bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumor immunity in dMMR colorectal cancers requires interferon-induced CCL5 and CXCL10
Authors: Mowat Courtney , Mosley Shayla R. , Namdar Afshin , Schiller Daniel , Baker Kristi 
Published: September 2020

SummaryColorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) are heavily infiltrated by CD8+ tumor infiltrating lymphocytes (TILs) and are associated with a better prognosis than the majority of CRCs. The immunogenicity of dMMR CRCs is commonly attributed to abundant neoantigen generation due to their extreme genomic instability. However, lack of neoantigenic overlap between these and other CRCs necessitates study of antigen-independent mechanisms of immune activation by dMMR CRCs in order identify therapeutic strategies for treating MMR proficient CRCs. We show here using organoid cocultures and orthotopic models that a critical component of dMMR CRC’s immunogenicity is the activation and recruitment of systemic CD8+ T cells into the tumor epithelium by overexpression of the chemokines CCL5 and CXCL10. This is dependent on endogenous activation of the cGAS/STING and IFN signaling pathways by the damaged DNA in dMMR CRCs. These signaling pathways remain sensitive to exogenous stimulation in other CRCs, identifying an attractive therapeutic avenue for increasing TIL infiltration into normally immune resistant CRC subtypes. We have thus identified a key neoantigen-independent mechanism that underlies the ability for dMMR CRCs to recruit TILs into the tumor epithelium. Given that TIL recruitment is a prerequisite for effective tumor killing either by the endogenous immune system or in the context of immunotherapies, treatments that activate IFN-induced chemokine-production by tumor cells promise to improve the prognosis of patients with many different CRC subsets.Statement of SignificanceA critical component of antitumor immunity in dMMR CRCs is their ability to recruit T cells into the tumor epithelium as a prerequisite to tumor cell killing. This occurs because their extensive genomic instability leads to endogenous activation of cGAS/STING and overexpression of CCL5 and CXCL10.
Robustness of individualized inferences from longitudinal resting state dynamics
Authors: Hommelsen Maximilian , Viswanathan Shivakumar , Daun Silvia 
Published: September 2020

ABSTRACTTracking how individual human brains change over extended timescales is crucial in scenarios ranging from healthy aging to stroke recovery. Tracking these neuroplastic changes with resting state (RS) activity is a promising but poorly understood possibility. It remains unresolved whether a person’s RS activity over time can be reliably decoded to distinguish neurophysiological changes from confounding differences in cognitive state during rest. Here, we assessed whether this confounding can be minimized by tracking the configuration of an individual’s RS activity that is shaped by their distinctive neurophysiology rather than cognitive state. Using EEG, individual RS activity was acquired over five consecutive days along with activity in tasks that were devised to simulate the confounding effects of inter-day cognitive variation. As inter-individual differences are shaped by neurophysiological differences, the inter-individual differences in RS activity on one day were analyzed (using machine learning) to identify a distinctive configuration in each individual’s RS activity. Using this configuration as a classifier-rule, an individual could be re-identified with high accuracy from 2-second samples of the instantaneous oscillatory power acquired on a different day both from RS and confounded-RS. Importantly, the high accuracy of cross-day classification was achieved only with classifiers that combined information from multiple frequency bands at channels across the scalp (with a concentration at characteristic fronto-central and occipital zones). These findings support the suitability of longitudinal RS to support robust individualized inferences about neurophysiological change in health and disease.
The zinc finger antiviral protein ZAP destabilises viral transcripts and restricts human cytomegalovirus
Authors: Gonzalez-Perez Ana Cristina , Stempel Markus , Wyler Emanuel , Urban Christian , Piras Antonio , Hennig Thomas , Heim Albert , Landthaler Markus , Pichlmair Andreas , Erhard Florian , Dölken Lars , Brinkmann Melanie M. 
Published: September 2020

AbstractInterferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonises several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is largely unknown. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. We show that expression of the two major isoforms of ZAP, the long (ZAP-L) and short (ZAP-S), is induced during HCMV infection and that both negatively affect HCMV replication. Transcriptome and proteome analyses demonstrated that the expression of ZAP decelerates the progression of HCMV infection. SLAM-sequencing revealed that ZAP restricts HCMV at early stages of infection by destabilising a distinct subset of viral transcripts with low CG content. In summary, this report provides evidence of an important antiviral role for ZAP in host defense against HCMV infection and highlights its differentiated function during DNA virus infection.
The influence of geneRv3671cinMycobacterium bovisto its replication and acid resistance
Authors: Lin Weidong , Xin Ting 
Published: September 2020

AbstractTo study the effect of Marp protein in Mycobacteriumbovisto the acid resistance and growth performance, this research constructed a knockout mutant (ΔMarp) with mycobacteriophage, complemented strain (ΔMarpComp), and overexpressing strain (PmvRv3671) of the geneRv3671cwith pmv261 plasmid. Culturing them in standard 7H9 medium to the early logarithmic phase and transferring them into 7H9 medium at pH 6.6 and pH 5.0 and maintenance solution at pH 6.6 and pH 4.5. Likewise, macrophages Raw264.7 were infected with multiple infections at 10. The results showed that while they grew in 7H9 medium at pH 5.0 or pH 6.6 and maintenance buffer at pH 4.5, the lived number of over-expressing strain PmvRv3671 is more than wild-type strain M.bovis, ΔMarpComp andΔMarpon the 14thday. After removing the effects of citrate solution, it can be found that the acid resistance abilities of them all are significantly lower on the 14thday than that on the 5thday. Using them infected Raw264.7 macrophages with IFNγ stimulation, the growth rate of the PmvRv3671 is better than An5,ΔMarpand ΔMarpComp. In conclusion,Rv3671cover-expressing strain had shown a better growth ability than wild-type An5,ΔMarpand ΔMarpComp under acidic environment. When exposed to pH 4.5 citrate maintenance solution for a long time, acid resistance abilities of them all have become weaker.
TMS cortical mapping of multiple muscles: absolute and relative test-retest reliability
Authors: Nazarova Maria , Novikov Pavel , Ivanina Ekaterina , Kozlova Ksenia , Dobrynina Larisa , Nikulin Vadim V. 
Published: September 2020

AbstractThe spatial accuracy of TMS may be as small as a few millimeters. Despite such great potential, navigated TMS (nTMS) mapping is still underused for the assessment of motor plasticity, particularly in clinical settings. Here we investigate the within-limb somatotopy gradient as well as absolute and relative reliability of three hand muscle cortical representations (MCRs) using a comprehensive grid-based sulcus-informed nTMS motor mapping. We enrolled 22 young healthy male volunteers. Two nTMS mapping sessions were separated by 5-10 days. Motor evoked potentials were obtained from abductor pollicis brevis (APB), abductor digiti minimi, and extensor digitorum communis. In addition to individual MRI-based analysis, we studied MNI normalized MCRs. For the reliability assessment, we calculated intra-class correlation and the smallest detectable change. Our results revealed a somatotopy gradient reflected by APB MCR having the most lateral location. Reliability analysis showed that the commonly used metrics of MCRs, such as areas, volumes, centers of gravity (COGs), and hotspots had a high relative and low absolute reliability for all three muscles. For within-limb TMS somatotopy, the most common metrics such as the shifts between MCR COGs and hotspots had poor relative reliability. However, overlaps between different muscle MCRs were highly reliable. We thus provide novel evidence that inter-muscle MCR interaction can be reliably traced using MCR overlaps while shifts between the COGs and hotspots of different MCRs are not suitable for this purpose. Our results have implications for the interpretation of nTMS motor mapping results in healthy subjects and patients with neurological conditions.
Essential gene analysis inAcinetobacter baumanniiby high-density transposon mutagenesis and CRISPR interference
Authors: Bai Jinna , Dai Yunfei , Farinha Andrew , Tang Amy Y. , Syal Sapna , Vargas-Cuebas German , Surujon Defne , Isberg Ralph R. , van Opijnen Tim , Geisinger Edward 
Published: September 2020

AbstractAcinetobacter baumanniiis a poorly understood bacterium capable of life-threatening infections in hospitals. Few antibiotics remain effective against this highly resistant pathogen. Developing rationally-designed antimicrobials that can targetA. baumanniirequires improved knowledge of the proteins that carry out essential processes allowing growth of the organism. Unfortunately, studying essential genes has been challenging using traditional techniques, which usually require time-consuming recombination-based genetic manipulations. Here, we performed saturating mutagenesis with dual transposon systems to identify essential genes inA. baumanniiand we developed a CRISPR-interference (CRISPRi) system for facile analysis of these genes. We show that the CRISPRi system enables efficient transcriptional silencing inA. baumannii. Using these tools, we confirmed the essentiality of the novel cell division protein AdvA and discovered a previously uncharacterized AraC-family transcription factor (ACX60_RS03245) that is necessary for growth. In addition, we show that capsule biosynthesis is a conditionally essential process, with mutations in late-acting steps causing toxicity in strain ATCC 17978 that can be bypassed by blocking early-acting steps or activating the BfmRS stress response. These results open new avenues for analysis of essential pathways inA. baumannii.ImportanceNew approaches are urgently needed to controlA. baumannii,one of the most drug resistant pathogens known. To facilitate the development of novel targets that allow inhibition of the pathogen, we performed a large-scale identification of genes whose products the bacterium needs for growth. We also developed a CRISPR-based gene knockdown tool that operates efficiently inA. baumannii, allowing rapid analysis of these essential genes. We used these methods to define multiple processes vital to the bacterium, including a previously uncharacterized gene-regulatory factor and export of a protective polymeric capsule. These tools will enhance our ability to investigate processes critical for the essential biology of this challenging hospital-acquired pathogen.
High affinity modified ACE2 receptors protect from SARS-CoV-2 infection in hamsters
Authors: Higuchi Yusuke , Suzuki Tatsuya , Arimori Takao , Ikemura Nariko , Mihara Emiko , Kirita Yuhei , Ohgitani Eriko , Mazda Osam , Motooka Daisuke , Nakamura Shota , Sakai Yusuke , Itoh Yumi , Sugihara Fuminori , Matsuura Yoshiharu , Matoba Satoaki , Okamoto Toru , Takagi Junichi , Hoshino Atsushi 
Published: September 2020

ABSTRACTThe SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor via receptor binding domain (RBD) to enter into the cell and inhibiting this interaction is a main approach to inhibit SARS-CoV-2 infection. We engineered ACE2 to enhance the affinity with directed evolution in 293T cells. Three cycles of random mutation and cell sorting achieved 100-fold higher affinity to RBD than wild-type ACE2. The extracellular domain of modified ACE2 fused to the human IgG1-Fc region had stable structure and neutralized SARS-CoV-2 without the emergence of mutational escape. Therapeutic administration protected hamsters from SARS-CoV-2 infection, decreasing lung virus titers and pathology. Engineering ACE2 decoy receptors with human cell-based directed evolution is a promising approach to develop a SARS-CoV-2 neutralizing drug that has affinity comparable to monoclonal antibodies yet displaying resistance to escape mutations of virus.One Sentence SummaryEngineered ACE2 decoy receptor has a therapeutic potential against COVID-19 without viral escape mutation.
An improved flower pollination algorithm for solving a Type-II U-shaped assembly line balancing problem with energy consideration
Authors: Zhang Beikun , Xu Liyun 
Published: September 2020

Purpose
The increasing energy shortage leads to worldwide attentions. This paper aims to develop a mathematical model and optimization algorithm to solve the energy-oriented U-shaped assembly line balancing problem. Different from most existing works, the energy consumption is set as a major objective.

Design/methodology/approach
An improved flower pollination algorithm (IFPA) is designed to solve the problem. The random key encoding mechanism is used to map the continuous algorithm into discrete problem. The pollination rules are modified to enhance the information exchange between individuals. Variable neighborhood search (VNS) is used to improve the algorithm performance.

Findings
The experimental results show that the two objectives are in conflict with each other. The proposed methodology can help manager obtain the counterbalance between them, for the larger size balancing problems, and the reduction in objectives is even more significant. Besides, the experiment results also show the high efficiency of the proposed IFPA and VNS.

Originality/value
The main contributions of this work are twofold. First, a mathematical model for the U-shaped assembly line balancing problem is developed and the model is dual foci including minimized SI and energy consumption. Second, an IFPA is proposed to solve the problem.
Study on the importance of wine bottle design on consumer choices
Authors: Chamorro Antonio , García-Gallego José Manuel , Trindade-Carlos Hermelinda da Conceição 
Published: September 2020

PurposeThe aim of this study is to analyse the importance of bottle design in relation to other purchasing criteria, and also to understand which design elements are most attractive to consumers.Design/methodology/approachA survey of a sample of 437 wine drinkers was carried out in Portugal using non-probabilistic sampling. The technique used was conjoint analysis based on the SPSS conjoint module.FindingsOne of the key findings was the low importance of bottle design in shaping consumer preferences compared to other attributes (origin, price and category of wine). In terms of design elements, the label had the biggest influence on consumer choice, followed by the type of bottle, bottle seal and brand name, in that order. Differences in consumer choice were evident according to the level of knowledge of wine and frequency of consumption.Practical implicationsThe findings of this study provide guidance for Portuguese wineries as regards the marketing and design decisions of their products and packaging.Originality/valueThis study sheds new light on the importance of wine bottle design on consumer preferences. Previous studies in the area have proved to be minimal and heterogeneous.
What do we mean by “transferable skills”? A literature review of how the concept is conceptualized in undergraduate health sciences education
Authors: Olesen Kristoffer Brix , Christensen Mette Krogh , O'Neill Lotte Dyhrberg 
Published: September 2020

PurposeDue to rapid changes in the future labor market, transferable skills are recognized as a vital learning outcome for students in undergraduate higher education. However, ambiguities surrounding the concept and content of transferable skills hamper the actual teaching and learning of transferable skills. Consequently, there is a great need for an overview of the literature on transferable skills to qualify and develop the approaches to transferrable skills in higher education. This study aims to outline a typology of how transferable skills are conceptualized in health sciences education, that is, medicine, nursing and related health professionals’ education.Design/methodology/approachThe study was a mixed studies literature review, which included quantitative, qualitative and mixed-methods studies. A seven-stage sequential exploratory synthesis of the included studies was conducted.FindingsThis review showed that transferable skills reflected three main conceptualizations: Program Requirements, Employability and Holistic Development. Overall, the global methodological quality of the empirical studies of interventions to further transferable skills development in health science education was weak.Research limitations/implicationsThis study aids clear conceptualization in future empirical studies.Practical implicationsBy distinguishing between three main conceptualizations of transferable skills, this study's typology supports alignment in transferable skills curricula because conceptually sound learning objectives provide teachers and students in health sciences education with a clear purpose and direct educators' choice of relevant teaching and assessment strategies.Originality/valueThis review – the first of its kind – contributes to conceptualization of transferable skills as the basis for curriculum development and research.
The roles of social enterprises in a Swedish labour market integration programme – opportunities and challenges for social innovation
Authors: Kraff Helena , Jernsand Eva Maria 
Published: September 2020

Purpose
The purpose of this paper is to explore the roles of work integration social enterprises (WISEs) in the Swedish establishment programme for newly arrived refugees, and how its set-up affects WISEs preconditions for social innovation.

Design/methodology/approach
The paper builds on a longitudinal and qualitative action research study of a WISE and its work in organising a course for labour market integration, in the context of the Swedish establishment programme. The authors were actively involved in the study as embedded researchers.

Findings
The exploration identifies a number of roles that WISEs take on in the establishment programme. It illustrates how WISEs hybrid character places participants at the centre of the innovation process, where their opinions and knowledge are considered crucial, and how this positively affects their ability to gain skills and confidence. However, the study also makes visible how issues of coordination between stakeholders in the programme lead to mismatches between course content and participant profiles, colliding activities and sporadic participation. In short, the bureaucracy embedded in labour market integration systems erodes the preconditions of WISEs to foster social innovation.

Originality/value
The embeddedness of the authors provides in-depth knowledge regarding how complex state systems affect WISEs in practice. Importantly, it also gives insights into the experiences of refugees, a group that is often mentioned in the literature on WISEs, although mainly in passing.
Experimental study on frequency‐dependent elastic properties of weakly consolidated marine sandstone: effects of partial saturation
Authors: Li Hui , Zhao Luanxiao , Han De‐hua , Gao Jinghuai , Yuan Hemin , Wang Yirong 
Published: September 2020

ABSTRACTInvestigating seismic dispersion and attenuation characteristics of loosely compacted marine sandstone is essential in reconciling different geophysical measurements (surface seismic, well logging and ultrasonic) for better characterization of a shallow marine sandstone reservoir. We have experimented with a typical high‐porosity and high‐permeability sandstone sample, extracted from the Paleogene marine depositional setting in the Gulf of Mexico, at the low‐frequency band (2–500 Hz) as well as ultrasonic point (106 Hz), to investigate the effects of varying saturation levels on a rock's elasticity. The results suggest that the Young's modulus of the measured sample with adsorbed moisture at laboratory conditions (room temperature, 60%–90% humidity) exhibits dispersive behaviours. The extensional attenuation can be as high as 0.038, and the peak frequency occurs around 60 Hz. The extensional attenuation due to moisture adsorption can be dramatically mitigated with the increase of confining pressure. For partial saturation status, extensional attenuation increases as increasing water saturation by 79% with respect to the measured frequencies. Additionally, the results show that extensional attenuation at the fully water‐saturated situation is even smaller than that at adsorbed moisture conditions. The Gassmann–Wood model can overall capture the P‐wave velocity‐saturation trend of measured data at seismic frequencies, demonstrating that the partially saturated unconsolidated sandstone at the measured seismic frequency range is prone to be in the relaxed status. Nevertheless, the ultrasonic velocities are significantly higher than the Gassmann–Wood predictions, suggesting that the rocks are in the unrelaxed status at the ultrasonic frequency range. The poroelastic modelling results based on the patchy saturation model also indicate that the characteristic frequency of the partially saturated sample is likely beyond the measured seismic frequency range.
St Thomas Becket and Medieval London
Authors: JENKINS JOHN 
Published: September 2020

AbstractThomas Becket was born in London, and throughout his life had a close if chequered relationship with the city. After his death, while his body lay in its shrine at Canterbury, the citizens of London made great efforts to reclaim his memory for themselves by seeding his commemoration throughout the city. He was swiftly adopted as London's patron saint, the ‘Light of Londoners’, and the strength of devotion to him was made manifest in such construction programmes as the first stone London Bridge, the hospital on his birth site and the city‐wide waterworks. By comparison with Canterbury's focus on Becket's martyrdom, London fostered a dynamic and vibrant cult based upon his birth and rebirth, centralising this element of the cult in their pageants and giving genesis to central elements of the wider Becket mythos such as the ‘Saracen mother’ story. The purpose of this article is to fill a lacuna in the historiography of both the saint and the city, and provide an overview of the importance of St Thomas Becket to medieval Londoners, and of London to the cult of St Thomas.