bluuebunny/crossref_metadata_2025_split huggingface dataset:
ω-imidazolyl-alkyl derivatives as new preclinical drug candidates for NASH therapy
Authors: Diesinger Torsten , Lautwein Alfred , Buko Vyacheslav , Belonovskaya Elena , Lukivskaya Oksana , Naruta Elena , Kirko Siarhei , Andreev Viktor , Dvorsky Radovan , Buckert Dominik , Bergler Sebastian , Renz Christian , Müller-Enoch Dieter , Wirth Thomas , Haehner Thomas 
Published: June 2019

AbstractCytochrome P450 2E1 (CYP2E1) and its production of ROS play an essential role in the development and progression of inflammatory liver diseases such as alcoholic steatohepatitis. For this isoenzyme we have developed two new inhibitors - 12-imidazolyl-1-dodecanol (I-ol) and 1-imidazolyldodecane (I-an) - and wanted to test their effect on the related disease of non-alcoholic steatohepatitis (NASH). The fat-rich Lieber-DeCarli diet, which was administered over the entire experimental period of 16 weeks, was used for disease induction in the rat model, while the experimental substances were administered in parallel over the last four weeks. This high-calorie diet pathologically altered the ROS balance, the amount of adipocytokines, TNF-α and lipids as well as the activities of liver enzymes. Together with the histological examinations, the conclusion could be drawn that the diet led to the formation of NASH. I-ol and to a lesser extent I-an were able to shift the pathological values towards the normal range - despite continued administration of the noxious agent. I-ol, in particular, showed an extremely good tolerability in the acute toxicity study in rats. Thus, CYP2E1 appears to be a suitable drug target as well as I-ol and I-an promising drug candidates for the treatment of NASH.
SAPdb: A database of nanostructures formed by self-assembly of short peptides
Authors: Mathur Deepika , Kaur Harpreet , Dhall Anjali , Sharma Neelam , Raghava Gajendra P. S. 
Published: June 2019

AbstractBackgroundNanostructures generated by self-assembly of peptides yield nanomaterial that has many therapeutic applications, including drug delivery and biomedical engineering, due to their low cytotoxicity and higher uptake by targeted cells owing to their high affinity and specificity towards cell surface receptors. Despite the promising implications of this rapidly expanding field, there is no dedicated resource to study peptide nanostructures.ResultThis study endeavours to create a dedicated repository of short peptides, which may prove to be the best models to study ordered nanostructures formed by peptide self-assembly. SAPdb has a repertoire of 1,049 entries of experimentally validated nanostructures formed by the self-assembling of small peptides. It includes 701 entries are of dipeptides, 328 entries belong to tripeptides, and 20 entries of single amino acid with some conjugated partners. Each entry encompasses comprehensive information about the peptide such as chemical modifications in the peptide sequences, the type of nanostructure formed, and experimental conditions like pH, temperature, and solvent required for the self-assembly of the peptide, etc. Further, our analysis has shown that the occurrence of aromatic amino acids favours the formation of self-assembling nanostructures, as indicated by a large number of entries in SAPdb contain aromatics amino acids. Besides, we have observed that these peptides form different nanostructures under different experimental conditions. SAPdb provides this comprehensive information in a hassle-free tabulated manner at a glance. User-friendly browsing, searching, and analysis modules are integrated for easy retrieval and comparison of data and examination of properties. We anticipate SAPdb to be a valuable repository for researchers engaged in the burgeoning arena of nanobiotechnology.AvailabilityThe database can be accessed on the web at https://webs.iiitd.edu.in/raghava/sapdb.
Targeting the Administration of Ecdysterone in Doping Control Samples
Authors: Parr Maria Kristina , Ambrosio Gabriella , Wuest Bernhard , Mazzarino Monica , de la Torre Xavier , Sibilia Francesca , Joseph Jan Felix , Diel Patrick , Botrè Francesco 
Published: June 2019

AbstractPurposeThe phytosteroid ecdysterone was recently reported to enhance performance in sports and may thus be considered as a substance of relevance in anti-doping control. To trace back an administration of ecdysterone from urine samples analytical properties have been investigated to assess its integration into initial testing procedures (ITP) in doping control laboratories.MethodsAnalytical properties of ecdysterone were evaluated using GC-QTOF-MS and LC-QTOF-MS. Its metabolism and elimination in human were studied using urines collected after administration.ResultsThe detectability of ecdysterone by GC-MS (after derivatization) and/or LC-MS(/MS) has been demonstrated and sample preparation methods were evaluated. Dilute-and-inject for LC-MS(/MS) or SPE using Oasis HLB for GC-MS or LC-MS were found most suitable, while liquid-liquid extraction was hampered by the high polarity of ecdysteroids.Most abundantly, ecdysterone was detected in the post administration urines as parent compound besides the metabolite desoxy-ecdysterone. Additionally desoxy-poststerone was tentatively assigned as minor metabolite, however further investigations are needed.ConclusionAn administration of ecdysterone can be targeted using existing procedures of anti-doping laboratories. Ecdysterone and desoxy-ecdysterone appeared as suitable candidates for integration in ITP. Using dilute-and-inject a detection of the parent compound was possible for more than two days after the administration of a single dose of ~50 mg.
Long-term activity drives dendritic branch elaboration of a C. elegans sensory neuron
Authors: Cohn Jesse A , Cebul Elizabeth R , Valperga Giulio , de Bono Mario , Heiman Maxwell G , Pierce Jonathan T 
Published: June 2019

ABSTRACTNeuronal activity often leads to alterations in gene expression and cellular architecture. The nematode Caenorhabditis elegans, owing to its compact translucent nervous system, is a powerful system in which to study conserved aspects of the development and plasticity of neuronal morphology. Here we focus on one sensory neuron in the worm, termed URX, which senses oxygen and signals tonically proportional to environmental oxygen. Previous studies have reported that URX has variable branched endings at its dendritic sensory tip. By controlling oxygen levels and analyzing mutants, we found that these branched endings grow over time as a consequence of neuronal activity. Furthermore, we observed that the branches contain microtubules, but do not appear to harbor the guanylyl cyclase GCY-35, a central component of the oxygen sensory transduction pathway. Interestingly, we found that although URX dendritic tips grow branches in response to long-term activity, the degree of branch elaboration does not correlate with oxygen sensitivity at the cellular or the behavioral level. Given the strengths of C. elegans as a model organism, URX may serve as a potent system for uncovering genes and mechanisms involved in activity-dependent morphological changes in neurons.
Simple spike dynamics of Purkinje cells in the macaque vestibulo-cerebellum reflect sensory prediction error
Authors: Laurens Jean , Angelaki Dora E. 
Published: June 2019

AbstractTheories of cerebellar functions posit that the cerebellum implements forward models for online correction of motor actions and sensory estimation. As an example of such computations, a forward model compensates for a sensory ambiguity where the peripheral otolith organs in the inner ear sense both head tilts and translations. Here we exploit the response dynamics of two functionally-coupled Purkinje cell types in the caudal vermis to understand their role in this computation. We find that one population encodes tilt velocity, whereas the other, translation-selective, population encodes linear acceleration. Using a dynamical model, we further show that these signals likely represent sensory prediction error for the on-line updating of tilt and translation estimates. These properties also reveal the need for temporal integration between the tilt-selective velocity and translation-selective acceleration population signals. We show that a simple model incorporating a biologically plausible short time constant can mediate the required temporal integration.
Negligible-Cost and Weekend-Free Chemically Defined Human iPSC Culture
Authors: Kuo Hui-Hsuan , Gao Xiaozhi , DeKeyser Jean-Marc , Fetterman K. Ashley , Pinheiro Emily A. , Weddle Carly J. , Fonoudi Hananeh , Orman Michael V. , Romero-Tejeda Marisol , Jouni Mariam , Blancard Malorie , Magdy Tarek , Epting Conrad L. , George Alfred L. , Burridge Paul W. 
Published: June 2019

SummaryHuman induced pluripotent stem cell (hiPSC) culture has become routine, yet pluripotent cell media costs, frequent media changes, and reproducibility of differentiation have remained restrictive, limiting the potential for large-scale projects. Here, we describe the formulation of a novel hiPSC culture medium (B8) as a result of the exhaustive optimization of medium constituents and concentrations, establishing the necessity and relative contributions of each component to the pluripotent state and cell proliferation. B8 eliminates 97% of the costs of commercial media, made possible primarily by the in-lab generation of three E. coli-expressed, codon-optimized recombinant proteins: an engineered form of fibroblast growth factor 2 (FGF2) with improved thermostability (FGF2-G3); transforming growth factor β3 (TGFβ3) - a more potent TGFβ able to be expressed in E. coli; and a derivative of neuregulin 1 (NRG1) containing the EGF-like domain. The B8 formula is specifically optimized for fast growth and robustness at low seeding densities. We demonstrated the derivation and culture of 34 hiPSC lines in B8 as well as maintenance of pluripotency long-term (over 100 passages). This formula also allows a weekend-free feeding schedule without sacrificing growth rate or capacity for differentiation. Thus, this simple, cost-effective, and open source B8 media, will enable large hiPSC disease modeling projects such as those being performed in pharmacogenomics and large-scale cell production required for regenerative medicine.
Alcohol Increases Aggression in Flies
Authors: Park Annie , Tran Tracy , Scheuermann Elizabeth , Gutierrez Linda , Stojanik Christopher , Plyler Julian , Thompson Grace , Smith Dean , Atkinson Nigel S. 
Published: June 2019

AbstractAlcohol-induced aggression is a destructive and widespread phenomenon, but we understand very little about the mechanisms that produce this behavior. We found that two different alcohol exposures potentiate aggression in male flies. (1) A pharmacologically relevant dose of alcohol increases aggression and decreases a goal-directed behavior in male flies. (2) In addition, the odor of alcohol itself enhances intermale aggression by potentiating olfactory signaling by cis-vaccenyl acetate (cVa), a volatile male pheromone. Characterizing these behaviors in the genetically tractable fruit fly can lead to a better understanding of the molecular correlates that regulate alcohol-induced aggression in humans and provide insights into an ethologically relevant behavior.One Sentence SummaryWe identified two pathways through which alcohol stimulates intermale aggression in flies; one acts by potentiating a male olfactory pheromone while the other is mediated by the systemic effects of alcohol.
Discovery of influenza drug resistance mutations and host therapeutic targets using a human airway chip
Authors: Si Longlong , Prantil-Baun Rachelle , Benam Kambez H , Bai Haiqing , Rodas Melissa , Burt Morgan , Ingber Donald E. 
Published: June 2019

AbstractHere we demonstrate that influenza virus replication, host responses to infection, evolution through mutation or gene reassortment, and clinical efficacy of antiviral drugs can be reconstituted in a human Airway Chip microfluidic culture device. Modeling human-to-human transmission of infection in the continued presence of antiviral drugs on chips led to the emergence of clinically prevalent mutations responsible for amantadine- and oseltamivir-resistance, as well as the discovery of new resistance mutations. Analysis of infection responses resulted in identification of host therapeutic targets and demonstration that existing non-antiviral drugs may be repurposed to inhibit viral replication and synergize with antiviral therapeutics by targeting the host response to infection rather than the virus itself. This Influenza Chip may represent an alternative preclinical tool for development of new antiviral drugs and vaccines.One Sentence SummaryNew drug resistance mutations and potential tolerance-inducing therapeutics were discovered using an organ chip model of influenza infection.
Lis1 activates dynein motility by pairing it with dynactin
Authors: Elshenawy Mohamed M. , Kusakci Emre , Volz Sara , Baumbach Janina , Bullock Simon L. , Yildiz Ahmet 
Published: June 2019

AbstractLissencephaly-1 (Lis1) is a key cofactor for dynein-mediated intracellular transport towards the minus-ends of microtubules (MTs). It remains unclear whether Lis1 serves as an inhibitor or an activator of mammalian dynein motility. Here we use single-molecule imaging and optical trapping to show that Lis1 does not directly alter the stepping and force production of individual dynein motors assembled with dynactin and a cargo adaptor. Instead, Lis1 binding releases dynein from its auto-inhibited state and thereby promotes the formation of an active complex with dynactin. Lis1 also favors recruitment of two dyneins to dynactin, resulting in increased velocity, higher force production and more effective competition against kinesin in a tug-of-war. Lis1 dissociates from motile complexes, indicating that its primary role is to orchestrate the assembly of the transport machinery. These results provide a mechanistic explanation for why Lis1 is required for efficient transport of many dynein-associated cargoes in cells.
Holes in wrist patches improve wearing comfort
Authors: Klous Lisa , Bergmann Tiest Wouter , Dorst Pim van , van der Linde Matthijs , Daanen Hein 
Published: June 2019

Purpose
The purpose of this paper was to investigate whether small holes in an impermeable patch at the wrist improve perceived comfort during exercise.

Design/methodology/approach
Nine male participants participated in this study. During the experiment, participants cycled 60 W in a hot room (35°C, 30 percent relative humidity) while an impermeable 20 cm2 patch was located on the ventral side of one wrist and at the same time a patch of identical shape with 5 mm diameter holes (17.7 percent uncovered) on the other wrist. The participants could not see the patches. Participants were forced to choose which patch they perceived as more comfortable. Chest and arm skin temperature, thermal comfort, thermal sensation and wetness perception were assessed.

Findings
Participants preferred 5 mm holes over no holes (p=0.017). Chest skin temperature (p=0.018) but not arm skin temperature correlates with this preference. Thermal comfort, thermal sensation and wetness perception did not differ significantly between patches. It is concluded that patches with 5 mm holes are preferred over impermeable patches during work in the heat in particular when the torso skin is warm.

Originality/value
The wrist is a preferred location for smart wearables. Generally, wrist bands are made of air-impermeable materials leading to sensation of wetness and discomfort. This study has shown that manufacturers should consider to make small holes in their wrist bands to optimize wearing comfort.
Using Vertically Integrated Projects to embed research-based education for sustainable development in undergraduate curricula
Authors: Strachan Scott Munro , Marshall Stephen , Murray Paul , Coyle Edward J. , Sonnenberg-Klein Julia 
Published: June 2019

PurposeThis paper aims to share the University of Strathclyde’s experience of embedding research-based education for sustainable development (RBESD) within its undergraduate curricula through the use of an innovative pedagogy called Vertically Integrated Projects (VIP), originated at Georgia Institute of Technology.Design/methodology/approachThis paper discusses how aligning VIP with the SDG framework presents a powerful means of combining both research-based education (RBE) and education for sustainable development (ESD), and in effect embedding RBESD in undergraduate curricula.FindingsThe paper reports on the University of Strathclyde’s practice and experience of establishing their VIP for Sustainable Development programme and presents a reflective account of the challenges faced in the programme implementation and those envisaged as the programme scales up across a higher education institution (HEI).Research limitations/implicationsThe paper is a reflective account of the specific challenges encountered at Strathclyde to date after a successful pilot, which was limited in its scale. While it is anticipated these challenges may resonate with other HEIs, there will also be some bespoke challenges that may not be discussed here.Practical implicationsThis paper offers a practical and scalable method of integrating SDG research and research-based education within undergraduate curricula.Social implicationsThe paper has the potential to deliver SDG-related impact in target communities by linking research-based teaching and learning with community outreach.Originality/valueThe alignment of VIP with the SDG research area is novel, with no other FE institutions currently using this approach to embed SDG research-based teaching within their curricula. Furthermore, the interdisciplinary feature of the VIP programme, which is critical for SDG research, is a Strathclyde enhancement of the original model.
A fragility approach to sustainability – researching effects of education
Authors: Platje Joost (Johannes) , Will Markus , Van Dam Ynte K. 
Published: June 2019

Purpose
Management education trainers are increasingly called upon to train students to devise interventions for sustainable development in business settings. Due to the dominant reductionist paradigm, these interventions may lead to unwanted side effects. Teaching students about unacknowledged feedback loops in complex systems should prevent them from choosing “the most obvious” intervention without considering unwanted side effects.The current study aims to report the effects of teaching a systems perspective, applied to transport systems, on students’ opinions and expressed paradigms. The following questions are addressed: Do students adhere to the techno-centric paradigm, believing technology, innovation and growth can solve all types of threats for sustainable development, while neglecting low probability, high impact events? Are paradigms held by students coherent? Can teaching lead to a change in opinions and paradigms held by students?

Design/methodology/approach
Measures for several systems concepts (i.e. functional stupidity, paradigms and fragility) are taken across a wide sample of university students. Posttests of some key items are taken for a subsample that followed a sustainability and systems perspective in a course on transport economics.

Findings
A large share of students think that technology can solve different types of problems in sustainable development (a kind of weak sustainability), but their paradigms tend to be a mix of conflicting opinions. Though student opinions on topics that were explicitly treated in the course have changed, neither a wider paradigm shift nor significantly more coherent paradigms can be confirmed.

Originality/value
The results show that even though students can be taught about the unwanted side effects and limitations on specific techno-fix interventions, this does not automatically translate into a critical mind-set toward techno-fixing in general.
Elastic wave mode conversion phenomenon in glass fiber-reinforced polymers
Authors: Wandowski Tomasz , Malinowski Pawel , Ostachowicz Wieslaw 
Published: June 2019

Purpose
The purpose of this paper is to present the results of experimental analysis of the elastic-guided wave mode conversion phenomenon in glass fiber-reinforced polymers. The results of this research presented in this paper are strictly focused on S0/A0’ mode conversion phenomenon caused by discontinuities in the form of circular Teflon inserts (artificial delaminations) and impact damage. Results of this research could be useful in problems of damage detection and localization.

Design/methodology/approach
In the research, guided waves are excited using a piezoelectric transducer and sensed in a non-contact manner using a scanning laser Doppler vibrometer. Full wavefield measurements are analyzed. Analysis of the influence of investigated discontinuities on S0/A0’ mode conversion is based on the elastic wave mode filtration in frequency-wavenumber domain. Mode filtration process allows us to remove the effects of the propagation of unwanted type of mode in forward or backward direction. Effects of S0/A0’ mode conversion are characterized by a mode conversion indicator (MCI) based on the amplitude of new mode A0’ and the amplitude of incident S0 mode.

Findings
It was noticed that the magnitude of MCI depends on the depth at which the Teflon inserts were located for all analyzed excitation frequencies and diameters of inserts (10 and 20 mm). The magnitude of MCI also increases with increasing impact energies. The S0/A0’ mode conversion phenomenon could be utilized for the detection of surface and internal located discontinuities.

Originality/value
This paper presents the original results of this research related to the influence of discontinuity location with respect to the sample thickness and severity of discontinuity on S0/A0’ mode conversion.
Online weakly paired similarity learning for surface material retrieval
Authors: Zheng Wendong , Liu Huaping , Wang Bowen , Sun Fuchun 
Published: June 2019

Purpose
For robots to more actively interact with the surrounding environment in object manipulation tasks or walking, they must understand the physical attributes of objects and surface materials they encounter. Dynamic tactile sensing can effectively capture rich information about material properties. Hence, methods that convey and interpret this tactile information to the user can improve the quality of human–machine interaction. This paper aims to propose a visual-tactile cross-modal retrieval framework to convey tactile information of surface material for perceptual estimation.

Design/methodology/approach
The tactile information of a new unknown surface material can be used to retrieve perceptually similar surface from an available surface visual sample set by associating tactile information to visual information of material surfaces. For the proposed framework, the authors propose an online low-rank similarity learning method, which can effectively and efficiently capture the cross-modal relative similarity between visual and tactile modalities.

Findings
Experimental results conducted on the Technischen Universität München Haptic Texture Database demonstrate the effectiveness of the proposed framework and the method.

Originality/value
This paper provides a visual-tactile cross-modal perception method for recognizing material surface. By the method, a robot can communicate and interpret the conveyed information about the surface material properties to the user; it will further improve the quality of robot interaction.