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Tigers & tea with Toppy : a true adventure in New York City with wildlife artist Charles R. Knight, who loved saber-toothed cats, parties at the Plaza, and people and animals of all stripes
Young Rhoda enjoys visiting the American Museum of Natural History, Central Park Zoo, and other places with her beloved grandfather, the famous wildlife artist Charles R. Knight.
Book
Recent advances and future directions in downstream processing of therapeutic antibodies
Despite the advent of many new therapies, therapeutic monoclonal antibodies remain a prominent biologics product, with a market value of billions of dollars annually. A variety of downstream processing technological advances have led to a paradigm shift in how therapeutic antibodies are developed and manufactured. A key driver of change has been the increased adoption of single-use technologies for process development and manufacturing. An early-stage developability assessment of potential lead antibodies, using both in silico and high-throughput experimental approaches, is critical to de-risk development and identify molecules amenable to manufacturing. Both statistical and mechanistic modelling approaches are being increasingly applied to downstream process development, allowing for deeper process understanding of chromatographic unit operations. Given the greater adoption of perfusion processes for antibody production, continuous and semi-continuous downstream processes are being increasingly explored as alternatives to batch processes. As part of the Quality by Design (QbD) paradigm, ever more sophisticated process analytical technologies play a key role in understanding antibody product quality in real-time. We should expect that computational prediction and modelling approaches will continue to be advanced and exploited, given the increasing sophistication and robustness of predictive methods compared to the costs, time, and resources required for experimental studies.
Journal Article
NEHA MEMBER SPOTLIGHT
An interview with Jared Matte, a risk control and loss prevention specialist at Maricopa County in Arizona, is presented. Among other things, he talks about being a member of NEHA, why he chooses the environmental health field, and his accomplishment that he is most proud of.
Journal Article
Groups of piecewise linear homeomorphisms of flows
To every dynamical system $(X,\\varphi )$ over a totally disconnected compact space, we associate a left-orderable group $T(\\varphi )$. It is defined as a group of homeomorphisms of the suspension of $(X,\\varphi )$ which preserve every orbit of the suspension flow and act by dyadic piecewise linear homeomorphisms in the flow direction. We show that if the system is minimal, the group is simple and, if it is a subshift, then the group is finitely generated. The proofs of these two statements are short and elementary, providing straightforward examples of finitely generated simple left-orderable groups. We show that if the system is minimal, every action of the corresponding group on the circle has a fixed point. These constitute the first examples of finitely generated left-orderable groups with this fixed point property. We show that for every system $(X,\\varphi )$, the group $T(\\varphi )$ does not have infinite subgroups with Kazhdan's property $(T)$. In addition, we show that for every minimal subshift, the corresponding group is never finitely presentable. Finally, if $(X,\\varphi )$ has a dense orbit, then the isomorphism type of the group $T(\\varphi )$ is a complete invariant of flow equivalence of the pair $\\{\\varphi , \\varphi ^{-1}\\}$.
Journal Article
Pyridoxine (Vitamin B6) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation
Vitamin B6 (B6) has a central role in the metabolism of amino acids, which includes important interactions with endogenous redox reactions through its effects on the glutathione peroxidase (GPX) system. In fact, B6-dependent enzymes catalyse most reactions of the transsulfuration pathway, driving homocysteine to cysteine and further into GPX proteins. Considering that mammals metabolize sulfur- and seleno-amino acids similarly, B6 plays an important role in the fate of sulfur-homocysteine and its seleno counterpart between transsulfuration and one-carbon metabolism, especially under oxidative stress conditions. This is particularly important in reproduction because ovarian metabolism may generate an excess of reactive oxygen species (ROS) during the peri-estrus period, which may impair ovulatory functions and early embryo development. Later in gestation, placentation raises embryo oxygen tension and may induce a higher expression of ROS markers and eventually embryo losses. Interestingly, the metabolic accumulation of ROS up-regulates the flow of one-carbon units to transsulfuration and down-regulates remethylation. However, in embryos, the transsulfuration pathway is not functional, making the understanding of the interplay between these two pathways particularly crucial. In this review, the importance of the maternal metabolic status of B6 for the flow of one-carbon units towards both maternal and embryonic GPX systems is discussed. Additionally, B6 effects on GPX activity and gene expression in dams, as well as embryo development, are presented in a pig model under different oxidative stress conditions.
Journal Article
Taking Stock of Two Decades of Attachment Transmission Gap: Broadening the Assessment of Maternal Behavior
This report aimed to investigate the capacity of maternal behaviors tailored to children's attachment and exploration systems to jointly explain the well-known mother–child transmission of attachment. Four home visits were conducted between ages 7 months and 2 years with 130 mother–child dyads to assess maternal attachment state of mind, sensitivity, autonomy support, and mother–child attachment security. Results showed that together, maternal sensitivity and autonomy support fully accounted for the relation between maternal and child attachment, that they each accounted for a unique portion of this relation, and that the magnitude of these mediated pathways was equivalent. These results suggest that the attachment transmission gap can be narrowed by the use of a theory-driven multidimensional approach to maternal behavior.
Journal Article
Dynamically stiffened matrix promotes malignant transformation of mammary epithelial cells via collective mechanical signaling
Breast cancer development is associated with increasing tissue stiffness over years. To more accurately mimic the onset of gradual matrix stiffening, which is not feasible with conventional static hydrogels, mammary epithelial cells (MECs) were cultured on methacrylated hyaluronic acid hydrogels whose stiffness can be dynamically modulated from “normal” (<150 Pascals) to “malignant” (>3,000 Pascals) via two-stage polymerization. MECs form and remain as spheroids, but begin to lose epithelial characteristics and gain mesenchymal morphology upon matrix stiffening. However, both the degree of matrix stiffening and culture time before stiffening play important roles in regulating this conversion as, in both cases, a subset of mammary spheroids remained insensitive to local matrix stiffness. This conversion depended neither on colony size nor cell density, and MECs did not exhibit “memory” of prior niche when serially cultured through cycles of compliant and stiff matrices. Instead, the transcription factor Twist1, transforming growth factor β (TGFβ), and YAP activation appeared to modulate stiffness-mediated signaling; when stiffness-mediated signals were blocked, collective MEC phenotypes were reduced in favor of single MECs migrating away from spheroids. These data indicate a more complex interplay of time-dependent stiffness signaling, spheroid structure, and soluble cues that regulates MEC plasticity than suggested by previous models.
Journal Article
Maternal perinatal transfer of vitamins and trace elements to piglets
Nursing piglets are entirely dependent, for their micronutrient provisions, upon in utero, colostrum and milk transfers from the dam. An adequate maternal transfer of micronutrients is all the more important during these periods which, in fact, lasts for approximately half the life cycle (conception to slaughter) of modern pigs. The present study aimed to set up a simple approach to assess the maternal perinatal transfer of vitamins and trace elements in sows. Prenatal transfer (R-u) was estimated as limited, passive or active using the ratio between pre-colostral serum concentrations of a given micronutrient in newborn piglets and corresponding pre-farrowing values in sows. Efficiency of the postnatal transfer (R-c) was estimated from the ratio between serum concentrations of post- and pre-colostral micronutrients in piglets. Data from literature (12 studies) were used for vitamins A, D, E, C, folic acid and B12, whereas vitamins B2, B3, B6 and B8 as well as Zn, Fe, Cu and Se were generated from a trial where blood sera from 20 sows, and their litter were collected during the perinatal period. In sow trial, statistical t tests were used to determine if ratios differed from 1. Prenatal transfer was active and in favour of piglets (R-u > 1, P < 0.03) for Zn and vitamins B6 and B8 (sow trial) as well as for vitamins C and B12 (literature data). This transfer was limited (R-u < 1, P < 0.01) for vitamin B2, Fe, Cu and Se (sow trial) and for vitamins A, E, D and folic acid (literature data) whereas it was passive for vitamin B3 (R-u = 1, P > 0.37). After birth, the early postnatal transfer through colostrum was active towards piglets for most micronutrients but vitamins B6 and B8 (R-c < 1, P < 0.01). Globally, the perinatal transfer (combination of R-u and R-c) was favourable to the neonatal piglets for most micronutrients except for vitamins A and D as well as Fe, Cu and Se whereas there is apparently a barrier for prenatal transfer which is not compensated by the colostrum provision to neonatal piglets. Then, post-colostral concentrations of these micronutrients in piglets remain below prenatal levels of their dam. Neonatal strategies of micronutrient provision are known for Fe (intramuscular injection) and Se (sow milk enrichment). Further studies are needed to assess the importance of the unfavourable perinatal transfer for Cu and vitamins A and D for piglet robustness later in life.
Journal Article
Weaning differentially affects mitochondrial function, oxidative stress, inflammation and apoptosis in normal and low birth weight piglets
Weaning is associated with increased occurrence of infections and diseases in piglets. Recent findings indicate that weaning induces mitochondrial dysfunction and oxidative stress conditions that more severely impact smaller piglets. The objective of this study was to characterize the molecular mechanisms underlying these physiological consequences and the relation with systemic inflammatory status in both normal and low birth weight (NBW and LBW) piglets throughout the peri-weaning period. To conduct the study, 30 sows were inseminated, and specific piglets from their litters were assigned to one of two experimental groups: NBW (n = 60, 1.73 ± 0.01 kg,) and LBW piglets weighing less than 1.2 kg (n = 60, 1.01 ± 0.01 kg). Then, 10 piglets from each group were selected at 14, 21 (weaning), 23, 25, 29 and 35 days of age to collect organ and plasma samples. Specific porcine RT 2 Profiler™ PCR Arrays related to mitochondrial function, oxidative stress, inflammation and apoptosis processes were first used to target genes that are modulated after weaning in NBW piglets (d 23 and d 35 vs. d 14). Expression of selected genes was evaluated by quantitative PCR. These analyses revealed that expression of inflammatory genes CXCL10 and CCL19 increased after weaning in intestinal mucosa, while expression of genes encoding subunits of the mitochondrial respiratory chain was downregulated in liver and kidney of both groups. Interestingly, major modulators of mitophagy ( BNIP3 ), cell survival ( BCL2A1 ) and antioxidant defense system ( TXNRD2 , GPx3 , HMOX1 ) were found to be highly expressed in NBW piglets. The systemic levels of TNF-α and IL1-β significantly increased following weaning and were higher in NBW piglets. These results provide novel information about the molecular origin of mitochondrial dysfunction and oxidative stress observed in weaned piglets and suggest that clearance of dysfunctional mitochondria, antioxidant defenses and inflammatory response are compromised in LBW piglets.
Journal Article
Perfusion for congenital heart surgery
A complete guide to the tools and techniques for modeling, simulating, and optimizing SSFE processes and phenomena
In Modeling, Simulation, and Optimization of Supercritical and Subcritical Fluid Extraction Processes, a team of expert chemical engineers delivers a comprehensive guide to the tools and techniques used to model supercritical and subcritical fluid extraction (SSFE) processes and phenomena. The book offers details on SSFE experiment management, as well as modeling and optimization of SSFE.
The authors begin with a discussion of the fundamentals of SSFE and the necessary experimental techniques to validate the models. They also discuss process simulators, conventional optimization techniques, and state-of-the-art genetic algorithm methods.
Several practical examples and case studies on SSFE modeling and optimization techniques are provided. Additionally, detailed thermodynamic modeling with and without co-solvent and non-equilibrium system modeling are covered.
Readers will also find:
* A detailed overview of the field of supercritical and subcritical fluid extraction and their importance to the food, cosmetics, and pharmaceutical industries
* Explorations of the concepts and methodologies for modeling, simulation, and optimization of SSFE, including conservation laws related to SSFE traditional first principle modeling
* Practical discussions of the characteristics and physical properties of palm oil as a solute and descriptions of some existing palm oil industrial processes
* An examination of first principle methodology as applied to the modeling of the properties of palm oil components and mixtures
Perfect for researchers, scientists, technologists, and engineers working in food science and the pharmaceutical, cosmetic, and agricultural industries, Modeling, Simulation, and Optimization of Supercritical and Subcritical Fluid Extraction Processes is also a must-read for those working with process design, development, quality control, and improvement in the chemical industries.
eBook