Synthesis and ADMET Study of Some 1, 8-Naphthyidine and Quinoline 3-Carboxylic Acid Derivatives

The extremely drug resistant may be a worldwide public ill health in recent years. Molecules with newer targets and an alternate mechanism of action is an urgent requirement of improvement of latest drugs. The utilization of heterocyclic compounds has been increased dramatically over the last 70 years due to their wide selection of technical applications and their favorable environmental and toxicological properties The 1,8-naphthyridine and quinoline 3-carboxylic acid derivatives that we'll manufacture during this method will change the potency and specificity of fluoroquinolones. Taking under consideration the findings, the goal is to style and manufacture 1, 8-naphthyridine and quinoline 3-carboxylic acid derivatives. The synthesized compounds are going to be characterized using multiple analytical techniques, virtual screening, and in-silico ADME/T prediction. Keywords: 1, 8-Naphthyridine, Quinoline, ADMET, Heterocyclic Compound

Differential adhesion regulates neurite placement via a retrograde zippering mechanism

During development, neurites and synapses segregate into specific neighborhoods or layers within nerve bundles. The developmental programs guiding placement of neurites in specific layers, and hence their incorporation into specific circuits, are not well understood. We implement novel imaging methods and quantitative models to document the embryonic development of the C. elegans brain neuropil, and discover that differential adhesion mechanisms control precise placement of single neurites onto specific layers. Differential adhesion is orchestrated via developmentally-regulated expression of the IgCAM SYG-1, and its partner ligand SYG-2. Changes in SYG-1 expression across neuropil layers result in changes in adhesive forces, which sort SYG-2-expressing neurons. Sorting to layers occurs, not via outgrowth from the neurite tip, but via an alternate mechanism of retrograde zippering, involving interactions between neurite shafts. Our study indicates that biophysical principles from differential adhesion govern neurite placement and synaptic specificity in vivo in developing neuropil bundles.

Effect of conservation of spatial volume on electromagnetism

This essay presents an alternate mechanism for electromagnetism and provides arguments supporting new concepts of this phenomenon. Electricity and magnetism are defined and influenced by the electric permittivity ε o and magnetic permeability μ o physical constants of the vacuum. This essay's concepts are predicated on the notion that the free-space vacuum appears to be composed of an energy field with characteristics of an elastic medium termed the “spatial energy field” or SEF. It is proposed that the geometric volume of the SEF requires conservation, and this is achieved via stretching or compression of space exhibiting wavelike qualities. The SEF, representing spacetime, has specific properties related to the emergence of an electrical field force via the Poynting vector. Magnetic field force appears to emanate from the SEF based on the Lorentz force. Space (SEF) appears to mediate energy fields, such as electrical and magnetic fields, and provides a framework for the transmission of electromagnetic waves in addition to momentum-gravitational waves. Conservation of spatial volume influences these phenomena.

CSR and appropriation potential of firm innovative knowledge

PurposeThe purpose of this paper is to study the moderating role of corporate social responsibility (CSR) in the knowledge asset–firm financial performance relationship.Design/methodology/approachThis paper first develops hypotheses based on multiple theoretical lenses and uses a sample of 3,030 US firms in 51 industries over 11 years to test these hypotheses.FindingsIt is found that CSR positively moderates the relationship between research and development (R&D) investments and the firm's financial performance, and the moderating effect declines when firms mistreat their employees.Practical implicationsThis paper provides evidence that when firms allocate their resources, they should consider the synthetic effect among different activities such as R&D and CSR.Originality/valueFirst, this study offers a new and alternate mechanism for the appropriability literature and also extends the boundary of CSR research. Second, this work shifts the CSR performance thought by considering CSR as an enabler rather than a driver for performance.

Emission of Dislocations from Grain Boundaries and Its Role in Nanomaterials

The Frank-Read model, as a way of generating dislocations in metals and alloys, is widely accepted. In the early 1960s, Li proposed an alternate mechanism. Namely, grain boundary sources for dislocations, with the aim of providing a different model for the Hall-Petch relation without the need of dislocation pile-ups at grain boundaries, or Frank-Read sources inside the grain. This article provides a review of his model, and supporting evidence for grain boundaries or interfacial sources of dislocations, including direct observations using transmission electron microscopy. The Li model has acquired new interest with the recent development of nanomaterial and multilayers. It is now known that nanocrystalline metals/alloys show a behavior different from conventional polycrystalline materials. The role of grain boundary sources in nanomaterials is reviewed briefly.

Information Infrastructures: the Conduit Power of ICTs in Africa

In this article, I make a case for considering Information and Communications Technology (ICT) infrastructures outside the narrow prism of ICT for development (ICT4D), but rather as an alternate mechanism to exercise political power in Africa. I refer to ‘infrastructures’ rather than ‘infrastructure’ because the former has a broader definition. Infrastructures may be material, informational or structural. Infrastructure relates to the physical and organisational structure and facilities a society or an organisation needs to function, such as roads, electricity and communication systems. Owing to the inability to overcome weaknesses in state capacity, the expression of power in the global South often differs from the global North. ICT infrastructure is transnational with power oscillating between state and non-state actors but offers African countries a surrogate system of administration for individual territories. I draw on the concept of infrastructural power to describe how a state may harness ICT infrastructure, or information infrastructures, to increase its influence within its territory and extraterritorially.

c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as “Yin and Yang” partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.

Intracellular Lipid Droplet Accumulation Occurs Early Following Viral Infection and Is Required for an Efficient Interferon Response

SummaryLipid droplets (LDs) are increasingly recognized as critical organelles in signalling events, transient protein sequestration and inter-organelle interactions. However, the role LDs play in antiviral innate immune pathways remains unknown. Here we demonstrate that induction of LDs occurs as early as 2 hours post viral infection, is transient, and returns to basal levels by 72 hours. This phenomenon occurred following viral infections, both in vitro and in vivo. Virally driven LD induction was type-I interferon (IFN) independent, however, was dependent on EGFR engagement, offering an alternate mechanism of LD induction in comparison to our traditional understanding of their biogenesis. Additionally, LD induction corresponded with enhanced cellular type-I and -III IFN production in infected cells, with enhanced LD accumulation decreasing viral replication of both HSV-1 and Zika virus (ZIKV). Here, we demonstrate for the first time, that LDs play vital roles in facilitating the magnitude of the early antiviral immune response specifically through the enhanced modulation of IFN following viral infection, and control of viral replication. By identifying LDs as a critical signalling organelle, this data represents a paradigm shift in our understanding of the molecular mechanisms which coordinate an effective antiviral response.