bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of individualized therapeutic vulnerabilities in cancer from genomic profiles
Authors: Aksoy Bülent Arman , Demir Emek , Babur Özgün , Wang Weiqing , Jing Xiaohong , Schultz Nikolaus , Sander Chris 
Published: March 2014

Abstract
Motivation: Somatic homozygous deletions of chromosomal regions in cancer, while not necessarily oncogenic, may lead to therapeutic vulnerabilities specific to cancer cells compared with normal cells. A recently reported example is the loss of one of the two isoenzymes in glioblastoma cancer cells such that the use of a specific inhibitor selectively inhibited growth of the cancer cells, which had become fully dependent on the second isoenzyme. We have now made use of the unprecedented conjunction of large-scale cancer genomics profiling of tumor samples in The Cancer Genome Atlas (TCGA) and of tumor-derived cell lines in the Cancer Cell Line Encyclopedia, as well as the availability of integrated pathway information systems, such as Pathway Commons, to systematically search for a comprehensive set of such epistatic vulnerabilities.
Results: Based on homozygous deletions affecting metabolic enzymes in 16 TCGA cancer studies and 972 cancer cell lines, we identified 4104 candidate metabolic vulnerabilities present in 1019 tumor samples and 482 cell lines. Up to 44% of these vulnerabilities can be targeted with at least one Food and Drug Administration-approved drug. We suggest focused experiments to test these vulnerabilities and clinical trials based on personalized genomic profiles of those that pass preclinical filters. We conclude that genomic profiling will in the future provide a promising basis for network pharmacology of epistatic vulnerabilities as a promising therapeutic strategy.
Availability and implementation : A web-based tool for exploring all vulnerabilities and their details is available at http://cbio.mskcc.org/cancergenomics/statius/ along with supplemental data files.
Contact : statius@cbio.mskcc.org
Supplementary information: Supplementary data are available at Bioinformatics online.
Conservation and fisheries effects of spawning aggregation marine protected areas: What we know, where we should go, and what we need to get there
Authors: Grüss Arnaud , Robinson Jan , Heppell Selina S. , Heppell Scott A. , Semmens Brice X. 
Published: March 2014

Abstract
There is a global trend in the depletion of transient reef fish spawning aggregations (“FSAs”), making them a primary target for management with marine protected areas (MPAs). Here, we review the observed and likely effectiveness of FSA MPAs, discuss how future studies could fill knowledge gaps, and provide recommendations for MPA design based on species' life history and behaviour, enforcement potential, and management goals. Modelling studies indicate that FSA MPAs can increase spawning-stock biomass and normalize sex ratio in protogynous fish populations, unless fishing mortality remains high outside protected FSA sites and spawning times. In the field, observations of no change or continued decline in spawning biomass are more common than population recovery. When empirical studies suggest that FSA MPAs may not benefit fish productivity or recovery, extenuating factors such as insufficient time since MPA creation, poor or lack of enforcement, inadequate design, and poorly defined management objectives are generally blamed rather than failure of the MPA concept. Results from both the empirical and modelling literature indicate that FSA MPAs may not improve exploitable biomass and fisheries yields; however, investigations are currently too limited to draw conclusions on this point. To implement effective FSA MPAs, additional modelling work, long-term monitoring programmes at FSA sites, and collections of fisheries-dependent data are required, with greater attention paid to the design and enforcement of area closures. We recommend a harmonized, adaptive approach that combines FSA MPA design with additional management measures to achieve explicitly stated objectives. Conservation objectives and, therefore, an overall reduction in mortality rates should be targeted first. Fisheries objectives build on conservation objectives, in that they require an overall reduction in mortality rates while maintaining sufficient access to exploitable biomass. Communication among researchers, regulatory agencies, park authorities, and fishers will be paramount for effective action, along with significant funds for implementation and enforcement.
Maintenance of Segmental Lordosis and Disk Height in Stand-alone and Instrumented Extreme Lateral Interbody Fusion (XLIF)
Authors: Malham Gregory M. , Ellis Ngaire J. , Parker Rhiannon M. , Blecher Carl M. , White Rohan , Goss Ben , Seex Kevin A. 
Published: March 2014

Study Design:
A prospective single-surgeon nonrandomized clinical study.

Objective:
To evaluate the radiographic and clinical outcomes, by fixation type, in extreme lateral interbody fusion (XLIF) patients and provide an algorithm for determining patients suitable for stand-alone XLIF.

Summary of Background Data:
XLIF may be supplemented with pedicle screw fixation, however, since stabilizing structures remain intact, it is suggested that stand-alone XLIF can be used for certain indications. This eliminates the associated morbidity, though subsidence rates may be elevated, potentially minimizing the clinical benefits.

Materials and Methods:
A fixation algorithm was developed after evaluation of patient outcomes from the surgeon’s first 30 cases. This algorithm was used prospectively for 40 subsequent patients to determine the requirement for supplemental fixation. Preoperative, postoperative, and 12-month follow-up computed tomography scans were measured for segmental and global lumbar lordosis and posterior disk height. Clinical outcome measures included back and leg pain (visual analogue scale), Oswestry Disability Index (ODI), and SF-36 physical and mental component scores (PCS and MCS).

Results:
Preoperatively to 12-month follow-up there were increases in segmental lordosis (7.9–9.4 degrees, P=0.0497), lumbar lordosis (48.8–55.2 degrees, P=0.0328), and disk height (3.7–5.5 mm, P=0.0018); there were also improvements in back (58.6%) and leg pain (60.0%), ODI (44.4%), PCS (56.7%), and MCS (16.1%) for stand-alone XLIF. For instrumented XLIF, segmental lordosis (7.6–10.5 degrees, P=0.0120) and disk height (3.5–5.6 mm, P<0.001) increased, while lumbar lordosis decreased (51.1–45.8 degrees, P=0.2560). Back (49.8%) and leg pain (30.8%), ODI (32.3%), PCS (37.4%), and MCS (2.0%) were all improved. Subsidence occurred in 3 (7.5%) stand-alone patients.

Conclusions:
The XLIF treatment fixation algorithm provided a clinical pathway to select suitable patients for stand-alone XLIF. These patients achieved positive clinical outcomes, satisfactory fusion rates, with sustained correction of lordosis and restoration of disk height.
An optimized CRISPR/Cas toolbox for efficient germline and somatic genome engineering inDrosophila
Authors: Port Fillip , Chen Hui-Min , Lee Tzumin , Bullock Simon L. 
Published: March 2014

AbstractThe type II CRISPR/Cas system has recently emerged as a powerful method to manipulate the genomes of various organisms. Here, we report a novel toolbox for high efficiency genome engineering ofDrosophila melanogasterconsisting of transgenic Cas9 lines and versatile guide RNA (gRNA) expression plasmids. Systematic evaluation reveals Cas9 lines with ubiquitous or germline restricted patterns of activity. We also demonstrate differential activity of the same gRNA expressed from different U6 snRNA promoters, with the previously untested U6:3 promoter giving the most potent effect. Choosing an appropriate combination of Cas9 and gRNA allows targeting of essential and non-essential genes with transmission rates ranging from 25% - 100%. We also provide evidence that our optimized CRISPR/Cas tools can be used for offset nicking-based mutagenesis and, in combination with oligonucleotide donors, to precisely edit the genome by homologous recombination with efficiencies that do not require the use of visible markers. Lastly, we demonstrate a novel application of CRISPR/Cas-mediated technology in revealing loss-of-function phenotypes in somatic cells following efficient biallelic targeting by Cas9 expressed in a ubiquitous or tissue-restricted manner. In summary, our CRISPR/Cas tools will facilitate the rapid evaluation of mutant phenotypes of specific genes and the precise modification of the genome with single nucleotide precision. Our results also pave the way for high throughput genetic screening with CRISPR/Cas.
Hybridization Alters Spontaneous Mutation Rates in a Parent-of-Origin-Dependent Fashion in Arabidopsis
Authors: Bashir Tufail , Sailer Christian , Gerber Florian , Loganathan Nitin , Bhoopalan Hemadev , Eichenberger Christof , Grossniklaus Ueli , Baskar Ramamurthy 
Published: March 2014

AbstractOver 70 years ago, increased spontaneous mutation rates were observed in Drosophila spp. hybrids, but the genetic basis of this phenomenon is not well understood. The model plant Arabidopsis (Arabidopsis thaliana) offers unique opportunities to study the types of mutations induced upon hybridization and the frequency of their occurrence. Understanding the mutational effects of hybridization is important, as many crop plants are grown as hybrids. Besides, hybridization is important for speciation and its effects on genome integrity could be critical, as chromosomal rearrangements can lead to reproductive isolation. We examined the rates of hybridization-induced point and frameshift mutations as well as homologous recombination events in intraspecific Arabidopsis hybrids using a set of transgenic mutation detector lines that carry mutated or truncated versions of a reporter gene. We found that hybridization alters the frequency of different kinds of mutations. In general, Columbia (Col) × Cape Verde Islands and Col × C24 hybrid progeny had decreased T→G and T→A transversion rates but an increased C→T transition rate. Significant changes in frameshift mutation rates were also observed in some hybrids. In Col × C24 hybrids, there is a trend for increased homologous recombination rates, except for the hybrids from one line, while in Col × Cape Verde Islands hybrids, this rate is decreased. The overall genetic distance of the parents had no influence on mutation rates in the progeny, as closely related accessions on occasion displayed higher mutation rates than accessions that are separated farther apart. However, reciprocal hybrids had significantly different mutation rates, suggesting parent-of-origin-dependent effects on the mutation frequency.
Bibliometric data and actual development in technology life cycles: flaws in assumptions
Authors: Suominen Arho , Seppänen Marko 
Published: March 2014

Purpose
– Motivated with the ever growing number of bibliometric trend extrapolation studies, the purpose of this paper is to demonstrate through two technologies how the selection of an upper limit of growth affects the correlation and causality of technology development measured with bibliometric data.

Design/methodology/approach
– The paper uses Gompertz and Fisher-Pry curves to model the technological development of white light emitting diodes and flash memory, and show with extrapolation results from several bibliometric sources how a typical bias is caused in trend extrapolations.

Findings
– The paper shows how drastic an effect the decision to set an upper bound has on trend extrapolations, to be used as a reference for applications. The paper recommends carefully examining the interconnection of actual development and bibliometric activity.

Originality/value
– Despite increasing interest in modelling technological data using this method, reports rarely discuss basic assumptions and their effects on outcomes. Since trend extrapolations are applied more widely in different disciplines, the basic limitations of methods should be explicitly expressed.
Effect of load type on temperature rise of a disc brake
Authors: Meng Qing-rui 
Published: March 2014

Purpose
– The purpose of this paper is to reveal the temperature rise characteristics of the disc and pads under different load types.

Design/methodology/approach
– Evolutions of the disc and pads temperature under a stable, gradual changing and sine-wave contact pressures widely used at present are analyzed numerically by using ANSYS software.

Findings
– The results show that during the loading process, the temperature increases most rapidly under a stable contact pressure, most slowly under a gradual changing contact pressure; the disc temperature rise curves expose saw-shaped character, the closer it is to the friction surface, the more serious the fluctuations will be, the pads temperature rise curves are rather smooth; temperature gradient in the axial direction is higher than that in the other two directions under all of the three types of contact pressure and shows a sine-wave variation under a sine-wave contact pressure.

Originality/value
– It indicates that a gradual changing contact pressure should be adopted preferentially in practical application. The simulation results of this work provide theoretical basis for load simulation.
The “conflict volcano”: methodological proposition for conflict analysis
Authors: Temirkulov Azamat 
Published: March 2014

Purpose– The purpose of this paper is to suggest to the conflict study scholars a new instrument – the “conflict volcano” that could be an effective and appropriate tool for conflict analysis.Design/methodology/approach– The “conflict volcano” model was designed as a qualitative method for conflict analysis with a focus on cause analysis. It was developed on the basis of “conflict tree” which underwent modifications.Findings– The benefit of the “conflict volcano” is that it covers all aspects of conflict starting from root cause to catalysts and can reveal a wide range of causes: material, immaterial, institutional. It clearly frames factors; this helps practitioners to determine what should be considered as causes and effects. Moreover, the “conflict volcano” reflects major theoretical representations of the conflict and its aspects. While the “conflict volcano” model can study conflict phases from latent until open violence, it cannot reflect the dynamic of conflict and cannot demonstrate its evolution to post-conflict phases.Practical implications– The “conflict volcano” can be used as a conflict analysis tool by practicing experts and scholars. Academicians can use it in order to understand conflict and especially to reveal its causes. Practicing experts can use it in order to design a conflict transformation strategy.Originality/value– This instrument does not pretend to be a new invention in the field of conflict studies, but rather a new conceptualization, schematization of old concepts and instruments.
The role of marketing in today's enterprises
Authors: Wirtz Jochen , Tuzovic Sven , G. Kuppelwieser Volker 
Published: March 2014

Purpose
– The purpose of this paper is to explore the role of marketing in today's enterprises and examines the antecedents of the marketing department's influence and its relationship with market orientation and firm performance.

Design/methodology/approach
– Data were collected from the West (i.e. the USA and Europe) and the East (i.e. Asia). Partial least squares (PLS) was used to estimate structural models.

Findings
– The findings support the idea that a strong and influential marketing department contributes positively to firm performance. This finding holds for Western and Asian, and for small/medium and large firms alike. Second, the marketing department's influence in a firm depends more on its responsibilities and resources, and less on internal contingency factors (i.e. a firm's competitive strategy or institutional attributes). Third, a marketing department's influence in the West affects firm performance both directly and indirectly (via market orientation). In contrast, this relationship is fully mediated among Eastern firms. Fourth, low-cost strategies enhance the influence of a firm's marketing department in the East, but not in the West.

Research limitations/implications
– The paper assumes explicitly that a marketing department's influence is an antecedent of its market orientation. While the paper finds support for this link, the paper did not test for dual causality between the constructs.

Originality/value
– Countering the frequent claim in anecdotal and journalistic work that the role of the marketing department diminishes, the findings show that across different geographic regions and firm sizes, strong marketing departments improve firm performance (especially in the marketing-savvy West), and that they should continue to play an important role in firms.
Systemic integration of holistic project- and hospitality management
Authors: Sibila Lebe Sonja , Vrecko Igor 
Published: March 2014

Purpose
– This conceptual paper aims to integrate and significantly extend past research cognitions from three different scientific fields: project management (PM), hospitality management (HM) and systems thinking (ST). As scarcely any scientific sources are available on these topics, this paper closes a gap in literature and invites to further research in this field. Special stress is given to the research of possible preventing or at least reducing of negative impacts/footprints of hospitality development to the social and physical environments.

Design/methodology/approach
– The authors present an overview of milestones in project- and HM development in Europe from the end of the Roman Empire till today. The main development stages are checked in view of SR and ST applications.

Findings
– This research is predominately theoretical, although it also presents several examples from practice that very clearly illustrate the need for merging the knowledge from these both (PM and HM) fields of expertise. The results of the evolution stages show that the development of both HM and PM has always been synchronic, and that PM has practically in all development stages been applied to HM, although this happened unconsciously and thus less effective than in other industries.

Originality/value
– The value of this research is an improved understanding of the need for merging the cognitions from HM and PM for more responsibility in further HM projects.
Ethical issues in shadowing research
Authors: Johnson Bart 
Published: March 2014

Purpose
– The purpose of this paper is to explore ethical issues associated with using the shadowing method.

Design/methodology/approach
– Ethical issues that arose during a 12-week shadowing study that examined the work activities and practices of Canadian healthcare CEOs are discussed.

Findings
– Dividing the ethics process into two phases – those addressed by ethics committees (procedural ethics) and those that revealed themselves in the field (ethics in practice) – issues and relating to sampling, informed consent, researcher roles, objectivity, participant discomforts, the impact of research on participants, confidentiality, and anonymity are investigated. This paper illustrates that while useful, procedural ethics committees are unable to establish ethical practice in and of themselves. In response, it suggests that the concept of reflexivity be applied to ethics to help researchers consider the implications of using the shadowing method, and develop a contingency for possible challenges, before they enter the field.

Practical implications
– This paper provides researchers considering using the shadowing method with critical insights into some of the ethical issues associated with the method. A number of questions are posed and a number of suggestions offered as to how ethical practice can be attained in the field. Given practice-based similarities between shadowing and other qualitative methodologies such as participant observation and ethnography, many of the lessons derived from this case study are also pertinent to researchers using other techniques to examine organizational and management phenomenon.

Originality/value
– Building on the formal and critical discussion about the shadowing method ignited by McDonald (2005), this paper identifies and discusses ethical issues associated with the shadowing method that have not been examined in either ethics or research methods literature.
Cross-cultural influences on e-value creation in supply chains
Authors: M. Davis Joshua , Mora-Monge Carlo , Quesada Gioconda , Gonzalez Marvin 
Published: March 2014

Purpose
– This paper seeks to report the results of an empirical study examining the influence of cross-cultural differences on the value creation process from e-business systems in the supply chain.

Design/methodology/approach
– A questionnaire was sent out to senior managers in companies operating in two culturally distinct national cultures. The effects of cross-cultural differences were examined by testing for between-group differences in the structural model using the multi-group partial least squares (PLS) statistical approach.

Findings
– Consistent with the resource-based view (RBV), contingency “fit” theory, and prior research, this study demonstrates that the value creation process from e-business systems is significantly enhanced in companies operating in national cultures that emphasize cooperation and interdependence, and promote group-level interests over individual interests.

Originality/value
– The mechanisms through which performance improvement is achieved from e-business systems are still not fully understood. Little is still known about how digital capabilities and environmental factors work together to influence e-business value creation along the supply chain. In addition, while contextual factors have been highlighted within the stream, the knowledge base is especially limited regarding the role of global factors in shaping the attainment of value from e-business systems in this context. Filling these gaps, this study simultaneously investigates the roles of intermediate capabilities and the macro-environment in creating value from e-business in the supply chain.