bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degeneracy in hippocampal physiology and plasticity
Authors: Rathour Rahul Kumar , Narayanan Rishikesh 
Published: October 2017

ABSTRACTDegeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis, that demonstrate the expression of degeneracy in hippocampal physiology and plasticity. We assess the potential of degeneracy as a framework to achieve the conjoint goals of encoding and homeostasis without cross-interferences. We postulate that biological complexity, involving interactions among the numerous parameters spanning different scales of analysis, could establish disparate routes towards accomplishing these conjoint goals. These disparate routes then provide several degrees of freedom to the encoding-homeostasis system in accomplishing its tasks in an input- and state-dependent manner. Finally, the expression of degeneracy spanning multiple scales offers an ideal reconciliation to several outstanding controversies, through the recognition that the seemingly contradictory disparate observations are merely alternate routes that the system might recruit towards accomplishment of its goals. Against the backdrop of the ubiquitous prevalence of degeneracy and its strong links to evolution, it is perhaps apt to add a corollary to Theodosius Dobzhansky’s famous quote and state “nothing in physiology makes sense except in the light of degeneracy”.HighlightsDegeneracy is the ability of structurally distinct elements to yield similar functionWe postulate a critical role for degeneracy in the emergence of stable encoding systemsWe catalog lines of evidence for the expression of degeneracy in the hippocampusWe suggest avenues for research to explore degeneracy in stable encoding systemsDobzhansky wrote: “nothing in biology makes sense except in the light of evolution”A corollary: “nothing in physiology makes sense except in the light of degeneracy”
HTX: a tool for the exploration and visualization of high-throughput image assays
Authors: Arteta Carlos , Lempitsky Victor , Zak Jaroslav , Lu Xin , Alison Noble J. , Zisserman Andrew 
Published: October 2017

AbstractHigh-throughput screening (HTS) techniques have enabled large scale image-based studies, but extracting biological insights from the imaging data in an exploratory setting remains a challenge. Existing packages for this task either require expert annotations, which can bias the outcome of the study, or are completely unsupervised, failing to leverage the information present in the assay design. We present HTX, an interactive tool to aid in the exploration of large microscopy data sets by allowing the visualization of entire image-based assays according to visual similarities between the samples in an intuitive and navigable manner. Underlying HTX are a collection of novel algorithmic techniques for deep texture descriptor learning, 2D data visualization, adversarial suppression of batch effects, and backprop-based image saliency estimation.We demonstrate that HTX can exploit the screen meta-data in order to learn screen-specific image descriptors, which are then used to quantify the visual similarity between samples in the assay. Given these similarities and the different visualization resources of HTX, it is shown that screens of small-molecule libraries on cell data can be easily explored, reproducing the results of previous studies where highly-specific domain knowledge was required.
How structural elements added by evolution from bacterial transporters to human SLC6 homologs have enabled new functional properties
Authors: Razavi Asghar M. , Khelashvili George , Weinstein Harel 
Published: October 2017

AbstractMuch of the structure-based mechanistic understandings of the function of SLC6A neurotransmitter transporters emerged from the study of their bacterial LeuT-fold homologs. It has become evident, however, that structural differences such as the long N- and C-termini of the eukaryotic neurotransmitter transporters impart an expanded set of functional properties to the eukaryotic transporters, which are not shared by the bacterial homologs that lack the structural elements that appeared later in evolution. However, mechanistic insights into some of the measured functional properties of the eukaryotic transporters, that have been suggested to involve these structural elements, are sparse. To learn how the structural elements added in evolution enable mechanisms of the eukaryotic transporters in ways not shared with their bacterial LeuT-like homologs, we focused on the human dopamine transporter (hDAT) as a prototype. We present the results of a study employing large-scale molecular dynamics simulations and comparative Markov State Model analysis of experimentally determined properties of the wild type and mutant hDAT constructs, which reveal a rich spectrum of interactions of the hDAT N-terminus and the mechanisms by which these contribute to regulation (e.g., by phosphorylation), or to entirely new phenotypes (e.g., reverse uptake – efflux) added in evolution. We reveal separate roles for the distal and proximal segments of the much larger N-terminus shared by the eukaryotic transporters compared to the bacterial ones, consistent with the proposal that the size of this region increased during evolution to enable more, and different, modes of regulation that are not shared with the bacterial homologs.
TRPV5, TRPV6, TRPM6, and TRPM7 do not contribute to hair-cell mechanotransduction
Authors: Morgan Clive P. , Zhao Hongyu , LeMasurier Meredith , Xiong Wei , Pan Bifeng , Avenarius Matthew R. , Bateschell Michael , Larisch Ruby , Ricci Anthony J. , Müller Ulrich , Barr-Gillespie Peter G. 
Published: October 2017

AbstractThe hair-cell mechanotransduction channel remains unidentified. We tested whether four transient receptor channel (TRP) family members, TRPV5, TRPV6, TRPM6, and TRPM7, participated in transduction. Using cysteine-substitution mouse knock-ins and methanethiosulfonate reagents selective for those alleles, we found that inhibition of TRPV5 or TRPV6 had no effect on transduction in mouse cochlear hair cells. TRPM6 and TRPM7 each interacted with the tip-link component PCDH15 in cultured eukaryotic cells, which suggested they could participate in transduction. Cochlear hair cell transduction was insensitive to shRNA knockdown ofTrpm6orTrpm7, however, and was not affected by manipulations of Mg2+, which normally perturbs TRPM6 and TRPM7. To definitively examine the role of these two channels in transduction, we showed that deletion of either or both of their genes selectively in hair cells had no effect on auditory function. We suggest that TRPV5, TRPV6, TRPM6, and TRPM7 are unlikely to be the pore-forming subunit of the hair-cell transduction channel.
Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation
Authors: Wodarz Dominik 
Published: October 2017

AbstractTissues are maintained by adult stem cells that self-renew and also differentiate into functioning tissue cells. Homeostasis is achieved by a set of complex mechanisms that involve regulatory feedback loops. Similarly, tumors are believed to be maintained by a minority population of cancer stem cells, while the bulk of the tumor is made up of more differentiated cells, and there is indication that some of the feedback loops that operate in tissues continue to be functional in tumors. Mathematical models of such tissue hierarchies, including feedback loops, have been analyzed in a variety of different contexts. Apart from stem cells giving rise to differentiated cells, it has also been observed that more differentiated cells can de-differentiate into stem cells, both in healthy tissue and tumors, aspects of which have also been investigated mathematically. This paper analyses the effect of de-differentiation on the basic and evolutionary dynamics of cells in the context of tissue hierarchy models that include negative feedback regulation of the cell populations. The models predict that in the presence of dedifferentiation, the fixation probability of a neutral mutant is lower than in its absence. Therefore, if de-differentiation occurs, a mutant with identical parameters compared to the wild-type cell population behaves like a disadvantageous mutant. Similarly, the process of de-differentiation is found to lower the fixation probability of an advantageous mutant. These results indicate that the presence of de-differentiation can lower the rates of tumor initiation and progression in the context of the models considered here.
A control theoretic model of adaptive behavior in dynamic environments
Authors: Ritz Harrison , Nassar Matthew R. , Frank Michael J. , Shenhav Amitai 
Published: October 2017

AbstractTo behave adaptively in environments that are noisy and non-stationary, humans and other animals must monitor feedback from their environment and adjust their predictions and actions accordingly. An under-studied approach for modeling these adaptive processes comes from the engineering field of control theory, which provides general principles for regulating dynamical systems, often without requiring a generative model. The proportional-integral-derivative (PID) controller is one of the most popular models of industrial process control. The proportional term is analogous to the “delta rule” in psychology, adjusting estimates in proportion to each successive error in prediction. The integral and derivative terms augment this update to simultaneously improve accuracy and stability. Here, we tested whether the PID algorithm can describe how people sequentially adjust their predictions in response to new information. Across three experiments, we found that the PID controller was an effective model of participants’ decisions in noisy, changing environments. In Experiment 1, we re-analyzed a change-point detection experiment, and showed that participants’ behavior incorporated elements of PID updating. In Experiments 2-3 we developed a task with gradual transitions that we optimized to detect PID-like adjustments. In both experiments, the PID model offered better descriptions of behavioral adjustments than both the classical delta-rule model and its more sophisticated variant, the Kalman filter. We further examined how participants weighted different PID terms in response to salient environmental events, finding that these control terms were modulated by reward, surprise, and outcome entropy. These experiments provide preliminary evidence that adaptive behavior in dynamic environments resembles PID control.
Antagonism in olfactory receptor neurons and its implications for the perception of odor mixtures
Authors: Reddy Gautam , Zak Joseph , Vergassola Massimo , Murthy Venkatesh N. 
Published: October 2017

AbstractNatural environments feature mixtures of odorants of diverse quantities, qualities and complexities. Olfactory receptor neurons (ORNs) are the first layer in the sensory pathway and transmit the olfactory signal to higher regions of the brain. Yet, the response of ORNs to mixtures is strongly non-additive, and exhibits antagonistic interactions among odorants. Here, we model the processing of mixtures by mammalian ORNs, focusing on the role of inhibitory mechanisms. Theoretically predicted response curves capture experimentally determined glomerular responses imaged by a calcium indicator expressed in ORNs of live, breathing mice. Antagonism leads to an effective “normalization” of the ensemble glomerular response, which arises from a novel mechanism involving the distinct statistical properties of receptor binding and activation, without any recurrent neuronal circuitry. Normalization allows our encoding model to outperform noninteracting models in odor discrimination tasks, and to explain several psychophysical experiments in humans.
Investigating feedback effects in the field of brand extension using brand concept maps
Authors: Kottemann Pascal , Plumeyer Anja , Decker Reinhold 
Published: October 2017

Purpose
The purpose of this paper is to apply the (advanced) brand concept maps (BCM) approach to reinvestigate previous findings on feedback effects resulting from brand extension information (BEI) and to explore whether this information affects the structure of a brand’s associative network.

Design/methodology/approach
This research builds on the associative network memory model, as well as Keller’s conceptualization of customer-based brand equity, and uses a series of empirical studies with a total of 839 respondents in two different countries.

Findings
The findings reveal that BEI has no significant impact on the structure of the parent brand’s associative network at the individual level. Furthermore, key brand image dimensions (i.e. favorability, strength, and uniqueness of brand associations) are not affected.

Research limitations/implications
By applying the (advanced) BCM approach, this paper is able to address shortcomings that are incorporated with the use of Likert scales for measuring a brand’s image and for investigating feedback effects in the field of brand extension. As the results indicate that the identification of feedback effects might be influenced by the approach used to measure a brand’s image, this paper calls for further investigations of feedback effects on a brand’s image.

Originality/value
Data from three empirical studies provide insights into the cognitive processing of BEI and their impact on a brand’s associative network.
Influences of workplace environment factors on employees’ training transfer
Authors: Na-nan Khahan , Chaiprasit Kanokporn , Pukkeeree Peerapong 
Published: October 2017

Purpose
The purpose of this paper is to investigate the direct and indirect influences of workplace environment factors on the motivation to transfer the acquired training (MT) and the transfer of training. The workplace environment factors under study encompass the organizational support, supervisor support, peer support, technological support and the opportunity to use the acquired training.

Design/methodology/approach
In the study, the empirical data were garnered from a sample of 220 business school students, using a 52-question questionnaire. A research framework was first proposed and the structural equation modeling subsequently utilized to test the research framework and determine the direct influence of the workplace environment factors on the transfer of training and also their indirect influence on TT through the MT variable.

Findings
The structural equation modeling model is congruent with the empirical data, with the χ2 statistic of 24.414, the degree of freedom of 21, the p-value of 0.273, the goodness of fit index of 0.977 and the root mean square error of approximation of 0.027. The findings revealed that the workplace environment factors directly influenced the training transfer behavior of the participants and indirectly through the MT of the individuals. Most importantly, the proposed model could achieve the coefficient of prediction (R2) as high as 82 percent.

Originality/value
Workplace environment is important to motivation to transfer and transfer of training. To enhance the training transfer effectiveness, businesses should take into account the contributions associated with each environment factor in the design and implementation of training programs.
Negotiating barriers: prisoner and staff perspectives on mental wellbeing in the open prison setting
Authors: Danks Kara , Bradley Alexandria 
Published: October 2017

PurposeThe purpose of this paper is to explore the perspectives of prisoners and prison staff in relation to mental wellbeing and the negotiation of barriers to accessing and providing support. This small-scale study includes the experiences of 11 prison staff and 9 prisoners within a Category D male prison.Design/methodology/approachA focus group was conducted with the prisoners and interviews with prison staff. Thematic analysis identified three core themes: “context enabling factors”, “barriers to accessing support for mental wellbeing” and “peer support roles”.FindingsPrisoners conveyed a reluctance in reporting mental health issues due to the fear of being transferred to closed conditions. All staff indicated the benefits of peer support roles.Research limitations/implicationsFurther research is required on a wider scale, as it is acknowledged that the findings of this study are from one prison and may not apply to other settings. Although there are barriers that may impact the reporting of mental wellbeing issues, there may be small relational steps that can be taken to address these.Originality/valueFew studies exist that explore the nuances and barriers within open prisons, perhaps due to the overwhelming need within closed conditions. A context-specific approach considering early prevention strategies to support a safer prison system and successful rehabilitation is explored. The combination of prisoner and staff experiences is of value to both academia and policymakers.
Cold-formed steel columns at both ambient and fire conditions
Authors: Craveiro Hélder , Rodrigues João Paulo Correia , Laim Luis 
Published: October 2017

Purpose
The use of cold-formed steel members has increased significantly in the past few years; however, its design is only briefly addressed in the current design codes, such as the EN 1993-1-3. To evaluate the compressive behavior of single and built-up cold-formed steel members, at ambient and simulated fire conditions with restrained thermal elongation, experimental and numerical tests were undertaken.

Design/methodology/approach
Four cross-section shapes were tested, namely, one single (lipped channel), one open built-up (I) and two closed built-up (R and 2R), considering two end support conditions, pinned and fixed. Two test set-ups were specifically developed for these tests. Based on the experimental results finite element models were developed and calibrated to allow future parametric studies.

Findings
This paper showed that increasing the level of restraint to thermal elongation and the initially applied load led to lower critical temperatures. Increasing the level of restraint to thermal elongation, the failure is governed by the generated axial restraining forces, whereas for lower levels of restraint to thermal elongation, the failure is controlled by the temperature increasing.

Originality/value
This paper is a contribution to the knowledge on the behavior of cold-formed steel columns subjected to fire, especially on the ones with a built-up cross-section, where results on thermal restrained ones are still scarce. It presented a set of experimental and numerical results useful for the development of numerical and analytical analysis concerning the development of new simplified calculation methods.
Does omalizumab modify a course of recalcitrant chronic spontaneous urticaria?: A retrospective study in Asian patients
Authors: Kulthanan Kanokvalai , Tuchinda Papapit , Likitwattananurak Chayanee , Weerasubpong Puncharas , Chularojanamontri Leena 
Published: October 2017

AbstractOmalizumab has been approved for the treatment of recalcitrant chronic spontaneous urticaria (CSU). However, it remains unanswered whether omalizumab modifies a CSU course. We aimed to study a course of CSU after omalizumab treatment in an Asian population. Medical records of recalcitrant CSU patients who attended Siriraj Hospital between 2013 and 2017 were reviewed. All patients receiving omalizumab treatment were followed after the first injection for at least 1 year. Of 15 patients receiving omalizumab treatment, 11 patients (73.3%) responded well to 150 mg while the rest required 300 mg. The median follow‐up period was 18 months (range, 13.5–25.3). Three patterns of response were proposed and measured: excellent (disease remission over than 6 months) was found in 20%; good (injection interval extended longer than 6 months) was found in 27%; and modest (frequently required injections) was found in 53%. The mean duration of complete remission was 33 weeks (range, 26–38). Two‐thirds of patients had disease relapse and required omalizumab injections to control symptoms. The other third did not show relapses for at least 69 weeks of the follow‐up period. After 1 year of treatment, Kaplan–Meier curves estimated that a higher percentage (86.7%) of recalcitrant CSU patients receiving omalizumab treatment would be free of symptoms (weekly Urticaria Activity Score = 0) without prednisolone and/or cyclosporin as compared with 42% of patients not receiving omalizumab treatment. In conclusion, patients seem to be easily and safely manageable with omalizumab. Prednisolone and cyclosporin could be discontinued in all patients. Further studies are needed to conclude whether omalizumab can exactly modify CSU.
Involvement of NF‐κB in the upregulation of cystathionine‐γ‐lyase, a hydrogen sulfide‐forming enzyme, and bladder pain accompanying cystitis in mice
Authors: Ozaki Tomoka , Tsubota Maho , Sekiguchi Fumiko , Kawabata Atsufumi 
Published: October 2017

SummaryHydrogen sulfide (H2S) is generated from l‐cysteine by multiple enzymes including cystathionine‐γ‐lyase (CSE), and promotes nociception by targeting multiple molecules such as Cav3.2 T‐type Ca2+ channels. Bladder pain accompanying cyclophosphamide (CPA)‐induced cystitis in mice has been shown to involve the functional upregulation of the CSE/H2S/Cav3.2 pathway. Therefore, we investigated whether NF‐κB, as an upstream signal of the CSE/H2S system, contributes to bladder pain in mice with CPA‐induced cystitis. Bladder pain‐like nociceptive behaviour was observed in CPA‐treated mice, and referred hyperalgesia was evaluated by the von Frey test. Isolated bladder weights were assessed to estimate bladder swelling, and protein levels were measured by Western blotting. CPA, administered intraperitoneally, induced nociceptive behaviour, referred hyperalgesia and increased bladder weights in mice. β‐Cyano‐l‐alanine, a reversible selective CSE inhibitor, prevented CPA‐induced nociceptive behaviour, referred hyperalgesia, and, in part, increases in bladder weight. CPA markedly increased phosphorylated NF‐κB p65 levels in the bladder, an effect that was prevented by pyrrolidine dithiocarbamate (PDTC), an NF‐κB inhibitor. PDTC and curcumin, which inhibits NF‐κB signals, abolished CPA‐induced nociceptive behaviour, referred hyperalgesia and, in part, increases in bladder weight. CPA caused the overexpression of CSE in the bladder, and this was prevented by PDTC or curcumin. The CPA‐induced activation of NF‐κB signals appeared to cause CSE overexpression in the bladder, contributing to bladder pain and in part swelling, possibly through H2S/Cav3.2 signaling. Therefore, NF‐κB‐inhibiting compounds including curcumin may be useful for the treatment of cystitis‐related bladder pain.