Siglec-5 and Siglec-14 are shown to be paired inhibitory/activating receptors expressed on neutrophils and amniotic epithelium and modulating immune responses to group B Streptococcus.

Sustained increases in mucosal surface area occur in remaining bowel following massive intestinal loss. The mechanisms responsible for expanding and perpetuating this response are not presently understood. We hypothesized that an increase in the number of intestinal stem cells (ISC) occurs following intestinal resection and is an important component of the adaptive response in mice. This was assessed in the jejunum of mice 2-3 days, 4-5 days, 6-7 days, 2 wk, 6 wk, and 16 wk following ileocecal resection (ICR) or sham operation. Changes in ISC following ICR compared with sham resulted in increased crypt fission and were assayed by 1) putative ISC population (SP) by flow cytometry, 2) Musashi-1 immunohistochemistry, and 3) bromodeoxyuridine (BrdU) label retention. Observed early increases in crypt depth and villus height were not sustained 16 wk following operation. In contrast, long-term increases in intestinal caliber and overall number of crypts per circumference appear to account for the enhanced mucosal surface area following ICR. Flow cytometry demonstrated that significant increases in SP cells occur within 2-3 days following resection. By 7 days, ICR resulted in marked increases in crypt fission and Musashi-1 immunohistochemistry staining. Separate label-retention studies confirmed a 20-fold increase in BrdU incorporation 6 wk following ICR, confirming an overall increase in the number of ISC. These studies support that expansion of ISC occurs following ICR, leading to an overall increase number of crypts through a process of fission and intestinal dilation. Understanding the mechanism expanding ISCs may provide important insight into management of intestinal failure.

Background: O-GlcNAc occupies histone H3, but specific sites and functions are unknown. Results: Threonine 32 is O-GlcNAcylated, and O-GlcNAc inhibits mitosis-specific phosphorylations on H3. Impaired removal of O-GlcNAc inhibits efficient cell cycle transition from G2 to mitosis. Conclusion:The reciprocal relationship between O-GlcNAc and phosphorylation on H3 contributes to a G2-M transition checkpoint. Significance: A mechanistic link between O-GlcNAc on H3 and mitosis has been revealed.

We demonstrate a compact waveguide-based high-speed Ge electro-absorption (EA) modulator integrated with a single mode 3 µm silicon-on-isolator (SOI) waveguide. The Ge EA modulator is based on a horizontally-oriented p-i-n structure butt-coupled with a deep-etched silicon waveguide, which transitions adiabatically to a shallow-etched single mode large core SOI waveguide. The demonstrated device has a compact active region of 1.0 × 45 µm(2), a total insertion loss of 2.5-5 dB and an extinction ratio of 4-7.5 dB over a wavelength range of 1610-1640 nm with -4V(pp) bias. The estimated Δα/α value is in the range of 2-3.3. The 3 dB bandwidth measurements show that the device is capable of operating at more than 30 GHz. Clear eye-diagram openings at 12.5 Gbps demonstrates large signal modulation at high transmission rate.

We demonstrate a compact, high speed Ge photodetector efficiently butt-coupled with a large cross-section silicon-on-insulate (SOI) waveguide in which the Ge p-i-n junction is placed in the horizontal direction to enable very high speed operation. The demonstrated photodetector has an active area of only 0.8×10 μm2, greater than 32 GHz optical bandwidth, and a responsivity of 1.1 A/W at a wavelength of 1550 nm. Very importantly the device can readily be integrated with high performance wavelength-division-multiplexing filters based on large cross-section SOI waveguide to form monolithic integrated silicon photonics receivers for multichannel terabit data transmission applications.

We demonstrate a high speed GeSi electro-absorption (EA) modulator monolithically integrated on 3 µm silicon-on-insulator (SOI) waveguide. The demonstrated device has a compact active region of 1.0 × 55 μm(2), an insertion loss of 5 dB and an extinction ratio of 6 dB at wavelength of 1550 nm. The modulator has a broad operating wavelength range of 35 nm and a 3 dB bandwidth of 40.7 GHz at 2.8 V reverse bias. This compact and energy efficient modulator is a key building block for optical interconnection applications.

The intracellular chaperone heat-shock protein 70 (Hsp70) can be secreted from cells, but its extracellular role is unclear, as the protein has been reported to both activate and suppress the innate immune response. Potential immunomodulatory receptors on myelomonocytic lineage cells that bind extracellular Hsp70 are not well defined. Siglecs are Ig-superfamily lectins on mammalian leukocytes that recognize sialic acid-bearing glycans and thereby modulate immune responses. Siglec-5 and Siglec-14, expressed on monocytes and neutrophils, share identical ligand-binding domains but have opposing signaling functions. Based on phylogenetic analyses of these receptors, we predicted that endogenous sialic acid-independent ligands should exist. An unbiased screen revealed Hsp70 as a ligand for Siglec-5 and Siglec-14. Hsp70 stimulation through Siglec-5 delivers an anti-inflammatory signal, while stimulation through Siglec-14 is pro-inflammatory. The functional consequences of this interaction are also addressed in relation to a SIGLEC14 polymorphism found in humans. Our results demonstrate that an endogenous non-sialic acid-bearing molecule can be either a danger-associated or self-associated signal through paired Siglecs, and may explain seemingly contradictory prior reports on extracellular Hsp70 action.

We demonstrate low loss shallow-ridge silicon waveguides with an average propagation loss of 0.274 + or - 0.008 dB/cm in the C-band (1530 nm - 1565 nm). These waveguides have a cross section of 0.25 microm by 2 microm and are fabricated by standard photolithography and dry etching. We also investigate a compact double-level taper which adiabatically couples light from these waveguides to silicon strip waveguides enabling tight bends.