bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adulticidal Activity of Metarhizium anisopliae s.l. (Hypocreales: Clavicipitaceae) Native Strains From Argentina Against Aedes aegypti (Diptera: Culicidae)
Authors: Falvo Marianel L , Musso Anahi , Ordoqui Eliana , López Lastra Claudia C , Luz Christian , García Juan J 
Published: November 2019

Abstract
The adulticidal activity of six fungal strains of Metarhizium anisopliae (Metschn.) Sorokin s.l. (Hypocreales: Clavicipitaceae) against Aedes aegypti (L.) (Diptera: Culicidae) was assessed. These strains (CEP 085, CEP 087, CEP 120, CEP 350, CEP 404, and CEP 423) were isolated from soil samples or nondipteran hosts collected from areas in Argentina where Ae. aegypti is distributed. Bioassays were performed with four conidial concentrations plus a control of each fungal strain to determine the lethal concentrations (LC50/LC90), the median survival times (ST50), the mean percentage of the surviving individuals, and the mean percentage of mycotized cadavers. The strains were able to infect and kill adult Ae. aegypti. Significant differences were found among the LC50 values, with CEP 423 as the most virulent strain with the lowest LC50 (2.4 × 106 conidia/ml). At 1 × 107 conidia/ml: no significant differences were found in the Kaplan–Meier survival functions among the strains; the ST50 ranged from 5 (CEP 085) to 8 d (CEP 350); and the mean percentage of the surviving adults was between 13.3 (CEP 085, CEP 350 and CEP 423) and 46.7% (CEP 087). Significant differences were also found among strains in the mean percentage of cadavers with fungal sporulation. Strain CEP 423 produced the highest percentage of mycotized adults (70%). The concentration of the inoculum significantly affected the survival of individuals and the percentage of mycotized cadavers within each strain. Metarhizium anisopliae s.l. CEP 423 was selected as the most promising candidate for further research aiming to develop a mycoinsecticide against Ae. aegypti.
First Use of an Entire Age Cohort to Evaluate the Role of Sex in the Development of the Forensically Important Chrysomya megacephala (Diptera: Calliphoridae)
Authors: Smith Joshua L , Cook Ashley K 
Published: November 2019

Abstract
The age of a blow fly larval specimen found on a body can be used to estimate a minimum postmortem interval by comparing a physical feature of a larva (e.g., length) to a reference growth curve created under similar conditions. A better understanding of factors known to influence growth rates would lead to more precise estimates of larval age. A factor known to influence insect development, but almost always lacking in blow fly larval growth curves, is sex. We wanted to understand how sex might affect larval growth rates and therefore lead to more precise age estimates, in the forensically important blow fly Chrysomya megacephala (F.). We examined sex for an entire age cohort at 70 h and found on average, males were longer than females. To assess whether this difference would cause an investigator to interpret the results differently if comparing a larval specimen of one sex based on reference data from the other sex, we made sex-specific 95% prediction intervals. We did not find a difference when comparing a male specimen with the female prediction interval, but did find more females outside the interval than expected using the male interval. All females outside the male interval were shorter. Investigators commonly remove the largest individuals from a body to estimate age, so these females are less likely to be chosen. These results do not support the generation of sex-specific growth curves for this species, though this study’s narrow scope means more information is required before making a final conclusion.
Surveillance of a kdr Resistance Mutation in Culex pipiens (Diptera: Culicidae) and Culex quinquefasciatus in California
Authors: Yoshimizu Melissa Hardstone , Padgett Kerry , Kramer Vicki 
Published: November 2019

Abstract
Culex pipiens Linnaeus and Culex quinquefasciatus Say are the primary vectors of West Nile and St. Louis encephalitis viruses in California. Pyrethrins and pyrethroids (synthetic pyrethrins) are the most widely used insecticides to control adult stage mosquitoes to prevent disease transmission. The most abundant and widespread mutation associated with pyrethroid resistance is the L1014F mutation of the voltage-sensitive sodium channel gene. Statewide, based on the testing of almost 2,000 mosquitoes from 14 counties, the resistant allele frequency was 71%. Although the L1014F mutation was found in all counties assessed, the resistance allele profiles differed between regions of California. The highest resistant allele frequency occurred in the Central region and lowest frequencies were from the Northern and Southern regions. Resistance allele frequencies observed in 2014–2016 are nearly 1.5 times higher than those from pre-2012, indicating that resistance profiles can change over time. Regular monitoring of the L1014F kdr mutation will help aid in operational decisions.
Comparison of Physician Data in Two Data Files Available for Cancer Health Services Research
Authors: White Dolly P , Enewold Lindsey , Geiger Ann M , Banks Robert , Warren Joan L 
Published: November 2019

Abstract

Introduction
Physicians are vital to health-care delivery, but assessing their impact on care can be challenging given limited data. Historically, health services researchers have obtained physician characteristics data from the American Medical Association (AMA) Physician Masterfile. The Center for Medicare and Medicaid Services’ Medicare Data on Provider Practice and Specialty (MD-PPAS) file was assessed, as an alternative source of physician data, particularly in the context of cancer health services research.

Methods
We used physician National Provider Identifiers in the MD-PPAS data (2008–2014) to identify physicians in the AMA data current as of July 18, 2016. Within each source, we grouped physicians into six broad specialty groups. Percent agreement and Cohen’s kappa coefficient (k) were calculated for age, sex, specialty, and practice state.

Results
Among the 698 202 included physicians, there was excellent agreement for age (percent agreement = 97.7%, k = 0.97) and sex (99.4%, k = 0.99) and good agreement for specialty (86.1%, k = 0.80). Within specialty, using AMA as the reference, agreement was lowest for oncologists (77%). Approximately 85.9% of physicians reported the same practice state in both data sets.

Conclusion
Although AMA data have been commonly used to account for physician-level factors in health services research, MD-PPAS data provide researchers with an alternative option depending on study needs. MD-PPAS data may be optimal if nonphysicians, provider utilization, practice characteristics, and/or temporal changes are of interest. In contrast, the AMA data may be optimal if more granular specialty, physician training, and/or a broader inclusion of physicians is of interest.
The ‘Host’ Label: Forming and Transforming a Community Identity at the Kakuma Refugee Camp
Authors: Rodgers Cory 
Published: November 2019

Abstract
In 1986, Robert Chambers argued that refugee-centric responses to displacement tend to neglect the populations that host them. Three decades later, the Comprehensive Refugee Response Framework (CRRF) has made assistance to host communities a matter of high priority for agencies, policymakers and other stakeholders involved in refugee protection. While recognizing the progressive principles of responsibility sharing and inclusivity that underlie this shift, this article calls for greater critical attention to the meaning of the term ‘host community’ and the ways in which it is applied. Taking the Kakuma refugee camps in north-western Kenya as a case study, I describe the rise of a ‘host community’ identity in the context of humanitarian programming, contested attempts to define it as a bureaucratic label and its transformations under a socio-economic-integration agenda. While the case presented here is specific to Kenya, the argument is relevant more broadly as hosts are brought under the purview of refugee-protection policies, especially in countries implementing the CRRF.
Artificial Womb Technology and the Choice to Gestate Ex Utero: Is Partial Ectogenesis the Business of the Criminal Law?
Authors: Romanis Elizabeth Chloe 
Published: November 2019

Abstract
It is frequently claimed that artificial wombs (AWs) could alleviate the burdens placed exclusively on women in reproduction. In this article, I demonstrate how AWs used for the partial gestation of preterm neonates could introduce new choices for women by changing perceptions of tolerable risks in gestation. In light of advancing medical technology, it is necessary to consider whether the current legal framework in England and Wales would support increased choice for women about alternative forms of gestation. I examine the ill-defined offence of ‘unlawfully procuring miscarriage’ in the Offences Against the Person Act 1861 and demonstrate that different conclusions about the legal significance of ending a pregnancy are evident, depending on the analytical lens adopted in interpreting ambiguities. Furthermore, I demonstrate that the defences available to pregnancy termination under the Abortion Act 1967 are too narrow to support choices about alternative forms of gestation, even if they become physically and medically possible. Therefore, we should decriminalise termination of pregnancy, or, if it is assumed that gestation is the business of the criminal law, specific reforms to the legal framework are necessary. The offence of unlawfully procuring miscarriage is too uncertain and broad, and the defences available are too restrictive.
An optical search for transients lasting a few seconds
Authors: Richmond Michael W , Tanaka Masaomi , Morokuma Tomoki , Sako Shigeyuki , Ohsawa Ryou , Arima Noriaki , Tominaga Nozomu , Doi Mamoru , Aoki Tsutomu , Arimatsu Ko , Ichiki Makoto , Ikeda Shiro , Ita Yoshifusa , Kasuga Toshihiro , Kawabata Koji S , Kawakita Hideyo , Kobayashi Naoto , Kokubo Mitsuru , Konishi Masahiro , Maehara Hiroyuki , Mito Hiroyuki , Miyata Takashi , Mori Yuki , Morii Mikio , Motohara Kentaro , Nakada Yoshikazu , Okumura Shin-Ichiro , Onozato Hiroki , Sarugaku Yuki , Sato Mikiya , Shigeyama Toshikazu , Soyano Takao , Takahashi Hidenori , Tanikawa Ataru , Tarusawa Ken’ichi , Urakawa Seitaro , Usui Fumihiko , Watanabe Junichi , Yamashita Takuya , Yoshikawa Makoto 
Published: November 2019

Abstract
Using a prototype of the Tomo-e Gozen wide-field CMOS mosaic camera, we acquire wide-field optical images at a cadence of $2\:$Hz and search them for transient sources of duration 1.5 to $11.5\:$s. Over the course of eight nights, our survey encompasses the equivalent of roughly two days on one square degree, to a fluence equivalent to a limiting magnitude of about $V = 15.6$ in a 1-s exposure. After examining by-eye the candidates identified by a software pipeline, we find no sources which meet all our criteria. We compute upper limits to the rate of optical transients consistent with our survey, and compare those to the rates expected and observed for representative sources of ephemeral optical light.
Electrostatic interactions modulate the differential aggregation propensities of IgG1 and IgG4P antibodies and inform charged residue substitutions for improved developability
Authors: Heads James T , Lamb Richard , Kelm Sebastian , Adams Ralph , Elliott Peter , Tyson Kerry , Topia Sarfaraj , West Shauna , Nan Ruodan , Turner Alison , Lawson Alastair D G 
Published: November 2019

AbstractNative state aggregation is an important concern in the development of therapeutic antibodies. Enhanced knowledge of mAb native state aggregation mechanisms would permit sequence-based selection and design of therapeutic mAbs with improved developability. We investigated how electrostatic interactions affect the native state aggregation of seven human IgG1 and IgG4P mAb isotype pairs, each pair having identical variable domains that are different for each set of IgG1 and IgG4P constructs. Relative aggregation propensities were determined at pH 7.4, representing physiological conditions, and pH 5.0, representing commonly used storage conditions. Our work indicates that the net charge state of variable domains relative to the net charge state of the constant domains is predominantly responsible for the different native state aggregation behavior of IgG1 and IgG4P mAbs. This observation suggests that the global net charge of a multi domain protein is not a reliable predictor of aggregation propensity. Furthermore, we demonstrate a design strategy in the frameworks of variable domains to reduce the native state aggregation propensity of mAbs identified as being aggregation-prone. Importantly, substitution of specifically identified residues with alternative, human germline residues, to optimize Fv charge, resulted in decreased aggregation potential at pH 5.0 and 7.4, thus increasing developability.
G-Graph: An interactive genomic graph viewer
Authors: Andrews Peter A. , Alexander Joan , Kendall Jude , Wigler Michael 
Published: November 2019

AbstractMotivationEffective and efficient exploration of numeric data and annotations as a function of genomic position requires specialized software.ResultsWe present G-Graph, an interactive genomic scatter plot viewer. G-Graph stacks or tiles multiple data series in one graph using different colors and markers. It displays gene annotation and other metadata, allows easy changes to the appearance of data series, implements stack-based undo functionality, and saves user-selected application views as image and pdf files. G-Graph delivers smooth and rapid scrolling and zooming even for datasets with millions of points and line segments. The primary target user is a researcher examining many copy number profiles to identify potentially deleterious variants. G-Graph runs under Linux, Mac OSX and Windows.Availabilityhttps://github.com/docpaa/mumdex/ or https://mumdex.com/ggraph/Contactandrewsp@cshl.edu (or paa@drpa.us)
Predictive coding models for pain perception
Authors: Song Yuru , Yao Mingchen , Kemprecos Helen , Byrne Áine , Xiao Zhengdong , Zhang Qiaosheng , Singh Amrita , Wang Jing , Chen Zhe S. 
Published: November 2019

AbstractPain is a complex, multidimensional experience that involves dynamic interactions between sensory-discriminative and affective-emotional processes. Pain experiences have a high degree of variability depending on their context and prior anticipation. Viewing pain perception as a perceptual inference problem, we propose a predictive coding paradigm to characterize evoked and non-evoked pain. We record the local field potentials (LFPs) from the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC) of freely behaving rats—two regions known to encode the sensory-discriminative and affective-emotional aspects of pain, respectively. We further use predictive coding to investigate the temporal coordination of oscillatory activity between the S1 and ACC. Specifically, we develop a phenomenological predictive coding model to describe the macroscopic dynamics of bottom-up and top-down activity. Supported by recent experimental data, we also develop a biophysical neural mass model to describe the mesoscopic neural dynamics in the S1 and ACC populations, in both naive and chronic pain-treated animals. Our proposed predictive coding models not only replicate important experimental findings, but also provide new prediction about the impact of the model parameters on the physiological or behavioral read-out—thereby yielding mechanistic insight into the uncertainty of expectation, placebo or nocebo effect, and chronic pain.
Geometric principles underlying the proliferation of a model cell system
Authors: Wu Ling Juan , Lee Seoungjun , Park Sungshic , Eland Lucy E. , Wipat Anil , Holden Seamus , Errington Jeff 
Published: November 2019

SUMMARYWall deficient variants of many bacteria, called L-forms, divide by a simple mechanism that does not depend on the complex FtsZ-based cell division machine. We have used microfluidic systems to probe the growth, chromosome cycle and division mechanism ofBacillus subtilisL-forms. The results show that forcing cells into a narrow linear configuration greatly improves the efficiency of cell growth and chromosome segregation. This reinforces the view that L-form division is driven by an excess accumulation of surface area over volume. Cell geometry was also found to play a dominant role in controlling the relative positions and movement of segregating chromosomes. The presence of the nucleoid appears to influence division both via a cell volume effect and by nucleoid occlusion, even in the absence of the FtsZ machine. Overall, our results emphasise the importance of geometric effects for a range of critical cell functions and are of relevance for efforts to develop artificial or minimal cell systems.
The kinesin-8 Kip3 depolymerizes microtubules with a collective force-dependent mechanism
Authors: Bugiel Michael , Chugh Mayank , Jörg Jachowski Tobias , Schäffer Erik , Jannasch Anita 
Published: November 2019

ABSTRACTMicrotubules are highly dynamic filaments with dramatic structural rearrangements and length changes during the cell cycle. An accurate control of the microtubule length is essential for many cellular processes in particular, during cell division. Motor proteins from the kinesin-8 family depolymerize microtubules by interacting with their ends in a collective and length-dependent manner. However, it is still unclear how kinesin-8 depolymerizes microtubules. Here, we tracked the microtubule end-binding activity of yeast kinesin-8, Kip3, under varying loads and nucleotide conditions using high-precision optical tweezers. We found that single Kip3 motors spent up to 200 s at the microtubule end and were not stationary there but took several 8-nm forward and backward steps that were suppressed by loads. Interestingly, increased loads, similar to increased motor concentrations, also exponentially decreased the motors’ residence time at the microtubule end. On the microtubule lattice, loads also exponentially decreased the run length and time. However, for the same load, lattice run times were significantly longer compared to end residence times suggesting the presence of a distinct force-dependent detachment mechanism at the microtubule end. The force dependence of the end residence time enabled us to estimate what force must act on a single motor to achieve the microtubule depolymerization speed of a motor ensemble. This force is higher than the stall force of a single Kip3 motor, supporting a collective force-dependent depolymerization mechanism that unifies the so-called “bump-off” and “switching” models. Understanding the mechanics of kinesin-8’s microtubule end activity will provide important insights into cell division with implications for cancer research.STATEMENT OF SIGNIFICANCEKinesin-8 motors are important for microtubule length regulation and are over-expressed in different types of cancer. Yet, on the molecular level, it is unclear how these motors depolymerize microtubules. Using high-precision optical tweezers, we measured how single yeast kinesin-8 motors, Kip3, interacted with the microtubule end. Interestingly, we found that single Kip3 motors were still motile at the microtubule end. The force dependence of how long single motors were associated with the microtubule end enabled us to estimate what force motors must exert onto each other to achieve the collective microtubule depolymerization speed of many motors. Our data support a collective force-dependent depolymerization mechanism. A better understanding of Kip3’s microtubule end activity has implications for cell division and associated diseases.
Isogenic sets of hiPSC-CMs harboringKCNH2mutations capture location-related phenotypic differences
Authors: Brandão Karina O. , van den Brink Lettine , Miller Duncan C. , Grandela Catarina , van Meer Berend J. , Mol Mervyn P.H. , Tertoolen Leon G.J. , Mummery Christine L. , Sala Luca , Verkerk Arie O. , Davis Richard P. 
Published: November 2019

AbstractAimsLong QT syndrome type 2 (LQT2) is caused by mutations in the geneKCNH2, encoding the hERG ion channel. Clinically, mild and severe phenotypes are associated with this cardiac channelopathy, complicating efforts to predict patient risk. The location of the mutation withinKCNH2contributes to this variable disease manifestation. Here we determined whether such phenotypic differences could be detected in cardiomyocytes derived from isogenic human induced pluripotent stem cells (hiPSCs) genetically edited to harbour a range ofKCNH2mutations.Methods and ResultsThe hiPSC lines heterozygous for missense mutations either within the pore or tail region of the ion channel were generated using CRISPR-Cas9 editing and subsequently differentiated to cardiomyocytes (hiPSC-CMs) for functional assessment. Electrophysiological analysis confirmed the mutations prolonged the action potentials and field potentials of the hiPSC-CMs, with differences detected between the pore and tail region mutations when measured as paced 2D monolayers. This was also reflected in the cytosolic Ca2+transients and contraction kinetics of the different lines. Pharmacological blocking of the hERG channel in the hiPSC-CMs also revealed that mutations in the pore-loop region conferred a greater susceptibility to arrhythmic events.ConclusionThese findings establish that subtle phenotypic differences related to the location of theKCNH2mutation in LQT2 patients are reflected in hiPSC-CMs under genetically controlled conditions. Moreover, the results validate hiPSC-CMs as a strong candidate for evaluating the underlying severity of individualKCNH2mutations in humans which could ultimately facilitate patient risk stratification.Translational perspectiveClinical management of patients diagnosed with cardiac channelopathy diseases such as LQT2 is complicated by the variable disease phenotypes observed among mutation carriers, creating challenges for diagnosis, risk stratification and treatment. The genotype of the patient contributes to this clinical heterogeneity, with the influence of the mutation’s location withinKCNH2on a patient’s risk of a cardiac event being an example. Here we demonstrate that under stringently controlled genetic and experimental conditions, hiPSC-CMs are able to reflect these subtle genotype-phenotype differences, thereby providing new opportunities to stratify and potentially lessen sudden cardiac death risk amongstKCNH2mutation carriers.
Long-term molecular evolutionary rate determines intraspecific genetic diversity
Authors: Wu Jiaqi , Yonezawa Takahiro , Kishino Hirohisa 
Published: November 2019

AbstractWhat determines genetic diversity and how it connects to the various biological traits is unknown. In this work, we offer answers to these questions. By comparing genetic variation of 14,671 mammalian gene trees with thousands of individual genomes of human, chimpanzee, gorilla, mouse and dog/wolf, we found that intraspecific genetic diversity is determined by long-term molecular evolutionary rates, rather thande novomutation rates. This relationship was established during the early stage of mammalian evolution. Expanding this new finding, we developed a method to detect fluctuations of species-specific selection on genes as the deviations of intra-species genetic diversity predicted from long-term rates. We show that the evolution of epithelial cells, rather than of connective tissue, mainly contributes to morphological evolution of different species. For humans, evolution of the immune system and selective sweeps subjected by infectious diseases are most representative of adaptive evolution.