902 research outputs found
A New Business Model of Electronic Commerce with Innovative Strategies
There are a lot of problems that make the business of electronic stores very difficult, especially for those firms that lack the required expertise and resources for running an electronic business. This study proposes a new business model of electronic commerce (EC), which aims to tackle those problems and help enterprises run electronic stores well. This model applies the franchise system of chain store, a very successful modern business model, to the management of electronic stores to take advantage of the chain’s competitive power by integrating individual affiliate sites as a whole. There are eight components in the model. Implementation strategies of the model, which are quite different from those generic strategies commonly used in implementing business models, are also proposed. The feasibility of the model and its implementation strategies were validated using the Nominal Group Technique (NGT), the case study, and the questionnaire survey approaches. Finally, practical implications for applying the model are discussed, and directions for further study are also suggested
2,2′-(p-Phenylene)bis(4,5-dihydro-1H-imidazol-3-ium) bis(3-nitrobenzoate)
In the title compound, C12H16N4
+·2C7H4NO4
−, the complete 2,2′-(p-phenylene)bis(4,5-dihydro-1H-imidazol-3-ium) (bib) dication is generated by crystallographic inversion symmetry. The bib cations reside on crystallographic inversion centers, which coincide with the centroids of the respective benzene rings. In the cation, the imidazole ring adopts an envelop conformation with the flap atom displaced by 0.082 (3) Å from the plane through the other ring atoms. In the crystal, the cations and anions are linked through intermolecular N—H⋯O hydrogen bonds, forming chains running along the a axis. C—H⋯O interactions also occur. Weak π–π contacts between the imidazole rings of bib and between the benzene rings of NB [centroid–centroid distances = 3.501 (1) and 3.281 (2) Å, respectively] may further stabilize the structure
Comparative analysis of protocols to induce human CD4+Foxp3+ regulatory T cells by combinations of IL‐2, TGF‐beta, retinoic acid, rapamycin and butyrate
Regulatory T cells (Tregs) suppress other immune cells and are critical mediators of peripheral
tolerance. Therapeutic manipulation of Tregs is subject to numerous clinical investigations
including trials for adoptive Treg transfer. Since the number of naturally occurring
Tregs (nTregs) is minute, it is highly desirable to develop a complementary approach of
inducing Tregs (iTregs) from naïve T cells. Mouse studies exemplify the importance of
peripherally induced Tregs as well as the applicability of iTreg transfer in different disease
models. Yet, procedures to generate iTregs are currently controversial, particularly for
human cells. Here we therefore comprehensively compare different established and define
novel protocols of human iTreg generation using TGF-β in combination with other compounds.
We found that human iTregs expressed several Treg signature molecules, such as
Foxp3, CTLA-4 and EOS, while exhibiting low expression of the cytokines Interferon-γ, IL-
10 and IL-17. Importantly, we identified a novel combination of TGF-β, retinoic acid and
rapamycin as a robust protocol to induce human iTregs with superior suppressive activity in
vitro compared to currently established induction protocols. However, iTregs generated by
these protocols did not stably retain Foxp3 expression and did not suppress in vivo in a
humanized graft-versus-host-disease mouse model, highlighting the need for further
research to attain stable, suppressive iTregs. These results advance our understanding of
the conditions enabling human iTreg generation and may have important implications for
the development of adoptive transfer strategies targeting autoimmune and inflammatory
diseases.Marie Curie Intra European Fellowship within the 7th European Community Framework Programme, FP7-PEOPLE-IEFDr. Ake Olssons FoundationKI Research FoundationsSwedish Research CouncilCERIC Linne CenterAFA insuranceStockholm County CouncilTorsten Soderberg FoundationPublishe
2-[4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]-4,5-dihydro-1H-imidazol-3-ium 4-aminobenzoate
In the cation of the title compound, C12H15N4
+·C7H6NO2
−, the benzene ring makes dihedral angles of 30.51 (9) and 25.64 (9)° with the imidazole and imidazolinium rings, respectively. In the crystal, intermolecular N—H⋯O and N—H⋯N hydrogen-bonding interactions link the molecules into a three-dimensional network
De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family
AIM: To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32. METHODS: A family with familial exudative vitreoretinopathy (FEVR) phenotype was included in the study. Whole-exome sequencing (WES) was initially used to locate copy number variations (CNVs) on 7q31.31-31.32, but failed to detect the precise breakpoint. The long-read sequencing, Oxford Nanopore sequencing Technology (ONT) was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction (QPCR) and Sanger Sequencing. RESULTS: The proband, along with her father and younger brother, were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32, which included the FEVR-related gene TSPAN12. The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del. The proband exhibited a phase 2A FEVR phenotype, characterized by a falciform retinal fold, macular dragging, and peripheral neovascularization with leaking of fluorescence. These symptoms led to a significant decrease in visual acuity in both eyes. On the other hand, the affected father and younger brother showed a milder phenotype. CONCLUSION: The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype. The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders
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Hypokalemia, Its Contributing Factors and Renal Outcomes in Patients with Chronic Kidney Disease
Background: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated. Design, Participants & Measurements 2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used. Results: The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m2. Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK 5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range. Conclusion: In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes
An Evaluation of the Additive Effect of Natural Herbal Medicine on SARS or SARS-like Infectious Diseases in 2003: A Randomized, Double-blind, and Controlled Pilot Study
Natural herbal medicine (NHM) has been used to control infectious diseases for thousands of years. In view of the possible beneficial effect of NHM on SARS, we conducted this study to examine whether NHM is of any benefit as a supplementary treatment of SARS or SARS-like infectious disease. This was a randomized, double-blind, placebo-controlled trial. Twenty-eight patients fulfilled the WHO inclusion criteria and our exclusion criteria. All enrolled patients received routine western-medicine treatment. Patients were randomly allocated to one of the three supplementary treatment groups: NHM A (Group A, n = 9) NHM B (Group B, n = 9) or placebo (Group C, n = 10). Chest X-ray was done every 1 or 2 days for every patient. Reading radiologists use a standard 0–3 scoring system (0: no infiltration; 1: focal haziness or even small patchy lesion; 2: ground glass picture; 3: lobar consolidation) according to the severity of infiltration in each lung field (three lung fields in both right and left lungs). The main outcome measurements were the improving chest radiographic scores (IRS) and the duration (days) till improvement (DI). One patient from the placebo group passed away. Patients from NHM A took less days before showing improvement (6.7 ± 1.8) compared with placebo group (11.2 ± 4.9), which showed statistical significance (P = 0.04). The cases were too few to be conclusive, the initial observations seem to indicate NHM appears to be safe in non-criticallly ill patients and clinical trials are feasible in the setting of pandemic outbreaks
Assessing Nurses' Workplace Social Capital : A Study Protocol for Culturally Appropriate Instrument Development
Workplace social capital positively influences the quality but reduces the cost of healthcare services. Academic research suffers from limited and inadequate culturally sensitive nurses' workplace social capital instruments. Here we report on the design and protocol of a culturally focused instrument development study in China. The overarching objective of our dual phase study is to develop and validate a questionnaire measuring nurses' workplace social capital tailored toward Chinese cultural values and norms. In the first phase of INSTRUMENT DEVELOPMENT, the qualitative phase, we will conduct interviews with purposefully sampled nurses from five geographically diverse regions capturing 16 provinces in China to formulate the initial version of the Nurses' Workplace Social Capital Questionnaire (NWSCQ). Data collection will be stopped at the saturation point and content analysis will be performed for interview data in parallel. The initial version of the NWSCQ will be evaluated and confirmed by two-rounds of expert consultation (target N = 20) and pre-tested among 70 nurses. During the second phase of INSTRUMENT VALIDATION or the quantitative phase, we will validate the psychometric properties of the NWSCQ. The validity and reliability of the questionnaire will be examined and validated through three cross-sectional surveys among nurses (target N = 1154) randomly selected from 12 tertiary hospitals. We have reported our study protocol with the intention of sharing our experience with researchers in other countries who are striving to advance the phenomenon of culturally sensitive and social normatively appropriate nurses' workplace social capital. Findings from our study should advance the development of culturally appropriate and valid instrument of nurses' workplace social capital, another important step toward recognition and incorporation of cultural diversity in the daily operation of healthcare industry.Peer reviewe
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Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study
Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research
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