Photochemical Electrocyclic Ring Closure and Leaving Group Expulsion from N-(9-oxothioxanthenyl)Benzothiophene Carboxamides

N-(9-Oxothioxanthenyl)benzothiophene carboxamides bearing leaving groups (LG− = Cl−, PhS−, HS−, PhCH2S−) at the C-3 position of the benzothiophene ring system photochemically cyclize with nearly quantitative release of the leaving group, LG−. The LG− photoexpulsions can be conducted with 390 nm light or with a sunlamp. Solubility in 75% aqueous CH3CN is achieved by introducing a carboxylate group at the C-6 position of the benzothiophene ring. The carboxylate and methyl ester derivatives regiospecifically cyclize at the more hindered C-1 position of the thioxanthone ring. Otherwise, the photocyclization favors the C-3 position of the thioxanthone. Quantum yields for reaction are 0.01–0.04, depending on LG− basicity. Electronic structure calculations for the triplet excited state show that excitation transfer occurs from the thioxanthone to the benzothiophene ring. Subsequent cyclization in the triplet excited state is energetically favourable and initially generates the triplet excited state of the zwitterionic species. Expulsion of LG− is thought to occur once this species converts to the closed shell ground state

Photochemical Eilmination Reactions via Zwitterionic Intermediates Generated by Electrocyclic Ring Closures

The research focuses on the design of photoremovable protecting groups that can be used to deprotect biological substrates of an organic compound by photolysis. The deprotection of the protecting group via photolysis requires heterolysis of a bond to the substrate. Heterolysis of a C-O or C-S σ-bonds in a zwitterionic intermediate is proposed. The photochemical electrocyclic reactions studied involve acrylanilides, benzothiophene carboxanilides, and N-(9-oxothioxanthenyl) benzothiophene carboxamides. α,β-Unsaturated anilides bearing leaving groups at the allylic position of the α-methylacrylamide group undergo photochemical electrocyclic ring closure with release of leaving group which could occur directly from a photochemically produced zwitterionic intermediate or via an enolate produced upon deprotonation of zwitterionic intermediate. An accompanying minor photoproduct retaining the leaving group is thought to be formed via a 1,5-H shift of the zwitterionic intermediate. The photolysis wavelength can be 365 nm by introducing a benzoyl group into the para position of the anilide. The photochemistry derives from the singlet excited state. The most efficient photochemical electrocyclic ring closure and leaving group expulsion found thus far occurs with benzothiophene carboxanilides, which has considerable potential for use as cage compounds. A variety of leaving groups, incorporated at the C-3 position of the benzothiophene ring system are photochemically expelled completely, and the quantum efficiencies for LG- expulsion vary with basicity of the LG- over the range 0.007-0.2. The approximate dependence of log Φ on the pKa of the leaving group conjugate acid suggests that the LG- expulsion competes with ring-dissertationing of the zwitterionic intermediate. The electrocyclic ring closure to form the zwitterionic intermediate occurs in the triplet excited state. Incorporation of benzophenone chromophore by replacing the N-phenyl group of the anilide allows photolyses to be conducted at 365 nm. Thioxanthones bearing a benzothiophene carboxamide group at the C-2 position are capable of expelling leaving groups such as Cl-PhS-, HS- and PhCH2S-. The leaving group expulsions can be achieved using 390 nm light. Moreover, the inclusion of a carboxylate group at the C-6 position of the benzothiophene ring improves solubility in aqueous media. The photocyclizations occur in the triplet excited state according to quenching experiments

Razlučivanje orijentacije linijskih indikacija pri ispitivanju ultrazvukom

Cilj ovog rada je provesti ultrazvučna ispitivanja pripremljenih uzoraka te izdvojiti zaključak o mjeri razlučivanja orijentacije linijskih indikacija u uzorcima. Na početku rada je opisan sustav za nerazornu metodu ispitivanja ultrazvukom s naglaskom na metodi koherentnog ultrazvučnog polja. Navedene su i analizirane glavne karakteristike uobičajenih tehnika ispitivanja ultrazvukom te su pobliže opisani sustavi za ispitivanje primjenom koherentnog ultrazvučnog polja. Pripremljen je skup od četiri uzorka sa linijskim indikacijama jednake visine, a različite orijentacije u odnosu na referentnu, kontaktnu plohu primopredajnika i ispitivanog objekta. Provedena su ultrazvučna ispitivanja te je ponuđen zaključak o razlučivanju orijentacije indikacija u uzorcima, te prednostima i nedostacima korištenja metode koherentnog ultrazvučnog polja u odnosu na konvencionalne metode ispitivanja ultrazvukom

Uređaj za mjerenje karakteristike pogonskih strojeva

Pogonskom stroju se želi odrediti zavisnost okretnog momenta o brzini vrtnje na izlaznom vratilu. Za ispitno postolje na kojemu bi se odvijala ispitivanja je potrebno da bude prilagodljivo za određeni spektar motora na kojima bi se vršila mjerenja. Potrebno je pronaći odgovarajući način kočenja pogonskog stroja kako bi se omogućilo određivanje karakteristike. Također je potrebno odrediti koji su sustavi nužni za funkcioniranje pogonskog stroja, te na koji bi se način izvodilo praćenje zadanih parametara: okretnog momenta i brzine vrtnje na izlaznom vratilu pogonskog stroja te karakteristična temperatur

Decission making process in taking care of children/adults - differences in attitudes among medical employeers

Cilj istraživanja: • Ispitati stavove zdravstvenih djelatnika o procesu donošenja odluka u vezi s njegom djece/odraslih osoba. • Ispitati postoje li razlike s obzirom na dob, spol, mjesto boravka, obrazovanje i socijalno stanje. Ustroj studije: presječna studija. Ispitanici i metode: istraživanje je provedeno na uzorku od 93 ispitanika. Ispitanike su činile dvije skupine: medicinske sestre/tehničari Klinike za pedijatriju (51,6 %) i medicinske sestre/tehničari Klinike za kirurgiju (48,4 %). Prikupljanje se odvijalo putem anketnog upitnika. Anketa je u potpunosti bila anonimna i u njoj su ispitanici isključivo dobrovoljno sudjelovali. Rezultati: istraživanje je pokazalo kako postoji povezanost između spola i mišljenja je li lakše donositi odluke za odrasle pacijente. Dokazano je kako su muškarci naklonjeniji mišljenju da je lakše donositi odluke vezane za odrasle pacijente, nego žene. Istraživanje je pokazalo kako su mlađi djelatnici daleko emotivnije vezani za pacijente te na njih bol i patnja pacijenta daleko više utječu nego na starije zdravstvene djelatnike. Također, istraživanje je pokazalo da su zdravstveni djelatnici koji žive u gradu ili prigradskim naseljima skloniji tvrdnji da nakon smrti pacijenta ne razmišljaju što bi bilo da su drugačije postupili, dok su zdravstveni djelatnici koji žive na selu skloniji razmišljanju nakon smrti pacijenta jesu li mogli drugačije postupiti. Zaključak: zaključno se može reći kako postoje određene statističke razlike u stavovima zdravstvenih djelatnika o procesu donošenja odluka u vezi s njegom djece/odraslih osoba i to s obzirom na spol, dob, mjesto boravka, obrazovanje, zanimanje, mjesečne prihode, radni staž te radno mjesto.Research Objective: • Examine the attitudes of healthcare professionals about the decision-making process related to the care of children / adults. • Examine the differences between health professionals in terms of age, gender, place of residence, education, and social status. Study structure: Term study. Subjects and methods: The survey was conducted on a sample of 93 examinees. The examinees were divided into two groups: Nurses / technicians of the Paediatric Clinic (51.6%) and nurses / technicians of the Surgery Clinic (48.4%). The survey was used for data collection. The survey was completely anonymous and the subjects participated voluntarily. Results: The research has shown that there is a correlation between gender and the opinion about whether it is easier to make decisions for adult patients. It has been shown that men are more inclined to think that it is easier to make decisions regarding adult patients. The research has shown that younger health care workers are far more emotional towards the patients and the pain and suffering of the patient affects them more than it affects older health workers. Also, the research has shown that health care professionals living in the city or in suburban areas are more inclined to say that they do not think about what would have happened if they had made a different decision, while healthcare workers living in the village are more inclined to think that they could have acted differently. Conclusion: There are certain statistical differences in the attitudes of healthcare professionals about the decision-making process regarding the care for children / adults, with regard to gender, age, place of residence, education, occupation, monthly income, working time, and workplace

No Longer a Complex, Not Yet a Molecule: A Challenging Case of Nitrosyl O-Hydroxide, HOON

N-(9-Oxothioxanthenyl)benzothiophene carboxamides bearing leaving groups (LG− = Cl−, PhS−, HS−, PhCH2S−) at the C-3 position of the benzothiophene ring system photochemically cyclize with nearly quantitative release of the leaving group, LG−. The LG− photoexpulsions can be conducted with 390 nm light or with a sunlamp. Solubility in 75% aqueous CH3CN is achieved by introducing a carboxylate group at the C-6 position of the benzothiophene ring. The carboxylate and methyl ester derivatives regiospecifically cyclize at the more hindered C-1 position of the thioxanthone ring. Otherwise, the photocyclization favors the C-3 position of the thioxanthone. Quantum yields for reaction are 0.01–0.04, depending on LG− basicity. Electronic structure calculations for the triplet excited state show that excitation transfer occurs from the thioxanthone to the benzothiophene ring. Subsequent cyclization in the triplet excited state is energetically favourable and initially generates the triplet excited state of the zwitterionic species. Expulsion of LG− is thought to occur once this species converts to the closed shell ground state

Preservation of Bovine Hide using Less Salt with Low Concentration of Antiseptic

Content: A Conventional technique of bovine hide preservation requires approximately 40-50% sodium chloride or table salt on raw hide weight or 95% saturated brine in case of wet salting. This salt resides in wastewater after the soaking process and generates a huge environmental pollution in the form of total dissolved solids (TDS) and chloride (Cl-) during leather processing. The current research has developed an antiseptic based hide curing formulation using 45% saturated brine solution which reduces 50% salt usage in compare to the traditional method. For hide preservation, it is essential to arrest microbial attack on hide as the main constituent of raw hide is protein which is very susceptible for bacterial degradation. The newly developed formulations have been found more effective in limiting microbial growth on cured hide than the conventional method preserving the bovine hide for more than 30 days. In-process analysis of cured hides during storage period reveals the compatibility of the alternative curing process. Post-leather analysis e.g. grain pattern, scanning electron microscopic images, mechanical properties and organoleptic evaluation reveal that the crust leather produced from alternatively cured hides are comparable to the control obtained from traditionally preserved hide. The efficacy of the alternative system is also assessed by monitoring the environmental impacts caused by the leather processing effluents on the basis of TDS and chloride content, total solids (TS), total aerobic bacterial counts in soaking liquor, Bio-Chemical oxygen demand (BOD) and Chemical oxygen demand (COD). The environmental advantages of the alternative hide curing method are determined particularly by 50% reduction of TDS and chloride content. Therefore, this new development will not only preserve hide through better protection from microorganisms but also offer improved conservation of the environment. Take-Away: Environmentally friendly technique of animal hide preservation Hide preservation through better protection from microbial degradatoin than the traditional techniqu

Comparison Of The Diagnostic Value Of Computed Tomography And Magnetic Resonance Imaging Of Schmorl’s Hernia In Young People

Uvod: Schmorlove hernije su često dijagnosticirane degenerativne promjene kralježaka koje se javljaju kod mladih osoba. U dijagnostici Schmorlove hernije najčešće se primjenjuju metode kompjuterizirana tomografija (CT) i magnetska rezonancija (MR). Oba modaliteta pružaju detaljne informacije o strukturi i stanju kralježaka, ali se razlikuju po principu rada i karakteristikama slike koje generiraju uz svoje prednosti i ograničenja. Materijal i metode: Istraživanje Schmorlovih hernija kod mladih osoba, s fokusom na usporedbu dijagnostičke vrijednosti kompjuterizirane tomografije i magnetske rezonancije, provedeno je u Zavodu za radiologiju Sveučilišne kliničke bolnice Mostar. Rezultati: Rezultati istraživanja pokazali su da je najmlađi ispitanik imao 14 godina, a najstariji 89 godina. Ispitanika mlađih od 45 godina bilo je 27 % u ukupnom broju ispitanika. U našem istraživanju bilo je više ispitanika muškog spola, njih 57 %. Znatno je više ispitanika imalo nalaz MR-a, njih 64 %, dok je ispitanika s nalazom MSCT-a bilo 36 %. Kod pretrage MSCT najčešće je nalaz Schmorlove hernije bio u torakalnoj regiji, 42 %. Za razliku od MSCT-a, kod MR-a su se pojavile diskretne promjene na pokrovnim plohama (10 %). Zaključak: Odabir između CT-a i MR-a ovisit će o kliničkim okolnostima, dostupnosti i ciljevima dijagnostičkog postupka. Važno je individualno prilagoditi dijagnostički pristup svakom pacijentu kako bi se postigla optimalna dijagnostička točnost i donijele informirane odluke o liječenju.Introduction: Schmorl’s hernias are frequently diagnosed as degenerative changes in the vertebrae that occur in young people. In the diagnosis of Schmorl’s hernia, the two most commonly used methods are computed tomography (CT) and magnetic resonance (MR). Both modalities provide detailed information on the structure and condition of the vertebrae, but they differ in the principle of operation and the characteristics of the image they generate with their advantages and limitations Material and methods: Research on Schmorl’s hernias in young people, with a focus on comparing the diagnostic value of computed tomography and magnetic resonance imaging, was conducted at the Department of Radiology of the University Clinical Hospital Mostar. Results: The results of the research showed that the youngest respondent was 14 years old, and the oldest was 89 years old. Respondents under the age of 45 were a total of 27% of the total number of respondents. In our research, there were more male respondents, 57% of them. Significantly more subjects had MRI findings, 64% of them, while 36% of subjects had MSCT findings. In the MSCT examination, Schmorl’s hernia was most often found in the thoracic region, 42%. In contrast to MSCT, MR showed discrete changes in the endplates (10%). Conclusion: The choice between CT and MR will depend on the clinical circumstances, availability and goals of the diagnostic procedure. It is important to individually adapt the diagnostic approach to each patient in order to achieve optimal diagnostic accuracy and make informed treatment decisions

Identification of inhibitors that target dual-specificity phosphatase 5 provide new insights into the binding requirements for the two phosphate pockets

Background: Dual-specificity phosphatase-5 (DUSP5) plays a central role in vascular development and disease. We present a p-nitrophenol phosphate (pNPP) based enzymatic assay to screen for inhibitors of the phosphatase domain of DUSP5. Methods: pNPP is a mimic of the phosphorylated tyrosine on the ERK2 substrate (pERK2) and binds the DUSP5 phosphatase domain with a Km of 7.6 ± 0.4 mM. Docking followed by inhibitor verification using the pNPP assay identified a series of polysulfonated aromatic inhibitors that occupy the DUSP5 active site in the region that is likely occupied by the dual-phosphorylated ERK2 substrate tripeptide (pThr-Glu-pTyr). Secondary assays were performed with full length DUSP5 with ERK2 as substrate. Results: The most potent inhibitor has a naphthalene trisulfonate (NTS) core. A search for similar compounds in a drug database identified suramin, a dimerized form of NTS. While suramin appears to be a potent and competitive inhibitor (25 ± 5 μM), binding to the DUSP5 phosphatase domain more tightly than the monomeric ligands of which it is comprised, it also aggregates. Further ligand-based screening, based on a pharmacophore derived from the 7 Å separation of sulfonates on inhibitors and on sulfates present in the DUSP5 crystal structure, identified a disulfonated and phenolic naphthalene inhibitor (CSD3 _2320) with IC50 of 33 μM that is similar to NTS and does not aggregate. Conclusions: The new DUSP5 inhibitors we identify in this study typically have sulfonates 7 Å apart, likely positioning them where the two phosphates of the substrate peptide (pThr-Glu-pTyr) bind, with one inhibitor also positioning a phenolic hydroxyl where the water nucleophile may reside. Polysulfonated aromatic compounds do not commonly appear in drugs and have a tendency to aggregate. One FDA-approved polysulfonated drug, suramin, inhibits DUSP5 and also aggregates. Docking and modeling studies presented herein identify polysulfonated aromatic inhibitors that do not aggregate, and provide insights to guide future design of mimics of the dual-phosphate loops of the ERK substrates for DUSPs. Keywords: DUSP5, Phosphatase, Drug discovery, Docking, Suramin, Vascular anomalie