bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fatal Case of COVID-19 in a Child with ALL: A Cytokine Storm and Hyperferritinemic MODS
Authors: Kamit Fulya , Malbora Baris , Atay Avni , Bayirli Derya Turan , Bektas Metin
Published: January 2021

Since little is known about dysregulated hyperinflammatory immunological responses causing acute severe infection and multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (COVID-19), the available data on therapies for severe presentations in children are very limited. Describing experiences of severe pediatric COVID-19 presentations in more detail will help improve clinical practice.

In this case report, we describe the complete clinical course of a 9-year-old girl previously diagnosed with Angelman syndrome and high-risk T cell acute lymphoblastic leukemia who had been receiving reinduction chemotherapy, presented with pneumonia and acute respiratory distress syndrome, and progressively developed hyperferritinemic multiple-organ failure, a cytokine storm, and coagulopathy associated with COVID-19. She was treated with therapeutic plasma exchange, tocilizumab, hydrocortisone, and favipiravir, but she died 7 days after her admission into our pediatric intensive care unit.

The utility of therapeutic plasma exchange with other immunomodulatory therapies in severe presentations requires further trials. The spectrum of the inflammatory phenotypes associated with COVID-19 should be investigated and well defined to initiate the optimal treatment strategy on time.
The Effects of Endotracheal Suctioning on Hemodynamic Parameters and Tissue Oxygenation in Pediatric Intensive Care Unit
Authors: Misirlioglu Merve , Horoz Ozden O. , Yildizdas Dinçer , Ekinci Faruk , Yontem Ahmet , Menemencioglu Ayse , Salva Gul
Published: January 2021

Airway secretions may increase in intubated patients due to the impaired mucociliary clearance, impaired cough reflex, abnormal glottic function, insufficient moisturizing, and respiratory tract infections. As with any intervention, patients should be cautiously monitored for possible complications during the endotracheal suctioning. Procedure-related changes in the cerebral and somatic tissue oxygenation, hemodynamics, and oxygen saturation can be observed in these patients. It is important to ensure maintenance of tissue oxygenation during these and other interventions performed in critically ill children. The aim of this study was to investigate the effects of the endotracheal suctioning on tissue oxygenation in patients undergoing mechanical ventilation in the pediatric intensive care unit. Cerebral and somatic near-infrared spectroscopy (NIRS) monitoring were performed noninvasively using standardized NIRS equipment as a means of monitoring regional tissue oxygenation. Vital signs, level of sedation, pain scores, and somatic and cerebral tissue oxygenation values of mechanically ventilated patients were recorded prospectively 5 minutes before, during, and after endotracheal suctioning. Cerebral NIRS measurements did not exhibit any statistically significant changes during endotracheal suctioning. Somatic NIRS levels changed significantly before, during, and after endotracheal suctioning and remained low throughout the procedure. Endotracheal suctioning is an invasive intervention that facilitates clearance of tracheal secretions and maintenance of the oxygenation and ventilation. The maintenance of the tissue oxygenation should be documented during these and other interventions performed on critically ill children. Somatic NIRS is a useful tool for monitoring tissue oxygenation during such procedures.
Teaching About Geometric Optics: Teacher’s Notes
Authors: Nelson Jane Bray , Nelson Jim
Published: January 2021

Teaching About Geometric Optics: Teacher’s Notes guides physics teachers to help students develop a foundational understanding of geometric optics. The cornerstone of photonics systems, geometric optics, have applications in a wide range of industries including technology, medical, and military sectors. This book covers the basics of light propagation, reflection and refraction and the use of simple optical elements such as mirrors, prisms, lenses, and optical fibers.

Key elements include:46 activities on geometric optics, covering a wide range of topicsEasy implementation, with a copy-ready student sheet and teacher notes includedReferences to appropriate Next Generation Science Standards

Physics educators and teachers in other science disciplines will fi nd this book to be an invaluable resource to teach the fundamentals. This volume contains only the notes for Teaching About Geometric Optics: Student Edition.
Capacitive and illumination systems based on printed and hybrid electronics
Authors: Peřinka Nikola , Pozo Borja , Fernández de Gorostiza Erlantz , Mendes-Felipe Cristian , Vilas-Vilela José Luis , Lanceros-Méndez Senentxu
Published: January 2021

Functional electronic systems have been screen- or inkjet-printed on different plastic substrates, including polyethylene terephthalate, polycarbonate and polycarbonate/acrylonitrile butadiene styrene blends. Mutual capacitive sensors were designed and printed on flexible substrates and the capacitive response and functionality of the printed sensor with integrated passive electronic components was demonstrated. The applicability of both, inkjet printing and screen printing for the development of such capacitive sensors was evaluated. The influence of the substrate, sensor design and the printing technique parameters on both printability and functionality are discussed. Further, a flexible illumination system was developed, where the printed circuit was combined with surface mounted light emitting diodes and integrated circuits. Finally, the developed capacitive sensors and the illumination system were connected to each other to demonstrate the connectivity and interoperability of the different printed circuit components.
Large gradients via correlation in random parameterized quantum circuits
Authors: Volkoff Tyler , Coles Patrick J
Published: January 2021

Scaling of variational quantum algorithms to large problem sizes requires efficient optimization of random parameterized quantum circuits. For such circuits with uncorrelated parameters, the presence of exponentially vanishing gradients in cost function landscapes is an obstacle to optimization by gradient descent methods. In this work, we prove that reducing the dimensionality of the parameter space by utilizing circuit modules containing spatially or temporally correlated gate layers can allow one to circumvent the vanishing gradient phenomenon. Examples are drawn from random separable circuits and asymptotically optimal variational versions of Grover’s algorithm based on the quantum alternating operator ansatz. In the latter scenario, our bounds on cost function variation imply a transition between vanishing gradients and efficient trainability as the number of layers is increased toward

O

(

2

n
/
2

)

, the optimal oracle complexity of quantum unstructured search.
Ferromagnetic gyroscopes for tests of fundamental physics
Authors: Fadeev Pavel , Timberlake Chris , Wang Tao , Vinante Andrea , Band Y B , Budker Dmitry , Sushkov Alexander O , Ulbricht Hendrik , Jackson Kimball Derek F
Published: January 2021

A ferromagnetic gyroscope (FG) is a ferromagnet whose angular momentum is dominated by electron spin polarization and that will process under the action of an external torque, such as that due to a magnetic field. Here we model and analyze FG dynamics and sensitivity, focusing on practical schemes for experimental realization. In the case of a freely floating FG, we model the transition from dynamics dominated by libration in relatively high externally applied magnetic fields, to those dominated by precession at relatively low applied fields. Measurement of the libration frequency enables in situ determination of the magnetic field and a technique to reduce the field below the threshold for which precession dominates the FG dynamics. We note that evidence of gyroscopic behavior is present even at magnetic fields much larger than the threshold field below which precession dominates. We also model the dynamics of an FG levitated above a type-I superconductor via the Meissner effect, and find that for FGs with dimensions larger than about 100 nm the observed precession frequency is reduced compared to that of a freely floating FG. This is due to an effect akin to negative feedback that arises from the distortion of the field from the FG by the superconductor. Finally we assess the sensitivity of an FG levitated above a type-I superconductor to exotic spin-dependent interactions under practical experimental conditions, demonstrating the potential of FGs for tests of fundamental physics.
Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema
Authors: Xiong Ao , Xiong Renping , Yu Jing , Liu Yijia , Liu Ke , Jin Ge , Xu Jianzhong , Yan Jun
Published: January 2021

Background

Traumatic brain edema (TBE) is caused by a specific water channel mediated by membrane aquaporins. Aquaporin-4 (AQP4) plays an especially important role in this process, but the relationship between AQP4 and TBE remains unclear. The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury (TBI), as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.

Methods

The adult male Wistar rats we divided into a sham group and a TBI group, the latter of which was further divided into 1, 3, 6, 12, 24 and 72 hours (h) and 15 days (d) post injury subgroups. A proper TBI model was established, and brain edema was assessed in each group by water content. We measured the abundance of various proteins, including hypoxia inducible factor-1α (HIF-1α), AQP4, microtubule-associated protein 2 (MAP2), tau-5 protein, phosphorylated level of TAU, synaptophysin, cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB and general control nonrepressed 2, in each group. Hippocampal neurons and spatial memory test were analyzed in different time points.

Results

Compared with that in the sham group, the level of AQP4 in hippocampal neurons began to significantly increase at 1 h post TBI and then decreased at 15 d post TBI. During this time frame, AQP4 level peaked at 12 and 72 h, and these peaks were closely correlated with high brain water content. HIF-1α displayed a similar trend. Conversely, levels of MAP2 began to decrease at 1 h post TBI and then increase at 15 d post TBI. In addition, the most severe brain edema in rats was found at 24 h post TBI, with neuronal loss and hippocampal dendritic spine injury. Compared to those in the sham group, rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time.

Conclusions

AQP4 level was closely correlated with severity of brain edema, and abnormal levels thereof aggravated such severity after TBI.
Hybrid Learning Approach Toward Situation Recognition and Handling
Authors: Rajaby Faghihi Hossein , Fazli MohammadAmin , Habibi Jafar
Published: January 2021

We propose a novel hybrid learning approach to gain situation awareness in smart environments by introducing a new situation identifier that combines an expert system and a machine learning approach. Traditionally, expert systems and machine learning approaches have been widely used independently to detect ongoing situations as the main functionality in smart environments in various domains. Expert systems lack the functionality to adapt the system to each user and are expensive to design based on each setting. On the other hand, machine learning approaches fail in the challenge of cold start and making explainable decisions. Using both of these approaches enables the system to use user’s feedback and capture environmental changes while exploiting the initial expert knowledge to solve the mentioned challenges. We use decision trees and situation templates as the core structure to interpret sensor data. To evaluate the proposed method, we generate a new human-annotated dataset simulating a smart environment. Our experiments show superior results compared with the initial expert system and the machine learning approach while preserving the initial expert system’s interpretability.
COMPARISON OF THE RESTRICTION ENDONUCLEASE DIGESTION PATTERNS OF MITOCHONDRIAL DNA FROM NORMAL AND MALE STERILE CYTOPLASMS OF ZEA MAYS L
Authors: Borck Kathleen S , Walbot Virginia
Published: January 2021

High resolution gel electrophoresis has allowed the assignment of fragment number and molecular weight to EcoRI, SalI and PstI restriction fragments of mitochondrial DNA from B37 normal (N) and B37 T, C and S male sterile cytoplasmic types of maize. A minimum complexity of 450-475 kb has been established. Hybridization of cloned EcoRI fragments to restriction digests of total mitochondrial DNA suggests that at least 80% of the genome is composed of unique sequences. Restriction fragments of identical size in N, T, C and S contain similar sequence information as evidenced by their hybridization behavior.—The total SalI digest and the larger PstI fragments representing 80% of the total complexity were used to calculate the fraction of shared fragments of each pairwise combination of cytoplasmic types. The C type mtDNA is most closely allied with the other mtDNAs and shares 67% of fragments with S, 65% with N, and 60% with T. The S type mtDNA is quite divergent from N (53% shared fragments) and T (56% shared fragments). N and T share 59% of the fragments. These results are discussed in terms of the origin of mtDNA diversity in maize.
MOLECULAR CHARACTERIZATION OF RIBOSOMAL GENES ON THE Ybb- CHROMOSOME OF DROSOPHILA MELANOGASTER
Authors: Endow Sharyn A
Published: January 2021

The question of whether the Ybb  - chromosome contains ribosomal genes has been examined by using Southern blot analysis and comparing rDNA hybridization patterns for X/X and X/Ybb  - DNA. The results demonstrate that the Ybb  - chromosome contains sequences that hybridize to an rDNA probe under stringent conditions. Differential hybridization of some of these sequences with DNAs corresponding to different regions of a complete ribosomal gene repeat provides evidence that some of the genes on the Ybb  - chromosome are type 2 repeats. Because data obtained by other workers suggest that type 2 repeats are transcribed only to low levels, these repeats may be classed as "nonfunctional". A further finding is that the ribosomal genes on the Ybb  - chromosome do not undergo multiple rounds of DNA replication during polytenization of X/Ybb  - cells.
MUTANTS OF PARAMECIUM DEFECTIVE IN CHEMOKINESIS TO FOLATE
Authors: DiNallo Mary C , Wohlford Mark , Van Houten Judith
Published: January 2021

Ten mutant lines of Paramecium tetraurelia defective in attraction to folate were isolated and examined. All mutants were normal in response to other attractants and repellents tested. One mutant was able to accumulate in folate given sufficient time. All mutations were recessive and behaved as single site Mendelian lesions. Complementation tests indicate that the mutants fall into three complementation groups. Mutants of Group 2 fall into two phenotypic classes and probably represent two alleles of the mutated fol2 gene. Possible sites of the mutants' blocks in chemoresponse are discussed.
RADIATION-SENSITIVE MUTANTS OF CAENORHABDITIS ELEGANS
Authors: Hartman Philip S , Herman Robert K
Published: January 2021

Nine rad (for abnormal radiation sensitivity) mutants hypersensitive to ultraviolet light were isolated in the small nematode Caenorhabditis elegans. The mutations are recessive to their wild-type alleles, map to four of the six linkage groups in C. elegans and define nine new games named rad-1 through rad-9. Two of the mutants—rad-1 and rad-2—are very hypersensitive to X rays, and three—rad-2, rad-3 and rad-4—are hypersensitive to methyl methanesulfonate under particular conditions of exposure. The hypersensitivity of these mutants to more than one DNA-damaging agent suggests that they may be abnormal in DNA repair. One mutant—rad-5, a temperature-sensitive sterile mutant—shows an elevated frequency of spontaneous mutation at more than one locus; rad-4, which shows a cold-sensitive embryogenesis, reduces meiotic X-chromosome nondisjunction tenfold and partially suppresses some but not all mutations that increase meiotic X-chromosome nondisjunction; the viability of rad-6 hermaphrodites is half that of rad-6 males at 25°; and newly mature (but not older) rad-8 hermaphrodites produce many inviable embryo progeny. Meiotic recombination frequencies were measured for seven rad mutants and found to be close to normal.
AN ASSESSMENT OF "HIDDEN" HETEROGENEITY WITHIN ELECTROMORPHS AT THREE ENZYME LOCI IN DEER MICE
Authors: Aquadro Charles F , Avise John C
Published: January 2021

Allelic heterogeneity within protein electromorphs at three loci was examined in populations of deer mice (Peromyscus maniculatus) collected from five localities across North America. We used a variety of electrophoretic techniques (including several starch and acrylamide conditions, gel-sieving, and isoelectric focusing) plus heat denaturation. Of particular interest was the supernatant glutamate oxalate transaminase system (GOT-1; aspartate aminotransferase-1 of some authors), which under standard electrophoretic conditions had been shown to exhibit basically a two-allele polymorphism throughout the range of maniculatus. The use of all of the above techniques failed to uncover any additional variation for GOT-1 in these populations. Similarly, no new scorable variation was resolved at the essentially monomorphic malate dehydrogenase-1 locus by additional conditions of electrophoresis. In marked contrast to the results for the above two enzymes, the use of multiple conditions of electrophoresis resolved the 8 standard-condition electromorphs of esterase-1 into a total of 23 variants showing strong geographic differentiation in frequency. These 23 electromorphs were further divided into a total of 35 variants by thermal stability studies. However, the allelic nature of all of the thermal stability esterase variants remains to be documented. The results of this study, taken together with the remarkable geographic heterogeneity for this species in ecology, morphology, karyotype and mitochondrial DNA sequence, suggest that some form of balancing selection may be acting to maintain the GOT-1 polymorphism.
DOMINANT X-CHROMOSOME NONDISJUNCTION MUTANTS OF CAENORHABDITIS ELEGANS
Authors: Herman Robert K , Kari Claire K , Hartman Philip S
Published: January 2021

Two classes of frameshift suppressors distributed at 22 different loci were identified in previous studies in the yeast Saccharomyces cerevisiae. These suppressors exhibited allele-specific suppression of +1 G:C insertion mutations in either glycine or proline codons, designated as group II and group III frameshift mutations, respectively. Genes corresponding to representative suppressors of each group have been shown to encode altered glycine or proline tRNAs containing four base anticodons.—This communication reports the existence of a third class of frameshift suppressor that exhibits a wider range in specificity of suppression. The suppressors map at three loci, suf12, suf13, and suf14, which are located on chromosomes IV, XV, and XIV, respectively. The phenotypes of these suppressors suggest that suppression may be mediated by genes other than those encoding the primary structure of glycine or proline tRNAs.
GENIC VARIATION IN ABUNDANT SOLUBLE PROTEINS OF DROSOPHILA MELANOGASTER AND DROSOPHILA PSEUDOOBSCURA
Authors: Singh Rama S , Coulthart Michael B
Published: January 2021

Genic variation was surveyed for 20 proteins of Drosophila melanogaster and 18 proteins of D. pseudoobscura. Analysis was by extraction and one-dimensional polyacrylamide gel electrophoresis under nondenaturing conditions, followed by staining with Coomassie Brilliant Blue to detect soluble proteins present in relatively large amounts ("abundant soluble proteins"). D. melanogaster was polymorphic for 65% of its protein loci and an individual was heterozygous for 10% of its loci. The respective figures for D. pseudoobscura were 61% and 11%. These estimates of genic variation fall between previously published estimates obtained for these species by one-dimensional electrophoresis of soluble enzymes and those obtained by two-dimensional electrophoresis of solubilized abundant proteins. However, variation for both species could be strongly partitioned between loci, on the basis of tissue and stage expression of the proteins. The results are discussed with respect to their bearing on the possibility that abundant proteins constitute a distinct class of proteins less polymorphic than soluble enzymes.
CHROMOSOME INTERACTIONS IN DROSOPHILA MELANOGASTER. II. TOTAL FITNESS
Authors: Seager Robert D , Ayala Francisco J , Marks R William
Published: January 2021

In a large experiment, using nearly 200 population cages, we have measured the fitness of Drosophila melanogaster homozygous (1) for the second chromosome, (2) for the third chromosome, and (3) for both chromosomes. Twentyfour second chromosomes and 24 third chromosomes sampled from a natural population were tested. The mean fitness of the homozygous flies is 0.081 ± 0.014 for the second chromosome, 0.080 ± 0.017 for the third chromosome, and 0.079 ± 0.024 for both chromosomes simultaneously. Assuming that fitnesses are multiplicative (the additive fitness model makes no sense in the present case because of the large selection coefficients involved), the expected mean fitness of the homozygotes for both chromosomes is 0.0066; their observed fitness is more than ten times greater. Thus, it appears that synergistic interactions between loci are considerable; and that, consequently, the fitness function substantially departs from linearity. Two models are tentatively suggested for the fitness function: a "threshold" model and a "synergistic" model.—The experiments reported here confirm previous results showing that the concealed genetic load present in natural populations of Drosophila is sufficient to account for the selective maintenance of numerous polymorphisms (of the order of 1000).
MARKER-DEPENDENT RECOMBINATION IN T4 BACTERIOPHAGE. I. OUTLINE OF THE PHENOMENON AND EVIDENCE SUGGESTING A MISMATCH REPAIR MECHANISM
Authors: Shcherbakov V P , Plugina L A , Kudryashova E A , Efremova O I , Sizova S T , Toompuu Oleg G
Published: January 2021

In standard crosses, some rIIB mutants of T4 phage were found to be susceptible to an extra recombination mechanism to which the other mutants were much less susceptible. The following observations were interpreted as evidence for the mismatch-repair nature of the phenomenon: (1) Marker-dependent recombination generates exclusively double exchanges at both sides of the marker. (2) Marker-dependent recombination is highly sensitive to DNA base sequence at the site of the marker and to that at the corresponding site on the chromosome of the other parent. (3) Within certain limits, the contribution of the marker-dependent mechanism to the total recombination frequency is distance-independent and thus constitutes a constant component.
INDUCTION OF MUTATIONS BY γ-RAYS IN PREGONIAL GERM CELLS OF ZEBRAFISH EMBRYOS
Authors: Walker Charline , Streisinger George
Published: January 2021

Specific locus (gol-1) germ line mutations are induced by γ-rays with high frequencies (about 10-5 r-1) during cleavage divisions in zebrafish. Mutant clone sizes range from 3 to 50% of the total number of germ cells, with a mean of about 10%, when embryos are exposed between the 16 and 103 cell stages. About five pregonial cells are calculated to be present during the cleavage period.
EVIDENCE FOR X-LINKAGE OF STEROID SULFATASE IN THE MOUSE: STEROID SULFATASE LEVELS IN OOCYTES OF XX AND XO MICE
Authors: Gartler Stanley M , Rivest Martha
Published: January 2021

The steroid sulfatase (STS) levels in mature oocytes of XX and XO mice were assayed along with lactate dehydrogenase (LDH), an autosomal marker, and glucose-6-phosphate dehydrogenase (G6PD), a known X-linked gene. LDH levels in XX and XO oocytes were equal, whereas STS and G6PD levels were approximately twice as high in XX oocytes as in XO oocytes. These results indicate that the STS gene is X-linked in the mouse just as it is in humans. Assays of STS in kidney tissue of XX and XO mice indicated dosage compensation for the gene, which is different from that observed in humans.
GENETIC CHARACTERIZATION OF THE SufJ FRAMESHIFT SUPPRESSOR IN SALMONELLA TYPHIMURIUM
Authors: Bossi Lionello , Kohno Tadahiko , Roth John R
Published: January 2021

A new suppressor of +1 frameshift mutations has been isolated in Salmonella typhimurium. This suppressor, sufJ, maps at minute 89 on the Salmonella genetic map between the argH and rpo(rif) loci, closely linked to the gene for the ochre suppressor tyrU(supM). The suppressor mutation is dominant to its wild-type allele, consistent with the suppressor phenotype being caused by an altered tRNA species. The sufJ map position coincides with that of a threonine tRNA(ACC/U) gene; the suppressor has been shown to read the related fourbase codons ACCU, ACCC, ACCA.—The ability of sufJ to correct one particular mutation depends on the presence of a hisT mutation which causes a defect in tRNA modification. This requirement is allele specific, since other frameshift mutations can be corrected by sufJ regardless of the state of the hisT locus.—Strains carrying both a sufJ and a hisT mutation are acutely sensitive to growth inhibition by uracil; the inhibition is reversed by arginine. This behavior is characteristic of strains with mutations affecting the arginine-uracil biosynthetic enzyme carbamyl phosphate synthetase. The combination of two mutations affecting tRNA structure may reduce expression of the structural gene for this enzyme (pyrA).
GENE INTERACTIONS BETWEEN POTASSIUM-SENSITIVE AND POTASSIUM-RESISTANT MUTATIONS OF PARAMECIUM TETRAURELIA
Authors: Cronkite Donald L
Published: January 2021

Two unlinked recessive mutations (ks-1 and ks-2) have been induced in Paramecium tetraurelia stock 51. Wild-type survives and grows when up to 30 mm KCl is added to the medium, but the mutants cease to grow and die when added KCl reaches 20-25 m m. These K+-sensitives have been crossed to stocks containing the K+-resistant genes, fA (very resistant) and kA(moderately resistant). All four genes are unlinked. Double mutants of ks-1 and either kA or fA are as resistant as the resistant member of the pair. Doubles of ks-2 and kA are like wild type, and doubles of ks-2 and fA are shifted from high resistance toward wild type. Gene ks-2 acts like a suppressor of kA and fA. This suppression can be understood in terms of the known biochemical defects of the mutants.
APPLICATION OF THE OVARIAN TERATOMA MAPPING METHOD IN THE MOUSE
Authors: Eppig Janan T , Eicher Eva M
Published: January 2021

Murine ovarian teratomas were used to determine recombination percentages for gene-gene and centromere-gene intervals. Data were obtained utilizing a recombinant inbred strain, LTXBJ, and a number of newly developed LT/SvEi congenic strains. ——Centromere-gene recombination was measured at 11.3 ± 1.2% for the centromere of chromosome 7 – Gpi-1 interval and 15.8 ± 2.4% for the centromere of chromosome 14 – Np-1 interval using the ovarian teratoma method. The centromere – Np-1 interval was measured at 26.5 ± 3.6% using a standard backcross involving the Rb6Bnr Robertsonian translocation as a centromere marker. ——To assess the accuracy of the ovarian teratoma mapping method, we compared the recombination frequency obtained for the Mpi-1–Mod-1 interval on chromosome 9 using the ovarian teratoma method to that obtained using a standard backcross. The recombination percentage was 22.9 ± 5.4 using the ovarian teratoma method and 18.6 ± 3.3 using the backcross method, indicating that the two methods produce equivalent estimates of recombination. In addition, for centromere-gene intervals known to be more than 30 cM in length, the ovarian teratoma method was consistent with classical recombination methods, yielding high recombination percentages. We conclude from these results that the ovarian teratoma mapping method is a reliable method for estimating recombination frequencies and the most accurate method available for estimating centromere-gene recombination frequency in the mouse.
THE EXPERIMENTAL ASSESSMENT OF FITNESS IN DROSOPHILA. II. A COMPARISON OF COMPETITIVE AND NONCOMPETITIVE MEASURES
Authors: Haymer D S , Hartl D L
Published: January 2021

Twelve diverse strains of Drosophila melanogaster have been examined with respect to their individual fitness components and with respect to their relative performance under competitive and noncompetitive conditions. Individual fitness components included estimates of time until successful copulation (t), fecundity (f) and egg-to-adult viability (v), and a composite index of overall fitness of the form fv/t was used for comparisons among strains. Noncompetitive performance was assessed in terms of the biomass (standing crop) and productivity of equilibrium experimental populations. Competitive performance was assessed in terms of relative competitive ability vis-à-vis a standard compound-autosome-bearing strain in single-generation tests. A significant correlation was found between the composite index of individual fitness components and the competitive compound-autosome test. Although the biomass and productivity of equilibrium populations were correlated with each other, neither of these noncompetitive measures was correlated with individual fitness components or with the composite index. We suggest that the performance of strains in such noncompetitive tests may be related to what Wright has called the "mean selective value" of the populations. Judging from their association with the composite index of individual fitness components, competitive tests such as the compound-autosome test seem to be related more nearly to the average Darwinian fitness of the populations.
MARKER RESCUE FROM BLEOMYCIN-TREATED CHLAMYDOMONAS REINHARDI
Authors: Hourcade Dennis E
Published: January 2021

A new method has been developed for gene transfer in eukaryotic cells. Chlamydomonas reinhardi, a unicellular eukaryotic alga, was treated with a lethal dose of bleomycin, an agent that induces chromosome breakage. Bleomycin-treated cells were mated with untreated cells, and the mixture was plated onto selective agar medium. The progeny that arose contained the genetic markers from the untreated parent plus a subset of the genetic markers from the bleomycin-treated parent. Those markers derived from the untreated parent were stable, whereas those recovered from the bleomycin-treated parent were often unstable. Markers closely linked in the bleomycin-treated parent were usually rescued or lost together, whereas distantly linked or unlinked markers were rescued or lost independently. These results suggest that bleomycin treatment of C. reinhardi leads to the formation of chromosome fragments, and fusion of bleomycin-treated cells to untreated cells results in the rescue of some of these fragments. This procedure provides a new means of gene transfer that may be useful for genetic mapping, genetic engineering and for the study of genetic organization.
TRANSPOSABLE ELEMENTS IN MENDELIAN POPULATIONS. III. STATISTICAL RESULTS
Authors: Kaplan Norman L , Brookfield John F Y
Published: January 2021

Methods are proposed for estimating the parameters in the frequency spectrum derived from the model of Langley, Brookfield and Kaplan for the evolution of a transposable element in a finite Mendelian population. Statistical properties of these estimates are studied, and the results are supported with simulation data. The effects on the estimates caused by possible insensitivities of the experimental technique are also discussed. To illustrate the proposed methodology, the data of Montgomery and Langley are analyzed.
STUDIES OF ENZYME POLYMORPHISM IN THE KAMUELA POPULATION OF DROSOPHILA MERCATORUM. III. EFFECTS OF VARIATION AT THE αGPD LOCUS AND SUBFLIGHT STRESS ON THE ENERGY CHARGE AND GLYCOLYTIC INTERMEDIATE CONCENTRATIONS
Authors: Clark R L , Boerwinkle Eric , Brewer G J , Sing C F
Published: January 2021

We have employed a "level crossing" strategy to study the primary effects of an enzyme polymorphism in Drosophila mercatorum. This strategy consists of following genetic differences across intervening phenotypes to possible fitness effects. In this paper, we report the steady state concentrations of the glycolytic intermediates and the adenylates (intervening phenotypes) in two genotypes (αGPD-F, αGPD-S) at two stress levels (rest, subflight). We did not detect a genotype or a genotype by stress interaction effect on glycolytic intermediate or adenylate concentrations despite the ability of the experimental design to detect a 20 to 50% difference from the mean of a control. The flux of glycolysis is adequate to maintain the energy charge in both strains under the stress levels considered. If there is a fitness difference between these αGPD variants, it is unlikely to be a result of modifications of glycolysis. Subflight stress, however, resulted in an increase in metabolic flux. The observed pattern of intermediate concentration differences is consistent with the modulation of glycolysis by the ratio of the ATP and AMP concentrations acting on phosphofructokinase activity.
PAIRING COMPETITION BETWEEN IDENTICAL AND HOMOLOGOUS CHROMOSOMES IN RYE AND GRASSHOPPERS
Authors: Santos J L , Orellana J , Giraldez R
Published: January 2021

Meiotic pairing preferences between identical and homologous but not identical chromosomes were analyzed in spontaneous tetraploid/diploid chimeras of three male grasshoppers (Eyprepocnemis plorans) whose chromosome pair 11 were heterozygous for C-banding pattern and in four induced tetraploid/diploid chimaeral rye plants (Secale cereale) heterozygous for telomeric heterochromatin C-bands in chromosomes 1R and 2R. In the grasshoppers, a preference for identical over homologous pairing was observed, whereas in rye both a preference for homologous rather than identical pairing and random pairing between the four chromosomes of the set was found. From the results in rye, it can be deduced that pairing preferences do not depend exclusively on the similarities between chromosomes involved. It is suggested that genotypic or cryptic structural differences between the homologous chromosomes of each pair analyzed might be responsible for the pairing preferences found. This hypothesis can also explain the results obtained in grasshoppers, although the possibility of premeiotic association cannot be excluded in this material.
CYCLOPHOSPHAMIDE-INDUCED IN VIVO SISTER CHROMATID EXCHANGES (SCE) IN MUS MUSCULUS. III. QUANTITATIVE GENETIC ANALYSIS
Authors: Reimer Dorothy L , Singh Shiva M
Published: January 2021

In vivo cyclophosphamide (CP)-induced sister chromatid exchanges (SCEs) were evaluated in females from five genetic strains of mice (C57BL/6J, C3H/S, 129/ReJ, BALB/c and DBA/2) and their F1 hybrids. Baseline (noninduced) SCE values differ significantly among strains, 129/ReJ having the lowest and DBA/2 having the highest mean SCE per cell values. In general, the baseline SCE of a given F1 is within the range of its corresponding parental strains or near the lower parental value. Furthermore, there is a genotype-dependent increase in mean SCEs per cell with CP dose. Strain differences in SCE induction are noted particularly at the two higher CP doses (4.50 and 45.0 mg/kg). In general, F1 hybrids involving a strain with high induced SCEs and a strain with low induced SCEs exhibit mean SCE values that are closer to the value of the lower strain. F1s involving two strains with high SCEs or two strains with low SCEs yield SCEs not different from parental strains. The method of diallel cross analysis showed the order of dominance of these strains in SCE induction to be 129/ReJ BALB/c C3H/S DBA/2 C57BL/6J. These results support the involvement of predominantly nonadditive genetic factors as major gene(s) in SCE induction. In addition, involvement of random and independent events in SCE induction is suggested by the distribution of SCEs which follows a Poisson distribution.
IDENTIFICATION OF AN AUTOSOMAL LOCUS AFFECTING STEROID SULFATASE ACTIVITY AMONG INBRED STRAINS OF MICE
Authors: Erickson Robert P , Harper Kenneth , Kramer James M
Published: January 2021

We have found an activity variant for testicular and liver steroid sulfatase among inbred strains of mice that is not X-linked. C57BL/6J, SM/J and SWR/J testicular extracts hydrolyze 3H-dehydroepiandrosterone sulfate twice as rapidly as do A/J extracts. The C3H/HeJ and DBA/2J strains were intermediate. The Km values for C57BL/6J and A/J are 2.29 ± 0.10 and 1.01 ± 0.02 μM, respectively. The F1 values in both directions were intermediate, which argues against X-linkage of this trait. F2 values show scattered high-intermediate-low values compatible with assay variation superimposed on the segregation of codominant alleles. When assayed for both testicular and liver steroid sulfatase, nine recombinant inbred lines between A/J and C57BL/6J segregate to near the parental strain values. Thus, this activity variation for steroid sulfatase appears to be determined by a single gene, which is not X-linked. Sex and steroidal hormone differences in liver steroid sulfatase activity were not present in the A/J strain, but females of the C57BL/6J and some recombinant inbred lines had higher levels. Electrophoretic studies only disclosed a variant in the SM/J strain, which seems to be secondary to the well-known neuraminidase variation in SM/J.
EPISTATIC GROUPING OF REPAIR-DEFICIENT MUTANTS IN NEUROSPORA: COMPARATIVE ANALYSIS OF TWO uvs-3 ALLELES, uvs-6 AND THEIR mus DOUBLE MUTANT STRAINS
Authors: Käfer Etta
Published: January 2021

The nuclease halo mutant, nuh-4, of Neurospora crassa was identified conclusively as an allele of uvs-3, a gene involved in error-prone DNA repair. Like uvs-3, nuh-4 showed spontaneous mutator effects, and any previous contradictory findings were found to be due to newly arisen mutants. In normal strains the two alleles are noncomplementing and indistinguishable for sensitivity to UV and methyl methanesulfonate (MMS). Like uvs-3, nuh-4 lacked secretion of the extracellular enzyme, DNase A, a Ca++-dependent strand-nonspecific endonuclease which was found to be phosphate repressible. However, nuh-4 differed from uvs-3 in showing much higher conidial viability and lower sensitivity to ionizing radiation and mitomycin C.——Epistatic relationships of the two uvs-3 alleles with seven other MMS-sensitive mutants were determined and compared with those of the highly X-ray-sensitive mutant, uvs-6. Three epistatic groups were found, based on survival of double mutant strains relative to that of their component single mutant strains after treatment with MMS. Both, uvs-3 and nuh-4, were epistatic to mus-9 which also is a mutator. None of the three produced viable double mutants in crosses to uvs-6. On the other hand, uvs-6, but not the uvs-3 alleles, was found to be epistatic to mus-7 and mus-10. The excision-defective uvs-2 and mus-8 both showed synergism with the uvs-3 alleles and with uvs-6, forming a third, separate epistatic group.
Twelve Years after the Financial Crisis—Too-big-to-fail is still with us
Authors: Hellwig Martin
Published: January 2021

This article comments on the Consultation Report published by the Financial Stability Board (FSB) evaluating the success of regulatory reforms since the global financial crisis of 2007–2009. It argues that the FSB’s assessment of the role of equity is too narrow, being phrased in terms of bankruptcy avoidance and risk-taking incentives, without attention to debt overhang creating distortions in funding choices, the systemic impact of ample equity reducing deleveraging needs after losses, or equity contributing to smoothing of lending and asset purchases over time. The FSB’s treatment of systemic risk also pays too little attention to the mutual interdependence of different parts of the system, which is not well captured by linear causal relationships. Finally, the article points out that bank resolution of systemically important institutions is still not viable, due to lack of political acceptance of single-point-of-entry procedures and bail-in. Within the European Union, this viability is further undermined by the lack of sufficient funding for banks in resolution and the lack of fiscal backstops.
Circumstance, Answerability, and Luck
Authors: Radoilska Lubomira
Published: January 2021

This paper identifies a distinctive kind of moral luck, deep circumstantial luck, and then explores its effects on moral responsibility. A key feature of the phenomenon is that it is recurrent rather than one-off. It also affects agents across a wide range of situations making it difficult to detect. Deeply unlucky agents are subject to unfavourable moral assessments through no fault of their own both in specific cases and when they try to respond to such initial assessments. In this respect, deep circumstantial luck takes the form of a normative burden that grows over time. A process-oriented conception of moral responsibility as answerability is proposed to explain this phenomenon and highlight its implications for rethinking vicarious responsibility.
A Novel Mathematical Model to Calculate the Osteotomy in Ankylosing Spondylitis
Authors: Akpolat Ahmet Onur , Tasci Fatih , Kilinc Bekir Eray , Celebi Mehmet Emin , Balioglu Mehmet Bülent
Published: January 2021

Mini

The authors developed a mathematical model to the sagittal vertical axis (SVA) change in ankylosing spondylitis whom PSO is planned. The mathematical model was developed using trigonometric equations. No significant difference exists between postop SVA change amount and SVA calculated. The mathematical model is reliable in restoring the global sagittal balance.

Study Design.

Retrospective study.

Objective.

This study aims to develop a mathematical model to help precalculate the sagittal vertical axis (SVA) change in patients with ankylosing spondylitis (AS) with rigid kyphotic deformity for whom pedicle subtraction osteotomy (PSO) is planned.

Summary of Background Data.

SVA is an important metric parameter used to evaluate the global sagittal balance. Previous studies have investigated angular changes in pelvic parameters using PSO; however, no mathematical model is available to calculate SVA change as a metric in these studies.

Methods.

Twenty-one patients who met the inclusion criteria were included in the study. The mathematical model was developed using basic trigonometric equations. Measurements for SVA, lumbar lordosis (LL), pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), and the mathematical model were performed in the preop and early postop period. The amount of SVA change in the poststop period was calculated in the mathematical model.

Results.

The mean age was 33.81 ± 6.01 years. No statistical difference was observed between MATLAB and the angles used in the mathematical modeling (P > 0.05). No significant difference exists between postop SVA change amount and SVA calculated via mathematical modeling (P > 0.05). A statistically significant difference was observed between preop and postop measurements of LL, SVA, PT, and SS variables (P < 0.001). No statistically significant difference existed between PI (P > 0.05).

Conclusion.

This novel mathematical model is reliable in restoring the global sagittal balance of the patients with AS scheduled for PSO and prevent the osteotomy complications.

Level of Evidence: 3
Pulmonary pathology of COVID-19: a review of autopsy studies
Authors: Borczuk Alain C.
Published: January 2021

Purpose of review

COVID-19 lung injury is a common manifestation of severe illness. Lung tissue examination has been largely derived from autopsy – a combination of case reports, small and moderately sized series with international scope. Common and uncommon histopathology provides insight into the progression of severe, fatal disease.

Recent findings

COVID-19 lung histology is most commonly diffuse alveolar damage as part of acute respiratory distress syndrome. Lung injury can be temporally heterogeneous, with patterns of healing alongside new injury. Viral studies, including immunohistochemistry, RNA in-situ hybridization, and tissue-based Polymerase chain reaction (PCR) assist in discerning complications of therapy (e.g. ventilator-associated pneumonia) from primary viral-induced injury. Response to viral infection produces systemic effects, and one major manifestation is thrombosis of micro-circulation and larger vessels. Less common patterns include neutrophil-rich inflammation, raising speculation that neutrophil extra-cellular traps may play a role in both viral control and exaggerated immune response.

The heterogeneity of fatal cases- persistence of viral infection in lung, clearance of virus but severe lung injury, thrombosis, and exaggerated immune response – suggest that antiviral, antithrombotic, anti-inflammatory, and supportive therapy play a role in treatment, but that the patient-specific cause and timing of the lung injury is important in choosing intervention.
Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations
Authors: Swanson Olivia , Rhodes Brianna , Wang Avivah , Xia Shi-Mao , Melissa Cooper , Parks Robert , Sanzone Aja , Louder Mark K. , Lin Bob C. , Doria-Rose Nicole A. , Saunders Kevin O. , Bonsignori Mattia , Wiehe Kevin , Haynes Barton F. , Azoitei Mihai L.
Published: January 2021

Elicitation of broadly neutralizing antibodies (bnAbs) by an HIV vaccine will involve priming the immune system to activate antibody precursors, followed by boosting immunizations to select for antibodies with functional features required for neutralization breadth. The higher the number of acquired mutations necessary for function, the more convoluted are the antibody developmental pathways. HIV bnAbs acquire a large number of somatic mutations, but not all mutations are functionally important. Here we identified a minimal subset of mutations sufficient for the function of the naturally occurring V3-glycan bnAb DH270.6. Using antibody library screening, candidate envelope immunogens that interacted with DH270.6-like antibodies containing this set of key mutations were identified and selectedin vitro. Our results demonstrate that less complex B cell evolutionary pathways than those naturally observed exist for the induction of HIV bnAbs by vaccination, and establish rational approaches to identify boosting sequential envelope candidate immunogens.