bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and performance tests of a modular 166.6-MHz 50-kW compact solid-state power amplifier for the HEPS-TF project
Authors: Luo Y. , Zhang P. , Lin H. , Wang Q. , Ma Q. , Pan W. 
Published: April 2021

Abstract
A 166.6-MHz 50-kW power transmitter is required to drive the
dressed superconducting radio-frequency (RF) cavity during
horizontal tests and to condition the fundamental power couplers as
well as higher-order-mode ferrite absorbers. A highly modular yet
compact amplifier adopting solid-state technologies was therefore
developed in the framework of High Energy Photon Source - Test
Facility. All power amplifier and power supply modules are pluggable
from the front panel of the amplifier system. A 3-stage power
combining topology was realized by using 32 power amplifier modules,
4 eight-way stripline power combiners, 2 two-way 35-kW coaxial power
combiners, and 1 two-way 65-kW coaxial power combiner. Each power
amplifier module is equipped with individual circulator and load
utilizing an optimized cooling circuit design to ensure the entire
amplifier system to be operational in both full-transmission and
full-reflection scenarios. No final-stage high-power circulator or
load is needed. The amplifier system is tunable in pulsed mode for
any duty factors and fully functional in the continuous-wave mode as
required. Excellent noise suppression and high wall-plug-to-RF
efficiency were achieved at nominal power. Comfortable redundancies
for both power amplifier and power supply modules were reserved to
compensate for any hardware degradations during
operations. Temperature, current, voltage, and RF signal of each
module as well as cooling were monitored and managed by using EPICS
in the control system of the amplifier. An interlock system was also
integrated as well as an event logging system for post-mortem
analysis. The system has accumulated over 2000 hours of
operation. The design and performance tests of the first 166.6-MHz
50-kW modular solid-state power amplifier are presented.
Measurement of neutrino source activity in the experiment BEST by calorimetric method
Authors: Gavrin V.N. , Ibragimova T.V. , Kozlova J.P. , Tarasov V.A. , Veretenkin E.P. , Zvir A.I. 
Published: April 2021

Abstract
Experiments to study non-standard properties of neutrinos using high-intensity artificial neutrino sources require high accuracy in determining their activity. A calorimetric system to determine the activity of a ^51Cr neutrino source in the experiment BEST with an accuracy better than 1% was created. The design of the calorimetric system and the main factors affecting the accuracy of measurements are considered. The results of measurements of the activity of the source made for the BEST experiment are presented. The value of the source activity from calorimetric measurements was 3.41 MCi at the beginning of the experiment.
A perfusable vascularized full-thickness skin model for potential topical and systemic applications
Authors: Salameh Sacha , Tissot Nicolas , Cache Kevin , Lima Joaquim , Suzuki Itaru , Marinho Paulo André , Rielland Maité , Soeur Jérémie , Takeuchi Shoji , Germain Stéphane , Breton Lionel 
Published: April 2021

Abstract
Vascularization of reconstructed tissues is one of the remaining hurdles to be considered to improve both the functionality and viability of skin grafts and the relevance of in vitro applications. Our study, therefore, sought to develop a perfusable vascularized full-thickness skin equivalent that comprises a more complex blood vasculature compared to existing models. We combined molding, auto-assembly and microfluidics techniques in order to create a vascularized skin equivalent representing (a) a differentiated epidermis with a physiological organization and correctly expressing K14, K10, Involucrin, TGM1 and Filaggrin, (b) three perfusable vascular channels with angiogenic sprouts stained with VE-Caderin and Collagen IV, (c) an adjacent microvascular network created via vasculogenesis and connected to the sprouting macrovessels. Histological analysis and immunostaining of CD31, Collagen IV, Perlecan and Laminin proved the integrity of vascular constructs. In order to validate the vascularized skin potential of topical and systemic applications, caffeine and minoxidil, two compounds with different chemical properties, were topically applied to measure skin permeability and benzo[a]pyrene pollutant was systemically applied to evaluate systemic delivery. Our results demonstrated that perfusion of skin reconstructs and the presence of a complex vascular plexus resulted in a more predictive and reliable model to assess respectively topical and systemic applications. This model is therefore aimed at furthering drug discovery and improving clinical translation in dermatology.
Fast approximate inference for multivariate longitudinal data
Authors: Hughes David M , García-Fiñana Marta , Wand Matt P 
Published: April 2021

SummaryCollecting information on multiple longitudinal outcomes is increasingly common in many clinical settings. In many cases, it is desirable to model these outcomes jointly. However, in large data sets, with many outcomes, computational burden often prevents the simultaneous modeling of multiple outcomes within a single model. We develop a mean field variational Bayes algorithm, to jointly model multiple Gaussian, Poisson, or binary longitudinal markers within a multivariate generalized linear mixed model. Through simulation studies and clinical applications (in the fields of sight threatening diabetic retinopathy and primary biliary cirrhosis), we demonstrate substantial computational savings of our approximate approach when compared to a standard Markov Chain Monte Carlo, while maintaining good levels of accuracy of model parameters.
O2: TOWARDS A LIVING BIOBANK OF SURGICALLY-RELEVANT 3-DIMENSIONAL GLIOBLASTOMA STEM CELL MODELS TO EVALUATE NOVEL THERAPEUTICS AND INTERROGATE INTRATUMOURAL HETEROGENEITY
Authors: Rominiyi O , Vanderlinden A , Myers K , Gomez-Roman N , Dar D , Bagga V , Jellinek DA , Chalmers AJ , Carroll TA , Al-Tamimi Y , Collis SJ 
Published: April 2021

Abstract

Introduction
Glioblastoma is the most common cancer arising within the brain. Despite surgery, followed by DNA-damaging chemoradiotherapy, average survival remains between 12-15 months. Unacceptable survival rates underline the need to develop preclinical research models which recapitulate features underpinning therapeutic resistance in patients, such as intratumoural heterogeneity and treatment resistant glioblastoma stem cell (GSC) subpopulations which demonstrate elevated DNA damage response (DDR) activity.

Method
Tumour specimens from patients were used to generate 2D and 3D scaffold-based GSC models, with a range of preclinical survival and molecular assays used to interrogate cancer biology and assess therapeutic responses.

Result
We have developed a ‘living biobank’ of 20+ ex-vivo GSC models which reflect key clinicopathological diversity. These models include residual disease models based on careful macrodissection of rare en-blocpartial lobectomy specimens to liberate parallel GSC lines from the tumour core and adjacent infiltrated brain, to represent cells typically left behind after surgery. Therapeutic strategies targeting fundamental DDR processes demonstrate preclinical efficacy, for example dual inhibition of ATR and the FA DNA damage repair pathways elicits profound radiosensitisation (sensitiser enhancement ratio of 3.23 (3.03-3.49, 95%-CI)) with evidence of delayed DNA damage repair on single-cell gel electrophoresis. Finally, characterisation of our surgically-relevant resected and residual models reveals numerous divergent properties including elevated stem cell marker expression in residual models (p=0.0021), which may partially explain treatment resistance in disease left behind after surgery.

Conclusion
Our living biobank represents a useful resource for preclinical glioblastoma research and demonstrates the value of partnership between surgeons and laboratory-based scientists.

Take-home message
Our living biobank represents a useful resource for preclinical glioblastoma research and demonstrates the value of partnership between surgeons and laboratory-based scientists.
O5: THE CLIFF AND CONOR STUDIES NOVEL ASSESSMENT TOOLS IN COLORECTAL LIVER METASTASES (CLIFF STUDY - CHANGE IN LIVER FUNCTION AND FAT IN PRE-OPERATIVE CHEMOTHERAPY FOR COLORECTAL LIVER METASTASES, CONOR STUDY
Authors: Parmar KL , Slawinski C , Malcomson L , OReilly D , Valle JW , Braun M , Naish JH , Williams SR , Renehan AG 
Published: April 2021

Abstract

Introduction
Hepatic resection is the only potentially curative treatment for patients with colorectal liver metastases (CLM). Patient selection is key, but there is wide variation in practice. Pre-operative chemotherapy can improve oncological outcomes, however chemotherapy-associated liver injury (CALI) may hinder liver regenerative capacity. Standard pre-operative assessments fail to accurately capture factors such as CALI and future liver remnant (FLR) function. The CLiFF and CoNoR studies utilise two novel assessment techniques, aiming to improve patient outcomes.

Method
The CLiFF study prospectively assesses two primary outcomes in 35 patients undergoing pre-operative chemotherapy for CLM: 1) change in liver function (via LiMAx test: direct assessment of hepatic functional capacity), and 2) change in liver fat (via advanced MR imaging (in-house spectroscopy and modified Dixon technique, scaled up via Perspectum LiverMultiScan)). The CoNoR study assesses potential added benefit of these novel tools in CLM resectability decision-making via sequential workstreams: a systematic review and international hepatobiliary expert interviews inform the online survey, assessing added benefit via online MDT scenarios.

Result
Preliminary CLiFF analysis suggests that CALI changes in liver fat and function are unrelated. Liver fat analysis techniques are compared and correlated with digital histological analysis. The CoNoR systematic review identifies key factors influencing CLM resectability decision-making and informs the international expert interviews, scheduled to occur during a February 2020 international hepatobiliary conference.

Conclusion
These studies are the first to assess where these novel tools might be utilised to maximal patient benefit within the Hepatobiliary MDT, and the first systematic review in CLM resectability decision-making.

Take-home message
These two linked studies evaluate the use of two novel assessment tools in the treatment of colorectal liver metastases, with the potential to improve patient selection for curative resection and patient outcomes.
PATEY PRIZE SESSION
O45: DEFINING CELL-ENRICHED MICRORNAS TO SUPPORT RATIONAL BIOMARKER SELECTION IN HUMAN RENAL TRANSPLANTATION
Authors: Connor K , Teenan O , Thomas R , Banwell V , Finnie S , Monaghan ML , Cairns C , Tannahill G , Harrison E , Conway B , Marson L , Denby L , Wigmore S 
Published: April 2021

Abstract

Introduction
MicroRNAs are promising biomarkers of renal disease, however the cellular origin of their expression is usually unclear limiting their interpretation when measured in renal biopsies and urine. We hypothesised that by first defining renal cell-enriched microRNAs, we could select biomarkers based on the expected histopathological profile.

Method
Small RNA-sequencing of cortical, proximal tubular (LTL), macrophage (F480), endothelial (CD31) and fibroblast (PDGFRb) populations from the reversible unilateral ureteric obstruction (rUUO) murine model was performed. Hierarchical clustering was used to identify clusters. Findings were translated into an ischaemia reperfusion injury (IRI) model and then into urine samples from renal transplant recipients (n=16) with delayed graft function (DGF) vs. those with primary function.

Result
Kidney injury resulted in significant macrophage infiltration and tubular injury which improved upon reversal. We characterised novel microRNA clusters enriched for each cell type. With injury there was a significant increase in macrophage (p&lt;0.0001), fibroblast (p&lt;0.01) and decrease in proximal tubule (p&lt;0.0001) enriched microRNAs vs. non-enriched microRNAs. We validated macrophage enriched miR-18a, miR-16 and tubular enriched miR-194 in the IRI model, demonstrating that microRNA expression reflected the histological profile. In humans, urinary miR-16 (FC 16.9; p&lt;0.05) and miR-18a (FC 10: p=0.06) were upregulated at day 2 in patients with DGF; outperforming the traditional injury marker KIM1.

Conclusion
This is the first study to characterise cell-enriched microRNAs during renal injury and repair. By defining the source of microRNA expression we were able to rationally select miR-16 and miR-18a as promising urinary biomarkers of renal injury.

Take-home message
We have found that microRNAs have differences in expression between cell types and renal injury states which is important when considering microRNA expression in samples composed of varying cellular composition. By defining the cellular origins of microRNA expression we were able to rationally select microRNA biomarkers of human renal injury.
Sleep Leads to Brain-Wide Neural Changes Independent of Allocentric and Egocentric Spatial Training in Humans and Rats
Authors: Samanta Anumita , van Rongen Laurens S , Rossato Janine I , Jacobse Justin , Schoenfeld Robby , Genzel Lisa 
Published: April 2021

AbstractSleep is important for memory consolidation and systems consolidation in particular, which is thought to occur during sleep. While there has been a significant amount of research regarding the effect of sleep on behavior and certain mechanisms during sleep, evidence that sleep leads to consolidation across the system has been lacking until now. We investigated the role of sleep in the consolidation of spatial memory in both rats and humans using a watermaze task involving allocentric- and egocentric-based training. Analysis of immediate early gene expression in rodents, combined with functional magnetic resonance imaging in humans, elucidated similar behavioral and neural effects in both species. Sleep had a beneficial effect on behavior in rats and a marginally significant effect in humans. Interestingly, sleep led to changes across multiple brain regions at the time of retrieval in both species and in both training conditions. In rats, sleep led to increased gene expression in the hippocampus, striatum, and prefrontal cortex. In the humans, sleep led to an activity increase in brain regions belonging to the executive control network and a decrease in activity in regions belonging to the default mode network. Thus, we provide cross-species evidence for system-level memory consolidation occurring during sleep.
The Recovery of the Anglo-Saxon Past, c.1770–1850
Authors: Sweet Rosemary 
Published: April 2021

Abstract
Between the eighteenth and the nineteenth centuries, a remarkable shift took place in the reception of England’s Anglo-Saxon past. During the eighteenth century the contributions of the Anglo-Saxons to English traditions of political liberty and the common law were acknowledged—and highly prized—but as a people, they were also indelibly associated with the barbarism of the Dark Ages. By the mid-nineteenth century, however, attitudes had shifted substantively. While the debt to Anglo-Saxon legal and political institutions was still acknowledged, it was, relatively speaking, diminished and the focus was rather upon their role in the development of the nation and the shaping of English national character. They were rendered more conformable forebears for the increasingly urban, domestic and commercial society of nineteenth-century England. This article analyses how such a reconceptualisation came about. Rather than concentrating on the emergence of a discourse of race or national character or tracing the emergence of rigorous philological inquiry into Old English, it focuses upon the production of historical knowledge that permitted the development of a more varied, nuanced and fuller history of the Anglo-Saxon period. In doing so, the article illuminates the porosity of the boundaries between antiquarian and historical activity, and argues that the recovery of the Anglo-Saxon past in this period was shaped by a complex set of influences, which an emphasis upon the emergence of a discourse of race alone obscures.
A Performance Analysis of Sawmills in Oregon from 2003 to 2017
Authors: Sun Changyou , Marcille Kate C , Daniels Jean M 
Published: April 2021

Abstract
The number of mills and employees in Oregon’s sawmill sector has continuously declined from 2003 to 2017, but the amount of lumber produced has stabilized in recent years. In this study, the performance of individual sawmills is evaluated by applying data envelopment analysis on a unique dataset for 146 mills over four survey years of 2003, 2008, 2013, and 2017. The scale efficiency of these mills is generally high, but their overall technical efficiency is only 85%. In 2017, the most efficient mills as a group used 14% fewer employees, processed 18% more sawlogs, and produced 32% more lumber than an average mill in Oregon. Across the four survey years, productivity growth over time is small at only 0.14% per year, and most of the growth can be attributed to changes in technology. The catch-up effect by individual mills is actually negative at −0.07% per year. These findings reveal that the growth of production efficiency in Oregon’s sawmill sector has been slow, and the direction for future improvement relies on better management of operations and resources by individual mills.
Gene Silencing by DNA Methylation and Dual Inheritance in Chinese Hamster Ovary Cells
Authors: Paulin R P , Ho T , Balzer H J , Holliday R 
Published: April 2021

Abstract
Chinese hamster ovary (CHO) cells strain D422, which has one copy of the adenine phosphoribosyl transferase (APRT) gene, were permeabilized by electroporation and treated with 5-methyl deoxycytidine triphosphate. Cells with a silenced APRT gene were selected on 2, 6-diaminopurine. Colonies were isolated and shown to be reactivated to APRT+ by 5-aza-cytidine and by selection in medium containing adenine, aminopterin and thymidine. Genomic DNA was prepared from eight isolates of independent origin and subjected to bisulphite treatment. This deaminates cytosine to uracil in single-stranded DNA but does not deaminate 5-methyl cytosine. PCR, cloning and sequencing revealed the methylation pattern of CpG doublets in the promoter region of the APRT− gene, whereas the active APRT gene had nonmethylated DNA. CHO strain K1, which has two copies of the APRT+ gene, could also be silenced by the same procedure but at a lower frequency. The availability of the 5-methyl dCTP-induced silencing, 5-aza-CR and a standard mutagen, ethyl methane sulphonate, makes it possible to follow concomitantly the inheritance of active, mutant or silenced gene copies. This analysis demonstrates “dual inheritance” at the APRT locus in CHO cells.
Gametocidal Genes Induce Chromosome Breakage in the Interphase Prior to the First Mitotic Cell Division of the Male Gametophyte in Wheat
Authors: Nasuda Shuhei , Friebe Bernd , Gill Bikram S 
Published: April 2021

Abstract
Male gametogenesis was cytologically analyzed in wheat lines homozygous or hemizygous for gametocidal (Gc) factors with different modes of action. The first and second meiotic divisions in all lines were cytologically normal. The postmeiotic mitoses were normal in the homozygous lines; however, chromosome fragments and bridges were observed in the mitoses of the hemizygous lines. The morphology of the chromosome fragments suggests that the Gc genes induce chromosome breaks in the G1 phase prior to DNA synthesis of the first postmeiotic mitosis. The age of an anther was correlated with the frequency of aberrant second mitosis. Younger anthers contained a higher number of pollen undergoing normal second mitosis. This observation suggests that the arresting of the cell cycle occurs as the result of chromosome breaks during the first mitosis. Because chromosome bridges were more frequent than fragments in the second mitosis, breakage-fusion-bridge cycles possibly occurred during gametogenesis, which led to further chromosomal rearrangements. The Gc factors located on chromosomes 2S of Aegilops speltoides and 4Ssh of Ae. sharonensis induce severe chromosome breakage in pollen lacking them. However, the Gc factor on telosome 2CcL of Ae. cylindrica only induced chromosome breaks at a low frequency. The observed partial fertility of Gc lines is presumably due to cell cycle arrest and the competition among gametes with and without chromosome breakage.
One-Locus Two-Allele Models With Maternal (Parental) Selection
Authors: Gavrilets Sergey 
Published: April 2021

Abstract
I formulate and study a series of simple one-locus two-allele models for maternal (parental) selection. I show that maternal (parental) selection can result in simultaneous stability of equilibria of different types. Thus, in the presence of maternal (parental) selection the outcome of population evolution can significantly depend on initial conditions. With maternal selection, genetic variability can be maintained in the population even if none of the offspring of heterozygous mothers survive. I demonstrate that interactions of maternal and paternal selection can result in stable oscillations of genotype frequencies. A necessary condition for cycling is strong selection.
Evidence for a Role for AtMYB2 in the Induction of the Arabidopsis Alcohol Dehydrogenase Gene (ADH1) by Low Oxygen
Authors: Hoeren Frank U , Dolferus Rudy , Wu Yingru , Peacock W James , Dennis Elizabeth S 
Published: April 2021

Abstract
The transcription factor AtMYB2 binds to two sequence motifs in the promoter of the Arabidopsis ADH1 gene. The binding to the GT-motif (5′-TGGTTT-3′) is essential for induction of ADH1 by low oxygen, while binding to the second motif, MBS-2, is not essential for induction. We show that AtMYB2 is induced by hypoxia with kinetics compatible with a role in the regulation of ADH1. Like ADH1, AtMYB2 has root-limited expression. When driven by a constitutive promoter, AtMYB2 is able to transactivate ADH1 expression in transient assays in both Arabidopsis and Nicotiana plumbaginifolia protoplasts, and in particle bombardment of Pisum sativum leaves. Mutation of the GT-motif abolished binding of AtMYB2 and caused loss of activity of the ADH1 promoter in both transient assays and transgenic Arabidopsis plants. These results are consistent with AtMYB2 being a key regulatory factor in the induction of the ADH1 promoter by low oxygen.
Genetics of the Deflagellation Pathway in Chlamydomonas
Authors: Finst Rip J , Kim Peter J , Quarmby Lynne M 
Published: April 2021

Abstract
Signal-induced deflagellation in Chlamydomonas involves Ca2+-activated breakage of the nine outer-doublet axonemal microtubules at a specific site in the flagellar transition zone. In this study, we isolated 13 new deflagellation mutants that can be divided into two phenotypic classes, the Adf class and the Fa class. Cells with the Adf deflagellation phenotype are defective in acid-stimulated Ca2+ influx, but can be induced to deflagellate by treatment with nonionic detergent and Ca2+. Genetic analyses show that the five new Adf mutations, as well as the previously identified adf1 mutation, are alleles of the ADF1 gene. Mutants in the second phenotypic class, the Fa mutants, fail to deflagellate in response to any known chemical stimulus and are defective in Ca2+-activated microtubule severing. Genetic analysis of these eight new Fa strains demonstrated that they define two complementation groups, and one of these contains the previously identified fa1 mutation. Diploid analysis showed that five alleles map to the FA1 gene, whereas four alleles define a novel gene that we have named FA2. The isolation of multiple mutant alleles of each gene, generated by either ultraviolet irradiation or insertional mutagenesis, indicates that ADF1, FA1, and FA2 may be the only genes that can be identified in a loss-of-function screen. These alleles should provide a better understanding of the regulation of microtubule severing by Ca2+.