bluuebunny/crossref_metadata_2025 huggingface dataset:
EMG based classification for pick and place task
Authors: Khan Salman Mohd , Khan Abid Ali , Farooq Omar
Published: April 2021

The hand amputee is deprived of number of activities of daily living. To help the hand amputee, it is important to learn the pattern of muscles activity. There are several elements of tasks, which involve forearm along with the wrist and hand. The one very important task is pick and place activity performed by the hand. A pick and place action is a compilation of different finger motions for the grasping of objects at different force levels. This action may be better understood by learning the electromyography signals of forearm muscles. Electromyography is the technique to acquire electrical muscle activity that is used for the pattern recognition technique of assistive devices. Regarding this, the different classification characterizations of EMG signals involved in the pick and place action, subjected to variable grip span and weights were considered in this study. A low-level force measuring gripper, capable to bear the changes in weights and object spans was designed and developed to simulate the task. The grip span varied from 6 cm to 9 cm and the maximum weight used in this study was 750 gms. The pattern recognition classification methodology was performed for the differentiation of phases of the pick and place activity, grip force, and the angular deviation of metacarpal phalangeal (MCP) joint. The classifiers used in this study were decision tree (DT), support vector machines (SVM) and k-nearest neighbor (k-NN) based on the feature sets of the EMG signals. After analyses, it was found that k-NN performed best to classify different phases of the activity and relative deviation of MCP joint with an average classification accuracy of 82% and 91% respectively. However; the SVM performed best in classification of force with a particular feature set. The findings of the study would be helpful in designing the assistive devices for hand amputee.
2. How arbitration works
Authors: Schultz Thomas , Grant Thomas
Published: April 2021

This chapter explains how arbitration works in practice. Arbitration takes place if and only if parties have consented to it. Their consent needs to make clear how, specifically, arbitration is going to work for them. Parties in some situations may use courts and through them the executive apparatus to assist in arbitral proceedings. Under most arbitration agreements, once the arbitrator or arbitral tribunal has given the final arbitral award, arbitral jurisdiction comes to an end, and so there is no place for a party to turn to appeal against an adverse award. However, a losing party nevertheless may have opportunities to challenge an award, including in proceedings in national courts.
3. The multiple lives of arbitration
Authors: Schultz Thomas , Grant Thomas
Published: April 2021

This chapter describes some of the main types of cases in which parties use arbitration. First, there are disputes that pit two countries one against the other, which can be referred to as ‘interstate’ or ‘international’ or sometimes ‘inter-governmental’ disputes. Then there are disputes between private parties: individuals in dispute with one another; individuals in dispute with companies; or companies in dispute with other companies. Legal scholars call these ‘private’ disputes. And, third, there are disputes between a private party, such as an individual or a company, and a government. In the field of dispute settlement, these types of disputes are known as ‘mixed’ disputes.
4. Arbitration and the law
Authors: Schultz Thomas , Grant Thomas
Published: April 2021

This chapter explores how arbitration relates to public courts, the law, and legal systems. Not all disputes are permitted to be arbitrated. The word lawyers use to describe disputes that the law permits parties to submit to arbitration is ‘arbitrability’. Disputes that the law does not permit parties to submit to arbitration are said to be ‘non-arbitrable’. The chapter then considers how parties can choose the law that applies in their arbitration. The typical arrangement is that the seat of arbitration is also the physical location where the proceedings take place—meaning that the law of the physical location is the procedural law of the arbitration.
Relativity and its philosophy
Authors: Wallace David
Published: April 2021

This chapter discusses how relativity theory affects our ideas about space, time, and motion. The special theory of relativity does not introduce the idea that motion is relative: it combines that idea, already present in Newtonian physics, with the idea that the speed of light does not depend on the motion of the source. This combination has surprising consequences: that moving clocks run slow; that moving rods shrink. This is apparently in flat contradiction with the relativity principle. The resolution of this paradox looks very different depending on one’s view of what spacetime is: is it simply a codification of physics, or can it do explanatory work in its own right. Thus the paradox lets us get clearer on what is at stake in these questions about the nature of spacetime. Relativity also imperils the idea that simultaneity—the relationship between two events when they occur at the same time—is relative and/or conventional. The epilogue of the chapter briefly discusses the general theory of relativity.
Mysteries of the quantum
Authors: Wallace David
Published: April 2021

This chapter introduces the central mysteries of quantum mechanics. Quantum mechanics is an enormously successful theory that lies at the heart of modern physics, but there is no agreement on how to understand it. Simple experiments with light demonstrate why: in understanding those experiments, we have to shift inconsistently back and forth between thinking of the theory as assigning indefinite, delocalized, but known properties to a system, and assigning definite, localized, but unknown properties (this is called the ‘problem of measurement’). Furthermore, when we break a system into subsystems, the state of the system is not determined by the states of the subsystem (this is called ‘entanglement’), and simple arguments seem to tell us that the physical properties of entangled subsystems can influence one another non-locally—faster than light. These three mysteries—measurement, entanglement, non-locality—need to be addressed by any attempt to make sense of quantum theory.
Ancient reefs and islands
Authors: Sheppard Charles
Published: April 2021

Reefs in deep geological time have been built by a succession of different kinds of life: plant, bacterial, and animal. Stromatolites and bryozoans were major reef-builders that persist today in minor or non-reef-building forms, sponges built entire reefs and are still important reef components, while several groups of major reef-builders flourished for a while and then became extinct: archaeocyathids which were similar to sponges, and coral-like forms including rugose and tabulate corals. Today’s reef-builders, cnidarian corals, appeared well after the great Permian-Triassic extinction event. All of these groups deposited vast quantities of limestone rock on which they live, often visible today as low mountain ranges. Reefs grow to the surface but not beyond, but upon them sand and sediments may build up, forming an island that attracts plants, then birds and other terrestrial forms of life. The sediments become cemented with the aid of rainwater too, and ‘low islands’ develop. Many islands also show their old, central volcanoes, resulting in the vast array of different combinations of coral island type. Today, however, there is a coral reef crisis due to overexploitation of a reef’s rich resources, from pollution of several kinds, and climate change.
Reef fish and other major predators
Authors: Sheppard Charles
Published: April 2021

Fish, like corals, have geographical patterns across regions and across individual reefs, being structured in the latter case by wave energy and depth. The thousands of species show a variety of feeding patterns. Detritus feeders are very abundant, feeding on the detritus on the seabed, especially in the fine, filamentous algal turf on apparently bare rock. Plankton feeders are common also, and herbivorous fishes show a large abundance, perhaps a quarter of the total species present, cropping algae that otherwise would grow unchecked and smother coral. Since turf algae also contain many micro-species and detritus, most herbivores also ingest much food other than simple plant material. Carnivores range from extreme specialists, such as polyp-picking butterflyfish, to generalists. Sharks and barracuda only consume other fish and generally are at the top of their food chains. The complicated ecological structure of the food webs can be clarified by analysing nitrogen isotope ratios in their tissues. Other important coral carnivores include the crown of thorns starfish, which can remove almost all living coral on a reef when it develops into plagues. Overfishing by humans greatly disturbs the equilibrium of a reef, and this is increasingly causing reef degradation.
Doing something about it
Authors: Sheppard Charles
Published: April 2021

Several political instruments are in place to tackle effects of climate change and help arrest the global decline of coral reefs. Unfortunately, most are inadequate and anyway are being ignored by many important nations. Rising ocean temperatures are not linear, but act in pulses, so that reefs degrade in steps rather than smoothly. Terminally degraded reefs are now common, and those in very good condition are rare. Several potential solutions have been proposed, none being adequate alone but all being needed to arrest the decline. Arresting the rise in CO2 is a key, long-term requirement, yet levels of this gas are still increasing, as are local requirements such as effective pollution and overfishing controls. Also important is limiting resource extraction, which essentially means limiting human populations. Most scientists consider saving coral reefs now to be a political and sociological problem, not a scientific one. We have lost nearly half the world’s coral reefs and if societies cannot act in what is becoming a diminishing window of opportunity, we will lose most of the rest within another human lifetime.
Build a better bootstrap and the RAWR shall beat a random path to your door: phylogenetic support estimation revisited
Authors: Wang Wei , Hejasebazzi Ahmad , Zheng Julia , Liu Kevin J
Published: April 2021

Motivation

The standard bootstrap method is used throughout science and engineering to perform general-purpose non-parametric resampling and re-estimation. Among the most widely cited and widely used such applications is the phylogenetic bootstrap method, which Felsenstein proposed in 1985 as a means to place statistical confidence intervals on an estimated phylogeny (or estimate ‘phylogenetic support’). A key simplifying assumption of the bootstrap method is that input data are independent and identically distributed (i.i.d.). However, the i.i.d. assumption is an over-simplification for biomolecular sequence analysis, as Felsenstein noted.

Results

In this study, we introduce a new sequence-aware non-parametric resampling technique, which we refer to as RAWR (‘RAndom Walk Resampling’). RAWR consists of random walks that synthesize and extend the standard bootstrap method and the ‘mirrored inputs’ idea of Landan and Graur. We apply RAWR to the task of phylogenetic support estimation. RAWR’s performance is compared to the state-of-the-art using synthetic and empirical data that span a range of dataset sizes and evolutionary divergence. We show that RAWR support estimates offer comparable or typically superior type I and type II error compared to phylogenetic bootstrap support. We also conduct a re-analysis of large-scale genomic sequence data from a recent study of Darwin’s finches. Our findings clarify phylogenetic uncertainty in a charismatic clade that serves as an important model for complex adaptive evolution.

Availability and implementation

Data and software are publicly available under open-source software and open data licenses at: https://gitlab.msu.edu/liulab/RAWR-study-datasets-and-scripts.
Weakly supervised learning of RNA modifications from low-resolution epitranscriptome data
Authors: Huang Daiyun , Song Bowen , Wei Jingjue , Su Jionglong , Coenen Frans , Meng Jia
Published: April 2021

Motivation

Increasing evidence suggests that post-transcriptional ribonucleic acid (RNA) modifications regulate essential biomolecular functions and are related to the pathogenesis of various diseases. Precise identification of RNA modification sites is essential for understanding the regulatory mechanisms of RNAs. To date, many computational approaches for predicting RNA modifications have been developed, most of which were based on strong supervision enabled by base-resolution epitranscriptome data. However, high-resolution data may not be available.

Results

We propose WeakRM, the first weakly supervised learning framework for predicting RNA modifications from low-resolution epitranscriptome datasets, such as those generated from acRIP-seq and hMeRIP-seq. Evaluations on three independent datasets (corresponding to three different RNA modification types and their respective sequencing technologies) demonstrated the effectiveness of our approach in predicting RNA modifications from low-resolution data. WeakRM outperformed state-of-the-art multi-instance learning methods for genomic sequences, such as WSCNN, which was originally designed for transcription factor binding site prediction. Additionally, our approach captured motifs that are consistent with existing knowledge, and visualization of the predicted modification-containing regions unveiled the potentials of detecting RNA modifications with improved resolution.

Availability implementation

The source code for the WeakRM algorithm, along with the datasets used, are freely accessible at: https://github.com/daiyun02211/WeakRM

Supplementary information

Supplementary data are available at Bioinformatics online.
Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation
Authors: Neudorfer Clemens , Elias Gavin J B , Jakobs Martin , Boutet Alexandre , Germann Jürgen , Narang Keshav , Loh Aaron , Paff Michelle , Horn Andreas , Kucharczyk Walter , Deeb Wissam , Salvato Bryan , Almeida Leonardo , Foote Kelly D , Rosenberg Paul B , Tang-Wai David F , Anderson William S , Mari Zoltan , Ponce Francisco A , Wolk David A , Burke Anna D , Salloway Stephen , Sabbagh Marwan N , Chakravarty M Mallar , Smith Gwenn S , Lyketsos Constantine G , Okun Michael S , Lozano Andres M
Published: April 2021

Abstarct

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied—at multiple international centres—58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer’s disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation—including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear—were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.
Prion potentiation after life-long dormancy in mice devoid of PrP
Authors: Martin Davy , Reine Fabienne , Herzog Laetitia , Igel-Egalon Angélique , Aron Naima , Michel Christel , Moudjou Mohammed , Fichet Guillaume , Quadrio Isabelle , Perret-Liaudet Armand , Andréoletti Olivier , Rezaei Human , Béringue Vincent
Published: April 2021

Prions are neurotropic pathogens composed of misfolded assemblies of the host-encoded prion protein PrPC which replicate by recruitment and conversion of further PrPC by an autocatalytic seeding polymerization process. While it has long been shown that mouse-adapted prions cannot replicate and are rapidly cleared in transgenic PrP0/0 mice invalidated for PrPC, these experiments have not been done with other prions, including from natural resources, and more sensitive methods to detect prion biological activity. Using transgenic mice expressing human PrP to bioassay prion infectivity and RT-QuIC cell-free assay to measure prion seeding activity, we report that prions responsible for the most prevalent form of sporadic Creutzfeldt–Jakob disease in human (MM1-sCJD) can persist indefinitely in the brain of intra-cerebrally inoculated PrP0/0 mice. While low levels of seeding activity were measured by RT-QuIC in the brain of the challenged PrP0/0 mice, the bio-indicator humanized mice succumbed at a high attack rate, suggesting relatively high levels of persistent infectivity. Remarkably, these humanized mice succumbed with delayed kinetics as compared to MM1-sCJD prions directly inoculated at low doses, including the limiting one. Yet, the disease that did occur in the humanized mice on primary and subsequent back-passage from PrP0/0 mice shared the neuropathological and molecular characteristics of MM1-sCJD prions, suggesting no apparent strain evolution during lifelong dormancy in PrP0/0 brain. Thus, MM1-sCJD prions can persist for the entire life in PrP0/0 brain with potential disease potentiation on retrotransmission to susceptible hosts. These findings highlight the capacity of prions to persist and rejuvenate in non-replicative environments, interrogate on the type of prion assemblies at work and alert on the risk of indefinite prion persistence with PrP-lowering therapeutic strategies.
Household Exposure to Severe Acute Respiratory Syndrome Coronavirus 2 and Association With Coronavirus Disease 2019 Severity: A Danish Nationwide Cohort Study
Authors: Broccia Marcella , de Knegt Victoria Elizabeth , Mills Elisabeth Helen Anna , Møller Amalie Lykkemark , Gnesin Filip , Fischer Thea K , Zylyftari Nertila , Blomberg Stig Nikolaj , Andersen Mikkel Porsborg , Schou Morten , Fosbøl Emil , Kragholm Kristian , Christensen Helle Collatz , Polcwiartek Laura Bech , Phelps Matthew , Køber Lars , Torp-Pedersen Christian
Published: April 2021

Background

Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severity of coronavirus disease 2019 (COVID-19) is likely associated with the infectious dose of SARS-CoV-2 exposure. We therefore aimed to assess the association between SARS-CoV-2 exposure within households and COVID-19 severity.

Methods

We performed a Danish, nationwide, register-based, cohort study including laboratory-confirmed SARS-CoV-2–infected individuals from 22 February 2020 to 6 October 2020. Household exposure to SARS-CoV-2 was defined as having 1 individual test positive for SARS-CoV-2 within the household. Cox proportional hazards models were used to estimate the association between “critical COVID-19” within and between households with and without secondary cases.

Results

From 15 063 multiperson households, 19 773 SARS-CoV-2–positive individuals were included; 11 632 were categorized as index cases without any secondary household cases; 3431 as index cases with secondary cases, that is, 22.8% of multiperson households; and 4710 as secondary cases. Critical COVID-19 occurred in 2.9% of index cases living with no secondary cases, 4.9% of index cases with secondary cases, and 1.3% of secondary cases. The adjusted hazard ratio for critical COVID-19 among index cases vs secondary cases within the same household was 2.50 (95% confidence interval [CI], 1.88–3.34), 2.27 (95% CI, 1.77–2.93) for index cases in households with no secondary cases vs secondary cases, and 1.1 (95% CI, .93–1.30) for index cases with secondary cases vs index cases without secondary cases.

Conclusions

We found no increased hazard ratio of critical COVID-19 among household members of infected SARS-CoV-2 index cases.
Continuous Leakage-Amplified Public-Key Encryption With CCA Security
Authors: Zhang Wenzheng , Qiao Zirui , Yang Bo , Zhou Yanwei , Zhang Mingwu
Published: April 2021

Secret key leakage has become a security threat in computer systems, and it is crucial that cryptographic schemes should resist various leakage attacks, including the continuous leakage attacks. In the literature, some research progresses have been made in designing leakage resistant cryptographic primitives, but there are still some remaining issues unsolved, e.g. the upper bound of the permitted leakage is fixed. In actual applications, the leakage requirements may vary; thus, the leakage parameter with fixed size is not sufficient against various leakage attacks. In this paper, we introduce some novel idea of designing a continuous leakage-amplified public-key encryption scheme with security against chosen-ciphertext attacks. In our construction, the leakage parameter can have an arbitrary length, i.e. the length of the permitted leakage can be flexibly adjusted according to the specific leakage requirements. The security of our proposed scheme is formally proved based on the classic decisional Diffie–Hellman assumption.
Predicting effects of warming requires a whole-of-life cycle perspective: a case study in the alpine herb Oreomyrrhis eriopoda
Authors: Satyanti Annisa , Liantoro Toton , Thomas Morgan , Neeman Teresa , Nicotra Adrienne B , Guja Lydia K
Published: April 2021

Global warming is affecting plant phenology, growth and reproduction in complex ways and is particularly apparent in vulnerable alpine environments. Warming affects reproductive and vegetative traits, as well as phenology, but seldom do studies assess these traits in concert and across the whole of a plant’s life cycle, particularly in wild species. Thus, it is difficult to extrapolate from such effects to predictions about the persistence of species or their conservation and management. We assessed trait variation in response to warming in Oreomyrrhis eriopoda, an Australian native montane herb, in which populations vary in germination strategy (degree of dormancy) and growth characteristics as a function of ecological factors. Warming accelerated growth in the early stages of development, particularly for populations with non-dormant seed. The differences in growth disappeared at the transition to reproduction, when an accelerating effect on phenology emerged, to varying degrees depending on germination strategy. Overall, warming reduced flower and seed production and increased mortality, indicating a reduction in reproductive opportunities, particularly for populations with dormant seed. Developmental condition affected germination strategy of the next generation seed, leading to increased degree of dormancy and slowed germination rate. But there were no whole-scale shifts in strategy or total germination percent. Following through the life cycle reveals that warming will have some potentially positive effects (early growth rates) and some negative effects (reduced reproductive output). Ultimately, warming impacts will depend on how those effects play out in the field: early establishment and an accelerated trajectory to seed maturity may offset the tradeoff with overall seed production. Small differences among germination strategies likewise may cascade to larger effects, with important implications for persistence of species in the alpine landscape. Thus, to understand and manage the response of wild species to warming takes a whole-of-life perspective and attention to ecologically significant patterns of within-species variation.
Supervised Obesity Reduction Trial for AF ablation patients: results from the SORT-AF trial
Authors: Gessler Nele , Willems Stephan , Steven Daniel , Aberle Jens , Akbulak Ruken Oezge , Gosau Nils , Hoffmann Boris A , Meyer Christian , Sultan Arian , Tilz Roland , Vogler Julia , Wohlmuth Peter , Scholz Susanne , Gunawardene Melanie A , Eickholt Christian , Lüker Jakob
Published: April 2021

Aims

Weight management seems to be beneficial for obese atrial fibrillation (AF) patients; however, randomized data are sparse. Thus, this study aimed to investigate the influence of weight reduction on AF ablation outcomes.

Methods and results

SORT-AF is an investigator-sponsored, prospective, randomized, multicentre, and clinical trial. Patients with symptomatic AF (paroxysmal or persistent) and body mass index (BMI) 30–40 kg/m2 underwent AF ablation and were randomized to either weight-reduction (group 1) or usual care (group 2), after sleep–apnoea–screening and loop recorder (ILR) implantation. The primary endpoint was defined as AF burden between 3 and 12 months after AF ablation. Overall, 133 patients (60 ± 10 years, 57% persistent AF) were randomized to group 1 (n = 67) and group 2 (n = 66), respectively. Complications after AF-ablation were rare (one stroke and no tamponade). The intervention led to a significant reduction of BMI (34.9 ± 2.6–33.4 ± 3.6) in group 1 compared to a stable BMI in group 2 (P < 0.001). Atrial fibrillation burden after ablation decreased significantly (P < 0.001), with no significant difference regarding the primary endpoint between the groups (P = 0.815, odds ratio: 1.143, confidence interval: 0.369–3.613). Further analyses showed a significant correlation between BMI and AF recurrence for patients with persistent AF compared with paroxysmal AF patients (P = 0.032).

Conclusion

The SORT-AF study shows that AF ablation is safe and successful in obese patients using continuous monitoring via ILR. Although the primary endpoint of AF burden after ablation did not differ between the two groups, the effects of weight loss and improvement of exercise activity were beneficial for obese patients with persistent AF demonstrating the relevance of life-style management as an important adjunct to AF ablation in this setting.

Trial registration number

NCT02064114.
Divergent Gene Expression Following Duplication of Meiotic Genes in the Stick InsectClitarchus hookeri
Authors: Wu Chen , Twort Victoria G , Newcomb Richard D , Buckley Thomas R
Published: April 2021

Some animal groups, such as stick insects (Phasmatodea), have repeatedly evolved alternative reproductive strategies, including parthenogenesis. Genomic studies have found modification of the genes underlying meiosis exists in some of these animals. Here we examine the evolution of copy number, evolutionary rate, and gene expression in candidate meiotic genes of the New Zealand geographic parthenogenetic stick insect Clitarchus hookeri. We characterized 101 genes from a de novo transcriptome assembly from female and male gonads that have homology with meiotic genes from other arthropods. For each gene we determined copy number, the pattern of gene duplication relative to other arthropod orthologs, and the potential for meiosis-specific expression. There are five genes duplicated in C. hookeri, including one also duplicated in the stick insect Timema cristinae, that are not or are uncommonly duplicated in other arthropods. These included two sister chromatid cohesion associated genes (SA2 and SCC2), a recombination gene (HOP1), an RNA-silencing gene (AGO2) and a cell-cycle regulation gene (WEE1). Interestingly, WEE1 and SA2 are also duplicated in the cyclical parthenogenetic aphid Acyrthosiphon pisum and Daphnia duplex, respectively, indicating possible roles in the evolution of reproductive mode. Three of these genes (SA2, SCC2, and WEE1) have one copy displaying gonad-specific expression. All genes, with the exception of WEE1, have significantly different nonsynonymous/synonymous ratios between the gene duplicates, indicative of a shift in evolutionary constraints following duplication. These results suggest that stick insects may have evolved genes with novel functions in gamete production by gene duplication.
REGULATORY MUTATIONS OF INOSITOL BIOSYNTHESIS IN YEAST: ISOLATION OF INOSITOL-EXCRETING MUTANTS
Authors: Greenberg Miriam L , Reiner Barry , Henry Susan A
Published: April 2021

The enzyme inositol-1-phosphate synthase (I-1-P synthase), product of the INO1 locus, catalyzes the synthesis of inositol-1-phosphate from the substrate glucose-6-phosphate. The activity of this enzyme is dramatically repressed in the presence of inositol. By selecting for mutants which overproduce and excrete inositol, we have identified mutants constitutive for inositol-1-phosphate synthase as well as a mutation in phospholipid biosynthesis. Genetic analysis of the mutants indicates that at least three loci (designated OPI1, OPI2 and OPI4) direct inositol-mediated repression of I-1-P synthase. Mutants of these loci synthesize I-1-P synthase constitutively. Three loci are unlinked to each other and to INO1, the structural gene for the enzyme. A mutant of a fourth locus, OPI3, does not synthesize I-1-P synthase constitutively, despite its inositol excretion phenotype. This mutant is preliminarily identified as having a defect in phospholipid synthesis.
THE Ah PHENOTYPE. SURVEY OF FORTY-EIGHT RAT STRAINS AND TWENTY INBRED MOUSE STRAINS
Authors: Nebert Daniel W , Jensen Nancy M , Shinozuka Hisashi , Kunz Heinz W , Gill Thomas J
Published: April 2021

Forty-four inbred and four randombred rat strains and 20 inbred mouse strains were examined for their Ah phenotype by determining the induction of liver microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity (EC 1.14.14.1) by intraperitoneal treatment with either β-naphthoflavone or 3-methylcholanthrene. All 48 rat strains were found to be Ah-responsive. The maximally induced hydroxylase specific activities of the ALB/Pit, MNR/Pit, MR/Pit, SHR/Pit, and Sprague-Dawley strains were of the same order of magnitude as the basal hydroxylase specific activities of the ACI/Pit, F344/Pit, OKA/Pit, and MNR/N strains. Six of the 20 mouse strains were Ah-nonresponsive (i.e. lacking the normal induction response and presumably lacking detectable amounts of the Ah receptor). The basal hydroxylase specific activities of the BDL/N, NFS/N, STAR/N, and ST/JN mouse strains were more than twice as high as the maximally induced hydroxylase specific activity of the CBA/HT strain.——To date, 24 Ah-nonresponsive mouse strains have been identified, out of a total of 68 known to have been characterized. The reasons for not finding a single Ah-nonresponsive inbred rat strain—as compared with about one Ah-nonresponsive inbred mouse strain found for every three examined—remain unknown.
GENETIC DISSECTION OF CLONALLY INHERITED GENOMES OF POECILIOPSIS: II. INVESTIGATION OF A SILENT CARBOXYLESTERASE ALLELE
Authors: Spinella Dominic G , Vrijenhoek Robert C
Published: April 2021

According to the ratchet mechanism hypothesis, deleterious mutations should accumulate in clonal genomes of unisexual fish of the genus Poeciliopsis. This study defines one such mutant, a silent carboxylesterase allele (Es-5o) which is found in the heterozygous condition in a particular population of P. monacha-occidentalis. An antiserum to purified Poeciliopsis carboxylesterase cross-reacts with the gene product of the Es-5o allele upon immunoelectrophoresis. This finding of cross-reacting material associated with the Es-5o allele provides a useful marker for the breeding of a carboxylesterase deficient strain.
ESTIMATES OF INBREEDING IN A NATURAL POPULATION: A COMPARISON OF SAMPLING PROPERTIES
Authors: Curie-Cohen Martin
Published: April 2021

The average inbreeding coefficient f of a population can be estimated in several different ways based solely on the genotypic frequencies at a single locus. The means and variances of four different estimates have been compared. While the four estimates are equivalent when there are two alleles, the best estimates when there are three or more alleles are based upon total heterozygosity (see PDF) where x and y are the expected and observed number of heterozygotes) and the proportion of alleles that are homozygous (see PDF) where k = the number of alleles, aii = the number of AiAi homozygotes, and 2aij = the number of AiAj heterozygotes). Both are minimally biased estimates of f and have identical sampling variances when all alleles are equally frequent. However, when alleles have different frequencies, the choice between these two estimates depends on the gene frequencies and the true inbreeding coefficient of a population; f  2 is the best estimate when the true average inbreeding coefficient is suspected to be low or f = 0, while f  1 is best in populations with large average inbreeding coefficients. Approximate sampling variances of these two estimates are given for any f and any number of alleles with arbitrary gene frequencies; these approximations are accurate for samples as small as n = 100. The chi-square and maximum likelihood estimates of f are not as good for realistic sample sizes.
THE ORIGIN OF ASCOGENOUS NUCLEI IN ENDOTHIA PARASITICA
Authors: Anagnostakis Sandra L
Published: April 2021

Two conidia can fertilize a single protoperithecium of Endothia parasitica, and reassortment can occur between genes in the male nuclei early in the perithecium development.
SELFISH DNA: A SEXUALLY-TRANSMITTED NUCLEAR PARASITE
Authors: Hickey Donal A
Published: April 2021

A quantitative population genetics model for the evolution of transposable genetic elements is developed. This model shows that "selfish" DNA sequences do not have to be selectively neutral at the organismic level; indeed, such DNA can produce major deleterious effects in the host organism and still spread through the population. The model can be used to explain the evolution of introns within eukaryotic genes; this explanation does not invoke a long-term evolutionary advantage for introns, nor does it depend on the hypothesis that eukaryotic gene structure may be an evolutionary relic. Transposable genes that carried information specifying sexual reproduction in the host organism would favor their own spread. Consequently, it is tempting to speculate that some of the genes controlling sex were originally selected as transposable elements.
The isolation and sequence of missense and nonsense mutations in the cloned bacteriophage P22 tailspike protein gene.
Authors: Schwarz J J , Berget P B
Published: April 2021

Twenty-seven new mutations in the structural gene for the Salmonella typhimurium bacteriophage P22 tailspike protein have been isolated, mapped using a powerful plasmid-based genetic system and their DNA sequence changes determined. The mutations were generated by hydroxylamine treatment of the cloned gene on a plasmid expression vector. Assaying the activity of the tailspike protein produced from this plasmid and screening for plasmid mutants were accomplished by the in situ complementation of P22 capsids imbedded in soft agar to produce infectious phage. Deletion mutations in the cloned gene have been constructed by a two step procedure involving oligonucleotide linker insertion and in vitro deletion by restriction endonuclease digestion. The deletions, whose physical endpoints were determined by DNA sequencing, define 12 genetic and physical intervals into which the new mutations were mapped by marker rescue experiments. These deletions were transferred to phage P22 by recombination and used to map mutations carried on plasmids. Following mapping, the nucleotide change for each of the mutations was determined by DNA sequencing. The majority were absolute missense mutations although both amber and ochre nonsense mutations were also identified in the protein coding portion of the gene. The suppression pattern of the nonsense mutations was determined on several nonsense suppressors. Four of the mutations cause severely depressed levels of tailspike protein expression from both the cloned gene on the plasmid expression vector and from P22 phage carrying these mutations. These mutations were identified as nucleotide changes in what is probably the P22 late operon transcription terminator which immediately follows the tailspike protein coding sequence.
Palindromy and the location of deletion endpoints in Escherichia coli.
Authors: Weston-Hafer K , Berg D E
Published: April 2021

The contributions of direct and inverted repeats to deletion formation were studied by characterizing Ampr revertants of plasmids with a series of insertion mutations at a specific site in the pBR322 ampicillin resistance (amp) gene. The inserts at this site are palindromic, variable in length, and bracketed by 9- or 10-bp direct repeats of amp sequence. There is an additional direct repeat composed of 4 bp within the insert and 4 bp of adjoining amp sequence. DNA sequencing and colony hybridization of Ampr revertants showed that they contained either the parental amp sequence, implying deletion endpoints in the flanking 9- or 10-bp repeats, or a specific 1-bp substitution, implying endpoints in the 4-bp repeats. Although generally direct repeats seem to be used as deletion endpoints with a frequency proportional to their lengths, we found that with uninterrupted palindromes longer than 32 bp, the majority of deletions ended in the 4 bp, not the 9- or 10-bp repeats. This preferential use of the shorter direct repeats associated with palindromes is interpreted according to a DNA synthesis-error model in which hairpin structures formed by intrastrand pairing foster the slippage of nascent strands during DNA synthesis.
Suppressors of yeast actin mutations.
Authors: Novick P , Osmond B C , Botstein D
Published: April 2021

Suppressors of a temperature-sensitive mutation (act1-1) in the single actin gene of Saccharomyces cerevisiae were selected that had simultaneously acquired a cold-sensitive growth phenotype. Five genes, called SAC (suppressor of actin) were defined by complementation tests; both suppression and cold-sensitive phenotypes were recessive. Three of the genes (SAC1, SAC2 and SAC3) were subjected to extensive genetic and phenotypic analysis, including molecular cloning. Suppression was found to be allele-specific with respect to actin alleles. The sac mutants, even in ACT1+ genetic backgrounds, displayed phenotypes similar to those of actin mutants, notably aberrant organization of intracellular actin and deposition of chitin at the cell surface. These results are interpreted as being consistent with the idea that the SAC genes encode proteins that interact with actin, presumably as components or controllers of the assembly or stability of the yeast actin cytoskeleton. Two unexpected properties of the SAC1 gene were noted. Disruptions of the gene indicated that its function is essential only at temperatures below about 17 degrees and all sac1 alleles are inviable when combined with act1-2. These properties are interpreted in the context of the evolution of the actin cytoskeleton of yeast.
The effect of novel chromosome position and variable dose on the genetic behavior of the Responder (Rsp) element of the Segregation distorter (SD) system of Drosophila melanogaster.
Authors: Lyttle T W
Published: April 2021

In the Segregation distorter (SD) system of meiotic drive, a minimum of two trans-acting elements [Sd and E(SD)] act in concert to cause a certain probability of dysfunction for sperm carrying a sensitive allele at the Responder (Rsp) target locus. By employing a number of insertional translocations of autosomal material into the long arm of the Y chromosome, Rsp can be mapped as the most proximal locus in the 2R heterochromatin as defined both by cytology and lethal complementation tests. Several of these insertional translocations result in the transposition of Rsp to the Y chromosome, where its sensitivity remains virtually unaltered. This argues that Rsp is separable from the second chromosome centromere, that its behavior does not depend on its gross chromosomal position, and that meiotic pairing of the chromosomes carrying the various SD elements is not a prerequisite for sperm dysfunction. Several other translocations apparently leave both resulting chromosomes at least partially sensitive to SD action, suggesting that Rsp is a large subdivisible genetic element. This view is compatible with observations published elsewhere that suggest that Rsp is a cytologically large region of highly repetitive AT-rich DNA. The availability of Y-linked copies of Rsp also allows the construction of SD males carrying two independently segregating Rsp alleles; this in turn allows the production of sperm with zero, one or two Rsp copies from the same male. Examination of the relative recovery proportions of progeny arising from these gametes suggests that sperm with two Rsp copies survive at much lower frequencies than would be predicted if each Rsp acted independently in causing sperm dysfunction. Possible explanations for such behavior are discussed.
Physical and genetic characterization of a 75-kilobase deletion associated with al, a recessive lethal allele at the mouse agouti locus.
Authors: Barsh G S , Epstein C J
Published: April 2021

The agouti locus (A) of the mouse determines the timing and type of pigment deposition in the growing hair bulb, and several alleles at this locus are lethal when homozygous. Apparent instances of intragenic recombination and complementation between different recessive lethal alleles have suggested that the locus has a complex structure. We have begun to investigate the molecular basis of agouti gene action and recessive lethality by using a series of genetically linked DNA probes and pulsed field gel electrophoresis to detect structural alterations in radiation-induced agouti mutations. Hybridization probes from the Src and Emv-15 loci do not reveal molecular alterations in DNA corresponding to the ae, ax, and al alleles, but a probe from the parotid secretory protein gene (Psp) detects a 75-kilobase (kb) deletion in DNA containing the non-agouti lethal allele (al). The deletion is defined by a 75-kb reduction in the size of BssHII, NotI, NruI and SacII high molecular weight restriction fragments detected with the Psp probe and is located between 25 kb and 575 kb from Psp coding sequences. Because the genetic distance between A and Emv-15 is much less than A and Psp, there may be a preferred site of recombination close to Psp, or suppression of recombination between A and Emv-15. The al deletion has allowed us to determine the genotype of mice heterozygous for different recessive lethal alleles. We find that three different recessive lethal complementation groups are present at the agouti locus, two of which are contained within the al deletion.
The rIIA gene of bacteriophage T4. I. Its DNA sequence and discovery of a new open reading frame between genes 60 and rIIA.
Authors: Daegelen P , Brody E
Published: April 2021

We have determined the DNA sequence of the rIIA gene and have discovered a small open reading frame, rIIA.1, between genes 60 and rIIA. The predicted molecular weights of these proteins are 82,840 for rIIA and 8,124 for rIIA.1. The rIIA protein has a repeated motif which suggests that the gene has evolved by duplication. It also has a motif which suggests that it belongs to a group of ompR-like proteins that control regulation of gene expression in response to changes in the external environment. We have sequenced three different missense mutants whose mutations lie in the Ala segment of the rIIA genetic map. All three changes are found within the first 35 bp of the rIIA coding sequence. The region of control of protein synthesis is identical in the rIIA gene and in gene 44 of T4. We relate this finding to the high sensitivity of both RNAs to translational repression by the T4 regA gene product.
Dominant maternal-effect mutations causing embryonic lethality in Caenorhabditis elegans.
Authors: Mains P E , Sulston I A , Wood W B
Published: April 2021

We undertook screens for dominant, temperature-sensitive, maternal-effect embryonic-lethal mutations of Caenorhabditis elegans as a way to identify certain classes of genes with early embryonic functions, in particular those that are members of multigene families and those that are required in two copies for normal development. The screens have identified eight mutations, representing six loci. Mutations at three of the loci result in only maternal effects on embryonic viability. Mutations at the remaining three loci cause additional nonmaternal (zygotic) effects, including recessive lethality or sterility and dominant male mating defects. Mutations at five of the loci cause visible pregastrulation defects. Three mutations appear to be allelic with a recessive mutation of let-354. Gene dosage experiments indicate that one mutation may be a loss-of-function allele at a haploin sufficient locus. The other mutations appear to result in gain-of-function "poison" gene products. Most of these become less deleterious as the relative dosage of the corresponding wild-type allele is increased; we show that relative self-progeny viabilities for the relevant hermaphrodite genotypes are generally M/+/+ greater than M/+ greater than M/M/+ greater than M/Df greater than M/M, where M represents the dominant mutant allele.
Spontaneous mutation rates in mammalian cells: effect of differential growth rates and phenotypic lag.
Authors: Rudd C J , Daston D S , Caspary W J
Published: April 2021

We calculated a spontaneous rate of 26-37 x 10(-6) mutations per cell division for L5178Y MOLY (mouse lymphoma) cells at the thymidine kinase locus (tk+/(-)----tk-/-) using a procedure that isolated and segregated cells during expression. This rate was 50 times higher than when cells expressed the mutant phenotype in suspension. The higher mutation rates obtained with the in situ procedure suggest that many of the mutants, whether expressed or unexpressed, grew more slowly than wild-type cells prior to selection with trifluorothymidine (TFT), implying that the slow growth phenotype is expressed earlier than the TFTr (TFT-resistant) phenotype. The loss of mutants was not restricted to cells forming small colonies; the mutation rate for cells forming large colonies was more than ten times higher using the in situ procedure. In this new procedure, the cells expressed spontaneous mutations while growing in semisolid medium for up to 3 days without TFT. Mutants were then selected in situ by adding an overlay of TFT and the visible colonies were analyzed after 11 days. Cells with spontaneous mutations at the tk locus required approximately 30 hr for the more rapidly expressing cells with new mutations to be detected. Most of the TFTr colonies selected after 60 hr of growth in semisolid medium represented independent mutations that had accumulated during the first 30 hr.(ABSTRACT TRUNCATED AT 250 WORDS)