bluuebunny/crossref_metadata_2025 huggingface dataset:
How innovators reframe resources in the strategy‐making process to gain innovation adoption
Authors: Kannan‐Narasimhan Rangapriya (Priya) , Lawrence Barbara S.
Published: December 2017

Research Summary: This multicompany qualitative field study combines strategy process and strategy‐as‐practice perspectives to show how innovators successfully gain adoption for their autonomous innovations by reframing the meaning and potential of the associated internal resources to create fit with their organization's strategy. Mapping the five steps involved in the resource reframing process onto the different parts of the Bower‐Burgelman process model of strategic change shows that innovators can shape the strategic context for their autonomous innovations before external market validation is available. These findings confirm the unique potential and importance of different forms of discourse in shaping the strategic innovation process.

Managerial Summary: How do innovators from lower levels of an organization gain approval for their innovations especially when their ideas do not readily fit their organization's strategy? To explore this question, we conducted 138 interviews with innovators and their decision makers in 14 firms based in Silicon Valley. We find that successful innovators shape a story supporting their innovation by rethinking their firm's current and potential resources. They then use this story to convince decision makers that their innovation creates unique competitive advantage. Contrary to conventional wisdom, decision makers approved such innovations even without external validation, solely based on the innovators' success in depicting their reorganization of the firm's resources.
Scope versus speed: Team diversity, leader experience, and patenting outcomes for firms
Authors: Choudhury Prithwiraj , Haas Martine R.
Published: December 2017

Research Summary:How does the organization of patenting activity affect a firm's patenting outcomes? We investigate how the composition of patenting teams relates to both the scope of their patent applications and the speed with which their patents are approved, by examining the main effects of team members’ intra‐organizational diversity (based on affiliations with formal organizational units and informal organizational communities) and the moderating effects of team leader experience. We test our moderated mediation model in a sample of 121 teams that filed patents in a Fortune 50 company's India R&D center between 2005 and 2015, using proprietary employee data combined with newly released micro‐data from the U.S Patent and Trademark Office (USPTO). Our findings illuminate the micro‐foundations of innovation in firms by highlighting a trade‐off between organizing patenting activity to maximize scope versus speed.

Managerial Summary:Patenting is an important strategic tool that firms can use to protect and create value from their innovations. A firm can benefit from filing a patent application that gives it a wider possible set of claims related to an innovation. It can also benefit from faster approval of a patent application by the Patent Office. However, our study shows that there is a trade‐off between patent application scope and patent approval speed, which creates tensions for the organization of patenting activities inside firms. In particular, we find that the diversity of a patenting team is positively related to patent scope but negatively related to patenting speed, and that these relationships vary with the experience of the team leader.
A Novel Approach to Single Cell RNA-Sequence Analysis Facilitates In Silico Gene Reporting of Human Pluripotent Stem Cell-Derived Retinal Cell Types
Authors: Phillips M. Joseph , Jiang Peng , Howden Sara , Barney Patrick , Min Jee , York Nathaniel W. , Chu Li-Fang , Capowski Elizabeth E. , Cash Abigail , Jain Shivani , Barlow Katherine , Tabassum Tasnia , Stewart Ron , Pattnaik Bikash R. , Thomson James A. , Gamm David M.
Published: December 2017

Cell type-specific investigations commonly use gene reporters or single-cell analytical techniques. However, reporter line development is arduous and generally limited to a single gene of interest, while single-cell RNA (scRNA)-sequencing (seq) frequently yields equivocal results that preclude definitive cell identification. To examine gene expression profiles of multiple retinal cell types derived from human pluripotent stem cells (hPSCs), we performed scRNA-seq on optic vesicle (OV)-like structures cultured under cGMP-compatible conditions. However, efforts to apply traditional scRNA-seq analytical methods based on unbiased algorithms were unrevealing. Therefore, we developed a simple, versatile, and universally applicable approach that generates gene expression data akin to those obtained from reporter lines. This method ranks single cells by expression level of a bait gene and searches the transcriptome for genes whose cell-to-cell rank order expression most closely matches that of the bait. Moreover, multiple bait genes can be combined to refine datasets. Using this approach, we provide further evidence for the authenticity of hPSC-derived retinal cell types.
Impacts and Implications of Temperature Variability on Chinook Salmon Egg Development and Emergence Phenology
Authors: Beer W. Nicholas , Steel E. Ashley
Published: December 2017

The nonlinear relationship of egg development rates to temperature due to compensatory mechanisms in Chinook Salmon Oncorhynchus tshawytscha has consequences for emergence timing in nonoptimal and/or highly variable temperature regimes. A mechanistic model of the relationship between temperature and development was used to better understand laboratory results on the primary effects of temperature variability leading to emergence. The model was then applied to a natural river system and used to predict emergence timing while considering additional factors associated with natural spawning such as an individual spawner's timing, the stock's spawning season, and spawning cue. In the natural system simulations, the largest source of emergence timing variability was due to interannual water temperature regimes and spawning date variation. Lesser emergence variability resulted from temperature variability, family lineage, egg size, individual spawner's timing, and spawning cue. An improved understanding of the role of riverine thermal regimes in inducing developmental variability can contribute to conservation planning and predictions of phenology under future climates.
Stress state of steel plate shear walls under compression–shear combination load
Authors: Lv Yang , Wu Di , Zhu Yuhao , Liang Xiao , Shi Yanchao , Yang Zhen , Li Zhong‐Xian
Published: December 2017

This paper investigates the stress state of the infill steel plate for the unstiffened steel plate shear walls (SPSWs) under compression–shear combination load. First, the infill steel plate is divided into three zones, the stress state of each zone under compression is derived, and the accuracy of the analytical model is verified by a series of numerical examples. Second, considering the combination effects of the gravity load and shear force from the adjacent boundary columns, the stress state of each zone is proposed and discussed. Then the shear capacity of the infill steel plate for the unstiffened SPSWs with gravity load acting on the top of the boundary columns is proposed. Finally, the shear capacity of 21 numerical SPSW specimens with various axial stresses of the boundary columns and different steel infill plate thicknesses is predicted.
Stability analysis of large‐span steel truss structure under local cooling from fire extinguishing system
Authors: Zhang Guowei , Zhu Guoqing , Yuan Guanglin , Li Qing
Published: December 2017

In case of a fire in large‐span steel structure buildings, the firefighters usually use water to cool the steelwork. However, during the cooling by the spraying water, the collapse of these structures is unclear. In this paper, a large‐span center is taken as an example to study the overall mechanical response process under local cooling conditions in fire. The Fire Dynamics Simulator has been used to investigate the temperature field distribution rule of large‐span buildings under fire. Using the coupled thermal‐mechanical method to study the overall mechanical response process of steel structure under local abrupt drop in temperature, displacement and stress variations of the large‐span steel structure under local cooling have been analyzed. Results of this study show that the temperature distribution in large‐span structures is nonuniform in fire. Using spraying water to cool the structural members in fire can cause the structural stress field redistributed that may lead to further damage to the structure.
Urbanization in Sub‐Saharan Africa: Declining Rates of Chronic and Recurrent Infection and Their Possible Role in the Origins of Non‐communicable Diseases
Authors: Bickler Stephen W. , Wang Andrew , Amin Said , Halbach Jonathan , Lizardo Radhames , Cauvi David M. , De Maio Antonio
Published: December 2017

Background

Non‐communicable diseases (NCDs), such as atherosclerosis and cancers, are a leading cause of death worldwide. An important, yet poorly explained epidemiological feature of NCDs is their low incidence in under developed areas of low‐income countries and rising rates in urban areas.

Methods

With the goal of better understanding how urbanization increases the incidence of NCDs, we provide an overview of the urbanization process in sub‐Saharan Africa, discuss gene expression differences between rural and urban populations, and review the current NCD determinant model. We conclude by identifying research priorities.

Results

Declining rates of chronic and recurrent infection are the hallmark of urbanization in sub‐Saharan Africa. Gene profiling studies show urbanization results in complex molecular changes, with almost one‐third of the peripheral blood leukocyte transcriptome altered. The current NCD determinant model could be improved by including a possible effect from declining rates of infection and expanding the spectrum of diseases that increase with urbanization.

Conclusions

Urbanization in sub‐Saharan Africa provides a unique opportunity to investigate the mechanism by which the environment influences disease epidemiology. Research priorities include: (1) studies to define the relationship between infection and risk factors for NCDs, (2) explaining the observed differences in the inflammatory response between rural and urban populations, and (3) identification of animal models that simulate the biological changes that occurs with urbanization. A better understanding of the biological changes that occur with urbanization could lead to new prevention and treatment strategies for some of the most common surgical diseases in high‐income countries.
Correction to: Impact of age at onset and newborn screening on outcome in organic acidurias
Authors: Heringer Jana , Valayannopoulos Vassili , Lund Allan M. , Wijburg Frits A. , Freisinger Peter , Barić Ivo , Baumgartner Matthias R. , Burgard Peter , Burlina Alberto B. , Chapman Kimberly A. , i Saladelafont Elisenda Cortès , Karall Daniela , Mühlhausen Chris , Riches Victoria , Schiff Manuel , Sykut‐Cegielska Jolanta , Walter John H. , Zeman Jiri , Chabrol Brigitte , Kölker Stefan ,   Additional individual contributors of the E‐IMD consortium
Published: December 2017

Due to an unfortunate error during the typesetting process, the collaborators were presented incorrectly.
The Beliefs and Intentions of Buridan's Ass
Authors: DELLSÉN FINNUR , SHARADIN NATHANIEL
Published: December 2017

The moral of Buridan's ass is that it can sometimes be rational to perform one action rather than another even though one lacks stronger reason to do so. Yet, it is also commonly believed that it cannot ever be rational to believe one proposition rather than another if one lacks stronger reason to do so. This asymmetry has been taken to indicate a deep difference between epistemic and practical rationality. According to the view articulated here, the asymmetry should instead be explained by the difference between rational intentions and rational actions. Thus, it turns out, cases such as Buridan's ass do not indicate an asymmetry between epistemic and practical rationality as such.
On the Limits of the Method of Phenomenal Contrast
Authors: FÜRST MARTINA
Published: December 2017

The method of phenomenal contrast aims to shed light on the phenomenal character of perceptual and cognitive experiences. Within the debate aboutcognitive phenomenology, phenomenal contrast arguments can be divided into two kinds. First, arguments based on actual cases that aim to provide the reader with a first-person experience of phenomenal contrast. Second, arguments that involve hypothetical cases and focus on the conceivability of contrast scenarios. Notably, in the light of these contrast cases, proponents and skeptics of cognitive phenomenology remain steadfast in their views. I provide an explanation of the method's dialectical ineffectiveness by focusing on first-person performances of phenomenal contrast tasks. In particular, I argue that introspective judgments about phenomenology are regimented by the view initially held. Understanding the underlying mechanisms responsible for the dialectical standoff in the face of phenomenal contrast cases casts light on introspection-based arguments for phenomenology in general.
Effective high-temperature estimates for intermittent maps
Authors: KLOECKNER BENOÎT R.
Published: December 2017

Using quantitative perturbation theory for linear operators, we prove a spectral gap for transfer operators of various families of intermittent maps with almost constant potentials (‘high-temperature’ regime). Hölder and bounded $p$-variation potentials are treated, in each case under a suitable assumption on the map, but the method should apply more generally. It is notably proved that for any Pommeau–Manneville map, any potential with Lipschitz constant less than 0.0014 has a transfer operator acting on $\operatorname{Lip}([0,1])$ with a spectral gap; and that for any two-to-one unimodal map, any potential with total variation less than 0.0069 has a transfer operator acting on $\operatorname{BV}([0,1])$ with a spectral gap. We also prove under quite general hypotheses that the classical definition of spectral gap coincides with the formally stronger one used in Giulietti et al [The calculus of thermodynamical formalism. J. Eur. Math. Soc., to appear. Preprint, 2015, arXiv:1508.01297], allowing all results there to be applied under the high-temperature bounds proved here: analyticity of pressure and equilibrium states, central limit theorem, etc.
A Lagrangian fluctuation–dissipation relation for scalar turbulence. Part III. Turbulent Rayleigh–Bénard convection
Authors: Eyink Gregory L. , Drivas Theodore D.
Published: December 2017

A Lagrangian fluctuation–dissipation relation has been derived in a previous work to describe the dissipation rate of advected scalars, both passive and active, in wall-bounded flows. We apply this relation here to develop a Lagrangian description of thermal dissipation in turbulent Rayleigh–Bénard convection in a right-cylindrical cell of arbitrary cross-section, with either imposed temperature difference or imposed heat flux at the top and bottom walls. We obtain an exact relation between the steady-state thermal dissipation rate and the time $\unicode[STIX]{x1D70F}_{mix}$ for passive tracer particles released at the top or bottom wall to mix to their final uniform value near those walls. We show that an ‘ultimate regime’ with the Nusselt number scaling predicted by Spiegel (Annu. Rev. Astron., vol. 9, 1971, p. 323) or, with a log correction, by Kraichnan (Phys. Fluids, vol. 5 (11), 1962, pp. 1374–1389) will occur at high Rayleigh numbers, unless this near-wall mixing time is asymptotically much longer than the free-fall time $\unicode[STIX]{x1D70F}_{free}$. Precisely, we show that $\unicode[STIX]{x1D70F}_{mix}/\unicode[STIX]{x1D70F}_{free}=(RaPr)^{1/2}/Nu,$ with $Ra$ the Rayleigh number, $Pr$ the Prandtl number, and $Nu$ the Nusselt number. We suggest a new criterion for an ultimate regime in terms of transition to turbulence of a thermal ‘mixing zone’, which is much wider than the standard thermal boundary layer. Kraichnan–Spiegel scaling may, however, not hold if the intensity and volume of thermal plumes decrease sufficiently rapidly with increasing Rayleigh number. To help resolve this issue, we suggest a program to measure the near-wall mixing time $\unicode[STIX]{x1D70F}_{mix}$, which is precisely defined in the paper and which we argue is accessible both by laboratory experiment and by numerical simulation.
Non-modal stability analysis of the boundary layer under solitary waves
Authors: Verschaeve Joris C. G. , Pedersen Geir K. , Tropea Cameron
Published: December 2017

In the present work, a stability analysis of the bottom boundary layer under solitary waves based on energy bounds and non-modal theory is performed. The instability mechanism of this flow consists of a competition between streamwise streaks and two-dimensional perturbations. For lower Reynolds numbers and early times, streamwise streaks display larger amplification due to their quadratic dependence on the Reynolds number, whereas two-dimensional perturbations become dominant for larger Reynolds numbers and later times in the deceleration region of this flow, as the maximum amplification of two-dimensional perturbations grows exponentially with the Reynolds number. By means of the present findings, we can give some indications on the physical mechanism and on the interpretation of the results by direct numerical simulation in Vittori & Blondeaux (J. Fluid Mech., vol. 615, 2008, pp. 433–443) and Özdemir et al. (J. Fluid Mech., vol. 731, 2013, pp. 545–578) and by experiments in Sumer et al. (J. Fluid Mech., vol. 646, 2010, pp. 207–231). In addition, three critical Reynolds numbers can be defined for which the stability properties of the flow change. In particular, it is shown that this boundary layer changes from a monotonically stable to a non-monotonically stable flow at a Reynolds number of $Re_{\unicode[STIX]{x1D6FF}}=18$.
Late Holocene forest contraction and fragmentation in central Africa
Authors: Maley Jean , Doumenge Charles , Giresse Pierre , Mahé Gil , Philippon Nathalie , Hubau Wannes , Lokonda Michel O. , Tshibamba John M. , Chepstow-Lusty Alex
Published: December 2017

During the warmer Holocene Period, two major climatic crises affected the Central African rainforests. The first crisis, around 4000 cal yr BP, caused the contraction of the forest in favor of savanna expansion at its northern and southern periphery. The second crisis, around 2500 cal yr BP, resulted in major perturbation at the forest core, leading to forest disturbance and fragmentation with a rapid expansion of pioneer-type vegetation, and a marked erosional phase. The major driver of these two climatic crises appears to be rapid sea-surface temperature variations in the equatorial eastern Atlantic, which modified the regional atmospheric circulation. The change between ca. 2500 to 2000 cal yr BP led to a large increase in thunderstorm activity, which explains the phase of forest fragmentation. Ultimately, climatic data obtained recently show that the present-day major rise in thunderstorms and lightning activity in Central Africa could result from some kind of solar influence, and hence the phase of forest fragmentation between ca. 2500 to 2000 cal yr BP may provide a model for the present-day global warming-related environmental changes in this region.
Death in Slawi: The “Sugar Factory Murders,” Ethnicity, Conflicted Loyalties and the Context of Violence in the Early Revolution in Indonesia, October 1945
Authors: Knight G. Roger
Published: December 2017

In mid-October 1945, Edward and Frederika van der Sluys were murdered in gruesome circumstances, along with a number of other Dutch Eurasians, most probably in the yard of a Dutch-owned sugar factory in the Slawi district of the north coast of Central Java at which the husband had been employed since his youth. Their fate forms part of a larger narrative of the Bersiap! (“Get Ready!”) period of the Indonesian national revolution, which has attracted considerable attention from historians. Indeed, there are already two well-trod narratives of the violence accompanying the revolution and of ethnic cleansing during the Bersiap. The present paper argues, however, that there is room for a third: that of the sugar industry—and factory communities that lay at its heart—as a much older arena of social difference and conflicted loyalties. The account proceeds on the assumption that, without being embedded in a broader and deeper narrative, the story of what happened to the Van der Sluys couple remains incomplete.
‘Yes, that's the best’: Short front vowel lowering in English today
Authors: Hickey Raymond
Published: December 2017

In different parts of the English-speaking world various vowel changes have been taking place in recent years, perhaps the most noticeable of which is the vowel lowering in words like DRESS and TRAP. This lowering would seem to have its origins some few decades ago in North America, probably in California and perhaps simultaneously in Canada. The shift, labelled here short front vowel lowering (SFVL), has spread quickly across the anglophone world and is found in locations as far apart as Ireland, South Africa and Australia. In each case where the change has been adopted there has been an adaptation of the change to local circumstances within the borrowing variety. The transmission of the change is also significant as the spread would seem not to be by direct speaker contact.
An Adaptive △M-ICCP Geomagnetic Matching Algorithm
Authors: Xiao Jing , Duan Xiusheng , Qi Xiaohui
Published: December 2017

In this paper, a novel method is proposed to generate the matching sequence of an ICCP algorithm for aircraft geomagnetic-aided navigation based on the M coding principle. The length of the matching sequence and the selection of the matching points directly affects the performance of the Iterated Closest Contour Point (ICCP) algorithm. This study proposes an adaptive geomagnetic matching method, ΔM-ICCP, to solve the problem of selecting suitable matching lengths, and matching points, when a vehicle is moving in a highly dynamic environment. First, the △M coding principle is adopted to select the matching points based on the information of the magnetic field, the resolution of the magnetic map, and the accuracy of the magnetic sensor. Then, the problem of selecting parameters for the △M-ICCP algorithm is turned into an optimisation problem, which can be solved by a Binary Particle Swarm Optimisation (BPSO) algorithm. Finally, the algorithm is verified through simulation experiments. The proposed algorithm can provide a basis to determine the matching length of the △M-ICCP algorithm and adaptively adjust the algorithm's parameters according to different trajectories. The algorithm is applicable even in the areas where the fluctuations of Earth's magnetic field are not significant.
THE BLUFF: THE POWER OF INSINCERE ACTIONS
Authors: Ferzan Kimberly Kessler
Published: December 2017

In addition to normative powers by which we alter our rights and duties, we can also forfeit rights. Culpable aggression forfeits the aggressor's right against the victim's use of defensive force. So, what happens when an aggressor “fakes it”? If a culpable aggressor is simply bluffing, has he still forfeited his rights? Because there is no threat, leading accounts of self-defense deny that there is forfeiture.

This paper argues that individuals alter their rights and duties through insincere acts. Specifically, when one person culpably causes another person to believe that a normative power has been exercised or a right forfeited, that normative power is in fact exercised or the right is forfeited. An insincere promise counts as a promise; insincere consent counts as consent; and insincere abandonment counts as abandonment. And, the insincere threat forfeits the bluffer's rights to the same extent as a real threat would.
GRADED CHAIN CONDITIONS AND LEAVITT PATH ALGEBRAS OF NO-EXIT GRAPHS
Authors: VAŠ LIA
Published: December 2017

We obtain a complete structural characterization of Cohn–Leavitt algebras over no-exit objects as graded involutive algebras. Corollaries of this result include graph-theoretic conditions characterizing when a Leavitt path algebra is a directed union of (graded) matricial algebras over the underlying field and over the algebra of Laurent polynomials and when the monoid of isomorphism classes of finitely generated projective modules is atomic and cancelative. We introduce the nonunital generalizations of graded analogs of noetherian and artinian rings, graded locally noetherian and graded locally artinian rings, and characterize graded locally noetherian and graded locally artinian Leavitt path algebras without any restriction on the cardinality of the graph. As a consequence, we relax the assumptions of the Abrams–Aranda–Perera–Siles characterization of locally noetherian and locally artinian Leavitt path algebras.
Impact of point sources on antibiotic resistance genes in the natural environment: a systematic review of the evidence
Authors: Bueno Irene , Williams-Nguyen Jessica , Hwang Haejin , Sargeant Jan M. , Nault André J. , Singer Randall S.
Published: December 2017

There is a growing concern about the role of the environment in the dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this systematic review, we summarize evidence for increases of ARG in the natural environment associated with potential sources of ARB and ARG such as agricultural facilities and wastewater treatment plants. A total of 5247 citations were identified, including studies that ascertained both ARG and ARB outcomes. All studies were screened for relevance to the question and methodology. This paper summarizes the evidence only for those studies with ARG outcomes (n= 24). Sixteen studies were at high (n= 3) or at unclear (n= 13) risk of bias in the estimation of source effects due to lack of information or failure to control for confounders. Statistical methods were used in nine studies; three studies assessed the effect of multiple sources using modeling approaches, and none reported effect measures. Most studies reported higher ARG concentration downstream/near the source, but heterogeneous findings hindered making any sound conclusions. To quantify increases of ARG in the environment due to specific point sources, there is a need for studies that emphasize analytic or design control of confounding, and that provide effect measure estimates.
A model of emerging intelligence in Universe
Authors: Zak Michail
Published: December 2017

The paper proposes a scenario of origin and emerging of intelligent life in Universe based upon the mathematical discovery of a new class of dynamical systems described by ordinary differential equation (ODE) coupled with their Liouville equation. These systems called self-controlled since the role of actuators is played by the probability produced by the Liouville equation. Following the Madelung equation that belongs to this class, non-Newtonian and quantum-like properties such as randomness, entanglement and probability interference typical for quantum systems have been described. At the same time, these systems expose properties of livings: decomposition into motor and mental dynamics, the capability of self-identification and self-awareness, as well as self-supervision. But the most surprising discovery is the existence of a special sub-class, in which the dynamical systems can violate the second law of thermodynamics, and that makes them different from both Newtonian and quantum physics. This sub-class should be associated with intelligent livings due to capability to move from disorder to order without external help. Based upon the mathematical discovery described above, one can assume that there are good chances that similar dynamical systems representing intelligent livings exist in real physical world. This provides a reason for a ‘rehabilitation’ of the Maxwell demon and put it into physics of intelligent systems. Indeed, the Maxwell demon is implemented by the feedback from the Liouville equation to the original ODE, while this feedback is capable to rearrange the probability distribution against the second law of thermodynamics. In addition to that, the same feedback removes the entropy paradox by explaining high order in our surrounding by ‘intelligent life support’. Two-steps transition: from the Newtonian physics to the linear model of life, and from the latter to the model of intelligent life are analysed. The first transition is triggered by the Hadamard instability of the Newtonian physics with respect to small random disturbances in linear terms of the Liouville feedback. The second transition is triggered by instability of linear model of life with respect to small random disturbances of non-linear terms of Liouville feedback. This transition could be implemented by such physical phenomena as shock waves or negative diffusion in probability space. Both transitions can be associated with catastrophe theory, in which sudden shifts in behaviour arises from small changes in parameters of the model. In view of the proposed model, possible competition between artificial and human intelligence are discussed.
Die Rolle der onkoplastischen Chirurgie in der Behandlung des	Mammakarzinoms
Authors: Kappos Elisabeth A. , Weber Walter P. , Soysal Savas D. , Schwab Fabienne , Kurzeder Christian , Haug Martin D.
Published: December 2017

Zusammenfassung. Ziel der onkoplastischen Chirurgie ist es, durch Verbindung von onkologisch sicherer Chirurgie und rekonstruktiven plastisch chirurgischen Techniken auch grössere Tumoren brusterhaltend operieren zu können. Durch innovative Techniken wird der ästhetische Outcome verbessert mit dem Ziel die Patientinnenzufriedenheit und Lebensqualität hoch zu halten, möglichst ohne deformierende Resultate als Folge der Brustkrebsbehandlung. Gemäss Patientinnenwunsch kann in der selben Operation die Gegenseite symmetrisierend angeglichen werden, ohne dass für die Patientinnen Kosten entstehen. Onkoplastik ist genauso sicher wie konventionelle brusterhaltende Chirurgie. Es gibt jedoch Hinweise für häufigere postoperative Komplikationen, am ehesten zurückzuführen auf anspruchsvollere Techniken und längere Operationszeit. Letztere führen jedoch nicht zu einer Verzögerung der adjuvanten Therapie. Um die vielfältigen neuen Techniken zu standardisieren, wurde Anfang 2017 in Basel ein sehr erfolgreiches internationales Expertentreffen abgehalten, dessen Resultate hier ebenfalls erläutert werden sollen.
Researchers Explore Carbon Footprints of Superheroes
Authors: Showstack Randy
Published: December 2017

A tongue-in-cheek exercise about comic book heroes aims to inspire people to consider the amount of greenhouse gas emissions they themselves cause.
Implication of 4E-BP1 protein dephosphorylation and accumulation in pancreatic cancer cell death induced by combined gemcitabine and TRAIL
Authors: Elia Androulla , Henry-Grant Ricky , Adiseshiah Charlotte , Marboeuf Catherine , Buckley Rebecca J , Clemens Michael J , Mudan Satvinder , Pyronnet Stéphane
Published: December 2017

Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1. This is associated with inhibition of mTOR activity, resulting from caspase-mediated cleavage of the Raptor and Rictor components of mTOR. Use of the pan-caspase inhibitor Z-VAD-FMK indicates that the increase in level of 4E-BP1 is also caspase-mediated. ShRNA-silencing of 4E-BP1 expression renders cells more resistant to cell death induced by the combination treatment. Since the levels of 4E-BP1 are relatively low in untreated pancreatic cancer cells these results suggest that combined therapy with gemcitabine and TRAIL could improve the responsiveness of tumours to treatment by elevating the expression of 4E-BP1.
PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle
Authors: Banerji Christopher R. S. , Panamarova Maryna , Hebaishi Husam , White Robert B. , Relaix Frédéric , Severini Simone , Zammit Peter S.
Published: December 2017

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to hypomethylation of D4Z4 repeats on chromosome 4q causing expression of the DUX4 transcription factor. However, DUX4 is difficult to detect in FSHD muscle biopsies and it is debatable how robust changes in DUX4 target gene expression are as an FSHD biomarker. PAX7 is a master regulator of myogenesis that rescues DUX4-mediated apoptosis. Here, we show that suppression of PAX7 target genes is a hallmark of FSHD, and that it is as major a signature of FSHD muscle as DUX4 target gene expression. This is shown using meta-analysis of over six FSHD muscle biopsy gene expression studies, and validated by RNA-sequencing on FSHD patient-derived myoblasts. DUX4 also inhibits PAX7 from activating its transcriptional target genes and vice versa. Furthermore, PAX7 target gene repression can explain oxidative stress sensitivity and epigenetic changes in FSHD. Thus, PAX7 target gene repression is a hallmark of FSHD that should be considered in the investigation of FSHD pathology and therapy.
RNA degradation by the plant RNA exosome involves both phosphorolytic and hydrolytic activities
Authors: Sikorska Natalia , Zuber Hélène , Gobert Anthony , Lange Heike , Gagliardi Dominique
Published: December 2017

The RNA exosome provides eukaryotic cells with an essential 3′–5′ exoribonucleolytic activity, which processes or eliminates many classes of RNAs. Its nine-subunit core (Exo9) is structurally related to prokaryotic phosphorolytic exoribonucleases. Yet, yeast and animal Exo9s have lost the primordial phosphorolytic capacity and rely instead on associated hydrolytic ribonucleases for catalytic activity. Here, we demonstrate that Arabidopsis Exo9 has retained a distributive phosphorolytic activity, which contributes to rRNA maturation processes, the hallmark of exosome function. High-density mapping of 3′ extremities of rRNA maturation intermediates reveals the intricate interplay between three exoribonucleolytic activities coordinated by the plant exosome. Interestingly, the analysis of RRP41 protein diversity across eukaryotes suggests that Exo9’s intrinsic activity operates throughout the green lineage, and possibly in some earlier-branching non-plant eukaryotes. Our results reveal a remarkable evolutionary variation of this essential RNA degradation machine in eukaryotes.
Evolution of sequence-specific anti-silencing systems in Arabidopsis
Authors: Hosaka Aoi , Saito Raku , Takashima Kazuya , Sasaki Taku , Fu Yu , Kawabe Akira , Ito Tasuku , Toyoda Atsushi , Fujiyama Asao , Tarutani Yoshiaki , Kakutani Tetsuji
Published: December 2017

The arms race between parasitic sequences and their hosts is a major driving force for evolution of gene control systems. Since transposable elements (TEs) are potentially deleterious, eukaryotes silence them by epigenetic mechanisms such as DNA methylation. Little is known about how TEs counteract silencing to propagate during evolution. Here, we report behavior of sequence-specific anti-silencing proteins used by Arabidopsis TEs and evolution of those proteins and their target sequences. We show that VANC, a TE-encoded anti-silencing protein, induces extensive DNA methylation loss throughout TEs. Related VANC proteins have evolved to hypomethylate TEs of completely different spectra. Targets for VANC proteins often form tandem repeats, which vary considerably between related TEs. We propose that evolution of VANC proteins and their targets allow propagation of TEs while causing minimal host damage. Our findings provide insight into the evolutionary dynamics of these apparently “selfish” sequences. They also provide potential tools to edit epigenomes in a sequence-specific manner.
Growth Associated Protein 43 (GAP-43) as a Novel Target for the Diagnosis, Treatment and Prevention of Epileptogenesis
Authors: Nemes Ashley D. , Ayasoufi Katayoun , Ying Zhong , Zhou Qi-Gang , Suh Hoonkyo , Najm Imad M.
Published: December 2017

We previously showed increased growth associated protein 43 (GAP-43) expression in brain samples resected from patients with cortical dysplasia (CD), which was correlated with duration of epilepsy. Here, we used a rat model of CD to examine the regulation of GAP-43 in the brain and serum over the course of epileptogenesis. Baseline GAP-43 expression was higher in CD animals compared to control non-CD rats. An acute seizure increased GAP-43 expression in both CD and control rats. However, GAP-43 expression decreased by day 15 post-seizure in control rats, which did not develop spontaneous seizures. In contrast, GAP-43 remained up-regulated in CD rats, and over 50% developed chronic epilepsy with increased GAP-43 levels in their serum. GAP-43 protein was primarily located in excitatory neurons, suggesting its functional significance in epileptogenesis. Inhibition of GAP-43 expression by shRNA significantly reduced seizure duration and severity in CD rats after acute seizures with subsequent reduction in interictal spiking. Serum GAP-43 levels were significantly higher in CD rats that developed spontaneous seizures. Together, these results suggest GAP-43 as a key factor promoting epileptogenesis, a possible therapeutic target for treatment of progressive epilepsy and a potential biomarker for epilepsy progression in CD.
Safety and Efficacy of Losartan 50 mg in Reducing Blood Pressure among Patients with Post-Dialysis Euvolemic Hypertension: A Randomized Control Trial
Authors: Aftab Raja Ahsan , Khan Amer Hayat , Adnan Azreen Syazril , Sulaiman Syed Azhar Syed , Khan Tahir Mehmood
Published: December 2017

The aim of current study was to assess the effectiveness of losartan 50 mg in reducing blood pressure among post-dialysis euvolemic hypertensive patients, observing their survival trends and adverse events during the course of study. A multicentre, prospective, randomised, single-blind trial was conducted to assess the effect of losartan 50 mg every other day (EOD), once a morning (OM) among post-dialysis euvolemic hypertensive patients. Post-dialysis euvolemic assessment was done by a body composition monitor (BCM). Covariate Adaptive Randomization was used for allocation of participants to the standard or intervention arm. Of the total 229 patients, 96 (41.9%) were identified as post-dialysis euvolemic hypertensive. Final samples of 88 (40.1%) patients were randomized into standard and intervention arms. After follow-up of 12 months’ pre-dialysis systolic (p < 0.001) and diastolic (p 0.01), intradialysis diastolic (p 0.02), post-dialysis systolic (p < 0.001) and diastolic (p < 0.001) blood pressure was reduced from the baseline among intervention-arm patients Compared to only pre-dialysis systolic blood pressure (p 0.003) among standard arm patients after 12 months of follow. Total of six deaths were reported among standard-arm patients compared to 2 deaths among the intervention arm. Losartan 50 mg achieve an overall significant decline in blood pressure among post-dialysis euvolemic hypertensive patients.
Structure and piezo-ferroelectricity relationship study of (K0.5Na0.5)0.985La0.005NbO3 epitaxial films deposited on SrTiO3 by sputtering
Authors: H´Mŏk H´Linh , Martínez-Aguilar E. , Gervacio-Arciniega J. J. , Vendrell X. , Siqueiros-Beltrones J. M. , Raymond-Herrera O.
Published: December 2017

This work demonstrates that the rf-sputtering technique, combined with appropriate heat treatments, is potentially effective to develop new materials and devices based on oxide-interface and strain engineering. We report a study of the structural-physical properties relationship of high crystalline quality, highly oriented and epitaxial thin films of the lead-free (K0.5Na0.5)0.985La0.005NbO3 (KNNLa) compound which were successfully deposited on Nb-doped SrTiO3 substrates, with orientations [100] (NSTO100) and [110] (NSTO110). The crystalline growth and the local ferroelectric and piezoelectric properties were evaluated by piezoresponse force microscopy combined with transmission electron microscopy and texture analysis by X-ray diffraction. Conditioned by the STO surface parameters, in the KNNLa films on NSTO100 coexist a commensurate [001]-tetragonal phase and two incommensurate [010]-monoclinic phases; while on NSTO110 the KNNLa films grew only in an incommensurate [101]-monoclinic phase. Both samples show excellent out-of-plane polarization switching patterns consistent with 180° domains walls; while for KNNLa/NSTO100 ferroelectric domains grow with the polarization pointing down, for KNNLa/NSTO110 they prefer to grow with the polarization pointing up. Comparing with previous reports on epitaxial KNN films, we find our samples to be of very high quality regarding their crystalline growth with highly ordered ferroelectric domains arrangements and, consequently, great potential for domain engineering.
Mechanically stable solvent-free lipid bilayers in nano- and micro-tapered apertures for reconstitution of cell-free synthesized hERG channels
Authors: Tadaki Daisuke , Yamaura Daichi , Araki Shun , Yoshida Miyu , Arata Kohei , Ohori Takeshi , Ishibashi Ken-ichi , Kato Miki , Ma Teng , Miyata Ryusuke , Tozawa Yuzuru , Yamamoto Hideaki , Niwano Michio , Hirano-Iwata Ayumi
Published: December 2017

The self-assembled bilayer lipid membrane (BLM) is the basic component of the cell membrane. The reconstitution of ion channel proteins in artificially formed BLMs represents a well-defined system for the functional analysis of ion channels and screening the effects of drugs that act on them. However, because BLMs are unstable, this limits the experimental throughput of BLM reconstitution systems. Here we report on the formation of mechanically stable solvent-free BLMs in microfabricated apertures with defined nano- and micro-tapered edge structures. The role of such nano- and micro-tapered structures on the stability of the BLMs was also investigated. Finally, this BLM system was combined with a cell-free synthesized human ether-a-go-go-related gene channel, a cardiac potassium channel whose relation to arrhythmic side effects following drug treatment is well recognized. Such stable BLMs as these, when combined with a cell-free system, represent a potential platform for screening the effects of drugs that act on various ion-channel genotypes.
Isolation and pathogenicity of Xylella fastidiosa associated to the olive quick decline syndrome in southern Italy
Authors: Saponari M. , Boscia D. , Altamura G. , Loconsole G. , Zicca S. , D’Attoma G. , Morelli M. , Palmisano F. , Saponari A. , Tavano D. , Savino V. N. , Dongiovanni C. , Martelli G. P.
Published: December 2017

In autumn 2013, the presence of Xylella fastidiosa, a xylem-limited Gram-negative bacterium, was detected in olive stands of an area of the Ionian coast of the Salento peninsula (Apulia, southern Italy), that were severely affected by a disease denoted olive quick decline syndrome (OQDS). Studies were carried out for determining the involvement of this bacterium in the genesis of OQDS and of the leaf scorching shown by a number of naturally infected plants other than olive. Isolation in axenic culture was attempted and assays were carried out for determining its pathogenicity to olive, oleander and myrtle-leaf milkwort. The bacterium was readily detected by quantitative polymerase chain reaction (qPCR) in all diseased olive trees sampled in different and geographically separated infection foci, and culturing of 51 isolates, each from a distinct OQDS focus, was accomplished. Needle-inoculation experiments under different environmental conditions proved that the Salentinian isolate De Donno belonging to the subspecies pauca is able to multiply and systemically invade artificially inoculated hosts, reproducing symptoms observed in the field. Bacterial colonization occurred in prick-inoculated olives of all tested cultivars. However, the severity of and timing of symptoms appearance differed with the cultivar, confirming their differential reaction.
Excellent Rectifying Properties of the n-3C-SiC/p-Si Heterojunction Subjected to High Temperature Annealing for Electronics, MEMS, and LED Applications
Authors: Tanner Philip , Iacopi Alan , Phan Hoang-Phuong , Dimitrijev Sima , Hold Leonie , Chaik Kien , Walker Glenn , Dao Dzung Viet , Nguyen Nam-Trung
Published: December 2017

This work examines the stability of epitaxial 3C-SiC/Si heterojunctions subjected to heat treatments between 1000 °C and 1300 °C. Because of the potential for silicon carbide in high temperature and harsh environment applications, and the economic advantages of growing the 3C-SiC polytype on large diameter silicon wafers, its stability after high temperature processing is an important consideration. Yet recently, this has been thrown into question by claims that the heterojunction suffers catastrophic degradation at temperatures above 1000 °C. Here we present results showing that the heterojunction maintains excellent diode characteristics following heat treatment up to 1100 °C and while some changes were observed between 1100 °C and 1300 °C, diodes maintained their rectifying characteristics, enabling compatibility with a large range of device fabrication. The parameters of as-grown diodes were J0 = 1 × 10−11 A/mm2, n = 1.02, and +/−2V rectification ratio of 9 × 106. Capacitance and thermal current-voltage analysis was used to characterize the excess current leakage mechanism. The change in diode characteristics depends on diode area, with larger areas (1 mm2) having reduced rectification ratio while smaller areas (0.04 mm2) maintained excellent characteristics of J0 = 2 × 10−10 A/mm2, n = 1.28, and +/−2V ratio of 3 × 106. This points to localized defect regions degrading after heat treatment rather than a fundamental issue of the heterojunction.