MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice

Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients. Here, we aim to seek for potential regulators that mediate functional aberrations of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease onset were compared for toll-like receptor (TLR) induced responses and microRNA profile changes. While pDCs derived from symptomatic mice were phenotypically comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed. Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented expression of Cd40, which is consistent with the increased CD40 expression in symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated regulation in pDC functional abnormalities in SLE. Findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular regulation in autoimmunity.     

Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide,A Biomarker of Diabetic Neuropathy

Diabetes-related neuropathy is a debilitating condition that may be averted if it can be detected early. One possible way this can be achieved at low cost is to utilise peptides to detect C-peptide, a biomarker of diabetic neuropathy. This depends on peptide-peptide co-assembly, which is currently in a nascent stage of intense study. Instead, we propose a bead-based triple-overlay combinatorial strategy that can preserve inter-residue information during the screening process for a suitable complementary peptide to co-assemble with C-peptide. The screening process commenced with a pentapeptide general library, which revealed histidine to be an essential residue. Further screening with seven tetrapeptide focused libraries led to a table of self-consistent peptide sequences that included tryptophan and lysine at high frequencies. Three complementary nonapeptides (9mer com-peptides), wpkkhfwgq (Trp-D), kwkkhfwgq (Lys-D), and KWKKHFWGQ (Lys-L) (as a negative control) were picked from this table for co-assembly studies with C-peptide. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopies were utilized to study inter-peptide interactions and changes in secondary structures respectively. ATR-FTIR studies showed that there is indeed inter-peptide interaction between C-peptide and the tryptophan residues of the 9mer com-peptides. CD studies of unaggregated and colloidal C-peptide with the 9mer com-peptides suggest that the extent of co-assembly of C-peptide with Trp-D is greatest, followed by Lys-D and Lys-L. These results are promising and indicate that the presented strategy is viable for designing and evaluating longer complementary peptides, as well as complementary peptides for co-assembly with other polypeptides of interest and importance. We discuss the possibility of designing complementary peptides to inhibit toxic amyloidosis with this approach.     

基于电子商务的县域就地城镇化与农村发展新模式研究

文章从电子商务的内涵和县域电子商务的发展概况谈起,分析了电子商务对我国城镇化格局的影响,探讨了在互联网时代电子商务普及的影响下,人才和经济体在各级城市中获得的机会将更加平等化,我国大城市的中心性地位受到挑战,县域及其所管辖的农村地区迎来了前所未有的机遇,农村地区可以实现由工业化带动到信息化带动的跃迁式发展的城镇化新形势。文章进一步指出在这种新形势下,电子商务所驱动的县域就地城镇化和农村发展是当前新型城镇化的一种新思路,并深入分析了县域就地城镇化的内涵和路径以及基于电子商务的农村发展的三种新模式,分别是延伸式("赶街"模式)、介入式("聚土地"模式)和内生式("沙集"模式),为我国信息化时代背景下的新型城镇化发展提供了一定的参考。     

Effects of ventilation rate per person and per floor area on perceived air quality,sick building syndrome symptoms,and decision‐making

Ventilation rates (VRs) in buildings must adequately control indoor levels of pollutants; however, VRs are constrained by the energy costs. Experiments in a simulated office assessed the effects of VR per occupant on perceived air quality (PAQ), Sick Building Syndrome (SBS) symptoms, and decision‐making performance. A parallel set of experiments assessed the effects of VR per unit floor area on the same outcomes. Sixteen blinded healthy young adult subjects participated in each study. Each exposure lasted four hours and each subject experienced two conditions in a within‐subject study design. The order of presentation of test conditions, day of testing, and gender were balanced. Temperature, relative humidity, VRs, and concentrations of pollutants were monitored. Online surveys assessed PAQ and SBS symptoms and a validated computer‐based tool measured decision‐making performance. Neither changing the VR per person nor changing the VR per floor area, had consistent statistically significant effects on PAQ or SBS symptoms. However, reductions in either occupant‐based VR or floor‐area‐based VR had a significant and independent negative impact on most decision‐making measures. These results indicate that the changes in VR employed in the study influence performance of healthy young adults even when PAQ and SBS symptoms are unaffected.     

Multi-breath dry powder inhaler for delivery of cohesive powders in the treatment of bronchiectasis

A series of co-engineered macrolide–mannitol particles were successfully prepared using azithromycin (AZ) as a model drug. The formulation was designed to target local inflammation and bacterial colonization, via the macrolide component, while the mannitol acted as mucolytic and taste-masking agent. The engineered particles were evaluated in terms of their physico-chemical properties and aerosol performance when delivered via a novel high-payload dry powder Orbital^? inhaler device that operates via multiple inhalation manoeuvres. All formulations prepared were of suitable size for inhalation drug delivery and contained a mixture of amorphous AZ with crystalline mannitol. A co-spray dried formulation containing 200?mg of 50:50?w/w AZ: mannitol had 57.6%?±?7.6% delivery efficiency with a fine particle fraction (≤6.8?µm) of the emitted aerosol cloud being 80.4%?±?1.1%, with minimal throat deposition (5.3?±?0.9%). Subsequently, it can be concluded that the use of this device in combination with the co-engineered macrolide–mannitol therapy may provide a means of treating bronchiectasis.     

Effects of branched‐chain amino acid addition on chemical constituents in lychee wine fermented with Saccharomyces cerevisiae

This study investigated the impact of single branched‐chain amino acid addition (L‐valine, L‐leucine, L‐isoleucine) on nonvolatile and volatile constituents in lychee wine fermented with Saccharomyces cerevisiae MERIT.ferm. The individual addition of branched‐chain amino acids decreased the consumption of proline with significantly different rates. The lychee wine with added L‐leucine and L‐isoleucine had higher odour activity values (OAVs) of isoamyl alcohol, active amyl alcohol and isoamyl acetate. The lychee wine with added L‐valine had higher OAVs of isobutyric acid and isobutyl alcohol (5.55 and 2.98, respectively), which were lower in the wine with added L‐leucine (2.91 and 1.02, respectively) or L‐isoleucine (3.43 and 1.73, respectively) relative to the control wine (4.18 and 1.77, respectively), suggesting interactive effects among the amino acids. These findings demonstrated that lychee wine aroma can potentially be manipulated via the addition of selected branched‐chain amino acids.     

A new probability transformation method based on a correlation coefficient of belief functions

The Dempster-Shafer evidence theory is widely used in many fields of information fusion because of its advantage in handling uncertain information. One of the key issues in this theory is how to make decision based on a basic probability assignment (BPA). Currently, a feasible scheme is transforming a BPA to a distribution of probabilities. However, little attention was paid to the correlation between BPA and probability distribution. In this paper, a novel method about the probability transformation based on a correlation coefficient of belief functions is proposed. The correlation coefficient is a new measurement, which can effectively measure the correlation between BPAs. The proposed method aims at maximizing the correlation coefficient between the given BPA and the transformed probability distribution. On the basis of this idea, the corresponding probability distribution can be obtained and could reflect the original information of the given BPA to the maximum extent. It is valid to consider that the proposed probability transformation method is reasonable and effective. Numerical examples are given to show the effectiveness of the proposed method.     

An energy-efficient cloud system with novel dynamic resource allocation methods

The Journal of Supercomputing - In the last decade, cloud computing has brought enormous changes to people’s lives. Cloud computing gives a client-driven computational model. In this case,...