bluuebunny/crossref_metadata_2025 huggingface dataset:
Venomics: integrative venom proteomics and beyond
Authors: Calvete Juan J.
Published: February 2017

Venoms are integrated phenotypes that evolved independently in, and are used for predatory and defensive purposes by, a wide phylogenetic range of organisms. The same principles that contribute to the evolutionary success of venoms, contribute to making the study of venoms of great interest in such diverse fields as evolutionary ecology and biotechnology. Evolution is profoundly contingent, and nature also reinvents itself continuosly. Changes in a complex phenotypic trait, such as venom, reflect the influences of prior evolutionary history, chance events, and selection. Reconstructing the natural history of venoms, particularly those of snakes, which will be dealt with in more detail in this review, requires the integration of different levels of knowledge into a meaningful and comprehensive evolutionary framework for separating stochastic changes from adaptive evolution. The application of omics technologies and other disciplines have contributed to a qualitative and quantitative advance in the road map towards this goal. In this review we will make a foray into the world of animal venoms, discuss synergies and complementarities of the different approaches used in their study, and identify current bottlenecks that prevent inferring the evolutionary mechanisms and ecological constraints that molded snake venoms to their present-day variability landscape.
Detection of co-orbital planets by combining transit and radial-velocity measurements
Authors: Leleu A. , Robutel P. , Correia A. C. M. , Lillo-Box J.
Published: February 2017

Co-orbital planets have not yet been discovered, although they constitute a frequent by-product of planetary formation and evolution models. This lack may be due to observational biases, since the main detection methods are unable to spot co-orbital companions when they are small or near the Lagrangian equilibrium points. However, for a system with one known transiting planet (with mass m1), we can detect a co-orbital companion (with mass m2) by combining the time of mid-transit with the radial-velocity data of the star. Here, we propose a simple method that allows the detection of co-orbital companions, valid for eccentric orbits, that relies on a single parameter α, which is proportional to the mass ratio m2/m1. Therefore, when α is statistically different from zero, we have a strong candidate to harbour a co-orbital companion. We also discuss the relevance of false positives generated by different planetary configurations.
La lumiére pourrait-elle traiter le cancer par interactions lumiére-vivant ?
Authors: Garcia Guillaume , Maillard Philippe , Mispelter Joël , Poyer Florent , Thomas Carole D.
Published: February 2017

Depuis plusieurs milliers d'années, la lumière qu'elle soit naturelle ou artificielle a été utilisée comme traitement de maladies de la peau, des yeux ou contre le cancer. Ce n'est qu'au début du XXe siècle que la science s'est intéressée aux interactions « lumière-vivant ». La compréhension de l'action conjuguée, dénommée « photothérapie dynamique », d'un médicament non toxique à l'obscurité, de l'oxygène et de la lumière a permis de mettre au point un protocole d'éradication de tumeurs bénignes ou malignes et d'anomalies vasculaires. Depuis environ 30 ans, on voit apparaître de nombreuses molécules photoactivables de plus en plus efficaces. Peu de molécules photosensibles ont encore atteint le stade clinique, mais les résultats publiés dans la littérature scientifique montrent que la photothérapie dynamique est en plein développement et a un avenir certain [1-3].
Quality-of-Life Outcomes of Patients following Patellofemoral Stabilization Surgery: The Influence of Trochlear Dysplasia
Authors: Hiemstra Laurie , Lafave Mark , Kerslake Sarah
Published: February 2017

Trochlear dysplasia is a well-described risk factor for recurrent patellofemoral instability. Despite its clear association with the incidence of patellofemoral instability, it is unclear whether the presence of high-grade trochlear dysplasia influences clinical outcome after patellofemoral stabilization. The purpose of this study was to assess whether trochlear dysplasia influenced patient-reported, disease-specific outcomes in surgically treated patellar instability patients, when risk factors were addressed in accordance with the à la carte surgical approach to the treatment of patellofemoral instability. The study design is of a case series. A total of 318 patellar stabilization procedures were performed during the study period. Of these procedures, 260 had adequate lateral radiographs and complete Banff Patellar Instability Instrument (BPII) scores available for assessment. A Pearson r correlation was calculated between four characteristics of trochlear dysplasia, the BPII total and the BPII symptoms, and physical complaints scores, a mean of 24 months following patellofemoral stabilization. Independent t-tests were performed between stratified trochlear dysplasia groups (no/low grade and high grade) and all BPII measures. There was a statistically significant correlation between measures of trochlear dysplasia and quality-of-life physical symptoms scores, an average of 2 years following patellofemoral stabilization surgery. The BPII symptoms and physical complaints domain score, as well as the individual weakness and stiffness questions, correlated with the classification of trochlear dysplasia as well as the presence of a trochlear bump (p < 0.05). Independent t-tests demonstrated statistically significant differences between the no/low-grade and high-grade dysplasia groups for the BPII stiffness (p = 0.002), BPII weakness (p = 0.05) and BPII symptom, and physical complaints values (p = 0.04). Two additional measures—the 24-month postoperative total BPII score (p = 0.11) and BPII pain score (p = 0.07)—demonstrated trends toward statistical significance. This research has established a statistically significant correlation between trochlear dysplasia and disease-specific quality-of-life outcomes following patellofemoral stabilization surgery. There was a significant correlation between patient-reported physical symptoms after surgery and high-grade trochlear dysplasia.
Arthroscopic Treatment of Isolated Hoffa Fractures
Authors: Baca Emre , Kural Cemal , Ercin Ersin
Published: February 2017

The goal of this study was to evaluate the results of a novel method, arthroscopic fixation of isolated Hoffa fractures.This is a prospective, case series and set at Level 1 trauma center. A total of eight patients with isolated Hoffa fractures who were operated by arthroscopic screw fixation method in the anterior posterior direction with 6.5 mm cannulated screws were followed up prospectively. Same surgical method used for all patients. All patients underwent the same rehabilitation program and active range of motion (ROM) exercises were started immediately. The International Knee Society (IKS) knee and functional scores, postoperative knee ROMs, and time of bone union were used as outcome measurements. Postoperative knee ROMs was compared with the contralateral healthy knee. The mean follow-up time was 29 months (26 − 41 months). At the final review, no significant difference (p = 0.159) was found between the ROM of healthy side and operated side of patients (153.1 ± 4.6 and 150 ± 3.8). The mean IKS knee and functional scores at 12 months were 87.2 ± 5.8 and 96.8 ± 3.7, respectively. Union was achieved in all patients at a mean duration of 3.8 months. Fracture side had no influence on the IKS knee scores, functional scores, and ROM (p = 0.846, p = 0.913, and p = 0.374, respectively). Concomitant intra-articular lesions identified in two patients (%25) during arthroscopy were one anterior cruciate ligament rupture and one medial meniscus tear. Patients undergoing arthroscopic Hoffa fracture fixation have excellent outcomes at average 29 months postoperatively with no apparent complications and no significant loss of ROM. Also 25% of patients had intra-articular injuries that were identified with arthroscopic technique that may have been missed with the open technique. The level of evidence was Level 4 (case series).
Single-Bundle versus Double-Bundle Anterior Cruciate Ligament Reconstruction: A Prospective Randomized Controlled Trial with 6-Year Follow-up
Authors: Dini Francesco , de Girolamo Laura , Cattani Massimo , Rosa Michele , Adravanti Paolo
Published: February 2017

Single-bundle (SB) anterior cruciate ligament (ACL) reconstruction is increasingly used in a large number of patients and it allows obtaining very good clinical and subjective results; however, functional tests show a persistent rotational instability. Biomechanical studies seem to indicate that double-bundle (DB) ACL reconstruction allows to obtain increased anterior and rotational stability compared with SB. The aim of this prospective randomized controlled study was to compare the clinical outcome and the possible osteoarthritic evolution of patients treated either with a SB (freehand transtibial femoral tunnel) or with a DB technique (outside-in for posterolateral femoral tunnel/inside-out for anteromedial femoral tunnel) at a final follow-up of 6 years. A total of 60 patients with complete ACL rupture (age, 16–40 years) were prospectively randomized to SB (n = 30) or DB (n = 30) groups. Patients were evaluated preoperatively and after surgery at 6 months, 1, 3, and 6 years with Lysholm score, International Knee Documentation Committee (IKDC) form, and KT-2000 (Medmetric Corp). The degree of osteoarthritis (OA) based on the Kellgren–Lawrence grade was also assessed. No significant differences in background factors between the two groups were observed. Homogeneity was also found in term of preoperative Lysholm score, IKDC, and KT-2000 between SB and DB groups. After 6 months from surgery, both groups showed significant improvements for Lysholm, IKDC, and KT-2000 score with respect to preoperative observations (p < 0.001); however, no significant differences have been observed in term of postoperative values between SB and DB groups at each time point (6-year evaluation: Lysholm score 98.14 ± 10.03 and 97.22 ± 12.82; IKDC normal + nearly normal 95 and 100%; KT-2000 1.68 ± 1.26 and 1.03 ± 1.92 for SB and DB, respectively; all p > 0.05). At the final follow-up, three patients (11.11%) in the DB group and two patients (7.69%) in the SB group presented signs of OA progression. Our study did not reveal any advantages in using DB ACL reconstruction in mid- to long-term follow-up in term of clinical outcome and knee stability, as well as in term of OA progression.
Resuscitation with Intact Placental Circulation in a Preterm Infant with Hydrops Fetalis
Authors: Pratesi Simone , Corsini Iuri , Coviello Caterina , Perugi Silvia , Dani Carlo
Published: February 2017

A preterm infant with prenatal diagnosis of hydrops fetalis was spontaneously delivered at 30 weeks of gestational age in a tertiary level hospital. Prenatal echography pointed out severe bilateral pleural effusions and diffused subcutaneous edema. A neonatologist team, alerted at the expulsion stage of labor, assisted the neonate immediately after birth and bilateral hydrothorax was drained with intact placental circulation to avoid a nonrespiratory period and its possible detrimental hemodynamic effects. The newborn was well stabilized in the delivery room before cutting the umbilical cord and starting mechanical ventilation. Unfortunately, our patient died due to refractory respiratory failure on the fourth day of life. However, the intact placental circulation procedure was performed without adverse effects to the infant and might represent a promising option in addition to other resuscitation procedures for the management of this type of patient.
Muscle Response to Complete Peripheral Nerve Injury: Changes of Acetylcholine Receptor and Creatine Kinase Activity over Time
Authors: Shainberg Asher , Rochkind Shimon
Published: February 2017

Background This study was designed to assess the changes of acetylcholine receptor (AChR) and creatine kinase (CK) levels, which are important biochemical markers for muscle viability in cases of long-term muscle denervation. Scientists and peripheral nerve surgeons may find these data important regarding maximal range of muscle viability applicable for timing of effective peripheral nerve reconstructive surgery.

Methods The study was conducted on 48 rats (96 gastrocnemius muscles), whose right legs were denervated by removing a 10-mm segment of sciatic nerve, while their left legs remained intact. Under general anesthesia, the rats were euthanized at seven points in time, on days 7, 14, 21, 30, 60, 120, and 210. In both legs, AChR was quantified by 125I-α-bungarotoxin, whereas CK activity was measured using a spectrophotometric method.

Results CK levels in the denervated limb reached a minimal level of 34% on day 30 in comparison to the intact limb and remained at this level up to 210 days after operation. AChR levels in the denervated limb reached a minimal level of 38% on day 120 in comparison to the intact limb and remained at this level up to 210 days after operation.

Conclusion The present study shows that AChR and CK levels in rat denervated muscles remain constant at about third of its intact condition for a period of at least a third of rat's lifetime postinjury.
Ergebnisse einer stationären Rauchentwöhnung bei Suchtpatienten im Rahmen einer 3-wöchigen, qualifizierten Entzugsbehandlung
Authors: Pätz T. , Frischknecht U. , Bielmeier P. , Dinter C. , Reinhard I. , Mann K. , Kiefer F. , Weber T.
Published: February 2017

Überprüft wurde der Effekt eines Rauchentwöhnungsprogramms während einer 3-wöchigen, stationären, qualifizierten Entzugsbehandlung. Dabei standen sowohl die Teilnahmebereitschaft, die Tabakkonsumreduktion bzw. die Tabakabstinenz und der Einfluss auf die Abstinenz von der komorbiden Abhängigkeit im Mittelpunkt der Untersuchung.

153 Suchtpatienten mit komorbider Tabakabhängigkeit wurden eingeschlossen. 88 Probanden nahmen an einem Rauchentwöhnungsprogramm mit kognitiv-behavioraler Gruppentherapie und Rauchentwöhnungsmitteln teil. 31 tabakabhängige Suchtpatienten ohne Rauchabstinenzmotivation bildeten die Vergleichsgruppe. 83% aller Probanden wiesen eine Alkoholabhängigkeit auf.

32,5% aller aufgenommenen tabakabhängigen Patienten nahmen an der Rauchentwöhnung teil. Probanden in der Rauchentwöhnungsgruppe konnten ihren durchschnittlichen Tabakkonsum signifikant zum Entlasszeitpunkt und beim Follow-up nach 3 Monaten reduzieren. 26% bzw. 16% der Probanden erreichten eine Tabakabstinenz zu den beiden Messzeitpunkten. Probanden der Therapie- und Vergleichsgruppe zeigten beim Follow-up identische Abstinenzquoten von der Abhängigkeit, die zur stationären Aufnahme geführt hatte (42,5% und 42,9%). Die Tabakabstinenz war dabei signifikant mit der Substanzabstinenz assoziiert.

Die Daten sprechen für eine hohe Bereitschaft zur Teilnahme an einer freiwilligen Rauchentwöhnungsbehandlung, welche erfolgreich im Rahmen einer qualifizierten Entzugstherapie angeboten werden kann, ohne dass hierdurch die Abstinenz von der komorbiden Abhängigkeit gefährdet wird.
Mechanisms of cytosolic calcium elevation in plants: the role of ion channels, calcium extrusion systems and NADPH oxidase-mediated 'ROS-Ca2+ Hub'
Authors: Demidchik Vadim , Shabala Sergey
Published: February 2017

Elevation in the cytosolic free calcium is crucial for plant growth, development and adaptation. Calcium influx into plant cells is mediated by Ca2+ depolarisation-activated, hyperpolarisation-activated and voltage-independent Ca2+-permeable channels (DACCs, HACCs and VICCs respectively). These channels are encoded by the following gene families: (1) cyclic nucleotide-gated channels (CNGCs), (2) ionotropic glutamate receptors (GLRs), (3) annexins, (4) ‘mechanosensitive channels of small (MscS) conductance’-like channels (MSLs), (5) ‘mid1-complementing activity’ channels (MCAs), Piezo channels, and hyperosmolality-induced [Ca2+]cyt. channel 1 (OSCA1). Also, a ‘tandem-pore channel1’ (TPC1) catalyses Ca2+ efflux from the vacuole in response to the plasma membrane-mediated Ca2+ elevation. Recent experimental data demonstrated that Arabidopsis thaliana (L.) Heynh. CNGCs 2, 5–10, 14, 16 and 18, GLRs 1.2, 3.3, 3.4, 3.6 and 3.7, TPC1, ANNEXIN1, MSL9 and MSL10,MCA1 and MCA2, OSCA1, and some their homologues counterparts in other species, are responsible for Ca2+ currents and/or cytosolic Ca2+ elevation. Extrusion of Ca2+ from the cytosol is mediated by Ca2+-ATPases and Ca2+/H+ exchangers which were recently examined at the level of high resolution crystal structure. Calcium-activated NADPH oxidases and reactive oxygen species (ROS)-activated Ca2+ conductances form a self-amplifying ‘ROS-Ca2+hub’, enhancing and transducing Ca2+ and redox signals. The ROS-Ca2+ hub contributes to physiological reactions controlled by ROS and Ca2+, demonstrating synergism and unity of Ca2+ and ROS signalling mechanisms.
Redirecting the agenda
Authors: Weimann Gabriel , Brosius Hans-Bernd
Published: February 2017

Since its initial introduction, the paradigm of agenda-setting has become more refined and complex. In addition to the introduction of intervening factors the agenda-setting paradigm is now challenged by a rapidly changing media environment. This paper reviews the impact of online media technologies and digital platforms on the basic assumptions of the theory. The review sets out to reassess the conceptualization of the agenda-setting theorem by highlighting the development of new processes, attributes and features applicable to the online media. Our review, based on the findings of numerous studies on new media and agenda-setting, suggests several modifications of the basic theory.
Local characterizations for the matrix monotonicity and convexity of fixed order
Authors: Heinävaara Otte
Published: February 2017

We establish local characterizations of matrix monotonicity and convexity of fixed order by giving integral representations connecting the Loewner and Kraus matrices, previously known to characterize these properties, to respective Hankel matrices. Our results are new already in the general case of matrix convexity, and our approach significantly simplifies the corresponding work on matrix monotonicity. We also obtain an extension of the original characterization for matrix convexity by Kraus and tighten the relationship between monotonicity and convexity.
A zero-one law for improvements to Dirichlet’s Theorem
Authors: Kleinbock Dmitry , Wadleigh Nick
Published: February 2017

We give an integrability condition on a function

ψ
\psi

guaranteeing that for almost all (or almost no)

x
∈

R

x\in \mathbb {R}

, the system

|

q
x
−
p

|

>
ψ
(
t
)

|qx-p|> \psi (t)

,

|

q

|

>
t

|q|>t

is solvable in

p
∈

Z

p\in \mathbb {Z}

,

q
∈

Z

∖
{
0
}

q\in \mathbb {Z}\smallsetminus \{0\}

for sufficiently large

t
t

. Along the way, we characterize such

x
x

in terms of the growth of their continued fraction entries, and we establish that Dirichlet’s Approximation Theorem is sharp in a very strong sense. Higher-dimensional generalizations are discussed at the end of the paper.
Existence of an extinction wave in the Fisher equation with a shifting habitat
Authors: Hu Haijun , Zou Xingfu
Published: February 2017

This paper deals with the existence of traveling wave solutions of the Fisher equation with a shifting habitat representing a transition to a devastating environment. By constructing a pair of appropriate upper/lower solutions and using the method of monotone iteration, we prove that for any given speed of the shifting habitat edge, this reaction-diffusion equation admits a monotone traveling wave solution with the speed agreeing to the habitat shifting speed, which accounts for an extinction wave. This predicts not only how fast but also in what manner a biological species will die out in such a shifting habitat.
The hematopoietic cell-specific transcription factor PU.1 is critical for expression of CD11c
Authors: Yashiro Takuya , Kasakura Kazumi , Oda Yoshihito , Kitamura Nao , Inoue Akihito , Nakamura Shusuke , Yokoyama Hokuto , Fukuyama Kanako , Hara Mutsuko , Ogawa Hideoki , Okumura Ko , Nishiyama Makoto , Nishiyama Chiharu
Published: February 2017

PU.1 is a hematopoietic cell-specific transcription factor belonging to the Ets family, which plays an important role in the development of dendritic cells (DCs). CD11c (encoded by Itgax) is well established as a characteristic marker of hematopoietic lineages including DCs. In the present study, we analyzed the role of PU.1 (encoded by Spi-1) in the expression of CD11c. When small interfering RNA (siRNA) for Spi-1 was introduced into bone marrow-derived DCs (BMDCs), the mRNA level and cell surface expression of CD11c were dramatically reduced. Using reporter assays, the TTCC sequence at −56/−53 was identified to be critical for PU.1-mediated activation of the promoter. An EMSA showed that PU.1 directly bound to this region. ChIP assays demonstrated that a significant amount of PU.1 bound to this region on chromosomal DNA in BMDCs, which was decreased in LPS-stimulated BMDCs in accordance with the reduced levels of mRNAs of Itgax and Spi-1, and the histone acetylation degree. Enforced expression of exogenous PU.1 induced the expression of the CD11c protein on the cell surface of mast cells, whereas control transfectants rarely expressed CD11c. Quantitative RT–PCR also showed that the expression of a transcription factor Irf4, which is a partner molecule of PU.1, was reduced in PU.1-knocked down BMDCs. IRF4 transactivated the Itgax gene in a synergistic manner with PU.1. Taken together, these results indicate that PU.1 functions as a positive regulator of CD11c gene expression by directly binding to the Itgax promoter and through transactivation of the Irf4 gene.
Detection of faint broad emission lines in type 2 AGN – II. On the measurement of the black hole mass of type 2 AGN and the unified model
Authors: Onori F. , Ricci F. , La Franca F. , Bianchi S. , Bongiorno A. , Brusa M. , Fiore F. , Maiolino R. , Marconi A. , Sani E. , Vignali C.
Published: February 2017

We report the virial measurements of the black hole (BH) mass of a sample of 17 type 2 active galactic nuclei (AGN), drawn from the Swift/BAT 70-month 14–195 keV hard X-ray catalogue, where a faint BLR component has been measured via deep NIR (0.8–2.5 μm) spectroscopy. We compared the type 2 AGN with a control sample of 33 type 1 AGN. We find that the type 2 AGN BH masses span the 5 < log(MBH/M⊙) < 7.5 range, with an average log(MBH/M⊙) = 6.7, which is ∼0.8 dex smaller than found for type 1 AGN. If type 1 and type 2 AGN of the same X-ray luminosity log($L_{\rm 14{\rm -}195}$/erg s−1) ∼ 43.5 are compared, type 2 AGN have 0.5 dex smaller BH masses than type 1 AGN. Although based on few tens of objects, this result disagrees with the standard AGN unification scenarios in which type 1 and type 2 AGN are the same objects observed along different viewing angles with respect to a toroidal absorbing material.
ICTV Virus Taxonomy Profile: Ascoviridae
Authors: Asgari Sassan , Bideshi Dennis K. , Bigot Yves , Federici Brian A. , Cheng Xiao-Wen ,   ICTV Report Consortium
Published: February 2017

The family Ascoviridae includes viruses with circular dsDNA genomes of 100–200 kbp characterized by oblong enveloped virions of 200–400 nm in length. Ascoviruses mainly infect lepidopteran larvae and are mechanically transmitted by parasitoid wasps in which they may also replicate. Most known members belong to the genus Ascovirus, except one virus, that of the genus Toursvirus, which replicates in both its lepidopteran and parasitoid vector hosts. Ascoviruses cause high mortality among economically important insect pests, thereby controlling insect populations. This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Ascoviridae, which is available at www.ictv.global/report/ascoviridae.
Heterogeneity of normal human breast stem and progenitor cells as revealed by transcriptional profiling
Authors: Colacino Justin A. , Azizi Ebrahim , Brooks Michael D. , Fouladdel Shamileh , McDermott Sean P. , Lee Michael , Hill David , Sartor Maureen A. , Rozek Laura S. , Wicha Max S.
Published: February 2017

During development and pregnancy, the human mammary gland undergoes extensive remodeling in processes driven by populations of stem and progenitor cells. We recently reported that breast cancers are also hierarchically organized and driven by distinct populations of cancer stem cells characterized as CD44+CD24low/−or by expression of Aldehyde dehydrogenase (ALDH). These sets of markers identify largely non-overlapping mesenchymal and epithelial populations, each of which is capable of tumor initiation when transplanted into immunosuppressed mice. Less is known about these two populations, individually or their overlap, in the normal human mammary gland. The goal of this study was to understand the biology of the ALDH+and CD44+CD24−populations in the normal human breast, using flow cytometry based sorting paired with functionalex vivoanalyses, RNA-sequencing, and single cell RNA expression profiling. ALDH+cells and ALDH−CD44+CD24−cells, generally, have epithelial-like and mesenchymal-like characteristics, respectively. Despite this, there are substantial similarities in the biological pathways activated in both populations when compared to differentiated cells. Additionally, we found a substantial proportion of cells that simultaneously express ALDH+and CD44+CD24−whose abundance varies between individuals. At the single cell level, these cells have the greatest mammosphere forming capacity and express high levels of stemness and EMT-associated genes includingID1, SOX2, TWIST1, and ZEB2.Through unbiased analysis of individual ALDH+ cells, we find cells with either epithelial or mesenchymal expression phenotypes. We also identify a subpopulation of cells with a hybrid epithelial/mesenchymal expression phenotype that overexpress genes associated with aggressive triple negative breast cancers. These results highlight the utility of single cell analyses to characterize tissue heterogeneity, even in marker enriched cell populations, and further identifies the genes and pathways that define this heterogeneity.
Gene knockout shows that PML (TRIM19) does not restrict the early stages of HIV-1 infection in human cell lines
Authors: Masroori Nasser , Cherry Pearl , Merindol Natacha , Li Jia-xin , Dufour Caroline , Poulain Lina , Plourde Mélodie B. , Berthoux Lionel
Published: February 2017

The PML (promyelocytic leukemia) protein is a member of the TRIM family, a large group of proteins that show high diversity in functions but possess a common tripartite motif giving the family its name. We and others recently reported that both murine PML (mPML) and human PML (hPML) strongly restrict the early stages of infection by HIV-1 and other lentiviruses when expressed in mouse embryonic fibroblasts (MEFs). This restriction activity was found to contribute to the type I interferon (IFN-I)-mediated inhibition of HIV-1 in MEFs. Additionally, PML caused transcriptional repression of the HIV-1 promoter in MEFs. By contrast, the modulation of the early stages of HIV-1 infection of human cells by PML has been investigated by RNAi with unclear results. In order to conclusively determine whether PML restricts HIV-1 or not in human cells, we used CRISPR-Cas9 to knock out its gene in epithelial, lymphoid and monocytic human cell lines. Infection challenges showed that PML knockout had no effect on the permissiveness of these cells to HIV-1 infection. IFN-I treatments inhibited HIV-1 equally whether PML was expressed or not. Over-expression of individual hPML isoforms, or of mPML, in a human T cell line did not restrict HIV-1. The presence of PML was not required for the restriction of nonhuman retroviruses by TRIM5α was inhibited by arsenic trioxide through a PML-independent mechanism. We conclude that PML is not a restriction factor for HIV-1 in human cell lines representing diverse lineages.

Importance

PML is involved in innate immune mechanisms against both DNA and RNA viruses. Although the mechanism by which PML inhibits highly divergent viruses is unclear, it was recently found that it can increase the transcription of interferon-stimulated genes (ISGs). However, whether human PML inhibits HIV-1 has been debated. Here we provide unambiguous, knockout-based evidence that PML does not restrict the early post-entry stages of HIV-1 infection in a variety of human cell types and does not participate in the inhibition of HIV-1 by IFN-I. Although this study does not exclude the possibility of other mechanisms by which PML may interfere with HIV-1, we nonetheless demonstrate that PML does not generally act as an HIV-1 restriction factor in human cells and that its presence is not required for IFN-I to stimulate the expression of anti-HIV-1 genes. These results contribute to uncovering the landscape of HIV-1 inhibition by ISGs in human cells.
Simulation Framework for Generating Intratumor Heterogeneity Patterns in a Cancer Cell Population
Authors: Iwasaki Watal M. , Innan Hideki
Published: February 2017

As cancer cell populations evolve, they accumulate a number of somatic mutations, resulting in heterogeneous subclones in the final tumor. Understanding the mechanisms that produce intratumor heterogeneity (ITH) is important for selecting the best treatment. Although some studies have involved ITH simulations, their model settings differed substantially. Thus, only limited conditions were explored in each. Herein, we developed a general framework for simulating ITH patterns and a simulator (tumopp). Tumopp offers many setting options so that simulations can be carried out under various settings. Setting options include how the cell division rate is determined, how daughter cells are placed, and how driver mutations are treated. Furthermore, to account for the cell cycle, we introduced a gamma function for the waiting time involved in cell division. Tumopp also allows simulations in a hexagonal lattice, in addition to a regular lattice that has been used in previous simulation studies. A hexagonal lattice produces a more biologically reasonable space than a regular lattice. Using tumopp, we investigated how model settings affect the growth curve and ITH pattern. It was found that, even under neutrality (with no driver mutations), tumopp produced dramatically variable patterns of ITH and tumor morphology, from tumors in which cells with different genetic background are well intermixed to irregular shapes of tumors with a cluster of closely related cells. This result suggests a caveat in analyzing ITH data with simulations with limited settings, and tumopp will be useful to explore ITH patterns in various conditions.

Author Summary

Understanding the mechanisms that produce intratumor heterogeneity (ITH) is important for selecting the best treatment. Despite a growing body of data and tools for analyzing ITH, the spatial structure and its evolution are poorly understood because of the lack of well established theoretical framework. Herein, we provide a general framework for simulating ITH patterns, under which a simulator (tumopp) is developed. Tumopp offers many setting options so that simulations can be carried out under various settings. Simulations using tumopp demonstrate that dramatically variable patterns of ITH and tumor morphology can be produced depending on the model setting. The present work provides a guideline for future simulation studies of cancer cell populations.
Simulating and optimizing compound refractive lens-based X-ray microscopes
Authors: Simons Hugh , Ahl Sonja Rosenlund , Poulsen Henning Friis , Detlefs Carsten
Published: February 2017

A comprehensive optical description of compound refractive lenses (CRLs) in condensing and full-field X-ray microscopy applications is presented. The formalism extends ray-transfer matrix analysis by accounting for X-ray attenuation by the lens material. Closed analytical expressions for critical imaging parameters such as numerical aperture, spatial acceptance (vignetting), chromatic aberration and focal length are provided for both thin- and thick-lens imaging geometries. These expressions show that the numerical aperture will be maximized and chromatic aberration will be minimized at the thick-lens limit. This limit may be satisfied by a range of CRL geometries, suggesting alternative approaches to improving the resolution and efficiency of CRLs and X-ray microscopes.
Establishment of new design criteria for GlidCop®X-ray absorbers
Authors: Collins Jeff T. , Nudell Jeremy , Navrotski Gary , Liu Zunping , Den Hartog Patric
Published: February 2017

An engineering research program has been conducted at the Advanced Photon Source (APS) in order to determine the thermomechanical conditions that lead to crack formation in GlidCop®, a material commonly used to fabricate X-ray absorbers at X-ray synchrotron facilities. This dispersion-strengthened copper alloy is a proprietary material and detailed technical data of interest to the synchrotron community is limited. The results from the research program have allowed new design criteria to be established for GlidCop®X-ray absorbers based upon the thermomechanically induced fatigue behavior of the material. X-ray power from APS insertion devices was used to expose 30 GlidCop®samples to 10000 thermal loading cycles each under various beam power conditions, and all of the samples were metallurgically examined for crack presence/geometry. In addition, an independent testing facility was hired to measure temperature-dependent mechanical data and uniaxial mechanical fatigue data for numerous GlidCop®samples. Data from these studies support finite element analysis (FEA) simulation and parametric models, allowing the development of a thermal fatigue model and the establishment of new design criteria so that the thermomechanically induced fatigue life of X-ray absorbers may be predicted. It is also demonstrated how the thermal fatigue model can be used as a tool to geometrically optimize X-ray absorber designs.
Interactively developed capabilities: evidence from dyadic servitization relationships
Authors: Raddats Chris , Zolkiewski Judy , Story Vicky Mary , Burton Jamie , Baines Tim , Ziaee Bigdeli Ali
Published: February 2017

Purpose

The purpose of this paper is to challenge the focal firm perspective of much resource/capability research, identifying how a dyadic perspective facilitates identification of capabilities required for servitization.

Design/methodology/approach

Exploratory study consisting of seven dyadic relationships in five sectors.

Findings

An additional dimension of capabilities should be recognised; whether they are developed independently or interactively (with another actor). The following examples of interactively developed capabilities are identified: knowledge development, where partners interactively communicate to understand capabilities; service enablement, manufacturers work with suppliers and customers to support delivery of new services; service development, partners interact to optimise performance of existing services; risk management, customers work with manufacturers to manage risks of product acquisition/operation. Six propositions were developed to articulate these findings.

Research limitations/implications

Interactively developed capabilities are created when two or more actors interact to create value. Interactively developed capabilities do not just reside within one firm and, therefore, cannot be a source of competitive advantage for one firm alone. Many of the capabilities required for servitization are interactive, yet have received little research attention. The study does not provide an exhaustive list of interactively developed capabilities, but demonstrates their existence in manufacturer/supplier and manufacturer/customer dyads.

Practical implications

Manufacturers need to understand how to develop capabilities interactively to create competitive advantage and value and identify other actors with whom these capabilities can be developed.

Originality/value

Previous research has focussed on relational capabilities within a focal firm. This study extends existing theories to include interactively developed capabilities. The paper proposes that interactivity is a key dimension of actors’ complementary capabilities.
Improving retail supply flexibility using buyer-supplier relational capabilities
Authors: Obayi Raymond , Koh S.C. , Oglethorpe David , Ebrahimi Seyed M.
Published: February 2017

Purpose

The purpose of this paper is to investigate the mediating role of three important relational capabilities – absorptive capacity (AC), transactive memory systems (TMS), and organisational interoperability (OI); on the flexibility of buyer-supplier relationships and performance in retail supply chains. Drawing on the relational view of strategic management, the impact of relational capabilities on two forms of supply chain flexibility is examined – configuration flexibility (CF) for switching suppliers with minimal penalties, and planning and control flexibility (PCF) for altering supply schedules, quality, and delivery lead-time.

Design/methodology/approach

Strategic- and tactical-level managers from 211 retail stores in the UK were surveyed. The authors validated a measurement model with structural equation modelling and tested four hypotheses on the mediating role of relational capabilities on supply chain flexibility and retail performance, controlling for size, duration of relationship, and market segment.

Findings

Results showed that the three relational capabilities partially mediated the positive effect of CF and PCF on operational performance in big middle and niche retailers. Examining the interaction effect of the forms of flexibility on the relational capabilities and performance, the authors found positive interaction effects on TMS and OI but a non-significant effect on AC.

Practical implications

In addition to providing novel theoretical insights on supply chain flexibility, the findings have practical implications for supplier selection and buyer-supplier relationship management.

Originality/value

Overall, the study highlights the impacts of relational capabilities on adopted operational strategies such as flexibility, buyer-supplier relationships, and retail performance.
Three‐term inversion of prestack seismic data using a weighted l2, 1 mixed norm
Authors: Pérez Daniel O. , Velis Danilo R. , Sacchi Mauricio D.
Published: February 2017

We present a new inversion method to estimate, from prestack seismic data, blocky P‐ and S‐wave velocity and density images and the associated sparse reflectivity levels. The method uses the three‐term Aki and Richards approximation to linearise the seismic inversion problem. To this end, we adopt a weighted mixed l2, 1‐norm that promotes structured forms of sparsity, thus leading to blocky solutions in time. In addition, our algorithm incorporates a covariance or scale matrix to simultaneously constrain P‐ and S‐wave velocities and density. This a priori information is obtained by nearby well‐log data. We also include a term containing a low‐frequency background model. The l2, 1 mixed norm leads to a convex objective function that can be minimised using proximal algorithms. In particular, we use the fast iterative shrinkage‐thresholding algorithm. A key advantage of this algorithm is that it only requires matrix–vector multiplications and no direct matrix inversion. The latter makes our algorithm numerically stable, easy to apply, and economical in terms of computational cost. Tests on synthetic and field data show that the proposed method, contrarily to conventional l2‐ or l1‐norm regularised solutions, is able to provide consistent blocky and/or sparse estimators of P‐ and S‐wave velocities and density from a noisy and limited number of observations.
Population dynamics of wild rodents induce stochastic fadeouts of a zoonotic pathogen
Authors: Guzzetta Giorgio , Tagliapietra Valentina , Perkins Sarah E. , Hauffe Heidi C. , Poletti Piero , Merler Stefano , Rizzoli Annapaola
Published: February 2017

Stochastic processes play an important role in the infectious disease dynamics of wildlife, especially in species subject to large population oscillations.

Here, we study the case of a free ranging population of yellow‐necked mice (Apodemus flavicollis) in northern Italy, where circulation of Dobrava‐Belgrade hantavirus (DOBV) has been detected intermittently since 2001, until an outbreak emerged in 2010.

We analysed the transmission dynamics of the recent outbreak using a computational model that accounts for seasonal changes of the host population and territorial behaviour. Model parameters were informed by capture‐mark‐recapture data collected over 14 years and longitudinal seroprevalence data from 2010 to 2013.

The intermittent observation of DOBV before 2010 can be interpreted as repeated stochastic fadeouts after multiple introductions of infectious rodents migrating from neighbouring areas. We estimated that only 20% of introductions in a naïve host population results in sustained transmission after 2 years, despite an effective reproduction number well above the epidemic threshold (mean 4·5, 95% credible intervals, CI: 0·65–15·8). Following the 2010 outbreak, DOBV has become endemic in the study area, but we predict a constant probability of about 4·7% per year that infection dies out, following large population drops in winter. In the absence of stochastic fadeout, viral prevalence is predicted to continue its growth to an oscillating equilibrium around a value of 24% (95% CI: 3–57).

We presented an example of invasion dynamics of a zoonotic virus where stochastic fadeout have played a major role and may induce future extinction of the endemic infection.
Caching reduces kleptoparasitism in a solitary, large felid
Authors: Balme Guy A. , Miller Jennifer R. B. , Pitman Ross T. , Hunter Luke T. B.
Published: February 2017

Food caching is a common strategy used by a diversity of animals, including carnivores, to store and/or secure food. Despite its prevalence, the drivers of caching behaviour, and its impacts on individuals, remain poorly understood, particularly for short‐term food cachers.

Leopards Panthera pardus exhibit a unique form of short‐term food caching, regularly hoisting, storing and consuming prey in trees. We explored the factors motivating such behaviour among leopards in the Sabi Sand Game Reserve, South Africa, associated with four not mutually exclusive hypotheses: food‐perishability, consumption‐time, resource‐pulse and kleptoparasitism‐avoidance.

Using data from 2032 prey items killed by 104 leopards from 2013 to 2015, we built generalized linear mixed models to examine how hoisting behaviour, feeding time and the likelihood of a kill being kleptoparasitized varied with leopard sex and age, prey size and vulnerability, vegetation, elevation, climate, and the immediate and long‐term risk posed by dominant competitors.

Leopards hoisted 51% of kills. They were more likely to hoist kills of an intermediate size, outside of a resource pulse and in response to the presence of some competitors. Hoisted kills were also fed on for longer than non‐hoisted kills. At least 21% of kills were kleptoparasitized, mainly by spotted hyaenas Crocuta crocuta. Kills were more likely to be kleptoparasitized at lower temperatures and if prey were larger, not hoisted, and in areas where the risk of encountering hyaenas was greatest. Female leopards that suffered higher rates of kleptoparasitism exhibited lower annual reproductive success than females that lost fewer kills.

Our results strongly support the kleptoparasitism‐avoidance hypothesis and suggest hoisting is a key adaptation that enables leopards to coexist sympatrically with high densities of competitors. We further argue that leopards may select smaller‐sized prey than predicted by optimal foraging theory, to balance trade‐offs between kleptoparasitic losses and the energetic gains derived from killing larger prey.

Although caching may provide the added benefits of delaying food perishability and enabling consumption over an extended period, the behaviour primarily appears to be a strategy for leopards, and possibly other short‐term cachers, to reduce the risks of kleptoparasitism.
Range shifting species reduce phylogenetic diversity in high latitude communities via competition
Authors: Fitt Robert N. L. , Lancaster Lesley T.
Published: February 2017

Under anthropogenic climate change, many species are expanding their ranges to higher latitudes and altitudes, resulting in novel species interactions. The consequences of these range shifts for native species, patterns of local biodiversity and community structure in high latitude ecosystems are largely unknown but critical to understand in light of widespread poleward expansions by many warm‐adapted generalists.

Using niche modelling, phylogenetic methods, and field and laboratory studies, we investigated how colonization of Scotland by a range expanding damselfly, Ischnura elegans, influences patterns of competition and niche shifts in native damselfly species, and changes in phylogenetic community structure.

Colonization by I. elegans was associated with reduced population density and niche shifts in the resident species least related to I. elegans (Lestes sponsa), reflecting enhanced competition. Furthermore, communities colonized by I. elegans exhibited phylogenetic underdispersion, reflecting patterns of relatedness and competition.

Our results provide a novel example of a potentially general mechanism whereby climate change‐mediated range shifts can reduce phylogenetic diversity within high latitude communities, if colonizing species are typically competitively superior to members of native communities that are least‐closely related to the colonizer.
Self‐efficacy of prospective Austrian and German primary school teachers regarding the implementation of inclusive education
Authors: Schwab Susanne , Hellmich Frank , Görel Gamze
Published: February 2017

This study examined the psychometric properties of the German version of the Teacher Inclusive Education Self‐Efficacy Scale (TIESES). Five hundred and nineteen teacher education students from Austria and 765 teacher education students from Germany participated in the study. Results of a multiple‐group confirmatory factor analysis (for the two countries) confirmed a single factor structure of the scale with partial scalar measurement invariance. Regression analysis showed that self‐efficacy when implementing inclusive education was explained by the motivation to deal with inclusive education during their studies, previous experience with inclusive education in internships, study interest and the country in which the students went to university.