Analysis of the crystallization process of a biopharmaceutical compound in the presence of impurities using process analytical technology (PAT) tools

BACKGROUND. The crystallization of biopharmaceuticals can be problematic since, because the biosynthesis of these compounds is very difficult to control, they can contain a significant amount of impurities that have to be eliminated. In fact, impurities can lead to changes in the properties of the drug that can significantly reduce its effectiveness or even put the user in danger. The aim of this work is to exploit process analytical technology (PAT) tools to study the crystallization step of vitamin B12 crude product extracted via fermentation. RESULTS. Linear cooling crystallization experiments were performed using different conditions. The effects of solvent, cooling rate, seeding and purity of the initial material on the final size distribution and purity of the crystals were investigated through the use of UV/Vis spectroscopy, focused beam reflectance measurement (FBRM) and the CryPRINS software (Crystallization Process Informatics System). It was found that impurities strongly inhibit the growth of vitamin B12 crystals, promoting nucleation and leading to poor final crystal size distribution. CONCLUSION. Slow cooling can help to increase the purity of the final product but also generates a broad crystal size distribution because of secondary nucleation. Preparing the solution with material already crystallized once and using purified seeds helped to obtain a narrower crystal size distribution and also to reduce breakage

Improved ENSO forecasting using Bayesian updating and the North American Multi Model Ensemble (NMME)

This study assesses the forecast skill of eight North American Multi Model Ensemble (NMME) models in predicting Niño3/3.4 indices and improves their skill using Bayesian updating (BU). The forecast skill that is obtained using the ensemble mean of NMME (NMME-EM) shows strong dependence on lead (initial) month and target month, and is quite promising in terms of correlation, root mean square error (RMSE), the standard deviation ratio (SDRatio) and probabilistic Brier Skill Score, especially at short lead months. However, the skill decreases in target months from late spring to summer due to the “Spring Predictability Barrier.” When BU is applied to eight NMME models (BU-Model), the forecasts tend to outperform NMME-EM in predicting Niño3/3.4 in terms of correlation, RMSE, and SDRatio. For Niño3.4, the BU-Model outperforms NMME- EM forecasts for almost all leads (1-12; particularly for short leads) and target months (from January to December). However, for Niño3, the BU-Model does not outperform NMME-EM forecasts for leads 7-11 and target months from June to October in terms of correlation and RMSE. Last, we test further potential improvements by preselecting “good” models (BU-Model-0.3) and by using principal components analysis to remove the multicollinearity among models, but these additional methodologies do not outperform the BU-Model, which produces the best forecasts of Niño3/3.4 for the 2015/2016 El Niño event

Geometry of the Wiman Pencil, I: Algebro-Geometric Aspects

In 1981 W.L. Edge discovered and studied a pencil $\mathcal{C}$ of highly symmetric genus $6$ projective curves with remarkable properties. Edge's work was based on an 1895 paper of A. Wiman. Both papers were written in the satisfying style of 19th century algebraic geometry. In this paper and its sequel [FL], we consider $\mathcal{C}$ from a more modern, conceptual perspective, whereby explicit equations are reincarnated as geometric objects.Comment: Minor revisions. Now 49 pages, 4 figures. To appear in European Journal of Mathematics, special issue in memory of W.L. Edg

Machining of Aluminum Alloy

Import 23/07/2015Diplomová práce se zabývá kvalitou opracované hliníkové slitiny EN AW-6082, speciálně drsností povrchu a měřením a vyhodnocením složek řezných sil. Teoretická část objasňuje základní pojmy věnované čelnímu frézování, obrobitelnosti hliníku, obráběným materiálům, řezným podmínkám a geometrii obrábění. V návrhu experimentální části práce je popsáno použití stroje, nástroje a vyměnitelných břitových destiček, přístrojů na měření drsnosti, velikosti řezných sil a navržené řezné podmínky. V experimentální části práce jsou změřeny drsnosti povrchu a presentovány výsledky naměřených hodnot drsnosti Ra a Rz. Řezné síly byly měřeny na piezoelektrickém dynamometru.This master thesis is concerned with the quality of machined aluminium alloy EN AW-6082, especially surface roughness and the measurement and evaluation components of the cutting forces. The theoretical part explains the basic concepts of frontal milling, machinability aluminium, machined material, cutting conditions and geometry processing. In the proposal of the experimental part is described the using of machine, tool and indexable inserts, devices for measuring roughness, cutting forces and proposed cutting conditions. In the experimental part of the work are measured surface roughnesses and presented the results of the measured values of roughness Ra and Rz. Cutting forces were measured on the piezoelectric dynamometer.346 - Katedra obrábění, montáže a strojírenské metrologievelmi dobř

School leadership development in China: a case study of schools in one district education bureau

This paper considers the effectiveness of leadership development (LD) processes in relation to school leaders’ needs within an eastern Chinese District Education Bureau (DEB). The analysis is based on Chinese and English sources relating to LD, documentary analysis of DEB initiatives and interviews with ten school leaders from two schools. The findings reveal that LD within the district stalled at principal level because of the tension between their managerial interpretation of the role and the expectation that they should develop as leaders. Although leaders reported that the emphasis in development activities on classroom teaching and learning, the interpretation of policy initiatives and school visits were helpful, much of what the government is doing is counter-productive. Informants also said that poor outcomes tended to arise from factors beyond the scope of the LD programme itself, for example from the centralised regulatory system, from their own lack of power and influence, from the absence of programme-based or wider in-school support, and from limited evaluative studies. School leaders believed that they needed to be trained to review their own real-world work collaboratively and to devise improvement. They suggested that policy-makers should encourage an inquiry-based approach

DFT study on Fe and N decorated graphene as the drug delivery system for β-lapachone anticancer drug

The β-lapachone anticancer drug performs efficiently in preventing the growth of cancer cells. Transporting the pharmaceutical compound to its target cell is a hot topic in target-direct treatment. Here, we propose a new kind of drug delivery, Fe and N decorated graphene (Fe-N-Graphene), based on density functional theory, showing high performance in the transportation of β-lapachone anticancer drugs. Results indicate Fe-N-Graphene exhibits high adsorption energies of 1.67–1.73 eV for β-lapachone molecules, which guarantees stability during drug transportation. After protonation in an acidic medium, β-lapachone molecules possess much lower binding energies of 0.51–0.88 eV, which benefits a lot in drug release. Our work demonstrates that Fe-N-Graphene is a promising drug delivery for β-lapachone to treat cancer.</p

The Influence of the Environment and Clothing on Human Exposure to Ultraviolet Light

<div><p>Objection</p><p>The aim of this study is to determine the effect of clothing and the environment on human exposure to ultraviolet light.</p><p>Methods</p><p>The ultraviolet (ultraviolet A and ultraviolet B) light intensity was measured, and air quality parameters were recorded in 2014 in Beijing, China. Three types of clothing (white polyester cloth, pure cotton white T-shirt, and pure cotton black T-shirt) were individually placed on a mannequin. The ultraviolet (ultraviolet A and ultraviolet B) light intensities were measured above and beneath each article of clothing, and the percentage of ultraviolet light transmission through the clothing was calculated.</p><p>Results</p><p>(1) The ultraviolet light transmission was significantly higher through white cloth than through black cloth; the transmission was significantly higher through polyester cloth than through cotton. (2) The weather significantly influenced ultraviolet light transmission through white polyester cloth; transmission was highest on clear days and lowest on overcast days (ultraviolet A: <i>P</i>=0.000; ultraviolet B: <i>P</i>=0.008). (3) Air quality parameters (air quality index and particulate matter 2.5 and 10) were inversely related to the ultraviolet light intensity that reached the earth’s surface. Ultraviolet B transmission through white polyester cloth was greater under conditions of low air pollution compared with high air pollution.</p><p>Conclusion</p><p>Clothing color and material and different types of weather affected ultraviolet light transmission; for one particular cloth, the transmission decreased with increasing air pollution.</p></div

An integrated damage modeling and assessment framework for overhead power distribution systems considering tree-failure risks

The overhead power distribution system (OPDS) is vulnerable to strong winds, such as hurricanes. Due to the challenges of including tree damage risks to the OPDS, tree failures are usually ignored in the risk assessment of the OPDS against strong winds. In the present study, an integrated damage modeling and assessment framework for the OPDS is proposed considering tree failure risks. The geographical information of trees surrounding the OPDS is extracted from satellite images using computer vision techniques, including CNN-based (convolutional neural network) image classifier and sliding window approach. The tree failure risk models are developed using tree geographical information in conjunction with tree height data, tree allometry and finite element analysis. With further integration of the conditional probability failure of poles under fallen tree impacts, the pole’s failure probability considering the combined wind and fallen trees is obtained using series system reliability analysis. The failure probability of the pole is obtained using physics-based modeling facilitated by Bayesian regularisation neural network (BRNN) algorithm. The poles and wires are connected for system reliability assessment using connectivity-based theory. When the wind direction is 300° counterclockwise from the east and the wind speed is 57 m/s, tree-failure can introduce 68.6% differences in OPDS’ failure probabilities compared with that without consideration of fallen trees.</p

Integration of Noble Metal Nanocrystals in a Hollow Metal–Organic Framework Shell

Metal–organic frameworks (MOFs) encapsulating noble metal nanocrystals (NCs) have aroused great attention in catalysis, especially for selective catalysis owing to the existence of strong interfacial interactions and synergistic functions. In noble metal NCs@MOF, the crystalline framework shell provides the molecular sieving effect, unsaturated metal sites, and functional channels. However, in many cases, it impedes the mass transfer and diffusion of precursors toward noble metal NCs, thus resulting in suboptimal catalytic performance and inefficient use of the noble metal catalysts. Integration of noble metal NCs in a hollow MOF shell could address this concern. Herein, by using ZIF-67 as a self-sacrificial template, we reported a simple strategy for synthesizing Pd@Hollow ZIF-67. Pre-formed Pd NCs are uniformly confined within a hollow ZIF-67 shell through the dissolution of the interior of a ZIF-67 sacrificial template and re-growth of a new ZIF-67 shell due to the competitive coordination of chloride ligands to cobalt ions in ethanol. This method can be easily extended to fabricate other hollow hybrid materials including Au@Hollow ZIF-67, Pt@Hollow ZIF-67, and sandwich Pd@Hollow ZIF-67. The synthesis of these hollow hybrid nanostructures is expected to provide possibilities for the development of a new category of organic–inorganic hybrid materials for catalytic applications

Establishing World Class Universities in China: Deploying a Quasi-experimental Design to Evaluate the Net Effects of Project 985

The rapid advances of China’s universities in major international league tables are generally believed to be an accomplishment of Project 985. A quasi-experimental study was, therefore, undertaken to test the belief and to evaluate the effectiveness of this policy intervention, using 15-year panel data between 1998 and 2013. Results from a difference-in-differences model showed that Project 985 had a positive effect on publication outputs of ‘985’ universities. Tier 2 ‘985’ universities gained strong momentum in publication growth in international and ISI journals. Additionally, Theil index decomposition was employed to examine the stratification effect of Project 985. Results confirmed the homogenising trend within ‘985’ universities. In contrast, the vertical differentiation between ‘985’ and ‘211’ universities was noticeably enlarged. While sustained public funding is still vital, the study findings inform policy makers and higher education leaders of greater sectorial and institutional reforms to fulfil individual higher education institutions’ needs and remove bottlenecks in publication growth