Methods and codes for neutronic calculations of the MARIA research reactor.

The core of the MARIA high flux multipurpose research reactor is highly heterogeneous. It consists of beryllium blocks arranged in 6 x 8 matrix, tubular fuel assemblies, control rods and irradiation channels. The reflector is also heterogeneous and consists of graphite blocks clad with aluminum. Its structure is perturbed by the experimental beam tubes. This paper presents methods and codes used to calculate the MARIA reactor neutronics characteristics and experience gained thus far at IAE and ANL. At ANL the methods of MARIA calculations were developed in connection with the RERTR program. At IAE the package of programs was developed to help its operator in optimization of fuel utilization

A Novel Mechanism of Programmed Cell Death in Bacteria by Toxin–Antitoxin Systems Corrupts Peptidoglycan Synthesis

Most genomes of bacteria contain toxin–antitoxin (TA) systems. These gene systems encode a toxic protein and its cognate antitoxin. Upon antitoxin degradation, the toxin induces cell stasis or death. TA systems have been linked with numerous functions, including growth modulation, genome maintenance, and stress response. Members of the epsilon/zeta TA family are found throughout the genomes of pathogenic bacteria and were shown not only to stabilize resistance plasmids but also to promote virulence. The broad distribution of epsilon/zeta systems implies that zeta toxins utilize a ubiquitous bacteriotoxic mechanism. However, whereas all other TA families known to date poison macromolecules involved in translation or replication, the target of zeta toxins remained inscrutable. We used in vivo techniques such as microscropy and permeability assays to show that pneumococcal zeta toxin PezT impairs cell wall synthesis and triggers autolysis in Escherichia coli. Subsequently, we demonstrated in vitro that zeta toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG) and that this activity is counteracted by binding of antitoxin. After identification of the product we verified the kinase activity in vivo by analyzing metabolite extracts of cells poisoned by PezT using high pressure liquid chromatograpy (HPLC). We further show that phosphorylated UNAG inhibitis MurA, the enzyme catalyzing the initial step in bacterial peptidoglycan biosynthesis. Additionally, we provide what is to our knowledge the first crystal structure of a zeta toxin bound to its substrate. We show that zeta toxins are novel kinases that poison bacteria through global inhibition of peptidoglycan synthesis. This provides a fundamental understanding of how epsilon/zeta TA systems stabilize mobile genetic elements. Additionally, our results imply a mechanism that connects activity of zeta toxin PezT to virulence of pneumococcal infections. Finally, we discuss how phosphorylated UNAG likely poisons additional pathways of bacterial cell wall synthesis, making it an attractive lead compound for development of new antibiotics

An ab initio and AIM investigation into the hydration of 2-thioxanthine

<p>Abstract</p> <p>Background</p> <p>Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an <it>ab initio </it>study of the hydration of 2TX, revealing water can form seven hydrated complexes.</p> <p>Results</p> <p>Hydrogen-bond (H-bond) interactions in 1:1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX^...H₂O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed.</p> <p>Conclusion</p> <p>2TX can interact with water by five different H-bonding regimes, N-H^...O, O-H^...N, O-H^...O, O-H^...S and C-H^...O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H^...O and O-H^...O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.</p

Real-world study of children and young adults with myeloproliferative neoplasms: identifying risks and unmet needs

Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN

Carboxymethyl Cellulose Oxidation to Form Aldehyde Group

Oxidation of carboxymethyl cellulose (CMC) is a method of its modification, which allows to improve the functionality of this compound by increasing its reactivity. Presented work describes two methods of oxidation of carboxymethyl cellulose. The first is the conversion of CMC to its dialdehyde derivatives (DCMC) by sodium periodate. In the second method, hydrogen peroxide in the presence of iron tetrasulfophthalocyanine (FePcS) as catalyst was applied. Oxidation degree of CMC in different process parameters and time intervals was estimated using hydroxylamine hydrochloride. Modified CMC will be used in nanoparticles preparation in medical diagnostics

Synteza nanocząstek karboksymetylocelulozowych z wykorzystaniem różnych czynników zwijających

Polysaccharide-based nanoparticles (NPs), due to their outstanding properties, attract much attention in the field of drug delivery systems. Presented work describes a method of carboxymethyl cellulose NPs synthesis which can serve as anticancer drugs carriers. The main goal of this research was to investigate the influence of type and amount of aliphatic amine and different carboxymethyl cellulose oxidation degree on the resulting NPs size.Nanocząstki polisacharydowe ze względu na swoje unikalne właściwości cieszą się dużym zainteresowaniem w systemach podawania leków. Prezentowana praca opisuje metodę syntezy nanocząstek karboksymetylocelulozowych, które mogą pełnić rolę nośnika leków przeciwnowotworowych. Celem wykonanych badań było zbadanie wpływu typu i ilości użytej aminy alifatycznej oraz różnych stopni utlenienia karboksymetylocelulozy na rozmiar powstających nanocząstek

Application of the generally available WIMS versions to modern PWRs

The generally available versions of WIMS (Winfrith improved multigroup scheme) code have been used at the Institute of Atomic Energy POLATOM (IEA POLATOM, Otwock/Świerk, Poland) for a variety of reactor lattice analyses since 1974. With planned construction of new generation PWRs (power water reactors) in Poland, a question of WIMSD-5B version applicability to lattice calculations of strongly heterogeneous assemblies with gadolinium poisoned pins became actual. The present paper deals with modeling of the fuel assemblies using the version of WIMSD-5B extended at the IEA POLATOM. It was shown that with a careful choice of computational options the code properly describes main physical parameters of modern PWR fuel assemblies