Conformational landscape and low lying excited states of imatinib

Abstract The conformational changes of imatinib (IMT) are crucial for understanding the ligand–receptor interaction and its mechanism of action [Agofonov et al. (2014) Nature Struct Mol Biol 21:848–853]. Therefore, here we investigated the free energy conformational landscape of the free IMT base, aiming to describe the three-dimensional structures and energetic stability of its conformers. Forty-five unique conformers, within an energy window of 4.8 kcal mol−1 were identified by a conformational search in gas-phase, at the B3LYP/6-31G(d) theoretical level. Among these, the 20most stable, as well as 4 conformers resulting from optimization of experimental structures found in the two known polymorphs of IMTand in the c- Abl complex were further refined using the 6-31+G(d,p) basis set and the polarizable continuum solvation model. The most stable conformers in gas-phase and water exhibit a V-shaped structure. The major difference between the most stable free conformers and the bioactive conformers consists in the relative orientation of the pyrimidine–pyridine groups responsible for hydrogen bonding interactions in the ATP-binding pocket. The ratio of mole fractions corresponding to the two known (α and β) polymorphic forms of IMT was estimated from the calculated thermochemical data, in quantitative agreement with the existing experimental data related to their solubility. The electronic absorption spectrum of this compound was investigated in water and explained based on the theoretical TD-DFT results, considering the Boltzmann populationaveraged computed data at CAM-B3LYP/6-31+G(d,p) level of theory for the nine most stable conformers

Optimizing PMMA solutions to suppress contamination in the transfer of CVD graphene for batch production

Mass production and commercial adoption of graphene-based devices are held back by a few crucial technical challenges related to quality control. In the case of graphene produced by chemical vapor deposition, the transfer process represents a delicate step that can compromise device performance and reliability, thus hindering industrial production. In this context, the impact of poly(methyl methacrylate) (PMMA), the most common support material for transferring graphene from the Cu substrate to any target surface, can be decisive in obtaining reproducible sample batches. Although effective in mechanically supporting graphene during the transfer, PMMA solutions needs to be efficiently designed, deposited, and post-treated to serve their purpose while minimizing potential contaminations. Here, we prepared and tested PMMA solutions with different average molecular weight (AMW) and weight concentration in anisole, to be deposited by spin coating. Optical microscopy and Raman spectroscopy showed that the amount of PMMA residues on transferred graphene is proportional to the AMW and concentration in the solvent. At the same time, the mechanical strength of the PMMA layer is proportional to the AMW. These tests served to design an optimized PMMA solution made of a mixture of 550,000 (550k) and 15,000 (15k) AMW PMMA in anisole at 3% concentration. In this design, PMMA550k provided suitable mechanical strength against breakage during the transfer cycles, while PMMA-15k promoted depolymerization, which allowed for a complete removal of PMMA residues without the need for any post-treatment. An XPS analysis confirmed the cleanness of the optimized process. We validated the impact of the optimized PMMA solution on the mass fabrication of arrays of electrolyte-gated graphene field-effect transistors operating as biosensors. On average, the transistor channel resistance decreased from 1860 to 690 Ω when using the optimized PMMA. Even more importantly, the vast majority of these resistance values are distributed within a narrow range (only ca. 300 Ω wide), in evident contrast with the scattered values obtained in non-optimized devices (about 30% of which showed values above 1 MΩ). These results prove that the optimized PMMA solution unlock the production of reproducible electronic devices at the batch scale, which is the key to industrial productionproject "GEMIS – Graphene-enhanced Electro-Magnetic Interference Shielding", with the reference POCI-01-0247-FEDER-045939, co-funded by COMPETE 2020 – Operational Programme for Competitiveness and Internationalization and the Portuguese Foundation for Science and Technology (FCT), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and the FCT via the Strategic Funding UIDB/04650/2020. C. D. Liao acknowledges a Marie Skłodowska-Curie COFUND Fellowship (H2020-MSCA-COFUND 2015). T. Queirós acknowledges a PhD grant from FCT with reference SFRH/BD/150646/2020 in the framework of the Quantum Portugal Initiative. T. Domingues acknowledges a PhD grant from FCT with reference SFRH/BD/08181/202

Cd and Cu interdiffusion in Cu(In,Ga)Se2/CdS hetero-interfaces

We report a detailed characterization of an industry-like prepared Cu(In,Ga)Se2 (CIGS)/CdS heterojunction by scanning transmission electron microscopy (STEM) and photoluminescence (PL). Energy dispersive x-ray spectroscopy (EDS) shows the presence of several regions in the CIGS layer that are Cu deprived and Cd enriched, suggesting the segregation of Cd-Se. Concurrently, the CdS layer shows Cd-deprived regions with the presence of Cu, suggesting a segregation of Cu-S. The two types of segregations are always found together, which, to the best of our knowledge, is observed for the first time. The results indicate that there is a diffusion process that replaces Cu with Cd in the CIGS layer and Cd with Cu in the CdS layer. Using a combinatorial approach we identified that this effect is independent of focused-ion beam sample preparation and of the TEM-grid. Furthermore, photoluminescence measurements before and after an HCl etch indicate a lower degree of defects in the post-etch sample, compatible with the segregates removal. We hypothesize that Cu2-xSe nanodomains react during the chemical bath process to form these segregates since the chemical reaction that dominates this process is thermodynamically favourable. These results provide important additional information about the formation of the CIGS/CdS interface.publishe

Efficient reSe2 photodetectors with CVD single-crystal graphene contacts

Rhenium-based 2D transition metal dichalcogenides such as ReSe2 are suitable candidates as photoactive materials for optoelectronic devices. Here, photodetectors based on mechanically exfoliated ReSe2 crystals were fabricated using chemical vapor deposited (CVD) graphene single-crystal (GSC) as lateral contacts. A "pick & place" method was adopted to transfer the desired crystals to the intended position, easing the device fabrication while reducing potential contaminations. A similar device with Au was fabricated to compare contacts' performance. Lastly, a CVD hexagonal boron nitride (hBN) substrate passivation layer was designed and introduced in the device architecture. Raman spectroscopy was carried out to evaluate the device materials' structural and electronic properties. Kelvin probe force measurements were done to calculate the materials' work function, measuring a minimal Schottky barrier height for the GSC/ReSe2 contact (0.06 eV). Regarding the electrical performance, I-V curves showed sizable currents in the GSC/ReSe2 devices in the dark and under illumination. The devices presented high photocurrent and responsivity, along with an external quantum efficiency greatly exceeding 100%, confirming the non-blocking nature of the GSC contacts at high bias voltage (above 2 V). When introducing the hBN passivation layer, the device under white light reached a photo-to-dark current ratio up to 106.This research was funded by National Funds through the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UIDB/04650/2020 and projects PTDC/FIS-NAN/3668/2014 (LA2D) and PTDC/FIS-MAC/28114/2017 (POCI-01-0145-FEDER-028114) (GRAPHSENS). A.C. acknowledges the financial support of the project "GEMISGraphene-enhanced Electro-Magnetic Interference Shielding," with the reference POCI-01-0247-FEDER-045939, co-funded by COMPETE 2020-Operational Programme for Competitiveness and Internationalization and FCT-Science and Technology Foundation, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)

Gallstone ileus- 20 years of interclinical experience

Universitatea de Medicină și Farmacie “Carol Davila”, Bucureşti, Clinica Chirurgie, Spitalul Clinic de Urgentă Bucureşti, Universitatea de Medicina si Farmacie “Carol Davila”, Facultatea de Farmacie, Catedra Matematici Aplicate şi Biostatistică, Bucureşti, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Introducere: Ileusul biliar reprezintă o complicaţie rară a litiazei veziculare (0.3-0.5 %), a cărui incidenţă a rămas practic neschimbată în decursul timpului. Actual diagnosticul şi tratamentul acestei boli au suferit schimbări majore dar , cu toate acestea, mortalitatea a rămas crescută fapt explicabil prin patologia asociată şi prezentarea tardivă la medic.Material şi metodă. Studiul retrospectiv al cazurilor de ileus biliar internate în perioada mai 1991-mai 2011 în SCUB şi Centrul Naţional Stiinţifico-Practic al Medicinei de Urgenţă Chişinău.Au fost înregistrate un număr de 40 de cazuri (34-SCUB, 6 cazuri CNSPMUC). 3 cazuri au reprezentat sindrom Bouveret, 4 cazuri de obstrucţie colonică restul de 33 de cazuri au fost ileusuri biliare clasice. Incidenţa globală a ileusului biliar în studiul nostru a fost 0.15 % (din numărul total de cazuri de litiază biliară internate în perioada menţionată). Vârsta medie a fost 71,62 ani cu predominenţa sexului feminin (37 cazuri, 92,5 %). Diagnosticul preoperator a fost stabilit in 17,5 % din cazuri. Terapeutic, lotul a fost împărţit în 2 grupe de pacienţi : enterolitotomie (grup I, 28 pacienţi) şi enterolitotomie cu desfiinţarea traiectului fistulos (grup II , 12 pacienţi). Nu s-au constatat diferenţe statistice semnificative între cele 2 grupuri referitor la vârsta durata simtomatologiei şi scorul ASA. Timpul operator a fost semnificativ crescut la pacienţii din grupul II . S-a inregistrat un număr total de 14 complicaţii chirurgicale, 9 complicaţii (33,33 %) în grupul I, şi 5 complicaţii ( 41,66 %) în grupul II . Mortalitatea globală a fost de 25 %, 8 cazuri în grupul I (28,57 %) şi 2 cazuri în grupul II (16,66 %). CONCLUZII : Ileusul biliar , ramâne o provocare pentru chirurg. Dificultatea diagnosticului preoperator, starea generală alterată şi vârsta avansată a pacienţilor impun o decizie chirurgicală realistă şi adaptată situaţiei intraoperatorii. În situaţiile dificile enterolitotomia rămâne soluţia terapeutică optimă, în absenţa endoscopiei intervenţionale.Background. Gallstone ileus represents a rare (0.3-0.5%), but serious complication of a common illness – the gallbladder lithiasis and the incidence of this fascinating disease has remained the same over the years. Actually, the diagnosis and management of gallstone ileus had suffered major changes, but despite these diagnostic and therapeutic possibilities, the mortality remains high and the common causes are associated comorbidities and late presentation to the physician.Materials and Methods.A retrospective and descriptive study of patients with diagnosis of gallstone ileus admitted to the Clinical Emergency Hospital Bucharest and National Scientific and Practical Center of Emergency Medicine Chisinau, between May 1991-May 2011. 40 consecutive patients with gallstone ileus (34 cases- ECHB; 6 cases- NSPCEMC) were included. Bouveret’s syndrome was diagnosticated in 3 cases, gallstone colonic obstruction in 4 cases and “classical” gallstone ileus in 33 cases. The overall incidence in our study was 0.15 % (from the total number of gallbladder lithiasis admitted in the mentioned period). Results.The mean age was 71,62 years with the female gender prevalence (92.5 %, 37 cases). In 17.5 % cases the diagnosis was made before the operation. Enterolithotomy was performed in 28 patients (group 1) and cholecystectomy and fistula closure (one-stage procedure) were added in 12 patients (group 2).We found no statistically significant differences between group 1 and group 2 on age, duration of symptoms and ASA score.Operating time was significantly longer for the one-stage procedure. The morbidity and mortality rate still have a high percentage. Complications occurred in 9 of 28 patients (33.33%) from group 1 and in 5 of 12 patients (41.66 %) from group 2. The overall mortality was 25 %, 8 cases in group 1 (28.57 %) and 2 cases (16.66 %) in group 2.ConclusionThe gallstone ileus remains a challenge for the general surgeon. The difficulty of preoperative diagnosis, general malaise and the advanced age of patients require a realistic and appropriate surgical decision adapted to the intraoperative situation. In difficult situations enterolithotomy remains the optimal solution in the absence of interventional endoscopy

Role of sublimation kinetics of ammonia borane in chemical vapor deposition of uniform, large-area hexagonal boron nitride

Hexagonal boron nitride (h-BN) is a critical 2D insulator used as a substrate, gate dielectric, or encapsulation layer for graphene and other 2D materials and their van der Waals heterostructures. It is also promising as an active layer in single-photon emitters and other photonic devices. With the chemical formula H3N-BH3, ammonia borane is the most attractive precursor for up-scalable growth of large-area h-BN, using chemical vapor deposition given its stoichiometric B:N ratio, high stability under ambient conditions, nontoxicity, and high solubility in common solvents. Here, the synthesis of large-area (100 × 150 mm2) crystalline hexagonal boron nitride layers by thermal activation and decomposition of the precursor ammonia borane is presented. We describe two different reaction pathways for h-BN synthesis, providing evidence for dissimilarities in the sublimation kinetics of ammonia borane and how these differences critically influence the growth of h-BN. This understanding helps us accelerate h-BN production, reuse precursors, and reduce machine runtime, paving the way for upscalability. Moreover, our work provides a consistent unified view explaining the diverse deposition conditions reported in the literature for h-BN grown by CVD using ammonia borane as a precursor.This work was supported by National Funds through the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding No. UIDB/04650/2020 and Project Nos. PTDC/FIS-NAN/3668/2014 (LA2D) and PTDC/FIS-MAC/28114/2017 (POCI-01-0145-FEDER-028114) (GRAPHSENS)