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Challenging Questions (challenging + question)
Selected AbstractsFrom molecules to ecosystems through dynamic energy budget modelsJOURNAL OF ANIMAL ECOLOGY, Issue 6 2000R. M. Nisbet Summary 1. Dynamic energy budget (DEB) models describe how individuals acquire and utilize energy, and can serve as a link between different levels of biological organization. 2. We describe the formulation and testing of DEB models, and show how the dynamics of individual organisms link to molecular processes, to population dynamics, and (more tenuously) to ecosystem dynamics. 3. DEB models offer mechanistic explanations of body-size scaling relationships. 4. DEB models constitute powerful tools for applications in toxicology and biotechnology. 5. Challenging questions arise when linking DEB models with evolutionary theory. [source] REVIEW: Stress, alcohol and drug interaction: an update of human researchADDICTION BIOLOGY, Issue 1 2009Magdalena Uhart ABSTRACT A challenging question that continues unanswered in the field of addiction is why some individuals are more vulnerable to substance use disorders than others. Numerous risk factors for alcohol and other drugs of abuse, including exposure to various forms of stress, have been identified in clinical studies. However, the neurobiological mechanisms that underlie this relationship remain unclear. Critical neurotransmitters, hormones and neurobiological sites have been recognized, which may provide the substrates that convey individual differences in vulnerability to addiction. With the advent of more sophisticated measures of brain function in humans, such as functional imaging technology, the mechanisms and neural pathways involved in the interactions between drugs of abuse, the mesocorticolimbic dopamine system and stress systems are beginning to be characterized. This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from occasional drug use to drug dependence. We also review factors that contribute to different levels of hormonal/brain stress activation, which has implications for understanding individual vulnerability to drug dependence. Ultimately, these efforts may improve our chances of designing treatment strategies that target addiction at the core of the disorder. [source] Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease)GLIA, Issue 4 2006Philipp Berger Abstract Over the last 15 years, a number of mutations in a variety of genes have been identified that lead to inherited motor and sensory neuropathies (HMSN), also called Charcot-Marie-Tooth disease (CMT). In this review we will focus on the molecular and cellular mechanisms that cause the Schwann cell pathologies observed in dysmyelinating and demyelinating forms of CMT. In most instances, the underlying gene defects alter primarily myelinating Schwann cells followed by secondary axonal degeneration. The first set of proteins affected by disease-causing mutations includes the myelin components PMP22, P0/MPZ, Cx32/GJB1, and periaxin. A second group contains the regulators of myelin gene transcription EGR2/Krox20 and SOX10. A third group is composed of intracellular Schwann cells proteins that are likely to be involved in the synthesis, transport and degradation of myelin components. These include the myotubularin-related lipid phosphatase MTMR2 and its regulatory binding partner MTMR13/SBF2, SIMPLE, and potentially also dynamin 2. Mutations affecting the mitochondrial fission factor GDAP1 may indicate an important contribution of mitochondria in myelination or myelin maintenance, whereas the functions of other identified genes, including NDRG1, KIAA1985, and the tyrosyl-tRNA synthase YARS, are not yet clear. Mutations in GDAP1, YARS, and the pleckstrin homology domain of dynamin 2 lead to an intermediate form of CMT that is characterized by moderately reduced nerve conduction velocity consistent with minor myelin deficits. Whether these phenotypes originate in Schwann cells or in neurons, or whether both cell types are directly affected, remains a challenging question. However, based on the advances in systematic gene identification in CMT and the analyses of the function and dysfunction of the affected proteins, crucially interconnected pathways in Schwann cells in health and disease have started to emerge. These networks include the control of myelin formation and stability, membrane trafficking, intracellular protein sorting and quality control, and may extend to mitochondrial dynamics and basic protein biosynthesis. © 2006 Wiley-Liss, Inc. [source] Current trends in quantitative proteomicsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2009Monica H. Elliott Abstract It was inevitable that as soon as mass spectrometrists were able to tell biologists which proteins were in their samples, the next question would be how much of these proteins were present. This has turned out to be a much more challenging question. In this review, we describe the multiple ways that mass spectrometry has attempted to address this issue, both for relative quantitation and for absolute quantitation of proteins. There is no single method that will work for every problem or for every sample. What we present here is a variety of techniques, with guidelines that we hope will assist the researcher in selecting the most appropriate technique for the particular biological problem that needs to be addressed. We need to emphasize that this is a very active area of proteomics research,new quantitative methods are continuously being introduced and some ,pitfalls' of older methods are just being discovered. However, even though there is no perfect technique,and a better technique may be developed tomorrow,valuable information on biomarkers and pathways can be obtained using these currently available methods Copyright © 2009 John Wiley & Sons, Ltd. [source] Balancing uncertainty of context in ERP project estimation: an approach and a case studyJOURNAL OF SOFTWARE MAINTENANCE AND EVOLUTION: RESEARCH AND PRACTICE, Issue 5 2010Maya DanevaArticle first published online: 28 JUN 2010 Abstract The increasing demand for Enterprise Resource Planning (ERP) solutions as well as the high rates of troubled ERP implementations and outright cancellations calls for developing effort estimation practices to systematically deal with uncertainties in ERP projects. This paper describes an approach,and a case study,to balancing uncertainties of context in the very early project stages, when an ERP adopter initiates a request-for-proposal process and when alternative bids are to be compared for the purpose of choosing an implementation partner. The proposed empirical approach leverages the complementary application of three techniques, an algorithmic estimation model, Monte Carlo simulation, and portfolio management. Our case study findings show how the ability of our approach to model uncertainty allows practitioners to address the challenging question of how to adjust project context factors so that chances of project success are increased. We also include a discussion on the implications of our approach for practice as well as on the possible validity threats and what the practitioner could do to counterpart them. Copyright © 2010 John Wiley & Sons, Ltd. [source] THE COST OF ILLIQUIDITY AND ITS EFFECTS ON HEDGINGMATHEMATICAL FINANCE, Issue 4 2010L. C. G. Rogers Though liquidity is commonly believed to be a major effect in financial markets, there appears to be no consensus definition of what it is or how it is to be measured. In this paper, we understand liquidity as a nonlinear transaction cost incurred as a function of rate of change of portfolio. Using this definition, we obtain the optimal hedging policy for the hedging of a call option in a Black-Scholes model. This is a more challenging question than the more common studies of optimal strategy for liquidating an initial position, because our goal requires us to match a random final value. The solution we obtain reduces in the case of quadratic loss to the solution of three partial differential equations of Black-Scholes type, one of them nonlinear. [source] New tools for labeling silica in living diatomsNEW PHYTOLOGIST, Issue 3 2008Julien Desclés Summary ,,Silicon biomineralization is a widespread mechanism found in several kingdoms that concerns both unicellular and multicellular organisms. As a result of genomic and molecular tools, diatoms have emerged as a good model for biomineralization studies and have provided most of the current knowledge on this process. However, the number of techniques available to study its dynamics at the cellular level is still rather limited. ,,Here, new probes were developed specifically to label the pre-existing or the newly synthesized silica frustule of several diatoms species. ,,It is shown that the LysoTracker Yellow HCK-123, which can be used to visualize silica frustules with common filter sets, presents an enhanced signal-to-noise ratio and allows details of the frustules to be imaged without of the use of ionophores. It is also demonstrated that methoxysilane derivatives can be coupled to fluorescein-5-isothiocyanate (FITC) to preferentially label the silica components of living cells. ,,The coupling of labeling procedures might help to address the challenging question of the process of frustule exocytosis. [source] Still falling short: protection and partnerships in the Lebanon emergency responseDISASTERS, Issue 4 2007David Shearer The Israeli,Hezbollah conflict in the summer of 2006, although brief, had a lasting impact on the region and prompted an intense humanitarian response. The conflict raised challenging questions for the United Nations (UN) about how to assist a middle-income yet extremely vulnerable population in a context where global and local relations are highly politicised. This paper focuses on two key questions that emerged from the humanitarian response. First, how can humanitarian agencies, and particularly the UN, improve the protection of civilians, and was what they did in Lebanon enough? Second, how can humanitarian agencies create partnerships with local actors and still remain true to core humanitarian principles when local actors are fiercely divided along confessional lines and influenced by external actors, and when some, such as Hezbollah, are parties to the conflict? This paper argues that despite the importance of protection and partnerships to the humanitarian response, their role in the UN emergency response still falls short. [source] Designer haem proteins: What can we learn from protein engineering?HETEROATOM CHEMISTRY, Issue 6 2002Emma Lloyd Raven Iron protoporphyrin(IX) is one of the most versatile and widespread pieces of catalytic machinery known in biology and is a key component of a multitude of proteins and enzymes. One of most challenging questions in this area has been to identify and understand the relationships that exist between different classes of haem proteins and to use protein engineering methods to rationalize the mechanisms by which the protein structure controls the specific chemical reactivity of the haem group. The application of this approach to the haem enzyme ascorbate peroxidase and the haem protein leghaemoglobin is discussed. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:501,505, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10094 [source] MLL: How complex does it get?JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Relja Popovic Abstract The mixed lineage leukemia (MLL) gene encodes a very large nuclear protein homologous to Drosophila trithorax (trx). MLL is required for the proper maintenance of HOX gene expression during development and hematopoiesis. The exact regulatory mechanism of HOX gene expression by MLL is poorly understood, but it is believed that MLL functions at the level of chromatin organization. MLL was identified as a common target of chromosomal translocations associated with human acute leukemias. About 50 different MLL fusion partners have been isolated to date, and while similarities exist between groups of partners, there exists no unifying property shared by all the partners. MLL gene rearrangements are found in leukemias with both lymphoid and myeloid phenotypes and are often associated with infant and secondary leukemias. The immature phenotype of the leukemic blasts suggests an important role for MLL in the early stages of hematopoietic development. Mll homozygous mutant mice are embryonic lethal and exibit deficiencies in yolk sac hematopoiesis. Recently, two different MLL-containing protein complexes have been isolated. These and other gain- and loss-of-function experiments have provided insight into normal MLL function and altered functions of MLL fusion proteins. This article reviews the progress made toward understanding the function of the wild-type MLL protein. While many advances in understanding this multifaceted protein have been made since its discovery, many challenging questions remain to be answered. © 2005 Wiley-Liss, Inc. [source] A community of practice approach to the development of non-traditional learners through networked learningJOURNAL OF COMPUTER ASSISTED LEARNING, Issue 3 2006K. Guldberg Abstract This paper analyses a sample of online discussions to evaluate the development of adult learners as reflective practitioners within a networked learning community. The context for our study is a blended learning course offering post-experience professional training to non-traditional university students. These students are parents and carers of people with autistic spectrum disorder (ASD). We use Lave and Wenger's ,communities of practice' as a theoretical framework for establishing how students develop a learning community based upon mutual engagement, joint enterprise and shared repertoires. Those three aspects are analysed according to two measures. The first focuses on learner appropriation of the professional discourse, values and goals of the ASD carer through the network. The second relates to changes in the quality of collaborative activity over time. Our analysis demonstrates that students belong to an overarching community of practice, with different subsets who work at sharing and co-constructing common understandings. This shared discourse and common notions of what constitutes good practice help create a safe interaction space for the students. Once group identity is consolidated, more challenging questions emerge and the group are able to define further common values, understandings and goals through processes of resolution. [source] PLANNING FOR THE FUTURE: Planning for the 2040s: everybody's businessBRITISH JOURNAL OF SPECIAL EDUCATION, Issue 1 2008Peter Mittler As we mark the publication of the 35th issue of the British Journal of Special Education, Peter Mittler, Emeritus Professor of Special Needs Education at the University of Manchester, looks into the future and asks a series of challenging questions: What kind of a future do we want to see for a baby born with a significant disability today? What changes will be needed in society and in our schools both for the child and for the family? What reforms might this year's newly qualified staff bring about in our schools and services and in society as a whole by the time they retire in the 2040s? Professor Mittler proposes that the time is ripe to take advantage of new international and national opportunities to lay the foundations for a society that fully includes disabled people and safeguards their basic human rights. He argues that each one of us can help to determine the values and priorities of the society in which today's baby will grow up and suggests that the Make Poverty History movement has provided powerful evidence that the voice of ordinary citizens can shape policies and set priorities. He encourages us all to think globally and to act locally on a host of issues, including supporting families, planning for transition, promoting quality of life, professional development and challenging inequality. [source] The More Things Change the More They Stay the Same?BRITISH JOURNAL OF SPECIAL EDUCATION, Issue 4 2002A Response to the Audit Commission's Report on Statutory Assessment, Statements of SEN This article provides a response to some of the issues raised by Anne Pinney's summary, published in the September issue of BJSE, of the Audit Commission's report on statutory assessment and Statements of Special Educational Needs. In developing her critique, Lani Florian, lecturer in special and inclusive education at the University of Cambridge Faculty of Education and Editor of the Journal of Research in Special Educational Needs, asks a series of important and challenging questions. Can the broad notion of ,special educational needs' complement ideas about ,areas of need' or ,categories of handicap' and enable young people with severe, complex or long,term disabilities to have their needs met? Is SEN funding fairly distributed, among pupils with special educational needs in particular and across the education system in general? Should the relationship between the processes of formative and statutory assessment and Statements of Special Educational Needs be reconceptualised? Can the protection offered by the Statement be maintained in association with the development of good inclusive practices? And if there is to be a move away from provision designed to address children's individual difficulties, what forms of thinking, procedure and practice will enable staff to develop new ways of meeting the needs of all learners? I hope that the questions raised by this article will stimulate other commentators to contribute to the debate about our responses to special educational needs in the pages of BJSE [source] 2 Incorporation of Audience Participation Technology into Resident Curriculum ReviewACADEMIC EMERGENCY MEDICINE, Issue 2008Brian Sayger We have incorporated audience participation technology (Turning Point) into our weekly curriculum review sessions. This audience response system consists of individual remote response keypads, a USB port-compatible receiver, and software which integrates into PowerPoint. Board-style questions are written into PowerPoint slides and presented by the speaker. Rather than selecting one resident to answer a question, all audience members select an answer using their keypad. The receiver registers the answers and immediately displays a graph of the audience's responses. Questions with more incorrect answers are discussed in detail while less time is spent on questions answered correctly by most of the audience. This encourages active participation for each question and eliminates the stress of a single resident giving an incorrect answer in front of a large number of peers. Audience members are engaged throughout the hour rather than concentrating only on questions assigned to them. Residents and students discover that challenging questions are answered incorrectly by a significant number of audience members. In a short time using this system, we've seen audience discussion increase dramatically. We plan to expand our use of this technology to other lectures. Speakers will administer end-of-lecture quizzes, immediately assessing how effectively their presentation achieved its learning objectives. All residents have an assigned keypad, and their percentage of correct answers is recorded during every session. This allows the program to monitor a resident's progress and to identify areas in which the resident may need more instruction. This system has potential applications for competency assessment. [source] | ||||||||||||||||