Effect of Vegetable Based Lubricants on Equal Channel Angular Extrusion Pressure

This research aimed at investigating vegetable based lubricant as a replacement for chemical based lubricants on extrusion pressure of equal channel angular extrusion of Aluminum. In the process, aluminum alloy (Al 6063) was heated at 350°C for one hour, machined and cut to billets size of 11.95 m x 11.95 m x 40 m (l × b × h). The billets were extruded through die of 12 mm x 12 mm channel cross-section area, the channel angle was 60°. Four vegetable based lubricants namely jatropha, neem, castor and cotton seed oils were used. The die was centrally located on the bed of vertical hydraulic testing machine and the billet was inserted into the entrance channel. Lubrication was applied to the billet to decrease its friction and with the channel inner wall. The ram displacement per plunger speed was 1 mm per 1 second respectively. For each lubricant, four samples were extruded through ECAE die to confirm the repeatability of the results and the average values of the extrusion pressure were computed. The results were compared to the sample extruded via conventional lubricants. It was discovered of all the extruded samples, jatropha oil gave the least extrusion pressure of 83 kN, cottonseed oil extruded at 104 kN and castor oil at 151.4 kN while neem oil require the highest pressure at 220.9 kN. The chemical based lubricants that serve as the control from the literature gave the extrusion pressure of 81 kN. It can be concluded that the oil from jatropha seed is the best in terms of extrusion pressure and can effectively replace the chemical based lubricants

Influence of spark plasma sintering temperature on the densification and micro-hardness behaviour of Ni-Cr-Al alloy

Abstract : Sintering temperature is essential towards attaining desired densification and formation of phases which in turn influences the microstructure and properties of a material. In this study, the densification and microhardness behaviour of Ni-Cr-Al alloy prepared by spark plasma sintering (SPS) at different sintering temperatures were investigated. After sintering operation, the density, hardness, phase analysis, and microstructural evolution were investigated using the Archimede’s principle, hardness tester, X-ray diffraction (XRD), and scanning electron microscopy (SEM) respectively. The nickel based alloy was sintered at temperatures of 600, 750, 950 and 1100 ºC. The results indicated that the densification, microstructure, and hardness values were influenced by changes in the sintering temperature. The relative density increased from 73.89 % at 600 ºC to 99.89 % at 1100 ºC, while the hardness value was enhanced from 131.9 ± 2.8 HV to 404 ± 1.2 HV respectively

The 'Ins and Outs' of Early Preclinical Models for Brain Tumor Research: Are They Valuable and Have We Been Doing It Wrong?

In this perspective, we congratulate the international efforts to highlight critical challenges in brain tumor research through a recent Consensus Statement. We also illustrate the importance of developing more accurate and clinically relevant early translational in vitro brain tumor models-a perspective given limited emphasis in the Consensus Statement, despite in vitro models being widely used to prioritize candidate therapeutic strategies prior to in vivo studies and subsequent clinical trials. We argue that successful translation of effective novel treatments into the clinic will require investment into the development of more predictive early pre-clinical models. It is in the interest of researchers, clinicians, and ultimately, patients that the most promising therapeutic candidates are identified and translated toward use in the clinic. Highlighting the value of early pre-clinical brain tumor models and debating how such models can be improved is of the utmost importance to the neuro-oncology research community and cancer research more broadly

Comparative study of spark plasma sintering features on the densification of Ni-Cr binary alloys

Abstract: Spark plasma sintering (SPS) has been widely regarded as an advanced powder consolidation technique which helps in the development of array of engineering materials. Many have been reported in the literature about sintering parameters such as temperature, pressure, heating rate and holding time. However, little or no reports has been made on some of the intricate features such as process time(s), power SPS (KW), pressing speed (mm/min), and average pressing force (KN) on which sintering parameters are directly related to. This study aims to investigate the behaviour of spark plasma sintered Ni-17Cr binary alloys with emphasis on the densification, hardness value and spark plasma sintering features such as process time (s), power SPS (KW), pressing speed (mm/min), and the average pressing force (KN). Nickel and chromium powders were milled individually using High energy ball milling for durations of 5hr, 10 hr prior to mixing and subsequent sintering. The sintered 5 hr and 10 hr milled Ni-17Cr binary alloys attained relative densities of 98.72 % and 99.1 % respectively. The Microstructural morphology was examined using Scanning electron microscopy (SEM). The sintered 10 hr milled Ni-17Cr binary alloy revealed the higher hardness

DNA damage response inhibitors enhance tumour treating fields (TTFields) potency in glioma stem-like cells

Background High-grade gliomas are primary brain cancers with unacceptably low and persistent survival rates of 10–16 months for WHO grade 4 gliomas over the last 40 years, despite surgical resection and DNA-damaging chemo-radiotherapy. More recently, tumour-treating fields therapy (TTFields) has demonstrated modest survival benefit and been clinically approved in several countries. TTFields is thought to mediate anti-cancer activity by primarily disrupting mitosis. However, recent data suggest that TTFields may also attenuate DNA damage repair and replication fork dynamics, providing a potential platform for therapeutic combinations incorporating standard-of-care treatments and targeted DNA damage response inhibitors (DDRi). Methods We have used patient-derived, typically resistant, glioma stem-like cells (GSCs) in combination with the previously validated preclinical Inovitro™ TTFields system together with a number of therapeutic DDRi. Results We show that TTFields robustly activates PARP- and ATR-mediated DNA repair (including PARylation and CHK1 phosphorylation, respectively), whilst combining TTFields with PARP1 or ATR inhibitor treatment leads to significantly reduced clonogenic survival. The potency of each of these strategies is further enhanced by radiation treatment, leading to increased amounts of DNA damage with profound delay in DNA damage resolution. Conclusion To our knowledge, our findings represent the first report of TTFields applied with clinically approved or in-trial DDRi in GSC models and provides a basis for translational studies toward multimodal DDRi/TTFields-based therapeutic strategies for patients with these currently incurable tumours

Tumour treating fields therapy for glioblastoma : current advances and future directions

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)—an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles—to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields

Subarachnoid haemorrhage with negative initial neurovascular imaging: a systematic review and meta-analysis

Abstract: Background: In patients with spontaneous subarachnoid haemorrhage (SAH), a vascular cause for the bleed is not always found on initial investigations. This study aimed to systematically evaluate the delayed investigation strategies and clinical outcomes in these cases, often described as “non-aneurysmal” SAH (naSAH). Methods: A systematic review was performed in concordance with the PRISMA checklist. Pooled proportions of primary outcome measures were estimated using a random-effects model. Results: Fifty-eight studies were included (4473 patients). The cohort was split into perimesencephalic naSAH (PnaSAH) (49.9%), non-PnaSAH (44.7%) and radiologically negative SAH identified on lumbar puncture (5.4%). The commonest initial vascular imaging modality was digital subtraction angiography. A vascular abnormality was identified during delayed investigation in 3.9% [95% CI 1.9–6.6]. There was no uniform strategy for the timing or modality of delayed investigations. The pooled proportion of a favourable modified Rankin scale outcome (0–2) at 3–6 months following diagnosis was 92.0% [95% CI 86.0–96.5]. Complications included re-bleeding (3.1% [95% CI 1.5–5.2]), hydrocephalus (16.0% [95% CI 11.2–21.4]), vasospasm (9.6% [95% CI 6.5–13.3]) and seizure (3.5% [95% CI 1.7–5.8]). Stratified by bleeding pattern, we demonstrate a higher rate of delayed diagnoses (13.6% [95% CI 7.4–21.3]), lower proportion of favourable functional outcome (87.2% [95% CI 80.1–92.9]) and higher risk of complications for non-PnaSAH patients. Conclusion: This study highlights the heterogeneity in delayed investigations and outcomes for patients with naSAH, which may be influenced by the initial pattern of bleeding. Further multi-centre prospective studies are required to clarify optimal tailored management strategies for this heterogeneous group of patients

Race and ‘omic’ data in glioma: a systematic review of contemporary research to explore the digital divide

Background The expanding repertoire of studies generating genome-scale omic datasets from glioma samples provides a generational opportunity to uncover mechanisms driving aggressive biology and develop new treatments. However, ensuring such studies reflect the breadth of racial groups and ethnicities affected by gliomas is critical to support equity in future therapeutic advances. We therefore report a contemporary snapshot of the representation of race and ethnicity in omic glioma studies. Methods We searched PubMed, Embase, Web of Science and Scopus and systematically reviewed articles published between January and November 2023 reporting de novo genome-scale sequencing data generated using samples from patients diagnosed with a glioma (according to WHO 2021 criteria) to characterise the reporting and composition of race and ethnicity data. Results Thirty-five studies involving 5,601 patients were analysed. Race or ethnicity data was reported in only 3 studies (8.6%), of which none provided omic data in a format that could be stratified by race or ethnicity. Reporting varied by continent with all 3 studies including race or ethnicity data based in North America. Where racial data was available, we found that samples used for genome-scale characterisation came from patients reported as being White in 91.1% cases (41 patients), with 6.7% (3 patients) reported as Black and 2.2% (1 patient) as Hispanic. Conclusions These studies underscore an urgent need for improved reporting and representation to enhance our understanding of glioma biology across different populations and guide targeted initiatives from policy makers and funders to support equitable improvements in healthcare