Novel Analysis of Hermite–Hadamard Type Integral Inequalities via Generalized Exponential Type m-Convex Functions

The theory of convexity has a rich and paramount history and has been the interest of intense research for longer than a century in mathematics. It has not just fascinating and profound outcomes in different branches of engineering and mathematical sciences, it also has plenty of uses because of its geometrical interpretation and definition. It also provides numerical quadrature rules and tools for researchers to tackle and solve a wide class of related and unrelated problems. The main focus of this paper is to introduce and explore the concept of a new family of convex functions namely generalized exponential type m-convex functions. Further, to upgrade its numerical significance, we present some of its algebraic properties. Using the newly introduced definition, we investigate the novel version of Hermite–Hadamard type integral inequality. Furthermore, we establish some integral identities, and employing these identities, we present several new Hermite–Hadamard H–H type integral inequalities for generalized exponential type m-convex functions. These new results yield some generalizations of the prior results in the literature.

Precision medicine in bronchiectasis

Bronchiectasis, due to its highly heterogenous nature, requires an individualised approach to therapy. Patients experience symptoms and exacerbations driven by a combination of impaired mucociliary clearance, airway inflammation and airway infection. Treatment of bronchiectasis aims to enhance airway clearance and to address the underlying causes of inflammation and infection susceptibility. Bronchiectasis has multiple causes and so the pathophysiology leading to individual symptoms and exacerbations are different between individuals. Standardised investigations are recommended by international guidelines to identify the underlying causes of bronchiectasis. The process of identifying the underlying biology within an individual is called “endotyping” and is an emerging concept across chronic diseases. Endotypes that have a specific treatment are referred to as “treatable traits” and a treatable traits approach to managing patients with bronchiectasis in a holistic and evidence-based manner is the key to improved outcomes. Bronchiectasis is an area of intense research. Endotyping allows identification of subsets of patients to allow medicines to be tested differently in the future where trials, rather than trying to achieve a “one size fits all” solution, can test efficacy in subsets of patients where the treatment is most likely to be efficacious.

The Role of Genetic Pathways in the Development of Chemoradiation Resistance in Nasopharyngeal Carcinoma (NPC) Patients

Management of nasopharyngeal carcinoma (NPC) remains elusive despite new developments and advancement that has been made in the current management approaches. A patient’s survival and prognosis remain dismal especially for a late-stage disease. This is highly attribute to the chemoradiation resistance. Arrays of genes and molecular mechanisms underlie the development of chemoradiation resistance in NPC. Imperatively, unravelling the true pathogenesis of chemoradiation resistance is crucial as these significant proteins and genes can be modulated to produce an effective therapeutic target. It is pivotal to identify the chemoradiation resistance at the very beginning in order to combat the chemoradiation resistance efficiently. Intense research in the genetic ecosphere is critical, as the discovery and development of novel therapeutic targets can be used for screening, diagnosis, and treating the chemoradiation resistance aggressively. This will escalate the management trajectory of NPC patients. This article highlights the significance of genetic and molecular factors that play critical roles in the chemoradiation resistance and how these factors may be modified for next-generation targeted therapy products.

Gallic acid: a dietary polyphenol that exhibits anti-neoplastic activities by modulating multiple oncogenic targets

: Phytochemicals are being used for thousands of years to prevent dreadful malignancy. Side effects of existing allopathic treatment have also initiated intense research in the field of bioactive phytochemicals. Gallic acid, a natural polyphenolic compound, exists freely as well as in polymeric forms. The anti-cancer properties of gallic acid are indomitable by a variety of cellular pathways such as induction of programmed cell death, cell cycle apprehension, reticence of vasculature and tumor migration, and inflammation. Furthermore, gallic acid is found to show synergism with other existing chemotherapeutic drugs. Therefore, the antineoplastic role of gallic acid suggests its promising therapeutic candidature in the near future. The present review describes all these aspects of gallic acid at a single platform. In addition nanotechnology-mediated approaches are also discussed to enhance bioavailability and therapeutic efficacy.

The That-Trace Effect: Evidence from Spanish–English Code-Switching

The that-trace effect is the fact that many languages (like English) ban the extraction of embedded-clause subjects but not objects over an overt complementizer like that, while many other languages (like Spanish) allow such extractions. The effect and its cross-linguistic variation have been the subject of intense research but remain largely a mystery, with no clear consensus on their underpinnings. We contribute novel evidence to these debates by using Spanish–English code-switching (the use of two languages in one sentence) to test five contemporary theoretical accounts of the that-trace effect. We conducted a formal acceptability judgment experiment, manipulating the extracted argument and code-switch site to test different combinations of linguistic features. We found that subject extraction is only permitted in Spanish–English code-switching when both the C head (que ‘that’) and the T head (i.e., the verb) are in Spanish, but not when either functional head is in English. Our results demonstrate indirect support for two of the five theories we test, failing to support the other three. Our findings also provide new evidence in favor of the view that the that-trace effect is tightly linked to the availability of post-verbal subjects. Finally, we outline how our results can narrow the range of possible theoretical accounts, demonstrating how code-switching data can contribute to core questions in linguistic theory.

In vivo proximity biotin ligation identifies the interactome of Egalitarian, a Dynein cargo adaptor

ABSTRACT Numerous motors of the Kinesin family contribute to plus-end-directed microtubule transport. However, almost all transport towards the minus-end of microtubules involves Dynein. Understanding the mechanism by which Dynein transports this vast diversity of cargo is the focus of intense research. In selected cases, adaptors that link a particular cargo with Dynein have been identified. However, the sheer diversity of cargo suggests that additional adaptors must exist. We used the Drosophila egg chamber as a model to address this issue. Within egg chambers, Egalitarian is required for linking mRNA with Dynein. However, in the absence of Egalitarian, Dynein transport into the oocyte is severely compromised. This suggests that additional cargoes might be linked to Dynein in an Egalitarian-dependent manner. We therefore used proximity biotin ligation to define the interactome of Egalitarian. This approach yielded several novel interacting partners, including P body components and proteins that associate with Dynein in mammalian cells. We also devised and validated a nanobody-based proximity biotinylation strategy that can be used to define the interactome of any GFP-tagged protein.

Dynamic modeling of defective gears

The use of geared transmissions has a long history and a rich experience, which has allowed the development of an intense research activity that has led to modern design methods, mostly standardized and execution technologies that have become traditional. As the fundamental sciences have provided more and more in-depth and refined knowledge, namely performance algorithms of optimal synthesis, the design in the field of gear transmissions has evolved by integrating in the calculation methods a growing number of elements. of influence (materials, geometry, dimensional and shape deviations, heat treatments, kinematic, energetic, dynamic factors, etc.). Automated modeling and simulation currently allow the prediction of behavior - from all points of view of a transmission - during operation.

Parity and gestational age are associated with vaginal microbiota composition in term and late term pregnancies

Vaginal microbiota and its potential contribution to preterm birth has been under intense research in recent years. However, only few studies have studied vaginal microbiota in later stages of pregnancy or at the onset of labor. We analyzed vaginal swab samples collected between 37- and 42-weeks of gestation from 324 Finnish women before elective cesarean section, at the onset of spontaneous labor, and in pregnancies continuing beyond 41 weeks of gestation. Vaginal microbiota composition associated strongly with parity, i.e. previous deliveries, and advancing gestational age. Absence of previous deliveries was a strong predictor of L. crispatus dominated vaginal microbiota, and the relative abundance of L. crispatus was higher in late term pregnancies, especially among nulliparous women. The results underscore the importance of the vaginal microbiota for improving the currently limited understanding on how the duration of gestation and timing of birth is regulated, with potentially vast clinical utilities.

Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities

Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. While complete remission can be obtained with intensive chemotherapy in young and fit patients, relapse is frequent and prognosis remains poor. Leukemic cells are thought to arise from a pool of leukemic stem cells (LSCs) which sit at the top of the hierarchy. Since their discovery, more than 30 years ago, LSCs have been a topic of intense research and their identification paved the way for cancer stem cell research. LSCs are defined by their ability to self-renew, to engraft into recipient mice and to give rise to leukemia. Compared to healthy hematopoietic stem cells (HSCs), LSCs display specific mutations, epigenetic modifications, and a specific metabolic profile. LSCs are usually considered resistant to chemotherapy and are therefore the drivers of relapse. Similar to their HSC counterpart, LSCs reside in a highly specialized microenvironment referred to as the “niche”. Bidirectional interactions between leukemic cells and the microenvironment favor leukemic progression at the expense of healthy hematopoiesis. Within the niche, LSCs are thought to be protected from genotoxic insults. Improvement in our understanding of LSC gene expression profile and phenotype has led to the development of prognosis signatures and the identification of potential therapeutic targets. In this review, we will discuss LSC biology in the context of their specific microenvironment and how a better understanding of LSC niche biology could pave the way for new therapies that target AML.

Boranils: Versatile Multifunctional Organic Fluorophores for Innovative Applications

Multifunctional stimuli-responsive fluorophores showing bright environment-sensitive emissions have fueled intense research due to their innovative applications in the fields of biotechnologies, optoelectronics, and materials. A strong structural diversity is observed among molecular materials, which has been enriched over the years with a growing responsiveness to stimuli. Boron dipyrromethene (BODIPY) dyes have long been the flagship of emissive boron complexes due to their outstanding properties until a decade ago when analogues based on N^O, N^N, or N^C π-conjugated chelates emerged. The finality of developing borate dyes was to compensate for BODIPYs’ lack of solid-state fluorescence and small Stokes shifts while keeping their excellent optical properties in solution. Among them, the borate complexes based on a salicylaldimine ligand, called by the acronym boranils appear as the most promising, owing to their facile synthesis and dual-state emission properties. Boranil dyes have proven to be good alternatives to BODIPY dyes and have been applied in applications such as bioimaging, bioconjugation, and detection of biosubstrates. Meanwhile, ab initio calculations have rationalized experimental results and provided insightful feedback for future designs. This review article aims at providing a concise yet representative overview of the chemistry around the boranil core with the subsequent applications.