bluuebunny/crossref_metadata_2025 huggingface dataset:
ADP‐glucose pyrophosphorylase genes, associated with kernel weight, underwent selection during wheat domestication and breeding
Authors: Hou Jian , Li Tian , Wang Yamei , Hao Chenyang , Liu Hongxia , Zhang Xueyong
Published: April 2017

ADP‐glucose pyrophosphorylase, comprising two small subunits and two large subunits, is considered a key enzyme in the endosperm starch synthesis pathway in wheat (Triticum aestivum L.). Two genes, TaAGP‐S1‐7A and TaAGP‐L‐1B, were investigated in this study. Haplotypes of these genes were associated with thousand kernel weight (TKW) in different populations. Mean TKWs of favoured haplotypes were significantly higher than those of nonfavoured ones. Two molecular markers developed to distinguish these haplotypes could be used in molecular breeding. Frequencies of favoured haplotypes were dramatically increased in cultivars released in China after the 1940s. These favoured haplotypes were also positively selected in six major wheat production regions globally. Selection of AGP‐S1 and AGP‐L‐1B in wheat mainly occurred during and after hexaploidization. Strong additive effects of the favoured haplotypes of with other genes for starch synthesis were also detected in different populations.
Selectivity of N170 for visual words in the right hemisphere: Evidence from single‐trial analysis
Authors: Yang Hang , Zhao Jing , Gaspar Carl M. , Chen Wei , Tan Yufei , Weng Xuchu
Published: April 2017

Neuroimaging and neuropsychological studies have identified the involvement of the right posterior region in the processing of visual words. Interestingly, in contrast, ERP studies of the N170 typically demonstrate selectivity for words more strikingly over the left hemisphere. Why is right hemisphere selectivity for words during the N170 epoch typically not observed, despite the clear involvement of this region in word processing? One possibility is that amplitude differences measured on averaged ERPs in previous studies may have been obscured by variation in peak latency across trials. This study examined this possibility by using single‐trial analysis. Results show that words evoked greater single‐trial N170s than control stimuli in the right hemisphere. Additionally, we observed larger trial‐to‐trial variability on N170 peak latency for words as compared to control stimuli over the right hemisphere. Results demonstrate that, in contrast to much of the prior literature, the N170 can be selective to words over the right hemisphere. This discrepancy is explained in terms of variability in trial‐to‐trial peak latency for responses to words over the right hemisphere.
Scripture and Theological Hermeneutics: Some Recent DevelopmentsTheology, History, and Biblical Interpretation: Modern Readings, DarrenSarisky (ed.), Bloomsbury T&T Clark, 2015 (ISBN 978‐0‐567‐45980‐0), viii + 490 pp., pb £27.99Scriptural Interpretation: A Theological Interpretation, DarrenSarisky, Wiley‐Blackwell, 2013 (ISBN 978‐1‐118‐36745‐2), xvi + 276 pp., hb £60Divine Eloquence and Human Transformation: Rethinking Scripture and History through Gregory of Nazianzus and Hans Frei, BenFulford, Fortress, 2013 (ISBN 978‐1‐4514‐6548‐8), xii + 301 pp., pb $59Hermeneutics and the Church: In Dialogue with Augustine, James A.Andrews, University of Notre Dame Press, 2012 (ISBN 978‐0‐268‐02041‐5), xvi + 303 pp., pb $35
Authors: Moberly Walter
Published: April 2017

This essay considers four recent contributions to the field of theological hermeneutics in relation to reading the Bible as Christian Scripture. All four contributions are found to be helpful, and Sarisky's Modern Readings could serve as an excellent MA textbook. The three monographs well model the practice of ressourcement, although they do not engage with the differences that gender issues and renewed appreciation of Jewish interpretations might make.
Irony as a Way of Life?Truth and Irony: Philosophical Meditations on Erasmus, Terence J.Martin, Catholic University of America Press, 2015 (ISBN 978‐0‐8132‐2809‐9), xii + 259 pp., hb $65A Case for Irony, JonathanLear, Harvard University Press, 2011 (ISBN 978‐0‐6744‐1688‐8), xiv + 210 pp., pb £15.95
Authors: Ravenscroft Simon
Published: April 2017

As a figure of speech for which a speaker's meaning is taken to be the opposite of what she says, irony may not ordinarily be linked to truthfulness. Two recent books by Terence J. Martin and Jonathan Lear nonetheless mount convincing cases for a more complex, philosophical understanding of irony as non‐cynical, and as having a constructive role to play in the truthful and well‐lived life. Taking Erasmus, and Socrates and Kierkegaard as their main sources respectively, both authors argue that the experience of irony allows for a specific form of truthfulness to emerge about who we are as finite beings. This review essay leads with an analysis of the argument developed in defence of this point in Martin's book on Erasmus, before bringing Lear into the conversation in order to reveal shortcomings in Martin's theorisation of irony. This is followed by a critical response to Lear's own account, which allows for further reflection on the relation between irony, religion, and theology in his and Martin's main sources.
Hematopoietic stem cell transplantation and cellular therapy
Authors: Kolb H.‐J.
Published: April 2017

Allogeneic stem cell transplantation is a form of immunotherapy that has increased the chances of survival for patients with relapsed leukemia and high risk leukemia in remission. The major obstacles are graft‐vs‐host disease (GVHD) involving vital organs and infections. A most efficacious prophylaxis of GVHD is by depleting of T cells from the graft. However, problems of T‐depleted transplants are rejection, slow recovery of the immune system and high incidence of relapse of leukemia and myeloma. The major problem of allogeneic transplantation is the separation of a graft‐vs‐leukemia (GVL) effect from GVHD. This review will summarize the factors influencing GVHD, ways to exploit rapid advances in our knowledge of histocompatibility, chimerism and tolerance for fostering GVL over GVHD, and in particular the use of cellular therapies including donor lymphocyte infusions for disease control.
Nitrate‐dependent shoot sodium accumulation and osmotic functions of sodium in Arabidopsis under saline conditions
Authors: Álvarez‐Aragón Rocío , Rodríguez‐Navarro Alonso
Published: April 2017

Improving crop plants to be productive in saline soils or under irrigation with saline water would be an important technological advance in overcoming the food and freshwater crises that threaten the world population. However, even if the transformation of a glycophyte into a plant that thrives under seawater irrigation was biologically feasible, current knowledge about Na+ effects would be insufficient to support this technical advance. Intriguingly, crucial details about Na+ uptake and its function in the plant have not yet been well established. We here propose that under saline conditions two nitrate‐dependent transport systems in series that take up and load Na+ into the xylem constitute the major pathway for the accumulation of Na+ in Arabidopsis shoots; this pathway can also function with chloride at high concentrations. In nrt1.1 nitrate transport mutants, plant Na+ accumulation was partially defective, which suggests that NRT1.1 either partially mediates or modulates the nitrate‐dependent Na+ transport. Arabidopsis plants exposed to an osmotic potential of −1.0 MPa (400 mOsm) for 24 h showed high water loss and wilting in sorbitol or Na/MES, where Na+ could not be accumulated. In contrast, in NaCl the plants that accumulated Na+ lost a low amount of water, and only suffered transitory wilting. We discuss that in Arabidopsis plants exposed to high NaCl concentrations, root Na+ uptake and tissue accumulation fulfil the primary function of osmotic adjustment, even if these processes lead to long‐term toxicity.
Healing of canine skin incisions made with monopolar electrosurgery versus scalpel blade
Authors: Scott Jacqueline E. , Swanson Elizabeth A. , Cooley Jim , Wills Robert W. , Pearce Emily C.
Published: April 2017

Objective

To determine the influence of monopolar electrosurgery in cutting mode set at 10, 20, or 30 W on surgery time, hemostasis, and healing of cutaneous wounds compared to scalpel incisions.

Study design

Randomized blinded control trial.

Animals

Dogs (n = 15).

Methods

Four skin incisions were created on either side of the dorsal midline with a scalpel, or monopolar electrosurgery at 10, 20, and 30 W. Surgical time and incisional bleeding were measured. Each incision was assessed daily for edema, erythema and discharge, and complications. Healing was evaluated via histology at 7 days. Results were analyzed for significance at P ≤ .05.

Results

Surgical time and hemostasis were improved in all electrosurgery groups. Erythema was reduced in all electrosurgical incisions for days 1‐4, but was greater in wounds created via electrosurgery at 20 W than those made with a scalpel blade by day 7. No difference was noted in the degree of edema or presence of wound discharge. All histologic variables of tissue healing were lower in electrosurgical incisions than scalpel incisions (P < .001). Ten incisional complications occurred, all associated with electrosurgery.

Conclusions

The use of monopolar electrosurgery at 10, 20, and 30 W in a cutting waveform improved hemostasis and surgical time when incising canine skin, but delayed healing and increased complications within the first 7 days compared to scalpel incisions.
Canine cranial cruciate ligament deficient stifle biomechanics associated with extra‐articular stabilization predicted using a computer model
Authors: Brown Nathan P. , Bertocci Gina E. , Marcellin‐Little Denis J.
Published: April 2017

Objective

To evaluate lateral fabellotibial suture (LFTS) and TightRope CCL (TR) extra‐articular stabilization biomechanics in the cranial cruciate ligament (CrCL)‐deficient canine stifle joint during the stance phase of gait.

Study design

Computer simulations.

Animals

Healthy 33‐kg Golden Retriever.

Methods

LFTS and TR were implemented in a previously developed 3‐D quasi‐static rigid body CrCL‐deficient canine pelvic limb computer model simulating the stance phase of gait. Ligament loads, relative tibial translation, and relative tibial rotation were determined and compared across the CrCL‐intact, CrCL‐deficient, and extra‐articular stabilized stifle joints.

Results

Compared to the CrCL‐intact stifle, peak caudal cruciate and lateral collateral ligament (LCL) loads were increased in the LFTS‐managed stifle, peak caudal cruciate and LCL loads were decreased in the TR‐managed stifle, and peak medial collateral and patellar ligament (PL) loads were similar for both techniques. Compared to the CrCL‐deficient stifle, peak caudal cruciate, lateral collateral, and medial collateral ligament loads decreased, and peak PL load was similar in the LFTS‐ and TR‐managed stifle joints. Peak relative tibial translation decreased, and peak relative tibial rotation changed from internal rotation to external rotation in the LFTS‐ and TR‐managed stifle joints compared to the CrCL‐deficient stifle.

Conclusion

Our computer model predicted controlled tibial translation, decreased cruciate and collateral ligament loads, and a change in femorotibial rotation from internal to external with LFTS and TR stifle management as compared to the CrCL‐deficient stifle. This study demonstrates how computer modeling can be used to evaluate biomechanics of stifle stabilization surgical techniques.
Secreted factors from equine mesenchymal stromal cells diminish the effects of TGF‐β1 on equine dermal fibroblasts and alter the phenotype of dermal fibroblasts isolated from cutaneous fibroproliferative wounds
Authors: Harman Rebecca M. , Bihun Ivanna V. , Van de Walle Gerlinde R.
Published: April 2017

The prevalence of cutaneous fibroproliferative disorders (CFPDs) is high and almost exclusively occurs in humans (keloids and hypertrophic scars) and horses (exuberant granulation tissue), making the horse a valuable translational model for studies on prevention and treatment of human CFPDs. CFPDs arise as a result of dysregulated wound healing characterized by persistently high levels of cytokines, such as transforming growth factor beta 1 (TGF‐β1), that contribute to excessive extracellular matrix deposition, and the physical disorganization of dermal fibroblasts (DF). The mesenchymal stromal cell (MSC) secretome, consisting of all factors secreted by MSC, has been shown to promote normal wound healing in both humans and horses, but its potential to treat CFPDs remains largely unexplored. Therefore, the objective of this study was to examine the effects of the equine MSC secretome on equine DF influenced by cytokines that contribute to the development of CFPDs. First, primary equine DF were treated with TGF‐β1 in vitro in the presence or absence of MSC secreted products. We found that MSC secreted products could block TGF‐β1‐induced changes in DF morphology, proliferation rate, gene expression, and contractile‐capacity. We then isolated primary DF from equine exuberant granulation tissue, to evaluate the potential of the MSC secretome to alter the phenotype of cells derived from a complex CFPD environment. These results showed that MSC secreted factors did not change proliferation or migration of these cells, but did lead to changes in expression of genes and proteins involved in extracellular matrix remodeling and did affect contractile capacity. These results warrant future studies designed to evaluate the potential of the MSC secretome to minimize the pathologies associated with CFPD in vivo.
Recurrent and other new foot ulcers after healed plantar forefoot diabetic ulcer
Authors: Örneholm Hedvig , Apelqvist Jan , Larsson Jan , Eneroth Magnus
Published: April 2017

Diabetic foot ulcer is a serious complication in patients with diabetes. In most outcome studies of this condition, there is a combination of various types of ulcer and ulcer locations. Plantar ulcers are usually localized to the forefoot, and constitute a quarter of all diabetic foot ulcers. There are a limited number of studies regarding development of new ulcers following healing of a plantar forefoot ulcer, and there are no uniform definitions of recurrent and other new ulcers. The aim of this study was to evaluate the outcome of a large cohort of consecutively treated patients with diabetes mellitus and a healed planter forefoot ulcer (n = 617) with regard to development, characteristics, and outcome of recurrent and other new ulcers. Patients were followed consecutively and prospectively with a 2‐year follow‐up, according to a preset protocol. Out of 617 patients, 250 (41%) did not develop any new ulcer, 262 (42%) developed a new ulcer, 87 (14%) died and 18 (3%) were lost at 2 years following healing of a plantar forefoot ulcer. Thirty‐four percent developed other new ulcers (112 on the same foot and 99 on the contralateral foot), whereas 51 patients (8%) developed a recurrent ulcer (at the same site and foot). Of the patients who died within 2 years, 30 patients had developed other new ulcers. The risk of a recurrent ulcer in patients with diabetes and a healed plantar forefoot ulcer was only 8% within 2 years, whereas other new ulcers, on the same foot or on the contralateral foot, was seen in 4 out of 10 patients indicating the need for further preventive measures and surveillance in these patients. We suggest a concise definition for new ulcer to be used in future research.
Wound healing in Mac‐1 deficient mice
Authors: Chen Lin , Nagaraja Sridevi , Zhou Jian , Zhao Yan , Fine David , Mitrophanov Alexander Y. , Reifman Jaques , DiPietro Luisa A.
Published: April 2017

Mac‐1 (CD11b/CD18) is a macrophage receptor that plays several critical roles in macrophage recruitment and activation. Because macrophages are essential for proper wound healing, the impact of Mac‐1 deficiency on wound healing is of significant interest. Prior studies have shown that Mac‐1−/− mice exhibit deficits in healing, including delayed wound closure in scalp and ear wounds. This study examined whether Mac‐1 deficiency influences wound healing in small excisional and incisional skin wounds. Three millimeter diameter full thickness excisional wounds and incisional wounds were prepared on the dorsal skin of Mac‐1 deficient (Mac‐1−/−) and wild type (WT) mice, and wound healing outcomes were examined. Mac‐1 deficient mice exhibited a normal rate of wound closure, generally normal levels of total collagen, and nearly normal synthesis and distribution of collagens I and III. In incisional wounds, wound breaking strength was similar for Mac‐1−/− and WT mice. Wounds of Mac‐1 deficient mice displayed normal total macrophage content, although macrophage phenotype markers were skewed as compared to WT. Interestingly, amounts of TGF‐β1 and its downstream signaling molecules, SMAD2 and SMAD3, were significantly decreased in the wounds of Mac‐1 deficient mice compared to WT. The results suggest that Mac‐1 deficiency has little impact on the healing of small excisional and incisional wounds. Moreover, the findings demonstrate that the effect of single genetic deficiencies on wound healing may markedly differ among wound models. These conclusions have implications for the interpretation of the many prior studies that utilize a single model system to examine wound healing outcomes in genetically deficient mice.
Novel coronaviruses, astroviruses, adenoviruses and circoviruses in insectivorous bats from northern China
Authors: Han H.‐J. , Wen H.‐L. , Zhao L. , Liu J.‐W. , Luo L.‐M. , Zhou C.‐M. , Qin X.‐R. , Zhu Y.‐L. , Liu M.‐M. , Qi R. , Li W.‐Q. , Yu H. , Yu X.‐J.
Published: April 2017

Bats are considered as the reservoirs of several emerging infectious disease, and novel viruses are continually found in bats all around the world. Studies conducted in southern China found that bats carried a variety of viruses. However, few studies have been conducted on bats in northern China, which harbours a diversity of endemic insectivorous bats. It is important to understand the prevalence and diversity of viruses circulating in bats in northern China. In this study, a total of 145 insectivorous bats representing six species were collected from northern China and screened with degenerate primers for viruses belonging to six families, including coronaviruses, astroviruses, hantaviruses, paramyxoviruses, adenoviruses and circoviruses. Our study found that four of the viruses screened for were positive and the overall detection rates for astroviruses, coronaviruses, adenoviruses and circoviruses in bats were 21.4%, 15.9%, 20% and 37.2%, respectively. In addition, we found that bats in northern China harboured a diversity of novel viruses. Common Serotine (Eptesicus serotinu), Fringed long‐footed Myotis (Myotis fimriatus) and Peking Myotis (Myotis pequinius) were investigated in China for the first time. Our study provided new information on the ecology and phylogeny of bat‐borne viruses.
(In)Efficiencies in Latin American ETFs
Authors: Kreis Yvonne , Licht Johannes W. , Useche Arévalo Alejandro José
Published: April 2017

Este estudio evalúa empíricamente la eficiencia en la valoración de varios ETFs latinoamericanos, expresada en desviaciones de sus precios de mercado frente a los valores liquidativos subyacentes. Se cuantifican tales ineficiencias y se implementa una estrategia de negociación verificada por regresiones basadas en el CAPM y el Modelo Fama-French. Los resultados discrepan con la Hipótesis de los Mercados Eficientes y son mejor explicados por aspectos de las finanzas comportamentales. Finalmente, se examina cómo las desviaciones influyen sobre la decisión de creación o redención de ETFs, mediante un análisis de regresión logística. Los resultados evidencian que los participantes autorizados reaccionan ante las ineficiencias realizando transacciones en el mercado primario.
NIIF y MIPYMES: retos de la contabilidad para el contexto y la productividad
Authors: Gómez Villegas Mauricio
Published: April 2017

Las micro, pequeñas y medianas empresas (MIPYMES) constituyen la mayoría de organizaciones en el tejido empresarial mundial. Dado el proceso de estandarización contable internacional liderado por el IASB, surge la NIIF-PYMES, esta norma asume el enfoque de las NIIF para empresas cotizadas. Dado que las MIPYMES no participan en mercados de valores este artículo examina si la regulación contable del IASB puede promover la preparación de información contable y financiera útil para la toma de decisiones y la productividad en las MIPYMES. El artículo caracteriza el enfoque y las limitaciones que impone la regulación contable internacional, para la información de estas empresas, enfatizando en los retos para que sea útil en la toma de decisiones y para la productividad
Interdisciplinary and Consistent Use of a 3D CAD Model for CAx Education in Engineering Studies
Authors: Faath Andreas , Anderl Reiner
Published: April 2017

Computer Aided Design (CAD) represents one of the key lectures in the studies of mechanical and process engineering as well as several other engineering disciplines. Furthermore Computer Aided x (CAx) systems are firmly established in the product development process.

A new concept of teaching for engineering studies at the Technical University of Darmstadt (TU Darmstadt) derived by project based learning is introduced using CAx process chains i.e. the CAD-Multi Body Simulation (MBS) process chain. For the first time in engineering degree a 3D CAD model is consistently used by different process chains in multiple lectures and exercises during the whole engineering study. The early integration of this 3D CAD model in the second semester lays a foundation for its usage in further lectures, courses, projects and theses. Due to the fact, that this 3D CAD model embodies a university groups’ race car, students are able to deepen their knowledge within the university group “TU Darmstadt Racing Team e.V. (DART)”. Therefore, synergies between private and student activities are promoted, e.g. students acquire knowledge about automotive engineering. Besides the virtual implementation and validation, concepts can use the prototype for implementation and validation.

The suitability of the 3D CAD model for CAD education in engineering studies especially the modelling and assembling of parts and assemblies is validated by the coached exercise of the course “Computer Aided Design”. The design education of students with mechanical engineering orientated fields of studies is held as a mandatory course in the second semester of mechanical engineering degrees at TU Darmstadt since 1995 and is solely taught with modern 3D CAD Systems.

The MBS process chain is validated by several projects and theses using the McNeil Swendler Corp. (MSC) Software Automated Dynamic Analysis of Mechanical Systems (ADAMS) Car. Students run MBS by using the 3D CAD model. Besides driving maneuvers, stamp tests are simulated. In this context the entire MBS process chain is passed. The 3D CAD model serves as a basis for structures, geometry and the representation of kinematic chains, guided by the 3D CAD models geometry.
A Comparative Investigation of Rheological and Flow Behavior Among Clean Polymeric and Surfactant Based Fluids
Authors: Kamel Ahmed H.
Published: April 2017

This study involves experimental investigation of rheological and hydraulic characteristics of aqueous based polymeric and surfactant fluids in straight and coiled tubing. The fluids matrix includes guar, HPG, PHPA, welan, xanthan, and surfactant. Bohlin rheometer was used to evaluate rheological and viscoelastic characteristics. For hydraulic characteristics, small- and large-scale flow loops were used.

It is observed that all fluids exhibit comparable non-Newtonian behavior and improved viscous and elastic properties. Among polymeric fluids, guar and welan provide better viscosity and suspension properties. Surfactant is significantly affected by the formation of rod-like micelles and other microstructures. Master curves for rheological and elastic properties are developed using the molecular theory approach. The foremost benefit of these curves is its dimensionless form that provides a unique technique to predict viscosity for all fluids.

For hydraulic properties, friction losses in coiled tubing are significantly higher than in straight tubing due to centrifugal forces and secondary flows. Surfactant is more sensitive to shear field applied where different microstructures are induced and thus they exhibit better drag reduction characteristics than polymeric fluids especially in coiled tubing with larger sizes. However, in straight tubing, guar shows better drag reduction characteristics than surfactant and other polymers, which diminishes as tubing size increases. However, welan gum exhibits a comparable performance. Overall, all fluids are considered good candidates as fracturing fluids with specific features for each. Unique characteristics of each fluid is discussed and explained in more details within the context of the present paper.
Incorporating Basic Systems Thinking and Systems Engineering Concepts in a Sophomore-Level Product Design and Development Course
Authors: Muci-Küchler Karim H. , Bedillion Mark D. , Degen Cassandra M. , Ellingsen Marius D. , Huang Shaobo
Published: April 2017

Although many US undergraduate mechanical engineering programs formally expose students to the basic concepts, methodologies, and tools used for the design and development of new products, the scope is usually limited to products of low complexity. There is a need to include activities in the undergraduate curriculum that allow students to learn basic systems engineering concepts, that promote the development of their systems thinking skills, and that allow them to practice these skills. This paper describes an initial effort at integrating systems engineering concepts in the curriculum focusing on a sophomore-level product development course. The paper discusses the approach that was used to identify topics related to systems thinking and systems engineering, provides the list of topics that were selected, and outlines the approach that will be used to incorporate those topics in the course. In addition, it provides the results of a pilot self-efficacy survey focusing on some of the topics selected that was delivered to junior students who had already taken a formal product development course. Although a specific course was considered, the same approach could be used in the context of the entire mechanical engineering undergraduate curriculum. Also, the results presented in the paper could be easily adapted to similar courses at other institutions.
Curriculum Change for Control Engineering Education in a Mechanical Engineering Undergrad Program
Authors: Vásquez Rafael E. , Posada Norha L. , Rúa Santiago , Zuluaga Carlos A. , Castrillón Fabio , Flórez Diego A.
Published: April 2017

This paper addresses the curriculum change performed for control engineering education in the mechanical engineering (ME) undergraduate program at the Universidad Pontificia Bolivariana (UPB), located in Medellín, Colombia. The new curriculum model of the UPB is based on learning, and promotes the achievement of outcome-related course learning objectives during the education process. The faculty of the ME department developed the Human Capabilities and Outcomes Map; such map explicitly shows the connection between general human capabilities that are strengthen through the ME program, the outcomes that are to be achieved, the way this outcomes are assessed, and the courses where the outcomes are addressed in the curriculum. The faculty responsible for the area of design, dynamic systems, and control, gathered during two years and defined educational objectives for all the courses in the area, considering the mechanical engineering program as a whole in order to provide the students with knowledge and skills necessary for their future professional career. As a result, three new courses to address control engineering education in the mechanical engineering curriculum were created: Measurement and Instrumentation, Control Engineering, and Control Engineering Lab. Since the courses have been recently created, faculty will assess the performance within a three-year period in order to quantify the impact of the curriculum change for control engineering education.
An Examination of How to Incorporate Ethics Into Systems Analysis and Vice Versa
Authors: Burgess Richard A. , Beruvides Mario G.
Published: April 2017

In their paper “Combining Systems Dynamics and Ethics: Towards More Science?” Erik Pruyt and Jan Kwakkel argue that ethics ought to play a larger role in systems dynamics and vice versa (2007). Including ethics, they contend, will add sensitivity to current systems models as well as provide guidance on how to achieve best outcomes; with respect to both efficiency and flourishing (Pruyt & Kwakkel, 2007).

At first blush, such a cross pollination promises to add much needed depth of analysis to systems modeling and a higher degree of precision in ethical analyses. Not surprisingly, however, achieving such outcomes is more complex than it initially appears. Indeed, the quest for additional precision in ethical analysis is not a new one to philosophers and ethicists. The problem remains, in many ways, intractable.

In Part I of this paper, the authors expand on Pruyt and Kwakkel’s thesis by examining specific insights and tools that can and should be incorporated into systems dynamics modeling. Emphasis will be placed on the mechanics of this inclusion and the resultant implications. Part II, then, focuses on how systems dynamics tools like causal loop modeling and behavior-over-time graphs can be incorporated into ethical analyses in a non-arbitrary manner. Finally, in Part III of the paper, the authors briefly discuss the ramifications of Parts I and II for engineering education; both among students and practicing engineers.

The authors argue that both directions of the cross pollination have merit (especially the inclusion of ethical considerations in systems dynamics modeling) and ought to be developed further.
Improving Competitiveness of Engineering Students With Disabilities Through Focused Learning
Authors: Zagrai Andrei N. , Ostergren Warren J. , Borden Laurie Tacheny , Zeman Scott
Published: April 2017

On many university campuses, students with disabilities form a noticeable group of the student population. Over the past years, enrollment of students with disabilities has markedly increased and this trend is expected to continue in the future. Although students with disabilities often prefer to major in non-technical areas, a considerable number of them choose to seek career opportunities in science, engineering and technology. The majority of prior studies on educating special engineering and STEM students have been oriented towards students with physical disabilities. A balanced approach is advocated in which individual aspects of the disability are given a special consideration and learning strategies and the environment are tailored in accordance with student’s needs. Such adjustments are critical in accommodating students with a wide spectrum of disabilities.

The aim of this paper is to consider various aspects of engineering education that may improve the competitiveness of engineering students with disabilities when they enter the professional workforce.
Exploring the fabrication of Co and Mn nanostructures with focused soft x-ray beam induced deposition
Authors: Tu Fan , Späth Andreas , Drost Martin , Vollnhals Florian , Krick Calderon Sandra , Fink Rainer H. , Marbach Hubertus
Published: April 2017

Focused soft X-ray beam induced deposition of metallic deposits from metal organic precursors is a promising novel technique for additive nanostructure fabrication. In the present work, the authors present a comparative study for deposition and in situ characterization of Co and Mn nanostructures in a scanning transmission x-ray microscope. The authors detect a significant selectivity of the deposition process with respect to the incident photon energy that arises from the enhanced x-ray absorption cross section of the precursor molecules for near-threshold excitation. This effect has been investigated for the L2,3-edges of the respective metal centers of two different precursor molecules as well as the N and O K-edges of the respective ligands. The authors find a photon-limited growth mode for deposition from cobalt tricarbonyl nitrosyl [Co(CO)3NO], while the process is precursor-limited for methylcyclopentadienyl manganese tricarbonyl [MeCpMn(CO)3] possibly due to a comparably low vapor pressure of the latter precursor.
Extent of lateralization at large interaural time differences in simulated electric hearing and bilateral cochlear implant users
Authors: Baumgärtel Regina M. , Hu Hongmei , Kollmeier Birger , Dietz Mathias
Published: April 2017

Normal-hearing (NH) listeners are able to localize sound sources with extraordinary accuracy through interaural cues, most importantly interaural time differences (ITDs) in the temporal fine structure. Bilateral cochlear implant (CI) users are also able to localize sound sources, yet generally at lower accuracy than NH listeners. The gap in performance can in part be attributed to current CI systems not faithfully transmitting interaural cues, especially ITDs. With the introduction of binaurally linked CI systems, the presentation of ITD cues for bilateral CI users is foreseeable. The current study therefore investigated extent-of-lateralization percepts elicited in bilateral CI listeners when presented with single-electrode pulse-trains carrying controlled ITD cues. The results were compared against NH listeners listening to broadband stimuli as well as simulations of CI listening. Broadband stimuli in NH listeners were perceived as fully lateralized within the natural ITD range. Using simulated as well as real CI stimuli, however, only a fraction of the full extent of lateralization range was covered by natural ITDs. The maximum extent of lateralization was reached at ITDs as large as twice the natural limit. The results suggest that ITD-enhancement might be a viable option for improving localization abilities with future binaural CI systems.
Shock formation and nonlinear saturation effects in the ultrasound field of a diagnostic curvilinear probe
Authors: Karzova Maria M. , Yuldashev Petr V. , Sapozhnikov Oleg A. , Khokhlova Vera A. , Cunitz Bryan W. , Kreider Wayne , Bailey Michael R.
Published: April 2017

Newer imaging and therapeutic ultrasound technologies may benefit from in situ pressure levels higher than conventional diagnostic ultrasound. One example is the recently developed use of ultrasonic radiation force to move kidney stones and residual fragments out of the urinary collecting system. A commercial diagnostic 2.3 MHz C5-2 array probe has been used to deliver the acoustic pushing pulses. The probe is a curvilinear array comprising 128 elements equally spaced along a convex cylindrical surface. The effectiveness of the treatment can be increased by using higher transducer output to provide a stronger pushing force; however nonlinear acoustic saturation can be a limiting factor. In this work nonlinear propagation effects were analyzed for the C5-2 transducer using a combined measurement and modeling approach. Simulations were based on the three-dimensional Westervelt equation with the boundary condition set to match low power measurements of the acoustic pressure field. Nonlinear focal waveforms simulated for different numbers of operating elements of the array at several output power levels were compared to fiber-optic hydrophone measurements and were found to be in good agreement. It was shown that saturation effects do limit the acoustic pressure in the focal region of a diagnostic imaging probe.
The acoustic counterpart to coarticulation resistance and aggressiveness in locus equation metrics and vowel dispersion
Authors: Bang Hye-Young
Published: April 2017

In speech articulation, a segment with high coarticulatory resistance in tongue configurations tends to exhibit greater coarticulatory aggressiveness on neighbouring segments. This study examined whether this articulatory relationship can be acoustically captured through locus equations and the magnitude of vowel dispersion. This question was investigated in CV sequences in English where C varies in the degree of articulatory constraints imposed on the tongue dorsum. The results show a tight relationship between locus equation slopes and vowel dispersion, where coarticulatory resistance and aggressiveness appear to be two sides of the same coin in speech acoustics.
The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression
Authors: Becchetti Andrea , Crescioli Silvia , Zanieri Francesca , Petroni Giulia , Mercatelli Raffaella , Coppola Stefano , Gasparoli Luca , D’Amico Massimo , Pillozzi Serena , Crociani Olivia , Stefanini Matteo , Fiore Antonella , Carraresi Laura , Morello Virginia , Manoli Sagar , Brizzi Maria Felice , Ricci Davide , Rinaldi Mauro , Masi Alessio , Schmidt Thomas , Quercioli Franco , Defilippi Paola , Arcangeli Annarosa
Published: April 2017

Whether hERG1 potassium channels promote proliferation or metastasis in breast cancer cells depends on channel conformation.
The lysine deacetylase Sirtuin 1 modulates the localization and function of the Notch1 receptor in regulatory T cells
Authors: Marcel Nimi , Perumalsamy Lakshmi R. , Shukla Sanjay K. , Sarin Apurva
Published: April 2017

Sirt1-mediated deacetylation of the intracellular domain of Notch1 promotes T
reg
cell survival.
Papers of note in
Science
355
(6332)
Authors: VanHook Annalisa M.
Published: April 2017

This week’s articles highlight the role of immune cell signaling heterogeneity in aging, the unlocking of poised chromatin states in migrating cells after they reach their destination, and insight into the mechanism by which PD-1–targeted immunotherapy is effective in killing cancer cells and eliminating chronic viral infections.
A link closer to glioblastoma therapy
Authors: Ferrarelli Leslie K.
Published: April 2017

A next-generation mTOR inhibitor combines features of its predecessors to more potently and durably inhibit the growth of glioblastoma in mice.
Papers of note in
Nature
543
(7647)
Authors: Foley John F.
Published: April 2017

This week’s articles highlight how cancer stem cells drive metastasis, but not primary tumor growth, and how a mitochondrial protein changes lipid metabolism to inhibit the proliferation of breast cancer cells.
Impaired phagocytosis in fragile X
Authors: Mushegian Alexandra A.
Published: April 2017

Defects in phagocytosis underlie both neurological and immunological symptoms in a fly model of fragile X syndrome.
Papers of note in
Science Immunology
2
(9)
Authors: Foley John F.
Published: April 2017

This month’s articles show how an anti-inflammatory mediator is required for allergic responses, how targeting of the deacetylase Sirtuin 1 may provide a therapy against
Mycobacterium tuberculosis
infection, and how an inhibitory receptor limits the proliferation of regulatory T cells in autoimmune diabetes.
In Vitro
Activity of Pexiganan and 10 Comparator Antimicrobials against 234 Isolates, Including 93 Pasteurella Species and 50 Anaerobic Bacterial Isolates Recovered from Animal Bite Wounds
Authors: Goldstein Ellie J. C. , Citron Diane M. , Tyrrell Kerin L. , Leoncio Eliza S.
Published: April 2017

Animal bite wounds affect more than 5 million Americans annually, resulting in 300,000 emergency department visits, 10,000 hospitalizations, and an untold number of physician office visits. Various forms of topical therapy are empirically self-employed by many patients prior to seeking medical attention. Pexiganan, a 22-amino-acid synthetic cationic analogue of the peptide magainin II, acts by selectively damaging bacterial cell membranes. We determined the MICs for pexiganan and other antimicrobial agents often used for treatment of bite wounds. Most isolates were from U.S. patients, and ∼10% were from European and Canadian patients. The comparator antimicrobials studied were penicillin, amoxicillin-clavulanate, piperacillin-tazobactam, meropenem, clindamycin, doxycycline, moxifloxacin, ceftriaxone, linezolid, and metronidazole. The MIC
90
s of pexiganan were 32 μg/ml (against
Pasteurella multocida
subsp.
multocida
), 16 μg/ml (
P. multocida
subsp.
septica
,
Pasteurella canis
, and
Pasteurella dagmatis
), 8 μg/ml (
Pasteurella stomatis
), 8 μg/ml (
Eikenella corrodens
), 2 μg/ml (
Neisseria weaveri
,
Neisseria zoodegmatis
, and
Moraxella canis-Moraxella lacunata
group), 16 μg/ml (
Bergeyella zoohelcum
), 64 μg/ml (
Bacteroides pyogenes
), 4 μg/ml (
Fusobacterium russii
), 32 μg/ml (
Fusobacterium canifelinum
), and 64 μg/ml (
Prevotella heparinolytica
). The concentration of pexiganan in the cream used was 8,000 μg/ml, more than 60 to 100 times the highest MIC obtained. Pexiganan exhibited a broad range of antimicrobial activity, showing potential for treating animal bite infections. A clinical trial seems warranted.
A Waterborne Outbreak of Shigella sonnei with Resistance to Azithromycin and Third-Generation Cephalosporins in China in 2015
Authors: Ma Qiuxia , Xu Xuebin , Luo Ming , Wang Jian , Yang Chaojie , Hu Xiaofeng , Liang Beibei , Wu Fuli , Yang Xiaoxia , Wang Jinyan , Liu Hongbo , Li Wen , Zhong Yu , Li Peng , Xie Jing , Jia Leili , Wang Ligui , Hao Rongzhang , Du Xinying , Qiu Shaofu , Song Hongbin , Sun Yansong
Published: April 2017

Here, we report for the first time a waterborne outbreak of
Shigella sonnei
in China in 2015. Eleven multidrug-resistant (MDR)
S. sonnei
isolates were recovered, showing high resistance to azithromycin and third-generation cephalosporins in particular, due to an
mph
(A)- and
bla
CTX-M-14
-harboring IncB/O/K/Z group transmissible plasmid of 104,285 kb in size. Our study highlights the potential prevalence of the MDR outbreak of
S. sonnei
in China and its further dissemination worldwide with the development of globalization.
A Case-Control Study of Molecular Epidemiology in Relation to Azithromycin Resistance in Neisseria gonorrhoeae Isolates Collected in Amsterdam, the Netherlands, between 2008 and 2015
Authors: Wind Carolien M. , Bruisten Sylvia M. , Schim van der Loeff Maarten F. , Dierdorp Mirjam , de Vries Henry J. C. , van Dam Alje P.
Published: April 2017

Neisseria gonorrhoeae
resistance to ceftriaxone and azithromycin is increasing, which threatens the recommended dual therapy. We used molecular epidemiology to identify
N. gonorrhoeae
clusters and associations with azithromycin resistance in Amsterdam, the Netherlands.
N. gonorrhoeae
isolates (
n
= 143) were selected from patients visiting the Amsterdam STI Outpatient Clinic from January 2008 through September 2015. We included all 69 azithromycin-resistant isolates (MIC ≥ 2.0 mg/liter) and 74 frequency-matched susceptible controls (MIC ≤ 0.25 mg/liter). The methods used were 23S rRNA and
mtrR
sequencing,
N. gonorrhoeae
multiantigen sequence typing (NG-MAST),
N. gonorrhoeae
multilocus variable-number tandem-repeat analysis (NG-MLVA), and a specific PCR to detect mosaic
penA
genes. A hierarchical cluster analysis of NG-MLVA related to resistance and epidemiological characteristics was performed. Azithromycin-resistant isolates had C2611T mutations in 23S rRNA (
n
= 62, 89.9%,
P
< 0.001) and were NG-MAST genogroup G2992 (
P
< 0.001), G5108 (
P
< 0.001), or G359 (
P
= 0.02) significantly more often than susceptible isolates and were more often part of NG-MLVA clusters (
P
< 0.001). Two resistant isolates (2.9%) had A2059G mutations, and five (7.3%) had wild-type 23S rRNA. No association between
mtrR
mutations and azithromycin resistance was found. Twenty-four isolates, including 10 azithromycin-resistant isolates, showed reduced susceptibility to extended-spectrum cephalosporins. Of these, five contained a
penA
mosaic gene. Four of the five NG-MLVA clusters contained resistant and susceptible isolates. Two clusters consisting mainly of resistant isolates included strains from men who have sex with men and from heterosexual males and females. The co-occurrence of resistant and susceptible strains in NG-MLVA clusters and the frequent occurrence of resistant strains outside of clusters suggest that azithromycin resistance develops independently from the background genome.
AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis
Authors: Castañeda Ximena , García-de-la-Mària Cristina , Gasch Oriol , Pericas Juan M. , Armero Yolanda , Soy Dolors , García-González Javier , Falces Carlos , Ninot Salvador , Almela Manel , Ambrosioni Juan , Quintana Eduardo , Vidal Barbara , Fuster David , Llopis Jaume , Soto Sara , Moreno Asuncion , Marco Francesc , Miró Jose M. ,   the Hospital Clinic Endocarditis Study Group
Published: April 2017

The aim of this
in vivo
study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant
Staphylococcus aureus
(MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (
P
= 0.343), while the medians (interquartile ranges [IQRs]) for log
10
CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (
P
= 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.
9-(2′-Deoxy-2′-Fluoro-β-
d
-Arabinofuranosyl) Adenine Is a Potent Antitrypanosomal Adenosine Analogue That Circumvents Transport-Related Drug Resistance
Authors: Ranjbarian Farahnaz , Vodnala Munender , Alzahrani Khalid J. H. , Ebiloma Godwin U. , de Koning Harry P. , Hofer Anders
Published: April 2017

Current chemotherapy against African sleeping sickness, a disease caused by the protozoan parasite
Trypanosoma brucei
, is limited by toxicity, inefficacy, and drug resistance. Nucleoside analogues have been successfully used to cure
T. brucei
-infected mice, but they have the limitation of mainly being taken up by the P2 nucleoside transporter, which, when mutated, is a common cause of multidrug resistance in
T. brucei
. We report here that adenine arabinoside (Ara-A) and the newly tested drug 9-(2′-deoxy-2′-fluoro-β-
d
-arabinofuranosyl) adenine (FANA-A) are instead taken up by the P1 nucleoside transporter, which is not associated with drug resistance. Like Ara-A, FANA-A was found to be resistant to cleavage by methylthioadenosine phosphorylase, an enzyme that protects
T. brucei
against the antitrypanosomal effects of deoxyadenosine. Another important factor behind the selectivity of nucleoside analogues is how well they are phosphorylated within the cell. We found that the
T. brucei
adenosine kinase had a higher catalytic efficiency with FANA-A than the mammalian enzyme, and
T. brucei
cells treated with FANA-A accumulated high levels of FANA-A triphosphate, which even surpassed the level of ATP and led to cell cycle arrest, inhibition of DNA synthesis, and the accumulation of DNA breaks. FANA-A inhibited nucleic acid biosynthesis and parasite proliferation with 50% effective concentrations (EC
50
s) in the low nanomolar range, whereas mammalian cell proliferation was inhibited in the micromolar range. Both Ara-A and FANA-A, in combination with deoxycoformycin, cured
T. brucei
-infected mice, but FANA-A did so at a dose 100 times lower than that of Ara-A.