Managing active pharmaceutical ingredient raw material variability during twin-screw blend feeding

Continuous powder feeding is a critical step in continuous manufacturing of solid dosage forms, as this unit operation should ensure the mass flow consistency at the desired powder feed rate to guarantee the process throughput and final product consistency. In this study, twin-screw feeding of a pharmaceutical formulation (i.e., blend) existing of a highly dosed very poorly flowing active pharmaceutical ingredient (API) leading to insufficient feeding capacity was investigated. Furthermore, the API showed very high batch-to-batch variability in raw material properties dominating the formulation blend properties. Formulation changes were evaluated to improve the flowability of the blends and to mitigate the impact of API batch-to-batch variability on the twin-screw feeding. Herewith, feeding evaluation tests and an extensive material characterization of the reformulated blends were performed to assess the impact of the formulation changes upon continuous twin-screw feeding. The transfer of the glidant from extra-granular to intra-granular phase allowed to improve the flowability of the blends. A sufficient feeding capacity for the downstream process and a mitigation of the impact of batch-to-batch variability of the API upon twin-screw feeding of the blends could be achieved. No effect of the formulation or of the API properties on the feeding stability was observed. The material characterization of the blends allowed identifying the material attributes which were critical for continuous twin-screw feeding (i.e., bulk density, mass charge and powder cohesiveness)

A comparison between the anthropological and modern day uses of this indigenous herb

Sceletium tortuosum (Fig. 1) is a scrambling succulent ground cover indigenous to the Western and Eastern Cape. It has probably been used for centuries as a mood-altering drug, especially by the Khoisan hunters and Nama shepherds, where it was often smoked or used as snuff. It also has hallucinogenic properties and high dosages were often used during trance dances. These properties have been associated with alkaloids such as mesembrine. The San people used it prior to hunting to sharpen their senses, and to diminish hunger and thirst. Even in excessive dosages its initial euphoric effect seems to be replaced with feelings of serene sedation. It was more often used for enjoyment and not primarily for medicine. Modern day medical and commercial use of Sceletium spp is primary as a mood enhancer, to decrease anxiety, stress, and in addiction therapy. The objectives of this study was to investigate and compare the historical and anthropological se of Sceletium with the modern day and current uses there of

Cumulative Component Damages on Collapse Capacity of Ductile Steel and CFT Moment Resisting Frames under Over-design Ground Motions

Great earthquakes are likely to generate ground motions larger than those considered in design codes (over-design ground motions) and hence leading to a seismic demand that causes severe damages of structural components in general high-rise steel moment-resisting frames (SMRFs). Overall seismic behavior of high-rise SMRFs may be significantly affected by the local failure of members. This paper focuses on the margins of deterioration and collapse of 40-story SMRFs and the equivalent MRFs with concrete-filled tubular (CFT) columns considering the strength deterioration effect in constitutive models designed by current building standards. The input long-period ground motions are synthetic earthquake waves with flat velocity spectral shape. Deterioration and collapse criteria of models based on the peak ground motion velocity are estimated by performing the incremental dynamic analysis (IDA). The results indicate that the collapse mechanism was formed in the lower stories of high-rise SMRFs under the very rare earthquake. The strength and stiffness deterioration significantly amplified the damage extent and the influence degree depends on the sectional compactness of components. And the MRF with concrete-filled tubular (CFT) columns has a higher collapse margin against overall collapse compared with SMRFs

Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors

Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs

Rapid Mass Movement of Chloroplasts during Segment Formation of the Calcifying Siphonalean Green Alga, Halimeda macroloba

is abundant on coral reefs and is important in the production of calcium carbonate sediments. The process by which new green segments are formed over-night is revealed here for the first time. indicated that the movement process is dependent on both microtubules and microfilaments.This unusual process involves the mass movement of chloroplasts at a high rate into new segments during the night and rapid calcification on the following day and may be an adaptation to minimise the impact of herbivorous activity

Validating module network learning algorithms using simulated data

In recent years, several authors have used probabilistic graphical models to learn expression modules and their regulatory programs from gene expression data. Here, we demonstrate the use of the synthetic data generator SynTReN for the purpose of testing and comparing module network learning algorithms. We introduce a software package for learning module networks, called LeMoNe, which incorporates a novel strategy for learning regulatory programs. Novelties include the use of a bottom-up Bayesian hierarchical clustering to construct the regulatory programs, and the use of a conditional entropy measure to assign regulators to the regulation program nodes. Using SynTReN data, we test the performance of LeMoNe in a completely controlled situation and assess the effect of the methodological changes we made with respect to an existing software package, namely Genomica. Additionally, we assess the effect of various parameters, such as the size of the data set and the amount of noise, on the inference performance. Overall, application of Genomica and LeMoNe to simulated data sets gave comparable results. However, LeMoNe offers some advantages, one of them being that the learning process is considerably faster for larger data sets. Additionally, we show that the location of the regulators in the LeMoNe regulation programs and their conditional entropy may be used to prioritize regulators for functional validation, and that the combination of the bottom-up clustering strategy with the conditional entropy-based assignment of regulators improves the handling of missing or hidden regulators.Comment: 13 pages, 6 figures + 2 pages, 2 figures supplementary informatio

Seagrass can mitigate negative ocean acidification effects on calcifying algae

The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm structure and experimental assistance.info:eu-repo/semantics/publishedVersio

Structural and functional protein network analyses predict novel signaling functions for rhodopsin

Proteomic analyses, literature mining, and structural data were combined to generate an extensive signaling network linked to the visual G protein-coupled receptor rhodopsin. Network analysis suggests novel signaling routes to cytoskeleton dynamics and vesicular trafficking