Development Of A High-Dose Engineered Tcr T Cell Manufacturing Process Using Automated Semi-Continuous Perfusion Bioreactors

Clinical activity with engineered TCR (eTCR) T cell products directed against solid tumor indications may require doses up to two orders of magnitude greater than those investigated during CAR-T studies in hematological malignancies.1 Novel methods for optimizing productivity and production times are required to progress the industrial feasibility of high-dose cell therapies. We developed an automated semi-continuous perfusion culture method suitable for rapidly generating high T cell densities with the aid of risk-based process models. The result is a robust manufacturing process capable of generating a target dose with high certainty, and minimal operational complexity and variability. Please click Additional Files below to see the full abstract

Megelolah Pohon Seho/Aren Dengan Wawasan Lingkungan Hidup: Mempersiapkan Masyarakat Pedesaan Yang Memilki kualitas Khususnya Bagi Petani “Pohon Aren/Seho” di Desa Motoling

This study aims at (1) finding out the general description of the location of the study, as well as the understanding of the farmers of the sugar palm tree in managing seho trees; (2) Studying the right theories about sugar palm trees, and the views of experts on the environment; (3) finding out the forms of sugar palm trees. This study used a qualitative approach using descriptive methods. Data were collected through observation and interviews. The results of the study showed that the farmers of sugar palm tree developed the abilities they had with the learning received. From here they really understand how to process sugar palm trees with an insight into the environment.  &nbsp

Towards Economical Lignin Utilization Through Reductive Catalytic Fractionation

In the last two centuries, humans have relied heavily on the utilization of fossil resources for energy and raw materials, leading to increases in atmospheric CO2 and other greenhouse gases. Analysis has shown that rapid transition away from GHG emitting processes to environmentally benign processes is necessary to avoid climate disaster. Plant biomass is a promising feedstock for difficult to decarbonize industries such as aviation. The goal of this thesis was to improve the economic outlook in the biorefinery by understanding lignin reactivity and molecular structures. First, the dependence of monomer yield and selectivity on catalyst identity is studied during reductive catalytic fractionation (RCF) without the addition of exogenous hydrogen gas (H2-free). Evidence is provided for coniferyl/sinapyl alcohol being the reactive intermediate, and the stabilization pathways to various RCF monomers is investigated through the use of model compounds. Next, a new method for the quantification and classification of phenolic hydroxyl groups in lignin and its derivatives, such as RCF oil, is described. Pentafluoropyridine is shown to react fully with phenols in the presence of base, allowing for cheap, safe, and accurate phenolic measurement. Next, a high throughput method for performing RCF is developed and validated, greatly expanding the capabilities of the RCF practitioner while reducing the time and material footprint. Finally, this methodology is then utilized to study the role of substrate, specifically poplar genotype, during RCF through reactions of approximately 600 genotypes. Variance in the extractability of different poplars was discovered with practical implications for the potential poplar RCF biorefinery.&nbsp;</p

The influence of mothers' and fathers' parenting stress and depressive symptoms on own and partner's parent-child communication

This study examines how parenting stress and depressive symptoms experienced by mothers and fathers influence their own (actor effects) and the partner's (partner effects) parent–child communication. Based on the Actor-Partner Interdependence Model, data from 196 families were analyzed, with both parents rating their parenting stress and depressive feelings, and parents as well as children rating the open parent–child communication. Actor effects were found between parenting stress and open parent–child communication, whereas partner effects were prominent between depressive symptoms and open parent–child communication. The results provide no evidence for gender differences in the strength of the pathways to open parent–child communication. Our findings demonstrate the need to include both parents in studies on parent–child communication to enhance our understanding of the mutual influence among family members

Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts.

BACKGROUND: Osteoporosis is a complex disease with a strong genetic contribution. A recently published genome-wide association study (GWAS) for estimated bone mineral density (eBMD) identified 1103 independent genome-wide significant association signals. Most of these variants are non-coding, suggesting that regulatory effects may drive many of the associations. To identify genes with a role in osteoporosis, we integrate the eBMD GWAS association results with those from our previous osteoclast expression quantitative trait locus (eQTL) dataset. RESULTS: We identify sixty-nine significant cis-eQTL effects for eBMD GWAS variants after correction for multiple testing. We detect co-localisation of eBMD GWAS and osteoclast eQTL association signals for 21 of the 69 loci, implicating a number of genes including CCR5, ZBTB38, CPE, GNA12, RIPK3, IQGAP1 and FLCN. Summary-data-based Mendelian Randomisation analysis of the eBMD GWAS and osteoclast eQTL datasets identifies significant associations for 53 genes, with TULP4 presenting as a strong candidate for pleiotropic effects on eBMD and gene expression in osteoclasts. By performing analysis using the GARFIELD software, we demonstrate significant enrichment of osteoporosis risk variants among high-confidence osteoclast eQTL across multiple GWAS P value thresholds. Mice lacking one of the genes of interest, the apoptosis/necroptosis gene RIPK3, show disturbed bone micro-architecture and increased osteoclast number, highlighting a new biological pathway relevant to osteoporosis. CONCLUSION: We utilise a unique osteoclast eQTL dataset to identify a number of potential effector genes for osteoporosis risk variants, which will help focus functional studies in this area

Perceptions of Problem Behavior in Adolescents’ Families: Perceiver, Target, and Family Effects

Considerable research has focused on the reliability and validity of informant reports of family behavior, especially maternal reports of adolescent problem behavior. None of these studies, however, has based their orientation on a theoretical model of interpersonal perception. In this study we used the social relations model (SRM) to examine family members’ reports of each others’ externalizing and internalizing problem behavior. Two parents and two adolescents in 69 families rated each others’ behavior within a round-robin design. SRM analysis showed that within-family perceptions of externalizing and internalizing behaviors are consistently due to three sources of variance; perceiver, target, and family effects. A family/contextual effect on informant reports of problem behavior has not been previously reported

Quantum physics in inertial and gravitational fields

Covariant generalizations of well-known wave equations predict the existence of inertial-gravitational effects for a variety of quantum systems that range from Bose-Einstein condensates to particles in accelerators. Additional effects arise in models that incorporate Born reciprocity principle and the notion of a maximal acceleration. Some specific examples are discussed in detail.Comment: 25 pages,1 figure,to appear in "Relativity in Rotating Frame

Healthcare professionals' perspectives on enrolled nurses, practical nurses and other second-level nursing roles: A systematic review and thematic synthesis.

BACKGROUND: Significant workforce shortages and economic pressures have led to the expanded scope and reintroduction of new roles for second-level nurses in many Organization for Economic Co-operation and Development countries. Given this, there is a need to understand the emic and etic perspectives of second-level nurses, to ensure collaborative teamwork and safe patient care. OBJECTIVE: This review aimed to systematically identify, appraise, and synthesize qualitative research evidence on healthcare professionals' perspectives on second-level nursing roles in the healthcare workforce. These findings inform recommendations that would influence the development and implementation of these roles in healthcare organisations. DESIGN: A systematic review and thematic synthesis of qualitative research was conducted. Six databases were systematically searched and forward and backwards searching completed. Included studies focused on healthcare professionals' perspectives (including views of second-level nurses themselves) on second-level nursing roles. All included articles were from Organization for Economic Co-operation and Development countries. The Critical Appraisal Skills Programme checklist for qualitative research was used to assess the evidence quality. The results section of each included article was coded and descriptive themes were developed. An interpretative and iterative process led to the final analytic themes. FINDINGS: Twenty-six qualitative studies were identified from five countries over 26 years. Four analytic themes were identified: undifferentiated role; efficient but limited; subordinated task-doers; and broadening scope and strengthened identity. The synthesis demonstrated dichotomies wherein some second-level nursing roles were devalued, and others had increasing scope and responsibility. Role and boundary confusion was evident and had not decreased over time. Hierarchies in nursing practice underlined the split between critical thinking and hands-on approaches to care which, in some cases, debased the second-level nursing role because of its association with practical hands-on care. CONCLUSIONS: The analytic themes in this synthesis suggest that second-level nurses have faced the same issues over decades with little change. Perceptions of second-level nursing roles are primarily influenced by meso (organisational level) factors and micro (individual, behavioural) factors. The synthesis concludes that a cultural shift in valuing the hands-on care provided by second-level nursing is necessary, along with systems-level shift that clarifies the role of second-level nursing within healthcare teams to enhance collaborative practice. Further research should attend to macro-level influences on perceptions of second-level nurses, the work they do, and how this is valued or institutionally embedded. Tweetable abstract: Healthcare professionals' perspectives on second-level nursing roles: a systematic review and thematic synthesis

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest