bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching and Learning Design Methods: Facing the Related Issues with TRIZ
Authors: Fiorineschi Lorenzo , Frillici Francesco Saverio , Rotini Federico
Published: July 2019

Design methods are claimed to support designers but, although they are largely taught in academia, their industrial uptake is still lacking. Many reasons have been identified about this flaw and some potential suggestions have been proposed and discussed in literature to overcome the problem. However, a further evidence is that although many students learn such methods from years, they partially or totally abandon the learned methods in their professional careers. This could partially explain the gap between academic and industrial diffusion of design methods. Literature provides suggestions for improving the learning experience of students but different didactical contexts may need more tailored solutions. The work shown in this paper exploits the problem solving potentialities of the TRIZ toolset to provide hints for improving a course focused on teaching a systematic conceptual design method. A set of suggestions has been obtained together some guidelines for applying the considered TRIZ tools to other didactical contexts.
The Finnish Product Development Teachers’ Perceptions of their Pedagogical Content Knowledge in Higher Education
Authors: Mäkelä Elina , Auvinen Petra , Juuti Tero
Published: July 2019

The paper concerns the Finnish product development teacherś perceptions on their pedagogical content knowledge in higher education settings. The aim is to describe and analyse what kind of pedagogical content knowledge the teachers have and, therefore, to provide a better understanding of the type of knowledge unique to product development teaching. The model of pedagogical content knowledge used here includes the components of product development content knowledge, pedagogical knowledge and pedagogical content knowledge. Based on seven teacher interviews, the main content knowledge concerns the process of product development, its different phases and methods as well as the usage of different software programs. The teachers use diverse teaching methods and their attitude towards educational technology is mostly positive. Course learning outcomes and working life are acknowledged when planning teaching, but only a few teachers take curriculum into account and participate in curriculum design. Even though the teachers use different evaluation methods in teaching, new ways of evaluation are needed. This may be something that innovative educational technology tools can make possible.
A Design Case Study: 3D Printer Software Interface Design Based on Home Users Preferences Knowledge
Authors: Li Xuenan , Zhao Danhua , Zhao Jianghong
Published: July 2019

The rapid development of 3D printing technology has an impact on all aspects of modern manufacturing, design and society. However, the home use of 3D printers is still limited by the difficulty in deploying the software and the technology which both need professional understanding and training. How to enable non-technical home users to use 3D printers without the need for training, becomes an urgent problem for both academics and the industry. This paper is concerned in an investigation into home use of 3D printers, their needs and preferences, their impacts on the interaction design of 3D printing. First, a questionnaire survey supported by 127 non-technical users is conducted to understand their preferences on several key steps of the 3D printing procedure. Then, we integrate the survey results into the interaction design process to improve the usability of the 3D printing software. Finally, the advantage of our implementation is tested via the user satisfaction and feedback towards the post-use period. Our design project shows a simple method to extend 3D printing interactive software to non-technical users, and pushes forward the landscape of the home use of 3D printers.
A Methodical Approach to Support Conceptual Design for Multi-Material Additive Manufacturing
Authors: Watschke Hagen , Kuschmitz Sebastian , Heubach Julius , Lehne Guido , Vietor Thomas
Published: July 2019

Additive manufacturing (AM) opens new possibilities for innovative product designs. However, due to a lack of knowledge and restrained creativity because of design fixations, design engineers do not take advantage of AM's design freedom. Especially multi-material AM provides new opportunities for functional integration that hardly considered in ideation. To overcome barriers in the development of solution ideas and utilizing such new design potentials, new design methods and tools are needed. Therefore, in this contribution, a methodological approach for a function-oriented provision of solution principles specific to material extrusion is presented. A tool is developed to facilitate effective guidance in developing solution ideas and to foster a realistic concretization by providing a combination of opportunistic and restrictive AM knowledge. Besides general levers of AM, process-specific design opportunities support the design engineers in exploiting AM's potentials, especially those who are not familiar with Design for AM. Finally, the applicability of the methodological approach is evaluated in an academic study by means of redesigning a hand prosthesis with a grab function.
Design Automation for Customised and Large-Scale Additive Manufacturing: A Case Study on Custom Kayaks
Authors: Lithgow Drew , Morrison Cara , Pexton George , Panarotto Massimo , Müller Jakob R. , Almefelt Lars , McLaren Andrew
Published: July 2019

Additive Manufacturing (AM) offers the potential to increase the ability to customise large-scale plastic components. However, a substantial amount of manual work is still required during the customisation process, both in design and manufacturing.

This paper looks into how the additive manufacturing of mass customised large-scale products can be supported. Data was collected through interaction with industrial partners and potential customers in a case study regarding the customisation of kayaks.

As a result, the paper proposes a model-based methodology which combines design automation with a user interface.

The results point to the benefit of the proposed methodology in terms of design efficiency, as well as in terms of displaying results to the end user in an understandable format.
Hybrid Prototyping: Pure Theory or a Practical Solution to Accelerating Prototyping Tasks?
Authors: Mathias David , Hicks Ben , Snider Chris
Published: July 2019

Physical prototyping is critical activity in the produce development process, but the cost and time required to produce prototypes hinders it use in the design process. Hybrid prototyping through coupling LEGO and FDM printing is presented as an approach to address these issues. After establishing the separate design rules for FDM printing and LEGO, this paper created new set of rules called Design for Fabrication (DfF) for hybrid prototyping. These cover the three main considerations (Technical, Process, and Design) that the designer and process planning must include to practically implement LEGO and FDM hybrid prototyping. The DfF rules were considered in a prototype of a computer mouse. While the fabrication time was not reduced as expected, it showed that the rules could be practically implemented in a real-world example. Additional considerations were identified that are to be included in the DfF rules.

Further work is required to realise the predicted step-change reduction in fabrication time. The first approach is to leverage multiple printers to parallelise the printing. The second is to reduce fidelity while maintaining high fidelity in key regions of interest.
Methodical Approach for Process Selection in Additive Manufacturing
Authors: Wortmann Nadine , Jürgenhake Christoph , Seidenberg Tobias , Dumitrescu Roman , Krause Dieter
Published: July 2019

In recent years, rapid technical progress has led to additive manufacturing achieving a high degree of technological maturity that enables a broad range of applications. This is reinforced in particular by the advantages of the technology, such as the production of complex components, smaller quantities and fast reaction times. However, a lack of knowledge of the various process techniques, such as insufficient potential assessment, specific design guidelines or even of process restrictions, often lead to different errors.

This paper presents a methodological approach to support designers in the manufacturing process selection of specific parts at an early stage of product development. In a four-stage procedure, potential part candidates are first identified and part classes formed on the basis of characteristics. Building on this, AM thinking is to be stimulated, for example, with the aid of design guidelines. A comparison between conventionally and additively manufactured parts can be made using a simplified cost model. The results are incorporated into a process model that supports companies in the systematic selection of manufacturing processes.
Print-On Strategies to Bond Injection Molded Parts with Structures Produced by Fused-Deposition-Modeling
Authors: Richter Alina , Kessing David , Fischer Fabian , Pelzer Lukas , Dilger Klaus
Published: July 2019

The biggest advantage of Additive Manufacturing is the individualization of products. Mass Customization is well known as a promising future application. The use of Additive Manufacturing for assembly groups is mostly not reasonable, however combining it with conventional manufacturing processes can lead to new opportunities.

This paper works out concepts to join, by using similar material combinations, an injection molded part with an additive deposited geometry by the Fused-Deposition-Modeling (FDM) process. Therefore, two of the main industrially used polymers, acrylonitrile butadiene styrene (ABS) and polypropylene (PP), are selected for further study. In particular, this investigation focuses on the procedural potentials and surface preparation of the injection molded part. By the variation of adhesive bonding, the fusion of similar materials can be identified and tested in several series of testing.

First in general a direct joining function by the FLM process will be tested. After proving this hypothesis, the results will be summarised in a recommendation of joining similar materials, which are manufactured in different ways.
Alarm Compliance in Healthcare: Design Considerations for Actionable Alarms (In Intensive Care Units)
Authors: Sanz-Segura Rosana , Manchado Pérez Eduardo , Özcan Elif
Published: July 2019

Intensive care units are technologically advanced environments that are designed to safeguard the patient while their vitals are stabilized for further treatment. Audible and visual alarms are part of the healthcare ecology. However, these alarms are so many that clinicians suffer from a syndrome called ‘alarm fatigue’ and often do not comply with the task alarm is conveying. Measuring compliance with rules in the workspace and determining the success of a system belongs to the field of ergonomics and is based on data collected through task observations and scoring. In this paper, we will explore compliance with critical alarms by not only from their potential success or failure perspective but also from the perspectives of the clinician capacity, needs, and motivations to comply with alarms in critical environments. We will finally, reflect on further possible design strategies to increase compliance in critical care that are beyond following rules per se but through intrinsic motivation.
An Affordable Insulin Pump for Type-1 Diabetic Patients: A Case Study of User-in-the-Loop Approach to Engineering Design
Authors: Karia Deval , Nambiar Rohit S , Arora Manish
Published: July 2019

Continuous subcutaneous insulin infusion using an insulin pump has been documented to have significant clinical benefits as a treatment plan for type 1 diabetes mellitus patients. However, despite this, adoption in resource constrained settings like India is severely limited. This is often attributed to the costs associated with the device.

The usage of such a device is closely associated with a patient's lifestyle and its design demands a more user-centric approach to engineering design. The stakeholder involvement is needed for validation and guiding the product development direction. In this paper, we've outlined a user-in-the-loop approach to engineering design using the design of an insulin pump as a case study.
Design Considerations for Therapeutic Devices - An Investigation of Pre-Schoolers’ Preferences for an Artefact’s Basic Characteristics
Authors: Balzan Emanuel , Farrugia Philip , Casha Owen , Camilleri Liberato , Wodehouse Andrew
Published: July 2019

Toys are children's first consumer products and while playing they acquire numerous skills, learn about their environment and socialise with other children and adults. Toys are adapted and used by clinicians as therapeutic devices because they allow them to create bonds and communicate with children. Aesthetical aspects should be considered early in the design process, especially since pre-schoolers’ views are still dominated by the appearance of artefacts, also known as, the perceptual salient characteristics. The study of emotions mediates the understanding of the relationships between a product, user and the process with which consumers set up preferences over products. Decisions taken in each design stage will influence whether therapeutic devices will be enjoyed by children. An experiment was carried out to test out pre-schoolers’ preferences on individual attributes: form, dimension, material (hardness and weight) and surface (appearance and texture). This study exposed dominant characteristic preferences and the fact that some are influenced by gender and age. Employing these findings in therapeutic devices will enable clinicians to better engage the children during therapy.
One British Thing: The Babies’ Anti-Gas Protective Helmet
Authors: Grayzel Susan R.
Published: July 2019

This one British thing, the baby gas mask, helps us understand the normalization of total war in modern Britain.
Image-based modelling of the skin-friction coefficient in compressible boundary-layer transition
Authors: Zheng Wenjie , Ruan Shanxin , Yang Yue , He Lin , Chen Shiyi
Published: July 2019

We develop a model of the skin-friction coefficient based on scalar images in the compressible, spatially evolving boundary-layer transition. The images are extracted from a passive scalar field by a sliding window filter on the streamwise and wall-normal plane. The multi-scale and multi-directional geometric analysis is applied to characterize the averaged inclination angle of spatially evolving filtered component fields at different scales ranging from a boundary-layer thickness to several viscous length scales. In general, the averaged inclination angles increase along the streamwise direction, and the variation of the angles for large-scale structures is smaller than that for small-scale structures. Inspired by the coincidence of the increasing averaged inclination angle and the rise of the skin-friction coefficient, we propose a simple image-based model of the skin-friction coefficient. The model blends empirical formulae of the skin-friction coefficient in laminar and fully developed turbulent regions using the normalized averaged inclination angle of scalar structures at intermediate and small scales. The model prediction calculated from scalar images is validated by the results from the direct numerical simulation at two Mach numbers, 2.25 and 6, and the relative error can be less than 15 %.
Defining Romantic Self-Sabotage: A Thematic Analysis of Interviews With Practising Psychologists
Authors: Peel Raquel , Caltabiano Nerina , Buckby Beryl , McBain Kerry
Published: July 2019

The term ‘self-sabotage’ is not well defined in the current literature. Self-sabotage is generally explained as a synonym of self-handicapping, which does not fully encompass intrinsic behaviours found in romantic relationships. Therefore, the aim of the present study was to explore the theme of self-sabotage as viewed by practising psychologists. A series of 15 semistructured interviews with psychologists specialising in romantic relationships around Australia identified the main issues contributing to self-sabotage in romantic relationships and the reason why it might happen. Future studies will need to be conducted to develop a scale to empirically test self-sabotage in romantic relationships.
Association of dietary patterns with depressive symptoms in Chinese postmenopausal women
Authors: Liao Kuan , Gu Yeqing , Liu Mingyue , Fu Jingzhu , Wang Xiaotong , Yang Guanlin , Zhang Qing , Liu Li , Meng Ge , Yao Zhanxin , Wu Hongmei , Xia Yang , Bao Xue , Zhang Shunming , Sun Shaomei , Wang Xing , Zhou Ming , Jiao Huanli , Jia Qiyu , Song Kun , Wu Yuntang , Niu Kaijun
Published: July 2019

Many components in diet have regulated oxidative stress, inflammatory reaction and even balance oestrogen levels. Because these factors are closely associated with depressive symptoms in postmenopausal women, it is considered that dietary factors are able to prevent and control depressive symptoms. On the other hand, a dietary pattern that considers the correlations and synergies between foods and nutrients is expected to have a greater impact on disease risk. The aim of the present study is to evaluate whether dietary patterns are associated with depressive symptoms in Chinese postmenopausal women. A cross-sectional study of 2051 postmenopausal women (mean age: 58·8 (sd 7·4) years) was conducted in Tianjin, China. Dietary consumption was assessed by a valid self-administered FFQ. Principal component analysis was used to derive three major dietary patterns: ‘healthy’, ‘sweets’ and ‘traditional Tianjin’ from eighty-eight food items. Depressive symptoms were assessed using the Zung Self-Rating Depression Scale, and cut-off point of 48 indicating serious depressive symptoms. The association between quartile of dietary patterns and depressive symptoms was assessed using multiple logistic regression analysis. The multivariable-adjusted OR of having depressive symptoms for increasing quartile of dietary patterns were as follows: healthy, 1·00, 0·79 (95 % CI 0·49, 1·28), 0·62 (95 % CI 0·37, 1·04) and 0·57 (95 % CI 0·33, 0·97); sweets, 1·00, 0·75 (95 % CI 0·42, 1·3), 1·08 (95 % CI 0·64, 1·81) and 1·66 (95 % CI 1·03, 2·71); and traditional Tianjin, 1·00, 1·02 (95 % CI 0·58, 1·79), 0·96 (95 % CI 0·54, 1·71) and 2·53 (95 % CI 1·58, 4·16), respectively. The present study demonstrated that a healthy dietary pattern was inversely associated with depressive symptoms. On the contrary, greater adherence to sweets and traditional Tianjin dietary patterns was associated with a higher prevalence of depressive symptoms.
THE CONTRIBUTIONS TO THE REFOUNDATION OF THEBES: A NEW EPIGRAPHIC AND HISTORICAL ANALYSIS
Authors: Kalliontzis Yannis , Papazarkadas Nikolaos
Published: July 2019

In the context of our ongoing work on the new corpus of Theban inscriptions (IGVII2, 4), we had the opportunity to study the famous inscription that records the contributions for the refoundation of Thebes after 315bc. The inscription consists of two fragments, the first of which has been known since the nineteenth century, whereas the second was published very recently by Professor Buraselis. Following Buraselis’ publication, the two fragments were physically joined in the Archaeological Museum of Thebes, where the inscription is currently on display. Our article provides the first ever full epigraphic edition of both fragments after autopsy. It is accompanied by detailed epigraphic notes, new supplements, apparatus criticus and a full historical analysis. By combining the study of abundant literary and epigraphic sources, we have attempted to place the inscription in its historical context, correcting certain earlier scholarly assumptions, making new suggestions about the motivations of the numerous contributors, and examining the modalities of the refoundation of Thebes.
Towards ultra-intense ultra-short ion beams driven by a multi-PW laser
Authors: Badziak J. , Domański J.
Published: July 2019

The multi-petawatt (PW) lasers currently being built in Europe as part of the Extreme Light Infrastructure (ELI) project will be capable of generating femtosecond light pulses of ultra-relativistic intensities (~1023–1024 W/cm2) that have been unattainable so far. Such laser pulses can be used for the production of high-energy ion beams with unique features that could be applied in various fields of scientific and technological research. In this paper, the prospect of producing ultra-intense (intensity ≥1020 W/cm2) ultra-short (pico- or femtosecond) high-energy ion beams using multi-PW lasers is outlined. The results of numerical studies on the acceleration of light (carbon) ions, medium-heavy (copper) ions and super-heavy (lead) ions driven by a femtosecond laser pulse of ultra-relativistic intensity, performed with the use of a multi-dimensional (2D3 V) particle-in-cell code, are presented, and the ion acceleration mechanisms and properties of the generated ion beams are discussed. It is shown that both in the case of light ions and in the case of medium-heavy and super-heavy ions, ultra-intense femtosecond multi-GeV ion beams with a beam intensity much higher (by a factor ~102) and ion pulse durations much shorter (by a factor ~104–105) than achievable presently in conventional radio frequency-driven accelerators can be produced at laser intensities of 1023 W/cm2 predicted for the ELI lasers. Such ion beams can open the door to new areas of research in high-energy density physics, nuclear physics and inertial confinement fusion.
Biological sensitivity to context: A test of the hypothesized U-shaped relation between early adversity and stress responsivity
Authors: Shakiba Nila , Ellis Bruce J. , Bush Nicole R. , Boyce W. Thomas
Published: July 2019

We conducted signal detection analyses to test for curvilinear, U-shaped relations between early experiences of adversity and heightened physiological responses to challenge, as proposed by biological sensitivity to context theory. Based on analysis of an ethnically diverse sample of 338 kindergarten children (4–6 years old) and their families, we identified levels and types of adversity that, singly and interactively, predicted high (top 25%) and low (bottom 25%) rates of stress reactivity. The results offered support for the hypothesized U-shaped curve and conceptually replicated and extended the work of Ellis, Essex, and Boyce (2005). Across both sympathetic and adrenocortical systems, a disproportionate number of children growing up under conditions characterized by either low or high adversity (as indexed by restrictive parenting, family stress, and family economic condition) displayed heightened stress reactivity, compared with peers growing up under conditions of moderate adversity. Finally, as hypothesized by the adaptive calibration model, a disproportionate number of children who experienced exceptionally stressful family conditions displayed blunted cortisol reactivity to stress.
Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis
Authors: Deng Liping , Ren Ruotong , Liu Zunpeng , Song Moshi , Li Jingyi , Wu Zeming , Ren Xiaoqing , Fu Lina , Li Wei , Zhang Weiqi , Guillen Pedro , Izpisua Belmonte Juan Carlos , Chan Piu , Qu Jing , Liu Guang-Hui
Published: July 2019

DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and attenuating aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its microRNA-processing activity. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1γ. Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathologically and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and mouse osteoarthritis. Taken together, these analyses uncovered a novel, microRNA processing-independent role in maintaining heterochromatin organization and attenuating senescence by DGCR8, thus representing a new therapeutic target for alleviating human aging-related disorders.
Extracellular matrix stiffness cues junctional remodeling for 3D tissue elongation
Authors: Chen Dong-Yuan , Crest Justin , Streichan Sebastian J. , Bilder David
Published: July 2019

Organs are sculpted by extracellular as well as cell-intrinsic forces, but how collective cell dynamics are orchestrated in response to environmental cues is poorly understood. Here we apply advanced image analysis to reveal extracellular matrix-responsive cell behaviors that drive elongation of the Drosophila follicle, a model system in which basement membrane stiffness instructs three-dimensional tissue morphogenesis. Through in toto morphometric analyses of wild type and round egg mutants, we find that neither changes in average cell shape nor oriented cell division are required for appropriate organ shape. Instead, a major element is the reorientation of elongated cells at the follicle anterior. Polarized reorientation is regulated by mechanical cues from the basement membrane, which are transduced by the Src tyrosine kinase to alter junctional E-cadherin trafficking. This mechanosensitive cellular behavior represents a conserved mechanism that can elongate edgeless tubular epithelia in a process distinct from those that elongate bounded, planar epithelia.
Self-sustained biphasic catalytic particle turbulence
Authors: Wang Ziqi , Mathai Varghese , Sun Chao
Published: July 2019

Turbulence is known for its ability to vigorously mix fluid and transport heat. Despite over a century of research for enhancing heat transport, few have exceeded the inherent limits posed by turbulent-mixing. Here we have conceptualized a kind of “active particle” turbulence, which far exceeds the limits of classical thermal turbulence. By adding a minute concentration (ϕv ∼ 1%) of a heavy liquid (hydrofluoroether) to a water-based turbulent convection system, a remarkably efficient biphasic dynamics is born, which supersedes turbulent heat transport by up to 500%. The system operates on a self-sustained dynamically equilibrated cycle of a “catalyst-like” species, and exploits several heat-carrier agents including pseudo-turbulence, latent heat and bidirectional wake capture. We find that the heat transfer enhancement is dominated by the kinematics of the active elements and their induced-agitation. The present finding opens the door towards the establishment of tunable, ultra-high efficiency heat transfer/mixing systems.
Molecular mechanism of cytoplasmic dynein tension sensing
Authors: Rao Lu , Berger Florian , Nicholas Matthew P. , Gennerich Arne
Published: July 2019

Cytoplasmic dynein is the most complex cytoskeletal motor protein and is responsible for numerous biological functions. Essential to dynein’s function is its capacity to respond anisotropically to tension, so that its microtubule-binding domains bind microtubules more strongly when under backward load than forward load. The structural mechanisms by which dynein senses directional tension, however, are unknown. Using a combination of optical tweezers, mutagenesis, and chemical cross-linking, we show that three structural elements protruding from the motor domain—the linker, buttress, and stalk—together regulate directional tension-sensing. We demonstrate that dynein’s anisotropic response to directional tension is mediated by sliding of the coiled-coils of the stalk, and that coordinated conformational changes of dynein’s linker and buttress control this process. We also demonstrate that the stalk coiled-coils assume a previously undescribed registry during dynein’s stepping cycle. We propose a revised model of dynein’s mechanochemical cycle which accounts for our findings.
A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration
Authors: Handa James T. , Bowes Rickman Cathy , Dick Andrew D. , Gorin Michael B. , Miller Joan W. , Toth Cynthia A. , Ueffing Marius , Zarbin Marco , Farrer Lindsay A.
Published: July 2019

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or “wet” form of AMD, no therapy is successful for the non-neovascular or “dry” form. Here we discuss the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments. In our view, these should emphasize system biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.
Regulation of antitumour CD8 T-cell immunity and checkpoint blockade immunotherapy by Neuropilin-1
Authors: Leclerc Marine , Voilin Elodie , Gros Gwendoline , Corgnac Stéphanie , de Montpréville Vincent , Validire Pierre , Bismuth Georges , Mami-Chouaib Fathia
Published: July 2019

Neuropilin-1 (Nrp-1) is a marker for murine CD4+FoxP3+ regulatory T (Treg) cells, a subset of human CD4+ Treg cells, and a population of CD8+ T cells infiltrating certain solid tumours. However, whether Nrp-1 regulates tumour-specific CD8 T-cell responses is still unclear. Here we show that Nrp-1 defines a subset of CD8+ T cells displaying PD-1hi status and infiltrating human lung cancer. Interaction of Nrp-1 with its ligand semaphorin-3A inhibits migration and tumour-specific lytic function of cytotoxic T lymphocytes. In vivo, Nrp-1+PD-1hi CD8+ tumour-infiltrating lymphocytes (TIL) in B16F10 melanoma are enriched for tumour-reactive T cells exhibiting an exhausted state, expressing Tim-3, LAG-3 and CTLA-4 inhibitory receptors. Anti-Nrp-1 neutralising antibodies enhance the migration and cytotoxicity of Nrp-1+PD-1hi CD8+ TIL ex vivo, while in vivo immunotherapeutic blockade of Nrp-1 synergises with anti-PD-1 to enhance CD8+ T-cell proliferation, cytotoxicity and tumour control. Thus, Nrp-1 could be a target for developing combined immunotherapies.
Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans
Authors: Khurana Surender , Hahn Megan , Coyle Elizabeth M. , King Lisa R. , Lin Tsai-Lien , Treanor John , Sant Andrea , Golding Hana
Published: July 2019

Several vaccines are approved in the United States for seasonal influenza vaccination every year. Here we compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. Fold change in HI and antibody binding to HA1 trends higher for H1N1pdm09 and H3N2 but not against B strains in groups vaccinated with FluBlok compared with FluCelvax and Fluzone. Antibody-affinity maturation occurs against HA1 domain of H1N1pdm09, H3N2 and B following vaccination with all vaccine platforms, but not against H1N1pdm09-HA2. Importantly, prior year vaccination of subjects receiving repeat vaccinations demonstrated reduced antibody-affinity maturation to HA1 of all three influenza virus strains irrespective of the vaccine platform. This study identifies an important impact of repeat vaccination on antibody-affinity maturation following vaccination, which may contribute to lower vaccine effectiveness of seasonal influenza vaccines in humans
Reconfigurable two-dimensional optoelectronic devices enabled by local ferroelectric polarization
Authors: Lv Liang , Zhuge Fuwei , Xie Fengjun , Xiong Xujing , Zhang Qingfu , Zhang Nan , Huang Yu , Zhai Tianyou
Published: July 2019

Ferroelectric engineered pn doping in two-dimensional (2D) semiconductors hold essential promise in realizing customized functional devices in a reconfigurable manner. Here, we report the successful pn doping in molybdenum disulfide (MoS2) optoelectronic device by local patterned ferroelectric polarization, and its configuration into lateral diode and npn bipolar phototransistors for photodetection from such a versatile playground. The lateral pn diode formed in this way manifests efficient self-powered detection by separating ~12% photo-generated electrons and holes. When polarized as bipolar phototransistor, the device is customized with a gain ~1000 by its transistor action, reaching the responsivity ~12 A W−1 and detectivity over 1013 Jones while keeping a fast response speed within 20 μs. A promising pathway toward high performance optoelectronics is thus opened up based on local ferroelectric polarization coupled 2D semiconductors.
The phosphatase PPM1A inhibits triple negative breast cancer growth by blocking cell cycle progression
Authors: Mazumdar Abhijit , Tahaney William M. , Reddy Bollu Lakshmi , Poage Graham , Hill Jamal , Zhang Yun , Mills Gordon B. , Brown Powel H.
Published: July 2019

Estrogen receptor (ER)-negative, progesterone receptor (PR)-negative and HER2-negative, or “triple negative,” breast cancer (TNBC) is a poor prognosis clinical subtype that occurs more frequently in younger women and is commonly treated with toxic chemotherapy. Effective targeted therapy for TNBC is urgently needed. Our previous studies have identified several kinases critical for TNBC growth. Since phosphatases regulate the function of kinase signaling pathways, we sought to identify critical growth-regulatory phosphatases that are expressed differentially in ER-negative, as compared to ER-positive, breast cancers. In this study, we examined the role of one of these differentially expressed phosphatases, the protein phosphatase Mg + 2/Mn + 2 dependent 1A (PPM1A) which is underexpressed in ER-negative breast cancer as compared to ER-positive breast cancers, in regulating TNBC growth. We found that PPM1A is deleted in ~40% of ER-negative breast cancers, and that induced expression of PPM1A suppresses in vitro and in vivo growth of TNBC cells. This study demonstrates that induction of PPM1A expression blocks the cell cycle and reduces CDK and Rb phosphorylation. These results suggest PPM1A is a crucial regulator of cell cycle progression in triple negative breast cancer. Our results also suggest that PPM1A loss should be explored as a predictive biomarker of CDK inhibitor sensitivity.
Quantum key distribution with flawed and leaky sources
Authors: Pereira Margarida , Curty Marcos , Tamaki Kiyoshi
Published: July 2019

In theory, quantum key distribution (QKD) allows secure communications between two parties based on physical laws. However, most of the security proofs of QKD today make unrealistic assumptions and neglect many relevant device imperfections. As a result, they cannot guarantee the security of the practical implementations. Recently, the loss-tolerant protocol (K. Tamaki et al., Phys. Rev. A, 90, 052314, 2014) was proposed to make QKD robust against state preparation flaws. This protocol relies on the emission of qubit systems, which, unfortunately, is difficult to achieve in practice. In this work, we remove such qubit assumption and generalise the loss-tolerant protocol to accommodate multiple optical modes in the emitted signals. These multiple optical modes could arise, e.g., from Trojan horse attacks and/or device imperfections. Our security proof determines some dominant device parameter regimes needed for achieving secure communication and, therefore, it can serve as a guideline to characterise QKD transmitters. Furthermore, we compare our approach with that of H.-K. Lo et al. (Quantum Inf. Comput., 7, 431–458, 2007) and identify which method provides the highest secret key generation rate as a function of the device imperfections. Our work constitutes an important step towards the best practical and secure implementation for QKD.
A non-enzymatic glucose sensor enabled by bioelectronic pH control
Authors: Strakosas Xenofon , Selberg John , Pansodtee Pattawong , Yonas Nebyu , Manapongpun Pattawut , Teodorescu Mircea , Rolandi Marco
Published: July 2019

Continuous glucose monitoring from sweat and tears can improve the quality of life of diabetic patients and provide data for more accurate diagnosis and treatment. Current continuous glucose sensors use enzymes with a one-to-two week lifespan, which forces periodic replacement. Metal oxide sensors are an alternative to enzymatic sensors with a longer lifetime. However, metal oxide sensors do not operate in sweat and tears because they function at high pH (pH > 10), and sweat and tears are neutral (pH = 7). Here, we introduce a non-enzymatic metal oxide glucose sensor that functions in neutral fluids by electronically inducing a reversible and localized pH change. We demonstrate glucose monitoring at physiologically relevant levels in neutral fluids mimicking sweat, and wireless communication with a personal computer via an integrated circuit board.
Development of latent Interferon alpha 2b as a safe therapeutic for treatment of Hepatitis C virus infection
Authors: Gull Iram , Aslam Muhammad Shahbaz , Tipu Imran , Mushtaq Roohi , Ali Tehseen Zamir , Athar Muhammad Amin
Published: July 2019

Interferon therapy for the treatment of hepatitis C virus infection has very limited clinical application due to short serum half-life and side effects of therapy in systemic route of administration. In the present study, we have focused to improve the interferon therapy by overcoming the limitation of side effects. We hypothesized that latent interferon alpha 2b (IFNα2b) produced by fusion of Latency associated protein (LAP) domain of TGFβ and IFNα2b having HCV NS3 protease cleavage site as linker that will be activated only at target site (liver) by viral protease (HCV NS3 protease) present on the surface of infected cells. The fusion proteins were expressed in pichia pastoris as homodimer and cleaved by recombinant HCV NS3 protease in vitro into two fragments corresponding to the IFNα-2b and LAP respectively. The latency of chimeric proteins and biological activity after treatment with HCV NS3 protease was assessed by cytopathic effect inhibition assay in A594 cells infected with encephalomyocarditis virus (EMCV) and reduction in HCV viral load in Huh7 cells. The HCV NS3 protease was present on the surface of HCV replicating Huh7 cells in amount that activated half of the effective concentration (EC50) of latent IFNα2b fusion protein. As free circulating HCV NS3 protease was not detected in sera from chronic HCV patients and in vitro cleavage of intact latent IFNα2b fusion protein was not observed with peripheral blood mononuclear cells (PBMCs) isolated from chronic HCV patients, thus there are less likely chances of activation and off target binding of latent IFNα2b to show side effects during systemic route of administration. Therefore, most of the side effects of interferon can be overwhelmed at the cost of 50% reduced biological activity. Thus, the use of latent IFNα2b can be considered again as an option for treatment of HCV infection in combination with direct acting antivirals rather than alone with improved safety profile.
Evidence for selection events during domestication by extensive mitochondrial genome analysis between japonica and indica in cultivated rice
Authors: Cheng Lin , Kim Kyu-Won , Park Yong-Jin
Published: July 2019

The history of the domestication of rice is controversial, as it remains unknown whether domestication processes occurred once or multiple times. To date, genetic architecture and phylogenetic studies based on the rice nuclear genome have been extensively studied, but the results are quite different. Here, we found interesting results for different selections in Oryza sativa based on comprehensive studies of the rice mitochondrial (mt) genome. In detail, 412 rice germplasms were collected from around the world for variant architecture studies. A total of 10632 variants were detected in the mt genome, including 7277 SNPs and 3355 InDels. Selection signal (πw/πc) indicated that the selection sites in Oryza sativa L. ssp. japonica were different from those of Oryza sativa L. indica rice. The fixation index (FST) was higher between indica and japonica than between indica and wild rice. Moreover, haplotype and phylogenetic analyses also revealed indica clusters and japonica clusters that were well separated from wild rice. As mentioned above, our studies indicate that the selection sites of the indica type were different from those of the japonica type. This means that indica and japonica have experienced different domestication processes. We also found that japonica may have experienced a bottleneck event during domestication.
Theoretical study of the adsorption characteristics and the environmental influence of ornidazole on the surface of photocatalyst TiO2
Authors: Tan Ruolan , Lv Zhongjian , Tang Jing , Wang Yiwei , Guo Jianmin , Li Laicai
Published: July 2019

In this paper, density functional theory (DFT) was performed to study the adsorption properties of ornidazole on anatase TiO2(101) and (001) crystal facets under vacuum, neutral and acid-base conditions. We calculated the adsorption structure of ornidaozle on the anatase TiO2 surface, optimal adsorption sites, adsorption energy, density of states, electronic density and Milliken atomic charge under different conditions. The results show that when the N(3) atom on the imidazole ring is adsorbed on the Ti(5) atom, the largest adsorption energy and the most stable adsorption configuration could be achieved. According to the analysis of the adsorption configuration, we found that the stability of C(2)-N(3) bond showed a weakening trend. The adsorption wavelengths of the electronic transition between the valence band and conduction band of ornidazole on the TiO2 surface were in the visible light wavelengths range, showing that the TiO2 crystal plane can effectively make use of visible light under different conditions. We speculate the possibility of ornidazole degradation on the surface of TiO2 and found that the reactive site is the C-N bond on the imidazole ring. These discoveries explain the photocatalytic degradation of ornidazole by TiO2 and reveal the microscopic nature of catalytic degradation.
Infrapatellar fat pad-derived MSC response to inflammation and fibrosis induces an immunomodulatory phenotype involving CD10-mediated Substance P degradation
Authors: Kouroupis Dimitrios , Bowles Annie C. , Willman Melissa A. , Perucca Orfei Carlotta , Colombini Alessandra , Best Thomas M. , Kaplan Lee D. , Correa Diego
Published: July 2019

The infrapatellar fat pad (IFP) serves as a reservoir of Mesenchymal Stem Cells (MSC), and with adjacent synovium plays key roles in joint disease including the production of Substance P (SP) affecting local inflammatory responses and transmitting nociceptive signals. Here, we interrogate human IFP-derived MSC (IFP-MSC) reaction to inflammatory and pro-fibrotic environments (cell priming by TNFα/IFNγ and TNFα/IFNγ/CTGF exposure respectively), compared with bone marrow-derived MSC (BM-MSC). Naïve IFP-MSC exhibit increased clonogenicity and chondrogenic potential compared with BM-MSC. Primed cells experienced dramatic phenotypic changes, including a sharp increase in CD10, upregulation of key immunomodulatory transcripts, and secreted growth factors/cytokines affecting key pathways (IL-10, TNF-α, MAPK, Ras and PI3K-Akt). Naïve, and more so primed MSC (both) induced SP degradationin vitro, reproduced with their supernatants and abrogated with thiorphan, a CD10 inhibitor. These findings were reproducedin vivoin a rat model of acute synovitis, where transiently engrafted human IFP-MSC induced local SP reduction. Functionally, primed IFP-MSC demonstrated sustained antagonism of activated human peripheral blood mononuclear cells (PBMC) proliferation, significantly outperforming a declining dose-dependent effect with naïve cohorts. Collectively, ourin vitroandin vivodata supports cell priming as a way to enhance the immunoregulatory properties of IFP-MSC, which selectively engraft in areas of active synovitis/IFP fibrosis inducing SP degradation, resulting in a cell-based product alternative to BM-MSC to potentially treat degenerative/inflammatory joint diseases.
Comparison of metaxylem vessels and pits in four sympodial bamboo species
Authors: Luo Junji , Lian Caiping , Liu Rong , Zhang Shuqin , Yang Feng , Fei Benhua
Published: July 2019

The anatomical morphologies of vessel elements and pits of bamboo plants are unique, however, intensive research about vessel elements and pits in bamboo species is very scarce. The vessel elements and pits of four sympodial bamboo species were analyzed by light microscopy and environmental scanning electron microscopy (ESEM). Results show that the length and width of vessel elements were significantly different across bamboo species. The simple (main type), scalariform, and reticulate perforation plates were discovered on the end of vessel elements. The four species also displayed distinct pit forms. Characteristics of vessel elements, perforation plates, and the shape and size of pit apertures were examined separately for their potential relationship of bamboo structure and function.
Sourdough technology as a novel approach to overcome quality losses in sugar-reduced cakes
Authors: Sahin Aylin W. , Rice Tom , Zannini Emanuele , Lynch Kieran M. , Coffey Aidan , Arendt Elke K.
Published: July 2019

Sugar reduction in sweet baked goods is one of the most popular trends on the food market.
Separation of isomeric glycans by ion mobility spectrometry – the impact of fluorescent labelling
Authors: Manz Christian , Grabarics Márkó , Hoberg Friederike , Pugini Michele , Stuckmann Alexandra , Struwe Weston B. , Pagel Kevin
Published: July 2019

Bloodgroup oligosaccharides have been derivatized with labels common in HPLC and evaluated regarding their ion mobility behaviour.
Uniform lithium deposition on N-doped carbon-coated current collectors
Authors: Zhang Na , Yu Seung-Ho , Abruña Héctor D.
Published: July 2019

A Cu foil current collector was coated with polydopamine-derived nitrogen-doped carbon (N-C) to regulate Li nucleation and growth.
High rate laser deposition of conductive copper microstructures from deep eutectic solvents
Authors: Shishov Andrey , Gordeychuk Dmitry , Logunov Lev , Tumkin Ilya
Published: July 2019

The phenomenon of the laser chemical deposition of copper using deep eutectic solvents (DESs) on a dielectric substrate has been shown for the first time.
Topology, magnetism and dye adsorption properties of metal organic frameworks (MOFs) synthesized from bench chemicals
Authors: Iman Khushboo , Shahid M. , Khan M. Shahnawaz , Ahmad Musheer , Sama Farasha
Published: July 2019

Two new MOFs (CuMOF-1 and CoMOF-2) are synthesized, characterized by spectral and magnetic studies and employed for selective dye adsorption properties.
Electronic structure modifications induced by increased molecular complexity: from triphenylamine to m-MTDATA
Authors: Zhang T. , Brumboiu I. E. , Lanzilotto V. , Grazioli C. , Guarnaccio A. , Johansson F. O. L. , Coreno M. , de Simone M. , Santagata A. , Brena B. , Puglia C.
Published: July 2019

The comprehensive electronic structure of a starburst molecule (m-MTDATA) is thoroughly characterized for the first time, unveiling its good electron donor properties.
Rate coefficient of the reaction CH2OO + NO2probed with a quantum-cascade laser near 11 μm
Authors: Luo Pei-Ling , Chung Chen-An , Lee Yuan-Pern
Published: July 2019

Employing a cw quantum-cascade laser coupled with Herriott mirrors to probe CH2OO, we report a rate coefficientk= (1.0 ± 0.2) × 10−12cm3molecule−1s−1for the reaction CH2OO + NO2at 298 K, which is much smaller than literature values.