Book Reviews

Reviews of the following books: Hardliners: A History of the Emery-Waterhouse Company by Edgar Allen Beem and Charles L. Hildreth, Jr.; L.L. Bean: The Making of an American Icon by Leon Gorman; Eminent Mainers: Succinct Biographies of Thousands of Amazing Mainers, Mostly Dead and a Few People from Away Who Have Done Something Useful Within the State Maine; Compiled by Arthur Douglas Stover and Maine: Downeast and Different: An Illustrated History by Neil Rolde; ; The Rangeley and Its Region: The Famous Boat and Lakes of Western Maine by Stephen A. Cole; Voyages: A Maine Franco-American Reader, edited by Nelson Madore and Barry Rodrigu

Exome resequencing and GWAS for growth, ecophysiology, and chemical and metabolomic composition of wood of Populus trichocarpa.

BackgroundPopulus trichocarpa is an important forest tree species for the generation of lignocellulosic ethanol. Understanding the genomic basis of biomass production and chemical composition of wood is fundamental in supporting genetic improvement programs. Considerable variation has been observed in this species for complex traits related to growth, phenology, ecophysiology and wood chemistry. Those traits are influenced by both polygenic control and environmental effects, and their genome architecture and regulation are only partially understood. Genome wide association studies (GWAS) represent an approach to advance that aim using thousands of single nucleotide polymorphisms (SNPs). Genotyping using exome capture methodologies represent an efficient approach to identify specific functional regions of genomes underlying phenotypic variation.ResultsWe identified 813 K SNPs, which were utilized for genotyping 461 P. trichocarpa clones, representing 101 provenances collected from Oregon and Washington, and established in California. A GWAS performed on 20 traits, considering single SNP-marker tests identified a variable number of significant SNPs (p-value < 6.1479E-8) in association with diameter, height, leaf carbon and nitrogen contents, and δ15N. The number of significant SNPs ranged from 2 to 220 per trait. Additionally, multiple-marker analyses by sliding-windows tests detected between 6 and 192 significant windows for the analyzed traits. The significant SNPs resided within genes that encode proteins belonging to different functional classes as such protein synthesis, energy/metabolism and DNA/RNA metabolism, among others.ConclusionsSNP-markers within genes associated with traits of importance for biomass production were detected. They contribute to characterize the genomic architecture of P. trichocarpa biomass required to support the development and application of marker breeding technologies

High Linearity Millimeter Wave Power Amplifiers with Novel Linearizer Techniques

Millimeter-wave communications have experienced phenomenal growth in recent years when limited frequency spectrum is occupied by the ever-developing communication services. The power amplifier, as the key component in the transmitter/receiver module of communication systems, affects performance of the whole system directly and receives much attention. For minimized distortion and optimum system performance, the non-constant en- velope modulation schemes used in communication systems have challenging requirements on linearity. As linearity is related to communication quality directly, several linearization techniques, such as predistortion and feedforward, are applied to power amplifier design. Predistortion method has the advantages over other techniques in relatively simple struc- ture and reasonable linearity improvement. But current predistortion circuits have quite limited performance improvement and relatively large insertion loss, which indicate the need for further research. In most of millimeter-wave amplifier design, great effort has been spent on output power or gain, while linearity is often ignored. As almost all the predistortion circuits operate at the RF frequencies, the linearized millimeter-wave com- munication circuit is still relatively immature and very challenging. This project is dedicated to solve the linearity problem faced by millimeter-wave power amplifier in communication systems, which lacks of e®ective techniques in this field. Linearity improvement with the predistortion method will be the key issue in this project and some original ideas for predistortion circuit design will be applied to millimeter-wave amplifiers. In this thesis, several predistortion circuits with novel structure were proposed, which provide a new approach for linearity improvement for millimeter-wave power am- plifier. A millimeter-wave power ampli¯er for LMDS applications built on GaAs pHEMT technology was developed to a high engineering standard, which works as the test bench for linearization. Actual operation and parasitic elements at tens of gigahertz have been taken into consideration during the design. Firstly, two novel predistorter structures based on the amplifier were proposed, one is based on an amplifier with a fixed bias circuit and the other is based on an amplifier with a nonlinear signal dependant bias circuit. These novel structures can improve the linearity while improving other metrics simultaneously, which can effectively solve the problem of insertion loss faced by the conventional structures. Besides this, an original predistortion circuit design methodology derived from frequency to signal amplitude transformation was proposed. Based on this methodology, several transfer functions were proposed and related predistortion circuits were built to linearize the power amplifier. As this methodology is quite different from the traditional approach, it can improve the linearity signifficantly while other metrics are affected slightly and has a broad prospect for application

Automated Analysis of Flow Cytometry Data to Reduce Inter-Lab Variation in the Detection of Major Histocompatibility Complex Multimer-Binding T Cells

Manual analysis of flow cytometry data and subjective gate-border decisions taken by individuals continue to be a source of variation in the assessment of antigen-specific T cells when comparing data across laboratories, and also over time in individual labs. Therefore, strategies to provide automated analysis of major histocompatibility complex (MHC) multimer-binding T cells represent an attractive solution to decrease subjectivity and technical variation. The challenge of using an automated analysis approach is that MHC multimer-binding T cell populations are often rare and therefore difficult to detect. We used a highly heterogeneous dataset from a recent MHC multimer proficiency panel to assess if MHC multimer-binding CD8+ T cells could be analyzed with computational solutions currently available, and if such analyses would reduce the technical variation across different laboratories. We used three different methods, FLOw Clustering without K (FLOCK), Scalable Weighted Iterative Flow-clustering Technique (SWIFT), and ReFlow to analyze flow cytometry data files from 28 laboratories. Each laboratory screened for antigen-responsive T cell populations with frequency ranging from 0.01 to 1.5% of lymphocytes within samples from two donors. Experience from this analysis shows that all three programs can be used for the identification of high to intermediate frequency of MHC multimer-binding T cell populations, with results very similar to that of manual gating. For the less frequent populations (<0.1% of live, single lymphocytes), SWIFT outperformed the other tools. As used in this study, none of the algorithms offered a completely automated pipeline for identification of MHC multimer populations, as varying degrees of human interventions were needed to complete the analysis. In this study, we demonstrate the feasibility of using automated analysis pipelines for assessing and identifying even rare populations of antigen-responsive T cells and discuss the main properties, differences, and advantages of the different methods tested

Adaptation of the methotrexate in rheumatoid arthritis knowledge questionnaire (MiRAK) for use with parents of children with juvenile idiopathic arthritis: a qualitative study

BACKGROUND: Although Methotrexate (MTX) is one of the most commonly prescribed disease-modifying drugs in JIA no questionnaire exists that assesses the knowledge of parents about this drug. A 60-item questionnaire was recently developed to measure rheumatoid arthritis (RA) patients\u27 knowledge about MTX; the Methotrexate in Rheumatoid Arthritis Knowledge Test (MiRAK; Ciciriello et al. (Arthritis Rheum 62:10-1009, 2010)). This study aimed to adapt the MiRAK for parents of children with JIA. METHODS: Adaption of the MiRAK involved: 1) email consultations with clinicians working in the field of paediatric rheumatology (Panel 1) to ascertain the potential adaptations of the MiRAK from a clinical perspective, 2) synthesis of clinicians\u27 suggestions by a panel of experts, researchers and MiRAK developers (Panel 2) to reach consensus on which items needed to be modified and create a draft Methotrexate in Juvenile Idiopathic Arthritis Knowledge Test (MiJIAK), 3) a review of the draft by 5 parents of children with JIA (Panel 3) using the cognitive \u27think-aloud\u27 method, 4) a second consultation with Panel 2 to review parents\u27 suggestions and determine the final items. RESULTS: A total of 9 items remained unchanged, e.g. "Methotrexate is effective at relieving joint stiffness", 19 were deemed inappropriate in the paediatric setting and deleted, e.g. "It is safe to become pregnant 3 weeks after methotrexate has been stopped", 32 underwent editorial changes largely to indicate that the questionnaire was about the children with JIA, e.g. "If you forget to give a dose of Methotrexate, you can still take it the next day" became "If your child misses a dose of Methotrexate, they can still take it the next day", and 1 new item was added. A new 42-item questionnaire was produced and was found to be well understood by parents of children with JIA. CONCLUSIONS: The systematic modification of the MiRAK, a patient-centred MTX knowledge questionnaire, has generated a comprehensive new questionnaire for use in the JIA setting. The wide consultation process, including cognitive testing, has ensured the tool is both relevant and acceptable to clinicians and will therefore be a valuable addition in understanding the parents\u27 perspective of this treatment in JIA

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development