-trapping regime. We identify a rich structure of split sidebands (by a mechanism unrelated to usual strong-coupling effects) and strong cooling even when one mode is blue detuned. We show the best regimes occur when both optical fields cooperatively cool and trap the nanosphere, where cooling rates are over an order of magnitude faster compared to corresponding single-sideband cooling rates.Comment: 8 Pages, 7 figure

Increased circulating T cell reactivity to GM3 and GQ1b gangliosides in primary progressive multiple sclerosis

We have previously shown that patients with primary progressive multiple sclerosis (MS) have significantly elevated plasma levels of antibody to GM3 ganglioside compared to patients with relapsing-remitting MS, healthy subjects and patients with other neurological diseases. Anti-GM3 antibody levels were elevated also in patients with secondary progressive MS but to a lesser extent than in primary progressive MS. As gangliosides are particularly enriched in the axonal membrane, these findings suggested that antiganglioside immune responses might contribute to the axonal damage in progressive forms of MS. The present study was performed to determine whether peripheral blood T cell responses to GM3 are also increased in progressive MS. Blood was collected from 98 untreated patients with MS (40 with relapsing-remitting, 27 with secondary progressive and 31 with primary progressive MS), 50 healthy subjects and 24 patients with other disorders of the CNS, and reactivity to GM1, GM3, GD1a, GD1b, GD3, GT1b, GQ1b and sulphatide was assessed by 6-day T cell proliferation assays. Increased T cell reactivity to GM3 and GQ1b occurred significantly more often in patients with primary progressive MS than in healthy subjects and patients with other CNS diseases. These findings suggest that ganglioside-specific T cells may contribute to the axonal damage in primary progressive MS. (C) 2002 Elsevier Science Ltd. All rights reserved

Dynamics of levitated nanospheres: towards the strong coupling regime

The use of levitated nanospheres represents a new paradigm for the optomechanical cooling of a small mechanical oscillator, with the prospect of realising quantum oscillators with unprecedentedly high quality factors. We investigate the dynamics of this system, especially in the so-called self-trapping regimes, where one or more optical fields simultaneously trap and cool the mechanical oscillator. The determining characteristic of this regime is that both the mechanical frequency $\omega_M$ and single-photon optomechanical coupling strength parameters $g$ are a function of the optical field intensities, in contrast to usual set-ups where $\omega_M$ and $g$ are constant for the given system. We also measure the characteristic transverse and axial trapping frequencies of different sized silica nanospheres in a simple optical standing wave potential, for spheres of radii $r=20-500$\,nm, illustrating a protocol for loading single nanospheres into a standing wave optical trap that would be formed by an optical cavity. We use this data to confirm the dependence of the effective optomechanical coupling strength on sphere radius for levitated nanospheres in an optical cavity and discuss the prospects for reaching regimes of strong light-matter coupling. Theoretical semiclassical and quantum displacement noise spectra show that for larger nanospheres with $r \gtrsim 100$\,nm a range of interesting and novel dynamical regimes can be accessed. These include simultaneous hybridization of the two optical modes with the mechanical modes and parameter regimes where the system is bistable. We show that here, in contrast to typical single-optical mode optomechanical systems, bistabilities are independent of intracavity intensity and can occur for very weak laser driving amplitudes

Decreased CD8+ T cell response to Epstein-Barr virus infected B cells in multiple sclerosis is not due to decreased HLA class I expression on B cells or monocytes

Background: Patients with multiple sclerosis (MS) have a decreased frequency of CD8(+) T cells reactive to their own Epstein-Barr virus (EBV) infected B cells. We have proposed that this might predispose to the development of MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. The decreased CD8(+) T cell response to EBV results from a general CD8(+) T cell deficiency and also a decreased proportion of EBV-specific T cells within the total CD8(+) T cell population. Because decreased HLA class I expression on monocytes and B cells has been reported in MS and could influence the generation and effector function of EBV-specific CD8(+) T cells, the present study was undertaken to measure the expression of HLA molecules on B cells and monocytes in patients with MS

Increased Immunoreactivity to Two Overlapping Peptides of Myelin Proteolipid Protein in Multiple Sclerosis

We tested the proliferative responses of peripheral blood mononuclear cells from 61 patients with multiple sclerosis, 56 healthy control subjects and 52 patients with other neurological diseases to seven synthetic peptides of myelin proteolipid protein (PLP) and 19 synthetic peptides of myelin basic protein (MBP). Increased proliferative responses to two overlapping PLP peptides, PLP184-199 and PLP190-209, were found significantly more frequently in blood from patients with relapsing-remitting or secondary progressive multiple sclerosis (52.3%), but not from those with primary progressive multiple sclerosis (18.2%), than in that from healthy control subjects (8.9%) and patients with other neurological diseases (20.8%). Reactivity to these PLP peptides was most frequently seen in blood from patients with multiple sclerosis of 6-15 years duration and with moderate to severe disability (Kurtzke's Expanded Disability Status Scale > 4.0); the blood from 15 of 19 patients in this group reacted to one or both of the peptides. Both peptides could be recognized by short-term T-cell lines specific for whole PLP, and lines specific for one or other of the two overlapping peptides were able to recognize whole PLP, indicating that these peptides can be processed naturally from the intact molecule. This region of PLP is encephalitogenic in a number of strains of mice. Samples from multiple sclerosis patients did not react more frequently to any of the MBP peptides than those from healthy control subjects. The proportions of patients with other neurological diseases whose blood responded to the MBP peptides that most frequently elicited responses in blood from multiple sclerosis patients were significantly lower than the proportions of multiple sclerosis patients and healthy control subjects whose blood responded to these peptides

Apneusis responding to buspirone in multiple sclerosis

Apneusis is a disturbance of respiratory rhythm characterized by severely prolonged inspiratory effort, and is caused by bilateral lesions in the dorsal pons. In humans it is most commonly caused by pontine infarction and has rarely been reported in multiple sclerosis (MS). Here we report on a patient with MS who developed episodic apneusis which responded to treatment with buspirone, a serotonin type 1A receptor agonist

Relationships Between Ion Channels, Mitochondrial Functions and Inflammation in Human Aging

Aging is often associated with a loss of function. We believe aging to be more an adaptation to the various, and often continuous, stressors encountered during life in order to maintain overall functionality of the systems. The maladaptation of a system during aging may increase the susceptibility to diseases. There are basic cellular functions that may influence and/or are influenced by aging. Mitochondrial function is amongst these. Their presence in almost all cell types makes of these valuable targets for interventions to slow down or even reserve signs of aging. In this review, the role of mitochondria and essential physiological regulators of mitochondria and cellular functions, ion channels, will be discussed in the context of human aging. The origins of inflamm-aging, associated with poor clinical outcomes, will be linked to mitochondria and ion channel biology

Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease

OBJECTIVE: The short isoform of thymic stromal lymphopoietin (TSLP), a cytokine constitutively expressed by epithelial cells, is crucial in preserving immune tolerance in the gut. TSLP deficiency has been implicated in sustaining intestinal damage in Crohn's disease. We explored mucosal TSLP expression and function in refractory and uncomplicated coeliac disease (CD), a T-cell-mediated enteropathy induced by gluten in genetically susceptible individuals. DESIGN: TSLP isoforms-long and short-and receptors-TSLPR and interleukin (IL)-7Rα-were assessed by immunofluorescence, immunoblotting and qRT-PCR in the duodenum of untreated, treated, potential and refractory patients with CD. The ability of the serine protease furin or CD biopsy supernatants to cleave TSLP was evaluated by immunoblotting. The production of interferon (IFN)-γ and IL-8 by untreated CD biopsies cultured ex vivo with TSLP isoforms was also assessed. RESULTS: Mucosal TSLP, but not TSLPR and IL-7Rα, was reduced in untreated CD and refractory CD in comparison to treated CD, potential CD and controls. Transcripts of both TSLP isoforms were decreased in active CD mucosa. Furin, which was overexpressed in active CD biopsies, was able to cleave TSLP in vitro. Accordingly, refractory and untreated CD supernatants showed higher TSLP-degrading capacity in comparison to treated CD and control supernatants. In our ex vivo model, both TSLP isoforms significantly downregulated IFN-γ and IL-8 production by untreated CD biopsies. CONCLUSIONS: Reduced mucosal TSLP expression may contribute to intestinal damage in refractory and untreated CD. Further studies are needed to verify whether restoring TSLP might be therapeutically useful especially in refractory patients with CD

Corrigendum to "A Study Of Human T-Cell Lines Generated From Multiple Sclerosis Patients And Controls By Stimulation With Peptides Of Myelin Basic Protein" (J. Neuroimmunol. 70, 65-74)

The amino acid sequences of the 5D and 5E synthetic peptides used in the above study inadvertently contained two lysine K residues (MYKKDSH) instead of the one K residue (MYKDSH) present in the natural sequences of the 21.5 and 20.2 kDa isoforms of human myelin basic protein. Thus, the sequences published in Table 1 correctly describe the peptides that were used, but peptides 5D and 5E differ from native myelin basic protein sequences by the insertion of an additional lysine residue. This extra lysine residue in peptides 5D and 5E should be considered when interpreting the proliferative and cytotoxic responses to these two peptides. However, it has no impact on the responses to any of the other peptides including all those representing the 18.5 kDa isoform or on the overall conclusions of the paper. The authors apologise for any confusion caused