Properties of nanostructured diamond-silicon carbide composites sintered by high pressure infiltration technique

A high-pressure silicon infiltration technique was applied to sinter diamond–SiC composites with different diamond crystal sizes. Composite samples were sintered at pressure 8 GPa and temperature 2170 K. The structure of composites was studied by evaluating x-ray diffraction peak profiles using Fourier coefficients of ab initio theoretical size and strain profiles. The composite samples have pronounced nanocrystalline structure: the volume-weighted mean crystallite size is 41–106 nm for the diamond phase and 17–37 nm for the SiC phase. The decrease of diamond crystal size leads to increased dislocation density in the diamond phase, lowers average crystallite sizes in both phases, decreases composite hardness, and improves fracture toughness

Distinct dynamics of social motivation drive differential social behavior in laboratory rat and mouse strains

Mice and rats are widely used to explore mechanisms of mammalian social behavior in health and disease, raising the question whether they actually differ in their social behavior. Here we address this question by directly comparing social investigation behavior between two mouse and rat strains used most frequently for behavioral studies and as models of neuropathological conditions: C57BL/6 J mice and Sprague Dawley (SD) rats. Employing novel experimental systems for behavioral analysis of both subjects and stimuli during the social preference test, we reveal marked differences in behavioral dynamics between the strains, suggesting stronger and faster induction of social motivation in SD rats. These different behavioral patterns, which correlate with distinctive c-Fos expression in social motivation-related brain areas, are modified by competition with non-social rewarding stimuli, in a strain-specific manner. Thus, these two strains differ in their social behavior, which should be taken into consideration when selecting an appropriate model organism

Dislocation density and graphitization of diamond crystals

Two sets of diamond specimens compressed at 2 GPa at temperatures varying between 1060 K and 1760 K were prepared; one in which graphitization was promoted by the presence of water and another in which graphitization of diamond was practically absent. X-ray diffraction peak profiles of both sets were analyzed for the microstructure by using the modified Williamson-Hall method and by fitting the Fourier coefficients of the measured profiles by theoretical functions for crystallite size and lattice strain. The procedures determined mean size and size distribution of crystallites as well as the density and the character of the dislocations. The same experimental conditions resulted in different microstructures for the two sets of samples. They were explained in terms of hydrostatic conditions present in the graphitized samples

Liberación y seguimiento de dos grupos de tití gris (saguinus leucopus) en el departamento de tolima

Este estudio fue realizado con dos grupos de tití gris (Saguinus leucopus), procedentes de decomisos y entregas voluntarias. Los animales fueron rehabilitados durante aproximadamente un año en la ciudad de Bogotá, con el fin de estimular el desarrollo y recuperación de las habilidades necesarias para su sobrevivencia al ser devueltos al medio ambiente natural. Se construyeron dos jaulas como plataformas de liberación en un bosque en el departamento del Tolima, y los animales fueron alojados en ellas para iniciar su proceso de acostumbramiento al medio. Durante este tiempo se realizó un estudio etológico, con el propósito de determinar las posibles variaciones comportamentales derivadas del cambio en el entorno. Los animales fueron liberados y se llevó a cabo el seguimiento visual para evaluar el proceso de rehabilitación y la adaptación de los individuos al nuevo hábitat. Se observó una variación en la presentación de comportamientos relacionados con actividades de desplazamiento, descanso e interacciones sociales en comparación con estudios realizados en cautiverio. Después de la liberación, los animales fueron vistos en sitios próximos a las jaulas de acostumbramiento, lo cual podría indicar que establecieron sus territorios en estas áreas; no se registraron variaciones significativas en la conformación de los grupos ni enfrentamientos entre las dos tropas. Estas observaciones indicarían que el proceso de liberación cumplió con su objetivo, y puede considerarse exitoso

Manifestaciones de la crisis de la rentabilidad en la industria farmacéutica colombiana 1970-1986

La década de los setentas y la primera mitad de los ochentas presenciaron marcados altibajos en la actividad económica. Después de un período de relativo auge, a partir de 1978 la economía colombiana evidenció la caída vertiginosa del crecimiento de su Producto Interno Bruto: la tasa anual superior al 8% registrada en 1978, descendió aI2.3% en 1981, y en 1982 alcazó su nivel más bajo, 1%. Los agregados económicos reflejaban la aguda recesión del país. El valor de las exportaciones de café apenas alcanzaba el 40% del observado en 1980; los ingresos externos en la cuenta de servicios y trasferencias se redujeron en 54.3%, generando efectos adversos en el mercado interno, a la vez que conducía a una política de austeridad en materia de importaciones. Las reservas internacionales se reducían en 13.1%. A partir de 1983 y hasta 1985 el PIB colombiano reflejaría una recuperación bastante inestable de la actividad económica: un leve crecimiento en 1983(1.9%), recuperación en 1984 (3.6%), y recaída en 1985(2.6%). Solo hasta 1986y 1987 la economía colombiana entra en una senda firme de recuperación (5.0%)

A Dynamic Programming Approach to Adaptive Fractionation

We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a "favorable" anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5 - 85%) depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting), and (iii) we allow large daily fraction size deviations.Comment: 17 pages, 4 figures, 1 tabl

Colony-forming cells in the adult mouse pancreas are expandable in Matrigel and form endocrine/acinar colonies in laminin hydrogel

The study of hematopoietic colony-forming units using semisolid culture media has greatly advanced the knowledge of hematopoiesis. Here we report that similar methods can be used to study pancreatic colony-forming units. We have developed two pancreatic colony assays that enable quantitative and functional analyses of progenitor-like cells isolated from dissociated adult (2–4 mo old) murine pancreas. We find that a methylcellulose-based semisolid medium containing Matrigel allows growth of duct-like “Ring/Dense” colonies from a rare (∼1%) population of total pancreatic single cells. With the addition of roof plate-specific spondin 1, a wingless-int agonist, Ring/Dense colony-forming cells can be expanded more than 100,000-fold when serially dissociated and replated in the presence of Matrigel. When cells grown in Matrigel are then transferred to a Matrigel-free semisolid medium with a unique laminin-based hydrogel, some cells grow and differentiate into another type of colony, which we name “Endocrine/Acinar.” These Endocrine/Acinar colonies are comprised mostly of endocrine- and acinar-like cells, as ascertained by RNA expression analysis, immunohistochemistry, and electron microscopy. Most Endocrine/Acinar colonies contain beta-like cells that secrete insulin/C-peptide in response to D-glucose and theophylline. These results demonstrate robust self-renewal and differentiation of adult Ring/Dense colony-forming units in vitro and suggest an approach to producing beta-like cells for cell replacement of type 1 diabetes. The methods described, which include microfluidic expression analysis of single cells and colonies, should also advance study of pancreas development and pancreatic progenitor cells

Colony-Forming Progenitor Cells in the Postnatal Mouse Liver and Pancreas Give Rise to Morphologically Distinct Insulin-Expressing Colonies in 3D Cultures

In our previous studies, colony-forming progenitor cells isolated from murine embryonic stem cell-derived cultures were differentiated into morphologically distinct insulin-expressing colonies. These colonies were small and not light-reflective when observed by phase-contrast microscopy (therefore termed “Dark” colonies). A single progenitor cell capable of giving rise to a Dark colony was termed a Dark colony-forming unit (CFU-Dark). The goal of the current study was to test whether endogenous pancreas, and its developmentally related liver, harbored CFU-Dark. Here we show that dissociated single cells from liver and pancreas of one-week-old mice give rise to Dark colonies in methylcellulose-based semisolid culture media containing either Matrigel or laminin hydrogel (an artificial extracellular matrix protein). CFU-Dark comprise approximately 0.1% and 0.03% of the postnatal hepatic and pancreatic cells, respectively. Adult liver also contains CFU-Dark, but at a much lower frequency (~0.003%). Microfluidic qRT-PCR, immunostaining, and electron microscopy analyses of individually handpicked colonies reveal the expression of insulin in many, but not all, Dark colonies. Most pancreatic insulin-positive Dark colonies also express glucagon, whereas liver colonies do not. Liver CFU-Dark require Matrigel, but not laminin hydrogel, to become insulin-positive. In contrast, laminin hydrogel is sufficient to support the development of pancreatic Dark colonies that express insulin. Postnatal liver CFU-Dark display a cell surface marker CD133^(+)CD49f^(low)CD107b^(low) phenotype, while pancreatic CFU-Dark are CD133^-. Together, these results demonstrate that specific progenitor cells in the postnatal liver and pancreas are capable of developing into insulin-expressing colonies, but they differ in frequency, marker expression, and matrix protein requirements for growth

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

BACKGROUND Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizu- mab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. METHODS In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approxi- mately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. RESULTS Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, −1.0; 95% CI, −2.5 to 0; P=0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, –7.6 to 8.2; nominal P=0.94). CONCLUSIONS In this randomized trial involving hospitalized patients with severe Covid-19 pneu- monia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann–La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov num- ber, NCT04320615.

Fast Multispectral Optoacoustic Tomography (MSOT) for Dynamic Imaging of Pharmacokinetics and Biodistribution in Multiple Organs

The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 µm through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research