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Hypoxia-induced SETX links replication stress with the unfolded protein response
YesTumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.SR, KBL, PV and MH were supported by a CRUK grant C5255/A23755 (awarded to E.M.H.). N.N. was supported by an MRC studentship (MC_ST_U16007). I. P.F. was supported by CRUK Oxford Centre Prize DPhil Studentship C38302/A12981. N.G. was supported by a Royal Society University Research fellowship. W.-C.C. was funded by CRUK grant 23969 (awarded to F.M.B.). S.F.E.-K. was supported by a Wellcome Trust Investigator Award (103844) and a Lister Institute of Preventative Medicine Fellowship (137661). J.G. was supported by a Jean Shanks Foundation/ Pathological Society of Great Britain and Ireland Clinical PhD Fellowship (JSPS CPhD 2018 01)
Allelopathic effects of Sonchus oleraceus L. on the germination and seedling growth of crop and weed species
Experimental and theoretical investigations of bolted joints for pultruded composite materials.
Fibre reinforced structural members are currently being produced using the pultrusion process. The mechanical properties of these members are fundamentally different from those of conventional metallic ones. Therefore, the approximate theories which are suitable for designing the latter elements have to be revised before they are applied to pultrusions. An important aspect of the design of building frames is that of joints. The bolting technique is considered as the most suitable method for on-site jointing. Accordingly, experimental investigations are undertaken in order to establish the behaviour of bolted joints in pultrusions. Numerical and analytical methods are used to investigate the stresses in these joints. Single and two-bolt joints were the subject of experimental investigations. It is shown that materials with high percentage of axial fibres do not develop bearing failure. However, provided the end distance is sufficient, the resulting shear failure will be ductile. The load distribution in joints with two bolts is measured and it is found that it varies with the load on the joint. The theoretical investigations compare the use of the laminated plate theory with three dimensional analyses. Because the use of the laminated plate theory is found to be reasonably accurate, an improvement for the case of a symmetrical laminate is proposed where the laminated shell theory is used to model half the plate only. This technique is based on the assumption of a bi-linear variation of the stress through the thickness of the laminate. The effect of the fastener is an important part of the behaviour of the joints. Three dimensional analyses are performed to assess its effect. To avoid the complications of performing three dimensional analyses, a two dimensional model for considering the effect of the washer on the joint is devised. In addition, a method which avoids iteration when considering the effect of friction is formulated. A finite element formulation for the non-linear and failure behaviour of uniaxial composite materials is developed to investigate the behaviour of the joints. Finally, a closed form analytical formula for calculating the tangential stress around a hole in an infinite orthotropic plate loaded on the hole is generated to simplify the design procedures
18-month progestogen-only contraception during breast-feeding in Libyan women
This study was undertaken to evaluate the efficacy and the influence of progestogen-only contraceptives (POCs) in
postpartum lactating mothers over a period of 18-months. 250 mothers were randomised to either the study
groups or the control group. In the study groups, 100 mothers were given an oral progestogen pill; lynestrenol and
another 100 mothers were assigned to injectable progestogens; depot medroxy-progesterone acetate (DMPA) and
norethisterone oenanthate (NET EN), 50 each.The control group (n=50) was given nonhormonal methods.There
was no contraceptive failure or negative influence on lactation among the medication groups.There were no
significant differences between the groups with respect to the continuation rates and to the adverse effects that led
to premature discontinuation. In conclusion, POCs can be used by lactating mothers effectively and safely for at least
18 months.Therefore, the wide use of these methods should be recommended if the international targets to
protect, promote and support breast-feeding as well as family planning are to be achieved
Interrelationship between major, minor and trace elements in Kalabsha wells and in high dam lake waters
Evening Telegram, 1895-02-15
The Evening Telegram began publication in St. John's on 3 April 1879 and remains in print today under the title The Telegram. It was published daily except Sunday through to 1958, the frequency changing thereafter. -- The total collection has been split into several parts; this portion contains the years 1879-1899. -- Not published: 9 June - 31 August 1892, 2-10 January 1894. Missing issue ranges: 3-7 April 1879, 5-6 May 1880, 29-31 December 1880, 31 March - 19 April 1881, 25-30 June 1895. In addition, these individual issues are missing from 1880: 16 January, 2 April, 17 April, 24 April, 11 May, 28 May, 11 October, 22 October, 13 November, 7 December
Minimally invasive sacroiliac fusion, a case series, and a literature review
Introduction: Non-autoimmune sacroiliac joint pain contributes to nearly a quarter of low back pain patients. Non-surgical management fails to satisfy patients. A new minimally invasive technique for sacroiliac stabilization has been introduced, defying the traditional rules of fusion. The results outside explanatory trials and in day-to-day practice have not been reported. Materials and methods: This case series includes 20 patients diagnosed with chronic sacroiliac pain resistant to conservative management for at least 6 months. The diagnosis was confirmed with a positive sacroiliac injection. Patients underwent stabilization using the iFuse® implant. Patients were followed up for a minimum of one year. The primary outcome was the functional outcomes, assessed using VAS, ODI, and SF36. Secondary procedure rates, complication rates, and radiological assessments of fusion were collected as secondary outcomes. Results: At one year, the mean VAS score improved from 81.25 ± 10.7 SD preoperatively to 52.5 ± 26.8, p-value 0.0013. The mean ODI improved from 54.8 ± 11.21 SD preoperatively to 41.315 ± 15.34, P value = 0.0079. The mean PCS and MCS of SF36 improved by 17 and 20 points, respectively. Only 55% of patients achieved the MCID for the VAS score. 35% of the cohort had secondary procedures. Discussion: Minimally invasive sacroiliac fusion resulted in an improvement in mean functional scores with a wide dispersion. Patients not achieving MCID are patients with either a malpositioned implant, an associated lumbar pathology, or an inaccurate diagnosis. Our results are underwhelming compared to similar work but are still better than conservative cohorts in comparative studies. Conclusion: Minimally invasive sacroiliac fusion can be used successfully in select patients. Attention to diagnosis and surgical technique can improve the reproducibility of results
Performance investigation and control design of SSI grid-connected system for PV applications with maximum power extraction
Split-source inverter (SSI) has been recently developed as an alternative to the commonly used ZSI where it can serve an interface between the renewable energy sources and the common grid. This paper presents a mathematical model and control strategy for grid-connected SSI system with either constant voltage source or photovoltaic (PV) source. The control strategy is based on linear PI controllers which are fine-tuned by the frequency loop shaping method with the help of the derived mathematical model to ensure the stability of the system with robust dynamic behavior. The derived mathematical model provides a straightforward and efficient understanding of the dynamics resulting from the interaction between the PV and the SSI grid-connected system. The simulation results indicate that the system has a robust dynamic behavior when subjected to various transient conditions. Finally, a downscaled prototype of SSI grid-connected system is implemented to experimentally validate both the mathematical model and control strategy