Cs vapor microcells with Ne-He buffer gas mixture for high operation-temperature miniature atomic clocks.

We report on the characterization of Cs vapor microfabricated cells filled with a Ne-He buffer gas mixture using coherent population trapping (CPT) spectroscopy. The temperature dependence of the Cs clock frequency is found to be canceled at the first order around a so-called inversion temperature higher than 80°C whose value depends on the buffer gas partial pressure ratio. This buffer gas mixture could be well-adapted for the development of miniature atomic clocks devoted to be used in specific applications such as defense and avionic systems with high operating temperature environment (typically higher than 85°C). This solution suggests an alternative to buffer gas mixtures generally used in optically-pumped vapor cell atomic clocks.

Metrological characterization of custom-designed 894.6 nm VCSELs for miniature atomic clocks.

We report on the characterization and validation of custom-designed 894.6 nm vertical-cavity surface-emitting lasers (VCSELs), for use in miniature Cs atomic clocks based on coherent population trapping (CPT). The laser relative intensity noise (RIN) is measured to be 1 × 10(-11) Hz(-1) at 10 Hz Fourier frequency, for a laser power of 700 µW. The VCSEL frequency noise is 10(13) · f(-1) Hz(2)/Hz in the 10 Hz < f < 10(5) Hz range, which is in good agreement with the VCSEL's measured fractional frequency instability (Allan deviation) of ≈ 1 × 10(-8) at 1 s, and also is consistent with the VCSEL's typical optical linewidth of 20-25 MHz. The VCSEL bias current can be directly modulated at 4.596 GHz with a microwave power of -6 to +6 dBm to generate optical sidebands for CPT excitation. With such a VCSEL, a 1.04 kHz linewidth CPT clock resonance signal is detected in a microfabricated Cs cell filled with Ne buffer gas. These results are compatible with state-of-the-art CPT-based miniature atomic clocks exhibiting a short-term frequency instability of 2-3 × 10(-11) at τ = 1 s and few 10(-12) at τ = 10(4) s integration time..

High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic leukemia.

We investigated the pattern of lipoprotein lipase (LPL) expression in B-cell chronic lymphocytic leukemia (B-CLL) and assessed its prognostic relevance. Expression of LPL mRNA as well as protein was highly restricted to leukemic B cells. The intensity of intracellular immunoreactivity of LPL was higher in samples of patients with unmutated immunoglobulin heavy-chain variable region genes (IGV(H)) compared to those with mutated IGV(H) genes. LPL mRNA levels in peripheral blood mononuclear cells (PBMNC) from 104 CLL patients differed by 1.5 orders of magnitude between cases with mutated (N=51) or unmutated (N=53) IGV(H) (median: 1.33 vs 45.22 compared to normal PBMNC). LPL expression correlated strongly with IGV(H) mutational status (R=0.614; P<0.0001). High LPL expression predicted unmutated IGV(H) status with an odds ratio of 25.90 (P<0.0001) and discriminated between mutated and unmutated cases in 87 of 104 patients (84%). LPL expression was higher in patients with poor risk cytogenetics. High LPL expression was associated with a shorter treatment-free survival (median 40 vs 96 months, P=0.001) and a trend for a shorter median overall survival (105 months vs not reached). Our data establish LPL as a prognostic marker and suggest functional consequences of LPL overexpression in patients with B-CLL.

High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia.

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation of B-cells. We investigated the expression of AID mRNA by real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 80 patients with B-CLL. AID expression was detected in 45 of 80 patients (56%) at various levels, but was undetectable in 35 patients (44%). AID PCR positivity was associated with unmutated IGV(H) gene status (22 of 25 patients; P=0.002) and unfavourable cytogenetics (18 of 23 patients with deletion in 11q or loss of p53; P=0.040). Using a threshold level of 0.01-fold expression compared to Ramos control cells, even more significant associations were observed (P=0.001 for IGVH; P=0.002 for cytogenetics). A correlation was observed between individual AID levels and the percentage of V(H) homology (R=0.41; P=0.001). AID positivity predicted unmutated IGV(H) status with an odds ratio of 8.31 (P=0.003) and poor risk cytogenetics with an odds ratio of 3.46 (P=0.032). Significance was retained after adjustment for Binet or Rai stages. AID mRNA levels were stable over time. These data suggest a potential role of AID as a prognostic marker in B-CLL.

Modulation of Fc gamma receptor-mediated early events by the tyrosine phosphatase CD45 in primary human monocytes. Consequences for interleukin-6 production.

Stimulation of primary human monocytes from several donors by cross-linking of Fc gamma receptor type I (Fc gamma RI) and Fc gamma RII gave rise to calcium mobilization and protein tyrosine phosphorylation. These early events were not observed without cross-linking. CD45, a transmembrane tyrosine phosphatase, when co-cross-linked with either Fc gamma RI or Fc gamma RII, could prevent Fc gamma RI and Fc gamma RII-mediated calcium mobilization and protein tyrosine phosphorylation. When interleukin (IL)-6 production was measured, we noted a strong IL-6 production after activation of primary human monocytes by cross-linking of Fc gamma RI or Fc gamma RII. In contrast to calcium mobilization and tyrosine phosphorylation of proteins, IL-6 production was not affected by co-cross-linking of CD45 with either Fc gamma RI or Fc gamma RII. Interestingly, cross-linking of the CD45 itself was sufficient to induce IL-6 production. Our results show that the CD45 molecule is important in modulating early events following stimulation of primary human monocytes by cross-linking of Fc gamma RI or Fc gamma RII. However, triggering of CD45 alone can also induce IL-6 production, indicating that CD45 ligation itself can give signals and may have an important role in cytokine induction pathways.