bluuebunny/crossref_metadata_2025_split huggingface dataset:
The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration
Authors: Jafar-nejad Paymaan , Powers Berit , Soriano Armand , Zhao Hien , Norris Daniel A. , Matson John , DeBrosse-Serra Beatrice , Watson Jamie , Narayanan Padmakumar , Mazur Curt , Kordasiewicz Holly , Swayze Eric E. , Rigo Frank 
Published: August 2020

ABSTRACTAntisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing the field to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal, and non-neuronal cells. Therefore, it is critically important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and robust activity throughout the CNS in neurons, oligodendrocytes, astrocytes, and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.
Injectable Myocardial Matrix Hydrogel Mitigates Negative Left Ventricular Remodeling in a Chronic Myocardial Infarction Model
Authors: Diaz Miranda D. , Tran Elaine , Wassenaar Jean W. , Spang Martin , Gaetani Roberto , Luo Colin G. , Braden Rebecca , Hill Ryan C. , Hansen Kirk C. , DeMaria Anthony N. , Christman Karen L. 
Published: August 2020

SummaryA first-in-man clinical study on a myocardial-derived decellularized extracellular matrix (ECM) hydrogel yielded evidence for potential efficacy in ischemic heart failure (HF) patients. However, little is understood about the mechanism of action in chronic myocardial infarction (MI). In this study we investigated efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a chronic model of MI. Assessment of cardiac function via magnetic resonance imaging (MRI) demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent worsening HF in a small animal chronic MI model through modulation of the immune response, downregulation of pathways involved in HF progression and fibrosis, and upregulation of genes important for cardiac muscle contraction.
Immunomodulatory Contribution of Mast Cells to the Regenerative Biomaterial Microenvironment
Authors: Wang Raymond M. , Mesfin Joshua M. , Ungerleider Jessica L. , Kawakami Yu , Kawakami Yuko , Kawakami Toshiaki , Christman Karen L. 
Published: August 2020

AbstractBioactive immunomodulatory biomaterials have shown promise for influencing the immune response to promote tissue repair and regeneration. Macrophages and T cells have been associated with this response; however, other immune cell types have been traditionally overlooked. In this study, we investigated the role of mast cells in the regulation of the immune response to decellularized biomaterial scaffolds using a subcutaneous implant model. In mast cell-deficient mice, there was dysregulation of the expected M1 to M2 macrophage transition typically induced by the biomaterial scaffold. Polarization progression deviated in a sex specific manner with an early transition to an M2 profile in female mice, while the male response was unable to properly transition past a pro-inflammatory M1 state. Both were reversed with adoptive mast cell transfer. Further investigation of the later stage immune response in male mice determined a greater sustained pro-inflammatory gene expression profile including the IL-1 cytokine family, IL-6, alarmins, and chemokines. These results highlight mast cells as another important cell type that influences the immune response to pro-regenerative biomaterials.
Hematopoietic stem cells fail to regenerate following inflammatory challenge
Authors: Bogeska Ruzhica , Kaschutnig Paul , Fawaz Malak , Mikecin Ana-Matea , Büchler-Schäff Marleen , Paffenholz Stella , Asada Noboru , Frauhammer Felix , Buettner Florian , Ball Melanie , Knoch Julia , Stäble Sina , Walter Dagmar , Petri Amelie , Carreño-Gonzalez Martha J. , Wagner Vinona , Brors Benedikt , Haas Simon , Lipka Daniel B. , Essers Marieke A.G. , Holland-Letz Tim , Mallm Jan-Philipp , Rippe Karsten , Frenette Paul S. , Rieger Michael A. , Milsom Michael D. 
Published: August 2020

AbstractHematopoietic stem cells (HSCs) are canonically defined by their capacity to maintain the HSC pool via self-renewal divisions. However, accumulating evidence suggests that HSC function is instead preserved by sustaining long-term quiescence. Here, we study the kinetics of HSC recovery in mice, following an inflammatory challenge that induces HSCs to exit dormancy. Repeated inflammatory challenge resulted in a progressive depletion of functional HSCs, with no sign of later recovery. Underlying this observation, label retention experiments demonstrated that self-renewal divisions were absent or extremely rare during challenge, as well as during any subsequent recovery period. While depletion of functional HSCs held no immediate consequences, young mice exposed to inflammatory challenge developed blood and bone marrow hypocellularity in old age, similar to elderly humans. The progressive, irreversible attrition of HSC function demonstrates that discreet instances of inflammatory stress can have an irreversible and therefore cumulative impact on HSC function, even when separated by several months. These findings have important implications for our understanding of the role of inflammation as a mediator of dysfunctional tissue maintenance and regeneration during ageing.
Tyrosine phosphorylation-dependent localization of TmaR, a novelE. colipolar protein that controls activity of the major sugar regulator by polar sequestration
Authors: Szoke Tamar , Albocher Nitsan , Govindarajan Sutharsan , Nussbaum-Shochat Anat , Amster-Choder Orna 
Published: August 2020

ABSTRACTThe poles ofE. colicells are emerging as hubs for major sensory systems, but the polar determinants that allocate their components to the pole are largely unknown. Here, we describe the discovery of a novel protein, TmaR, which localizes to theE. colicell pole when phosphorylated on a tyrosine residue. TmaR is shown here to control the subcellular localization of the general PTS protein Enzyme I (EI) by preventing it from exerting its activity by binding and polar sequestration, thus regulating sugar uptake and metabolism. Depletion or overexpression of TmaR results in EI release from the pole or enhanced recruitment to the pole, which leads to increasing or decreasing the rate of sugar consumption, respectively. Notably phosphorylation of TmaR is required to release EI and enable its activity. Like TmaR, the ability of EI to be recruited to the pole depends on phosphorylation of one of its tyrosines. In addition to hyperactivity in sugar consumption, the absence of TmaR also leads to detrimental effects on the ability of cells to survive in mild acidic conditions. Our results argue that this survival defect, which is sugar- and EI-dependent, reflects the difficulty of cells lacking TmaR to enter stationary phase. Our study identifies TmaR as the firstE. coliprotein reported to localize in a tyrosine-dependent manner and to control the activity of other proteins by their polar sequestration and release.SIGNIFICANCEIn recent years, we have learnt that bacterial cells have intricate spatial organization despite the lack of membrane-bounded organelles. The endcaps of rod-shaped bacteria, termed poles, are emerging as hubs for sensing and responding, but the underlying mechanisms for positioning macromolecules there are largely unknown. We discovered a novel protein, TmaR, whose polar localization depends on a phospho-tyrosine modification. We show that TmaR controls the activity of EI, the major regulator of sugar metabolism in most bacteria, by polar sequestration and release. Notably, TmaR is essential for survival in conditions thatE. colioften encounters in nature. Hence, TmaR is a key regulator that connects tyrosine phosphorylation, spatial regulation, sugar metabolism and survival in bacteria and the first protein reported to recruit proteins to theE. colicell poles.
Expansion Segments in Bacterial and Archaeal 5S Ribosomal RNAs
Authors: Stepanov Victor G. , Fox George E. 
Published: August 2020

ABSTRACTThe large ribosomal RNAs of eukaryotes frequently contain expansion sequences that add to the size of the rRNAs but do not affect their overall structural layout and are compatible with major ribosomal function as an mRNA translation machine. The expansion of prokaryotic ribosomal RNAs is much less explored. In order to obtain more insight into the structural variability of these conserved molecules, we herein report the results of a comprehensive search for the expansion sequences in prokaryotic 5S rRNAs. Overall, 89 expanded 5S rRNAs of 15 structural types were identified in 15 archaeal and 36 bacterial genomes. Expansion segments ranging in length from 13 to 109 residues were found to be distributed among 17 insertion sites. The strains harboring the expanded 5S rRNAs belong to the bacterial ordersClostridiales,Halanaerobiales,Thermoanaerobacterales, andAlteromonadalesas well as the archael orderHalobacterales. When several copies of 5S rRNA gene are present in a genome, the expanded versions may co-exist with normal 5S rRNA genes. The insertion sequences are typically capable of forming extended helices, which do not seemingly interfere with folding of the conserved core. The expanded 5S rRNAs have largely been overlooked in 5S rRNA databases.
Emergence of Non-Linear Mixed Selectivity in Prefrontal Cortex after Training
Authors: Dang Wenhao , Jaffe Russell J. , Qi Xue-Lian , Constantinidis Christos 
Published: August 2020

ABSTRACTNeurons in the prefrontal cortex (PFC) are typically activated by different cognitive tasks, and also by different stimuli and abstract variables within these tasks. A single neuron’s selectivity for a given stimulus dimension often changes depending on its context, a phenomenon known as nonlinear mixed selectivity (NMS). It has previously been hypothesized that NMS emerges as a result of training to perform tasks in different contexts. We tested this hypothesis directly by examining the neuronal responses of different PFC areas before and after monkeys were trained to perform different working memory tasks involving visual stimulus locations and/or shapes. We found that training induces a modest increase in the proportion of PFC neurons with NMS exclusively for spatial working memory, but not shape working memory tasks, with area 9/46 undergoing the most significant increase in NMS cell proportion. We also found that increased working memory task complexity, in the form of simultaneously storing location and shape combinations, does not increase the degree of NMS for stimulus shape with other task variables. Lastly, in contrast to the previous studies, we did not find evidence that NMS is predictive of task performance. Our results thus provide critical insights on the representation of stimuli and task information in neuronal populations, which may pave the way to a greater understanding of neural selectivity in working memory.SIGNIFICANCE STATEMENTHow multiple types of information are represented in working memory remains a complex computational problem. It has been hypothesized that nonlinear mixed selectivity allows neurons to efficiently encode multiple stimuli in different contexts, after subjects have been trained in complex tasks. Our analysis of prefrontal recordings obtained before and after training monkeys to perform working memory tasks only partially agreed with this prediction, in that nonlinear mixed selectivity emerged for spatial but not shape information, and mostly in mid-dorsal PFC. Nonlinear mixed selectivity also displayed little modulation across either task complexity or correct performance. These results point to other mechanisms, in addition to nonlinear mixed selectivity, to represent complex information about stimulus and context in neuronal activity.
Operational matrix of two dimensional Chebyshev wavelets and its applications in solving nonlinear partial integro-differential equations
Authors: Rostami Yaser 
Published: August 2020

Purpose
This paper aims to present a new method for the approximate solution of two-dimensional nonlinear Volterra–Fredholm partial integro-differential equations with boundary conditions using two-dimensional Chebyshev wavelets.

Design/methodology/approach
For this purpose, an operational matrix of product and integration of the cross-product and differentiation are introduced that essentially of Chebyshev wavelets. The use of these operational matrices simplifies considerably the structure of the computation used for a set of the algebraic system has been obtained by using the collocation points and solved.

Findings
Theorem for convergence analysis and some illustrative examples of using the presented method to show the validity, efficiency, high accuracy and applicability of the proposed technique. Some figures are plotted to demonstrate the error analysis of the proposed scheme.

Originality/value
This paper uses operational matrices of two-dimensional Chebyshev wavelets and helps to obtain high accuracy of the method.
Study on the integration effect of multiple vehicles’ delayed velocities on traffic stability in intelligent transportation system environment
Authors: Zhang Geng , Ma Qinglu , Pan Dongbo , Zhang Yu , Huang Qiaoli , Jiang Shan 
Published: August 2020

Purpose
In an intelligent transportation system (for short, ITS) environment, a vehicle’s motion is affected by the information in a large scale. The purpose of this paper is to study the integration effect of multiple vehicles’ delayed velocities on traffic flow.

Design/methodology/approach
This paper constructed a new car-following model to study the integration effect of multiple vehicles’ delayed velocities on traffic flow. The new model is analyzed by linear and nonlinear perturbation method theoretically and also verified by simulation.

Findings
It is found out that the integration of preceding vehicles’ delayed velocities affect the stability of traffic flow importantly, and three preceding vehicles’ delayed velocities information should be considered in real traffic.

Originality/value
The new car-following model by considering the integration effect of multiple vehicles’ delayed velocities is firstly proposed in this paper. The research result shows that three preceding vehicles’ delayed velocities information is the best choice to stabilizing traffic flow.
Application of a novel grey forecasting model with time power term to predict China's GDP
Authors: Liu Chong , Xie Wanli , Lao Tongfei , Yao Yu-ting , Zhang Jun 
Published: August 2020

PurposeGross domestic product (GDP) is an important indicator to measure a country's economic development. If the future development trend of a country's GDP can be accurately predicted, it will have a positive effect on the formulation and implementation of the country's future economic development policies. In order to explore the future development trend of China's GDP, the purpose of this paper is to establish a new grey forecasting model with time power term to forecast GDP.Design/methodology/approachFirstly, the shortcomings of the traditional grey prediction model with time power term are found out through analysis, and then the generalized grey prediction model with time power term is established (abbreviated as PTGM (1,1, α) model). Secondly, the PTGM (1,1, α) model is improved by linear interpolation method, and the optimized PTGM (1,1, α) model is established (abbreviated as OPTGM (1,1, α) model), and the parameters of the OPTGM (1,1, α) model are solved by the quantum genetic algorithm. Thirdly, the advantage of the OPTGM (1,1, α) model over the traditional grey models is illustrated by two real cases. Finally the OPTGM (1,1, α) model is used to predict China's GDP from 2020 to 2029.FindingsThe OPTGM (1,1, α) model is more suitable for predicting China's GDP than other grey prediction models.Originality/valueA new grey prediction model with time power term is proposed.
Moment of dialogic leadership in Finnish IT organisation
Authors: Lemmetty Soila , Collin Kaija 
Published: August 2020

Purpose
The purpose of this study is to describe the construction of leadership through authentic dialogues at work and leaders’ actions as contributors to dialogic leadership.

Design/methodology/approach
The authors collected the data by recording the organisation’s meetings and discussions and used content analysis of dialogic leadership and typifying of critical moments as analytical methods.

Findings
On the basis of the findings, this paper suggests that dialogic leadership begins with a startup critical moment and progresses through the different positions by manager and employees through democratic interaction. Individual and collective level learning of participants and the formation of new knowledge were used in decision- or conclusion-making. The manager promoted the construction of dialogic leadership in conversation by creating important critical moments, which enabled a dialogue to start or contributed to already ongoing dialogue.

Originality/value
The study proposes concrete actions that can be applied in working life. This study provides a new understanding of the leader’s activities in promoting dialogue.
Reducing the resource acquisition costs for returnee entrepreneurs: role of Chinese national science parks
Authors: Xia Senmao , Xiong Yu , Zhang Min , Cornford James , Liu Yipeng , Lim Ming K. , Cao Dongmei , Chen Fengwen 
Published: August 2020

PurposeThe purpose of this paper is to empirically explore the mechanisms through which Chinese National Science Parks' (NSPs) services facilitate returnee entrepreneurs' (REs) acquisition of resources for their new ventures. Resource acquisition is crucial for new ventures, but it inevitably leads to significant costs increase. Although the NSPs offer various services to REs to reduce these costs, they still struggle to find the right mix of services.Design/methodology/approachFrom the transaction cost's perspective, an exploratory multiple-case study was conducted with data collected from six NSPs in China.FindingsThe results reveal that four types of NSP services (mentoring and training, social event, promotion of REs and accreditation of resource holders (RHs)) have both individual and joint effects on reducing REs' resource acquisition costs. Specifically, the “accreditation of RHs” service directly helps REs reduce search costs. The combination of “accreditation of RHs”, “promotion of REs” and “social event” services help REs and RHs to establish guanxi. Further, guanxi, working along with the “mentoring and training” service, helps REs to reduce contracting, monitoring and enforcement costs.Originality/valueThis study is among the first to explore the matching mechanisms between science parks’ services and entrepreneurs' cost reduction. This helps reconcile the inconsistent findings on science parks' effect by explaining why some NSPs are able to provide strong support to REs while others are less successful. In addition, the findings are useful for NSPs to develop the right mix of tailored services for REs. Finally, REs will find this study useful to evaluate which NSP is a more suitable location for their new ventures.
Muḍārabah and mushārakah as micro-equity finance: perception of Selangor’s disadvantaged women entrepreneurs
Authors: Islam Reazul , Ahmad Rubi 
Published: August 2020

Purpose
This study aims to gain the perception of Selangor’s disadvantaged women on the Sharīʿah (Islamic law) rules on two micro-equity financing instruments, namely, muḍārabah (profit sharing) and mushārakah (profit-and-loss sharing) (M&M).

Design/methodology/approach
A survey was carried out in the rural area of Selangor district in Malaysia by administering a self-generated structured questionnaire. A total of 330 completed questionnaires were retrieved from the members of an Islamic microfinance institution (IsMFI), namely, Amanah Ikhtiar Malaysia (AIM). The data were analysed by using structural equation modelling.

Findings
The female borrowers of AIM perceive the Sharīʿah rules of M&M requiring high moral and ethical values and diligent repayment performance. They are aware of some other underlying provisions such as business liquidation, share transfer, information discloser and business termination. The overall findings of this study suggest that the perceived Sharīʿah rules are akin to those that are commonly used in general partnership businesses between Muslims. It also indicates that disadvantaged entrepreneurs would accept the rules that are easy to comprehend as well as favourable to their interests. It further suggests that respondents’ experiences of microfinance and business operation do not have a significant influence on their perception of M&M instruments.

Research limitations/implications
This study was limited to Selangor. So, the perception of Muslim women surveyed may not represent the views of all women in Malaysia. However, it can offer a primary understanding of the said issue.

Practical implications
The findings of this study can help IsMIFs take initiatives to offer M&M as micro-equity finance to poor women entrepreneurs.

Originality/value
So far, limited studies have been carried out on M&M-based microfinancing. This paper offers new insights presenting disadvantaged women entrepreneurs’ perception of these financing instruments.
Perspectives on smokefree prison policy among people in custody in Scotland
Authors: Brown Ashley , Eadie Douglas , Purves Richard , Mohan Andrea , Hunt Kate 
Published: August 2020

Purpose
This paper aims to explore smokefree prison policy, from the perspective of people in custody in Scotland.

Design/methodology/approach
In total, 77 people in custody in Scotland were interviewed in the period leading up to implementation of a nationwide prison smokefree policy. Data were thematically analysed to identify the diversity of views and experiences.

Findings
Participants described a widespread awareness in prisons of plans to implement a smokefree policy from 30 November 2018. Opinions about smokefree prisons varied among participants based on perceptions of the fairness, and anticipated positive and negative consequences of removing tobacco from prisons. At the time of the interviews, people in custody were responding to the impending smokefree policy, either by proactively preparing for the smokefree rule change or by deploying avoidance strategies. Participants described opportunities and challenges for implementing smokefree policy in prisons across three main themes: the role of smoking in prison, prison smoking cessation services and motivations for quitting smoking among people in custody.

Originality/value
This study exploring smokefree prisons from the perspectives of people in custody has several novel features which extend the evidence base. The findings highlight measures for jurisdictions to consider when planning to prohibit smoking in their prisons in the future. These include the need for evidence-based smoking cessation support in advance of smokefree policy, effective communication campaigns, consideration of broader structural determinants of health in prison and ongoing measures to reduce rates of return to smoking post release.