Equilibria,kinetics and mechanism for the degradation of the cytotoxic compound L-NG-nitroarginine

L-N^G-nitroarginine (LNNA), an analog of L-arginine, is a competitive inhibitor of nitric oxide synthase which causes the selective reduction of blood flow to tumor cells. Despite the potential of LNNA to function as an adjuvant in cancer therapies, its poor solubility and stability have hindered the development of an injectable formulation of LNNA that is suitable for human administration. This work, for the first time, details a systematic study on the determination of equilibrium K_a constants and the rate law of LNNA degradation. The four K_a values of LNNA were determined to be 1.03, 1.10?×?10^?2, 2.51?×?10^?10, and 1.33?×?10^?13 M. From the kinetic and equilibrium studies, we have shown that the deprotonated form of LNNA is the main form of LNNA that undergoes degradation in aqueous media at room temperature. The rate law of LNNA degradation was found to be first order with respect to OH^? concentration and first order with respect to LNNA^? concentration. The rate constant at 25?°C and 1?atm was determined to be 0.04453 M^?1min^?1. A base catalyzed mechanism of LNNA degradation was proposed based on the kinetic study. The mechanism was found to be very useful in explaining the discrepancies and changes of the rate law at different pH values. It is thus recommended that LNNA should be formulated as a concentrated solution in acidic conditions for maximum chemical stability during storage and be diluted with a basic solution to near physiological pH just before administration.     

Predicting Survival Outcomes in the Presence of Unlabeled Data

Many clinical studies require the follow-up of patients over time. This is challenging: apart from frequently observed drop-out, there are often also organizational and financial challenges, which can lead to reduced data collection and, in turn, can complicate subsequent analyses. In contrast, there is often plenty of baseline data available of patients with similar characteristics and background information, e.g., from patients that fall outside the study time window. In this article, we investigate whether we can benefit from the inclusion of such unlabeled data instances to predict accurate survival times. In other words, we introduce a third level of supervision in the context of survival analysis, apart from fully observed and censored instances, we also include unlabeled instances. We propose three approaches to deal with this novel setting and provide an empirical comparison over fifteen real-life clinical and gene expression survival datasets. Our results demonstrate that all approaches are able to increase the predictive performance over independent test data. We also show that integrating the partial supervision provided by censored data in a semi-supervised wrapper approach generally provides the best results, often achieving high improvements, compared to not using unlabeled data.

     

High‐Pressure Thermal Sterilization: Food Safety and Food Quality of Baby Food Puree

The benefits that high‐pressure thermal sterilization offers as an emerging technology could be used to produce a better overall food quality. Due to shorter dwell times and lower thermal load applied to the product in comparison to the thermal retorting, lower numbers and quantities of unwanted food processing contaminants (FPCs), for example, furan, acrylamide, HMF, and MCPD‐esters could be formed. Two spore strains were used to test the technique; Geobacillus stearothermophilus and Bacillus amyloliquefaciens, over the temperature range 90 to 121 °C at 600 MPa. The treatments were carried out in baby food puree and ACES‐buffer. The treatments at 90 and 105 °C showed that G. stearothermophilus is more pressure‐sensitive than B. amyloliquefaciens. The formation of FPCs was monitored during the sterilization process and compared to the amounts found in retorted samples of the same food. The amounts of furan could be reduced between 81% to 96% in comparison to retorting for the tested temperature pressure combination even at sterilization conditions of F₀‐value in 7 min.     

Air-dictated bottom spray process: impact of fluid dynamics on granule growth and morphology

Background: Growing interest in the use of the less-explored bottom spray technique for fluidized bed granulation provided impetus for this study. Aim: The impact of fluid dynamics (air accelerator insert diameter; partition gap) and wetting (binder spray rate) on granule properties were investigated. Method: In this 3³ full factorial study, the results were fitted to a quadratic model using response surface methodology. The air velocity at the spray granulation zone for the investigated conditions was measured using a pitot tube. Results: Air accelerator insert diameter correlated to measured air velocity at the spray granulation zone and was found to not only dictate growth but also influence granule morphology. The partition gap was found to play important roles in regulating particle movement into the spray granulation zone and optimizing process yields, whereas binder spray rate significantly affected granule morphology but not granule size. Conclusions: Unlike conventional fluidized bed granulation, ease of modulation of fluid dynamics and insensitivity of the bottom spray process to wetting allow flexible control of granule size, shape, and flow. Its good drying ability also indicated potential use in granulating moisture-sensitive materials.     

Carbon nanotubes for interconnects in future integrated circuits: The challenge of the density

A CVD process with a high density of CNTs has been developed on doped silicon material thanks to plasma pre-treatment of the catalyst. With this process small diameter double and triple wall CNTs with an average diameter of 3.8 nm have been grown. The density of the best materials on blanket substrate is larger than 10¹² cm^? 2. These materials have been successfully integrated in via holes with a diameter ranging between 1 µm and 0.3 µm with an equivalent density. In 140 nm hole diameter large 70 nm bundle formations have been observed. In these bundles a density of CNT walls close to 10¹³ cm^? 2 has been estimated.     

Greywater recycling in Vietnam — Application of the HUBER MBR process

Greywater is the part of domestic wastewater that is free of faeces. The volume and concentration of this separately collected wastewater flow depend on the consumer behaviour and vary according to its source. The average amount of greywater produced per day in a German household is 70 l per person, which is more than 50% of the total wastewater production [5]. This figure corresponds with the average figures provided for Chinese households (80 l per person/day, GB/T 50331-2002), but significantly exceeds the South African average of 20 l per person and day [1].Compared to domestic wastewater, greywater generally contains less organic pollutants, less nutrients but a high amount of tensides. The effluent from bath tubs, showers or wash hand basins contains for example a by approx. two decimal orders lower number of total and faecal coliform bacteria (Escherichiacoli) [2] and [6].Due to its relatively low content of pollutants, greywater is easy to treat with MBRs. The pollutants contained are decomposed by the bacteria of the activated sludge tank. The following membrane filtration unit separates the treated greywater from the activated sludge. The treated greywater is of high quality and hygienically safe so that it can be reused, alone or combined with rain water, for toilet flushing water, laundry washing or for irrigation purposes.Within the scope of the SANSED II research project HUBER has been successful in adapting the MBR system for greywater treatment to the specific conditions in Vietnam and testing the system in operation in a small city in the Mekong delta, South Vietnam. The wastewater from kitchen sinks and the bathrooms of a dormitory on the campus of Can Tho University was clarified in the HUBER GreyUse^® plant over a period of three months. The project aim was the production of high quality service water from greywater for safe reuse as toilet flush water.     

Recycled paperboard with a barrier layer for food contact: set-off during stacking or reeling. Analytical method and preliminary results

The use of recycled paperboard for packaging dry foods is in the interest of sustainability of resources, but in most applications, the food must be protected against contamination, such as by a functional barrier on the internal surface of the paperboard box. After application, the paperboard is usually stacked or reeled before making boxes. During this period, the food-contact surface of the barrier layer is in contact with the outer side of the paperboard, which may result in set-off and subsequent contamination of food. A method is described for the determination of this path of migration, based on the taped format also used for the measurement of the barrier efficiency. Recycled paperboard containing the three surrogate substances n-heptadecane, 4-methyl benzophenone and dipropyl phthalate was taped to the food-contact side of the barrier layer. Pressure onto the test packs did not seem to be a relevant parameter. After periods of interest, a piece of the paperboard with the barrier layer was extracted and analysed for the surrogate substances. Another piece may be brought into contact with silicone paper to simulate the transfer to food. After 2 weeks at 60°C (simulating about 1 year at 25°C), set-off and the transfer to the silicone paper exceeded 1% for all barrier materials tested, but after 6 weeks at 40°C (around half a year at 25°C), set-off remained below 1% for all barrier layers except a multilayer with polyethylene on the food-contact surface. The preliminary conclusion is that set-off should be taken seriously, but may be kept low enough to provide sufficient protection of the packed food.