Recapitulation of primary nailing in open diaphyseal fractures of tibia

Tibia fractures are the commonest long bone fracture, most commonly resulting from high velocity injury. We investigated whether primary nailing in open tibia fractures were producing satisfactory outcomes and we compared the outcomes in terms of fracture union and rates of infection. We identified 202 citations related to our searches from our key words, out of which 89 were original articles, which were eligible and others were case reports and review articles. We found 4 from these references which had the parallel inclusion criteria and were reviewed. All 4 studies had almost similar time period for the fracture union. Infection rates in this study were directly related to the severity of the grade of injury, which were commonly experienced in grade III injuries. In conclusion, our analysis had no significant difference in postoperative healing duration, implant failure rates, postoperative infection and secondary operation rates in primary nailing for open tibia fractures.

Replication stress and chromatin context link ATM activation to a role in DNA replication

ATM-mediated signaling in response to DNA damage is a barrier to tumorigenesis. Here we asked whether replication stress could also contribute to ATM signaling. We demonstrate that, in the absence of DNA damage, ATM responds to replication stress in a hypoxia-induced heterochromatin-like context. In certain hypoxic conditions, replication stress occurs in the absence of detectable DNA damage. Hypoxia also induces H3K9me3, a histone modification associated with gene repression and heterochromatin. Hypoxia-induced replication stress together with increased H3K9me3 leads to ATM activation. Importantly, ATM prevents the accumulation of DNA damage in hypoxia. Most significantly, we describe a stress-specific role for ATM in maintaining DNA replication rates in a background of increased H3K9me3. Furthermore, the ATM-mediated response to oncogene-induced replication stress is enhanced in hypoxic conditions. Together, these data indicate that hypoxia plays a critical role in the activation of the DNA damage response, therefore contributing to this barrier to tumorigenesis

Efficient and Secured Swarm Pattern Multi-UAV Communication

Unmanned Aerial Vehicle (UAV) or drone, is an evolving technology in today's market with an enormous number of applications. Mini UAVs are developed in order to compensate the performance constraints imposed by larger UAVs during emergency situations. Multiple mini autonomous UAVs require communication and coordination for ubiquitous coverage and relaying during deployment. Multi-UAV coordination or swarm optimization is required for reliable connectivity among UAVs, due to its high mobility and dynamic topology. In this paper, a Secured UAV (S-UAV) model is proposed which takes the location of the UAVs as inputs to form a Wireless Mesh Network (WMN) among multiple drones with the help of a centralized controller. After WMN formation, efficient communication takes place using A∗ search, an intelligent algorithm that finds the shortest communication path among UAVs. Further, the S-UAV model utilizes cryptographic techniques such as Advanced Encryption Standard (AES) and Blowfish to overcome the security attacks efficiently. Simulation results show that the S-UAV model offers higher throughput, reduced power consumption and guaranteed message transmission with reduced encryption and decryption time

TP53 modulates radiotherapy fraction size sensitivity in normal and malignant cells

Recent clinical trials in breast and prostate cancer have established that fewer, larger daily doses (fractions) of radiotherapy are safe and effective, but these do not represent personalised dosing on a patient-by-patient basis. Understanding cell and molecular mechanisms determining fraction size sensitivity is essential to fully exploit this therapeutic variable for patient benefit. The hypothesis under test in this study is that fraction size sensitivity is dependent on the presence of wild-type (WT) p53 and intact non-homologous end-joining (NHEJ). Using single or split-doses of radiation in a range of normal and malignant cells, split-dose recovery was determined using colony-survival assays. Both normal and tumour cells with WT p53 demonstrated significant split-dose recovery, whereas Li-Fraumeni fibroblasts and tumour cells with defective G1/S checkpoint had a large S/G2 component and lost the sparing effect of smaller fractions. There was lack of split-dose recovery in NHEJ-deficient cells and DNA-PKcs inhibitor increased sensitivity to split-doses in glioma cells. Furthermore, siRNA knockdown of p53 in fibroblasts reduced split-dose recovery. In summary, cells defective in p53 are less sensitive to radiotherapy fraction size and lack of split-dose recovery in DNA ligase IV and DNA-PKcs mutant cells suggests the dependence of fraction size sensitivity on intact NHEJ

Identification of novel strategies to radiosensitise tumour cells

In this study we found that tumour cells can be radiosensitised by targeting the DNA damage response kinases, ATM and ATR. Furthermore, we highlight that Wee1 inhibitors, which are already under the clinical trials need to be further investigated in combination with radiation in the context of tumour hypoxia. In addition, we observed that induction of autophagy using STF-62247 can lead to radiosensitisation of VHL deficient RCC cells. Our studies with the rapamycin analogue temsirolimus, already in the clinic for the treatment of various cancers, can be a potential candidate as a radiosensitiser for RCC cells. Overall, these finding led us to investigate further whether autophagy inducing compounds, which are either in clinic or in clinical trials, can effect the response to radiation. From a panel of candidate drugs which are known to induce autophagy we identified an aminopeptidase inhibitor, CHR-2797. CHR-2797 induces autophagy in the oesophageal cancer cell lines FLO-1 and OE21. Although, our results with CHR-2797 demonstrate it as a potential radiosensitiser, the mechanism of its radiosensitisation needs to be established. Our results from CHR-2797-induced radiosensitisation, further led us to investigate if other aminopeptidase inhibitors have a role in radiosensitisation. Therefore, we selectively screened candidate aminopeptidase inhibitors and identified some promising effects on radiosensitivity.</p

Identification of novel strategies to radiosensitise tumour cells

In this study we found that tumour cells can be radiosensitised by targeting the DNA damage response kinases, ATM and ATR. Furthermore, we highlight that Wee1 inhibitors, which are already under the clinical trials need to be further investigated in combination with radiation in the context of tumour hypoxia. In addition, we observed that induction of autophagy using STF-62247 can lead to radiosensitisation of VHL deficient RCC cells. Our studies with the rapamycin analogue temsirolimus, already in the clinic for the treatment of various cancers, can be a potential candidate as a radiosensitiser for RCC cells. Overall, these finding led us to investigate further whether autophagy inducing compounds, which are either in clinic or in clinical trials, can effect the response to radiation. From a panel of candidate drugs which are known to induce autophagy we identified an aminopeptidase inhibitor, CHR-2797. CHR-2797 induces autophagy in the oesophageal cancer cell lines FLO-1 and OE21. Although, our results with CHR-2797 demonstrate it as a potential radiosensitiser, the mechanism of its radiosensitisation needs to be established. Our results from CHR-2797-induced radiosensitisation, further led us to investigate if other aminopeptidase inhibitors have a role in radiosensitisation. Therefore, we selectively screened candidate aminopeptidase inhibitors and identified some promising effects on radiosensitivity.This thesis is not currently available in ORA

Stochastic Numerical Simulation for the Evaluation of Mechanical Properties of Filled Polymer Composites

Reinforced polymeric composites are profoundly used in variety of applications due to its high strength to weight ratio and ease of fabrication. The wide spread application of reinforced polymeric materials in the electronic industries have created a great demand in fabricating a kind of reinforced polymeric system, which is light but has better mechanical strength and good thermal properties. Especially glass microsphere filled epoxy resin composites is used as a potting compound in electronic and aviation industries. Therefore, knowledge of the fundamental thermal and mechanical properties of these systems is highly essential in the formulation of advanced electronic potting compounds. In this work, the effective mechanical properties of glass microsphere filled epoxy system is investigated numerically by stochastic simulation. Numerical simulation software ANSYS is used to characterise the microstructure of the filled epoxy system. MATLAB code has been developed to model the randomness of the particle. The geometric model generated from the MATLAB code is given as an input to ANSYS. Random particle Representative Volume Element (RVE) model is used to evaluate the mechanical properties at various loading fractions. The effect of particle size on mechanical properties of glass microsphere filled epoxy composite is studied. Further the random RVE modeling scheme is compared with single RVE modeling scheme and its significance is reported. The numerically predicted values of effective modulus is then compared with the analytical models and with the literature experimental data. Also the significance of the analytical model on the determination of properties is reported. Then, the effect of interface on the mechanical characterisation by stochastic model is analysed and the debonding of the particle is also simulated

(E)-2-[(2-Formylphenoxy)methyl]-3-(4-isopropylphenyl)acrylonitrile

In the title compound, C20H19NO2, the dihedral angle between the benzene rings is 77.12&#8197;(8)&#176;. The terminal isopropyl group is disordered over two orientations, with site occupancies of 0.720&#8197;(14) and 0.280&#8197;(14). In the crystal, molecules are linked through a weak C&#8212;H...O interaction, forming a zigzag chain along the c-axis direction