Discovery of Novel Pyridine Derivatives as Anti-Cancer Agents

The International Agency for Research on Cancer indicated that cancer burden was raised in 2012 to 14.1 million incidence cases and 8.2 mortality cases. Consequently, novel approaches are urgently required for further improvement in existing cancer therapies. Synthesis of the pyridine ring system and its derivatives occupy an important place in the realm of synthetic organic chemistry, due to their therapeutic and pharmacological properties. The current study investigated the anti-cancer activity of novel pyridine derivatives. Twenty novel Pyridine Derivatives were screened using WST-1 assay on several cell lines to assess their toxicity and to determine whether the effect is tumor or cell type specific. Dose response curves were obtained for compound 9a for further investigations. Detection of apoptosis and cell cycle checkpoint analysis was done using flow cytometry and expression of several apoptotic and anti-apoptotic proteins was carried out by Western Blot. Initial screening revealed that 100μM treatment with pyridine derivatives for the above mentioned cell lines for 24 hours suppressed the viability as follows: compound 9a reduced the viability by 40% in MCF-7 cells and by 45% in HCT-116, compound 7b reduced the viability in SKOV-3 by 35% and finally compound 11 suppressed the viability of SKOV-3 by 44%. Compound 9a induced growth inhibition in MCF-7 cells and resulted in the induction of apoptosis with an IC50 of 20μM. It upregulated the expression of p53, Bax and Caspase-3 in MCF-7 cells. In addition, it caused significant down-regulation of Bcl-2, Mdm-2 and Akt. Compound 9a exhibited less toxicity on non-tumorigenic breast epithelial cell line MCF-12a. Findings of the study indicated that compound 9a possesses potent anti-proliferative activity against MCF-7 cells and could be a promising chemotherapeutic agent with less toxicity on non-tumorigenic cells. Further screening and investigating molecular mechanisms of this potent agent on other cancer cell lines is highly required

Virus-like particle vaccinology, from bench to bedside.

Virus-like particles (VLPs) have become key tools in biology, medicine and even engineering. After their initial use to resolve viral structures at the atomic level, VLPs were rapidly harnessed to develop antiviral vaccines followed by their use as display platforms to generate any kind of vaccine. Most recently, VLPs have been employed as nanomachines to deliver pharmaceutically active products to specific sites and into specific cells in the body. Here, we focus on the use of VLPs for the development of vaccines with broad fields of indications ranging from classical vaccines against viruses to therapeutic vaccines against chronic inflammation, pain, allergy and cancer. In this review, we take a walk through time, starting with the latest developments in experimental preclinical VLP-based vaccines and ending with marketed vaccines, which earn billions of dollars every year, paving the way for the next wave of prophylactic and therapeutic vaccines already visible on the horizon

A non-adiabatic approach to entanglement distribution over long distances

Entanglement distribution between trapped-atom quantum memories, viz. single atoms in optical cavities, is addressed. In most scenarios, the rate of entanglement distribution depends on the efficiency with which the state of traveling single photons can be transferred to trapped atoms. This loading efficiency is analytically studied for two-level, $V$-level, $\Lambda$-level, and double-$\Lambda$-level atomic configurations by means of a system-reservoir approach. An off-resonant non-adiabatic approach to loading $\Lambda$-level trapped-atom memories is proposed, and the ensuing trade-offs between the atom-light coupling rate and input photon bandwidth for achieving a high loading probability are identified. The non-adiabatic approach allows a broad class of optical sources to be used, and in some cases it provides a higher system throughput than what can be achieved by adiabatic loading mechanisms. The analysis is extended to the case of two double-$\Lambda$ trapped-atom memories illuminated by a polarization-entangled biphoton.Comment: 15 pages, 15 figure

Increased receptor affinity of SARS-CoV-2: a new immune escape mechanism.

‘Affinity escape’: Novel SARS-CoV-2 variants may escape immunity by raising the RBD-ACE2 affinity high enough to outcompete the avidity of neutralizing antibodies

Geologic environments for nuclear waste repositories

© The Authors, published by EDP Sciences, 2017. High-level radioactive waste (HLW) results from spent reactor fuel and reprocessed nuclear material. Since 1957 the scientific consensus is that deep geologic disposal constitutes the safest means for isolating HLW for long timescales. Nuclear power is becoming significant for the Arab Gulf countries as a way to diversify energy sources and drive economic developments. Hence, it is of interest to the UAE to examine the geologic environments currently considered internationally to guide site selection. Sweden and Finland are proceeding with deep underground repositories mined in bedrock at depths of 500m, and 400m, respectively. Equally, Canada\u27s proposals are deep burial in the plutonic rock masses of the Canadian Shield. Denmark and Switzerland are considering disposal of their relative small quantities of HLW into crystalline basement rocks through boreholes at depths of 5,000m. In USA, the potential repository at Yucca Mountain, Nevada lies at a depth of 300m in unsaturated layers of welded volcanic tuffs. Disposal of low and intermediate-level radioactive wastes, as well as the German HLW repository favour structurally-sound layered salt stata and domes. Our article provides a comprehensive review of the current concepts regarding HLW disposal together with some preliminary analysis of potentially appropriate geologic environments in the UAE

Evidence-Based Medicine; Climbing a Mountain for a Better Decision-Making

Evidence-Based Medicine is a relatively new term used in medical sittings and Health Information Technology (HIT). It is a form of medicine that integrates practitioners’ expertise with the best available practical evidences to improve better patient care. Evidence-Based Medicine has increasingly been used and incorporated into daily medical practices to overcome the shortcomings in the conventional standard care. The purpose of this literature review is to highlight the importance of Evidence-Based Medicine and how it can act as a crucial tool in decision-making to empower the quality of medical services for better patient outcomes

Sustainable energy development and nuclear energy legislation in the uae

© Springer Nature Switzerland AG 2020. The MENA region has been experiencing the highest population growth rate in the world since the last century. Concomitantly, energy needs in the region are projected to exceed 50% of the current demand in the upcoming two decades. The United Arab Emirates (UAE) has become the newest addition to the countries that utilize nuclear energy for electricity production. For MENA countries, UAE constitutes the model in operational and regulatory actions in their pursuit of nuclear power. UAE’s principles of transparency, nonproliferation, safety, and security, as well as its willingness to provide full operational access to international organizations, have been the key factors for this development. This study analyzes UAE’s regulatory framework with the emphasis on the organizational structure of FANR, the country’s nuclear regulatory body. Comparisons are made with USA and France, which have mature institutional structures and suggestions are provided for improving FANR’s organizational chart. Our article also discusses issues of independence and accountability of regulatory bodies, pertinent to MENA countries’ agencies

Integrated mixing machine for sulfur concrete production

The production of sulfur concrete (SC) from its ingredient materials requires controlled heating and mixing conditions at a temperature level of 130°-150 °C. Although this process considered to be common and applicable at the industrial level, it is difficult at the laboratory/research level. This paper presents the design and manufacturing details of a relatively inexpensive laboratory machine for heating and mixing sulfur concrete. The different components of the machine are described in detail to help researchers to produce high-quality sulfur concrete. In this work, the quality of the machine is verified through experimental testing of the physical and mechanical properties of different prepared SC mixtures. Thus, the homogeneity and mixing efficiency required a certain level of workability, and the full controlling of temperature during the production process has been realized. The machine is proven to be efficient, safe, and durable. The comparative study on the physical and mechanical properties of the prepared SC relative to other SC of the same ingredients but heated and mixed through other small-scale machines, showed the superiority of the mixing machine in the production of high strength concrete