bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of cold rolling on plastic deformation and microstructure of bearing ring
Authors: Deng S. , Hua L. , Shi D.
Published: October 2016

Bearing ring blanks of the high-speed rail bearings, machine tool spindle bearings and wind power bearings have been manufactured through the ring rolling technology. Yet, the microstructure evolution of bearing ring in cold ring rolling remains unclear. In this work, the plastic strain distribution of the rolled ring is first simulated. Then, the microstructure of bearing ring is studied by the electron backscatter diffraction technique. Furthermore, the microstructure changes in cold ring rolling are investigated through band contrast images, and the texture evolutions after various deformation ratios are analysed by the technique of 3D-Euler space distribution. This work provides valuable guidelines for enhanced understanding the role of the cold ring rolling technology on the microstructure evolution of bearing rings.
Multiyear Tracking of Nassau Grouper Spawning Migrations
Authors: Dahlgren C. P. , Buch K. , Rechisky E. , Hixon M. A.
Published: October 2016

An understanding of temporal patterns of migration and spatial connectivity between home ranges and spawning sites is necessary for effective management of species that form transient spawning aggregations. The Nassau Grouper Epinephelus striatus is a Caribbean coral reef fish that displays such spawning aggregations, which have been overfished to the point of threatening the species. Using acoustic telemetry, we examined the size at which Nassau Grouper migrate to spawning aggregations, the timing of migrations, and the distance of migration routes used by Nassau Grouper from within and outside of a large, no-take marine reserve in the central Bahamas. Fish (total n = 19) were tagged in 2004 (n = 6) and 2005 (n = 13) and were tracked for one to four spawning seasons. Fish that were 54 cm TL or greater made spawning migrations, with all but one migrating southward along the shelf edge of Exuma Sound for a distance of 70 km to over 200 km, usually during the December full moon. Fish typically made one migration annually, which lasted from 1 to 3 weeks, with fish remaining at spawning sites for only 1–2 d; however, when the full moon was early in the spawning season, several fish remained away from their home reefs through two lunar cycles or delayed their migrations by a month, and one fish made two migrations. Fish that were migrating for the first time had slower swimming speeds to spawning sites than did experienced fish, but swimming speeds were similar between the two groups during return migrations, suggesting that their migration behavior was learned. Our results demonstrate that spawning migration patterns for this species may be more variable in The Bahamas than at other Caribbean locations. The present findings also have important implications for the management of the species, including increasing the minimum size limit to 54 cm or larger and the use of both marine protected areas and seasonal closures to rebuild the spawning stock.

Received February 1, 2016; accepted July 27, 2016
The Ark: a customizable web-based data management tool for health and medical research
Authors: Bickerstaffe Adrian , Ranaweera Thilina , Endersby Travis , Ellis Christopher , Maddumarachchi Sanjaya , Gooden George E , White Paul , Moses Eric K , Hewitt Alex W , Hopper John L
Published: October 2016

The Ark is an open-source web-based tool that allows researchers to manage health and medical research data for humans and animals without specialized database skills or programming expertise. The system provides data management for core research information including demographic, phenotype, biospecimen and pedigree data, in addition to supporting typical investigator requirements such as tracking participant consent and correspondence, whilst also being able to generate custom data exports and reports. The Ark is ‘study generic’ by design and highly configurable via its web interface, allowing researchers to tailor the system to the specific data management requirements of their study.

Availability and Implementation

Source code for The Ark can be obtained freely from the website https://github.com/The-Ark-Informatics/ark/. The source code can be modified and redistributed under the terms of the GNU GPL v3 license. Documentation and a pre-configured virtual appliance can be found at the website http://sphinx.org.au/the-ark/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Analysis of vertebral chemistry to assess stock structure in a deep-sea shark, Etmopterus spinax
Authors: McMillan Matthew N. , Izzo Christopher , Junge Claudia , Albert Ole Thomas , Jung Armelle , Gillanders Bronwyn M.
Published: October 2016

Deep-sea sharks play a valuable ecological role helping maintain food web balance, yet they are vulnerable to commercial fishing because of slow growth rates and low reproductive capacity. Overfishing of sharks can heavily impact marine ecosystems and the fisheries these support. Knowledge of stock structure is integral to sustainable management of fisheries. The present study analysed vertebral chemistry using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to assay concentrations of 7Li, 23Na, 24Mg, 55Mn, 59Co, 60Ni, 63Cu, 66Zn, 85Rb, 88Sr, 138Ba and 208Pb to assess stock structure in a deep-sea shark, Etmopterus spinax, in Norwegian and French waters. Few studies have applied this technique to elasmobranch vertebrae and the present study represents its first application to a deep-sea shark. Three stocks were identified at the regional scale off western Norway, southern Norway, and France. At finer spatial scales there was evidence of strong population mixing. Overall, the general pattern of stock structure outlined herein provides some indication of the spatial scales at which stocks should be viewed as distinct fisheries management units. The identification of an effective multi-element signature for distinguishing E. spinax stocks utilizing Sr, Ba, Mg, Zn and Pb and the methodological groundwork laid in the present study could also expedite future research into stock structure for E. spinax and deep-sea elasmobranchs more generally.
Impact of the fishery for late-larval European sardine (Sardina pilchardus) on the adult stock in the Adriatic Sea
Authors: Carpi Piera , Morello Elisabetta B. , Uriarte Andres , Panfili Monica , Roel Beatriz , Santojanni Alberto , Donato Fortunata , Arneri Enrico
Published: October 2016

Bianchetto [“white” late-larval and juvenile stages (‘fry’) mainly of sardine (Sardina pilchardus)] was fished traditionally along most of the Italian coast. The Gulf of Manfredonia (southwest Adriatic Sea) hosts a sardine nursery which was historically exploited by the bianchetto fishery using trawlnets; the fishery was banned in 2010. Here, we model this larval fishery under different assumptions of catch and natural mortality to assess its impact on the adult sardine stocks in the Adriatic Sea. The results show that the impact of the fishery is heavily dependent on the choice of early-stage natural mortality. The model proposed by Pepin (1991). Effect of temperature and size on development, mortality, and survival rates of the pelagic early life history stages of marine fish. Canadian Journal of Fisheries and Aquatic Sciences, 48: 503–518. was selected as the most plausible. Under this assumption, the direct effect of the bianchetto fishery in the Gulf of Manfredonia on the Adriatic adult sardine stock appears to be low, but not negligible, with impacts estimated as a 0.1–2% increase in the numbers of sardine at age 1 in the absence of a bianchetto fishery. Projections show that a 5% impact on age 1 sardine may be sufficient to bring the adult stock below safe levels. Therefore, given the uncertainties surrounding the impact assessment and the current status of the stock, if this fishery were to be resumed, catches should be kept at the lowest possible level until the underlying processes are better understood.
Complicated Meckel diverticulum in a 15-year-old boy
Authors: Swickard Amanda , Grosel John M.
Published: October 2016

Meckel diverticulum is the most common gastrointestinal (GI) anomaly, occurring in 2% of the population. This condition often presents symptomatically similar to acute appendicitis in children. The most common presentation is GI hemorrhage, followed closely by obstruction due to intussusception. Laparoscopy is the standard in both diagnosing and treating a complicated Meckel diverticulum.
Distant Migration of Multiple Siliconomas in Lower Extremities following Breast Implant Rupture: Case Report
Authors: Oh Joo Hyun , Song Seung Yong , Lew Dae Hyun , Lee Dong Won
Published: October 2016

Siliconoma from ruptured breast implants has been reported in multiple body sites, including but not limited to the breast parenchyma, axillary lymph nodes, upper arm, and even lower leg. In this regard, we report a rare case of distant silicone migration to the lower extremities after traumatic breast implant rupture. A 55-year-old Asian woman who received bilateral augmentation mammoplasty 20 years ago presented with ruptured breast implants from a car accident 2 years earlier. Magnetic resonance imaging confirmed intracapsular and extracapsular rupture of the right breast implant, showing “linguine sign.” We removed the bilateral breast implants and performed capsulectomy and bilateral reduction mammoplasty using inverted-T incisions. The implant was confirmed as a smooth, silicone gel–filled mammary implant of 125 cm3 by a Japanese manufacturer, Koken. During her regular follow-up outpatient visits, physical examination revealed 2.5- × 1.5-cm ill-defined, tender, subcutaneous nodules on both knees and 8.5- × 3.0-cm inflammatory changes in the inguinal area with persistent pain. Computed tomography showed no definite mass, but rather infiltrative, nonenhancing soft-tissue densities in the subcutaneous layers of the bilateral inguinal and knee areas. Surgical excision was performed, and pathologic findings confirmed variable vacuoles with foreign body reaction and fibrosis, consistent with siliconoma. It is important to acknowledge that siliconomas can be encountered in patients with ruptured breast implants, especially those manufactured decades ago. Our patient with masses as remote as the inguinal and knee areas is a prime example of how far siliconomas can migrate.
Factors Influencing the Incidence of Severe Complications in Head and Neck Free Flap Reconstructions
Authors: Broome Martin , Juilland Naline , Litzistorf Yann , Monnier Yan , Sandu Kishore , Pasche Philippe , Plinkert Peter K. , Federspil Philippe A. , Simon Christian
Published: October 2016

Background:

Complications after head and neck free-flap reconstructions are detrimental and prolong hospital stay. In an effort to identify related variables in a tertiary regional head and neck unit, the microvascular reconstruction activity over the last 5 years was captured in a database along with patient-, provider-, and volume-outcome–related parameters.

Methods:

Retrospective cohort study (level of evidence 3), a modified Clavien-Dindo classification, was used to assess severe complications.

Results:

A database of 217 patients was created with consecutively reconstructed patients from 2009 to 2014. In the univariate analysis of severe complications, we found significant associations (P < 0.05) between type of flap used, American Society of Anesthesiologists classification, T-stage, microscope use, surgeon, flap frequency, and surgeon volume. Within a binomial logistic regression model, less frequently versus frequently performed flap (odds ratio [OR] = 3.2; confidence interval [CI] = 2.9–3.5; P = 0.000), high-volume versus low-volume surgeon (OR = 0.52; CI = −0.22 to 0.82; P = 0.007), and ASA classification (OR = 2.9; CI = 2.4–3.4; P = 0.033) were retained as independent predictors of severe complications. In a Cox-regression model, surgeon (P = 0.011), site of reconstruction (P = 0.000), T-stage (P = 0.001), and presence of severe complications (P = 0.015) correlated with a prolonged hospitalization.

Conclusions:

In this study, we identified a correlation of patient-related factors with severe complications (ASA score) and prolonged hospital stay (T-stage, site). More importantly, we identified several provider- (surgeon) and volume-related (frequency with which a flap was performed and high-volume surgeon) factors as predictors of severe complications. Our data indicate that provider- and volume-related parameters play an important role in the outcome of microvascular free-flap procedures in the head and neck region.
Intralipotherapy, the State of the Art
Authors: Amore Roberto , Pinto Hernán , Gritzalas Kostas , Hernández Carlota , Skwara-Guzikowska Katarzyna , Amuso Domenico , Leonardi Vincenza
Published: October 2016

Background:

Reconstruction intralipotherapy is a term commonly used in the field of aesthetic medicine, above all in Europe, which defines a specific injection technique developed for the treatment of localized fat with substances that provoke the lysis of adipocytes by means of an injection directly into the adipose tissue with a long needle. The aim of this study is to define the technique in detail and everything that is associated with it, on the basis of years of multicenter experience by doctors who perform it.

Materials and Methods:

From January 2010 to December 2014, 3,080 European physicians were trained in intralipotherapy technique, and approximately 152,500 patients were treated. The adipocytolytic agent used is a Conformité Européene-certified device. The technique, equipment, protocol, posology, postoperative management, and adverse events are described below.

Results:

The intralipotherapy technique combined with the appropriate adipocytolytic agent has been shown to be effective in every zone on the average of 76.7% of the cases. The variability is due to the area treated and the patient. The standardization of the technique, homogeneity of the protocol, and the posttreatment management have been essential for standardizing the results and minimizing any adverse events. The latter occurred only in a small percentage of the cases, while those more serious have been extremely rare.

Conclusion:

This study shows how the intralipotherapic technique, when performed properly with an appropriate adipocytolytic device and when proper precautions are taken, can be effective and safe for reducing undesirable subcutaneous fat deposits.
The future of imaging in cardiovascular disease intervention trials: 2017 and beyond
Authors: Doris Mhairi K. , Dweck Marc R. , Fayad Zahi A.
Published: October 2016

Purpose of review

As our understanding of cardiovascular disease has advanced over the past decades, multiple novel treatment strategies have been developed with the hope of reducing the global morbidity and mortality associated with this condition. Large-scale trials to test such novel therapies using clinical end points are expensive, leading to interest in phase II clinical trials with imaging-derived outcome measures.

Recent findings

Noninvasive imaging techniques that assess changes in both atherosclerotic disease burden and plaque composition in response to therapy are well established. With the advent of molecular techniques and hybrid imaging, we now have the ability to assess disease activity alongside these standard anatomic assessments. This multifaceted approach has the potential to provide a more comprehensive assessment of the actions and efficacy of novel therapies in the carotids, aorta and coronary arteries.

This review will examine how advanced noninvasive imaging strategies have been used to investigate drug efficacy in intervention trials to date, and crucially how these approaches are set to evolve and play a central role in developing the next generation of atherosclerotic medication.
Unique Educational Needs of Emergency Nurse Practitioners
Authors: Keough Vicki A. , Tell Dina , Andreoni Colleen , Tanabe Paula
Published: October 2016

The purpose of this study is to identify the unique educational needs of emergency nurse practitioners (ENPs). A survey from 167 nurse practitioners (NPs) practicing in the emergency department (ED) settings was analyzed. A variety of certified NPs practice in EDs: family NPs (30%), adult NPs (18%), acute care NPs (40%), and some with 2 or more certifications (12%). NPs come with a variety of basic educational preparations. The top educational needs specific to ENP preparation identified were managing critically ill patients, pharmacology, interpretation of laboratory tests, electrocardiograms, radiographs, and computed tomographic scans, suturing superficial lacerations, and mentoring by MDs and NPs. The unique and complex ED environment requires that NPs practicing in the ED receive a unique set of standardized education and skills to meet the demands of current practice. A standardized educational curriculum that includes the findings from this and other studies, along with additional clinical and a national certification examination, is discussed.
The Triage Interruptions Assessment Tool
Authors: Johnson Kimberly D. , Gillespie Gordon L. , Vance Kimberly
Published: October 2016

Interruptions contribute to catastrophic errors in health care. Interruptions are breaks in the performance of a human activity initiated by a source internal or external to the recipient. Errors during the initial triage assessment can lead to errors in estimating the acuity of a patient and resources required for appropriate care. To advance the science, a valid and reliable instrument to measure this phenomenon is required. The purpose of this mixed-methods/exploratory sequential study was to develop an instrument sensitive to the uniqueness of the triage assessment that would categorize and measure the number and causes of triage interruptions. The study included 3 phases. Phase 1: Qualitative focus groups were used to qualitatively explore interruptions in triage. In Phase 2: Content Validity Assessment, an online survey was used and a content validity index was calculated for each item to determine which items should be modified or removed. A descriptive correlational design was used to assess interrater reliability in Phase 3. Many of the items identified during the focus group sessions were already on the study instrument; some new items were added. Content validity for the entire instrument was 0.82 and increased to 0.91 once irrelevant items were removed. Interrater reliability for the entire instrument demonstrated substantial agreement at 0.773. The study instrument was shown to have strong psychometrics and can be used in practice to better understand what interruptions are occurring in triage and how they affect the triage process.
TheC. elegansfemale state: Decoupling the transcriptomic effects of aging and sperm-status
Authors: Angeles-Albores David , Leighton Daniel H. W. , Tsou Tiffany , Khaw Tiffany H. , Antoshechkin Igor , Sternberg Paul W.
Published: October 2016

Understanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. AlthoughC. elegansis traditionally thought of as a hermaphrodite, XX animals exhaust their sperm and become endogenous females after 3days of egg-laying. Themolecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism that occur at this stage. To study the female state ofC. elegans, we measured the transcriptomes of 1st day adult hermaphrodites; endogenous, 6th day adult females; and at the same time points, mutantfog-2(lf)worms that have a feminized germline phenotype. At these time points, we could separate the effects of biological aging from the transition into the female state.fog-2(lf)mutants partially phenocopy 6 day adult wild-type animals and exhibit fewer differentially expressed genes as they age throughout these 6 days. Therefore,fog-2is epistatic to age as assessed by this transcriptomic phenotype, which indicates that both factors act on sperm status to mediate entry into the female state. These changes are enriched in transcription factors canonically associated with neuronal development and differentiation. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm.
Pooled CRISPR screening with single-cell transcriptome read-out
Authors: Datlinger Paul , Schmidl Christian , Rendeiro André F , Traxler Peter , Klughammer Johanna , Schuster Linda , Bock Christoph
Published: October 2016

CRISPR-based genetic screens have revolutionized the search for new gene functions and biological mechanisms. However, widely used pooled screens are limited to simple read-outs of cell proliferation or the production of a selectable marker protein. Arrayed screens allow for more complex molecular read-outs such as transcriptome profiling, but they provide much lower throughput. Here we demonstrate CRISPR genome editing together with single-cell RNA sequencing as a new screening paradigm that combines key advantages of pooled and arrayed screens. This approach allowed us to link guide-RNA expression to the associated transcriptome responses in thousands of single cells using a straightforward and broadly applicable screening workflow.
Predictive representations can link model-based reinforcement learning to model-free mechanisms
Authors: Russek Evan M. , Momennejad Ida , Botvinick Matthew M. , Gershman Samuel J. , Daw Nathaniel D.
Published: October 2016

Humans and animals are capable of evaluating actions by considering their long-run future rewards through a process described using model-based reinforcement learning (RL) algorithms. The mechanisms by which neural circuits perform the computations prescribed by model-based RL remain largely unknown; however, multiple lines of evidence suggest that neural circuits supporting model-based behavior are structurally homologous to and overlapping with those thought to carry out model-free temporal difference (TD) learning. Here, we lay out a family of approaches by which model-based computation may be built upon a core of TD learning. The foundation of this framework is the successor representation, a predictive state representation that, when combined with TD learning of value predictions, can produce a subset of the behaviors associated with model-based learning, while requiring less decision-time computation than dynamic programming. Using simulations, we delineate the precise behavioral capabilities enabled by evaluating actions using this approach, and compare them to those demonstrated by biological organisms. We then introduce two new algorithms that build upon the successor representation while progressively mitigating its limitations. Because this framework can account for the full range of observed putatively model-based behaviors while still utilizing a core TD framework, we suggest that it represents a neurally plausible family of mechanisms for model-based evaluation.

Author Summary

According to standard models, when confronted with a choice, animals and humans rely on two separate, distinct processes to come to a decision. One process deliberatively evaluates the consequences of each candidate action and is thought to underlie the ability to flexibly come up with novel plans. The other process gradually increases the propensity to perform behaviors that were previously successful and is thought to underlie automatically executed, habitual reflexes. Although computational principles and animal behavior support this dichotomy, at the neural level, there is little evidence supporting a clean segregation. For instance, although dopamine — famously implicated in drug addiction and Parkinson’s disease — currently only has a well-defined role in the automatic process, evidence suggests that it also plays a role in the deliberative process. In this work, we present a computational framework for resolving this mismatch. We show that the types of behaviors associated with either process could result from a common learning mechanism applied to different strategies for how populations of neurons could represent candidate actions. In addition to demonstrating that this account can produce the full range of flexible behavior observed in the empirical literature, we suggest experiments that could detect the various approaches within this framework.
Time dependent genetic analysis links field and controlled environment phenotypes in the model C4grassSetaria
Authors: Feldman Max J. , Paul Rachel E. , Banan Darshi , Barrett Jennifer F. , Sebastian Jose , Yee Muh-Ching , Jiang Hui , Lipka Alexander E. , Brutnell Thomas P. , Dinneny José R. , Leakey Andrew D.B. , Baxter Ivan
Published: October 2016

Vertical growth of plants is a dynamic process that is influenced by genetic and environmental factors and has a pronounced effect on overall plant architecture and biomass composition. We have performed twelve controlled growth trials of an interspecificSetaria italicaxSetaria viridisrecombinant inbred line population to assess how the genetic architecture of plant height is influenced by developmental queues, water availability and planting density. The nondestructive nature of plant height measurements has enabled us to monitor vertical growth throughout the plant life cycle in both field and controlled environments. We find that plant height is reduced under water limitation and high density planting and affected by growth environment (field vs. growth chamber). The results support a model where plant height is a heritable, polygenic trait and that the major genetic loci that influence plant height function independent of growth environment. The identity and contribution of loci that influence height changes dynamically throughout development and the reduction of growth observed in water limited environments is a consequence of delayed progression through the genetic program which establishes plant height inSetaria.In this population, alleles inherited from the weedyS. viridisparent act to increase plant height early, whereas a larger number of small effect alleles inherited from the domesticatedS. italicaparent collectively act to increase plant height later in development.
The transcriptional repressor HIC1 regulates intestinal immune homeostasis
Authors: Burrows Kyle , Antignano Frann , Bramhall Michael , Chenery Alistair , Scheer Sebastian , Korinek Vladimir , Underhill T. Michael , Zaph Colby
Published: October 2016

The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor Hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T cell-specific deletion of HIC1 have reduced numbers of T cells in the LP. HIC1 expression is regulated by the Vitamin A metabolite retinoic acid, as mice raised on a Vitamin A-deficient diet lack HIC1-positive cells in the intestine. HIC1-deficient T cells overproduce IL-17A in vitro and in vivo, and fail to induce intestinal inflammation, identifying a critical role for HIC1 in the regulation of T cell function in the intestinal microenvironment under both homeostatic and inflammatory conditions.
A defensive body plan was pre-adaptive for termitophily in the rove beetle tribe Termitohospitini (Staphylinidae: Aleocharinae)
Authors: Kanao T. , Eldredge K.T. , Maruyama M.
Published: October 2016

Termitophily—the symbiosis of organisms with termite societies—has evolved a disproportionate number of times within the rove beetle subfamily Aleocharinae (Staphylinidae). Among aleocharine termitophiles, defensive (limuloid) and mimetic (physogastric & physothoracic) body forms have evolved convergently, but due to lack of a comprehensive aleocharine phylogeny, the context in which termitophily and associated adaptations evolve is unknown. We present the first example of a robust, morphology-based phylogenetic placement of an exclusively termitophilous tribe, the Termitohospitini. Termitohospitini is recovered to be nested within Myllaeninisensu nov, and sister to Myllaena (new synonymy). Furthermore, we also recovered the small tribe Masuriini nested within Myllaeninisensu nov(new status).

Reconstructing ecological transitions within this clade, we present evidence that the stem lineage of Myllaenini sensu nov invaded intertidal marine habitats, the common ancestor for Myllaena + Termitohospitini then transitioned to freshwater riparian habitats, with Termitohospitini alone subsequently shifting to termitophily. We conclude that: (1) Termitohospitini was ancestrally a limuloid-bodied riparian inhabitant; (2) a limuloid form may have been pre-adaptive for defense against host attack during the evolution of termitophily; (3) the strongly tapered abdomen of an ancestral limuloid body was a constraint on the evolution of physogastry, leading to the emergence of the unusual physothoracic body form observed in termitohospitines that likely integrates these obligate termitophiles to life inside termite colonies.

“one of the most astonishing spectacles in all natural history.” — Richard Dawkins
Cultural transmission and biological markets
Authors: Loverdo Claude , Viciana Hugo
Published: October 2016

Active cultural transmission of fitness-enhancing behavior can be seen as a costly strategy, one whose evolutionary stability poses a Darwinian puzzle. In this article, we offer a biological market model of cultural transmission that substitutes or complements existing kin-selection based theories for the evolution of cultural capacities. We explicitly formulate how a biological market can account for the evolution of deference and prestige-related phenomena, as well as how it can affect the dynamics of cumulative culture. We show that, under certain conditions, teaching evolves even when innovations are not sufficiently opaque and can be acquired by emulators via inadvertent transmission. Furthermore, teaching in a biological market is a precondition for enhanced individual learning abilities.
FSTand kinship for arbitrary population structures I: Generalized definitions
Authors: Ochoa Alejandro , Storey John D.
Published: October 2016

FSTis a fundamental measure of genetic differentiation and population structure, currently defined for subdivided populations.FSTin practice typically assumesindependent, non-overlapping subpopulations, which all split simultaneously from their last common ancestral population so that genetic drift in each subpopulation is probabilistically independent of the other subpopulations. We introduce a generalizedFSTdefinition for arbitrary population structures, where individuals may be related in arbitrary ways, allowing for arbitrary probabilistic dependence among individuals. Our definitions are built on identity-by-descent (IBD) probabilities that relate individuals through inbreeding and kinship coefficients. We generalizeFSTas the mean inbreeding coefficient of the individuals’ local populations relative to their last common ancestral population. We show that the generalized definition agrees with Wright’s original and the independent subpopulation definitions as special cases. We define a novel coancestry model based on “individual-specific allele frequencies” and prove that its parameters correspond to probabilistic kinship coefficients. Lastly, we extend the Pritchard-Stephens-Donnelly admixture model in the context of our coancestry model and calculate itsFST. To motivate this work, we include a summary of analyses we have carried out in follow-up papers, where our new approach has been applied to simulations and global human data, showcasing the complexity of human population structure, demonstrating our success in estimating kinship andFST, and the shortcomings of existing approaches. The probabilistic framework we introduce here provides a theoretical foundation that extendsFSTin terms of inbreeding and kinship coefficients to arbitrary population structures, paving the way for new estimators and novel analyses.

Note: This article is Part I of two-part manuscripts. We refer to these in the text as Part I and Part II, respectively.

Part I:Alejandro Ochoa and John D. Storey. “FSTand kinship for arbitrary population structures I: Generalized definitions”.bioRxiv(10.1101/083915) (2019).https://doi.org/10.1101/083915. First published 2016-10-27.

Part II:Alejandro Ochoa and John D. Storey. “FSTand kinship for arbitrary population structures II: Method of moments estimators”.bioRxiv(10.1101/083923) (2019).https://doi.org/10.1101/083923. First published 2016-10-27.
Effects of dimethyl sulfoxide on surface water near phospholipid bilayers
Authors: Lee Yuno , Pincus Philip A. , Hyeon Changbong
Published: October 2016

Despite much effort to probe the properties of dimethyl sulfoxide (DMSO) solution, effects of DMSO on water, especially near plasma membrane surfaces still remain elusive. By performing molecular dynamics (MD) simulations at varying DMSO concentrations (XDMSO), we study how DMSO affects structural and dynamical properties of water in the vicinity of phospholipid bilayers. As proposed by a number of experiments, our simulations confirm that DMSO induces dehydration from bilayer surfaces and disrupts the H-bond structure of water. However, DMSO enhanced water diffusivity at solvent-bilayer interfaces, an intriguing discovery reported by a spin-label measurement, is not confirmed in our simulations. In order to resolve this discrepancy, we examine the location of the spin-label (Tempo), relative to the solvent-bilayer interface. In accord with the evidence in the literature, our simulations, which explicitly model Tempo-PC, find that the Tempo moiety is equilibrated at ~ 8 – 10 Åbelowthe bilayer surface. Furthermore, the DMSO-enhanced surface water diffusion is confirmed only when water diffusion is analyzed around the Tempo moiety that is immersed below the bilayer surface, which implies that the experimentally detected signal of water using Tempo stems from the interior of bilayers, not from the interface. Our analysis finds that the increase of water diffusion below the bilayer surface is coupled to the increase of area per lipid with an increasingXDMSO(≲ 10 mol%). Underscoring the hydrophobic nature of Tempo moiety, our study calls for careful re-evaluation of the use of Tempo in the measurement on lipid bilayer surfaces.
The Identification of Source and Vector of a Prolific Marine Invader
Authors: Krueger-Hadfield Stacy A. , Kollars Nicole M. , Strand Allan E. , Byers James E. , Shainker Sarah J. , Terada Ryuta , Greig Thomas W. , Hammann Mareike , Murray David C. , Weinberger Florian , Sotka Erik E.
Published: October 2016

The source and vector of an introduced species inform its ecological and evolutionary history and may guide management that seeks to prevent future introductions. Surprisingly, few studies have successfully used genetic tools to independently inform the specific source and pathway of biological invasions. The ecological history of many introduced species, including their origins and vectors, is often based on suppositions or educated guesses. Here, we used mitochondrial and microsatellite genotyping to trace the invasion of the Asian seaweedGracilaria vermiculophylla(Rhodophyta) along the three coastlines of the Northern Hemisphere to which it has been introduced: the western coast of North America, eastern coast of the United States and the coasts of Europe and northwest Africa. Analyzing 37 native and 53 introduced sites, we identified the Pacific coastline of northeastern Japan as the ultimate source of the Northern Hemisphere invasion. Coincidentally, most exports of the oysterCrassostrea gigashistorically originated from this region and both species often grow in close proximity. Based on genetic signatures, each of the three coastlines likely received thalli directly from Japan, as well as material from another introduced coastline (i.e., a secondary invasion). Our ability to document a source region, which was enabled by a robust sampling of locations and loci that previous studies lacked, reflected strong phylogeographic structure along native coastlines. We suggestGracilaria vermiculophyllais an important representative example of many species likely exported out of Japan by the oyster trade and its genetic signatures that may be a hallmark of oyster introduction legacies.
Transposable element exaptation is the primary source of novelty in the primate gene regulatory landscape
Authors: Trizzino Marco , Park YoSon , Holsbach-Beltrame Marcia , Aracena Katherine , Mika Katelyn , Caliskan Minal , Perry George H. , Lynch Vincent J. , Brown Christopher D.
Published: October 2016

Gene regulation plays a critical role in the evolution of phenotypic diversity. We investigated the evolution of liver promoters and enhancers in six primate species. We performed ChlP-seq for two histone modifications and RNA-seq to profile cis-regulatory element (CRE) activity and gene expression. The primate regulatory landscape is largely conserved across the lineage. Conserved CRE function is associated with sequence conservation, proximity to coding genes, cell type specificity of CRE function, and transcription factor binding. Newly evolved CREs are enriched in immune response and neurodevelopmental functions, while conserved CREs bind master regulators. Transposable elements (TEs) are the primary source of novelty in primate gene regulation. Newly evolved CREs are enriched in young TEs that affect gene expression. However, only 17% of conserved CREs overlap a TE, suggesting that target gene expression is under strong selection. Finally, we identified specific genomic features driving the functional recruitment of newly inserted TEs.
Mocap: Large-scale inference of transcription factor binding sites from chromatin accessibility
Authors: Chen Xi , Yu Bowen , Carriero Nicholas , Silva Claudio , Bonneau Richard
Published: October 2016

Differential binding of transcription factors (TFs) atcis-regulatory loci drives the differentiation and function of diverse cellular lineages. Understanding the regulatory interactions that underlie cell fate decisions requires characterizing TF binding sites (TFBS) across multiple cell types and conditions. Techniques, e.g. ChIP-Seq can reveal genome-wide patterns of TF binding, but typically requires laborious and costly experiments for each TF-cell-type (TFCT) condition of interest. Chromosomal accessibility assays can connect accessible chromatin in one cell type to many TFs through sequence motif mapping. Such methods, however, rarely take into account that the genomic context preferred by each factor differs from TF to TF, and from cell type to cell type. To address the differences in TF behaviors, we developed Mocap, a method that integrates chromatin accessibility, motif scores, TF footprints, CpG/GC content, evolutionary conservation and other factors in an ensemble of TFCT-specific classifiers. We show that integration of genomic features, such as CpG islands improves TFBS prediction in some TFCT. Further, we describe a method for mapping new TFCT, for which no ChIP-seq data exists, onto our ensemble of classifiers and show that our cross-sample TFBS prediction method outperforms several previously described methods.
MSMBuilder: Statistical Models for Biomolecular Dynamics
Authors: Harrigan Matthew P. , Sultan Mohammad M. , Hernández Carlos X. , Husic Brooke E. , Eastman Peter , Schwantes Christian R. , Beauchamp Kyle A. , McGibbon Robert T. , Pande Vijay S.
Published: October 2016

MSMBuilder is a software package for building statistical models of high-dimensional time-series data. It is designed with a particular focus on the analysis of atomistic simulations of biomolecular dynamics such as protein folding and conformational change. MSMBuilder is named for its ability to construct Markov State Models (MSMs), a class of models that has gained favor among computational biophysicists. In addition to both well-established and newer MSM methods, the package includes complementary algorithms for understanding time-series data such as hidden Markov models (HMMs) and time-structure based independent component analysis (tICA). MSMBuilder boasts an easy to use command-line interface, as well as clear and consistent abstractions through its Python API (application programming interface). MSMBuilder is developed with careful consideration for compatibility with the broader machine-learning community by following the design of scikit-learn. The package is used primarily by practitioners of molecular dynamics but is just as applicable to other computational or experimental time-series measurements.http://msmbuilder.org
An exactly solvable, spatial model of mutation accumulation in cancer
Authors: Paterson Chay , Nowak Martin A. , Waclaw Bartlomiej
Published: October 2016

One of the hallmarks of cancer is the accumulation of driver mutations which increase the net reproductive rate of cancer cells and allow them to spread. This process has been studied in mathematical models of well mixed populations, and in computer simulations of three-dimensional spatial models. But the computational complexity of these more realistic, spatial models makes it difficult to simulate realistically large and clinically detectable solid tumours. Here we describe an exactly solvable mathematical model of a tumour featuring replication, mutation and local migration of cancer cells. The model predicts a quasi-exponential growth of large tumours even if different fragments of the tumour grow sub-exponentially due to nutrient and space limitations. The model reproduces clinically observed tumour growth times using biologically plausible rates for cell birth, death, and migration rates. We also show that the expected number of accumulated driver mutations increases exponentially in time if the average fitness gain per driver is constant, and that it reaches a plateau if the gains decrease over time. We discuss the realism of the underlying assumptions and possible extensions of the model.
Crystal structure determination as part of an undergraduate laboratory experiment: 1′,3′,3′-trimethylspiro[chromene-2,2′-indoline] and 1′,3′,3′-trimethyl-4-[(E)-(1,3,3-trimethylindolin-2-ylidene)methyl]spiro[chroman-2,2′-indoline]
Authors: Beckett Joseph O. S. , Olmstead Marilyn M. , Fettinger James C. , Gray David A. , Manabe Shuhei , Mascal Mark
Published: October 2016

The crystal structures of the title compounds, C19H19NO and C31H34N2O, were determined as part of an experiment in an undergraduate teaching laboratory that demonstrates the relationship between molecular structure and function. 1′,3′,3′-Trimethylspiro[chromene-2,2′-indoline] is both a photoswitch and thermochromic molecule. Students synthesized it and a bis-indoline adduct and compared the crystallographically determined structures to computed gas-phase models.
Crystal structure of poly[dichlorido(μ-2,5-dicarboxybenzene-1,4-dicarboxylato-κ2
O
1:O
4)bis[μ-4′-(pyridin-3-yl)-4,2′:6′,4′′-terpyridine-κ2
N
1:N
4′]dizinc]
Authors: Tian Yue , Xu Sha-Sha , Su Jian , Zhang Yang , Zhao Shao-Shuai , Tian Yu-Peng
Published: October 2016

In the title polymeric ZnII complex, [Zn2(C10H4O8)Cl2(C20H14N4)2]
n
, the ZnII cations are bridged by both 2,5-dicarboxybenzene-1,4-dicarboxylate dianions and 4′-(pyridin-3-yl)-4,2′:6′,4′′-terpyridine ligands, forming ladder-like polymeric chains propagating along [1-10]. The Cl− anion further coordinates the ZnII cation to complete a distorted tetrahedral environment. In the 4′-(pyridin-3-yl)-4,2′:6′,4′′-terpyridine ligand, the three sideward pyridine rings are twisted with respect to the central pyridine ring by 39.27 (12), 14.89 (13) and 3.36 (13)°, respectively. In the crystal, classical O—H...N hydrogen bonds and weak C—H...O and C—H...Cl hydrogen bonds link the chains into a three-dimensional supramolecular architecture. π–π stacking is observed between the pyridine and benzene rings of neighbouring polymeric chains, with a centroid-to-centroid distance of 3.7280 (14) Å.
Crystal structure of 5-butylamino-3-methyl-1-(pyridin-2-yl)-1H-pyrazole-4-carbaldehyde obtained from a microwave-assisted reaction using caesium carbonate as catalyst
Authors: Macías Mario A. , Orrego-Hernández Jessica , Portilla Jaime
Published: October 2016

The title compound, C14H18N4O, synthesized from an unconventional microwave-assisted method using caesium carbonate as catalyst, has an approximately planar conformation with the pyridyl and pyrazole rings inclined by a dihedral angle of 7.94 (3)°, allowing the formation of an intramolecular N—H...N hydrogen bond. The supramolecular assembly has a three-dimensional arrangement controlled mainly by weak C—H...O and C—H...π interactions.
A public database of macromolecular diffraction experiments
Authors: Grabowski Marek , Langner Karol M. , Cymborowski Marcin , Porebski Przemyslaw J. , Sroka Piotr , Zheng Heping , Cooper David R. , Zimmerman Matthew D. , Elsliger Marc-André , Burley Stephen K. , Minor Wladek
Published: October 2016

The low reproducibility of published experimental results in many scientific disciplines has recently garnered negative attention in scientific journals and the general media. Public transparency, including the availability of `raw' experimental data, will help to address growing concerns regarding scientific integrity. Macromolecular X-ray crystallography has led the way in requiring the public dissemination of atomic coordinates and a wealth of experimental data, making the field one of the most reproducible in the biological sciences. However, there remains no mandate for public disclosure of the original diffraction data. The Integrated Resource for Reproducibility in Macromolecular Crystallography (IRRMC) has been developed to archive raw data from diffraction experiments and, equally importantly, to provide related metadata. Currently, the database of our resource contains data from 2920 macromolecular diffraction experiments (5767 data sets), accounting for around 3% of all depositions in the Protein Data Bank (PDB), with their corresponding partially curated metadata. IRRMC utilizes distributed storage implemented using a federated architecture of many independent storage servers, which provides both scalability and sustainability. The resource, which is accessibleviathe web portal at http://www.proteindiffraction.org, can be searched using various criteria. All data are available for unrestricted access and download. The resource serves as a proof of concept and demonstrates the feasibility of archiving raw diffraction data and associated metadata from X-ray crystallographic studies of biological macromolecules. The goal is to expand this resource and include data sets that failed to yield X-ray structures in order to facilitate collaborative efforts that will improve protein structure-determination methods and to ensure the availability of `orphan' data left behind for various reasons by individual investigators and/or extinct structural genomics projects.