bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza H3 and H1 hemagglutinins have different genetic barriers for resistance to broadly neutralizing stem antibodies
Authors: Wu Nicholas C. , Thompson Andrew J. , Lee Juhye M. , Su Wen , Arlian Britni M. , Xie Jia , Lerner Richard A. , Yen Hui-Ling , Bloom Jesse D. , Wilson Ian A. 
Published: December 2019

ABSTRACTIn the past decade, the discovery and characterization of broadly neutralizing antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have provided valuable insights for development of a universal influenza vaccine. However, the genetic barrier for resistance to stem bnAbs has not been thoroughly evaluated. Here, we performed a series of deep mutational scanning experiments to probe for resistance mutations. We found that the genetic barrier to resistance to stem bnAbs is generally very low for the H3 subtype but substantially higher for the H1 subtype. Several resistance mutations in H3 cannot be neutralized by stem bnAbs at the highest concentration tested, do not reducein vitroviral fitness andin vivopathogenicity, and are often present in circulating strains as minor variants. Thus, H3 HAs have a higher propensity than H1 HAs to escape major stem bnAbs and creates a potential challenge in the development of abona fideuniversal influenza vaccine.ONE SENTENCE SUMMARYAcquisition of resistance by influenza virus to broadly neutralizing hemagglutinin stem antibodies varies tremendously depending on subtype.
Capturing multiple timescales of adaptation to second-order statistics with generalized linear models: gain scaling and fractional differentiation
Authors: Latimer Kenneth W. , Fairhall Adrienne L. 
Published: December 2019

AbstractSingle neurons can dynamically change the gain of their spiking responses to account for shifts in stimulus variance. Moreover, gain adaptation can occur across multiple timescales. Here, we examine the ability of a simple statistical model of spike trains, the generalized linear model (GLM), to account for these adaptive effects. The GLM describes spiking as a Poisson process whose rate depends on a linear combination of the stimulus and recent spike history. The GLM successfully replicates gain scaling observed in Hodgkin-Huxley simulations of cortical neurons that occurs when the ratio of spike-generating potassium and sodium conductances approaches one. Gain scaling in the GLM depends on the length and shape of the spike history filter. Additionally, the GLM captures adaptation that occurs over multiple timescales as a fractional derivative of the stimulus variance, which has been observed in neurons that include long timescale after hyperpolarization conductances. Fractional differentiation in GLMs requires long spike history that span several seconds. Together, these results demonstrate that the GLM provides a tractable statistical approach for examining single-neuron adaptive computations in response to changes in stimulus variance.
Meta-Learning Biologically Plausible Semi-Supervised Update Rules
Authors: Gu Keren , Greydanus Sam , Metz Luke , Maheswaranathan Niru , Sohl-Dickstein Jascha 
Published: December 2019

AbstractThe question of how neurons embedded in a network update their synaptic weights to collectively achieve behavioral goals is a longstanding problem in systems neuroscience. Since Hebb’s hypothesis [10] that cells that fire together strengthen their connections, cellular studies [6] have shed light on potential synaptic mechanisms underlying learning. These mechanisms have directly driven the careful hand design of biologically plausible models of learning and memory in computational neuroscience [1]. However, these hand designed rules have yet to achieve satisfying success training large neural networks, and are dramatically outperformed by biologically implausible approaches such as backprop. We propose an alternative paradigm for designing biologically plausible learning rules: using meta-learning tolearna parametric synaptic update rule which is capable of training deep networks. We demonstrate this approach by meta-learning an update rule for semi-supervised tasks, where sparse labels are provided to a deep network but the majority of inputs are unlabeled. The meta-learned plasticity rule integrates bottom-up, top-down, and recurrent inputs to each neuron, and generates weight updates as the product of pre- and post- synaptic neuronal outputs. The way in which the inputs to each neuron are combined to produce a learning signal, however, is itself ameta-learnedfunction, parameterized by a neural network. Critically, the meta-learned update rule integrates only neuron-local information when proposing updates–that is, our learning rule is spatially localized to individual neurons. After meta-learning, the resulting synaptic update rule is capable of driving task-relevant learning for semi-supervised tasks. We demonstrate this capability on two simple classification problems. In general, we believe meta-learning to be a powerful approach to finding more effective synaptic plasticity rules, which will motivate new hypotheses for biological neural networks, and new algorithms for artificial neural networks.
A possible coding for experience: ripple-like events and synaptic diversity
Authors: Ishikawa J , Tomokage T , Mitsushima D 
Published: December 2019

AbstractThe hippocampal CA1 is necessary to maintain experienced episodic memory in many species, including humans. To monitor the temporal dynamics of processing, we recorded multiple-unit firings of CA1 neurons in male rats experiencing one of four episodes for 10 min: restraint stress, social interaction with a female or male, or observation of a novel object. Before an experience, the neurons mostly exhibited sporadic firings with some synchronized (≈ 50 ms) ripple-like firing events in habituated home cage. After experience onset, restraint or social interaction with other rats induced spontaneous high-frequency firings (super bursts) intermittently, while object observation induced the events inconsistently. Minutes after experience initiation, CA1 neurons frequently exhibited ripple-like firings with less-firing silent periods. The number of ripple-like events depended on the episode experienced and correlated with the total duration of super bursts. Experience clearly diversified multiple features of individual ripple-like events in an episode-specific manner, sustained for more than 30 min in the home cage.Ex vivopatch clamp analysis further revealed experience-promoted synaptic plasticity. Compared with unexposed controls, animals experiencing the female, male, or restraint episodes showed cell-dependently increased AMPA- or GABAAreceptor– mediated postsynaptic currents, whereas contact with a novel object increased only GABAergic currents. Multivariate ANOVA in multi-dimensional virtual space revealed experience-specific super bursts with subsequent ripple-like events and synaptic plasticity, leading us to hypothesize that these factors are responsible for creating experience-specific memory. It is possible to decipher encrypted experience through the deep learning of the orchestrated ripple-like firings and synaptic plasticity in multiple CA1 neurons.
Corticosterone as a potential confounding factor in delineating mechanisms underlying ketamine’s rapid antidepressant actions
Authors: Wegman-Points Lauren , Pope Brock , Zobel Allison , Semke Lori , Wauson Eric , Duric Vanja , Yuan Li-Lian 
Published: December 2019

AbstractAlthough ketamine represents a new line of antidepressants with unique clinical advantages, its use as a long-term treatment has limitations, particularly its dissociative/psychotomimetic effects and abuse potential. In rats, we observed that a subanesthetic dose of ketamine (10mg/kg) induced a 3-fold increase in corticosterone (CORT) levels in both serum and brain tissue, within an hour of administration. This increase took place in both male and female rats, in both naïve and stressed animals. However, no CORT increase was detected in rats injected with (2R, 6R)-hydroxynorketamine (HNK), an active metabolite of ketamine, that is believed to contribute to ketamine’s antidepressant effect. In response to the release in CORT, ketamine injected animals displayed a significant increase in the expression ofsgk1, a downstream effector of glucocorticoid receptor signaling, in the hippocampus indicating the initiation of a transcriptional program. We hypothesized this surge in CORT release was a manifestation of stress experienced by the rat in response to ketamine’s psychotropic effects. When sensory perception was blocked under isoflurane anesthesia, administration of ketamine did not increase circulating CORT levels as compared to animals injected with saline. Taken together, ketamine administration triggers a behavioral stress response that has downstream molecular consequences. The resulting CORT release, virtually concurrent with the timing of ketamine’s rapid-acting antidepressant actions, necessitates the consideration of this pathway’s potential involvement when trying to dissect out the relevant molecular mechanisms underlying ketamine’s action.
Valeriana Officinalis Crude Extracts Impair Hair Cell Regeneration in Larval Zebrafish Lateral Line
Authors: Rodríguez-Morales Roberto , Santana-Cruz Alexis , Tossas-Deida Tiffany , Torrado-Tapias Aranza , Behra Martine 
Published: December 2019

AbstractIrreversible hair cell (HC) loss in the inner ear is the leading cause for hearing and balance disorders. Discovery of therapeutic molecules preventing HC death and promoting regeneration, which does not occur in mammals like it does in lower vertebrates, is of major interest. In fish, HCs are also found in a superficial mechano-sensory organ called the lateral line (LL). LL-HCs are exposed to surrounding waters and are accessible to waterborne molecules providing a potent mean to study in vivo HC stability and regeneration. Commercial small molecule libraries were tested in screens for HC survival and regeneration in zebrafish, but ethnobotanical pharmacopeias remain totally unexplored because of the challenge that such complex mixtures represent. A rapid and cost-effective first-pass assay informing about the regenerative potential of an extract is therefore critical before embarking on cumbersome purification steps. We chose to test Valerian crude root extracts (Val), which are typically composed of more than 150 different components, amongst which is a main and abundant compound: valeric acid (VA). VA discovery and purification led to the commercialization of a synthetic analog: Valproic acid (VPA) which is a first-line drug for epilepsy and bipolar disorders that was also shown to significantly hamper LL-HC regeneration. We reasoned that if Val is not toxic, it would elicit effects like VPA. Thus, we synchronously ablated HCs in 5-day post-fertilization (dpf) larvae and monitored regeneration over the following 3 days in the presence of Val at the highest well-tolerated concentration (Val1 = 1mg/ml), or VPA (= 150μM) as previously published. Both treatments significantly decreased HC regeneration without affecting HC-survival suggesting a similar mode of action. Furthermore, Val application as early as 3dpf and prolonged for up to 4 days did not affect larval survival, indicating that reduced HC-regeneration was not due to overall toxicity. Taken together, Val and VPA-treatments displayed a comparable response in a simple and up-scalable HC-regeneration assay which is an in-first-pass potent approach for drug discovery.
Evaluating the worth of nascent old vine cues for South African wines
Authors: Priilaid David , Steyn Jonathan 
Published: December 2019

Purpose
In increasingly competitive markets, opportunities exist to meaningfully differentiate product offerings by cue signalling the claims of emergent categories. Therefore, and within the context of wine sales, the purpose of this study models the supply-led price importance of nascent, extrinsic old vine (OV) cues for South African wines to establish whether to what extent and how producers prioritise such nascent cues relative to more established extrinsic cues of worth.

Design/methodology/approach
A data set was compiled of 159 South African wines with OV category cues signalled on front labels, back labels or via marketing material. The play of contending cue variables was computed through an ordinary least square hedonic pricing model.

Findings
In addition to the contribution of established cues such as aggregated critic ratings, grape varieties and area of origin, this study confirms that vineyard age contributes significantly to wine price, particularly when signalled on back labels.

Practical implications
In price setting and positional models, such as brand extensions, the findings prove useful in understanding the inherent value of nascent cues and specifically vineyard age, relative to competing established wine cues of worth.

Originality/value
This study extends the wine pricing theory by validating the viability of nascent OV cues in the modelling of a wine’s value.
A comprehensive framework to rank cloud-based e-learning providers using best-worst method (BWM)
Authors: Pour Mona Jami , Mesrabadi Javad , Hosseinzadeh Mahnaz 
Published: December 2019

Purpose
Today, the high cost of e-learning systems’ implementation and the difficulty of managing the infrastructures motivate educational institutions toward application of cloud-based e-learning systems. This new system should be aligned with the academics’ aims and pedagogical principles to be beneficial for learners and instructors. Therefore, the vendor selection of learning systems is one of the most important processes to migrate toward cloud-based e-learning. The purpose of this paper is to develop a new framework to facilitate the vendor selection of cloud-based e-learning systems in the cloud market.

Design/methodology/approach
To identify the initial criteria as to the vendor selection of cloud-based e-learning services, a literature review is done. To enrich the initial criteria, a focus group of experts is investigated, and the framework developed; then, a survey analysis is conducted to validate the proposed framework. The extracted criteria and sub-criteria are weighted and prioritized using best-worst method (BWM).

Findings
The results indicate that the main dimensions of vendor selection framework as regards cloud-based e-learning systems are managerial, technological and pedagogical factors. The rank orders and weights of the mentioned aspects and their sub-criteria are calculated using the BWM.

Practical implications
The proposed framework helps managers to get a big picture of requirements as to cloud-based e-learning and more effectively to select appropriate vendors in this initiative. In the vendor selection process, managers must pay attention to technological issues as well as managerial and pedagogical considerations.

Originality/value
Cloud-based e-learning systems are getting increasingly essential to offer training courses more efficiently in educational institutions. Although the intersection between cloud computing and e-learning has increasingly grown in both practical and academic contexts, there are little studies on how educational institutions and organizations could be able to select appropriate cloud-based e-learning systems. This paper explores the ignored but critically important subject of cloud-based e-learning. The main contribution of this paper is to propose a novel and integrated framework containing the important aspects of vendor selection in cloud-based e-learning services. The proposed framework comprises managerial, technological and pedagogical aspects simultaneously as well as sub-criteria denoting each aspect.
Algorithmic equity in the hiring of underrepresented IT job candidates
Authors: Yarger Lynette , Cobb Payton Fay , Neupane Bikalpa 
Published: December 2019

Purpose
The purpose of this paper is to offer a critical analysis of talent acquisition software and its potential for fostering equity in the hiring process for underrepresented IT professionals. The under-representation of women, African-American and Latinx professionals in the IT workforce is a longstanding issue that contributes to and is impacted by algorithmic bias.

Design/methodology/approach
Sources of algorithmic bias in talent acquisition software are presented. Feminist design thinking is presented as a theoretical lens for mitigating algorithmic bias.

Findings
Data are just one tool for recruiters to use; human expertise is still necessary. Even well-intentioned algorithms are not neutral and should be audited for morally and legally unacceptable decisions. Feminist design thinking provides a theoretical framework for considering equity in the hiring decisions made by talent acquisition systems and their users.

Social implications
This research implies that algorithms may serve to codify deep-seated biases, making IT work environments just as homogeneous as they are currently. If bias exists in talent acquisition software, the potential for propagating inequity and harm is far more significant and widespread due to the homogeneity of the specialists creating artificial intelligence (AI) systems.

Originality/value
This work uses equity as a central concept for considering algorithmic bias in talent acquisition. Feminist design thinking provides a framework for fostering a richer understanding of what fairness means and evaluating how AI software might impact marginalized populations.
Internal auditor perceptions of corporate governance in Greece after the crisis
Authors: Mertzanis Charilaos , Balntas Vangelis , Pantazopoulos Thodoris 
Published: December 2019

PurposeThis paper aims to present the views of internal auditors in Greece on the relation between the internal audit function (IAF) and corporate governance (CG) after several years of European market integration and in the aftermath of the sovereign debt crisis.Design/methodology/approachData are collected using semi-structured interviews with 15 internal auditors working in firms with different size and in different sectors of activity. Interviewees have diverse experience and hold various positions in the firm.FindingsRespondents perceive a strong relation between the IAF and CG. They view the IAF as a preventive tool that provides monitoring and advisory services to firms. They stress the inadequate monitoring role of the board in the IAF, and they support a proactive intervention in the strategic audit planning process. They see a small role for shareholders in CG. They stress the need to focus more on the efficiency and effectiveness considerations in carrying out the IAF. They perceive CG-related information as important for meeting formal compliance needs rather than contributing to decision-making or audit process planning. They believe that audit committees (AC) are weak in implementing effective monitoring, due to inadequate knowledge and expertise of their members. They would like to see a two-way interaction between auditors, AC and management. They would like to enjoy more independence through the implementation of international standards of auditing and statutory regulation.Research limitations/implicationsThe sample covers 15 auditors from an equivalent number of firms and few sectors of activity. Accessing potential interviewees was difficult due to the perceived conflict between their work requirements and public statement of their views.Practical implicationsThe proposed method adds to the qualitative analysis literature with regard to measuring and evaluating the personal views of auditors on CG. The study provides empirical evidence of the need to use extensive qualitative research to assess the auditors’ views on the role of CG for their work.Originality/valueThe role of internal audit in CG effectiveness is a key policy concern, especially in countries with diverse market environments. Greece is such an environment for it has undergone a major institutional change within a short period and suffered greatly from its sovereign debt crisis. Further, few studies have sought and evaluated the views of internal auditors by using semi-structured interviews. The latter provide details, which other methods cannot capture. The results of this study are especially useful to the competent regulators, for they reflect market perceptions on the importance and effectiveness of CG practices. They are also useful to practitioners to identify potential root causes of audit deficiencies.
The determinants of corporate social irresponsibility: a case study of the Soma mine accident in Turkey
Authors: Atay Erhan , Terpstra-Tong Jane Lai Yee 
Published: December 2019

PurposeTaking the deadliest mine accident in Turkey’s history as a case of corporate social irresponsibility (CSI), this study aims to examine the adequacy of Campbell’s (2007) model to explain firms’ CSI behaviour.Design/methodology/approachThe authors applied a case study research method and collected secondary data in both English and Turkish from multiple sources between 2010 and 2017.FindingsThe authors found seven of the eight propositions in Campbell’s framework applicable. The only condition that did not fit the authors’ case was financial pressure. The authors concluded that top management’s greed and lack of conscience significantly contributed to their gross negligence of safety measures and employee welfare. Their exploitative human resource practices, supported by low employee voice culture, added to the vulnerability of the mining workers.Research limitations/implicationsThe authors depended on secondary data in developing and analysing the case. The authors had no primary data collected directly from the participants involved in the accident. Moreover, relying on a single case to challenge an established framework may not achieve the necessary rigour, although an in-depth case study is likely to produce a good story.Practical implicationsTo prevent mining accidents from happening, Turkey needs to strengthen all three types of institutions (legal and regulative, normative and cultural-cognitive) related to mining safety. As coal mining is harmful to the environment and public health, regulators and policymakers need to consider their dependence on coal mining as a source of energy and actively seek to adopt other clean energy alternatives.Originality/valueThis study contributes to the under-researched field of CSI by applying a dual economic and institutional perspective and refining it with the authors’ data.
Is the survival rate for acral melanoma actually worse than other cutaneous melanomas?
Authors: Lim Youngkyoung , Lee Jongeun , Lee Dong‐Youn 
Published: December 2019

AbstractIt is still not clear whether the survival rate for acral melanoma (AM) is better or worse than that of cutaneous melanoma developed at other sites. We sought to evaluate the difference in survival depending on the primary tumor site of cutaneous melanoma. We retrospectively reviewed primary cutaneous melanoma cases diagnosed at Samsung Medical Center, a tertiary institution in Korea, from January 1995 to July 2017. The cohort consisted of 642 patients, with 389 non‐acral cutaneous melanoma (NACM) patients and 253 AM patients. The AM patients had a higher percentage of stage 0 diagnoses than the NACM patients (31.6% vs 6.9%, respectively). The factors associated with overall survival were primary tumor site, sex, age, American Joint Committee on Cancer stage, surgery and medical treatment (P < 0.05). Non‐acral sites showed worse survival in multivariable analysis (hazard ratio [HR], 1.457; 95% confidence interval [CI], 1.051–2.020; P = 0.0240). Among the NACM, melanomas on the trunk were associated with a higher risk of mortality compared with AM (HR, 1.883; 95% CI, 1.142–3.107; P = 0.0131). Acral melanoma was associated with a better prognosis than non‐acral melanoma, specifically when located on the trunk, in Korean patients.