bluuebunny/crossref_metadata_2025_split huggingface dataset:
FLASH irradiation enhances the therapeutic index of abdominal radiotherapy for the treatment of ovarian cancer
Authors: Levy Karen , Natarajan Suchitra , Wang Jinghui , Chow Stephanie , Eggold Joshua T. , Loo Phoebe , Manjappa Rakesh , Lartey Frederick M. , Schüler Emil , Skinner Lawrie , Rafat Marjan , Ko Ryan , Kim Anna , Rawi Duaa Al , von Eyben Rie , Dorigo Oliver , Casey Kerriann M. , Graves Edward E. , Bush Karl , Yu Amy S. , Koong Albert C. , Maxim Peter G. , Loo Billy W. , Rankin Erinn B. 
Published: December 2019

AbstractPeritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Despite current surgery, chemotherapy and targeted therapies, the majority of patients diagnosed with advanced epithelial ovarian cancer develop recurrent disease and overall survival rates remain poor. It is known that ovarian cancer is a radiosensitive tumor. Historically, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of chemotherapy sensitive and resistant ovarian cancer. However, TAI fell out of favor due to high toxicity, particularly of the gastrointestinal tract. We have developed a preclinical irradiation platform that allows for total abdominal ultrahigh dose rate FLASH irradiation. We demonstrate that TAI-FLASH reduces radiation-induced intestinal injury in both healthy and tumor-bearing mice compared to conventional dose rate (CONV) irradiation. Single high dose TAI-FLASH reduced mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and decreased cell death in crypt base columnar cells. Importantly, FLASH and CONV irradiation had similar efficacy in the reduction of ovarian cancer peritoneal metastases. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of radiotherapy for the treatment of metastatic ovarian cancer in women.
Brain-machine interface learning is facilitated by specific patterning of distributed cortical feedback
Authors: Abbasi A. , Lassagne H. , Estebanez L. , Goueytes D. , Shulz D. E. , Ego-Stengel V. 
Published: December 2019

AbstractNeuroprosthetics offer great hope for motor-impaired patients. One obstacle is that fine motor control requires near-instantaneous, rich somatosensory feedback. Such distributed feedback may be recreated in a brain-machine interface using distributed artificial stimulation across the cortical surface. Here, we hypothesized that neuronal stimulation must be contiguous in its spatiotemporal dynamics in order to be efficiently integrated by sensorimotor circuits. Using a closed-loop brain-machine interface, we trained head-fixed mice to control a virtual cursor by modulating the activity of motor cortex neurons. We provided artificial feedback in real time with distributed optogenetic stimulation patterns in the primary somatosensory cortex. Mice developed a specific motor strategy and succeeded to learn the task only when the optogenetic feedback pattern was spatially and temporally contiguous while it moved across the topography of the somatosensory cortex. These results reveal new properties of sensorimotor cortical integration and set new constraints on the design of neuroprosthetics.TeaserTargeting a brain-machine interface feedback to a cortical map reveals unexpected constraints.
Characterization of the adaptation to visuomotor rotations in the muscle synergies space
Authors: Severini Giacomo , Zych Magdalena 
Published: December 2019

AbstractThe adaptation to visuomotor rotations is one of the most studied paradigms of motor learning. Previous literature has presented evidence of a dependency between the process of adaptation to visuomotor rotations and the constrains dictated by the workspace of the biological actuators, the muscles, and their co-activation strategies, modeled using muscle synergies analysis. To better understand this relationship, we asked a sample of healthy individuals (N =7) to perform two experiments aiming at characterizing the adaptation to visuomotor rotations in terms of rotations of the activation space of the muscle synergies during isometric reaching tasks. In both experiments, subjects were asked to adapt to visual rotations altering the position mapping between the force exerted on a fixed manipulandum and the movement of a cursor on a screen. In the first experiment subjects adapted to three different visuomotor rotation angles (30°, 40° and 50° clockwise) applied to the whole experimental workspace. In the second experiment subjects adapted to a single visuomotor rotation angle (45° clockwise) applied to eight different sub-spaces of the whole workspace, while also performing movements in the rest of the unperturbed workspace. The results from the first experiment confirmed the observation that visuomotor rotations induce rotations in the synergies activation workspace that are proportional to the visuomotor rotation angle. The results from the second experiment showed that rotations affecting limited sub-spaces of the whole workspace are adapted for by rotating only the synergies involved in the movement, with an angle proportional to the distance between the preferred angle of the synergy and the sub-space covered by the rotation. Moreover, we show that the activation of a synergy is only rotated when the sub-space covered by the visual perturbation is applied at the boundaries of workspace of the synergy. We found these results to be consistent across subjects, synergies and sub-spaces. Moreover, we found a correlation between synergies and muscle rotations further confirming that the adaptation process can be well described, at the neuromuscular level, using the muscle synergies model. These results provide information on how visuomotor rotations can be used to induce a desired neuromuscular response.
The lipid transfer function of RDGB at ER-PM contact sites is regulated by multiple interdomain interactions
Authors: Basak Bishal , Krishnan Harini , Raghu Padinjat 
Published: December 2019

SummaryInDrosophilaphotoreceptors, following Phospholipase C-β activation, the phosphatidylinositol transfer protein (PITP) RDGB, is required to maintain lipid homeostasis at endoplasmic reticulum (ER) plasma membrane (PM) membrane contact sites (MCS). Depletion or mis-localization of RDGB results in multiple defects in photoreceptors. Previously, interaction between the FFAT motif of RDGB with the integral ER protein dVAP-A was shown to be important for its localization at ER-PM MCS. Here, we report that in addition to FFAT motif, a large unstructured region (USR1) of RDGB is required to support the RDGB/dVAP-A interaction. However, interaction with dVAP-A alone is insufficient for accurate localization of RDGB: this also requires association of RDGB with apical PM, through its C-terminal LNS2 domain. Deletion of LNS2 domain results in complete mis-localisation of RDGB and also induces large mis-regulated interdomain movements abrogating RDGB function. Thus, multiple independent interactions between individual domains of RDGB supports its function at ER-PM MCS.
A modular RNA interference system for multiplexed gene regulation
Authors: Dwijayanti Ari , Storch Marko , Stan Guy-Bart , Baldwin Geoff S. 
Published: December 2019

ABSTRACTThe rational design and realisation of simple-to-use genetic control elements that are modular, orthogonal and robust is essential to the construction of predictable and reliable biological systems of increasing complexity. To this effect, we introducemodularArtificialRNAinterference (mARi), a rational, modular and extensible design framework that enables robust, portable and multiplexed post-transcriptional regulation of gene expression inEscherichia coli. The regulatory function of mARi was characterised in a range of relevant genetic contexts, demonstrating its independence from other genetic control elements and the gene of interest, and providing new insight into the design rules of RNA based regulation inE. coli, while a range of cellular contexts also demonstrated it to be independent of growth-phase and strain type. Importantly, the extensibility and orthogonality of mARi enables the simultaneous post-transcriptional regulation of multi-gene systems as both single-gene cassettes and poly-cistronic operons. To facilitate adoption, mARi was designed to be directly integrated into the modular BASIC DNA assembly framework. We anticipate that mARi-based genetic control within an extensible DNA assembly framework will facilitate metabolic engineering, layered genetic control, and advanced genetic circuit applications.
A novel system for maintaining Varroa destructor mites on artificial diets and its application for studying mites as a vector for honey bee viruses
Authors: Posada-Florez Francisco , Ryabov Eugene V. , Heerman Matthew C. , Chen Yanping , Evans Jay D. , Cook Steven C. , Sonenshine Daniel E. 
Published: December 2019

AbstractThe mite Varroa destructor is one of the most destructive parasites of the honey bee (Apis mellifera) and the primary cause of colony collapse in most regions of the world. These mites cause serious injury to their hosts, especially during the larval and pupal stages, and serve as the vector for several viruses, which affect honey bee health causing colony death. Attempts by beekeepers to control these mites have yielded limited success. The inability to rear populations of mites in vitro that excludes contact with their honey bee hosts has stymied research of Varroa biology. Previous attempts to rear and/or maintain Varroa mites in vitro by feeding them on artificial diets have had limited success. Several methods were plagued by mechanical failures including leaking membranes and, thus far, none have been widely adopted. Here we report a robust system for maintaining Varroa mites that includes an artificial diet, which does not contain honey bee tissue-derived components, thus making it particularly valuable in studying mite vectoring of honey bee viruses. With our system we demonstrated for the first time that Varroa mites maintained on an artificial diet supplemented with the particles of honey bee viruses, cDNA clone-derived genetically tagged Varroa destructor virus-1 and wild-type Deformed wing virus, can acquire and later transmit these viruses to recipient honey bee pupae. Along with providing an opportunity to study parasites and pathogens in the absence of honey bee hosts, this in vitro system for Varroa mite maintenance is both scalable and consistent. These features can be used to better understand mite nutritional needs, metabolic activity, responses to chemicals and other biological functions.
Human intestinal tissue-resident memory CD8+ T cells comprise transcriptionally and functionally distinct subsets
Authors: FitzPatrick Michael E.B. , Provine Nicholas M. , Garner Lucy C. , Powell Kate , Amini Ali , Irwin Sophie , Ferry Helen , Ambrose Tim , Friend Peter , Vrakas Georgios , Reddy Srikanth , Soilleux Elizabeth , Klenerman Paul , Allan Philip J. 
Published: December 2019

AbstractTissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined, and definitive markers of CD103-TRM cells are lacking. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through the study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified four conventional TRM populations, with two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating the two CD8+ populations, including differential expression of key residency-associated genes and cytotoxic molecules. Flow cytometry of recipient-derived cells infiltrating the graft and intestinal lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes, with β2-integrin acting as a CD103-CD8+ TRM marker. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103-TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal TRM cells, and suggest a role for β2-integrin in TRM development.SummaryHeterogeneity within human tissue-resident memory T (TRM) cells is poorly understood. We show that transcriptionally, phenotypically, and functionally distinct CD4+ and CD8+ TRM subsets exist in the human intestine, and that β2-integrin expression identifies a distinct population of CD8+ TRM cells.
Dimensions of anxiety and depression and neurophysiological indicators of error-monitoring: Relationship with delta and theta oscillatory power and error-related negativity amplitude
Authors: Muir Alexandra M. , Hedges-Muncy Ariana , Clawson Ann , Carbine Kaylie A. , Larson Michael J. 
Published: December 2019

AbstractError-monitoring processes may be affected by transdiagnostic dimensions of psychopathology symptoms including trait anxiety, worry, and severity of depressive symptoms. We tested the relationship between continuous measures of anxiety and depressive symptomology and neural correlates of error-monitoring as measured by time-frequency domain delta and theta oscillatory power and time domain error-related negativity (ERN) amplitude extracted from the electroencephalogram (EEG). Secondary analyses tested for diagnostic group differences in error-related neural responses in individuals with generalized anxiety disorder (GAD), major depressive disorder (MDD), and comorbid psychiatric disorders. 178 participants (104 female,M[SD]age= 21.7[4.6]) with a wide range of psychopathology symptoms completed a modified version of the Eriksen flanker task and symptom questionnaires. Residualized difference values between correct and error trials for delta/theta power and error/correct ERN amplitude were dependent variables. Linear regression analyses adjusted for age and sex showed nonsignificant associations of symptom dimension measures with error-related residualized delta/theta power or residualized ERN amplitude. Subset analyses on those with confirmed psychopathology diagnoses also did not predict residualized error-related delta/theta power nor ERN amplitude. Exploratory analyses with only error trial delta/theta power and ERN amplitude also revealed nonsignificant relationships. Taken in the context of previous literature, results suggest a heterogeneous relationship between depressive and anxiety symptom dimensions and neurophysiological indices of error-monitoring.Impact StatementIn line with the RDoC framework, we tested the relationship between anxiety and depressive symptom dimensions and neural indices of error-processing (delta and theta power, error-related negativity ERP amplitude) in 178 participants with a range of pathology symptoms. A non-significant relationship emerged between neural and symptom measures suggesting anxiety and depressive symptomology have a nuanced relationship with error-monitoring in a large sample across a range of anxiety and depression symptoms.
FGF9 and FGF10 use distinct signaling pathways to direct lung epithelial specification and branching
Authors: Yin Yongjun , Ornitz David M. 
Published: December 2019

AbstractFibroblast Growth Factors (FGFs) 9 and 10 are essential during the pseudoglandular stage of lung development. Mesothelial produced FGF9 is principally responsible for mesenchymal growth, whereas epithelial produced FGF9 and mesenchymal produced FGF10 guide lung epithelial development, and loss of either of these ligands affects epithelial branching. Because FGF9 and FGF10 activate distinct FGF receptors (FGFRs), we hypothesized that they would control distinct developmental mechanisms. Here, we show that FGF9 signaled through epithelial FGF receptor 3 (FGFR3) to directly promote distal epithelial fate specification and inhibit epithelial differentiation. By contrast, FGF10 signaled through epithelial FGFR2b to promote epithelial proliferation and differentiation. Furthermore, FGF9-FGFR3 signaling functionally opposed FGF10-FGFR2b signaling, and FGFR3 preferentially used downstream PI3K pathways, whereas FGFR2b relied on downstream RAS-MAPK pathways. These data demonstrate that within lung epithelial cells, different FGFRs function independently; they bind receptor-specific ligands and direct unique developmental functions through activation of distinct downstream signaling pathways.
Examining US business undergraduates’ use of career information sources during career exploration
Authors: Chin Mun Yuk , Blackburn Cohen Chelsea A. , Hora Matthew T. 
Published: December 2019

Purpose
Campus career services are increasingly scrutinized as the primary career development resource for undergraduates. The purpose of this paper is to use Career Construction Theory to examine all sources of career information used by undergraduate business students and their contributions toward career exploration and development.

Design/methodology/approach
Using a mixed-methods design, a survey was first administered to 372 university students enrolled in an undergraduate business school in the USA. Focus group interviews were conducted with 35 students from the survey sample. Descriptive statistics are reported, and inductive themes and causal networks were derived from qualitative data.

Findings
In order of prominence, students endorsed using sociocultural (e.g. family) and institutional (e.g. career services center) resources, and exploratory activities (e.g. work experience) as career information sources. These sources contributed toward students’ vocational development by enhancing their psychological readiness for work, building social capital and facilitating decisions.

Research limitations/implications
Participants were sampled from one undergraduate business school in the USA and were self-selected into the study.

Practical implications
Career services and higher education professionals should think of the career-related information sources available to students as a complex ecosystem of advice instead of singular resources that exist in isolation. Professionals should also attend to students existing sources of career information and consider ways to support students’ development of social and professional networks and opportunities. Furthermore, universities should consider the potential for integrating career exploration into course curricula as opposed to tasking career services offices to be fully responsible for students’ career-related outcomes.

Originality/value
This study is the first to examine undergraduate business students’ sources of career information and their contributions to career development. Its insights offer evidence for ways to tailor interventions to support students’ use of available information sources beyond campus career services.
Rethinking competition-based entrepreneurship education in higher education institutions
Authors: Watson Kayleigh , McGowan Pauric 
Published: December 2019

Purpose
The purpose of this paper is to focus with the university-based business plan competition (BPC) and proposes how the theory of effectuation might inform a new model. Such a purpose is timely given the under-challenged nature of the BPC methodology.

Design/methodology/approach
Extant literature pertaining to business planning and the business plan within entrepreneurship education and effectuation is reviewed; numerous conceptual issues which undermine BPC provision in its traditional form are then identified. In response to these identified issues, a series of principles which could underpin the introduction of an effectuation-led business coopetition (EBC) are outlined.

Findings
Strong emphasis on business plan production within a conventional BPC model raises questions about its capacity to release the entrepreneurial potential of the higher education institution student and provide them with an authentic and relevant entrepreneurial learning experience. Through using the ideas of effectuation to rethink provision, the action of business plan production can usefully be replaced with the action of business implementation. As well as facilitate a beneficial shift from competition to coopetition-based entrepreneurship education.

Originality/value
This paper valuably critiques the efficacy of a commonly employed yet under-challenged methodology for entrepreneurship education; the BPC. The propositions offered can guide competition provision in a more authentic, realistic and relevant way that is potentially better suited to inspiring and supporting entrepreneurial new venturing amongst students and graduates now rather than in the future. The paper thus has practical value to those designing and delivering competition-based entrepreneurship education.
Learning from design-prototyping interaction for engineering innovation from a cross-functional perspective
Authors: Lee Demei 
Published: December 2019

PurposeNovel engineering designs are usually infeasible for manufacturing or fail to meet the required performance. The dissimilar functionalities and mindsets between design and manufacturing pose challenges, as well as opportunities for innovation projects. This paper aims to report the innovation process that prototyped a novel engineering design of a haptic device in an engineering research lab. The innovation process went through several design generations. Interaction between design and manufacturing drove the innovation toward both better and worse directions between generations.Design/methodology/approachUsing the case research method, the steps of theoretical proposition development, case selection, data collection, data analysis and theory modification were followed. By interviewing the key persons, the characteristics, issues and recommendations for improvement of the innovation process were identified.FindingsIt was found that technical issues were not the hurdles in the innovation process. Instead, managing the inter-organizational mechanism proved critical to its eventual success. The educational gap between the design and manufacturing groups gave rise to communicational and perceptional distance, while the gap in terms of work experience between the two groups enlarged that distance.Research limitations/implicationsThe research results may be limited to cases with similar organizational and technological contexts.Practical implicationsWithin an organization, the design and the manufacturing divisions are separated by a functional gap. The functional gap should be managed with multiple views, namely, technical, personal and organizational perspectives. The identified innovation process could help bridge such a gap and facilitate innovative engineering designs in research institutes.Originality/valueThe effectiveness of the innovation process was, thus, found to be determined by the positive or negative reinforcement of these two gaps between the design and manufacturing of the research institute.