The timing of the formation and usage of replicase clusters in S-phase nuclei of human diploid fibroblasts

The sites of nascent DNA synthesis were compared with the distribution of the proliferating cell nuclear antigen (PCNA) in S-phase nuclei of human diploid fibroblasts (HDF) by two in vitro techniques. Firstly, proliferating fibroblasts growing in culture that had been synchronised at S-phase were microinjected with the thymidine analogue biotin-11-dUTP. The sites of incorporation of biotin into injected cells were compared with the distribution of PCNA by indirect immunofluorescence microscopy and laser scanning confocal microscopy (LSCM). In common with other studies, a progression of patterns for both biotin incorporation and PCNA localisation was observed. However, we did not always observe coincidence in these patterns, the pattern of biotin incorporation often resembling the expected, preceding distribution of PCNA. In nuclei in which the pattern of biotin incorporation appeared to be identical to the distribution of PCNA, LSCM revealed that not all of the sites of PCNA immunofluorescence were incorporating biotin at the same time. Secondly, nuclei which had been isolated from quiescent cultures of HDF were innoculated into cell-free extracts of Xenopus eggs which support DNA replication in vitro. Following innoculation into these extracts DNA replication was initiated in each nucleus. The sites of DNA synthesis were detected by biotin-11-dUTP incorporation and compared with the distribution of PCNA by indirect immunofluorescence. Only a single pattern of biotin incorporation and PCNA distribution was observed. PCNA accumulated at multiple discrete spots some 15min before any biotin incorporation was observed. When biotin incorporation did occur, LSCM revealed almost complete coincidence between the sites of DNA synthesis and the sites at which PCNA was localised.Brunel Open Access Publishing Fun

Exaptation dynamics and entrepreneurial performance: evidence from the internet video industry

This paper explores entrepreneurial strategy by analyzing the Internet video industry. Data on entrants to the Chinese Internet video industry from 2006 to 2011 reveal how those that adapt to shifts in the environment outperform less flexible firms. The paper also shows how exaptive processes, including strategic commitment to user communities, increase resilience in start-ups that face such shifts. These findings introduce an expanded view of entrepreneurial strategy by directly linking strategic choice to venture performance and clarifying the role of exaptation in entrepreneurship

PENGARUH MEDIA SOSIAL FACEBOOK TERHADAP PRILAKU MENYIMPANG ANAK DI KELAS 8 DAN 9 PADA SMPN 2 SUMBERJAMBE KABUPATEN JEMBER TAHUN PELAJARAN 2015/2016

Media sosial akun facebook dan prilaku menyimpang anak menjadi pembicaraan dikalangan pemerhati dunia informasi dankomunikasi. Dengan seringnya membuka dan menambah banyak pertemanan didunia maya akan berdampak terhadap prilaku seseorang. Penelitian ini mencoba mengembangkan pengaruh facebook terhadap prilaku menyimpang siswa kelas 8 dan 9 di SMPN 2 Sumberjambe Kabupaten Jember tahun pelajaran 2015/2016. Setelah dilakukan survey awal dengan pertimbangan siswa sebagai subyek penelitian dapat memberi jawaban akurat berkaitan dengan kegiatan mereka di sekolah. Subyek siswa ini dipakai karena mereka tergolong remaja yang rawan dengan prilaku menyimpang. Pengamatan selama tiga kali salah satunya dengan menyebar angket kepada siswa ternyata cukup mengejutkan bahwa memiliki facebook tidak berpengaruh terhadap prilaku menyimpang anak, bahkan diantara mereka yang memiliki maupun yang tidak memiliki akun face book hampir berimbang . Dari 221 siswa yang diteliti 106 siswa atau 48 % memiliki akun facebook, dan 115 siswa atau 53 % tidak memilikinya.&nbsp

Investigating the effects of inorganic nitrate on vascular function, inflammation and platelet reactivity in healthy volunteers and patients with stable angina

This thesis is studying nitric oxide (NO) as a fundamental basis for health and disease and investigating as well as modifying its properties for therapeutic purposes. In the UK, nearly 3.5 million people have angina symptoms or have had a myocardial infarction (MI), or both. The mainstay treatment for reducing the symptoms of angina and long-term risk of MI in patients with heart disease is stent implantation in the diseased coronary artery. While this procedure has revolutionised treatment, the incidence of secondary events remains a concern. These repeat events are thought to be due, in part, to an increased inflammatory state that predisposes to continued enhanced platelet reactivity, endothelial dysfunction, and ultimately restenosis of the stented artery. In addition, CVD in general including atherosclerotic disease occurs at a lower incidence in premenopausal females compared with age-matched males. There has been considerable interest in why this might be the case but whether sex differences in inflammation underlie these differences is uncertain. Greater understanding of the role of inflammation and strategies that might selectively reduce inflammation within the CVD setting may offer novel approaches to therapeutics. Thus, I prospectively investigated whether inflammation and components of the inflammatory response are altered in females compared with males using two healthy volunteer studies. In the first study, I assessed systemic inflammatory markers and vascular function using brachial artery flow-mediated dilation (FMD). Typhoid vaccine induced mild systemic inflammation at 8 hours, reflected by increased white cell count in both sexes. Systemic inflammation in turn caused a decrease in FMD in males, but an increase in females, at 8 hours. To investigate the differences in inflammatory responses between the sexes further in a separate study, I measured inflammatory exudate mediators and cellular recruitment in cantharidin-induced skin blisters. At 24 hours, cantharidin formed blisters of similar volume in both sexes; however, at 72 hours, blisters had only resolved in females. The activation state of all major leukocytes was lower in blisters of females, which was associated with enhanced levels of the resolving lipids. Together these findings suggest that in females, resolution of inflammation is accelerated compared with males, and that within the cardiovascular system this is likely to result in improved vascular function. The second part of my thesis studies was focussed on using the techniques established in the healthy volunteer studies to investigate whether a once a day inorganic nitrate (NO3-) administration might, through modification of inflammatory pathways, favourably modulate platelet reactivity and endothelial function leading to a decrease in restenosis. This was conducted in the form of the NITRATE-OCT study, which is a phase II trial enrolling 246 patients with stable angina due to have elective stent implantation. Patients have been randomised to receive 6 months of a once a day dose of either NO3--rich beetroot juice or NO3--deplete beetroot juice (placebo) before their procedure. The primary outcome is reduction of in-stent late loss assessed by quantitative coronary angiography (QCA) and optical coherence tomography (OCT) at 6 months. Thus far, we have baseline demographic data for 200 patients in total and the study is still ongoing to ensure the investigators remain blinded. At baseline there were no significant differences in demographic or procedural characteristics between the two groups

Control versus execution: endogenous appropriability and entrepreneurial strategy

This article considers the role of Rosenbergian uncertainty (i.e., economic uncertainties that arise after successful invention) in shaping appropriability for start-up innovators. Rather than assuming that the appropriability regime surrounding an innovation is exogenous, we focus on the endogenous choice entrepreneurs face between investing in ensuring control-based appropriability versus investing in the execution and operation of their fledgling businesses. Investment in execution allows entrepreneurs to advance more quickly than competitors, while control requires delays in commercialization. Control and execution are strategic substitutes, as they represent alternative paths to earning future rents. Because the size and likelihood of these rents are uncertain, entrepreneurs may be unable to rank these alternative paths in advance, and so their endogenous choice will be grounded in factors such as individual preferences, capabilities, or coherence with their overall entrepreneurial strategy. A subtle consequence is that the appropriability regime ultimately governing an innovation will be the result of the endogenous choices of the entrepreneur rather than more traditional environmental factors. Motivated by notable historical examples such as the invention and commercialization of the telephone, we explore these ideas by considering the choice of appropriability regime among a sample of academic entrepreneurs: within a sample of ventures that could have been developed by either faculty or students (or both), we find that faculty-led ventures are much more closely associated with formal intellectual property, student-led ventures are more rapid in their commercialization activities, and, relative to faculty-led ventures, student-led ventures display a trade-off between patenting and commercialization speed

Elemental Analysis and Biological Activities of Chrysophyllum roxburghii G. Don (Sapotaceae) Leaves

The present study was performed to estimate elementals and to determine bioactivities namely anticariogenic, antioxidant, pancreatic lipase inhibitory and cytotoxic activity of Chrysophyllum roxburghii leaves. Elemental analysis revealed that calcium and manganese were present in high concentration among principal and trace elements respectively. Preliminary phytochemical analysis revealed the presence of tannins, alkaloids and terpenoids in the extract. Total phenolic content was found to be 179.05mg Gallic acid equivalents/g of extract. The methanol extract caused a dose dependent inhibition of Streptomyces mutans isolates. All the isolates tested were found to be sensitive to extract. In DPPH assay, the extract exhibited marked dose dependent scavenging activity against DPPH free radical with an IC50 value of 3.54ìg/ml. In Ferric reducing assay, the absorbance of the reaction mixture was found to increase with the concentration of extract which is suggestive of reducing power. The activity of chicken pancreatic lipase was affected by the extract and the effect was concentration dependent. Higher inhibition of enzyme (>50%) was observed at extract concentration 50mg/ml. In cytotoxic study, the lethality was found to be directly proportional to extract concentration. Highest mortality (>80%) of shrimps was observed at extract concentration 1000µg/ml. LC50 of extract was 83.04µg/ml. The bioactivities of the extract could be attributed to the presence of secondary metabolites in the plant material. The plant material could be used as a source of important elements required for the body. In suitable form, the plant could be used in the prevention and treatment of dental caries, oxidative damage, obesity and cancer

Control Versus Execution: Endogenous Appropriability and Entrepreneurial Strategy

This paper considers the role of Rosenbergian uncertainty (i.e., economic uncertainties that arise after successful invention) in shaping appropriability for start-up innovators. Rather than assuming that the appropriability regime surrounding an innovation is exogenous, we focus on the endogenous choice entrepreneurs face between investing in ensuring control-based appropriability versus investing in the execution and operation of their fledgling businesses. Investment in execution allows entrepreneurs to advance more quickly than competitors, while control requires delays in commercialization. Control and execution are strategic substitutes as they represent alternative paths to earning future rents. Because the size and likelihood of these rents is uncertain, entrepreneurs may be unable to rank these alternative paths in advance, and so their endogenous choice will be grounded in factors such as individual preferences, capabilities, or coherence with their overall entrepreneurial strategy. A subtle consequence is that the appropriability regime ultimately governing an innovation will be the result of the endogenous choices of the entrepreneur rather than more traditional environmental factors. Motivated by notable historical examples such as the invention and commercialization of the telephone, we explore these ideas by considering the choice of appropriability regime among a sample of academic entrepreneurs: within a sample of ventures that could have been developed by either faculty or students (or both), we find that faculty-led ventures are much more closely associated with formal intellectual property, student-led ventures are more rapid in their commercialization activities, and, relative to faculty-led ventures, student-led ventures display a tradeoff between patenting and commercialization speed