bluuebunny/crossref_metadata_2025 huggingface dataset:
Third head of gastrocnemius - a case report
Authors: Shalini R , Suriyakumari K VP
Published: January 2020

Gastrocnemius is a superficial muscle of the posterior compartment of leg. It usually arises by two heads- a medial and a lateral head. A third head of Gastrocnemius has been reported to occur in 2.9 - 5.5% of subjects. This anomaly has been implicated as a cause for popliteal vessel entrapment syndrome.Variations of the heads of origin of Gastrocnemius muscle were studied in 20 lower extremities of ten adult cadavers during routine Popliteal Fossa dissection at Sri Manakula Vinayagar Medical College and Hospital, Puducherry. An accessory third head of Gastrocnemius was found in four lower limbs (20% ). This third head originated along with the lateral head of Gastrocnemius.
Morphometric study of suprascapular notch
Authors: R. Vandana , Patil Sudha
Published: January 2020

Background and aims: Suprascapular nerve may be compressed anywhere along its course but most commonly at the level of SSN (suprascapular notch) and spinoglenoid notch. The variation in the morphological and morphometric features of SSN, spinoglenoid notch, therefore plays a crucial role in the suprascapular nerve entrapment syndrome. The purpose of present study was to determine the variation in morphology and dimensions of SSN and to determine posterosuperior and posterior limits of safe zone for shoulder joint procedures from posterior approach. Material & methods: We conducted study on 134 dry scapulae of north Karnataka region and classified the SSN into various shapes according to Iqbal et al and I-VI types based on description by Natsis et al, along with this, the mean distance from the SSN to supraglenoid tubercle and the mean distance between posterior rim of glenoid cavity and medial wall of spinoglenoid notch at the base of scapular spine were also measured. Results: Based on Iqbal et al classification, 'U' shaped notch found to be most common (35%) whereas least common was W shaped (0.7%).The incidence of complete ossification of STSL was 12.6%. Based on Natsis classification most common was type II (TD>VL) seen in 69% and least common was type VI (notch & foramen) 0% .The mean distance from SSN to supraglenoid tubercle was 27.3 mms ± 1.7 and mean distance between posterior rim of glenoid cavity and medial wall of spinoglenoid notch at the base of scapular spine was 13mms ± 0.2 which are comparatively less than the other population studies which are mentioned in the article. Conclusions: There are variations in the shape and size of SSN and safe zone critical distance in different populations so it requires still more population specific studies on suprascapular notch.
Nanoscale electro-thermal interactions in AlGaN/GaN high electron mobility transistors
Authors: Chatterjee Bikramjit , Dundar Canberk , Beechem Thomas E. , Heller Eric , Kendig Dustin , Kim Hyungtak , Donmezer Nazli , Choi Sukwon
Published: January 2020

Self-heating in AlGaN/GaN high electron mobility transistors (HEMTs) negatively impacts device performance and reliability. Under nominal operating conditions, a hot-spot in the device channel develops under the drain side corner of the gate due to a concentration of volumetric heat generation leading to nonequilibrium carrier interactions and non-Fourier heat conduction. These subcontinuum effects obscure identification of the most salient processes impacting heating. In response, we examine self-heating in GaN-on-Si HEMTs via measurements of channel temperature using above-bandgap UV thermoreflectance imaging in combination with fully coupled electrothermal modeling. The methods together highlight the interplay of heat concentration and subcontinuum thermal transport showing that channel temperature cannot be determined solely by continuum scale heat transfer principles. Under conditions of equal power dissipation (PDISS = VDS × IDS = 250 mW), for example, a higher VDS bias (∼23 V) resulted in an ∼44% larger rise in peak junction temperature compared to that for a lower VDS (∼7.5 V) condition. The difference arises primarily due to reduction in the heat generating volume when operating under partially pinched-off (i.e., high VDS) conditions. Self-heating amplifies with this reduction as heating now takes place primarily over length scales less than the mean free path of the phonons tasked with energy dissipation. Being less efficient, the subcontinuum transport restricts thermal transport away from the device hot-spot causing a net increase in channel temperature. Taken together, even purely thermally driven device mean-time-to-failure is not, therefore, based on power dissipation alone as both bias dependence and subcontinuum thermal transport influence device lifetime.
Laser power density dependence on charge state distribution of Ta ion laser plasma
Authors: Okamura Masahiro , Tamis Andrew , Whelan Tommy , Kanesue Takeshi , Ikeda Shunsuke , Cannavò Antonino
Published: January 2020

Laser power density per pulse, which is commonly expressed with the unit of “W/cm2,” is an important parameter to characterize ablation plasma. To match a design charge state of heavy ion beam induced by a laser ion source, a laser power density must be carefully chosen. Above around 108 W/cm2 of laser power density, laser ablation plasma is emitted from the surface of solid material. Then, up to 109 W/cm2, the most abundant charge state is 1+. Because the ionization energy increases with higher charge states, increasing the laser intensity leads to the charge state distribution shifting higher. Increasing the density to increase charge states also results in lower time of flight due to higher velocities. The maximum laser power density is obtained by the smallest available laser spot size on the target material which is determined by the quality of the laser beam. For many accelerator applications, higher charge state beams are preferred. In particular cases, singly charge ion beams are demanded. Therefore, production of intermediate charge state beams has not been investigated well. In this study, we selected Ta4+ as an example demanded beam and tried to clarify how the transition of charge state distribution depends on laser power density. Conclusively, the possible specification of a laser ion source for Ta4+ delivery was elucidated.
Fabrication of vertically aligned ferromagnetic ZnO nanopillar arrays on sapphire substrates by polymer-assisted deposition
Authors: Luo Jia , Ren Hongtao , Zhang Xi , Xiang Gang
Published: January 2020

Vertically aligned ferromagnetic ZnO nanopillar arrays have been fabricated on single-crystal sapphire substrates through polymer-assisted deposition. X-ray diffraction and transmission electron microscopy analysis show that the arrays are ZnO hexagonal crystal structure along the c-axial direction. The existence of room temperature ferromagnetism of the arrays was confirmed by the superconducting quantum interference device measurements. The enhancement of ferromagnetism in ZnO nanopillar arrays is found to be correlated with the increase in Zn1− vacancies and the decrease in oxygen interstitials, which was shown by photoluminescence measurements of the samples. Our results provide a viable way to fabricate ferromagnetic vertical arrays of ZnO nanopillars.
The importance of O3 excited potential energy surfaces in O2–O high-temperature kinetics
Authors: Andrienko Daniil A.
Published: January 2020

The mechanism of vibrational relaxation and dissociation in the O2–O system at elevated temperatures is investigated by means of molecular dynamics. The most recent O3 potential energy surfaces (PESs), obtained from the first principles quantum mechanical calculations [Varga et al., J. Chem. Phys. 147, 154312 (2017)], are used to derive a complete set of state-specific rate coefficients of vibrational energy transfer and dissociation. Unlike most of the previous efforts that utilize only the lowest and supposedly most reactive 11A′ O3 PES [A. Varandas and A. Pais, Mol. Phys. 65, 843 (1988)], this paper demonstrates the necessity to account for a complete ensemble of all excited O3 PESs that correlate with O2(X) and O(3P) when high-temperature kinetics is of interest. At the same time, it is found that the Varandas 11A′ O3 PES adequately describes vibrational energy transfer and dissociating dynamics when compared to the most recent 11A′ O3 PES by Varga et al. [J. Chem Phys. 147, 154312 (2017)]. The differences between this new dataset and previous rate coefficients are quantified by the master equation model.
Simulations reveal the shape of crystal nuclei to be consistent with classical theory
Authors: Bandari Anashe
Published: January 2020

Using molecular dynamics simulation results, researchers found the average shape of a crystal nucleus to be close to spherical.
Beef production from yearling calves under conventional or organic management
Authors: Román-Trufero A. , Martínez A. , Osoro K. , García-Prieto V. , Celaya R.
Published: January 2020

The objective of this research was to compare yearling beef calf production (bodyweight – BW gains and carcass characteristics) under organic and conventional (semi-extensive) management. The study comprised three production cycles (from weaning to slaughter) with a total of 67 calves. For the grazing periods, three replicates (1.6-ha paddocks with Lolium perenne–Trifolium repens pasture) per treatment were established, and 4–5 animals per paddock were managed. Conventional paddocks were fertilised with synthetic NPK, whereas manure was used in the organic ones. During finishing, conventional feeding consisted of concentrate ad libitum with straw (CC). Under organic regulation, pasture grazing (PG), herbage silage (HS) and maize silage (MS), all supplemented with organic concentrate, were tested. Results showed similar individual performances before finishing in both treatments. Daily BW gain per unit area during spring was greater in conventional than in organic system (5.62 vs 4.27 kg/ha; P < 0.01), propitiating greater final production in the former, a result of greater herbage production allowing higher stocking rates managed on conventional pastures. During finishing, CC yearlings had greater (P < 0.001) BW gains (1340 g/day) compared with organic feeding systems, although MS feeding enhanced the gains (1116 g/day) over those achieved in PG or HS (average 709 g/day). There were no differences among feeding systems in carcass weight and conformation, while the rib dissection revealed greater fat contents in CC and MS relative to PG and HS (10.2 vs 7.5%; P < 0.05). Feeding with maize silage during finishing could be a good option to achieve organic beef production levels close to the conventional ones. However, the high price of organic concentrate raised feeding costs during finishing in a way that organic beef fattening was 36% less efficient than the conventional system in terms of product sales (applying the same price per kg carcass weight) minus feeding costs per unit of land area.
Ordering towards disorder
Authors: Denk Lukas
Published: January 2020

In Athabascan languages, verbal morphological structure does not follow the cross-linguistically more common and stable ‘layered’ order: derivational and lexical affixes are not necessarily closer to the stem than inflectional affixes. While the emergence of the Athabascan order is understandable through different layers of grammaticalization (Mithun 2011), the question of why this order is relatively stable in the language family has not yet been satisfactorily answered. The distributional properties of cognate Athabascan morphemes reveal historical tendencies for fusion and reordering that suggest that affixes remain in or change their position depending on the semantic relevance tootheraffixes, not necessarily to thestemalone, asBybee’s (1985)morphological theory would predict. An additional factor for the stability of non-layered structure of morphemes is the high degree of semantic generality found in affixes between the stem and other lexical and derivational affixes.
Membrane fusion drives pronuclear meeting in the one-cell embryo
Authors: Ma Linda , Starr Daniel A.
Published: January 2020

The mechanisms that control how the two parental pronuclei fuse in the first mitosis of the embryo are poorly understood. In this issue, Rahman et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.201909137) found that membrane fusion between pronuclear envelopes, followed by fenestration, promotes pronuclear fusion.
Hierarchical biomechanics: student engagement activities with a focus on biological physics
Authors: Hanson Benjamin S , Brown Christa P , Laurent Harrison , Hughes Matt D G , Dougan Lorna
Published: January 2020

Hierarchical structure and mechanics are crucial in biological systems as they allow for smaller molecules, such as proteins and sugars, to be used in the construction of large scale biological structures exhibiting properties such as structural support functionality. By exploring the fundamental principles of structure and mechanics at the macroscale, this general theme provides a clear insight into how physics can be applied to the complex questions of biology. With a focus on biopolymer networks and hydrogels, we present a series of interactive activities which cover a range of biophysical concepts at an introductory level, such as viscoelasticity, biological networks and ultimately, hierarchical biomechanics. These activities enable us to discuss multidisciplinary science with a general audience and, given the current trends of research science, this conceptualisation of science is vital for the next generation of scientists.
Improving the dynamics of quantum sensors with reinforcement learning
Authors: Schuff Jonas , Fiderer Lukas J , Braun Daniel
Published: January 2020

Recently proposed quantum-chaotic sensors achieve quantum enhancements in measurement precision by applying nonlinear control pulses to the dynamics of the quantum sensor while using classical initial states that are easy to prepare. Here, we use the cross-entropy method of reinforcement learning (RL) to optimize the strength and position of control pulses. Compared to the quantum-chaotic sensors with periodic control pulses in the presence of superradiant damping, we find that decoherence can be fought even better and measurement precision can be enhanced further by optimizing the control. In some examples, we find enhancements in sensitivity by more than an order of magnitude. By visualizing the evolution of the quantum state, the mechanism exploited by the RL method is identified as a kind of spin-squeezing strategy that is adapted to the superradiant damping.
Climate variability or anthropogenic emissions: which caused Beijing Haze?
Authors: Pei Lin , Yan Zhongwei , Chen Deliang , Miao Shiguang
Published: January 2020

Beijing Haze has been phenomenal, especially for winter, and widely considered a result of the increasing anthropogenic emissions of atmospheric pollutants in the region. Since 2013, the pollutant emissions have been reduced with the help of a series of emission-control actions. However, severe haze events still occurred frequently in Beijing in recent winters, e.g., those of 2015 and 2016, implying that other factors such as meteorological conditions and interannual climate variability have also played an important role in forming the haze. Based on homogenized station observations, atmospheric circulation reanalysis and anthropogenic emissions data for the period 1980–2017, this paper attempts to quantify the relative importance of anthropogenic emissions and climatic conditions to the frequency and intensity of Beijing Haze in winter. It is found that the frequency (number) of hazy days exhibits large interannual variability and little trend, and its variations were mainly controlled by climate variability, with a correlation coefficient of 0.77. On the other hand, the intensity of haze displays strong interannual variability and a significant increasing trend during 1980–2012 and a notable decreasing trend during 2012–2017. The multiple linear regression model suggests that about half of the total variance of the haze intensity is explained by climate variability (mainly for interannual variations), and another half by the changing emissions (mainly for the trends).
The influence of ZnO layer thickness on the performance and electrical bias stress instability in ZnO thin film transistors
Authors: Ngwashi Divine Khan , Mih Thomas Attia , Cross Richard B M
Published: January 2020

Thin Film Transistors (TFTs) are the active elements for future large area electronic applications, in which low cost, low temperature processes and optical transparency are required. Zinc oxide (ZnO) thin film transistors (TFTs) on SiO2/n+-Si substrate are fabricated with the channel thicknesses ranging from 20 nm to 60 nm. It is found that both the performance and gate bias stress related instabilities of the ZnO TFTs fabricated were influenced by the thickness of ZnO active channel layer. The effective mobility was found to improve with increasing ZnO thickness by up to an order in magnitude within the thickness range investigated (20–60 nm). However, thinner films were found to exhibit greater stability in threshold voltage and turn-on voltage shifts with respect to both positive and negative gate bias stress. It was also observed that both the turn on voltage (Von) and the threshold voltage (VT) decrease with increasing channel thickness. Moreover, the variations in subthreshold slope (S) with ZnO thickness as well as variations in VT and Von suggest a possible dependence of trap states in the ZnO on the ZnO thickness. This is further correlated by the dependence of VT and Von instabilities with gate bias stress.
Electrospun Na3V2(PO4)3/C nanofibers as self-standing cathode material for high performance sodium ion batteries
Authors: Luo Longlong , Cheng Bin , Chen Yuxin , Chen Shaojun , Liu Guanlun , Zhuo Haitao
Published: January 2020

This work focuses on the preparation of a 3D flexible Na3V2(PO4)3/C fiber membrane, as self-standing cathode for Na-ion batteries, via a facile and simple electrospinning method, is followed by a hot-pressing process. A series of heat treatment temperatures are studied in detail, it is found that the temperature of the thermal process is a key parameter for controlling the structural organization of the material, as well as the size and dispersion of Na3V2(PO4)3 nanoparticles on the carbon surface. Hence, Na3V2(PO4)3 nanoparticles, with a size of 40 nm and highly disperse on the carbon nanofibers, are obtained after calcination at 800 °C. In addition, this sample (Na3V2(PO4)3/C Nanofiber-800) exhibits the best electrochemical performances among all the samples. For instance, it displays a considerably high initial discharge capacity of 109, 84, 77, and 71 mA h g−1 at a current density of 0.1, 10, 20, and 30 C, respectively. Moreover, the Na3V2(PO4)3/C Nanofiber-800 shows notable cycle stability with about 95.3% capacity retention of its initial capacity after 1000 cycles at 2 C, These high performances is attributed to the unique nanofiber structure and uniform distribution of Na3V2(PO4)3 nanoparticles in the highly conductive carbon matrix.
The effect of Zn interlayer on microstructure and mechanical performance during TIG overlap welding-brazing of Al to Ti
Authors: Li Xiaofeng , Li Caixia , Cao Zhiliang , Yang Ping
Published: January 2020

Tungsten inert gas welding-brazing technology was investigated to achieve the sound joining of Al-Ti alloys with the addition of Zn interlayer. Experiment results show that the Zn interlayer was beneficial to enhance the wettability of weld metal on Ti alloy substrate and improve the weld appearance. With low heat input, a Zn rich layer was observed near the brazing zone. As the heat input increased, TiAl3 phase was generated in fusion area and the morphology of interfacial brazing layer changed from lamellar to serrate. With the welding current increased to 85A, the micro hardness of fusion area increased and presented a great fluctuation owing to the excessive formation of TiAl3 phase. Under the optimal welding current of 75A, the sound Al-Ti weldment with the maximum tensile strength of 175MPa was obtained. Eventually, the improvement mechanism of wettability was investigated.
Reconstruction: A Very Short Introduction
Authors: Guelzo Allen C.
Published: January 2020

Reconstruction: A Very Short Introduction delves into the constitutional, political, and social issues behind Reconstruction to describe a historical moment that left an indelible mark on American social fabric. The Reconstruction era was one of the unhappiest times in American history. It succeeded in reuniting the nation politically after the Civil War, but it failed to chart a progressive course for race relations after the abolition of slavery and rise of Jim Crow, and struggled to successfully manage the Southern resistance towards a Northern, free-labor pattern. Despite this, there were some notable accomplishments: the 14th and 15th Amendments to the Constitution and the election of the first African American representatives to the US Congress.
2. Sines, cosines, and their relatives
Authors: Van Brummelen Glen
Published: January 2020

‘Sines, cosines, and their relatives’ begins by defining the basic trigonometric functions—sine, cosine, and tangent—and explaining their use. These functions are geometric quantities defined using the ratios of the Opposite, Adjacent, and Hypotenuse sides of the right triangle. Less common functions are the cosecant, secant, and cotangent functions. The history of the naming of the trigonometric functions is discussed along with an explanation of even more obscure functions: the versed sine, versed cosine, exsecant, and excosecant. The versed sine was used frequently in practical applications like astronomy, navigation, and surveying. Finally, inverse trigonometric functions and graphs of trigonometric functions are considered.
3. Building a sine table with your bare hands
Authors: Van Brummelen Glen
Published: January 2020

Technological advances, so pervasive in almost every aspect of our modern lives, become mundane to us almost overnight. How does a calculator find out, apparently effortlessly, that sin 33° = 0.5446? There are no right triangles drawn inside of the calculator, so where did that number come from? ‘Building a sine table with your bare hands’ looks at how different sine values have been calculated through history without any mechanical aids. It aintroduces the sine sum and difference laws, the half- and double-angle formulas, the golden triangle, and one of the most remarkable numbers in all of mathematics, the golden ratio, which appears in a dazzling array of areas of mathematics, natural phenomena, works of art, and architecture.
5. The psychology of superstition
Authors: Vyse Stuart
Published: January 2020

Holding superstitious beliefs in a time when the fruits of science are all around us seems somewhat paradoxical, so why do people believe? ‘The psychology of superstition’ considers the prevalence and demographics of superstitious belief. Research shows that belief in luck is correlated with belief in superstition and that they correlate with a number of personality dimensions and traits that are, in most cases, not particularly desirable, such as stress, anxiety, seeking control, pessimism, and depression. How do people learn superstitions and what sustains their superstitious behaviour? The great majority of common superstitions are relatively inexpensive and harmless and they may help reduce anxiety and provide a welcome illusion of control.
6. Elder statesman
Authors: Heilbron J. L.
Published: January 2020

Bohr worked briefly at Los Alamos, the centre of the American atomic bomb project, after fleeing to Sweden with most of Danish Jewry in 1943. As an ‘elder statesman’ he secured audiences with Churchill and Roosevelt to argue (invoking complementarity!) that if the Allies shared information about nuclear weapons with the Russians they might avoid a postwar arms race. He continued to argue this position in various forums after the war and received the first Atoms for Peace Award for his efforts. Back in Denmark, he used his prestige to advance scientific and cultural causes. In his last years, he took an increasingly strong interest in the history of physics as a means of acquainting a wider public with the difficult birth of the splendid science he and his collaborators had made.
Introduction
Authors: Seth Michael J.
Published: January 2020

The Introduction explains that the aim of this VSI is to introduce Korea’s history by focusing on several historical questions: what does it mean to be Korean? How did the various peoples of the Korean peninsula become a single nation? How did this nation evolve, in a single lifetime, into today’s sharply contrasting societies? And how does Korea fit into the larger narrative of world history? The geographical setting of the Korean peninsula is also described. Although it is small and mountainous, Korea has been able to support large populations. Today fifty million people live in South Korea and twenty-five million in North Korea.
Art History: A Very Short Introduction
Authors: Arnold Dana
Published: January 2020

Art history encompasses the study of the history and development of painting, sculpture, and the other visual arts. Art History: A Very Short Introduction considers the issues, debates, and artefacts that make up art history. It explores the emergence of social histories of art and, using a wide range of images, it discusses key aspects of the discipline including how we write about, present, read, and look at art, and the impact this has on our understanding of art history. This second edition includes a new chapter on global art histories, considering how the traditional emphasis on periods and styles in art originated in Western art and can obscure other critical approaches and artwork from non-Western cultures.
Lower Serum Magnesium Concentrations are associated With Specific Heavy Drinking Markers, Pro-Inflammatory Response and Early-Stage Alcohol-associated Liver Injury§
Authors: Vatsalya Vatsalya , Gala Khushboo S , Mishra Maithili , Schwandt Melanie L , Umhau John , Cave Matthew C , Parajuli Dipendra , Ramchandani Vijay A , McClain Craig J
Published: January 2020

Aim

Chronic heavy alcohol intake frequently causes liver inflammation/injury, and altered mineral metabolism may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking, changes in serum magnesium levels and biochemical evidence of liver injury in alcohol-use-disorder (AUD) patients who had no clinical signs or symptoms of liver injury. We also aimed to identify any sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking.

Methods

114 heavy drinking alcohol-dependent (AD) female and male patients aged 21–65 years without clinical manifestations of liver injury, who were admitted to an alcohol treatment program, were grouped by alanine aminotransaminase (ALT) levels: ≤ 40 IU/L, as no liver injury (GR.1), and ALT>40 IU/L as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic biochemistry results, fatty acid panel, serum magnesium and drinking history data were collected at admission; and study-specific measures were evaluated.

Results

In all AD patients, lower magnesium was significantly associated with the heavy drinking marker and heavy drinking days past 90 days (HDD90). A lower serum magnesium concentration was observed in AD patients with mild liver injury. Females of both groups had mean levels of magnesium in the deficient range. A clinically significant drop in magnesium levels was observed only in the GR.2 (mild liver injury) male AD patients. Females showed a significant association between low magnesium levels and the ω6:ω3 polyunsaturated fatty acids (PUFAs) ratio.

Conclusions

Specific heavy drinking markers showed an association with lower magnesium levels. Low serum magnesium levels are common in subjects with AUD and appear to be associated with the onset of liver injury.
Investigating social and environmental predictors of natal dispersal in a cooperative breeding bird
Authors: Suh Young Ha , Pesendorfer Mario B , Tringali Angela , Bowman Reed , Fitzpatrick John W
Published: January 2020

Natal dispersal is a crucial life-history trait that affects both individual fitness and population structure, yet drivers of variation in dispersal probability and distance are difficult to study in wild populations. In cooperatively breeding species, individuals typically delay dispersal beyond their first breeding season and remain on the natal territory as nonbreeders, which prolongs social dynamics that can affect dispersal decisions. Using a 35-year data set covering almost 600 dispersal events in the cooperatively breeding Florida scrub-jay (Aphelocoma coerulescens), we examined the environmental and social parameters that predict dispersal probability over time and distance. In both sexes, dispersal probability increased with age, which, in turn, was negatively correlated with dispersal distance. In males, individuals occupying low-quality natal territories and living with a stepfather had an increased probability of dispersal. Older and more dominant males were more likely to inherit their natal territory. In females, which generally disperse earlier and farther than males, socially subordinate jays dispersed farther than dominant ones. Overall, jays that delayed dispersal the longest were more likely to attain breeding status near their natal territory, which was previously found to be associated with increased survival and lifetime fitness. Our results suggest that social dynamics and environmental factors on the natal territory affect delayed dispersal patterns differently for the two sexes in this cooperative breeder.
High-dimensional variable selection for ordinal outcomes with error control
Authors: Fu Han , Archer Kellie J
Published: January 2020

Many high-throughput genomic applications involve a large set of potential covariates and a response which is frequently measured on an ordinal scale, and it is crucial to identify which variables are truly associated with the response. Effectively controlling the false discovery rate (FDR) without sacrificing power has been a major challenge in variable selection research. This study reviews two existing variable selection frameworks, model-X knockoffs and a modified version of reference distribution variable selection (RDVS), both of which utilize artificial variables as benchmarks for decision making. Model-X knockoffs constructs a ‘knockoff’ variable for each covariate to mimic the covariance structure, while RDVS generates only one null variable and forms a reference distribution by performing multiple runs of model fitting. Herein, we describe how different importance measures for ordinal responses can be constructed that fit into these two selection frameworks, using either penalized regression or machine learning techniques. We compared these measures in terms of the FDR and power using simulated data. Moreover, we applied these two frameworks to high-throughput methylation data for identifying features associated with the progression from normal liver tissue to hepatocellular carcinoma to further compare and contrast their performances.
MODER2: first-order Markov modeling and discovery of monomeric and dimeric binding motifs
Authors: Toivonen Jarkko , Das Pratyush K , Taipale Jussi , Ukkonen Esko
Published: January 2020

Motivation

Position-specific probability matrices (PPMs, also called position-specific weight matrices) have been the dominating model for transcription factor (TF)-binding motifs in DNA. There is, however, increasing recent evidence of better performance of higher order models such as Markov models of order one, also called adjacent dinucleotide matrices (ADMs). ADMs can model dependencies between adjacent nucleotides, unlike PPMs. A modeling technique and software tool that would estimate such models simultaneously both for monomers and their dimers have been missing.

Results

We present an ADM-based mixture model for monomeric and dimeric TF-binding motifs and an expectation maximization algorithm MODER2 for learning such models from training data and seeds. The model is a mixture that includes monomers and dimers, built from the monomers, with a description of the dimeric structure (spacing, orientation). The technique is modular, meaning that the co-operative effect of dimerization is made explicit by evaluating the difference between expected and observed models. The model is validated using HT-SELEX and generated datasets, and by comparing to some earlier PPM and ADM techniques. The ADM models explain data slightly better than PPM models for 314 tested TFs (or their DNA-binding domains) from four families (bHLH, bZIP, ETS and Homeodomain), the ADM mixture models by MODER2 being the best on average.

Availability and implementation

Software implementation is available from https://github.com/jttoivon/moder2.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Role of Pharmaceutical Companies in Antimicrobial Stewardship: A Case Study
Authors: Hermsen Elizabeth D , Sibbel Richard L , Holland Silas
Published: January 2020

Rising levels of antimicrobial resistance pose serious dangers to patients, population health, food security, and economic stability worldwide. In response to this threat, the United Nations and the World Health Organization have called for multisectoral, multidisciplinary action, recognizing that human, animal, and environmental health are interdependent. Although the pharmaceutical industry clearly has a leading role in developing novel antimicrobials and vaccines, it is also active in many areas supporting antimicrobial stewardship. This article describes why pharmaceutical companies invest in antimicrobial stewardship, outlines why they are well suited to help address this issue, and provides examples of how the pharmaceutical industry can support the responsible use of antimicrobials. Merck & Co., Inc. (Kenilworth, NJ, USA), a large, globally operating pharmaceutical company that develops and markets both human and veterinary antimicrobials and vaccines is used as a case study for illustrating industry involvement in antimicrobial stewardship efforts.
REPCAT: Desktop expert system for interpreting and validating laboratory data for pheochromocytoma diagnosis with the database application Omnis 7™
Authors: Smythe George A , Drew Cathryn M
Published: January 2020

To aid in the validation and interpretive reporting of results from multianalyte diagnostic testing for pheochromocytoma (PHEO), we have developed a desktop personal computer-based laboratory expert system (REPCAT). REPCAT utilizes a commercial database application to run procedures that assess analytical and clinical data relating to patient urine or plasma samples. REPCAT was used to evaluate the raw data from >4000 24-h urine samples submitted to our laboratory for testing for the presence of PHEO. REPCAT performed equivalently to an expert pathologist in assessing the presence and class of PHEO (epinephrine, norepinephrine, or mixed secretor). No false negatives were generated and it assigned a correct interpretation (on the basis of subsequent clinical and biochemical investigation) for each of the primary diagnostic samples from these patients.
Optimization of single-strand conformation polymorphism analysis in the presence of polyethylene glycol
Authors: Markoff Arseni , Savov Alex , Vladimirov Vladimir , Bogdanova Nadia , Kremensky Ivo , Ganev Varban
Published: January 2020

We report optimization of single-strand conformation polymorphism (SSCP) analysis in the presence of polyethylene glycol. The protocol developed separates single-strand conformers in a much shorter time (1–3 h) than conventional SSCP protocols and broadens the applicability of SSCP analysis from 150 to as much as 500 bp of DNA by different percentages of GC content present. We conclude that addition of polyethylene glycol helps improve the differential separation of conformers and, in combination with high-resolution polyacrylamide gel electrophoresis, offers an alternative to previous SSCP analysis protocols. This protocol should be very useful for clinical applications in routine detection of mutations as well as for research purposes.
Ligase chain reaction assay for human mutations: the Sickle Cell by LCR assay
Authors: Reyes Antonio A , Carrera Paola , Cardillo Elena , Ugozzoli Luis , Lowery Jimmie D , Lin Ching-I P , Go Matthew , Ferrari Maurizio , Wallace R Bruce
Published: January 2020

We can detect the β-globin gene sickle cell mutation by using an assay based on the ligase chain reaction. The simultaneous amplification of the human growth hormone gene in the same reaction serves as a control for the amount of template DNA or amplification efficiency. Ligation products, which are biotinylated at one end and tagged with an arbitrary “tail” sequence at the other, are captured by hybridization to “tail”-complementary oligonucleotides immobilized on polystyrene microwells. The captured ligation products are detected colorimetrically by use of streptavidin–alkaline phosphatase conjugate. In a study of 24 subjects, the assay unequivocally discriminated among normal, carrier, and sickle cell genotypes.
Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications
Authors: Macy Elizabeth M , Hayes Timothy E , Tracy Russell P
Published: January 2020

We developed a reproducible ELISA for C-reactive protein (CRP), calibrated with WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%. The distribution of CRP in a healthy blood donor population (n = 143) was nongaussian, with 2.5th, 50th, and 97.5th percentile values of 0.08, 0.64, and 3.11 mg/L, respectively. There was no sex-related difference, and the association with age was weak. In a study of variability [by the method of Fraser and Harris (Crit Rev Clin Lab Sci 1989;27:409–37)], the analytical variability was 5.2%; the within-subject variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%. The critical difference for sequential values significant at P ≤0.05 (i.e., the smallest percentage change unlikely to be due to analytical variability or CVI) was calculated as 118%, and the index of individuality, CVI/CVG, was 0.46. This suggests that CRP, like many clinical chemistry analytes, has limited usefulness in detecting early disease-associated changes when used in conjunction with a healthy reference interval. From a molecular epidemiological standpoint, the usefulness of CRP in longitudinal studies is suggested by the small index of individuality and by observations that (a) short-term fluctuations were infrequent, (b) all data stayed within the reference interval, and (c) relative rankings of the subjects over 6 months only moderately deteriorated.
Two-site immunofluorometric assay of intact salmon calcitonin with improved sensitivity
Authors: Rong Haiqin , Deftos Leonard J , Ji Hong , Bucht Elisabet
Published: January 2020

We recently developed a two-site immunofluorometric assay (IFMA) of salmon calcitonin (SCT) by DELFIA (dissociation enhancement lanthanide fluoroimmunoassay) technique using the same polyclonal antibodies both for “catching” the antigen and for signaling. In the present study we used a monoclonal antibody to SCT 1–11 as the capture antibody. This antibody was biotinylated before use in streptavidin-coated microtitration plates. The polyclonal antibody labeled with Eu chelate was used as a signaling marker. This combination of antibodies resulted in an assay that was three to four times more sensitive than the previous IFMA, with a detection limit of 0.3 pmol/L serum. Intact SCT 1–32 was detected by the assay (recoveries 94–96%), but not the fragments SCT 1–11 and SCT 10–32 or human calcitonin. Dilutions of plasma samples containing SCT were parallel to the calibration curve of SCT 1–32. Pharmacokinetic studies of SCT, 100 IU administered intramuscularly to 10 men, indicated peak serum concentrations of 32–128 pmol/L within 10–20 min with apparent half-life of 56 ± 18 min (mean ± SD). This new assay will allow study of the pharmacokinetics of new calcitonin preparations that do not require injection.
Adaptation of latex-enhanced assay for percent glycohemoglobin to a Dade Dimension® analyzer
Authors: Holownia Peter , Bishop Elizabeth , Newman David J , John W Gary , Price Christopher P
Published: January 2020

At present no method for glycohemoglobin (%HbA1c) is automated on a main-line analyzer to allow joint measurement with other indicators of diabetic control such as glucose and cholesterol. We describe an adaptation of a latex-enhanced competitive immunoassay for quantifying %HbA1c to the Dade International Dimension® analyzer. After a manual hemolysis step, HbA1c and total hemoglobin (Hb) are determined separately. The concentration of glycated β-subunit is obtained from the immunoassay, whereas Hb is assessed colorimetrically from a derivatized form. Both reactions were fully optimized for accuracy, precision, and specificity on the Dimension; stabilities of reagents and calibration were established; and potential interferences were assessed. The analyzer gave reliable results over the required clinical range of 1–15% HbA1c. Within-run and total assay variation were within 5% of the target CV limits, as determined by ANOVA with three representative sample pools across 20 days. Close agreement with an established HPLC procedure and a commercially available enzyme immunoassay was observed for 140 samples from clinically defined patient groups. Additional samples from patients with hemoglobinopathies (n = 20) demonstrated a more complex relationship between methods. We conclude that adaptation of the method for use with the Dimension analyzer is a valid method for quantifying %HbA1c.
Molecular diagnosis of B- and T-cell lymphomas: fundamental principles and clinical applications
Authors: Rezuke William N , Abernathy Evelyn C , Tsongalis Gregory J
Published: January 2020

Molecular diagnostic assays have become routine in the evaluation of lymphoid malignancies. Both Southern transfer and polymerase chain reaction (PCR) technologies are used to assess for B- and T-cell clonality, the presence of rearrangements involving protooncogenes such as bcl-1 and bcl-2, and the monitoring of minimal residual disease. We review the fundamentals of B- and T-cell ontogeny as well as the basic principles of the Southern transfer and PCR assays and their applications to the diagnosis of lymphoid malignancies.
Point On the meaning of “sensitivity”
Authors: Ekins Roger , Edwards Philip
Published: January 2020

The term “sensitivity” (as applied to an analytical method’s performance) has again become a subject of controversy. Certain authorities (e.g., IUPAC) define a system’s sensitivity as the response curve slope (or response/dose), others (e.g., IFCC) in terms of the detection limit. Many investigators have failed to perceive the contradiction between these concepts, wrongly assuming that maximizing “sensitivity” in the first sense maximizes it in the second (i.e., that they are inversely related). The existence of different meanings for this term (when used in the present context) is a source of confusion that has, among other things, led to erroneous ideas relating to immunoassay design. Such confusion should be terminated by adoption of one or the other of the definitions. However, the definitions are not of equal merit. We advance arguments against retention of the “slope” definition, which conflicts with the word’s common meaning and is meaningless as an indicator of the performance of a measuring system.
Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry
Authors: Chace Donald H , Hillman Steven L , Van Hove Johan L K , Naylor Edwin W
Published: January 2020

We report the application of tandem mass spectrometry to prospective newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. MCAD deficiency is diagnosed from dried blood spots on filter paper cards from newborns on the basis of the increase of medium chain length acylcarnitines identified by isotope dilution mass spectrometry methods. A robust and accurate semiautomated method for the analysis of medium chain length acylcarnitines as their butyl esters was developed and validated. Quantitative data from the analyses of 113 randomly collected filter paper blood spots from healthy newborns showed low concentrations of medium chain length acylcarnitines such as octanoylcarnitine. The maximum concentration of octanoylcarnitine was 0.22 μmol/L, with the majority being at or below the detection limit. In all 16 blood spots from newborns with confirmed MCAD deficiency, octanoylcarnitine was highly increased [median 8.4 μmol/L (range 3.1–28.3 μmol/L)], allowing easy detection. The concentration of octanoylcarnitine was significantly higher in these 16 newborns (<3 days of age) than in 16 older patients (ages 8 days to 7 years) with MCAD deficiency (median 1.57 μmol/L, range 0.33–4.4). The combined experience of prospective newborn screening in Pennsylvania and North Carolina has shown a disease frequency for MCAD deficiency of 1 in 17 706. No false-positive and no known false-negative results have been found. A validated method now exists for prospective newborn screening for MCAD deficiency.
Effect of analytical run length on quality-control (QC) performance and the QC planning process
Authors: Parvin Curtis A , Gronowski Ann M
Published: January 2020

The performance measure traditionally used in the quality-control (QC) planning process is the probability of rejecting an analytical run when an out-of-control error condition exists. A shortcoming of this performance measure is that it doesn’t allow comparison of QC strategies that define analytical runs differently. Accommodating different analytical run definitions is straightforward if QC performance is measured in terms of the average number of patient samples to error detection, or the average number of patient samples containing an analytical error that exceeds total allowable error. By using these performance measures to investigate the impact of different analytical run definitions on QC performance demonstrates that during routine QC monitoring, the length of the interval between QC tests can have a major influence on the expected number of unacceptable results produced during the existence of an out-of-control error condition.
Disappearance of human chorionic gonadotropin and its α- and β-subunits after term pregnancy
Authors: Korhonen Juha , Alfthan Henrik , Ylöstalo Pekka , Veldhuis Johannes , Stenman Ulf-Håkan
Published: January 2020

We have used high-specificity and precision immunofluorometric assays to measure the elimination half-times of human chorionic gonadotropin (hCG), hCGα, and hCGβ in serum over 21 days after delivery in six women with term pregnancies. Baseline concentrations and half-times were calculated with the use of a curve-fitting algorithm for multiexponential decay. In contrast to the two-component model, a three-component exponential function with baseline provided a fit for which predicted values could not be distinguished from the observed values by analysis of variance. Median half-times were 3.6, 18.0, and 53.0 h for hCG; 1.0, 23.4, and 194 h for hCGβ; and 0.6, 6.2, and 21.9 h for hCGα. The mean ratio of hCGα to hCG decreased rapidly from 36.9% to 3.3% on day 3; thereafter it increased to 64.3% 21 days after delivery because of a higher baseline concentration of hCGα. hCGβ had the slowest total elimination rate, and the ratio of hCGβ to hCG in serum increased from 0.8% before delivery to 26.7% after 21 days. If the metabolism of hCG and hCGβ is similar in patients with trophoblastic disease, the ratio of hCGβ to hCG must be evaluated with caution in samples taken several days after initiating therapy. We conclude that the disappearance of hCGβ from plasma is slower than previously recognized and that the ratios of hCGβ or hCGα to intact hCG vary as a function of postpartum time. Such information may be important in clinical studies of pregnancy disorders.