bluuebunny/crossref_metadata_2025_split huggingface dataset:
TelNet- a database for human and yeast genes involved in telomere maintenance
Authors: Braun Delia M. , Chung Inn , Kepper Nick , Deeg Katharina I. , Rippe Karsten 
Published: April 2017

AbstractThe ends of linear chromosomes, the telomeres, comprise repetitive DNA sequences that are protected by the shelterin protein complex. Cancer cells need to extend these telomere repeats for their unlimited proliferation, either by reactivating the reverse transcriptase telomerase or by using the alternative lengthening of telomeres (ALT) pathway. The different telomere maintenance (TM) mechanisms appear to involve hundreds of proteins but their telomere repeat length related activities are only partly understood. Currently, a database that integrates information on TM relevant genes is missing. To provide a reference for studies that dissect TM features, we here introduce theTelNetdatabase athttp://www.cancertelsys.org/telnet/. It offers a comprehensive compilation of more than 2,000 human and over 1,100 yeast genes linked to telomere maintenance. These genes were annotated in terms of TM mechanism, associated specific functions and orthologous genes, a TM significance score and information from peer-reviewed literature. This TM information can be retrieved via different search and view modes and evaluated for a set of genes on a statistics page. With these features TelNet can be integrated into the annotation of genes identified from bioinformatics analysis pipelines to determine possible connections with TM networks as illustrated by an exemplary application. We anticipate thatTelNetwill be a helpful resource for researchers that study TM processes.
Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models
Authors: Yousefi Safoora , Amrollahi Fatemeh , Amgad Mohamed , Dong Coco , Lewis Joshua E. , Song Congzheng , Gutman David A , Halani Sameer H. , Velazquez Vega Jose Enrique , Brat Daniel J , Cooper Lee AD 
Published: April 2017

ABSTRACTTranslating the vast data generated by genomic platforms into accurate predictions of clinical outcomes is a fundamental challenge in genomic medicine. Many prediction methods face limitations in learning from the high-dimensional profiles generated by these platforms, and rely on experts to hand-select a small number of features for training prediction models. In this paper, we demonstrate how deep learning and Bayesian optimization methods that have been remarkably successful in general high-dimensional prediction tasks can be adapted to the problem of predicting cancer outcomes. We perform an extensive comparison of Bayesian optimized deep survival models and other state of the art machine learning methods for survival analysis, and describe a framework for interpreting deep survival models using a risk backpropagation technique. Finally, we illustrate that deep survival models can successfully transfer information across diseases to improve prognostic accuracy. We provide an open-source software implementation of this framework calledSurvivalNetthat enables automatic training, evaluation and interpretation of deep survival models.
Epistatic interactions within the influenza virus polymerase complex mediate mutagen resistance and replication fidelity
Authors: Pauly Matthew D. , Lyons Daniel M. , Lauring Adam S. 
Published: April 2017

AbstractLethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses. Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. We have previously demonstrated the effective lethal mutagenesis of influenza virus using three nucleoside analogs as well as the virus’s high genetic barrier to mutagen resistance. Here, we investigate the mutagen-resistant phenotypes of mutations that were enriched in drug-treated populations. We find that PB1 T123A has higher replicative fitness than the wild type, PR8, and maintains its level of genome production during 5-fluorouracil treatment. Surprisingly, this mutagen-resistant variant also has an increased baseline rate of C to U and G to A mutations. A second drug-selected mutation, PA T97I, interacts epistatically with PB T123A to mediate high-level mutagen resistance, predominantly by limiting the inhibitory effect of nucleosides on polymerase activity. Consistent with the importance of epistatic interactions in the influenza polymerase, we find that nucleoside analog resistance and replication fidelity are strain dependent. Two previously identified ribavirin-resistance mutations, PB1 V43I and PB1 D27N, do not confer drug resistance in the PR8 background, and the PR8-PB1 V43I polymerase exhibits a normal baseline mutation rate. Our results highlight the genetic complexity of the influenza virus polymerase and demonstrate that increased replicative capacity is a mechanism by which an RNA virus can counter the negative effects of elevated mutation rates.ImportanceRNA viruses exist as genetically diverse populations. This standing genetic diversity gives them the potential to adapt rapidly, evolve resistance to antiviral therapeutics, and evade immune responses. Viral mutants with altered mutation rates or mutational tolerance have provided insights into how genetic diversity arises and how it affects the behavior of RNA viruses. To this end, we identified variants within the polymerase complex of influenza virus that are able tolerate drug-mediated increases in viral mutation rates. We find that drug resistance is highly dependent on interactions among mutations in the polymerase complex. In contrast to other viruses, influenza virus counters the effect of higher mutation rates primarily by maintaining high levels of genome replication. These findings suggest the importance of maintaining large population sizes for viruses with high mutation rates and show that multiple proteins can affect both mutation rate and genome synthesis.
Germ cell connectivity enhances cell death in response to DNA damage inDrosophilatestis
Authors: Lu Kevin L. , Yamashita Yukiko M. 
Published: April 2017

AbstractTwo broadly known characteristics of germ cells in many organisms are their development as a ‘cyst’ of interconnected cells and their high sensitivity to DNA damage. Here we provide evidence that these characteristics are linked, and that interconnectivity is a mechanism that confers to theDrosophilatestis a high sensitivity to DNA damage. We show that all germ cells within a cyst die simultaneously even when only a subset of them exhibit detectable DNA damage. Compromising connectivity results in cysts in which only a subset of germ cells die upon DNA damage, lowering overall germ cell death. Our data indicate that a death-promoting signal is shared through the intercellular connections of germ cells. Taken together, we propose that intercellular connectivity is a mechanism that uniquely increases the sensitivity of the germline to DNA damage, thereby protecting the integrity of gamete genomes that are passed on to the next generation.
Feature engineering coupled machine learning algorithms for epileptic seizure forecasting from intracranial EEGs
Authors: Kumar Rishav , Jhelumi Rishi Raj Singh , Singh Achintye Madhav , Kumar Prasoon 
Published: April 2017

AbstractEpilepsy is one of the major neurological disorders affecting nearly 1 percentage of the global population. The major blunt is born by under developed and developing countries due to expensive treatment of epileptic conditions. Further, the lack of proper forecasting methods for an occurrence of epileptic seizures in epileptic-drug resistant patients or patients not amenable for surgery affects their psychological behaviour and restricts their daily activities. The forecasting is usually performed by human experts that leave a wide gap for human-bias and human error. Therefore, in the current work, we have evaluated the efficiency of several machine learning algorithms to automatically identify the preictal patterns corresponding to epileptic seizures from intracranial EEG signals. The robustness of the machine learning algorithms were tested after the data set was pre-processed using carefully chosen feature engineering strategies viz. denoised Fourier transforms as well as cross-correlation across electrodes in time and frequency domain. Extensive experimentations were carried out to determine the best combination of feature engineering techniques and machine learning algorithms. The best combination of feature engineering techniques and machine learning algorithm resulted in 0.7685 AUC (Area under the Receiver Operating Characteristic curve) on the random test samples. The suggested approach was fairly good at prediction of epilepsy in random samples and therefore, it can be used in epileptic seizure forecasting in patients where medication/surgery is ineffective. Eventually, our strategy reveals a robust method for brain disorders forecasting from EEGs.
International drug policy – health before politics
Authors: Ford Chris , Saville Sebastian 
Published: April 2017

Purpose
The purpose of this paper is to explain how international drug policy continues to have a hugely damaging effect on population health, human rights and wellbeing, not only on individuals who consume and/or sell drugs but also on societies as a whole. And to review whether anything has changed after United Nations General Assembly Special Session.

Design/methodology/approach
UNGASS had been seen as a real opportunity for scientific evidence to become the driver of future drug policy. This paper looks at any changes that have since taken place that might support such an aspiration.

Findings
The authors found the criminalisation and incarceration of people who use drugs, mainly from the most marginalised sections of society, remains the primary response in almost every member state of the UN and there are at least 33 countries that retain the death penalty for drug offences. The impact on the health of people who inject drugs (PWIDs) living with HIV is devastating and overdose and AIDS related mortality are the leading causes of death. Hepatitis C infections among PWIDs are increasing at epidemic levels even though this now a curable disease.

Practical implications
Changes in drug policy urgently needed.

Originality/value
This paper is an important review of the health implications of bad drug policy.
A turning point for UK drug policy: opportunity or stasis
Authors: Stothard Blaine 
Published: April 2017

Purpose
The purpose of this paper is to explore the current policy stasis in UK drug policy.

Design/methodology/approach
This paper examines reports, statistics and policy statements by government agencies.

Findings
Delays in revising a national strategy appear to have no clear explanation. Responses to drugs issues, including drug-related deaths, appear to lack urgency or concern at a policy making level.

Research limitations/implications
Complacency and lack of regard to evidence appear to inform current policy and strategy. Ways of overcoming this stasis are not identified.

Practical implications
There is a need for factors leading to reform and change to be identified and implemented, by government and others.

Social implications
The situations and needs of drug users do not appear as a government priority. Continued reductions in public spending – austerity – are reducing treatment provision.

Originality/value
The paper attempts to identify factors which inhibit policy reform in the UK so that future reform becomes more realistic.
The influence of global players on the drug control system: an analysis of the role of the Russian Federation
Authors: Tinasti Khalid , Barbosa Isabela 
Published: April 2017

Purpose
The negotiations leading to the UN Special Session (UN General Assembly Special Session on drugs (UNGASS)) on drugs have highlighted the lack of consensus among the global players, with some strengthening the prohibitionist approach and others seeking policy reforms. The purpose of this paper is to focus on the Russian Federation’s national policies and diplomatic activism to influence the outcome of the negotiations at the multilateral level.

Design/methodology/approach
A systematic review of the federal legislation on drug control and the legislation on HIV/AIDS has been undertaking in October 2016. Peer-reviewed, grey literature, policy documents, UN reports and news reports were used to gather information on the country’s response to drugs internally and externally.

Findings
Despite its limited regional influence on harm reduction and declining financial power, the Russian Federation has been successful in preserving its international priorities by opposing harm reduction and maintaining the prohibition paradigm in the UNGASS outcome.

Research limitations/implications
Every effort was made to identify valid sources of information on the levers of influence of the Russian Federation. Little data were available on the real outcome of the efforts deployed in influencing the BRICS and other regional and international assemblies.

Originality/value
This paper presents an overview of the national policies of the Russian Federation, a global player, and provides a better understanding of how the national approach to illicit drugs and their perception influences its international position. It analyses the geographic, economic and diplomatic sphere of influence of the country in drug policies, and provides explanations on the successes and shortcomings of the Russian influence at the multilateral discussions on drugs.
Refocusing metrics: can the sustainable development goals help break the “metrics trap” and modernise international drug control policy?
Authors: Bewley-Taylor David R. 
Published: April 2017

PurposeThe purpose of this paper is to examine the extent to which the dominant metrics currently used to measure the success of the UN based global drug prohibition regime are in many ways inadequate and consequently contribute to systemic inertia. Within this context, it seeks to explore the potential of explicitly linking drug policy to the recently launched sustainable development agenda (SDA) and the associated sustainable development goals (SDGs) to initiate a change in approach.Design/methodology/approachFraming the topic in terms of international relations (IR) and regime analysis, prominent examples of where current metrics are imprecise (the relationship between production and seizures), misconceived (drug use) and missing (a range of drug and drug policy related harms) are explored. Attention is then given to an examination of international development as a model for measuring drug control outcomes, including a discussion of the SDGs in general and the intersection between drug policy interventions and several goals in particular.FindingsWhile aware of the complexity of the issue area, the paper finds that there are considerable shortcomings in the way international drug policy outcomes are currently assessed. Although methodological problems are likely to persist, linking drug policy with the SDGs and their associated metrics offers the potential to help to shift the focus of international policy in a manner that would benefit not only UN system-wide coherence on the issue, but also assist in the achievement of the regime’s own overarching goal; to safeguard the “health and welfare” of humankind.Practical implicationsWith the next high-level review of international drug policy due to take place in 2019, the paper offers policy makers with a way to begin to refocus drug policy metrics, and subsequently review outcomes, in line with the UN system-wide SDA.Originality/valueAs an emerging domain of inquiry, the paper not only explores a hitherto largely unexplored – yet increasingly important – facet of UN level policy evaluation, formulation and implementation, but also helps to fill a gap in the IR literature on regime dynamics.
The relational expectations of women managing women
Authors: Hurst Jane , Leberman Sarah , Edwards Margot 
Published: April 2017

Purpose
The purpose of this paper is to examine the expectations women have of their women managers and/or women employees and to suggest personal and organizational strategies to strengthen those relationships.

Design/methodology/approach
Building on a first phase of research using narrative inquiry into the lived experiences of women managing and/or being managed by women, workshops were held with 13 participants to explore their relationship expectations of women managers and/or employees.

Findings
While the participants initially believed they expected the same things of a manager or employee irrespective of gender, a closer examination revealed gender-based expectations. Women expect a higher degree of emotional understanding and support from a woman manager, than they would from a man. They also expect a woman manager to see them as an equal, take a holistic view of them as people, understand the complexities of their lives and provide flexibility to accommodate those complexities.

Research limitations/implications
This is an exploratory study in an under-researched area. Extensive further research is warranted.

Practical implications
Understanding the expectations women have of their women managers enables the development of both personal and organizational strategies aimed at strengthening those relationships.

Originality/value
These findings begin a dialogue on the often-unspoken and unrecognized gender-based expectations women have of their relationships with women managers and/or women employees. Although considerable research exists on gender stereotypes in the workplace, little research exists on these gender-based relational expectations.
Women in leadership in Kuwait: a research agenda
Authors: Al-Salem Athmar , Speece Mark 
Published: April 2017

PurposeThis study aims to examine perceptions in Kuwait about women’s leadership in management.Design/methodology/approachThis study includes a review of data on the gender gap across Middle East/North Africa (MENA) countries, comparison with selected Asian and Western countries and summaries of multiple small surveys in Kuwait on women in management. The surveys were all convenience samples ranging from 100-500, targeting middle-class respondents.FindingsThe MENA is behind most of the world in closing the gender gap, but progress among Gulf Cooperation Council countries has been fairly rapid. Many Gulf Cooperation Council (GCC) indicators are comparable to other non-Western cultural areas. Multiple surveys in Kuwait show fairly widespread acceptance of women in leadership positions. Respondents feel that characteristics of women vs men managers are different, but strengths and weaknesses by gender balance out, so that men and women perform about the same. Traditional Kuwaiti culture seems conducive to women in management, but some specific cultural barriers remain. In particular, thediwaniyya, social gatherings to network and discuss current affairs, andwasta, connections, are dominated by men in modern Kuwaiti society. These are essentially social capital issues.Practical implicationsFostering continued progress for women in management requires recognition of the actual social and cultural situation; simply arguing that Kuwait should be more Western in how it does things does not seem very useful.Originality/valueResearch on women in management in MENA is not very extensive, but is important for understanding how to facilitate opportunities for women. In Kuwait, there seems to be general acceptance that women can be leaders in managerial positions, and little overt discrimination. However, lack of access to traditional social capital networks puts women at a disadvantage. Research needs to focus on this issue to help develop ways to overcome this subtle obstacle to further progress.
The effects of gender role orientation and career/family role salience on organizational identification and intention to leave
Authors: Liu Huimin , Ngo Hang-yue 
Published: April 2017

PurposeThe purpose of this study is to examine how gender role orientation (i.e. masculinity and femininity) and career/family role salience affect individuals’ organizational identification (OID) and intention to leave. Alternative models were developed to specify different relationships among the study variables.Design/methodology/approachData were collected via a questionnaire survey of 362 employees from three large companies in China. Structural equation modeling was used to evaluate alternative models and test the hypotheses.FindingsThis paper found that masculinity was positively related to career role salience, whereas femininity was positively related to family role salience. Career role salience, but not family role salience, was positively related to OID, which in turn was negatively related to intention to leave. A positive relationship was also found between femininity and OID, as well as between family role salience and intention to leave.Research limitations/implicationsThe cross-sectional nature of the data of this study precludes any definitive inferences about causality and directionality. The use of self-report measures also invites the potential threat of common method variance. The generalizability of results has been restricted, given that the respondents were drawn from three large companies.Practical implicationsOrganizations may provide more resources and support for their employees so as to increase their career role salience, which in turn enhances their level of OID. For employees who are high in femininity, employers may offer family-friendly programs to help them address resource drain from family to work, and hence to retain them.Originality/valueThis study provided evidence for the linkage between gender role orientation with career/family role salience. It also revealed the impacts of career/family role salience on OID and intention to leave. Some gender differences in this regard were highlighted.
MyManagement: women managers in gendered and sexualised workplaces
Authors: McKie Linda , Jyrkinen Marjut 
Published: April 2017

Purpose
The authors report on research with women managers, documenting their strategies in response to gendered and sexualised working life. The paper aims to offer a conceptual framework and suggest ways in which employing organisations and workers might recognise and address the myriad forms of discrimination.

Design/methodology/approach
A qualitative design was pursued with 15 one-to-one interviews and two focus groups involving 12 women managers aged from their 30s to 60s. Data were collected in Finland. Women were recruited through business networks. Participants worked in a range of private sector and voluntary sector organisations.

Findings
Finland is a country which enjoys an international reputation for gender equality, but across the data, women recounted numerous examples of how they navigate working life to manage sexualised and discriminatory encounters and comments. Women reported feeling under constant surveillance for their looks, dress and behaviours in and outside the workplace. Further, ageing brought with it challenges to remain energetic and youthful and enhance the image of the organisation.

Originality/value
Although a considerable body of research exists on (gendered) aesthetic labour at work in service and hospitality work, there are limited data on this in business and middle management. With an ageing workforce, and women continuing to encounter pressures with their physical appearance, behaviours and dress, they continually develop ways to negotiate their careers. The authors propose the concept of “MyManagement” as a self-technology to denote the ways how women manage workplace relationships, working life and career development as organisational practices remain gendered.