Elimination of the light shift in rubidium gas cell frequency standards using pulsed optical pumping

Changes in the intensity of the light source in an optically pumped, rubidium, gas cell frequency standard can produce corresponding frequency shifts, with possible adverse effects on the long-term frequency stability. A pulsed optical pumping apparatus was constructed with the intent of investigating the frequency stability in the absence of light shifts. Contrary to original expectations, a small residual frequency shift due to changes in light intensity was experimentally observed. Evidence is given which indicates that this is not a true light-shift effect. Preliminary measurements of the frequency stability of this apparatus, with this small residual pseudo light shift present, are presented. It is shown that this pseudo light shift can be eliminated by using a more homogeneous C-field. This is consistent with the idea that the pseudo light shift is due to inhomogeneity in the physics package (position-shift effect)

Development of a sub-miniature rubidium oscillator for SEEKTALK application

Warm-up and size challenges to oscillator construction are presented as well as the problems involved in these tasks. The performance of M-100 military rubidium oscillator is compared to that of a subminiture rubididum oscillator (M-1000). Methods of achieving 1.5 minute warm-up are discussed as well as improvements in performance under adverse environmental conditions, including temperature, vibration, and magnetics. An attempt is made to construct an oscillator error budget under a set of arbitrary mission conditions

Metrological characterization of the pulsed Rb clock with optical detection

We report on the implementation and the metrological characterization of a vapor-cell Rb frequency standard working in pulsed regime. The three main parts that compose the clock, physics package, optics and electronics, are described in detail in the paper. The prototype is designed and optimized to detect the clock transition in the optical domain. Specifically, the reference atomic transition, excited with a Ramsey scheme, is detected by observing the interference pattern on a laser absorption signal. \ The metrological analysis includes the observation and characterization of the clock signal and the measurement of frequency stability and drift. In terms of Allan deviation, the measured frequency stability results as low as $1.7\times 10^{-13} \ \tau^{-1/2}$, $\tau$ being the averaging time, and reaches the value of few units of $10^{-15}$ for $\tau=10^{4}$ s, an unprecedent achievement for a vapor cell clock. We discuss in the paper the physical effects leading to this result with particular care to laser and microwave noises transferred to the clock signal. The frequency drift, probably related to the temperature, stays below $10^{-14}$ per day, and no evidence of flicker floor is observed. \ We also mention some possible improvements that in principle would lead to a clock stability below the $10^{-13}$ level at 1 s and to a drift of few units of $10^{-15}$ per day

Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones

The human T cell response to the myelin basic protein (MBP) has been studied with respect to T cell receptor (TCR) usage, HLA class II restriction elements, and epitope specificity using a total of 215 long-term MBP-specific T cell lines (TCL) isolated from the peripheral blood of 13 patients with multiple sclerosis (MS) and 10 healthy donors. In most donors, the anti-MBP response was exceedingly heterogeneous. Using a panel of overlapping synthetic peptides spanning the entire length of human MBP, at least 26 epitopes recognized by human TCL could be distinguished. The MBP domain most commonly recognized was sequence 80-105 (31% of MS TCL, and 24% of control TCL). Sequence 29-48 was recognized more frequently by control-derived TCL (24%) than by TCL from MS patients (5%). The MBP epitopes were recognized in the context of DRB1 *0101, DRB5*0101, DRB1*1501, DRB1*0301, DRB1*0401, DRB1*1402, and DRB3*0102, as demonstrated using a panel of DR gene-transfected L cells. The TCR gene usage was also heterogeneous. V beta 5.2, a peptide of which is currently being used in a clinical trial for treatment of MS patients, was expressed by only one of our TCL. However, within this complex pattern of MBP-specific T cell responses, a minority of MS patients were found to exhibit a more restricted response with respect to their TCL epitope specificity. In these patients 75-87% of the TCL responded to a single, patient-specific cluster of immunodominant T cell epitopes located within a small (20-amino acid) domain of MBP. These nested clusters of immunodominant epitopes were noted within the amino acids 80-105, 108-131, and 131-153. The T cell response to the immunodominant epitopes was not monoclonal, but heterogeneous, with respect to fine specificity, TCR usage, and even HLA restriction. In one patient (H.K.), this restricted epitope profile remained stable for > 2 yr. The TCR beta chain sequences of TCL specific for the immunodominant region of HK are consistent with an oligoclonal response against the epitopes of this region (80-105). Further, two pairs of identical sequences were established from TCL generated from this patient at different times (June 1990 and June 1991), suggesting that some TCL specific for the immunodominant region persisted in the peripheral repertoire. The possible role of persistent immunodominant epitope clusters in the pathogenesis of MS remains to be established

Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones.

The human T cell response to the myelin basic protein (MBP) has been studied with respect to T cell receptor (TCR) usage, HLA class II restriction elements, and epitope specificity using a total of 215 long-term MBP-specific T cell lines (TCL) isolated from the peripheral blood of 13 patients with multiple sclerosis (MS) and 10 healthy donors. In most donors, the anti-MBP response was exceedingly heterogeneous. Using a panel of overlapping synthetic peptides spanning the entire length of human MBP, at least 26 epitopes recognized by human TCL could be distinguished. The MBP domain most commonly recognized was sequence 80-105 (31% of MS TCL, and 24% of control TCL). Sequence 29-48 was recognized more frequently by control-derived TCL (24%) than by TCL from MS patients (5%). The MBP epitopes were recognized in the context of DRB1 *0101, DRB5*0101, DRB1*1501, DRB1*0301, DRB1*0401, DRB1*1402, and DRB3*0102, as demonstrated using a panel of DR gene-transfected L cells. The TCR gene usage was also heterogeneous. V beta 5.2, a peptide of which is currently being used in a clinical trial for treatment of MS patients, was expressed by only one of our TCL. However, within this complex pattern of MBP-specific T cell responses, a minority of MS patients were found to exhibit a more restricted response with respect to their TCL epitope specificity. In these patients 75-87% of the TCL responded to a single, patient-specific cluster of immunodominant T cell epitopes located within a small (20-amino acid) domain of MBP. These nested clusters of immunodominant epitopes were noted within the amino acids 80-105, 108-131, and 131-153. The T cell response to the immunodominant epitopes was not monoclonal, but heterogeneous, with respect to fine specificity, TCR usage, and even HLA restriction. In one patient (H.K.), this restricted epitope profile remained stable for > 2 yr. The TCR beta chain sequences of TCL specific for the immunodominant region of HK are consistent with an oligoclonal response against the epitopes of this region (80-105). Further, two pairs of identical sequences were established from TCL generated from this patient at different times (June 1990 and June 1991), suggesting that some TCL specific for the immunodominant region persisted in the peripheral repertoire. The possible role of persistent immunodominant epitope clusters in the pathogenesis of MS remains to be established