bluuebunny/crossref_metadata_2025 huggingface dataset:
Reward-driven enhancements in motor control are robust to TMS manipulation
Authors: Codol Olivier , Galea Joseph M. , Jalali Roya , Holland Peter J.
Published: January 2020

A wealth of evidence describes the strong positive impact that reward has on motor control at the behavioural level. However, surprisingly little is known regarding the neural mechanisms which underpin these effects, beyond a reliance on the dopaminergic system. In recent work, we developed a task that enabled the dissociation of the selection and execution components of an upper limb reaching movement. Our results demonstrated that both selection and execution are concommitently enhanced by immediate reward availability. Here, we investigate what the neural underpinnings of each component may be. To this end, we disrupted activity of the ventromedial prefrontal cortex and supplementary motor area using continuous theta-burst transcranial magnetic stimulation (cTBS) in a within-participant design (N=23). Both cortical areas are involved in reward processing and motor control, and we hypothesised that disruption of their activity would result in disruption of the reward-driven effects on action selection and execution, respectively. To increase statistical power, participants were pre-selected based on their sensitivity to reward in the reaching task. While reward did lead to enhanced perforance during the cTBS sessions and a control sham session, cTBS was ineffective in altering these effects. These results may provide evidence that other areas, such as the primary motor cortex or the premotor area, may drive the reward-based enhancements of motor performance.
Accelerating Prediction of Chemical Shift of Protein Structures on GPUs
Authors: Wright Eric , Ferrato Mauricio , Bryer Alex , Searles Robert , Perilla Juan , Chandrasekaran Sunita
Published: January 2020

Experimental chemical shifts (CS) from solution and solid state magic-angle-spinning nuclear magnetic resonance spectra provide atomic level information for each amino acid within a protein or protein complex. However, structure determination of large complexes and assemblies based on NMR data alone remains challenging due the complexity of the calculations. Here, we present a hardware accelerated strategy for the estimation of NMR chemical-shifts of large macromolecular complexes based on the previously published PPM_One software. The original code was not viable for computing large complexes, with our largest dataset taking approximately 14 hours to complete. Our results show that the code refactoring and acceleration brought down the time taken of the software running on an NVIDIA V100 GPU to 46.71 seconds for our largest dataset of 11.3M atoms. We use OpenACC, a directive-based programming model for porting the application to a heterogeneous system consisting of x86 processors and NVIDIA GPUs. Finally, we demonstrate the feasibility of our approach in systems of increasing complexity ranging from 100K to 11.3M atoms.

Author summary
The peptide sensor motif stabilizes the outward-facing conformation of TmrAB
Authors: Millan Cinthia R. , Francis Martina , Thompson Valery F. , Thaker Tarjani M. , Tomasiak Thomas M.
Published: January 2020

The ATP binding cassette (ABC) family of transporters move diverse small molecules across membranes in nearly all organisms. Transport activity requires conformational switching between inward-facing and outward-facing states driven by ATP-dependent dimerization of two nucleotide binding domains (NBDs). The allosteric mechanism that connects ATP binding and hydrolysis in the NBDs to conformational changes in a substrate binding site in the transmembrane domains (TMDs) presents an unresolved question. Here we use sequence coevolution analyses together with biochemical characterization to investigate the role of a highly conserved motif called the peptide sensor in coordinating domain rearrangements in the heterodimeric peptide exporter fromThermus thermophilus, TmrAB. Mutations in the peptide sensor motif alter ATP hydrolysis rates as well as substrate release. Disulfide crosslinking, evolutionary trace, and evolutionary coupling analysis reveal that these effects likely destabilize a network between the peptide sensor motif and the Q-loop and X-loop, two known allosteric elements in the NBDs. We further find that disruption of this network in TmrA versus TmrB has different functional consequences, hinting at an intrinsic asymmetry in heterodimeric ABC transporters extending beyond that of the NBDs. These results support a mechanism in which the peptide sensor motifs help coordinate the transition of TmrAB to an outward open conformation, and each half of the transporter likely plays a different role in the conformational cycle of TmrAB.
sgRNA level is a major factor affecting CRISPRi knockdown efficiency in K562 cells
Authors: Wang Y. , Xie Y. , Dong Z. C. , Jiang X. J. , Gong P. , Lu J. , Wan F.
Published: January 2020

To determine how nuclease deactivated Cas9 (dCas9) or sgRNA expression level affects the knockdown efficiency of CRISPRi, K562 cell clones expressing KRAB-dCas9 protein either with the inducible Tet-on system or with the constitutive SFFV promotor were created by lentiviral transduction, and single clones were selected by fluorescence-activated cell sorting (FACS) for further study. Six genes with various expression levels were targeted using lentiviral sgRNA from two libraries in four cell clones with various KRAB-dCas9 expression levels. We determined the knockdown efficiency and the expression level of the dCas9 protein /sgRNA level by flow cytometry. The cell clone with the highest KRAB-dCas9 expression level achieved effective CRISPRi knockdown, and is statistically different from other clones, indicating enough KRAB-dCas9 expression might be a prerequisite for CRISPRi. Utilizing this clone, we modified the expression level of sgRNA by adopting different multiplicity of infection (MOI)in lentiviral transduction and found that the knockdown efficiency was neither affected by the target gene expression level nor does it correlate with KRAB-dCas9 level, which remained relatively constant (CV=2.2%) across knockdown experiments. 74.72%, 72.28%, 39.08% knockdown ofmmadhc, rpia, znf148genes were achieved, and the knockdown efficiency correlated well with the sgRNA expression level. Linear regression modeling of the data revealed that the knockdown efficiency is significantly affected by both KRAB-dCas9 and sgRNA level, and the sgRNA level has a greater impact, based on the standardized coefficient (0.525 for KRAB-dCas9, 0.981 for sgRNA), indicating that sgRNA level is a major factor affecting CRISPRi efficiency.
A broad and potent H1-specific human monoclonal antibody produced in plants prevents influenza virus infection and transmission in guinea pigs
Authors: Park Jun-Gyu , Ye Chengjin , Piepenbrink Michael S. , Nogales Aitor , Wang Haifeng , Shuen Michael , Meyers Ashley J. , Martinez-Sobrido Luis , Kobie James J.
Published: January 2020

Although seasonal influenza vaccines block most predominant influenza types and subtypes, humans still remain vulnerable to waves of seasonal and new potential pandemic influenza viruses for which no immunity may exist because of viral antigenic drift and/or shift, respectively. Previously, we have described a human monoclonal antibody (hMAb), KPF1, which was produced in human embryonic kidney 293T cells (KPF1-HEK) with broad and potent neutralizing activity against H1N1 influenza A viruses (IAV)in vitro, and prophylactic and therapeutic activitiesin vivo. In this study, we produced hMAb KPF1 in tobacco plants (KPF1-Antx) and demonstrate how the plant-produced KPF1-Antx hMAb possesses similar biological activity compared with the mammalian produced KPF1-HEK hMAb. KPF1-Antx hMAb shows broad binding to recombinant HA proteins and H1N1 IAV, including A/California/04/2009 (pH1N1)in vitro, that are comparable to those observed with KPF1-HEK hMAb. Importantly, prophylactic administration of KPF1-Antx hMAb to guinea pigs prevented pH1N1 infection and transmission in both prophylactic and therapeutic experiments, substantiating its clinical potential to prevent and treat H1N1 infections. Collectively, this study demonstrates, for the first time, that plant-produced influenza hMAbs have similarin vitroandin vivobiological properties to those produced in mammalian cells. Because of the many advantages of plant-produced hMAbs, such as rapid batch production, low cost, and the absence of mammalian cell products, they represent an alternative strategy for the production of immunotherapeutics for the treatment of influenza viral infections, including emerging seasonal and/or pandemic strains.
Dynamic interactions between the RNA chaperone Hfq, small regulatory RNAs and mRNAs in live bacterial cells
Authors: Park Seongjin , Prévost Karine , Heideman Emily M. , Carrier Marie-Claude , Reyer Matthew A. , Liu Wei , Massé Eric , Fei Jingyi
Published: January 2020

RNA binding proteins play myriad roles in controlling and regulating RNAs and RNA-mediated functions, often through simultaneous binding to other cellular factors. In bacteria, the RNA chaperone Hfq modulates post-transcriptional gene regulation. Absence of Hfq leads to the loss of fitness and compromises the virulence of bacterial pathogens. Using live-cell super-resolution imaging, we are able to distinguish Hfq binding to different sizes of cellular RNAs. We demonstrate that under normal growth conditions, Hfq exhibits widespread mRNA binding activity. Particularly, the distal face of Hfq contributes mostly to the mRNA bindingin vivo. In addition, binding of Hfq to these mRNAs can recruit RNase E to promote turnover of these mRNAs in an sRNA-independent manner, providing one mechanism to release Hfq from the pre-bound mRNAs. Finally, our data indicate that sRNAs, once expressed, can either co-occupy Hfq with the mRNA or displace the mRNA from Hfq, suggesting mechanisms through which sRNAs rapidly access Hfq to induce sRNA-mediated gene regulation. Our data collectively demonstrate that Hfq dynamically changes its interactions with different RNAs in response to changes in cellular conditions.
Supra-molecular assemblies of ORAI1 at rest precede local accumulation into punctae after activation
Authors: Peckys Diana B. , Gaa Daniel , Alansary Dalia , Niemeyer Barbara. A. , de Jonge Niels
Published: January 2020

The Ca2+selective channel ORAI1 and endoplasmic reticulum (ER)-resident STIM proteins form the core of the channel complex mediating store operated Ca2+entry (SOCE). Using liquid phase electron microscopy (LPEM) the distribution of ORAI1 proteins was examined at rest and after SOCE-activation at nanoscale resolution. The analysis of over seven hundred thousand of ORAI1 positions showed that already at rest, a majority of the ORAI1 channels formed STIM-independent distinct supra-molecular clusters. Upon SOCE activation and in the presence of STIM proteins, ORAI1 assembled in micron-sized two-dimensional (2D) structures, such as the known punctae at the ER plasma membrane contact zones, but also in divergent structures such as strands, and ring-like shapes. Our results thus question the hypothesis that stochastically migrating single ORAI1 channels are trapped at regions containing activated STIM, and we propose instead that supra-molecular ORAI1 clusters fulfill an amplifying function for creating dense ORAI1 accumulations upon SOCE-activation.

STATEMENT OF SIGNIFICANCE

ORAI1 proteins form channels mediating store operated Ca2+entry, an important trigger for many cellular functions, especially in the immune system. ORAI1 channels at rest are assumed to be randomly distributed in the plasma membrane, while they accumulate into so-called “punctae” upon activation, where binding by STIM proteins activate the Ca2+channels. Using liquid phase electron microscopy, we discovered that ORAI1 forms small, elongated clusters indicating the existence of supramolecular assemblies. The role of such supramolecular organization of ORAI1 is possibly an amplifying function for the effective creation of ORAI1 accumulations in punctae, since the binding of only one ORAI1 protein would trap a multiple of channels.
Comparison of de-duplication methods used by WHO Global Antimicrobial Resistance Surveillance System (GLASS) and Japan Nosocomial Infections Surveillance (JANIS) in the surveillance of antimicrobial resistance
Authors: Kajihara Toshiki , Yahara Koji , Stelling John , Eremin Sergey Romualdovich , Tornimbene Barbara , Thamlikitkul Visanu , Hirabayashi Aki , Anzai Eiko , Wakai Satoyo , Matsunaga Nobuaki , Hayakawa Kayoko , Ohmagari Norio , Sugai Motoyuki , Shibayama Keigo
Published: January 2020

A major issue in the surveillance of antimicrobial resistance (AMR) is “de-duplication” or removal of repeated isolates, for which there exist multiple methods. The World Health Organization (WHO) Global Antimicrobial Resistance Surveillance System (GLASS) requires de-duplication by selecting only the first isolate of a given bacterial species per patient per surveillance period per specimen type per age group, gender, and infection origin stratification. However, no study on the comparative application of this method has been reported. The objective of this study was to evaluate differences in data tabulation between the WHO GLASS and the Japan Nosocomial Infections Surveillance (JANIS) system, which counts both patients and isolates after removing repeated isolates of the same bacterial species per multiresistance phenotype isolated from a patient within 30 days, regardless of specimen type. All bacterial data, consisting of approximately 8 million samples from 1795 Japanese hospitals in 2017 were exported from the JANIS database, and were tabulated using either the de-duplication algorithm of GLASS, or JANIS. We compared the tabulated results of the total number of patients whose blood and urine cultures were taken and of the percentage of resistant isolates ofEscherichia colifor each priority antibiotic. The number of patients per specimen type tabulated by the JANIS method was always smaller than that of GLASS. There was a small (< 3%) difference in the percentage of resistance ofE. colifor any antibiotic between the two methods in both out- and inpatient settings and blood and urine isolates. The two tabulation methods did not show considerable differences in terms of the tabulated percentages of resistance forE. coli. We further discuss how the use of GLASS tabulations to create a public software and website that could help to facilitate the understanding of and treatment against AMR.
Complete genome and phylogenetic analysis of bovine papillomavirus type 15 in Southern Xinjiang dairy cow
Authors: Hu Jianjun , Zhang Wanqi , Chauhan Surinder Singh , Shi Changqing , Song Yumeng , Qiu Zhitao , Zhao Yubing , Wang Zhehong , Cheng Long , Zhang Yingyu
Published: January 2020

In this study, the complete genome sequence of bovine papillomavirus (BPV) type 15 (BPV Aks-02), a novel putative BPV type from a skin sample of a cow in southern Xinjiang, China was determined by collecting cutaneous neoplastic lesion, followed by DNA extraction and amplicon sequencing. The complete genome consisted of 7189 base pairs (G+C content of 42.50%) that encoded five early (E8, E7, E1, E2, E4) and two late (L1 and L2) genes. The E7 protein contained a consensus CX2CX29CX2C zinc-binding domain and an LxCxE motif. The nucleotide sequence of the L1 open reading frame (ORF) was related mostly (99%) to the L1 ORF of putative type BAPV-3 reference strain from GenBank. Phylogenetic analysis and sequence similarities based on the L1 ORF suggest that BPV type (BPV Aks-02) clustered with members of genusXipapillomavirusas BPV15, and closely related toXipapillomavirus1.
Correlative cryo-structured illumination fluorescence microscopy and soft X-ray tomography elucidates reovirus intracellular release pathway
Authors: Kounatidis Ilias , Stanifer Megan L , Phillips Michael A. , Paul-Gilloteaux Perrine , Helligenstein Xavier , Wang Hongchang , Okolo Chidinma A. , Fish Thomas M. , Spink Matthew C. , Stuart David I. , Davis Ilan , Boulant Steeve , Grimes Jonathan M. , Dobbie Ian M. , Harkiolaki Maria
Published: January 2020

Imaging of biological matter across resolution scales presents the challenge of preserving the direct and unambiguous correlation of subject features from the macroscopic to the microscopic level. We present here a correlative imaging platform developed specifically for imaging cells in 3D, under cryogenic conditions. Rapid cryo-preservation of biological specimens is the current gold standard in sample preparation for ultrastructural analysis in X-ray imaging. However, cryogenic fluorescence localisation methods are by and large diffraction-limited and fail to deliver matching resolution. We addressed this technological gap by developing an integrated, user-friendly, platform for 3D correlative imaging of cells in cryo-preserved states using super-resolution structured illumination microscopy (SIM) in conjunction with soft X-ray tomography (SXT). The power of this new approach is demonstrated by studying the process of reovirus release from intracellular vesicles during the early stages of infection and identifying novel virus-induced structures.
Chemical, physical and biological triggers of evolutionary conserved Bcl-xL-mediated apoptosis
Authors: Ianevski Aleksandr , Kulesskiy Evgeny , Krpina Klara , Lou Guofeng , Aman Yahyah , Bugai Andrii , Aasumets Koit , Akimov Yevhen , Bulanova Daria , Gildemann Kiira , Arutyunyan Albert F. , Susova Olga Yu. , Zhuze Alexei L. , Ji Ping , Wang Wei , Holien Toril , Bugge Marit , Zusinaite Eva , Oksenych Valentyn , Lysvand Hilde , Gerhold Joachim M. , Bjørås Magnar , Johansen Pål , Waage Anders , Heckman Caroline , Fang Evandro F. , Kainov Denis E.
Published: January 2020

The evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected or RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. Here, we show that Bcl-xL-specific agent A-1155463 prematurely kills cells of different origins and the small roundworms (C. elegans), when combined with DNA-damaging agent 4-nitroquinoline-1-oxide (4NQO). The synergistic effect of 4NQO-A-1155463 combination was p53-dependent, was associated with the release of Bad and Bax from Bcl-xL, which triggered mitochondrial outer membrane permeabilization (MOMP). Combinations of Bcl-xL-specific inhibitors with certain anticancer compounds or physical insults also killed cells. Collectively, our results suggest that biological, chemical and physical factors trigger evolutionary conserved Bcl-xL-mediated apoptotic pathway.
ComBat-Seq: batch effect adjustment for RNA-Seq count data
Authors: Zhang Yuqing , Parmigiani Giovanni , Johnson W. Evan
Published: January 2020

The benefit of integrating batches of genomic data to increase statistical power in differential expression is often hindered by batch effects, or unwanted variation in data caused by differences in technical factors across batches. It is therefore critical to effectively address batch effects in genomic data. Many existing methods for batch effect adjustment assume continuous, bell-shaped Gaussian distributions for data. However in RNA-Seq studies where data are skewed, over-dispersed counts, this assumption is not appropriate and may lead to erroneous results. Negative binomial regression models have been used to better capture the properties of counts. We developed a batch correction method, ComBat-Seq, using negative binomial regression. ComBat-Seq retains the integer nature of count data in RNA-Seq studies, making the batch adjusted data compatible with common differential expression software packages that require integer counts. We show in realistic simulations that the ComBat-Seq adjusted data result in better statistical power and control of false positives in differential expression, compared to data adjusted by the other available methods. We further demonstrated in a real data example where ComBat-Seq successfully removes batch effects and recovers the biological signal in the data.
Obesity-linked PPARγ S273 phosphorylation promotes insulin resistance through Growth Differentiation Factor 3
Authors: Hall Jessica A. , Ramachandran Deepti , Roh Hyun C. , DiSpirito Joanna R. , Belchior Thiago , Zushin Peter-James H. , Palmer Colin J. , Hong Shangyu , Mina Amir I. , Liu Bingyang , Deng Zhaoming , Aryal Pratik , Jacobs Christopher , Tenen Danielle , Brown Chester W. , Charles Julia F. , Shulman Gerald I. , Kahn Barbara B. , Tsai Linus T.Y. , Rosen Evan D. , Spiegelman Bruce M. , Banks Alexander S.
Published: January 2020

Overnutrition and obesity promote adipose tissue dysfunction, often leading to systemic insulin resistance. The thiazolidinediones (TZDs) are a potent class of insulin-sensitizing drugs and ligands of PPARγ that improve insulin sensitivity, but their use is limited due to significant side effects. Recently, we demonstrated a mechanism by which TZDs improve insulin sensitivity distinct from receptor agonism and adipogenesis: reversal of obesity-linked phosphorylation of PPARγ at Serine 273. However, the role of this modification has not been tested genetically. Here we demonstrate that mice encoding an allele of PPARγ which cannot be phosphorylated at S273 are protected from insulin resistance, without exhibiting differences in body weight or TZD-associated side effects. Indeed, hyperinsulinemic-euglycemic clamp experiments confirm improved insulin sensitivity, as evidenced by increased whole-body glucose uptake. RNA-seq experiments reveal PPARγ S273 phosphorylation specifically enhances transcription of Gdf3, a BMP family member. Ectopic expression of Gdf3 is sufficient to induce insulin resistance in lean, healthy mice. We find that Gdf3 can impact metabolism by inhibition of BMP signaling. Together, these results highlight the diabetogenic role of PPARγ S273 phosphorylation and focuses attention on a putative target, Gdf3.
Pan-cancer landscape of homologous recombination deficiency
Authors: Nguyen Luan , Martens John , Van Hoeck Arne , Cuppen Edwin
Published: January 2020

Homologous recombination deficiency (HRD) results in impaired double strand break repair and is a frequent driver of tumorigenesis. Here, we developed a genome-wide mutational scar-based pan-cancerClassifier ofHOmologousRecombinationDeficiency (CHORD) that can discriminate BRCA1- and BRCA2-subtypes. Analysis of a metastatic (n=3,504) and primary (n=1,854) pan-cancer cohort revealed HRD was most frequent in ovarian and breast cancer, followed by pancreatic and prostate cancer. Biallelic inactivation of BRCA1, BRCA2, RAD51C or PALB2 was the most common genetic cause of HRD, with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD. While the specific genetic cause of HRD was cancer type specific, biallelic inactivation was predominantly associated with loss-of-heterozygosity (LOH), with increased contribution of deep deletions in prostate cancer. Our results demonstrate the value of pan-cancer genomics-based HRD testing and its potential diagnostic value for patient stratification towards treatment with e.g. poly ADP-ribose polymerase inhibitors (PARPi).
Structural analysis ofSulfolobus solfataricusTF55β chaperonin in open and filamentous states
Authors: Zeng Yi Cheng , Sobti Meghna , Stewart Alastair G
Published: January 2020

Chaperonins are biomolecular complexes that assist protein folding. Thermophilic Factor 55 (TF55) is a group II chaperonin found in the archaeal genusSulfolobusthat has α, β and γ subunits. Using cryo-electron microscopy, we have determined the structure of the β-only complex ofS. solfataricusTF55 complexes to 3.6–4.2 Å resolution and a filamentous form to 5.2 Å resolution. The structures of the TF55β complexes formed in the presence of ADP or ATP highlighted an open state in which nucleotide exchange can occur before progressing in the refolding cycle. The structure of the filamentous state indicates how helical protrusions facilitate end-on-end interactions.

Synopsis

The isolated complex and filamentous forms of TF55β chaperonin from the thermophilic archaeaSulfolobus solfataricusare reported. Using cryo-EM, nucleotide-bound complexes of TF55β at 3.6–4.2 Å resolution reveal an open conformation, while a 5.2 Å reconstruction of the filamentous chaperonin reveals contacts at the apical domain similar to crystal-packed structures.
Chemotaxis overrides Barotaxis during Directional Decision-Making inDictyostelium discoideum
Authors: Belotti Yuri , McGloin David , Weijer Cornelis J.
Published: January 2020

Neutrophils and dendritic cells have, besides their well characterised chemotactic movement responses, been shown to be able to detect and respond to local differences in hydraulic resistance (barotaxis). Furthermore, for neutrophils, it has been suggested that barotaxis overrides chemotaxis. Here, we investigate whether Dictyostelium cells also respond to hydraulic resistance or primarily to chemical gradients using an asymmetric bifurcating micro-channel. This channel design allows us to decouple hydraulic and chemical stimuli, by providing a choice between moving up a chemical gradient or down a chemical gradient into a channel with 100 times lower hydraulic resistance. Under these conditions chemotaxis always overrides barotaxis. Cells confronted by a microchannel bifurcation are observed to often partially split their leading edge and to start moving into both channels. Cells in steeper cAMP gradients, that move faster, split more readily. The decision to retract the pseudopod moving away from the cAMP source is made when the average velocity of the pseudopod moving up the cAMP gradient is 20% higher than the average velocity of the pseudopod moving down the gradient. Surprisingly, this decision threshold is independent of the steepness of the cAMP gradient and speed of movement. It indicates that a critical force imbalance threshold underlies the repolarisation decision.

Significance Statement

We investigate the directional ‘decision-making’ of Dictyostelium discoideum cells migrating within engineered micro-channels harbouring asymmetric bifurcations. Unlike neutrophils and immature dendritic cells, Dictyostelium cells strongly prioritise chemical over barotactic guidance cues. Cells in steeper cAMP gradients migrate at higher speeds, split their leading edges more readily when confronted with a bifurcation in the channel. The decision to retract a pseudopod pointing in an unfavourable direction occurs when a critical tension gradient between two competing pseudopods is surpassed. These experiments show that although barotaxis is not a major guidance cue, cellular mechanics plays a major role in leading edge dynamics, including front splitting and polarisation and retraction.
Single molecule mass photometry of nucleic acids
Authors: Li Yiwen , Struwe Weston B. , Kukura Philipp
Published: January 2020

Mass photometry is a recently developed methodology capable of detection, imaging and mass measurement of individual proteins under solution conditions. Here, we show that this approach is equally applicable to nucleic acids, enabling their facile, rapid and accurate detection and quantification using sub-picomoles of sample. The ability to count individual molecules directly measures relative concentrations in complex mixtures without need for separation. Using a dsDNA ladder, we find a linear relationship between the number of bases per molecule and the associated imaging contrast for up to 1200 bp, enabling us to quantify dsDNA length with 4 bp accuracy. These results introduce mass photometry as an accurate and rapid single molecule method complementary to existing DNA characterisation techniques.
Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices
Authors: Sadjadi Z. , Zhao R. , Hoth M. , Qu B. , Rieger H.
Published: January 2020

CD8+cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (= target cells). To find their targets they have to navigate and migrate through a complex biological microenvironments, a key component of which is the extracellular matrix (ECM). The mechanisms underlying killer cell’s navigation are not well understood. To mimic an ECM we use a matrix formed by different collagen concentrations, and analyze migration trajectories of primary human CTLs. Different migration patterns are observed and can be grouped into three motility types: slow, fast and mixed. The dynamics are well described by a two-state persistent random walk model which allows cells to switch between slow motion with low persistence, and fast motion with high persistence. We hypothesize that the slow motility mode describes CTLs creating channels through the collagen matrix by deforming and tearing apart collagen fibers, and that the fast motility mode describes CTLs moving within these channels. Experimental evidence supporting this scenario is presented by visualizing migrating T cells following each other on exactly the same track and showing cells moving quickly in channel-like cavities within the surrounding collagen matrix. Consequently, the efficiency of the stochastic search process of CTLs in the ECM should strongly be influenced by a dynamically changing channel network produced by the killer cells themselves.
Crystal structures of two very similar 2 × 2 × 2 superstructures of γ-brass-related phases in ternary Ir–Cd–Cu system
Authors: Ghanta Sivaprasad , Roy Nilanjan , Jana Partha Pratim
Published: January 2020

A binary phase Ir8Cd41in the Ir–Cd binary system and novel ternary phases in the Ir–Cd–Cu system have been synthesized from the constituent elements using high-temperature solid-state synthesis. The structure of previously reported Ir8Cd41and newly found ternary phases in the Ir–Cd–Cu system have been characterized by single crystal X-ray diffraction and EDS analysis. The structural analysis reveals that Ir8Cd41adopts V8Ga41-type structure and ternary Ir–Cd–Cu phases adopt two 2 × 2 × 2-superstructures of the γ-brass-related phase. The structures of ternary Ir–Cd–Cu phases are associated with structural disorder (vacancies as well as mixed site occupancies). The crystal structures of the ternary phases are viewed using layer description and cluster concept. The 2 × 2 × 2-superstructure of γ-brass-related phases in the Cu-poor region are not isostructural with the phases in the Cu-rich region, and they are consistent with the absence of a continuous phase region between two 2 × 2 × 2-superstructures of γ-brass-related phases. In the Cu-poor region, the structures contain ∼404 atoms per unit cell, whereas in the Cu-rich phases the structures contain ∼411 atoms in their respective unit cells. The crystal structures in the Cu-poor region represent a new type in the 2 × 2 × 2-superstructure of γ-brass-related phases in view of the combination of constituent cluster types, whereas the structures in the Cu-rich region adopt the Rh7Mg44structure type.
When do customer orientation and innovation capabilities matter? An investigation of contextual impacts
Authors: Racela Olimpia C. , Thoumrungroje Amonrat
Published: January 2020

Purpose

Grounded on resource-advantage (R-A) theory, the purpose of this paper is to investigate how customer orientation, as a higher-order or interconnected operant resource, enhances firm performance through creativity capability (i.e. idea generation and problem solving) and innovation capability (i.e. the implementation of creative ideas) – among firms of different sizes and within different market contexts. The authors conceptualize customer orientation as a firm’s capacity to create and deliver superior customer value through the processing of market intelligence, as demonstrated by the firm’s composite operant resources of market-sensing, customer-relating and customer-response capabilities.

Design/methodology/approach

Data were collected via qualitative in-depth interviews for scale development followed by a mail questionnaire survey for quantitative responses. A final sample size of 190 firms based in Thailand participated and the data were analyzed using structural equation modeling and bootstrapping multi-group comparisons to investigate the hypothesized mediation and moderation effects.

Findings

Customer orientation enhances organizational creativity and innovation capabilities, which improve firm revenue and financial performance. The relationships among customer orientation, creativity capability, innovation capability and firm performance vary depending on firm size, market dynamism and customer type.

Practical implications

Managers need to consider contextual factors, particularly firm size, market dynamism and the nature of their buyer markets as key contingencies in their resource deployment decisions intended to develop customer orientation and innovation capabilities.

Originality/value

This study advocates R-A theory by empirically revealing how different hierarchical resources within a firm are intertwined to provide firms with competitive R-A. The findings further highlight a contingent nature of customer orientation–innovation–performance relationships among firms in an emerging economy.
Rethinking the effect of floods and financial development on economic growth
Authors: Parida Yashobanta , Prasad Dash Devi
Published: January 2020

Purpose

The purpose of this paper is to evaluate the effect of floods and the role of financial development on per capita gross state domestic product (GSDP) growth, controlling for growth-enhancing factors across Indian states.

Design/methodology/approach

The paper uses the pooled mean group (PMG) method using state-level panel data for 19 Indian states over the period 1981-2011.

Findings

The PMG estimate shows that floods negatively affect the per capita GSDP growth in the long run. The results show that the mean of economic losses, the population affected and the area affected by floods increase by 10 per cent, leading to a decline in per capita GSDP growth by 0.0303, 0.0633 and 0.0232 per cent, respectively, in the long run. Furthermore, the population affected by floods exerts a higher adverse impact on the per capita GSDP growth compared to other flood measures. The results further show that states with better financial development experience a higher per capita GSDP growth, supported by additional capital expenditure, enrolment in higher education, better road infrastructure and higher urbanization. The crime rate is negatively correlated with per capita GSDP growth.

Originality/value

The results based on PMG estimates suggest that not only floods but also crime activities adversely affect the per capita GSDP growth across Indian states. Better financial market increases the per capita GSDP growth in the long run. This study not only contributes to empirical growth literature but also provides some useful policy suggestions. Moreover, the results lead to the conclusion that long-term flood management policies are essential to mitigate the adverse impact of floods on per capita GSDP growth across Indian states.
Risk of natural hazards and the coping capacity of the South African community in Auckland
Authors: Odiase Osamuede , Wilkinson Suzanne , Neef Andreas
Published: January 2020

Purpose

The risks of natural hazards such as flooding, earthquakes, tsunami, landslides, tornado, coastal erosion and volcano are apparent in Auckland because of its vulnerability to multiple risks. The coping capacity of individuals serves as a precursor to the adaptation to inherent challenges. The purpose of this paper was to examine the coping capacity of the South African community in Auckland to a disaster event.

Design/methodology/approach

This study gathered information from both primary and secondary sources. Interviews and survey were the main sources of primary data. The research used parametric and non-parametric statistical tools for quantitative data analysis, and the general inductive process and a three-step coding process to analyse qualitative data. The research findings are discussed in line with existing studies.

Findings

The results indicated that the aggregate coping capacity of the community was above average on the scale of 1-5 with communication and economic domains having the highest and least capacities, respectively. An improvement in disaster response activities and economic ability among the vulnerable population should be considered in future policy to enhance coping capacity.

Research limitations/implications

The study was limited to the time of the investigation. The practical coping capacity of the community during challenges will be determined. This study excludes the roles of institutions and the natural environment in coping capacity because the unit of analysis was the individual members of the community.

Originality/value

The research is a pioneer study on the coping capacity of the South African community in Auckland.
Where are fossil fuels prices heading?
Authors: Rostan Pierre , Rostan Alexandra
Published: January 2020

Purpose

The purpose of this paper is to present forecasts of fossil fuels prices until 2030 with spectral analysis to provide a clearer picture of this energy sector.

Design/methodology/approach

Fossil fuels prices time series are decomposed in simpler signals called approximations and details in the framework of the one-dimensional discrete wavelet analysis. The simplified signals are recomposed after Burg extension.

Findings

In 2019-2030 average price forecasts of: West Texas intermediate (WTI) oil ($58.67) is above its 1986-2030 long-term mean of $47.83; and coal ($81.01) is above its 1980-2030 long-term mean of $60.98. On the contrary, 2019-2030 average of price forecasts of: Henry Hub natural gas ($3.66) is below its 1997-2030 long-term mean of $4; heating oil ($0.64) is below its 1986-2030 long-term mean of $1.16; propane ($0.26) is below its 1992-2030 long-term mean of $0.66; and regular gasoline ($1.45) is below its 2003-2030 long-term mean of $1.87.

Originality/value

Fossil fuels prices projections may relieve participants of WTI oil and coal markets but worry participants of Henry Hub, heating oil, propane and regular gasoline markets including countries whose economy is tied to energy prices.
Effect of education–occupation mismatch on happiness
Authors: Chen Naiwei , Chen Ho-Chyuan , Lin Shih-Yu
Published: January 2020

Purpose

Prior research mostly focuses on the effect of over-education on happiness, whereas the effect of under-education on happiness has received minimal attention. In addition, no research to date has examined the effect of both over- and under-education on happiness by using a full spectrum of workers. Thus, the purpose of this paper is to fill this research gap.

Design/methodology/approach

The ordered probit model is estimated to examine the effect of the education–occupation mismatch on happiness based on 2012 survey data from Taiwan.

Findings

The results generally indicate that over-education positively affects happiness, whereas under-education has a minimal effect. The effect of the education–occupation mismatch on happiness also varies with different age groups. Specifically, over-education positively affects happiness except for workers aged 42 and above, whereas negative effects of under-education are found only among workers aged between 32 and 42 when their social network is insufficiently extensive. Moreover, a worker’s social network as a non-pecuniary factor, rather than income as a pecuniary factor, is a major channel through which education enhances happiness.

Originality/value

Given the limited and mixed evidence on the relationship between over-education and happiness, this study contributes to the existing literature by examining whether and how the education–occupation mismatch (over- and under-education) affects the happiness of workers both directly and indirectly via pecuniary and non-pecuniary factors. The research issue remains unexplored to date. Addressing such a question should help explain the persistent trend in pursuing higher education in Taiwan, although highly educated people may suffer from unemployment and an education–occupation mismatch.

Peer review

The peer review history for this paper is available at: https://publons.com/publon/10.1108/IJSE-04-2019-0283
Business improvement districts in the UK: a review and synthesis
Authors: Grail Julie , Mitton Catherine , Ntounis Nikos , Parker Cathy , Quin Simon , Steadman Chloe , Warnaby Gary , Cotterill Emily , Smith Diane
Published: January 2020

Purpose

The purpose of this paper is to review the development and current position of Business Improvement Districts (BIDs) in the UK, drawing on the content within a State-of-the-Art Review of Business Improvement Districts in the UK: setting the agenda for policy, practice and research, commissioned by The BID Foundation and produced by members of the Institute of Place Management.

Design/methodology/approach

The paper is divided into seven main sections. The first section defines the concept of BIDs, outlines their process of establishment and provides a brief critique of BIDs from the academic literature. Second, the process of introducing BIDs into the UK is discussed. Third, the different types of BIDs that currently exist are detailed. The fourth section outlines the development of BIDs since their introduction in 2004. Fifth, an analysis of BID ballots is provided, involving details of ballot results, demonstrating a general improvement as BIDs develop over time. The sixth section comprises a discussion of unsuccessful ballots and BID terminations. The paper concludes with a brief analysis of issues BIDs face in the UK, looking into the future.

Findings

The paper contains three main empirical contributions: first, a numerical analysis of the different types of BIDs in the UK; second, a timeline of their development from 2005 to 2018; and third, a statistical analysis of BID ballot results over this period, with an indication of the numbers of unsuccessful ballots and BID terminations.

Originality/value

This paper provides the first comprehensive overview of BIDs in the UK detailing development and performance (e.g. ballot results) in the 15 years since their introduction.
Positive aspects of disability among college students
Authors: Sniatecki Jessica L. , Ashton Jennifer Randhare , Perry Holly B. , Snell Linda H.
Published: January 2020

Purpose

The number of students with disabilities pursuing a college education has increased dramatically in recent years (Hall and Belch, 2000; Hitchings et al., 2011; Horn et al., 2006; Retish and Horvath, 2005; Snyder et al., 2016; Stodden et al., 2001), yet, evidence suggests that these students continue to encounter significant challenges and barriers that may have a dramatic effect on their college experience (Madaus and Shaw, 2006; Sniatecki et al., 2015; Stodden et al., 2001). The paper aims to discuss this issue.

Design/methodology/approach

Positive experiences and aspects of being a college student with a disability have not garnered as much consideration and have received little attention in the professional literature to date. The current study sought to address this gap through examination of positive aspects of disability among 12 undergraduate students. Data were gathered via qualitative interviews.

Findings

Results included five distinct themes related to students’ experiences: personal growth and self-acceptance; empathy/understanding; advocacy and teaching others; unique relationship experiences and opportunities; and drive/determination/perseverance.

Research limitations/implications

The implications of these themes and future directions for research on positive aspects of disability are also addressed.

Originality/value

The results of this study provide support for the social model of disability as a lens to view individuals with disabilities as complete people who, with their impairments, can and do go on to lead positive and meaningful lives.
Targeting the structural environment at multiple social levels for systemic change
Authors: Kemper Joya A. , Ballantine Paul W.
Published: January 2020

Purpose

This paper aims to explore how the socio-ecological model can be expanded to address wicked problems that are perpetuated by marketing systems through examining the ways the external environment can be targeted.

Design/methodology/approach

The authors used an extended socio-ecological model to provide a framework for social marketers to combat climate change through the food system in the external environment.

Findings

The socio-ecological model is extended to examine how social marketers can influence the micro and macro environment through targeting the physical structure, economic, political and socio-cultural environment of desirable (sustainable) and undesirable (unsustainable) food products.

Practical implications

The authors highlight that social marketers should focus on the various ways the external environment at multiple levels can be targeted to produce systemic change.

Originality/value

This paper broadens the current macro-social marketing knowledge by providing a framework to analyse where and how change can be affected at the various levels of society.
Direct texturing for additive manufacturing: software support and build tests
Authors: Armillotta Antonio
Published: January 2020

Purpose

This paper aims to investigate the feasibility of adding macro-textures to triangle meshes for additive manufacturing (AM) focusing on possible time and quality issues in both software processing and part fabrication.

Design/methodology/approach

A demonstrative software tool was developed to apply user-selected textures to existing meshes. The computational procedure is a three-dimensional extension of the solid texturing method used in computer graphics. The tool was tested for speed and quality of results, considering also the pre- and post-processing operations required. Some textured meshes were printed by different processes to test build speed and quality.

Findings

The tool can handle models with realistic complexity in acceptable computation times. Parts are built without difficulties or extra-costs achieving a good aesthetic yield of the texture.

Research limitations/implications

The tool cannot reproduce sample patterns but requires the development of a generation algorithm for different type of textures. Mesh processing operations may take a long time when very fine textures are added to large parts.

Practical implications

Direct texturing can help obtain parts with aesthetic or functional textures without the need for surface post-treatments, which can be especially difficult and expensive for plastic parts.

Originality/value

The proposed method improves the uniformity and consistency of textures compared to existing approaches, and can support future systematic studies on the detail resolution of AM processes.
Large-format fused deposition additive manufacturing: a review
Authors: Moreno Nieto Daniel , Molina Sergio I.
Published: January 2020

Purpose

The build volumes of additive manufacturing (AM) technologies are increasing in size. This improvement is associated with the growing reliability of AM processes and is driven by a rise in demand from several industries. Large-format additive manufacturing (LFAM), when referring to polymeric extrusion systems, is quite new in the field of AM. The purpose of this paper is to present a review of large-format (those with build volumes over 1 m3) fused deposition or extrusion-based AM equipment.

Design/methodology/approach

This paper presents an exhaustive literature review for all the publications in the field of AM in the current decade, as well as technological coverage in the news, specialized blogs and technology fairs since the year 2015.

Findings

This review reveals growing scientific and industrial activity, as well as in equipment, in the field of LFAM. An increase in research activity is also occurring in parallel with a growing interest, potential and adaptation of these technologies in certain industries.

Originality/value

This review may be the first publication to collect the majority of existing information on LFAM for polymeric extrusion systems in terms of applied extrusion technologies, commercial products, specific material research and developments, intellectual property, design and simulation solutions, as well as its practical applications.