It takes three to tango: The length of the oligothiophene chain determines the nature of the long‐lived excited state and the resulting photocytotoxicity of a ruthenium(II) Photodrug

Abstract TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally‐related Ru(II)‐imidozo[4,5‐f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter‐ or quaterthiophene changes the nature of the long‐lived triplet state from metal‐to‐ligand charge‐transfer to 3 ππ* character. The addition of the third thiophene thus presents a critical juncture which not only determines the photophysics of the complex but most importantly its capacity for 1 O 2 generation and hence the potential of the complex to be used as a photocytotoxic agent

Ultrastrong Magnon-Magnon Coupling and Chiral Symmetry Breaking in a 3D Magnonic Metamaterial

Strongly-interacting nanomagnetic arrays are ideal systems for exploring the frontiers of magnonic control. They provide functional reconfigurable platforms and attractive technological solutions across storage, GHz communications and neuromorphic computing. Typically, these systems are primarily constrained by their range of accessible states and the strength of magnon coupling phenomena. Increasingly, magnetic nanostructures have explored the benefits of expanding into three dimensions. This has broadened the horizons of magnetic microstate spaces and functional behaviours, but precise control of 3D states and dynamics remains challenging. Here, we introduce a 3D magnonic metamaterial, compatible with widely-available fabrication and characterisation techniques. By combining independently-programmable artificial spin-systems strongly coupled in the z-plane, we construct a reconfigurable 3D metamaterial with an exceptionally high 16N microstate space and intense static and dynamic magnetic coupling. The system exhibits a broad range of emergent phenomena including ultrastrong magnon-magnon coupling with normalised coupling rates of $\frac{\Delta \omega}{\gamma} = 0.57$ and magnon-magnon cooperativity up to C = 126.4, GHz mode shifts in zero applied field and chirality-selective magneto-toroidal microstate programming and corresponding magnonic spectral control

Genetic dissection of photoperiod response based on GWAS of pre-anthesis phase duration in spring barley

Heading time is a complex trait, and natural variation in photoperiod responses is a major factor controlling time to heading, adaptation and grain yield. In barley, previous heading time studies have been mainly conducted under field conditions to measure total days to heading. We followed a novel approach and studied the natural variation of time to heading in a world-wide spring barley collection (218 accessions), comprising of 95 photoperiod-sensitive (Ppd-H1) and 123 accessions with reduced photoperiod sensitivity (ppd-H1) to long-day (LD) through dissecting pre-anthesis development into four major stages and sub-phases. The study was conducted under greenhouse (GH) conditions (LD; 16/8 h; ∼20/∼16°C day/night). Genotyping was performed using a genome-wide high density 9K single nucleotide polymorphisms (SNPs) chip which assayed 7842 SNPs. We used the barley physical map to identify candidate genes underlying genome-wide association scans (GWAS). GWAS for pre-anthesis stages/sub-phases in each photoperiod group provided great power for partitioning genetic effects on floral initiation and heading time. In addition to major genes known to regulate heading time under field conditions, several novel QTL with medium to high effects, including new QTL having major effects on developmental stages/sub-phases were found to be associated in this study. For example, highly associated SNPs tagged the physical regions around HvCO1 (barley CONSTANS1) and BFL (BARLEY FLORICAULA/LEAFY) genes. Based upon our GWAS analysis, we propose a new genetic network model for each photoperiod group, which includes several newly identified genes, such as several HvCO-like genes, belonging to different heading time pathways in barley

A catalogue of Triticum monococcum genes encoding toxic and immunogenic peptides for celiac disease patients

The celiac disease (CD) is an inflammatory condition characterized by injury to the lining of the small-intestine on exposure to the gluten of wheat, barley and rye. The involvement of gluten in the CD syndrome has been studied in detail in bread wheat, where a set of “toxic” and “immunogenic” peptides has been defined. For wheat diploid species, information on CD epitopes is poor. In the present paper, we have adopted a genomic approach in order to understand the potential CD danger represented by storage proteins in diploid wheat and sequenced a sufficiently large number of cDNA clones related to storage protein genes of Triticum monococcum. Four bona fide toxic peptides and 13 immunogenic peptides were found. All the classes of storage proteins were shown to contain harmful sequences. The major conclusion is that einkorn has the full potential to induce the CD syndrome, as already evident for polyploid wheats. In addition, a complete overview of the storage protein gene arsenal in T. monococcum is provided, including a full-length HMW x-type sequence and two partial HMW y-type sequences

Cysteamine Suppresses Invasion, Metastasis and Prolongs Survival by Inhibiting Matrix Metalloproteinases in a Mouse Model of Human Pancreatic Cancer

Background: Cysteamine, an anti-oxidant aminothiol, is the treatment of choice for nephropathic cystinosis, a rare lysosomal storage disease. Cysteamine is a chemo-sensitization and radioprotection agent and its antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis. Here, we investigated whether cysteamine has anti-tumor and anti-metastatic effects in transplantable human pancreatic cancer, an aggressive metastatic disease. Methodology/Principal Findings: Cysteamine’s anti-invasion effects were studied by matrigel invasion and cell migration assays in 10 pancreatic cancer cell lines. To study mechanism of action, we examined cell viability and matrix metalloproteinases (MMPs) activity in the cysteamine-treated cells. We also examined cysteamine’s anti-metastasis effect in two orthotopic murine models of human pancreatic cancer by measuring peritoneal metastasis and survival of animals. Cysteamine inhibited both migration and invasion of all ten pancreatic cancer cell lines at concentrations (,25 mM) that caused no toxicity to cells. It significantly decreased MMPs activity (IC50 38–460 mM) and zymographic gelatinase activity in a dose dependent manner in vitro and in vivo; while mRNA and protein levels of MMP-9, MMP-12 and MMP-14 were slightly increased using the highest cysteamine concentration. In vivo, cysteamine significantly decreased metastasis in two established pancreatic tumor models, although it did not affect the size of primary tumors. Additionally, cysteamin

Resource-aware Research on Universe and Matter: Call-to-Action in Digital Transformation

Given the urgency to reduce fossil fuel energy production to make climate tipping points less likely, we call for resource-aware knowledge gain in the research areas on Universe and Matter with emphasis on the digital transformation. A portfolio of measures is described in detail and then summarized according to the timescales required for their implementation. The measures will both contribute to sustainable research and accelerate scientific progress through increased awareness of resource usage. This work is based on a three-days workshop on sustainability in digital transformation held in May 2023.Comment: 20 pages, 2 figures, publication following workshop 'Sustainability in the Digital Transformation of Basic Research on Universe & Matter', 30 May to 2 June 2023, Meinerzhagen, Germany, https://indico.desy.de/event/3748

A qualitative study of the feasibility and community perception on the effectiveness of artemether-lumefantrine use in the context of home management of malaria in south-west Nigeria

<p>Abstract</p> <p>Background</p> <p>In Nigeria ACT use at the community level has not been evaluated and the use of antimalarial drugs (commonly chloroquine (CQ)) at home has been shown to be largely incorrect. The treatment regimen of ACT is however more complicated than that of CQ. There is thus a need to determine the feasibility of using ACT at the home level and determine community perception on its use.</p> <p>Methods</p> <p>A before and after qualitative study using key informant interviews (KII) and focus group discussions (FGDs) was conducted in selected villages in Ona-Ara local government area. At baseline, 14 FGDs and 14 KIIs were conducted. Thereafter, community medicine distributors (CMDs) were trained in each village to dispense artemeter-lumenfantrine (AL) to febrile children aged 6–59 months presumed to have uncomplicated malaria. After one year of drug distribution, nine KIIs and 10 FGDs were conducted. Participants and key informants were mothers and fathers with children under five years, traditional heads of communities, opinion leaders and health workers.</p> <p>Results</p> <p>None of the participants have heard of AL prior to study. Participants were favourably disposed to introduction of AL into the community. Mothers/caregivers were said to have used AL in place of the orthodox drugs and herbs reported commonly used prior to study after commencement of AL distribution. The use of CMDs for drug distribution was acceptable to the participants and they were judged to be efficient as they were readily available, distributed correct dose of AL and mobilised the community effectively. AL was perceived to be very effective and no significant adverse event was reported. Major concerns to the sustainability of the program were the negative attitudes of health workers towards discharge of their duties, support to the CMDs and the need to provide CMDs incentives. In addition regular supply of drugs and adequate supervision of CMDs were advised.</p> <p>Conclusion</p> <p>Our findings showed that the use of AL at home and community level is feasible with adequate training of community medicine distributors and caregivers. Community members perceived AL to be effective thus fostering acceptability. The negative attitudes of the health workers and issue of incentives to CMDs need to be addressed for successful scaling-up of ACT use at community level.</p

Searching for Higgs : From LEP towards LHC

After a brief introduction to the theoretical basis of the Higgs mechanism for generating the masses of elementary particles, the experimental searches for Higgs particles will be summarized, from bounds at LEP to inferences for LHC. The report will focus on the Standard Model, though some central results on extended Higgs systems, as conjectured for example in supersymmetric theories, will also be recapitulated. Alternative scenarios based on spontaneous symmetry breaking by novel strong interactions are adumbrated at the theoretical level.Comment: Added reference