24 research outputs found

    Intrusion detection and management over the world wide web

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    As the Internet and society become ever more integrated so the number of Internet users continues to grow. Today there are 1.6 billion Internet users. They use its services to work from home, shop for gifts, socialise with friends, research the family holiday and manage their finances. Through generating both wealth and employment the Internet and our economies have also become interwoven. The growth of the Internet has attracted hackers and organised criminals. Users are targeted for financial gain through malware and social engineering attacks. Industry has responded to the growing threat by developing a range defences: antivirus software, firewalls and intrusion detection systems are all readily available. Yet the Internet security problem continues to grow and Internet crime continues to thrive. Warnings on the latest application vulnerabilities, phishing scams and malware epidemics are announced regularly and serve to heighten user anxiety. Not only are users targeted for attack but so too are businesses, corporations, public utilities and even states. Implementing network security remains an error prone task for the modern Internet user. In response this thesis explores whether intrusion detection and management can be effectively offered as a web service to users in order to better protect them and heighten their awareness of the Internet security threat

    A Tumor Vascularâ Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia

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    Vascularâ targeted photodynamic therapy (VTP) is a recently approved strategy for treating solid tumors. However, the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality approach. Here, a new graphene oxide (GO)â based nanosystem for rationally designed, interlocking trimodal cancer therapy that enables VTP using photosensitizer verteporfin (VP) (1) with codelivery of banoxantrone dihydrochloride (AQ4N) (2), a hypoxiaâ activated prodrug (HAP), and HIFâ 1α siRNA (siHIFâ 1α) (3) is reported. The VTPâ induced aggravated hypoxia is highly favorable for AQ4N activation into AQ4 (a topoisomerase II inhibitor) for chemotherapy. However, the hypoxiaâ induced HIFâ 1α acts as a â hidden brake,â through downregulating CYP450 (the dominant HAPâ activating reductases), to substantially hinder AQ4N activation. siHIFâ 1α is rationally adopted to suppress the HIFâ 1α expression upon hypoxia and further enhance AQ4N activation. This trimodal nanosystem significantly delays the growth of PCâ 3 tumors in vivo compared to the control nanoparticles carrying VP, AQ4N, or siHIFâ 1α alone or their pairwise combinations. This multimodal nanoparticle design presents, the first example exploiting VTP to actively induce hypoxia for enhanced HAP activation. It is also revealed that HAP activation is still insufficient under hypoxia due to the hidden downregulation of the HAPâ activating reductases (CYP450), and this can be well overcome by GO nanoparticleâ mediated siHIFâ 1α intervention.Vascularâ targeted photodynamic therapy (VTP) is integrated with hypoxiaâ activated prodrug (AQ4N) and HIFâ 1α siRNA (siHIFâ 1α) for interlocking trimodal therapy. The VTPâ induced aggravated hypoxia is exploited for efficient AQ4N activation for chemotherapy. HIFâ 1α induced by hypoxia acts as a â hidden brake,â through downregulating CYP450 reductases, to hinder AQ4N activation. siHIFâ 1α is rationally adopted to suppress HIFâ 1α expression upon VTP to enhance AQ4N activation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/1/advs661-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/2/advs661.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/3/advs661_am.pd

    The trans-ancestral genomic architecture of glycemic traits

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    Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Synthesis and Anti-Tumor Activities of 4-Anilinoquinoline Derivatives

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    Twenty-two 7-fluoro (or 8-methoxy)-4-anilinoquinolines compounds were designed and synthesized as potentially potent and selective antitumor inhibitors. All the prepared compounds were evaluated for their in vitro antiproliferative activities against the HeLa and BGC823 cell lines. Ten compounds (1a–g; 2c; 2e and 2i) exhibited excellent antitumor activity superior to that of gefitinib. Among the ten compounds; seven (1a–c; 1e–1g and 2i) displayed excellent selectivity for BGC823 cells. In particular; 1f and 2i exhibited potent cytotoxic activities against HeLa cells and BGC823 cells with better IC50 values than gefitinib
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