Real-time transmission of 16 Tb/s over 1020km using 200Gb/s CFP2-DCO.

We demonstrate real-time transmission of 16 Tb/s (80x200Gb/s) over 1020km TeraWave ULL fiber with 170km span length using the world's first 200Gb/s CFP2-DCO module with a record low power consumption less than 0.1W/Gbps.

800Gb/s (8x128Gb/s) unrepeatered transmission over 515-km large-area ultra-low-loss fiber using 2nd-order Raman pumping.

We demonstrate unrepeatered transmission of 8x128Gb/s PDM-QPSK signals over a 515k-m fiber link. This ultra-long distance of 800 Gb/s unrepeatered transmission in a single fiber configuration is achieved by employing enabling techniques such as large-effective-area ultra-low-attenuation fibers, co-propagating and counter-propagating 2nd-order-pumped distributed Raman amplification, and remote optically pumped amplifier (ROPA). The ROPA itself is also counter-propagating 2nd-order Raman pumped. The designs and characteristics of the ROPA and 2nd-order pumped distributed Raman amplification are described, and optimization of the transmission performance of this ultra-long reach 800Gb/s unrepeatered transmission fiber link is discussed in this paper.

Analysis of high and low responses to Staphylococcus aureus and interleukin 2 in human B lymphocytes.

Fixed protein A-bearing staphylococci (SAC) stimulate human B cells via surface Ig, whereas IL-2 has been reported to provide a sufficient second signal for proliferation and differentiation. Using an ELISPOT assay to count cells secreting IgM, IgA, and IgG and flow cytometry with acridine orange to assess cell cycle progress, we have found that the purified B lymphocytes of a substantial minority (5/13) of healthy volunteers with normal serum Ig levels failed to differentiate to Ig secreting cells (ISC) in response to SAC + IL-2 (IgM, IgA, or IgG secreting cells, < 5% of input B cells). High-responders generally formed 10-35% ISC. The proportions of B cells expressing IgG, IgA, IgM, or IgD were not different in the two groups. By average linkage cluster analysis, SAC/IL-2 high- and low-responders were shown to fall into two separate populations with respect to ISC. High- and low-responders tended to remain in the same group with repeated testing over several months, although some convergence was seen. The low-responders also showed significantly less advancement to late G1 and S phase than the high-responders, in the presence of SAC +/- IL-2. Induction of IL-2 receptors on B cells by SAC + IL-2 was much greater in high-responders than in low-responders, as shown by flow cytometry with phycoerythrin-conjugated IL-2. However, SAC + IL-2 induced transferrin receptors normally in low-responders, showing that some early activation steps occur in these cells. Low-responder B cells often improved their responses in the presence of macrophages and T cell supernatants. Finally, bypassing the surface Ig pathway using anti-CD3-activated T cells to stimulate B cells produced normal differentiation in low-responder B cells. Thus a subset of clinically normal individuals possesses B cells which fail to express IL-2 receptors, proliferate, and differentiate normally in vitro in response to SAC + IL-2 yet can respond well to alternative activation pathways via T cells, monocytes, and their products.

CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry.

Isolated murine splenic B cells undergo spontaneous apoptosis. Motifs containing unmethylated CpG dinucleotides in bacterial DNA or in synthetic oligodeoxynucleotides (ODN) are known to activate murine B cells. Now we show that ODN that induce spleen B cell cycle entry also inhibit spontaneous apoptosis in a sequence-specific fashion. Reversal of the CG to GC abolished activity. Methylation of the central cytosine decreased activity. When CpG is preceded by a cytosine or followed by a guanine, activity was abolished. Other substitutions at the same positions had no effect. Dose-response curves for apoptosis protection and G1 entry suggested that a uniform population of ODN recognition sites controlled downstream ODN effects. A CpG ODN with a nuclease-resistant phosphorothioate backbone (S-ODN) was also active, and increased the levels of c-myc, egr-1, c-jun, bclXL, and bax mRNA and c-Myc, c-Jun, Bax, and BclXL protein in spleen B cells. Levels of c-myb, myn, c-Ki-ras, and bcl2 mRNA remained unchanged. When protein synthesis was inhibited, at 16 h ODN-induced cell cycle entry was abolished and apoptosis protection was partially preserved. Under these conditions, c-Myc was still present, but c-Jun and BclXL were not detected. Our results suggest that CpG containing ODN motifs provide signals for both survival and cell cycle entry. Single base changes determine whether this signal proceeds through a rate-limiting step governing at least two steps in apoptosis (plasma membrane transition, DNA cleavage) and two phases of the cell cycle (G1 and S phase entry). This biologic action is associated with increased c-Myc, c-Jun, and BclXL expression.

Broadband fiber dispersion compensation for sub-100-fs pulses with a compression ratio of 300.

We report what is, to our knowledge, the first experimental demonstration of nearly dispersion-free transmission of sub-100-fs pulses over several tens of meters of fiber. 62-fs pulses are broadened initially and recompressed by a ratio of 300 over a 42-m concatenated fiber link consisting of standard single-mode and dispersioncompensating fibers. This dispersion-compensated fiber link is estimated to have a third-order dispersion ~6 times lower than that of dispersion-shifted fiber.

CpG DNA rescues B cells from apoptosis by activating NFkappaB and preventing mitochondrial membrane potential disruption via a chloroquine-sensitive pathway.

Isolated murine splenic B cells gradually undergo spontaneous apoptosis while WEHI-231 B lymphoma cells undergo activation-induced apoptosis. Unmethylated CpG dinucleotides in a particular sequence context (CpG motif) in bacterial DNA or in synthetic oligodeoxynucleotides (CpG DNA) rescue both splenic B cells and WEHI-231 cells from apoptosis, an effect which could potentially contribute to autoimmune disease. Chloroquine has been used as an effective therapeutic agent for some autoimmune diseases, although the mechanism of action is not clearly understood. Low concentrations of chloroquine (<5 microM) selectively abolished CpG DNA-mediated protection against spontaneous apoptosis of splenic B cells and against anti-IgM-induced apoptosis of WEHI-231 cells without affecting anti-apoptotic activities of anti-CD40 or lipopolsaccharide. CpG DNA effectively prevented mitochondrial membrane potential disruption through a chloroquine-sensitive pathway in splenic B cells. Apoptosis protection by CpG DNA was also associated with increased expression of several proto-oncogenes and oncoproteins directly and/or indirectly through a rapid and sustained activation of NFkappaB in splenic B cells and WEHI-231 cells. These effects were also suppressed by chloroquine. Our results suggest that despite the difference in maturation phenotype of splenic B cells and WEHI-231 cells, CpG DNA rescues both from apoptosis by similar pathway, which is blocked at an early step by chloroquine.

Decreased membrane phospholipid packing and decreased cell size precede DNA cleavage in mature mouse B cell apoptosis.

Mature resting mouse spleen B cells progress stochastically into apoptosis at a uniform rate over the first 16 h in vitro in 3 stages. In stage 1, early apoptotic B cells decreased the normal phospholipid packing of their plasma membranes, detected as increased binding of the lipophilic dye merocyanine 540, and also decreased in volume, detected as decreased forward scatter. In stage 2 there was abrupt internucleosomal cleavage of DNA, quantitated as hypodiploid nuclei by flow cytometry. Some stage 2 cells entered stage 3, where the plasma membrane became permeable to propidium iodide. B cells in later stages of this sequence retained the characteristics of earlier stages, whereas nonapoptotic B cells remained in their original state. Cycloheximide increased the progression of B cells through these three stages, whereas dextran sulfate inhibited stage 1 more effectively than stages 2 or 3. Increased orthogonal scatter also occurred late in some of the cells that had passed through stage 1, but did not correlate well with propidium iodide permeability. Fresh small dense spleen B cells contained 5% to 7% stage 1 cells but only about 1% stage 2 cells. Macrophages have been reported to destroy preferentially apoptotic thymocytes by recognizing plasma membrane alterations deriving from loose packing of phospholipid head groups. The recognition of stage 1 rather than stage 2 B cells by macrophages may help to keep the proportion of apoptotic cells low in vivo.