Combinatorial biomaterials discovery strategy to identify new macromolecular cryoprotectants

Cryoprotective agents (CPAs) are typically solvents or small molecules, but there is a need for innovative CPAs to reduce toxicity and increase cell yield, for the banking and transport of cells. Here we use a photochemical high-throughput discovery platform to identify macromolecular cryoprotectants, as rational design approaches are currently limited by the lack of structure–property relationships. Using liquid handling systems, 120 unique polyampholytes were synthesized using photopolymerization with RAFT agents. Cryopreservation screening identified “hit” polymers and nonlinear trends between composition and function, highlighting the requirement for screening, with polymer aggregation being a key factor. The most active polymers reduced the volume of dimethyl sulfoxide (DMSO) required to cryopreserve a nucleated cell line, demonstrating the potential of this approach to identify materials for cell storage and transport

Modeling the large runup along a narrow segment of the Kaikoura coast, New Zealand following the November 2016 tsunami from a potential landslide

Appendix A. Supplementary data: The following is the Supplementary data to this article: Download Word document (https://ars.els-cdn.com/content/image/1-s2.0-S0029801818318286-mmc1.docx - 3MB).Copyright © 2019 The Authors. The 2016 Mw 7.8 Kaikoura earthquake and consequent tsunami have been controversial because of uncertainty over whether and where the plate interface ruptured and the incapability of the proposed source models to reproduce the near-field runup of 7 m. Existing models identify a wide range of locations for the interface rupture, from on land to offshore, and fail to reproduce runup of 7 m near Kaikoura. To generate the large tsunami peak in Kaikoura tide gauge record and the observed runup height, offshore seafloor movement is necessary, but the offshore extension of the plate-interface rupture and its type, either seismic rupture or a landslide, is uncertain. Here, we propose a submarine landslide in addition to the earthquake source, with the landslide delayed 10–20 min after the earthquake rupture. The landslide volume is 4.5–5.2 km3, located within 173.7–174.3oE (longitude) and 42.6–42.15oS (latitude). Our proposed dual tsunami source successfully reproduces near-field tide gauge records as well as observed near-field runup height of 7 m. We showed that more accurate source models of earthquakes can be achieved by considering observed runup data through runup inversions in addition to waveform inversions.Brunel Research Initiative and Enterprise Fund 2017/18 (BUL BRIEF) at Brunel University Londo

Numerical modeling of the subaerial landslide source of the 22 December 2018 Anak Krakatoa volcanic tsunami, Indonesia

The eruption of the Anak Krakatoa volcano (Indonesia) in December 2018 produced a destructive tsunami with maximum runup of 13 m killing 437 people. Since the occurrence of this rare tsunami, it has been a challenge as how to model this tsunami and to reconstruct the network of coastal observations. Here, we apply a combination of qualitative physical modeling and wavelet analyses of the tsunami as well as numerical modeling to propose a source model. Physical modeling of a volcano flank collapse showed that the initial tsunami wave mostly involves a pure-elevation wave. We identified initial tsunami period of 6.3–8.9 min through Wavelet analysis, leading to an initial tsunami dimension of 1.8–7.4 km. Twelve source models were numerically modelled with source dimensions of 1.5–4 km and initial tsunami amplitudes of 10–200 m. Based on the qualities of spectral and amplitude fits between observations and simulations, we constrained the tsunami source dimension and initial amplitude in the ranges of 1.5–2.5 km and 100–150 m, respectively. Our best source model involves potential energy of 7.14 × 1013–1.05 × 1014 J equivalent to an earthquake of magnitude 6.0–6.1. The amplitude of the final source model is consistent with the predictions obtained from published empirical equations.Royal Society, Great Britain Sasakawa Foundatio

High-resolution resonant inelastic x-ray scattering study of the electron-phonon coupling in honeycomb α-Li₂IrO₃

The excitations in honeycomb α − Li 2 IrO 3 have been investigated with high-resolution resonant inelastic x-ray scattering (RIXS) at the O K edge. The low-energy response is dominated by a fully resolved ladder of excitations, which we interpret as being due to multiphonon processes in the presence of strong electron-phonon coupling (EPC). At higher energies, the orbital excitations are shown to be dressed by phonons. The high quality of the data permits a quantitative test of the analytical model for the RIXS cross section, which has been proposed to describe EPC in transition-metal oxides (TMOs). We find that the magnitude of the EPC is comparable to that found for a range of 3 d TMOs. This indicates that EPC may be of equal importance in determining the phenomenology displayed by corresponding 5 d -based systems

Cigarette smoking, cytochrome P4501A1 polymorphisms, and breast cancer among African-American and white women

INTRODUCTION: Previous epidemiologic studies suggest that women with variant cytochrome P4501A1 (CYP1A1) genotypes who smoke cigarettes are at increased risk for breast cancer. METHODS: We evaluated the association of breast cancer with CYP1A1 polymorphisms and cigarette smoking in a population-based, case–control study of invasive breast cancer in North Carolina. The study population consisted of 688 cases (271 African Americans and 417 whites) and 702 controls (285 African Americans and 417 whites). Four polymorphisms in CYP1A1 were genotyped using PCR/restriction fragment length polymorphism analysis: M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4) RESULTS: No associations were observed for CYP1A1 variant alleles and breast cancer, ignoring smoking. Among women who smoked for longer than 20 years, a modest positive association was found among women with one or more M1 alleles (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2–3.5) but not among women with non-M1 alleles (OR = 1.2, 95% CI = 0.9–1.6). Odds ratios for smoking longer than 20 years were higher among African-American women with one or more M3 alleles (OR = 2.5, 95% CI = 0.9–7.1) compared with women with non-M3 alleles (OR = 1.3, 95% CI = 0.8–2.2). ORs for smoking in white women did not differ appreciably based upon M2 or M4 genotypes. CONCLUSIONS: Cigarette smoking increases breast cancer risk in women with CYP1A1 M1 variant genotypes and in African-American women with CYP1A1 M3 variant genotypes, but the modifying effects of the CYP1A1 genotype are quite weak

Decorin is a novel antagonistic ligand of the Met receptor

Decorin, a member of the small leucine-rich proteoglycan gene family, impedes tumor cell growth by down-regulating the epidermal growth factor receptor. Decorin has a complex binding repertoire, thus, we predicted that decorin would modulate the bioactivity of other tyrosine kinase receptors. We discovered that decorin binds directly and with high affinity (Kd = ∼1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF). Binding of decorin to Met is efficiently displaced by HGF and less efficiently by internalin B, a bacterial Met ligand. Interaction of decorin with Met induces transient receptor activation, recruitment of the E3 ubiquitin ligase c-Cbl, and rapid intracellular degradation of Met (half-life = ∼6 min). Decorin suppresses intracellular levels of β-catenin, a known downstream Met effector, and inhibits Met-mediated cell migration and growth. Thus, by antagonistically targeting multiple tyrosine kinase receptors, decorin contributes to reduction in primary tumor growth and metastastic spreading

Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study

Background: It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. Methods: We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat. Results: In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and ≥800 cigarette-years were 0.65 (95 % confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with ≥400 cigarette-years (OR 1.60, 95 % CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorecta