Laserska izravna dvofotonska fotoliza guanina u DNK

Nanosecond laser-induced oxidative lesions at guanines within DNA were investigated using sequencing gel electrophoresis analysis. Strong sequence-specific lesions on guanines were revealed by either Fpg or piperidine treatments and assigned to 8-oxoG and oxazolone, respectively. It was shown that both the biphotonic ionization process and the chemical reactivity of the radical cation (G+) are dependent on the DNA sequence. The former were explained by the occurrence of energy and charge migration phenomena, while the latter in terms of local DNA hydration peculiarities.Istraživali smo lomove DNK izazvane nanosekundnim laserskim impulsima primjenom gel elektroforeze za određivanje nizova. Otkrili smo snažne nizovno specifične lomove kod guanina djelovanjem sa Fpg ili piperidinom i oni se pripisuju 8-oxoG odnosno oxazolonu. Pokazali smo da su i dvofotonski ionizacijski proces i kemijska reaktivnost radikala kationa (G+) nizovno ovisni. Prvi se objašnjava selenjem energije i naboja, a drugi kao posebnosti lokalnog hidriranja DNK

Laserska izravna dvofotonska fotoliza guanina u DNK

Nanosecond laser-induced oxidative lesions at guanines within DNA were investigated using sequencing gel electrophoresis analysis. Strong sequence-specific lesions on guanines were revealed by either Fpg or piperidine treatments and assigned to 8-oxoG and oxazolone, respectively. It was shown that both the biphotonic ionization process and the chemical reactivity of the radical cation (G+) are dependent on the DNA sequence. The former were explained by the occurrence of energy and charge migration phenomena, while the latter in terms of local DNA hydration peculiarities.Istraživali smo lomove DNK izazvane nanosekundnim laserskim impulsima primjenom gel elektroforeze za određivanje nizova. Otkrili smo snažne nizovno specifične lomove kod guanina djelovanjem sa Fpg ili piperidinom i oni se pripisuju 8-oxoG odnosno oxazolonu. Pokazali smo da su i dvofotonski ionizacijski proces i kemijska reaktivnost radikala kationa (G+) nizovno ovisni. Prvi se objašnjava selenjem energije i naboja, a drugi kao posebnosti lokalnog hidriranja DNK

Mjerenje prinosa međusustavnog prijelaza s4U u tRNA vremenski-razlučenim izbjeljivanjem

The rare base 4-thiouridine (s4U), present in various transfer RNA (tRNA) molecules from Escherichia coli, occupies usually the strategically important 8 th position between the double helices of the acceptor and the dihydrouridine stems of the cloverleaf. This unusual base is largely used as an intrinsic build-in probe for RNA conformational and RNA(DNA)–protein interaction studies through triplet excited state photochemistry related to covalent adducts formation. Here, by applying laser transient absorption saturation spectroscopy, we measured the intersystem crossing yield ϕST and the excited triplet state absorption εT−T of s4U within tRNA. While the incorporation of s4U in tRNA induced appreciable changes in the latter, no important variation of the intersystem crossing yield was observed, which is in contrasts with the published data.Rijetka baza 4-thiouridine (s4U), koju nalazimo u raznim prijenosnim molekulama RNA (tRNA) Escherichie coli, obično uzima strateški važan 8. položaj između dviju zavojnica primatelja i dihidrouridinskih stapki lista djeteline. Ta se neobična baza najviše rabi kao unutarnja ugradbena proba za proučavanje interakcija konformalne RNA s RNA(DNA)–proteinima preko fotokemije tripletnog uzbuđenog stanja, povezanog sa stvaranjem kovalentnih adukata. U ovom smo radu primjenom laserske prijelazne apsorpcijske spektroskopije sa zasićenjem mjerili prinos međusustavnih prijelaza ϕST i apsorpciju tripletnog stanja εT−T s 4U u tRNA. Dok ugrađivanje s4U u tRNA uzrokuje prilične promjene u tRNA, nismo opazili promjene prinosa međusustavnih prijelaza, što nije u skladu s objavljenim rezultatima

Mjerenje prinosa međusustavnog prijelaza s4U u tRNA vremenski-razlučenim izbjeljivanjem

The rare base 4-thiouridine (s4U), present in various transfer RNA (tRNA) molecules from Escherichia coli, occupies usually the strategically important 8 th position between the double helices of the acceptor and the dihydrouridine stems of the cloverleaf. This unusual base is largely used as an intrinsic build-in probe for RNA conformational and RNA(DNA)–protein interaction studies through triplet excited state photochemistry related to covalent adducts formation. Here, by applying laser transient absorption saturation spectroscopy, we measured the intersystem crossing yield ϕST and the excited triplet state absorption εT−T of s4U within tRNA. While the incorporation of s4U in tRNA induced appreciable changes in the latter, no important variation of the intersystem crossing yield was observed, which is in contrasts with the published data.Rijetka baza 4-thiouridine (s4U), koju nalazimo u raznim prijenosnim molekulama RNA (tRNA) Escherichie coli, obično uzima strateški važan 8. položaj između dviju zavojnica primatelja i dihidrouridinskih stapki lista djeteline. Ta se neobična baza najviše rabi kao unutarnja ugradbena proba za proučavanje interakcija konformalne RNA s RNA(DNA)–proteinima preko fotokemije tripletnog uzbuđenog stanja, povezanog sa stvaranjem kovalentnih adukata. U ovom smo radu primjenom laserske prijelazne apsorpcijske spektroskopije sa zasićenjem mjerili prinos međusustavnih prijelaza ϕST i apsorpciju tripletnog stanja εT−T s 4U u tRNA. Dok ugrađivanje s4U u tRNA uzrokuje prilične promjene u tRNA, nismo opazili promjene prinosa međusustavnih prijelaza, što nije u skladu s objavljenim rezultatima

Učinci UV zračenja visokog intenziteta na izdvojen i s dna interkaliran etidium bromid

High-intensity picosecond laser flash photolysis has been used for investigating ethidium bromide (EtBr). The quantum yield of primary photoproducts as a function of the laser intensity has been obtained. DNA intercalated EtBr and water solutions of EtBr have been investigated. The results have been compared. They show that two-photon processes are predominantly responsible for generation of hydrated electron (eaq-). The primary processes of DNA photosensitization have also been discussed.Istraživali smo etidium bromid (EtBr) pomoću pikosekundne bljeskovne fotolize velikog intenziteta. Određeni su kvantni prinosi fotoprodukata u ovisnosti o intenzitetu laserskog snopa. Istraživao se je EtBr u vodenoj otopini i interkalirani s DNA. Rezultati se uspoređuju i oni pokazuju da pretežno dvofotonski procesi tvore hidrirane elektrone eaq-. Raspravljaju se također primarni procesi fotosenzitiranja DNA

Učinci UV zračenja visokog intenziteta na izdvojen i s dna interkaliran etidium bromid

High-intensity picosecond laser flash photolysis has been used for investigating ethidium bromide (EtBr). The quantum yield of primary photoproducts as a function of the laser intensity has been obtained. DNA intercalated EtBr and water solutions of EtBr have been investigated. The results have been compared. They show that two-photon processes are predominantly responsible for generation of hydrated electron (eaq-). The primary processes of DNA photosensitization have also been discussed.Istraživali smo etidium bromid (EtBr) pomoću pikosekundne bljeskovne fotolize velikog intenziteta. Određeni su kvantni prinosi fotoprodukata u ovisnosti o intenzitetu laserskog snopa. Istraživao se je EtBr u vodenoj otopini i interkalirani s DNA. Rezultati se uspoređuju i oni pokazuju da pretežno dvofotonski procesi tvore hidrirane elektrone eaq-. Raspravljaju se također primarni procesi fotosenzitiranja DNA

Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries:results of an internet-based global point prevalence survey

Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux

Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries

BACKGROUND: Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. METHODS: 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. FINDINGS: Of the 23 572 patients included from 56 countries, 18 305 were children (77·7%) and 5267 were neonates (22·3%). Access antibiotic use in children ranged from 7·8% (China) to 61·2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77·3%) and lowest in Finland (23·0%). In neonates, Access antibiotic use was highest in Singapore (100·0%) and lowest in China (24·2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. INTERPRETATION: There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. FUNDING: GARPEC was funded by the PENTA Foundation. GARPEC-China data collection was funded by the Sanming Project of Medicine in Shenzhen (SZSM2015120330). bioMérieux provided unrestricted funding support for the Global-PPS

Neverlang 2 : a framework for modular language implementation

Neverlang 2 is a JVM-based framework for language development that emphasizes code reuse through composition of language features. This paper is aimed at showing how to develop extensible, custom languages using Neverlang's component-based model of implementation. Using this model, each feature of the language can be implemented as a separate, conceptually isolated unit that can be compiled and distributed separately from the others. A live tutorial of the framework can be found at http://youtu.be/Szxvg7XLbX