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.     

Physicochemical characteristics and bronchial epithelial cell cytotoxicity of Folpan 80 WG® and Myco 500®, two commercial forms of folpet

Background

Pesticides, in particular folpet, have been found in rural and urban air in France in the past few years. Folpet is a contact fungicide and has been widely used for the past 50 years in vineyards in France. Slightly water-soluble and mostly present as particles in the environment, it has been measured at average concentration of 40.1 μg/m³ during its spraying, 0.16–1.2 μg/m³ in rural air and around 0.01 μg/m³ in urban air, potentially exposing both the workers and the general population. However, no study on its penetration by inhalation and on its respiratory toxicity has been published. The objective of this study was to determine the physicochemical characteristics of folpet particles (morphology, granulometry, stability) in its commercial forms under their typical application conditions. Moreover, the cytotoxic effect of these particles and the generation of reactive oxygen species were assessed in vitro on respiratory cells.

Results

Granulometry of two commercial forms of folpet (Folpan 80WG^® and Myco 500^®) under their typical application conditions showed that the majority of the particles (>75%) had a size under 5 μm, and therefore could be inhaled by humans. These particles were relatively stable over time: more than 75% of folpet remained in the particle suspension after 30 days under the typical application conditions. The inhibitory concentration (IC₅₀) on human bronchial epithelial cells (16HBE14o-) was found to be between 2.89 and 5.11 μg/cm² for folpet commercial products after 24 h of exposure. Folpet degradation products and vehicles of Folpan 80 WG^® did not show any cytotoxicity at tested concentrations. At non-cytotoxic and subtoxic concentrations, Folpan 80 WG^® was found to increase DCFH-DA fluorescence.

Conclusion

These results show that the particles of commercial forms of folpet are relatively stable over time. Particles could be easily inhaled by humans, could reach the conducting airways and are cytotoxic to respiratory cells in vitro. Folpet particles may mediate its toxicity directly or indirectly through ROS-mediated alterations. These data constitute the first step towards the risk assessment of folpet particles by inhalation for human health. This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.     

Rheology of fiber filled polymer melts: Role of fiber‐fiber interactions and polymer‐fiber coupling

An experimental study and a numerical modeling analysis are carried out to examine the effects of fiber‐fiber interactions and coupling between fiber orientation and polymer chains conformation on the rheological properties of fiber suspensions. The experimental study allowed examination of large fiber volume fractions up to 35% over a range of shear rates that spans eight decades. This study confirmed already known results and led to new ones. In particular, a peak in the steady shear viscosity at the low shear rate region is observed at large volume fractions. Furthermore, new results regarding the applicability of the Cox‐Merz rule, the behavior of the damping factor, and the end pressure drops are reported, and physical interpretations are proposed. The results of the numerical modeling showed that it is necessary to account for the polymer‐fiber coupling factor to obtain a good fit between the model predictions and the experimental measurements. Comparisons between the model predictions and the experimental measurements allowed study of the variation of the parameters that govern the fiber‐fiber interactions and the polymer‐fiber coupling with the properties of the suspension and the flow. POLYM. ENG. SCI., 45:385–399, 2005. © 2005 Society of Plastics Engineers     

Transition to adulthood as a parent-youth project: Governance transfer, career promotion, and relational processes.

This study determined how youth (ages 17-21) and their parents jointly constructed and acted on goals and strategies pertinent to the transition to adulthood. Twenty parent-youth dyads were followed over an 8-month period using the qualitative action-project method. Data included their joint conversations, video recall of internal processes, self-monitoring logs, and researcher telephone monitoring. Detailed and repeated analysis of elements, functional steps, and goals resulted in the identification of an explicit joint project for each dyad that the participants saw as pertinent to the transition to adulthood. These projects referred broadly to the youth development of identity and social inclusion in the adult world and included the specific projects of career promotion, governance transfer, and parent-youth relational processes. The findings illustrate the complexity of the transition-to-adulthood process as well as its joint construction by parent and youth. Implications for practice include identifying and following the joint parent-youth transition project. (PsycINFO Database Record (c) 2010 APA, all rights reserved)