Design response to rising sea levels in the Maldives: A study into aquatic architecture

Climate change and rising sea levels present immediate threats to humanity. However, the global catastrophe fails to generate sufficient action. Subject to total submergence within 80 years, this study undertakes an iterative design process seeking sustainable adaptation strategies for the coastal island nation of the Maldives, specifically, Malé, its capital, which exists under a “state of alert” by order of government. Research methods include literature reviews, site analysis, mapping, and iterative design processes to develop an implementation framework strategy. Infrastructure concepts are presented as speculative images with context-specific spatial relationships and functions. Concepts do not intend to represent a conclusive prototype, rather, an ideation—a solution-based discourse among key audiences highlighting the need to act decisively and adaptively.     

25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor

4-(2-((2-hydroxybenzyl)amino)ethyl)-2,5-dimethoxybenzonitrile (25CN-NBOH) was first reported as a potent and selective serotonin 2A receptor (5-HT_2AR) agonist in 2014, and it has since found extensive use as a pharmacological tool in a variety of in vitro, ex vivo and in vivo studies. 25CN-NBOH is readily available from a synthetic perspective using standard chemical transformations, and displays favorable physiochemical properties in terms of stability and solubility. Due to its superior selectivity for 5-HT_2AR, 25CN-NBOH has been used to investigate the effects of selective 5-HT_2AR activation in vivo, and has thus become an important pharmacological tool for the exploration of 5-HT_2AR signaling in a range of animal models. In the present review, we outline the discovery of 25CN-NBOH, its pharmacological profile and major findings from studies where it has been used.     

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters–ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.     

Experimental Study of Classical and Quantum Internal Friction in Solid 4He

We measured the dissipation resulting from internal friction in hcp solid ⁴He at temperatures between 0.8 K and 2.5 K. Solid ⁴He is contained inside an annular metal cell forming a part of a torsional oscillator. An oscillatory motion of the cell walls applies shear stress on the solid ⁴He. The resulting shear strain within the solid ⁴He generates dissipation because of the internal friction. The experimental sensitivity was high enough to detect dissipation caused by internal friction associated with elementary excitations of the solid. At temperatures below 1.6 K, internal friction is associated with diffusion of single point defects responsible for the climb of dislocations. At higher temperatures, the main mechanism of internal friction appears to be associated with phonon exchange between parts of the solid moving relative to each other under the applied shear stress. This particular dissipative mechanism was called “quantum phonon friction” [Popov in Phys. Rev. Lett. 83:1632–1635, 1999]. The physical mechanism associated with this type of friction involves an irreversible transfer of momentum from the phonons to the lattice via an Umklapp process. Our data are in a very good agreement with this model.

     

Augmented low-rank methods for gaussian process regression

Applied Intelligence - This paper presents techniques to improve the prediction accuracy of approximation methods used in Gaussian process regression models. Conventional methods such as...     

Assessment of wind load factors for hurricane-prone regions

We study the issue of whether the wind load factors specified in the ASCE 7–95 Standard for hurricane- prone regions on the one hand and extratropical storm regions on the other are mutually consistent with respect to risk. We consider structures or elements whose design is governed by wind loads and for which wind directionality effects are not significant. We present estimates according to which ASCE 7–95 Standard provisions for wind loads inducing the design strength result in (1) safety levels that are considerably lower for hurricane-prone than for extratropical storm regions, and (2) estimates of mean recurrence intervals of hurricane wind loads inducing the design strength of about 500 y if epistemic uncertainties are neglected, and significantly lower than 500 years otherwise.     

Small Alterations in Cobinamide Structure Considerably Influence sGC Activation

Specially designed B‐ring‐modified cobalamin derivatives were synthesized and tested as potential activators of soluble guanylyl cyclase (sGC). Herein, we disclose the influence of substituents at the c‐ and d‐positions in hydrophilic and hydrophobic cobyrinic acid derivatives on their capacities to activate sGC. The presence of the amide group at c‐/d‐position in cobyrinic acid derivatives strongly influence the level of sGC activation. Removal of the d‐position altogether has a profound effect for hydrophobic compounds. In contrast, little differences were observed in hydrophilic ones.