Simple annealing process for producing unique one-dimensional fullerene crystal named fullerene finned-micropillar.

We propose a process for easily fabricating a unique one-dimensional fullerene crystal, i.e., a fullerene finned-micropillar (FFMP). To fabricate a one-dimensional fullerene crystal more easily than when using current processes, fullerene was first annealed at 1173 K for 1 h with an argon gas flow of 0.5 L/min. We then examined how the FFMP structure changed when the fabrication process conditions, such as temperature, annealing time, and argon gas flow rate, were varied. FFMPs can be prepared within a short time and may have the same electrical characteristics as other one-dimensional crystals, e.g., fullerene nanowhiskers, so they are expected to be very useful for field-effect transistors, organic photovoltaics, and so on in the near future.

Industry Perspective of Pediatric Drug Development in the United States: Involvement of the European Union Countries.

BACKGROUND: Efforts to promote the development of pediatric pharmacotherapy include regulatory frameworks and close collaboration between the US Food and Drug Administration and the European Medicines Agency. We characterized the current status of pediatric clinical trials conducted in the United States by the pharmaceutical industry, focusing on the involvement of the European Union member countries, to clarify the industry perspective. METHODS: Data on US pediatric clinical trials were obtained from ClinicalTrials.gov . Binary regression analysis was performed to identify what factors influence the likelihood of involvement of European Union countries. RESULTS: A total of 633 US pediatric clinical trials that met inclusion criteria were extracted and surveyed. Of these, 206 (32.5%) involved a European Union country site(s). The results of binary regression analysis indicated that attribution of industry, phase, disease area, and age of pediatric participants influenced the likelihood of the involvement of European Union countries in US pediatric clinical trials. Relatively complicated or large pediatric clinical trials, such as phase II and III trials and those that included a broad age range of participants, had a significantly greater likelihood of the involvement of European Union countries ( P < .05). CONCLUSION: Our results suggest that (1) the pharmaceutical industry utilizes regulatory frameworks in making business decisions regarding pediatric clinical trials, (2) disease area affects the involvement of European Union countries, and (3) feasibility of clinical trials is mainly concerned by pharmaceutical industry for pediatric drug development. Additional incentives for high marketability may further motivate pharmaceutical industry to develop pediatric drugs.

Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks.

PURPOSE: A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. METHODS: We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (<18 years old) between 2006 and 2014. Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006-2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. FINDINGS: Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P < 0.001) and 0.066 (P = 0.498), respectively. Those between Japan and the United States were 0.560 (P < 0.001) and 0.281 (P = 0.002), indicating that pediatric drug development in Japan was more active after the introduction of these premiums, even reaching the level of the European Union. The Pediatric Regulation and the Paediatric Committee promoted pediatric drug development in the European Union. The registered number of clinical trials that includes at least 1 participants <18 years old in the European Union Clinical Trials Register increased by 247 trials (from 672) in the 1000 days after regulation. The ratio of pediatric clinical trials with an approved Paediatric Investigation Plan increased to >15% after 2008. IMPLICATIONS: Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and community. Expanding the regulatory steps taken in the European Union, United States, and Japan and using innovative clinical trial tools can move pediatric pharmacotherapy out of its current therapeutic orphan state.

Theoretical calculations of effective exchange integrals by spin projected and unprojected broken-symmetry methods. III. Cluster models of three-dimensional KNiF3 solid.

Previously, we have performed the spin-polarized hybrid-density functional theory (HUDFT) calculations for elucidating magnetic properties of the two-dimensional (2D) K2NiF4 and K2CuF4 solids. In Part I, it has been concluded that the half-and-half-(HH-) type HUDFT method is one of the best calculation methods for these species. On the other hand, in Part II, we have demonstrated that potential curves for cluster models of K2CuF4 and KCuF3 are reasonably calculated by the HH-type HUDFT method under the approximate spin projection, and the lattice distortion resulted by Jahn-Teller effect is expressed as the second-order polynomial. In this study, we pay attention to the three-dimensional (3D) magnetic interactions in KNiF3. Our effective exchange integral Jab schemes for 3D cluster models such as KNi8F12 (4) with and without point charges have provided the reasonable Jab values (-30.24-34.48 cm(-1)), in comparison with the experimental one (-30.58 cm(-1)). The 3D magnetic interactions have been investigated from viewpoints of the Mulliken spin density and charge density populations, the natural orbital analysis, and chemical indices. Point charges located in positions of fluorine anion adjacent to cluster model have reproduced Jab values well. Roles of potassium as counter cation in KNiF3 solid were also investigated. It was concluded that potassium has a role of stabilizing the 3D magnetic structures. Finally, the mutual relationships between broken-symmetry and symmetry-adapted approaches are discussed on the basis of chemical indices.

Theoretical studies of magnetic interactions in Mn(II)(hfac)(2)[di(4-pyridyl)phenylcarbene] and Cu(II)(hfac)(2)[di(4-pyridyl)phenylcarbene].

Bis(hexafluoroacetylacetonato(hfac))manganese(II) coordinated with di(4-pyridyl)phenylcarbene, Mn(II)(hfac)(2)[di(4-pyridyl)phenylcarbene] (1a) and its copper analogue Cu(II)(hfac)(2)[di(4-pyridyl)phenylcarbene] (2a) have attracted great interest from the viewpoint of photoinduced magnetism. The complexes 1a and 2a are regarded as the new d-pi-p conjugated systems containing transition metal ion and carbene as spin sources. The magnetic measurements demonstrated antiferromagnetic and ferromagnetic effective exchange interactions for 1a and 2a, respectively. Here, we have performed UHF and UHF plus DFT hybrid calculations (UB3LYP) to elucidate the nature of the through-bond effective exchange interaction between Mn(II) (or Cu(II)) ion and triplet carbene sites in 1a (or 2a) and their model complexes. The natural orbital analysis of the UHF and UB3LYP solutions and CASCI calculations for the simplest models of 1a and 2a are performed to elucidate relative contributions of spin polarization (SP) and spin delocalization (SD) (or superexchange (SE)) interactions for determination of the sign of J(ab) values. Mn(II) carbene complex 1a shows an antiferromagnetic interaction because of the pi-type antiferromagnetic SE effect and the pi-type SP effect, while the positive J(ab) value for Cu(II) carbene complex 2a can be explained by the fact that ferromagnetic SE and SP interactions due to orbital orthogonality are more effective than the sigma-type antiferromagnetic SE interaction. The ligand coordination effects of both 4-pyridylcarbene and hfac play crucial roles for determination of the J(ab) values, but the ligand coordination effect of hfac is more important for the active control of charge or spin density distributions than that of 4-pyridylcarbene. The spin alignment mechanisms of 1a and 2a are indeed consistent with SE plus SP rule, which is confirmed with the shape and symmetry of natural orbitals, together with charge and spin density distributions.