A mini transmissionγ-ray Compton polarimeter and measurements of the sign of magnetic moments of radioactive nuclei

A mini transmission-ray Compton polarimeter was developed for the measurement of the sign of magnetic moments of radioactive nuclei with low-temperature nuclear orientation. The signs of the magnetic moments of the following isotopes were determined:¹⁹³Os [=+0.7297(16) _N];^191m Ir [=+6.20(9) _N];¹⁹²Ir [=+1.924(10) _N];¹⁹⁴Ir [=+0.39(1) _N];^195m Pt [=–0.605(15) _N].Dedicated to Prof. Dr. P. Kienle on the occasion of his 60th birthday     

Interaction and lipid-induced conformation of two cecropin-melittin hybrid peptides depend on peptide and membrane composition

The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-9)] with liposomes was studied by differential scanning calorimetry (DSC), circular dichroism (CD), and quasi-elastic light scattering (QELS). The study was carried out with large unilamellar vesicles (LUVs) of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a binary mixture of DMPC/DMPG, in a wide range of peptide-to-lipid (P:L) molar ratios (0 to 1:7). DSC results indicate that, for both peptides, the interaction depends on membrane composition, with very different behavior for zwitterionic and anionic membranes. CD data show that, although the two peptides have different secondary structures in buffer (random coil for CA(1-7)M(2-9) and predominantly beta-sheet for CA(1-8)M(1-18)), they both adopt an alpha-helical structure in the presence of the membranes. Overall, results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, which gives place to aggregation in the gel phase and precipitation after a threshold peptide concentration. In the case of zwitterionic membranes, a progressive surface coverage with peptide molecules destabilizes the membrane, eventually leading to membrane disruption. Moreover, delicate modulations in behavior were observed depending on the peptide.     

Antibody-recruiting protein-catalyzed capture agents to combat antibiotic-resistant bacteria

Antibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting protein-catalyzed capture agents (AR-PCCs), to address this challenge. We applied the combinatorial protein catalyzed capture agent (PCC) technology to identify macrocyclic peptide ligands against highly conserved surface protein epitopes of carbapenem-resistant Klebsiella pneumoniae, an opportunistic Gram-negative pathogen with drug resistant strains. Multi-omic data combined with bioinformatic analyses identified epitopes of the highly expressed MrkA surface protein of K. pneumoniae for targeting in PCC screens. The top-performing ligand exhibited high-affinity (EC₅₀ ∼50 nM) to full-length MrkA, and selectively bound to MrkA-expressing K. pneumoniae, but not to other pathogenic bacterial species. AR-PCCs that bear a hapten moiety promoted antibody recruitment to K. pneumoniae, leading to enhanced phagocytosis and phagocytic killing by macrophages. The rapid development of this highly targeted antibiotic implies that the integrated computational and synthetic toolkit described here can be used for the accelerated production of antibiotics against drug resistant bacteria.

Antibody-recruiting protein-catalyzed capture agent (AR-PCCs) are a new class of all-synthetic and highly targeted antibiotics that recruit endogenous immune responses to eliminate drug-resistant microbes.     

Beyond generative models: superfast traversal,optimization, novelty,exploration and discovery (STONED) algorithm for molecules using SELFIES

Inverse design allows the generation of molecules with desirable physical quantities using property optimization. Deep generative models have recently been applied to tackle inverse design, as they possess the ability to optimize molecular properties directly through structure modification using gradients. While the ability to carry out direct property optimizations is promising, the use of generative deep learning models to solve practical problems requires large amounts of data and is very time-consuming. In this work, we propose STONED – a simple and efficient algorithm to perform interpolation and exploration in the chemical space, comparable to deep generative models. STONED bypasses the need for large amounts of data and training times by using string modifications in the SELFIES molecular representation. First, we achieve non-trivial performance on typical benchmarks for generative models without any training. Additionally, we demonstrate applications in high-throughput virtual screening for the design of drugs, photovoltaics, and the construction of chemical paths, allowing for both property and structure-based interpolation in the chemical space. Overall, we anticipate our results to be a stepping stone for developing more sophisticated inverse design models and benchmarking tools, ultimately helping generative models achieve wider adoption.

Interpolation and exploration within the chemical space for inverse design.     

Generation and reactivity of 3‐carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate

3‐Carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate was generated from (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid and its reactivity studied. This münchnone showed low reactivity as dipole although from the reaction with dimethyl acetylenedicarboxylate the corresponding (3R)‐3‐phenyl‐17H,3H‐pyrrolo[1,2‐c]thiazole‐5,6,7‐tricarboxylate could be isolated. The thermolysis of (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid in refluxing acetic anhydride led to the synthesis of N‐(1‐ethoxycarbonyl‐2‐phenylvinyl)‐2‐phenyl‐4‐thioxo‐1,3‐thiazolidine. The structure of methyl (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazoliddine‐4‐carboxylate was determined by X‐ray crystallography.     

Seedling Development and Evaluation of Genetic Stability of Cryopreserved Dendrobium Hybrid Mature Seeds

Vitrification, a simple, fast, and recommended cryopreservation method for orchid germplasm conservation, was evaluated for Dendrobium hybrid “Dong Yai” mature seeds. The genetic stability of regenerated seedlings was also evaluated using flow cytometry. Mature seeds from this hybrid were submitted to plant vitrification solution (PVS2) for 0, 0.5, 1, 2, 3, 4, 5, or 6 h at 0 °C. Subsequently, they were plunged into liquid nitrogen (LN) at ?196 °C for 1 h and recovered in half-strength Murashige and Skoog culture medium (1/2 MS), and seed germination was evaluated after 30 days. Seeds directly submitted to LN did not germinate after cryopreservation. Seeds treated with PVS2 between 1 and 3 h presented the best germination (between 51 and 58 %), although longer exposure to PVS2 returned moderated germination (39 %). Germinated seeds were further subcultured in P-723 culture medium and developed whole seedlings in vitro after 180 days, with no abnormal characteristics, diseases, or nutritional deficiencies. Seedlings were successfully acclimatized under greenhouse conditions with over 80 % survival. Flow cytometry analysis revealed no chromosomal changes on vitrified seedlings, as well as seedlings germinated from the control treatment (direct exposure to LN). These findings indicate that vitrification is a feasible and safe germplasm cryopreservation method for commercial Dendrobium orchid hybrid conservation.     

Layer‐by‐layer deposition of antimicrobial polymers on cellulosic fibers: a new strategy to develop bioactive textiles

In recent years, there has been an increase of infectious diseases caused by different microorganisms and the development of antibiotic resistance. In this way, the search for new and efficient antibacterial materials is imperative. The main polysaccharides currently used in the biomedical and pharmaceutical domains are chitin and its derivative chitosan (CH) and alginates (ALG). In this study, a simple technique of Layer by Layer (LbL) of applying polycation CH and polyanion ALG was used to prepare CH/ALG multilayers on cotton samples via the electrostatic assembly with success. The CH/ALG cotton samples (functionalized) were investigated for their antibacterial properties towards Staphylococcus aureus and Klebsiella pneumonia using the international standard method JIS L 1902:2002. The antibacterial activity of the functionalized samples was tested in terms of bacteriostatic and bactericidal activity, and results showed that the samples exhibited a bacteriostatic effect on the two bacteria tested, as expected. In addition, samples with five layers (CH/ALG/CH/ALG/CH) were more effective in inhibiting bacterial growth. This new coating for cellulosic fibers is a new strategy and may open new avenues for the development of antimicrobial polymers with potential application in health‐care field. Copyright © 2013 John Wiley & Sons, Ltd.