3714 research outputs found
Sort by
HDAC inhibitors with potential to overcome drug resistance in castration-resistant prostate cancer
No full textEpigenetic mechanisms play an important role in the development and persistence of cancer, and histone deacetylase (HDAC) inhibitors are promising anticancer drugs targeting epigenetic modes. Efficient anticancer drugs for the treatment of castration-resistant prostate cancer (CRPC) are sought, and approved HDAC inhibitors have shown promising results on the one hand and severe drawbacks on the other hand. Hence, ways to break the drug resistance mechanisms of existing HDAC inhibitors as well as the design of new promising HDAC inhibitors which can overcome the disadvantages of the classic HDAC inhibitors are of great importance. In this work, HDAC inhibitors with the potential to become a mainstay for the treatment of CRPC in the future as well as suitable combination treatments of HDAC inhibitors with other anticancer drugs leading to considerable synergistic effects in treated CRPCs are discussed
Potential mechanisms of resistance to current anti-thrombotic strategies in Multiple Myeloma
No full textMultiple Myeloma (MM) is a common haematological malignancy that is associated with a high rate of venous thromboembolism (VTE) with almost 10% of patients suffering thrombosis during their disease course. Recent studies have shown that, despite current thromboprophylaxis strategies, VTE rates in MM remain disappointingly high. The pathophysiology behind this consistently high rate of VTE is likely multifactorial. A number of factors such as anti-thrombin deficiency or raised coagulation Factor VIII levels may confer resistance to heparin in these patients, however, the optimal method of clinically evaluating this is unclear at present, though some groups have attempted its characterisation with thrombin generation testing (TGT). In addition to testing for heparin resistance, TGT in patients with MM has shown markedly varied abnormalities in both endogenous thrombin potential and serum thrombomodulin levels. Apart from these thrombin-mediated processes, other mechanisms potentially contributing to thromboprophylaxis failure include activated protein C resistance, endothelial toxicity secondary to chemotherapy agents, tissue factor abnormalities and the effect of immunoglobulins/“M-proteins” on both the endothelium and on fibrin fibre polymerisation. It thus appears clear that there are a multitude of factors contributing to the prothrombotic milieu seen in MM and further work is necessitated to elucidate which factors may directly affect and inhibit response to anticoagulation and which factors are contributing in a broader fashion to the hypercoagulability phenotype observed in these patients so that effective thromboprophylaxis strategies can be employed
Android App Antiforensics
No full textAim: Android is one of the most popular platforms in the market. This popularity has led the operating system to be a potential tool for criminal activities. Law enforcement has noted this development and started incorporating smartphone evidence into their cases. However, digital evidence is susceptible to data modification, and thus anti-forensic techniques have been developed to counter forensic investigations. This research investigates the possibility of generating false data using automation techniques.Methods: A rooted Android device was acquired. The device screen coordinates were mapped using screenshots and Gimp. The coordinates were used to develop a Python script to automate common user tasks such as making a phone call, sending a text message, or adding a contact. These tasks were performed manually and using the automation script. A system image was acquired of the device before and after data population. The images were analyzed using Autopsy and Cellebrite’s Inspector. The forensic artifacts retrieved were compared between the manual and automatic data population.Results: The artifacts show that the data was added successfully and that forensic tools may not detect that the data was automatically generated.Conclusion: This research shows that it is possible to populate an Android device with false forensic artifacts using automation scripts. Being able to generate forensic artifacts using automation scripts can allow educators to more easily generate datasets to teach forensic techniques. Additionally, it can also be used by malicious actors to generate false forensic artifacts to mislead an investigator. Future work could improve the proposed data generation technique via machine learning to prevent hardcoding the screen coordinates in the automation script or improve the technique to generate data with old timestamps. Another avenue of future work includes the development of techniques to identify false data
Mesenchymal stem cell-derived extracellular vesicles for cell-free therapy of ocular diseases
No full textMesenchymal stem cells-derived extracellular vesicles (MSC-EVs) have noticeably attracted clinicians’ attention in treating ocular diseases. As the paracrine factor of MSCs and an alternative for cell-free therapies, MSC-EVs can be conveniently dropped over the ocular surface or diffused through the retina upon intravitreal injection, without increasing the risks of cellular rejection and tumor formation. For clinical translation, a standardized and scalable production, as well as reprogramming the MSC-EVs, are highly encouraged. This review aims to assess the potential approaches for EV production and functional modification, in addition to summarizing the worldwide clinical trials initiated for various physiological systems and the specific biochemical effects of MSC-EVs on the therapy of eye diseases. Recent advances in the therapy of ocular diseases based on MSC-EVs are reviewed, and the associated challenges and prospects are discussed as well
A new scoring system for operational indicators guiding leprosy monitoring and surveillance in Brazil
No full textObjective: We aimed to develop a new score to facilitate and enhance the quantitative assessment of operational standard indicators guiding leprosy monitoring and surveillance, based on data from Brazilian hyperendemic regions, 2004-2019.Methods: We analyzed epidemiological and operational standard indicators of leprosy control from the database of the Notifiable Diseases Information System in Brazil’s North and Northeast regions. The so-called IntegraHans Operational Score (IHOS) was generated, integrating 10 indicators, with a final semi-quantitative score varying from 0 (worst scenario) to 1 (best scenario). We then applied the IHOS within an ecological and population-based study to assess temporal and spatial leprosy distributions from 2004 to 2019.Results: In total, 343,888 new leprosy cases were analyzed (61% of cases in the country). There was a significant temporal trend of the IHOS annual percentage change [-0.3; 95% confidence interval (CI): -0.5 to 0.0] during 2010-2019, with large cities showing a worsening trend (average annual percentage change -0.8, 95%CI: -1.1 to -0.4). After 2010, municipalities with low and medium social vulnerability, and those with medium human development and medium and high social prosperity, showed improved IHOS scores. Spatial patterns with the best IHOS scenarios were observed in the states of Rondônia, Tocantins, and Pernambuco.Conclusion: The IHOS combines different operational parameters and is an effective and simple tool to assess leprosy control programs in Brazil. The worst IHOS scores over time were identified in critical areas, such as large cities in hyperendemic areas and municipalities with lower endemicity
A critical review of the mechanical properties of CoCrNi-based medium-entropy alloys
No full textThe CoCrFeMnNi alloy is one of the most notable first-generation high-entropy alloys and is also known as a Cantor alloy. This alloy was first proposed in 2004 and shows promising performance at cryogenic temperatures (CTs). Subsequent research has indicated that the equiatomic ternary CoCrNi medium-entropy alloy (MEA), as a subset of the Cantor alloy family, has better mechanical properties than the CoCrFeMnNi alloy. Interestingly, both the strength and ductility of the CoCrNi MEA are higher at CTs than at room temperature. CoCrNi-based alloys have attracted considerable attention in the metallic materials community and it is therefore important to generalize and summarize the latest progress in CoCrNi-based MEA research. The present review initially briefly introduces the discovery of the CoCrNi MEA. Subsequently, its tensile response and deformation mechanisms are summarized. In particular, the effects of parameters, such as critical resolved shear stress, stacking fault energy and short-range ordering, on the deformation behavior are discussed in detail. The methods for strengthening the CoCrNi MEA are then reviewed and divided into two categories, namely, modifying microstructures and adjusting chemical compositions. In addition, the mechanical performance of CoCrNi-based MEAs, including their dynamic shear properties, creep behavior and fracture toughness, is also deliberated. Finally, the development prospects of CoCrNi-based MEAs are proposed
K6Sn4F12I2•0.5H2O: a zero-dimensional alkali metal tin mixed halide compound exhibiting color change due to crystal water loss
No full textA new zero-dimensional alkali-metal tin mixed halide, K6Sn4F12I2•0.5H2O, is synthesized by a hydrothermal method. It crystallizes in the cubic centrosymmetric space group of Fd-3m (No. 227) and its structure consists of crystal water molecules and ordered arranged [Sn4F12I4] fundamental structural blocks trapped in [K18] cages. Interestingly, K6Sn4F12I2•0.5H2O exhibits a color change from colorless to orange when exposed to air. Experimental measurements combined with theoretical calculations reveal that the color change in K6Sn4F12I2•0.5H2O is attributed to the loss of crystal water
Influence of softening annealing on microstructural heredity and mechanical properties of medium-Mn steel
No full textSoftening annealing (SA) is often required for producing medium-Mn steels (MMS) as it lowers hardness so that they can be cold rolled to reduce thickness. The influences of different SA processes on the microstructural heredity during the processing route and the final tensile properties were studied. It was found that the SA process could either intensify or weaken the influence of the Mn segregation resulting from solidification on the subsequent microstructural evolution during the process, i.e., microstructural heredity. In the case when no SA was employed, both recrystallization and rapid growth of ferrite grains preceded the reverse austenitic transformation during the intercritical annealing (IA) in the Mn-lean regions, where very coarse ferrite grains were formed. This deteriorated ductility due to the propagation of cracking along the boundary of the coarse-grained and fine-grained regions. In contrast, SA at a sufficiently high temperature could dissolve cementite, producing uniformly distributed austenite grains. They transformed to martensite during cold rolling but were reborn during IA. As a result, ultrafine austenite and ferrite grains were uniformly distributed, which improved ductility significantly. This study hints at a new approach to altering the microstructural heredity resulting from the heterogeneous Mn distribution in MMS
Topochemical synthesis and structural characteristics of orientation-controlled (Bi0.5Na0.5)0.94Ba0.06TiO3 perovskite microplatelets
No full textTwo-dimensional perovskite microcrystals have important applications in various electronic and energy devices. In this work, 0.94(Bi0.5Na0.5)TiO3-0.06BaTiO3 (0.94BNT-0.06BT) microplatelets with a pure perovskite structure, (h00) orientation, good crystallinity and remarkable electromechanical strain are fabricated through topochemical microcrystal conversion from Aurivillius-structured Bi4.5Na0.5Ti4O15 precursors. The formation process of the Bi4.5Na0.5Ti4O15 precursors and the topochemical conversion mechanism of the 0.94BNT-0.06BT target are systematically studied. Intermediate phases, such as Bi4Ti3O12 and Bi8.5Na0.5Ti7O27, appear before the formation of pure Bi4.5Na0.5Ti4O15 at 950 °C in a NaCl molten salt. For the topochemical microcrystal conversion process, although the Aurivillius to perovskite structural transformation is completed at 900 °C, the original single-crystal precursor platelets are replaced by polycrystalline aggregates because of extensive exfoliation and disintegration events. Such microstructural damage is healed by recrystallization via Ostwald ripening through further heating to produce single-crystal 0.94BNT-0.06BT microplatelets with flat surfaces, regular shapes and homogenous distributions of Bi, Na, Ba, Ti and O at 1150 °C. Both labyrinth and stripe-like domains can be detected from these microplatelets, suggesting the coexistence of both rhombohedral and tetragonal phases, in agreement with the X-ray diffraction analysis. Furthermore, local electromechanical strain with an amplitude of ~600 pm (at 10 V) is observed from the platelets along the <001>c direction
Design of Zn anode protection materials for mild aqueous Zn-ion batteries
No full textRechargeable aqueous Zn-ion batteries (AZIBs) are considered alternative stationary storage systems for large-scale applications due to their high safety, low cost, and high power density. However, Zn anode issues including dendrite formation and side reactions greatly hinder the practical application of AZIBs. To solve the Zn anode issues, various strategies based on material designs have been developed. It is necessary to analyze and classify these strategies according to different materials, because different properties of materials determine the underlying mechanisms. In this review, we briefly introduce the fundamental issues in Zn anodes. Furthermore, this review highlights the material designs for the protection of Zn anodes in mild AZIBs. Finally, we also offer insight into potential directions in the material designs to promote the development of AZIBs in the future
Data sources:
Access Repository Dashboard
Do you manage OAE Publishing (via Crossref)? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!