bluuebunny/crossref_metadata_2025_split huggingface dataset:
Through a Glass, Darkly: Artificial Intelligence and the Problem of Opacity
Authors: Chesterman Simon 
Published: April 2021

Abstract
As computer programs become more complex, the ability of non-specialists to understand how a given output has been reached diminishes. Opaqueness may also be built into programs to protect proprietary interests. Both types of systems are capable of being explained, either through recourse to experts or an order to produce information. Another class of system may be naturally opaque, however, using deep learning methods that are impossible to explain in a manner that humans can comprehend. An emerging literature describes these phenomena or specific problems to which they give rise, notably the potential for bias against specific groups. Drawing on examples from the United States, the European Union, and China, this Article develops a novel typology of three discrete regulatory challenges posed by opacity. First, it may encourage—or fail to discourage—inferior decisions by removing the potential for oversight and accountability. Second, it may allow impermissible decisions, notably those that explicitly or implicitly rely on protected categories such as gender or race in making a determination. Third, it may render illegitimate decisions in which the process by which an answer is reached is as important as the answer itself. The means of addressing some or all of these concerns is routinely said to be through transparency. Yet, while proprietary opacity can be dealt with by court order and complex opacity through recourse to experts, naturally opaque systems may require novel forms of “explanation” or an acceptance that some machine-made decisions cannot be explained—or, in the alternative, that some decisions should not be made by machine at all.
The cost of non-response to cardiac resynchronization therapy: characterizing heart failure events following cardiac resynchronization therapy
Authors: Varma Niraj , Auricchio Angelo , Connolly Allison T , Boehmer John , Bahu Marwan , Costanzo Maria Rosa , Leonelli Fabio , Yoo Dale , Singh Jagmeet , Nabutovsky Yelena , Gold Michael 
Published: April 2021

Abstract

Aims
The aim of this study is to quantify healthcare resource utilization among non-responders to cardiac resynchronization therapy (CRT-NR) by heart failure (HF) events and influence of comorbidities.

Methods and results
The ADVANCE CRT registry (2013–2015) prospectively identified responders/CRT-NRs 6 months post-implant using the clinical composite score. Heart failure event rates and associated cost, both overall and separated for inpatient hospitalizations, office visits, emergency room visits, and observational stays, were quantified. Costs of events were imputed from payments for similar real-world encounters in subjects with CRT-D/P devices in the MarketScan™ commercial and Medicare Supplemental insurance claims databases. Effects of patient demographics and comorbidities on event rates and cost were evaluated. Of 879 US patients (age 69 ± 11 years, 29% female, ischaemic disease 52%), 310 (35%) were CRT-NR. Among CRT-NRs vs. responders, more patients developed HF (41% vs. 11%, P &lt; 0.001), HF event rate was higher (67.0 ± 21.7 vs. 11.4 ± 3.7/100 pt-year, P &lt; 0.001), and HF readmission within 30 days was more common [hazard ratio 7.06, 95% confidence interval (2.1–43.7)]. Inpatient hospitalization was the most common and most expensive event type in CRT-NR. Comorbid HF was increased by diabetes, hypertension, and pulmonary disorders. Over 2 years, compared to CRT responders, each CRT-NR resulted in excess cost of $6388 ($3859–$10 483) to Medicare (P = 0.015) or $10 197 ($6161–$17 394) to private insurances (P = 0.014).

Conclusion
Healthcare expenditures associated with contemporary CRT non-response management are among the highest for any HF patient group. This illustrates an unmet need for interventions to improve HF outcomes and reduce costs among some CRT recipients.
Multiple Marker Mapping of Quantitative Trait Loci in a Cross Between Outbred Wild Boar and Large White Pigs
Authors: Knott Sara A , Marklund Lena , Haley Chris S , Andersson Kjell , Davies William , Ellegren Hans , Fredholm Merete , Hansson Ingemar , Hoyheim Bjorn , Lundström Kerstin , Moller Maria , Andersson Leif 
Published: April 2021

Abstract
A quantitative trait locus (QTL) analysis of growth and fatness data from a three generation pig experiment is presented. The population of 199 F2 animals was derived from a cross between wild boar and Large White pigs. Animals were typed for 240 markers spanning 23 Morgans of 18 autosomes and the X chromosome. A series of analyses are presented within a least squares framework. First, these identify chromosomes containing loci controlling trait variation and subsequently attempt to map QTLs to locations within chromosomes. This population gives evidence for a large QTL affecting back fat and another for abdominal fat segregating on chromosome 4. The best locations for these QTLs are within 4 cM of each other and, hence, this is likely to be a single QTL affecting both traits. The allele inherited from the wild boar causes an increase in fat deposition. A QTL for intestinal length was also located in the same region on chromosome 4 and could be the same QTL with pleiotropic effects. Significant effects, owing to multiple QTLs, for intestinal length were identified on chromosomes 3 and 5. A single QTL affecting growth rate to 30 kg was located on chromosome 13 such that the Large White allele increased early growth rate, another QTL on chromosome 10 affected growth rate from 30 to 70 kg and another on chromosome 4 affected growth rate to 70 kg.
Properties of Maximum Likelihood Male Fertility Estimation in Plant Populations
Authors: Morgan M T 
Published: April 2021

Abstract
Computer simulations are used to evaluate maximum likelihood methods for inferring male fertility in plant populations. The maximum likelihood method can provide substantial power to characterize male fertilities at the population level. Results emphasize, however, the importance of adequate experimental design and evaluation of fertility estimates, as well as limitations to inference (e.g., about the variance in male fertility or the correlation between fertility and phenotypic trait value) that can be reasonably drawn.
Position Effects of Ribosomal RNA Multigene Loci on Meiotic Recombination in Wheat
Authors: Luo Ming-Cheng , Yang Zu-Li , Dvořák Jan 
Published: April 2021

Abstract
Homeologous wheat chromosome arms that differ by the presence or absence of a Nor locus or greatly differ in the numbers of copies of rRNA genes per Nor locus show conspicuous differences in the distribution of recombination. To assess directly the position effects of Nor loci on recombination across chromosome arms, a Triticum monococcum Nor9 haplotype was substituted for Triticum aestivum Nor9 haplotypes on two T. aestivum 1A chromosomes in the isogenic background of cv Chinese Spring. The numbers of rRNA genes in the 1A Nor9 haplotypes are greatly reduced relative to the T. monococcum haplotype. The substitution resulted in reduced recombination rate in the vicinity of the Nor9 locus. An intra-arm compensatory increase was observed in the proximal region of the arm so that the genetic length of the chromosome arm was unchanged. These findings suggest that Nor loci suppress recombination in their vicinity and change recombination patterns in Nor-bearing chromosome arms.
Arabidopsis Mutants Define an in Vivo Role for Isoenzymes of Aspartate Aminotransferase in Plant Nitrogen Assimilation
Authors: Schultz Carolyn J , Hsu Meier , Miesak Barbara , Coruzzi Gloria M 
Published: April 2021

Abstract
Arabidopsis contains five isoenzymes of aspartate aminotransferase (AspAT) localized to the cytosol, chloroplast, mitochondria, or peroxisomes. To define the in vivo function of individual isoenzymes, we screened for Arabidopsis mutants deficient in either of the two major isoenzymes, cytosolic AAT2 or chloroplastic AAT3, using a native gel activity assay. In a screen of 8,000 M2 seedlings, three independent mutants deficient in cytosolic AAT2 (aat2) and two independent mutants deficient in chloroplastic AAT3 (aat3) were isolated. Mapping of aat2 and aat3 mutations and the five AspAT genes (ASP1–ASP5) established associations as follows: the mutation affecting aat2 maps with and cosegregates with ASP2, one of two expressed genes for cytosolic AspAT; the mutation affecting aat3 maps to the same location as the ASP5 gene encoding chloroplastic AspAT. Phenotypic analysis of the aat2 and aat3 mutants revealed a dramatic aspartate-related phenotype in one of the mutants deficient in cytosolic AAT2. The aat2-2 mutant displays an 80% reduction in levels of aspartate transported in the phloem of light-grown plants, and a 50% reduction in levels of asparagine transported in dark-adapted plants. These results indicate that cytosolic AAT2 is the major isoenzyme controlling aspartate synthesized for nitrogen transport in the light, and that this aspartate pool is converted to asparagine when plants are dark adapted.
A Transgene Encoding a Plasma Membrane H+-ATPase That Confers Acid Resistance in Arabidopsis thaliana Seedlings
Authors: Young Jeff C , DeWitt Natalie D , Sussman Michael R 
Published: April 2021

AbstractProton pumps (H+-ATPases) are the primary active transport systems in the plasma membrane of higher plant cells. These enzymes are encoded by a large gene family expressed throughout the plant, with specific isoforms directed to various specialized cells. While their involvement in membrane energetics has been suggested by a large body of biochemical and physiological studies, a genetic analysis of their role in plants has not yet been performed. We report here that mutant Arabidopsis thaliana plants containing a phloem-specific transgene encoding a plasma membrane H+-ATPase with an altered carboxy terminus show improved growth at low pH during seedling development. These observations provide the first genetic evidence for a role of the plasma membrane H+-ATPase in cytoplasmic pH homeostasis in plants.
Somatic Embryogenesis in Arabidopsis thaliana Is Facilitated by Mutations in Genes Repressing Meristematic Cell Divisions
Authors: Mordhorst Andreas P , Voerman Keete J , Hartog Marijke V , Meijer Ellen A , van Went Jacques , Koornneef Maarten , de Vries Sacco C 
Published: April 2021

Abstract
Embryogenesis in plants can commence from cells other than the fertilized egg cell. Embryogenesis initiated from somatic cells in vitro is an attractive system for studying early embryonic stages when they are accessible to experimental manipulation. Somatic embryogenesis in Arabidopsis offers the additional advantage that many zygotic embryo mutants can be studied under in vitro conditions. Two systems are available. The first employs immature zygotic embryos as starting material, yielding continuously growing embryogenic cultures in liquid medium. This is possible in at least 11 ecotypes. A second, more efficient and reproducible system, employing the primordia timing mutant (pt allelic to hpt, cop2, and amp1), was established. A significant advantage of the pt mutant is that intact seeds, germinated in 2,4-dichlorophenoxyacetic acid (2,4-D) containing liquid medium, give rise to stable embryonic cell cultures, circumventing tedious hand dissection of immature zygotic embryos. pt zygotic embryos are first distinguishable from wild type at early heart stage by a broader embryonic shoot apical meristem (SAM). In culture, embryogenic clusters originate from the enlarged SAMs. pt somatic embryos had all characteristic embryo pattern elements seen in zygotic embryos, but with higher and more variable numbers of cells. Embryogenic cell cultures were also established from seedling, of other mutants with enlarged SAMs, such as clavata (clv). pt clv double mutants showed additive effects on SAM size and an even higher frequency of seedlings producing embryogenic cell lines. pt clv double mutant plants had very short fasciated inflorescence stems and additive effects on the number of rosette leaves. This suggests that the PT and CLV genes act in independent pathways that control SAM size. An increased population of noncommitted SAM cells may be responsible for facilitated establishment of somatic embryogenesis in Arabidopsis.
Modulation of Tubulin Polypeptide Ratios by the Yeast Protein Pac10p
Authors: Alvarez Pablo , Smith Adelle , Fleming James , Solomon Frank 
Published: April 2021

Abstract
Normal assembly and function of microtubules require maintenance of the proper levels of several proteins, including the tubulin polypeptides themselves. For example, in yeast a significant excess of β-tubulin causes rapid microtubule disassembly and subsequent cell death. Even the modest excess of β-tubulin produced by genetic alterations such as deletion of the minor α-tubulin gene TUB3 affects cell growth and can confer microtubule phenotypes. We show here that the levels of the yeast protein Pac10p affect the relative levels of the tubulin polypeptides. Cells deleted for PAC10 have the same phenotypes as do cells that express reduced levels of α-tubulin or Rbl2p, two proteins that bind β-tubulin. Conversely, overexpression of Pac10p enhances the ability of α-tubulin or Rbl2p to suppress the lethality associated with excess β-tubulin. However, Pac10p is itself not a β-tubulin binding protein. Pac10 null cells show a 30% decrease in the ratio of α-tubulin to β-tubulin. The results suggest that Pac10p modulates the level of α-tubulin in the cell, and so influences microtubule morphogenesis and tubulin metabolism.
Mot3, a Zn Finger Transcription Factor That Modulates Gene Expression and Attenuates Mating Pheromone Signaling in Saccharomyces cerevisiae
Authors: Grishin Anatoly V , Rothenberg Michael , Downs Maureen A , Blumer Kendall J 
Published: April 2021

Abstract
In the yeast Saccharomyces cerevisiae, mating pheromone response is initiated by activation of a G protein- and mitogen-activated protein (MAP) kinase-dependent signaling pathway and attenuated by several mechanisms that promote adaptation or desensitization. To identify genes whose products negatively regulate pheromone signaling, we screened for mutations that suppress the hyperadaptive phenotype of wild-type cells overexpressing signaling-defective G protein β subunits. This identified recessive mutations in MOT3, which encodes a nuclear protein with two Cys2-His2 Zn fingers. MOT3 was found to be a dosage-dependent inhibitor of pheromone response and pheromone-induced gene expression and to require an intact signaling pathway to exert its effects. Several results suggested that Mot3 attenuates expression of pheromone-responsive genes by mechanisms distinct from those used by the negative transcriptional regulators Cdc36, Cdc39, and Mot2. First, a Mot3-lexA fusion functions as a transcriptional activator. Second, Mot3 is a dose-dependent activator of several genes unrelated to pheromone response, including CYC1, SUC2, and LEU2. Third, insertion of consensus Mot3 binding sites (C/A/T)AGG(T/C)A activates a promoter in a MOT3-dependent manner. These findings, and the fact that consensus binding sites are found in the 5′ flanking regions of many yeast genes, suggest that Mot3 is a globally acting transcriptional regulator. We hypothesize that Mot3 regulates expression of factors that attenuate signaling by the pheromone response pathway.
An Intragenic Suppressor of Cold Sensitivity Identifies Potentially Interacting Bases in the Peptidyl Transferase Center of Tetrahymena rRNA
Authors: Sweeney Rosemary , Yao Meng-Chao 
Published: April 2021

Abstract
Peptidyl transfer of a growing peptide on a ribosome-bound transfer RNA (tRNA) to an incoming amino acyl tRNA is the central step in translation, and it may be catalyzed primarily by the large subunit (LSU) ribosomal RNA (rRNA). Genetic and biochemical evidence suggests that the central loop of domain V of the LSU rRNA plays a direct role in peptidyl transfer. It was previously found that a single base change at a universally conserved site in this region of the Tetrahymena thermophila LSU rRNA confers anisomycin resistance (an-r) as well as extremely slow growth, cold sensitivity, and aberrant cell morphology. Because anisomycin specifically inhibits peptidyl transfer, possibly by interfering with tRNA binding, it is likely that this mutant rRNA is defective in efficiently completing one of these steps. In the present study, we have isolated an intragenic suppressor mutation located only three bases away from the original mutation that partially reverses the slow growth and cold-sensitive phenotypes. These data imply that the functional interaction of these two bases is necessary for normal rRNA function, perhaps for peptidyl transfer or tRNA binding. These data provide the first demonstration of a functional interaction between bases within this rRNA region.
Fission Yeast cdc24+ Encodes a Novel Replication Factor Required for Chromosome Integrity
Authors: Gould Kathleen L , Burns C Geoffrey , Feoktistova Anna , Hu Ching-Pei , Pasion Sally G , Forsburg Susan L 
Published: April 2021

AbstractA mutation within the Schizosaccharomyces pombe cdc24+ gene was identified previously in a screen for cell division cycle mutants and the cdc24+ gene was determined to be essential for S phase in this yeast. We have isolated the cdc24+ gene by complementation of a new temperature-sensitive allele of the gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null mutant was generated by homologous recombination. Haploid cells lacking cdc24+ are inviable, indicating that cdc24+ is an essential gene. The transcript of cdc24+ is present at constant levels throughout the cell cycle. Cells lacking cdc24+ function show a checkpoint-dependent arrest with a 2N DNA content, indicating a block late in S phase. Arrest is accompanied by a rapid loss of viability and chromosome breakage. An S. pombe homolog of the replicative DNA helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that Cdc24p plays a role in the progression of normal DNA replication and is required to maintain genomic integrity.
The PBN1 Gene of Saccharomyces cerevisiae: An Essential Gene That Is Required for the Post-translational Processing of the Protease B Precursor
Authors: Naik Rajesh R , Jones Elizabeth W 
Published: April 2021

Abstract
The vacuolar hydrolase protease B in Saccharomyces cerevisiae is synthesized as an inactive precursor (Prb1p). The precursor undergoes post-translational modifications while transiting the secretory pathway. In addition to N- and O -linked glycosylations, four proteolytic cleavages occur during the maturation of Prb1p. Removal of the signal peptide by signal peptidase and the autocatalytic cleavage of the large aminoterminal propeptide occur in the endoplasmic reticulum (ER). Two carboxy-terminal cleavages of the post regions occur in the vacuole: the first cleavage is catalyzed by protease A and the second results from autocatalysis. We have isolated a mutant, pbn1-1, that exhibits a defect in the ER processing of Prb1p. The autocatalytic cleavage of the propeptide from Prb1p does not occur and Prb1p is rapidly degraded in the cytosol. PBN1 was cloned and is identical to YCL052c on chromosome III. PBN1 is an essential gene that encodes a novel protein. Pbn1p is predicted to contain a sub-C-terminal transmembrane domain but no signal sequence. A functional HA epitope-tagged Pbn1p fusion localizes to the ER. Pbn1p is N-glycosylated in its amino-terminal domain, indicating a lumenal orientation despite the lack of a signal sequence. Based on these results, we propose that one of the functions of Pbn1p is to aid in the autocatalytic processing of Prb1p.
Evaluating Gene Flow Using Selected Markers: A Case Study
Authors: Lenormand Thomas , Guillemaud Thomas , Bourguet Denis , Raymond Michel 
Published: April 2021

AbstractThe extent to which an organism is locally adapted in an environmental pocket depends on the selection intensities inside and outside the pocket, on migration, and on the size of the pocket. When two or more loci are involved in this local adaptation, measuring their frequency gradients and their linkage disequilbria allows one to disentangle the forces—migration and selection—acting on the system. We apply this method to the case of a local adaptation to organophosphate insecticides in the mosquito Culex pipiens pipiens in southern France. The study of two different resistance loci allowed us to estimate with support limits gene flow as well as selection pressure on insecticide resistance and the fitness costs associated with each locus. These estimates permit us to pinpoint the conditions for the maintenance of this pocket of adaptation as well as the effect of the interaction between the two resistance loci.
Chromosome Rearrangements Induce Both Variegated and Reduced, Uniform Expression of Heterochromatic Genes in a Development-Specific Manner
Authors: Weiler Karen S , Wakimoto Barbara T 
Published: April 2021

AbstractIn Drosophila melanogaster, chromosome rearrangements that juxtapose euchromatin and heterochromatin can result in position effect variegation (PEV), the variable expression of heterochromatic and euchromatic genes in the vicinity of the novel breakpoint. We examined PEV of the heterochromatic light (lt) and concertina (cta) genes in order to investigate potential tissue or developmental differences in chromosome structure that might be informative for comparing the mechanisms of PEV of heterochromatic and euchromatic genes. We employed tissue pigmentation and in situ hybridization to RNA to assess expression of lt in individual cells of multiple tissues during development. Variegation of lt was induced in the adult eye, larval salivary glands and larval Malpighian tubules for each of three different chromosome rearrangements. The relative severity of the effect in these tissues was not tissue-specific but rather was characteristic of each rearrangement. Surprisingly, larval imaginal discs did not exhibit variegated lt expression. Instead, a uniform reduction of the lt transcript was observed, which correlated in magnitude with the degree of variegation. The same results were obtained for cta expression. These two distinct effects of rearrangements on heterochromatic gene expression correlated with the developmental stage of the tissue. These results have implications for models of heterochromatin formation and the nuclear organization of chromosomes during development and differentiation.