Design of Trehalose-Based Amide/Sulfonamide C-type Lectin Receptor Signaling Compounds

Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha (TNF) and promote the development of a Th1/Th17 immune response that might be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6′-amide and sulfonamide α,α-d -trehalose compounds with various substituents on the aromatic ring was synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-type lectin receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure–activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human-Mincle-specific stimulation in a HEK reporter cell line.     

Decorative near-infrared transmission filters featuring high-efficiency and angular-insensitivity employing 1D photonic crystals

We present a new scheme for visibly-opaque but near-infrared-transmitting filters involving 7 layers based on one-dimensional ternary photonic crystals, with capabilities in reaching nearly 100% transmission efficiency in the near-infrared region. Different decorative reflection colors can be created by adding additional three layers while maintaining the near-infrared transmission performance. In addition, our proposed structural colors show great angular insensitivity up to ±60° for both transverse electric and transverse magnetic polarizations, which are highly desired in various fields. The facile strategy described here involves a simple deposition method for the fabrication, thereby having great potential in diverse applications such as image sensors, anti-counterfeit tag, and optical measurement systems.

     

Phytoplankton primary production, chlorophyll-a and nutrient concentrations in the water column of mountainous Lake Phewa, Nepal

The seasonal patterns of phytoplankton primary production, chlorophyll‐a concentration, cell number and several other limnological variables in Lake Phewa, located in the active monsoon zone in Central Himalaya, Nepal, were studied for a year beginning in April 2001. During the study period, the gross primary production and chlorophyll‐a concentrations were relatively low during the monsoon season. The phytoplankton cell number, represented by 24 genera, also fluctuated seasonally, but tended to increase in the pre‐ and post‐monsoon period. These results suggest that the monsoon plays a crucial role in the primary production and phytoplankton dynamics for Lake Phewa. Among the phytoplankton species, Microcystis aeruginosa, a representative species for eutrophic lakes, was the dominant phytoplankton. At the same time, however, it is clear that the lake is not yet heavily eutrophic. The present study suggests that the exchange of lake water during the monsoon season contributes to maintaining the health of the lake against further degradation. Nevertheless, the silt carried in the monsoon rain run‐off from the lake's catchment area suggests increasingly serious degradation problems for this small mountainous lake.     

Enhancing both network and user performance for networks supporting best effort traffic

With a view on improving user-perceived performance on networks supporting best effort flows, e.g., multimedia/data file transfers, we propose a family of bandwidth allocation criteria that depends on the residual work of on-going transfers. Analysis and simulations show that allocating bandwidth in this fashion can significantly improve the user-perceived delay, bit transmission delay, and throughput over traditional approaches, e.g., by 58% on an 80% loaded linear network. A simple implementation based on TCP Reno, exemplifies how one might approach practically realizing such gains. We discuss several other advantages of incorporating such differentiation at the transport level. In particular we make the case that favoring small transfers combined with user impatience or peak rate constraints, both of which are natural mechanisms for users to express the utility of completing transfers, offers a lightweight approach to achieving good overall network goodput and/or utility for best effort networks.     

Biochemical identification of transmembrane segments of the Ca(2+)-ATPase of sarcoplasmic reticulum

The transmembrane segments of sarcoplasmic reticulum Ca(2+)-ATPase were determined by trypsinization of cytoplasmic side-out intact sarcoplasmic reticulum vesicles. The membrane portion of tryptic digest comprising the transmembrane fragments, joined by the intravesicular segments, was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after labeling with fluorescein 5-maleimide in the presence of sodium dodecyl sulfate. In this way, seven fluorescent bands of tryptic fragments below 11 kDa were observed which were derived from 4 pairs of membrane spanning segments and one hydrophobic sequence at the C-terminal end. Two peptides of 10.8 and 10.6 kDa had the identical N-terminal sequence beginning at Glu826, representing the transmembrane segments M7 and M8 and their connecting loop. A band at 8.1 kDa contained one peptide beginning at Tyr36 (M1/loop/M2). A 7.7-kDa peptide starting at Leu253 (M3/loop/M4) and a 7.3-kDa peptide beginning at Ala752 (M5/loop/M6) were also observed. A band at 6.7 kDa contained two peptides, one beginning at Ser48 (M1/loop/M2) and another beginning at Tyr763 (M5/loop/M6). In addition, a 4-kDa peptide beginning at Met925 was observed. The size of this peptide did not allow for a complete pair of transmembrane segments, but this peptide could have been derived from trypsinolysis between the last pair of membrane spanning segments. These data therefore provide biochemical evidence for at least 8 transmembrane segments and perhaps two more at the C-terminal end of the enzyme.