Mucoadhesive 3D printed vaginal ovules to treat endometriosis and fibrotic uterine diseases.

Gynaecological health is a neglected field of research that includes conditions such as endometriosis, uterine fibroids, infertility, viral and bacterial infections, and cancers. There is a clinical need to develop dosage forms for gynecological diseases that increase efficacy and reduce side effects and explore new materials with properties tailored to the vaginal mucosa and milieu. Here, we developed a 3D printed semisolid vaginal ovule containing pirfenidone, a repurposed drug candidate for endometriosis. Vaginal drug delivery allows direct targeting of the reproductive organs via the first uterine pass effect, but vaginal dosage forms can be challenging to self-administer and retain in situ for periods of more than 1-3 h. Here, we show that a semisoft alginate-based vaginal suppository manufactured using semisolid extrusion additive manufacturing is superior to vaginal ovules made using standard excipients. The 3D-printed ovule showed a controlled release profile of pirfenidone in vitro in standard and biorelevant release tests, as well as better mucoadhesive properties ex vivo. An exposure time of 24 h of pirfenidone to a monolayer culture of an endometriotic epithelial cell line, 12Z, is necessary to reduce the cells' metabolic activity, which demonstrates the need for a sustained release formulation of pirfenidone. 3D printing allowed us to formulate mucoadhesive polymers into a semisolid ovule with controlled release of pirfenidone. This work enables further preclinical and clinical studies into vaginally administered pirfenidone to assess its efficacy as a repurposed endometriosis treatment

Анализ причин отказов установок электроцентробежных насосов при эксплуатации в осложненных условиях на Игольско-Таловом нефтяном месторождении (Томская область)

Объектом исследования являются установки электроцентробежных насосов на Игольско-Таловом нефтяном месторождении. Целью данной работы является анализ существующих на данном месторождении причин отказов установок электроцентробежных насосов, а также изучение и рассмотрение оптимальных методов для устранения преждевременных отказов. В процессе исследования был проведен анализ статистики отказов УЭЦН на Игольско-Таловом месторождении, рассмотрены мероприятия по борьбе и предотвращению осложнений, проведен расчет экономической эффективности внедрения капиллярной системы подачи реагента в скважину Самотлорского месторождения.The object of the study is the installation of electric centrifugal pumps on the needle-Melt oil field. The purpose of this work is to analyze the existing causes of failures of electric centrifugal pumps in this field, as well as to study and consider the best methods to eliminate premature failures. In the course of the study, the statistics of ESP failures at the igol-Talovoye field were analyzed, measures to combat and prevent complications were considered, the economic efficiency of the introduction of a capillary system for supplying reagent to the well of the Samotlor field was calculated

Accurate structure factors from pseudopotential methods

Highly accurate experimental structure factors of silicon are available in the literature, and these provide the ideal test for any \emph{ab initio} method for the construction of the all-electron charge density. In a recent paper [J. R. Trail and D. M. Bird, Phys. Rev. B {\bf 60}, 7863 (1999)] a method has been developed for obtaining an accurate all-electron charge density from a first principles pseudopotential calculation by reconstructing the core region of an atom of choice. Here this method is applied to bulk silicon, and structure factors are derived and compared with experimental and Full-potential Linear Augmented Plane Wave results (FLAPW). We also compare with the result of assuming the core region is spherically symmetric, and with the result of constructing a charge density from the pseudo-valence density + frozen core electrons. Neither of these approximations provide accurate charge densities. The aspherical reconstruction is found to be as accurate as FLAPW results, and reproduces the residual error between the FLAPW and experimental results.Comment: 6 Pages, 3 figure

Polyenylphosphatidylcholines as bioactive excipient in tablets for the treatment of liver fibrosis.

Liver fibrosis is a condition characterized by the accumulation of extracellular matrix (ECM) arising from the myofibroblastic transdifferentiation of hepatic stellate cells (HSCs) occurring as the natural response to liver damage. To date, no pharmacological treatments have been specifically approved for liver fibrosis. We recently reported a beneficial effect of polyenylphosphatidylcholines (PPCs)-rich formulations in reverting fibrogenic features of HSCs. However, unsaturated phospholipids' properties pose a constant challenge to the development of tablets as preferred patient-centric dosage form. Profiting from the advantageous physical properties of the PPCs-rich Soluthin® S 80 M, we developed a tablet formulation incorporating 70% w/w of this bioactive lipid. Tablets were characterized via X-ray powder diffraction, thermogravimetry, and Raman confocal imaging, and passed the major compendial requirements. To mimic physiological absorption after oral intake, phospholipids extracted from tablets were reconstituted as protein-free chylomicron (PFC)-like emulsions and tested on the fibrogenic human HSC line LX-2 and on primary cirrhotic rat hepatic stellate cells (PRHSC). Lipids extracted from tablets and reconstituted in buffer or as PFC-like emulsions exerted the same antifibrotic effect on both activated LX-2 and PRHSCs as observed with plain S 80 M liposomes, showing that the manufacturing process did not interfere with the bioactivity of PPCs

CRYSTAL14: A program for the ab initio investigation of crystalline solids

The capabilities of the CRYSTAL14 program are presented, and the improvements made with respect to the previous CRYSTAL09 version discussed. CRYSTAL14 is an ab initio code that uses a Gaussian-type basis set: both pseudopotential and all-electron strategies are permitted; the latter is not much more expensive than the former up to the first-second transition metal rows of the periodic table. A variety of density functionals is available, including as an extreme case Hartree–Fock; hybrids of various nature (global, range-separated, double) can be used. In particular, a very efficient implementation of global hybrids, such as popular B3LYP and PBE0 prescriptions, allows for such calculations to be performed at relatively low computational cost. The program can treat on the same grounds zero-dimensional (molecules), one-dimensional (polymers), two-dimensional (slabs), as well as three-dimensional (3D; crystals) systems. No spurious 3D periodicity is required for low-dimensional systems as happens when plane-waves are used as a basis set. Symmetry is fully exploited at all steps of the calculation; this permits, for example, to investigate nanotubes of increasing radius at a nearly constant cost (better than linear scaling!) or to perform self-consistent-field (SCF) calculations on fullerenes as large as (10,10), with 6000 atoms, 84,000 atomic orbitals, and 20 SCF cycles, on a single core in one day. Three versions of the code exist, serial, parallel, and massive-parallel. In the second one, the most relevant matrices are duplicated, whereas in the third one the matrices in reciprocal space are distributed for diagonalization. All the relevant vectors are now dynamically allocated and deallocated after use, making CRYSTAL14 much more agile than the previous version, in which they were statically allocated.The program now fits more easily in low-memory machines (as many supercomputers nowadays are). CRYSTAL14 can be used on parallel machines up to a high number of cores (benchmarks up to 10,240 cores are documented) with good scalability, the main limitation remaining the diagonalization step. Many tensorial properties can be evaluated in a fully automated way by using a single input keyword: elastic, piezoelectric, photoelastic, dielectric, as well as first and second hyperpolarizabilies, electric field gradients, Born tensors and so forth. Many tools permit a complete analysis of the vibrational properties of crystalline compounds. The infrared and Raman intensities are now computed analytically and related spectra can be generated. Isotopic shifts are easily evaluated, frequencies of only a fragment of a large system computed and nuclear contribution to the dielectric tensor determined. New algorithms have been devised for the investigation of solid solutions and disordered systems. The topological analysis of the electron charge density, according to the Quantum Theory of Atoms in Molecules, is now incorporated in the code via the integrated merge of the TOPOND package. Electron correlation can be evaluated at the Möller–Plesset second-order level (namely MP2) and a set of double-hybrids are presently available via the integrated merge with the CRYSCOR program

Praezisionsbestimmung von Strukturfaktoren mit einem Doppelkristalldiffraktometer im Laue-Fall

SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Zum Querkrafttragverhalten von Spannbetonträgern unter Ermüdungsbeanspruchung

The demands on the load-carrying capacity of bridges have increased over the last decades due to higher traffic volume. In the future, even a further increase of traffic loads is expected. Many existing bridge structures in Germany built in the 1960s and 1970s were designed for lower traffic loads applying the principal tensile strength criterion for shear. These structures typically feature a high degree of prestressing and low shear reinforcement ratios. In addition to the verification of the shear strength under static loading in the ultimate limit state, the shear fatigue resistance under service loads must be proved to account for the increased fatigue loads. In the past, the load-bearing behaviour of reinforced and prestressed concrete beams without shear reinforcement and with low shear reinforcement ratios under static shear loads has been investigated thoroughly and systematically. In contrast, the knowledge on the load-bearing behaviour under cyclic shear loads is very limited. Furthermore, the investigated parameters and material parameters of the available fatigue tests vary significantly impeding a direct comparison of the test results. Since the deterioration caused by cyclic loading and the resulting redistribution of forces within a member are not yet quantified, the existing approaches for shear fatigue do not yield safe and economic results at the same time. In case of prestressed concrete structures with a low amount of shear reinforcement it is not yet answered, if the provided shear reinforcement ensures a ductile failure behaviour. The aim of the presented work is a thorough analysis of the load-bearing behaviour of prestressed profiled concrete beams without shear reinforcement and with low shear reinforcement ratios under cyclic shear. At first, the state of knowledge on the fatigue behaviour of concrete and reinforcing steel as well as the shear strength of prestressed concrete beams under static and cyclic loading is summarized. Subsequently, own experimental investigations on prestressed beams without shear reinforcement (13 beams) and with low shear reinforcement ratios (14 beams) are presented. Numerical investigations of the tested beams under static and cyclic loading allow for an evaluation of the existing approaches of the static shear strength and a further analysis of the states of stress. Based on the experimental and numerical investigations models to determine the shear strength of prestressed concrete beams without shear reinforcement and with low shear reinforcement ratios under fatigue loading are developed. These models are then implemented in a modular verification procedure for shear fatigue of prestressed concrete bridges. Finally, the application of the developed verification procedure to a typical bridge structure is presented. The proposed procedure allows for a safer and more economical assessment of the shear strength under cyclic loading of existing bridges. It is incorporated in the revised edition of the "German structural assessment provisions for older road bridges" published by the German Ministry of Transport, Building and Urban Development