bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontoparietal action-oriented codes support novel instruction implementation
Authors: González-García Carlos , Formica Silvia , Wisniewski David , Brass Marcel 
Published: November 2019

AbstractA key aspect of human cognitive flexibility concerns the ability to convert complex symbolic instructions into novel behaviors. Previous research proposes that this transformation is supported by two neurocognitive states: an initial declarative maintenance of task knowledge, and an implementation state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this process. However, whether declarative and procedural signals independently contribute to implementation remains unknown. We report the results of an fMRI experiment in which participants executed novel instructed stimulus-response associations. We then used a pattern-tracking procedure to quantify the contribution of format-unique signals during instruction implementation. This revealed independent procedural and declarative representations of novel S-Rs in frontoparietal areas, prior to execution. Critically, the degree of procedural activation predicted subsequent behavioral performance. Altogether, our results suggest an important contribution of frontoparietal regions to the neural architecture that regulates cognitive flexibility.
Molecular Screening of Hemoglobin S Variant in Anemia Patients of Eastern UP Population
Authors: Rai Vandana , Yadav Upendra , Kumar Pradeep 
Published: November 2019

AbstractHemoglobinopathies are the most common type of inherited disease in human. in India the most frequent and clinically significant hemoglobin structural variants are HbS, HbD and HbE. The HbS mutation, in which a glutamic acid at position 6 in the β chain is substituted for valine Sickle cell disease is a major health problem in some parts of India. 2 ml blood sample was collected from 350 anemia patient and PCR-RFLP method was used for hemoglobin S analysis. Out of 350 samples, in four individuals, HbS mutation was found in homozygous (β 6/β 6) condition. All four individuals are Sickle cell cases. In conclusion, the percentage of Sickle cell disease was observed as 1.14% in Eastern UP anemic patients.
ProSPr: Democratized Implementation of Alphafold Protein Distance Prediction Network
Authors: Billings Wendy M , Hedelius Bryce , Millecam Todd , Wingate David , Corte Dennis Della 
Published: November 2019

AbstractDeep neural networks have recently enabled spectacular progress in predicting protein structures, as demonstrated by DeepMin’s winning entry with Alphalfold at the latest Critical Assessment, of Structure Prediction competition (CASP13). The best protein prediction pipeline leverages intermolecular distance predictions to assemble a final protein model, but this distance prediction network has not been published. Here, we make a trained implementation of this network available to the broader scientific community. We also benchmark its predictive power in the related task of contact prediction against the CASP13 contact prediction winner TripletRes. Access to ProSPr will enable other labs to build on best in class protein distance predictions and to engineer superior protein reconstruction methods.
Mul1 suppresses Nlrp3 inflammasome activation through ubiquitination and degradation of Asc
Authors: Kim June-Hyung , Lee Yunjong , Suh Gee Young , Lee Yun-Song 
Published: November 2019

AbstractActivation of the Nlrp3 inflammasome consisting of three major components, Nlrp3, Asc, and pro-caspase-1, results in the activation of caspase-1 and subsequent proteolytic cleavage of pro-IL-1β and pro-IL-18. To avoid excessive inflammatory response, the Nlrp3 inflammasome has to be precisely controlled. In this study, we show that the mouse mitochondrial E3 ubiquitin protein ligase (Mul1) suppresses Nlrp3 inflammasome activation through ubiquitination and degradation of Asc. In J774A.1 cells, Mul1 overexpression attenuated Nlrp3 activation, whereas Mul1 knockdown augmented Nlrp3 activation in terms of IL-1β secretion and cleavage of pro-caspase-1 and pro-IL-1β. Mul1 interacted with Asc, and ubiquitinated it at K21, K22, K26, and K55 residues, in a K48-linked manner, leading to proteasomal degradation. Convincingly, Mul1-mediated suppression of Nlrp3 activation was inhibited by K21R-, K22R-, K26R-, K52R-Asc mutants in RAW264.7 cells, when compared with the wild-type Asc. Furthermore, Aim2 inflammasome activation was also inhibited by Mul1 in the wild-type Asc-, but not in mutant Asc-expressing RAW264.7 cells. Taken together, these data suggest that Mul1 suppresses Nlrp3 inflammasome activation, through Asc ubiquitination and degradation.
Genetic interaction between two unlinked loci underlies the loss of self-incompatibility inArabidopsis lyrata
Authors: Li Yan , van Kleunen Mark , Stift Marc 
Published: November 2019

AbstractAs the first step towards the evolution of selfing from obligate outcrossing, identifying the key mutations underlying the loss of self-incompatibility is of particular interest. However, our current knowledge is primarily based on sequence-based comparisons between selfing species and their self-incompatible relatives, which makes it hard to distinguish causal from secondary mutations. To by-pass this problem, we inferred the genetic basis of the loss of self-incompatibility by intercrossing plants from twelve geographically interspersed outcrossing and selfing populations of North-AmericanArabidopsis lyrataand determining the breeding system of 1,580 progeny. Self-incompatibility was not restored after crosses between different self-compatible populations. Equal frequencies of self-compatible and self-incompatible progeny emerged from crosses between parents with different breeding systems. We propose a two-locus genetic model for the loss of self-incompatibility in which specificS-locus haplotypes (S1andS19) are associated with loss of self-incompatibility through their interaction with an unlinked modifier.
A hidden integral structure endows Absolute Concentration Robust systems with resilience to dynamical concentration disturbances
Authors: Cappelletti Daniele , Gupta Ankit , Khammash Mustafa 
Published: November 2019

AbstractBiochemical systems that express certain chemical species of interest at the same level at any positive equilibrium are called “absolute concentration robust” (ACR). These species behave in a stable, predictable way, in the sense that their expression is robust with respect to sudden changes in the species concentration, regardless the new positive equilibrium reached by the system. Such a property has been proven to be fundamentally important in certain gene regulatory networks and signaling systems. In the present paper, we mathematically prove that a well-known class of ACR systems studied by Shinar and Feinberg in 2010 hides an internal integral structure. This structure confers these systems with a higher degree of robustness that what was previously unknown. In particular, disturbances much more general than sudden changes in the species concentrations can be rejected, and robust perfect adaptation is achieved. Significantly, we show that these properties are maintained when the system is interconnected with other chemical reaction networks. This key feature enables design of insulator devices that are able to buffer the loading effect from downstream systems - a crucial requirement for modular circuit design in synthetic biology.
Alpha-synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson’s disease
Authors: Cole Tracy A. , Zhao Hien , Collier Timothy J. , Sandoval Ivette , Sortwell Caryl E. , Steece-Collier Kathy , Daley Brian F. , Booms Alix , Lipton Jack , Welch Mackenzie , Berman Melissa , Jandreski Luke , Graham Danielle , Weihofen Andreas , Celano Stephanie , Schulz Emily , Cole-Strauss Allyson , Luna Esteban , Quach Duc , Mohan Apoorva , Bennett C. Frank , Swayze Eric E. , Kordasiewicz Holly B. , Luk Kelvin C. , Paumier Katrina L. 
Published: November 2019

AbstractParkinson’s disease (PD) is a prevalent neurodegenerative disease with no approved disease-modifying therapies. Multiplications, mutations, and single nucleotide polymorphisms in the SNCA gene, encoding alpha-synuclein protein (aSyn), either cause or increase risk for PD. Intracellular accumulations of aSyn are pathological hallmarks of PD. Taken together, reduction of aSyn production may provide a disease-modifying therapy for PD. We show that antisense oligonucleotides (ASOs) reduce production of aSyn in rodent pre-formed fibril (PFF) models of PD. Reduced aSyn production leads to prevention and removal of established aSyn pathology and prevents dopaminergic cell dysfunction. In addition, we address the translational potential of the approach through characterization of human SNCA targeting ASOs that efficiently suppress the human SNCA transcript in vivo. We demonstrate broad activity and distribution of the human SNCA ASOs throughout the non-human primate brain and a corresponding decrease in aSyn cerebral spinal fluid (CSF) levels. Taken together, these data suggest that by inhibiting production of aSyn it may be possible to reverse established pathology and thus supports the development of SNCA ASOs as a potentially disease modifying therapy for PD and related synucleinopathies.SummaryAntisense oligonucleotides designed against SNCA, which are progressing to the clinic, have the potential to be a disease modifying therapeutic for Parkinson’s disease patients.
Microfluidic Chip for Label-Free Removal of Teratoma-forming Cells from Therapeutic Human Stem Cells
Authors: Wellmerling Kyle , Lehmann Christian , Singh Ankur , Kirby Brian 
Published: November 2019

ABSTRACTTeratoma formation remains a safety concern in therapeutic cells derived from human-induced pluripotent stem cells (hiPSCs). Residual Teratoma forming cells are present in small numbers in differentiated hiPSC cultures and yet are of significant roadblock to the manufacturing and clinical translation of stem cell therapies. Rare cells are often difficult to remove with standard flow cytometry or magnetic bead sorting techniques. Here, we first characterized time-dependent expression of a teratoma marker, stage-specific embryonic antigen (SSEA)-5, which binds the H type-1 glycan during neural differentiation of hiPSCs. We engineered a microfluidic geometrically enhanced differential immunocapture (GEDI) technology to remove SSEA-5+ rare cells from hiPSC-derived neural progenitor cells (hiPSC-NPCs). The GEDI chip presents a facile tool to potentially functionalize with multiple antibodies and robustly enhance hiPSC-derived cell population safety prior to therapeutic transplantation. The approach is potentially amenable to generate a wide variety of high-quality therapeutic cells and can be integrated within the pipeline of cell manufacturing to improve patient safety and reduce the cost of manufacturing through early removal of undesirable cell types.
Functional connectivity between the cerebellum and somatosensory areas implements the attenuation of self-generated touch
Authors: Kilteni Konstantina , Ehrsson H. Henrik 
Published: November 2019

AbstractSince the early 1970s, numerous behavioral studies have shown that self-generated touch feels less intense than the same touch applied externally. Computational motor control theories have suggested that cerebellar internal models predict the somatosensory consequences of our movements and that these predictions attenuate the perception of the actual touch. Despite this influential theoretical framework, little is known about the neural basis of this predictive attenuation. This is due to the limited number of neuroimaging studies, the presence of conflicting results about the role and the location of cerebellar activity, and the lack of behavioral measures accompanying the neural findings. Here, we combined psychophysics with functional magnetic resonance imaging to detect the neural processes underlying somatosensory attenuation in male and female healthy human participants. Activity in bilateral secondary somatosensory areas was attenuated when the touch was presented during a self-generated movement (self-generated touch) than in the absence of movement (external touch). An additional attenuation effect was observed in the cerebellum that is ipsilateral to the passive limb receiving the touch. Importantly, we further found that the degree of functional connectivity between the ipsilateral cerebellum and the contralateral primary and bilateral secondary somatosensory areas was linearly and positively related to the degree of behaviorally assessed attenuation; that is, the more participants perceptually attenuated their self-generated touches, the stronger this corticocerebellar coupling. Collectively, these results suggest that the ipsilateral cerebellum is fundamental in predicting self-generated touch and that this structure implements somatosensory attenuation via its functional connectivity with somatosensory areas.Significance statementWhen we touch our hand with the other, the resulting sensation feels less intense than when another person or a machine touches our hand with the same intensity. Early computational motor control theories have proposed that the cerebellum predicts and cancels the sensory consequences of our movements; however, the neural correlates of this cancelation remain unknown. By means of functional magnetic resonance imaging, we show that the more participants attenuate the perception of their self-generated touch, the stronger the functional connectivity between the cerebellum and the somatosensory cortical areas. This provides conclusive evidence about the role of the cerebellum in predicting the sensory feedback of our movements and in attenuating the associated percepts via its connections to early somatosensory areas.
Regulation of islet function and gene expression by prolactin during pregnancy
Authors: Shrivastava Vipul , Lee Megan , Pretorius Marle , Makkar Guneet , Huang Carol 
Published: November 2019

AbstractPancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell proliferation and increase insulin secretion. Previously, we found that prolactin receptor (Prlr) signaling is important for this process, as heterozygous prolactin receptor-null (Prlr+/−) mice are glucose intolerant, had a lower number of β cells and lower serum insulin levels than wild type mice during pregnancy. However, since Prlr expression is ubiquitous, to determine its β-cell specific effects, we generated a transgenic mouse with a floxed Prlr allele under the control of an inducible promoter, allowing conditional deletion of Prlr from β cells in adult mice. In this study, we found that β-cell-specific Prlr reduction resulted in elevated blood glucose during pregnancy. Similar to our previous finding in mouse with global Prlr reduction, β-cell-specific Prlr loss led to a lower β-cell mass and a lower in vivo insulin level during pregnancy. However, these islets do not have an intrinsic insulin secretion defect when tested in vitro. Interestingly, when we compared the islet gene expression profile, using islets isolated from mice with global versus β-cell-specific Prlr reduction, we found some important differences in genes that regulate apoptosis and insulin secretion. This suggests that Prlr has both cell-autonomous and non-cell-autonomous effect on β cells, beyond its regulation of pro-proliferative genes.
HIV Envelope Trimer-Elicited Autologous Neutralizing Antibodies Bind a Region Overlapping the N332 Glycan Supersite
Authors: Nogal Bartek , McCoy Laura E. , van Gils Marit J. , Cottrell Christopher A. , Voss James E. , Andrabi Raiees , Pauthner Matthias , Liang Chi-Hui , Messmer Terrence , Nedellec Rebecca , Shin Mia , Turner Hannah L. , Ozorowski Gabriel , Sanders Rogier W. , Burton Dennis R. , Ward Andrew B. 
Published: November 2019

AbstractTo date, immunization studies of rabbits with the BG505 SOSIP.664 HIV envelope glycoprotein trimers have revealed the 241/289 glycan hole as the dominant neutralizing antibody epitope. Here, we isolated monoclonal antibodies from a rabbit that did not exhibit glycan hole-dependent autologous serum neutralization. The antibodies did not compete with a previously isolated glycan hole-specific antibody but did compete with N332 glycan supersite broadly neutralizing antibodies. A high resolution cryoEM structure of one of the antibodies in complex with the BG505 SOSIP.664 trimer demonstrated that, while the epitope recognized overlapped with the N332 glycan supersite by contacting the GDIR motif at the base of V3, the primary contacts were located in the variable V1 loop. These data suggest that strain-specific responses to V1 may interfere with broadly neutralizing responses to the N332 glycan supersite and vaccine immunogens may require engineering to minimize these off-target responses or steer them toward a more desirable pathway.
Applying uses and gratifications theory to understand customer participation in social media brand communities
Authors: Kamboj Shampy 
Published: November 2019

Purpose
The purpose of this paper is to investigate how various gratifications obtained in the social media context affect customer participation, and its sequential effect on brand trust, brand commitment and word of mouth (WOM) in social media brand communities.

Design/methodology/approach
The data were collected from 352 respondents who used social media using a survey method. The data were assessed using AMOS with structural equation modeling.

Findings
The findings depicted that among all gratifications obtained in the social media context, information seeking, incentive and brand likeability strongly affect customer participation, which sequentially affect brand trust, commitment and WOM in social media brand communities. In the context of social media brand communities, brand trust partially mediates the relationship between customer participation and its two outcome variables (brand commitment and WOM).

Originality/value
The present paper contributes that theory of uses and gratifications has particular significance and supposed to be provided further importance in the field of social media. It also presents a vivid and rich understanding of why customers use social media and participate in social media brand communities.
An Imbizo at the busy corner
Authors: Maphalala Jabu , Zwane Steven 
Published: November 2019

Learning outcomes
The learning outcomes provide insights into how organisations have emerged out of such changes in the external environment, additional complexities that female entrepreneurs have to navigate in patriarchal societies and complexities of handing over control of a family business by the founding generation takes.

Case overview/synopsis
This case is about Rita Zwane’s dilemma as she was about to hand over the management and leadership of Imbizo Shisanyama Restaurant to her son. As founder and Chairperson of the enterprise, Zwane founded the business over 20 years ago and had seen it grow from being housed in a customised shipping container to annually turning over millions of rands per year. Her dilemma was borne out of the belief that many family businesses collapsed after being taken over by the second generation. While Zwane grudgingly admitted that Senzo’s involvement in the business had increased turnover and efficiencies, she was reluctant to let go. This raises a question of whether her dilemma was not only her concern on Senzo’s management abilities but also her difficulty in letting go. The case is suitable for management and change leadership courses on a post graduate level where theories such as attachment theory could be taught to demonstrate that the problem is not always the new leadership in transitioning businesses from the founding generation to second generation of leaders. This is particularly for small and medium-sized enterprises where Imbizo Shisanyama Restaurant is situated. Imbizo Shisanyama Restaurant was founded in 1997 during a period when the abolition of many apartheid laws saw an unprecedented urbanisation process leading to the mushrooming of informal settlements. It is this mushrooming of informal settlements that enabled the establishment of Imbizo Shisanyama Restaurant. The case will provide some insights into opportunities that opened up for Zwane in this pivotal period.

Complexity academic level
Post Graduate Level

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 3: Entrepreneurship.
UCOOK: growth challenges faced by a small- to medium-sized South African venture
Authors: Bick Geoff , Odendaal Jeanné 
Published: November 2019

Learning outcomes
The learning outcomes are as follows: to understand how technology can be used to create innovative entrepreneurial opportunities; to develop analytical and critical thinking skills to understand organisations, industries and their dynamics; to analyse strategic options for an entrepreneurial organisations and motivate a proposed strategic direction; and to assess the inter-functional requirements for an entrepreneurship to successfully implement a strategy.

Case overview/synopsis
UCOOK, a successful emerging economy SME, is confronted with the threat of retail giants (e.g. Checkers and Woolworths) entering the meal kit space. No longer the only “new kid on the block”, UCOOK has to consider a sustainable growth strategy to remain competitive. The case provides the reader with a snapshot of experiences of a meal kit entrepreneurial venture and what it entails for them to grow in the South African milieu. Principally, this case is designed to impart knowledge and stimulate a practical understanding of entrepreneurship and strategic decision-making in the meal kit industry. Additionally, the purpose is to serve as inspiration for business students to see the opportunities that lie within strategically astute emerging market ventures.

Complexity academic level
The primary target audience for this teaching case is postgraduate business students, especially students of entrepreneurship, strategy and e-commerce. This teaching case is intended to be used as case study in post graduate business programmes such as Master of Business Administration (MBA), a specialist Masters programme such as MM (Entrepreneurship), post-graduate diploma in management (PGDip), as well as selected executive education programmes.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 3: Entrepreneurship.
Irreversibility in two-dimensional magneto-nanomaterial flow of Jeffrey fluid with Arrhenius activation energy
Authors: Ahmad Salman , Ijaz Khan Muhammad , Hayat Tasawar , Waqas Muhammad , Alsaedi Ahmed 
Published: November 2019

Purpose
The purpose of this paper is to study entropy generation in magneto-Jeffrey nanomaterial flow by impermeable moving boundary. Adopted nanomaterial model accounts Brownian and thermophoretic diffusions. Modeling is arranged for thermal radiation, nonlinear convection and viscous dissipation. In addition, the concept of Arrhenius activation energy associated with chemical reaction are introduced for description of mass transportation.

Design/methodology/approach
Homotopy algorithms are used to compute the system of ordinary differential equations.

Findings
The afore-stated analysis clearly notes that simultaneous aspects of activation energy and entropy generation are not yet investigated. Therefore, the intention here is to consider such effects to formulate and investigate the magneto-Jeffrey nanoliquid flow by impermeable moving surface.

Originality/value
As per the authors’ knowledge, no such work has yet been published in the literature.