Nutritional status of young children with inherited blood disorders in western Kenya.

To determine the association between a range of inherited blood disorders and indicators of poor nutrition, we analyzed data from a population-based, cross-sectional survey of 882 children 6–35 months of age in western Kenya. Of children with valid measurements, 71.7% were anemic (hemoglobin < 11 g/dL), 19.1% had ferritin levels < 12 μg/L, and 30.9% had retinol binding protein (RBP) levels < 0.7 μmol/L. Unadjusted analyses showed that compared with normal children, homozygous α(+)-thalassemia individuals had a higher prevalence of anemia (82.3% versus 66.8%, P = 0.001), but a lower prevalence of low RBP (20.5% versus 31.4%, P = 0.024). In multivariable analysis, homozygous α(+)-thalassemia remained associated with anemia (adjusted odds ratio [aOR] = 1.8, P = 0.004) but not with low RBP (aOR = 0.6, P = 0.065). Among young Kenyan children, α(+)-thalassemia is associated with anemia, whereas G6PD deficiency, haptoglobin 2-2, and HbS are not; none of these blood disorders are associated with iron deficiency, vitamin A deficiency, or poor growth

Improving file distribution performance by grouping in peer-to-peer networks

It has been shown that the peer-to-peer paradigm is more efficient than the traditional client-server model for file sharing among a large number of users. Given a group of leechers who wants to download a single file and a group of seeds who possesses the whole file, the minimum time needed for distributing the file to all users can be calculated based on their bandwidth availabilities. A scheduling algorithm has been developed so that every leecher can obtain the file within this minimum time. Unfortunately, this mechanism is not optimal with regard to the average download time among the peers. In this paper, we study how to reduce the average download time without prolonging the time needed for all leechers to obtain the file from a theoretical perspective. Based on the bandwidth capacities, the seeds and leechers are divided into different groups. We identify the necessary conditions for grouping to bring about benefits. We also study the impact on performance when leechers leave the system before the downloading process is complete. To evaluate our mechanism, we conduct extensive simulations and compare the performance with a BitTorrentlike file sharing algorithm. The results show that our grouping protocol successfully reduces the average download time over a wide range of system configurations. © 2009 IEEE.published_or_final_versio

Novel bandwidth strategy for wireless P2P file sharing

With the rapid development of the mobile device technology and wireless network technology, the need of an efficient file sharing method on wireless network becomes more and more significant. Peer-to-Peer(P2P) file distribution, as a quite popular method being used now, is a promising choice. However, the limitation of bandwidth of wireless networks greatly restricts the performance of wireless P2P. In this paper, we propose a new idea of better utilizing the limited bandwidth to improve the file distribution performance. The criteria of an optimal splitting of the half-duplex bandwidth is deduced with mathematical analysis. To achieve a further improvement on the average distribution time, we also propose a grouping strategy which works with the bandwidth strategy. Simulation results show that our mechanism can efficiently reduce the file distribution time among wireless peers. © 2011 IEEE.published_or_final_versionThe 2011 IEEE Wireless Communications and Networking Conference (WCNC), Cancun, Mexico, 28-31 March 2011. In IEEE Wireless Communications and Networking Conference Proceedings, 2011, p. 2161-216

A novel grouping strategy for reducing average distribution time in P2P file sharing

Peer-to-Peer(P2P) file distribution has been widely used for file sharing in recent years. When compared with the traditional client-server model, the P2P model is a lot more efficient as each user can act as both a client and a server. This enables the P2P file distribution to scale well with increasing number of users. Grouping strategy has been introduced to reduce the average distribution time among peers without prolonging the total time needed to obtain a file. In this paper, a novel grouping strategy which groups peers of similar bandwidth together is introduced. We mathematically illustrate that under certain circumstances, this new grouping strategy performs better than the Greedy Grouping mechanism. To understand the performance of our grouping mechanism more comprehensively, we conduct extensive simulations. The results show that our mechanism can enhance the performance significantly in different network settings. ©2010 IEEE.published_or_final_versionThe 2010 IEEE International Conference on Communications (ICC), Cape Town, South Africa, 1-5 May 2010. In IEEE International Conference on Communications, 201

Increased basal insulin secretion in Pdzd2-deficient mice

Expression of the multi-PDZ protein Pdzd2 (PDZ domain-containing protein 2) is enriched in pancreatic islet β cells, but not in exocrine or α cells, suggesting a role for Pdzd2 in the regulation of pancreatic β-cell function. To explore the in vivo function of Pdzd2, Pdzd2-deficient mice were generated. Homozygous Pdzd2 mutant mice were viable and their gross morphology appeared normal. Interestingly, Pdzd2-deficient mice showed enhanced glucose tolerance in intraperitoneal glucose tolerance tests and their plasma insulin levels indicated increased basal insulin secretion after fasting. Moreover, insulin release from mutant pancreatic islets was found to be twofold higher than from normal islets. To verify the functional defect in vitro, Pdzd2 was depleted in INS-1E cells using two siRNA duplexes. Pdzd2-depleted INS-1E cells also displayed increased insulin secretion at low concentrations of glucose. Our results provide the first evidence that Pdzd2 is required for normal regulation of basal insulin secretion. © 2009 Elsevier Ireland Ltd. All rights reserved.postprin

Epstein-barr virus-encoded latent membrane protein 1 impairs G2 checkpoint in human nasopharyngeal epithelial cells through defective Chk1 activation

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, particularly in southern regions of China. EBV infection is closely associated with NPC and has long been postulated to play an etiological role in the development of NPC. However, the role of EBV in malignant transformation of nasopharyngeal epithelial cells remains enigmatic. The current hypothesis of NPC development is that premalignant nasopharyngeal epithelial cells harboring genetic alterations support EBV infection and expression of EBV genes induces further genomic instability to facilitate the development of NPC. The latent membrane protein 1 (LMP1) is a well-documented EBV-encoded oncogene. The involvement of LMP1 in human epithelial malignancies has been implicated, but the mechanisms of oncogenic actions of LMP1, particularly in nasopharyngeal cells, are unclear. Here we observed that LMP1 expression in nasopharyngeal epithelial cells impaired G2 checkpoint, leading to formation of unrepaired chromatid breaks in metaphases after γ-ray irradiation. We further found that defective Chk1 activation was involved in the induction of G2 checkpoint defect in LMP1-expressing nasopharyngeal epithelial cells. Impairment of G2 checkpoint could result in loss of the acentrically broken chromatids and propagation of broken centric chromatids in daughter cells exiting mitosis, which facilitates chromosome instability. Our findings suggest that LMP1 expression facilitates genomic instability in cells under genotoxic stress. Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development. © 2012 Deng et al.published_or_final_versio

Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.published_or_final_versio

Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance

FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated beta-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer cells and deregulated in the paclitaxel-resistant MCF-7TaxR cells. KIF20A depletion also renders MCF-7 and MCF-7TaxR cells more sensitive to paclitaxel-induced cellular senescence. Crucially, resembling paclitaxel treatment, silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle morphology and chromosome alignment, which have been shown to induce mitotic catastrophe-dependent senescence. The physiological relevance of the regulation of KIF20A by FOXM1 is further highlighted by the strong and significant correlations between FOXM1 and KIF20A expression in breast cancer patient samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA expression significantly associates with poor survival, consistent with a role of FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A expression may confer paclitaxel resistance. These findings provide insights into the underlying mechanisms of paclitaxel resistance and have implications for the development of predictive biomarkers and novel chemotherapeutic strategies for paclitaxel resistance.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.152.published_or_final_versio

The association between internet addiction and psychiatric co-morbidity: A meta-analysis

Background: This study evaluates the association between Internal Addiction (IA) and psychiatric co-morbidity in the literature.Methods: Meta-analyses were conducted on cross-sectional, case-control and cohort studies which examined the relationship between IA and psychiatric co-morbidity. Selected studies were extracted from major online databases. The inclusion criteria are as follows: 1) studies conducted on human subjects; 2) IA and psychiatric co-morbidity were assessed by standardised questionnaires; and 3) availability of adequate information to calculate the effect size. Random-effects models were used to calculate the aggregate prevalence and the pooled odds ratios (OR).Results: Eight studies comprising 1641 patients suffering from IA and 11210 controls were included. Our analyses demonstrated a significant and positive association between IA and alcohol abuse (OR = 3.05, 95% CI = 2.14-4.37, z = 6.12, P < 0.001), attention deficit and hyperactivity (OR = 2.85, 95% CI = 2.15-3.77, z = 7.27, P < 0.001), depression (OR = 2.77, 95% CI = 2.04-3.75, z = 6.55, P < 0.001) and anxiety (OR = 2.70, 95% CI = 1.46-4.97, z = 3.18, P = 0.001).Conclusions: IA is significantly associated with alcohol abuse, attention deficit and hyperactivity, depression and anxiety. © 2014 Ho et al.; licensee BioMed Central Ltd