Seeing is believing: Applications for nanotechnology in medical imaging and drug discovery

In recent years, progress has been made on in both micro- and nano-sized materials. At the same time, the advances in biology, specifically in genomics, have provided us with a wealth of information that can now be put into research applications and hopefully clinical practice. In our research center in Niskayuna, NY, we have been working on advanced technologies and novel approaches in both areas. Here we show several examples of how we have addressed different topics in our research. In addition, we will show, how we are combining nanotechnology with advanced biology. In particular, we will show examples of using nanoparticles for different applications in vitro and in vivo. We will also show the context for both technology areas and the applications of strategic importance.     

The roles of integration in molecular systems biology

A common way to think about scientific practice involves classifying it as hypothesis- or data-driven. We argue that although such distinctions might illuminate scientific practice very generally, they are not sufficient to understand the day-to-day dynamics of scientific activity and the development of programmes of research. One aspect of everyday scientific practice that is beginning to gain more attention is integration. This paper outlines what is meant by this term and how it has been discussed from scientific and philosophical points of view. We focus on methodological, data and explanatory integration, and show how they are connected. Then, using some examples from molecular systems biology, we will show how integration works in a range of inquiries to generate surprising insights and even new fields of research. From these examples we try to gain a broader perspective on integration in relation to the contexts of inquiry in which it is implemented. In today's environment of data-intensive large-scale science, integration has become both a practical and normative requirement with corresponding implications for meta-methodological accounts of scientific practice. We conclude with a discussion of why an understanding of integration and its dynamics is useful for philosophy of science and scientific practice in general.     

A career structure for general practice.

Training for general practitioners usually provides little experience in research, business management, or dealing with chronic disease. It is these areas that could provide scope for further training after becoming a general practitioner principal and provided career goals. Formally recognised research practices, perhaps with one partner coordinating research but all participating, and district research facilitators could increase both the quality and the quantity of research in general practice. Recognising the different skills of doctors in the partnership and referring patients to the most appropriate partner will improve care for patients as well as provide career development. Further training could be aimed at filling gaps in the practice''s pool of skills. Good management skills are becoming more important as practice teams get bigger and fundholding spreads. Some doctors may wish to become full time or part time managers and the idea of accredited courses for management has been raised.     

Empirical power and sample size calculations for cluster-randomized and cluster-randomized crossover studies

In recent years, the number of studies using a cluster-randomized design has grown dramatically. In addition, the cluster-randomized crossover design has been touted as a methodological advance that can increase efficiency of cluster-randomized studies in certain situations. While the cluster-randomized crossover trial has become a popular tool, standards of design, analysis, reporting and implementation have not been established for this emergent design. We address one particular aspect of cluster-randomized and cluster-randomized crossover trial design: estimating statistical power. We present a general framework for estimating power via simulation in cluster-randomized studies with or without one or more crossover periods. We have implemented this framework in the clusterPower software package for R, freely available online from the Comprehensive R Archive Network. Our simulation framework is easy to implement and users may customize the methods used for data analysis. We give four examples of using the software in practice. The clusterPower package could play an important role in the design of future cluster-randomized and cluster-randomized crossover studies. This work is the first to establish a universal method for calculating power for both cluster-randomized and cluster-randomized clinical trials. More research is needed to develop standardized and recommended methodology for cluster-randomized crossover studies.     

The use of Caenorhabditis elegans in parasitic nematode research

There is increasing interest in the use of the free-living nematode Caenorhabditis elegans as a tool for parasitic nematode research and there are now a number of compelling examples of its successful application. C. elegans has the potential to become a standard tool for molecular helminthology researchers, just as yeast is routinely used by molecular biologists to study vertebrate biology. However, in order to exploit C. elegans in a meaningful manner, we need a detailed understanding of the extent to which different aspects of C. elegans biology have been conserved with particular groups of parasitic nematodes. This review first considers the current state of knowledge regarding the conservation of genome organisation across the nematode phylum and then discusses some recent evolutionary development studies in free-living nematodes. The aim is to provide some important concepts that are relevant to the extrapolation of information from C. elegans to parasitic nematodes and also to the interpretation of experiments that use C. elegans as a surrogate expression system. In general, examples have been specifically chosen because they highlight the importance of careful experimentation and interpretation of data. Consequently, the focus is on the differences that have been found between nematode species rather than the similarities. Finally, there is a detailed discussion of the current status of C. elegans as a heterologous expression system to study parasite gene function and regulation using successful examples from the literature.     

Amphibians as models for studying environmental change

The use of amphibians as models in ecological research has a rich history. From an early foundation in studies of amphibian natural history sprang generations of scientists who used amphibians as models to address fundamental questions in population and community ecology. More recently, in the wake of an environment that human disturbances rapidly altered, ecologists have adopted amphibians as models for studying applied ecological issues such as habitat loss, pollution, disease, and global climate change. Some of the characteristics of amphibians that make them useful models for studying these environmental problems are highlighted, including their trophic importance, environmental sensitivity, research tractability, and impending extinction. The article provides specific examples from the recent literature to illustrate how studies on amphibians have been instrumental in guiding scientific thought on a broad scale. Included are examples of how amphibian research has transformed scientific disciplines, generated new theories about global health, called into question widely accepted scientific paradigms, and raised awareness in the general public that our daily actions may have widespread repercussions. In addition, studies on amphibian declines have provided insight into the complexity in which multiple independent factors may interact with one another to produce catastrophic and sometimes unpredictable effects. Because of the complexity of these problems, amphibian ecologists have been among the strongest advocates for interdisciplinary research. Future studies of amphibians will be important not only for their conservation but also for the conservation of other species, critical habitats, and entire ecosystems.     

What constitutes fair shared decision-making in global health research collaborations?

Funders (located primarily in high-income countries) and high-income country researchers have historically dominated decision-making within global health research collaborations: from setting agendas and research design to determining how data are collected and analysed and what happens with findings and outputs. The ethical principle of shared decision-making has been proposed as a way to help address these imbalances within collaborations and to reduce semicolonial and exploitative forms of global health research. It is important to be clear about what shared decision-making means in order to ensure that it is not done in a tokenistic, shallow way. Thus far, the principle’s content has not been examined and articulated in detail. This paper aims to start the process of delineating a concept of fair shared decision-making as a minimum standard for global health research. Using two hypothetical case examples, the paper will demonstrate that global health research practice is often inconsistent with ideal shared decision-making. In such instances, it can be difficult to decide whether shared decision-making within collaborations is fair. The paper describes how the two cases do not meet criteria for unfair or non-ideal shared decision-making, despite having potentially morally troubling features. The nuances of these examples of research practice help to generate clearer ideas about how to judge fairness in shared decision-making. The paper concludes by presenting ideas about when soft power can be fairly employed between high-income-country and low- and middle-income-country partners and what fair compromise agreements may look like in shared decision-making.     

Analysis of continuous covariables in epidemiological studies: Dose‐response modelling and confounder adjustment

The analysis of continuous covariables with regression models commonly used in epidemiology are reviewed and compared. While some methods have been in use for decades, other more recent methods are not yet common or have not yet been formally described. It is shown that recently developed methods such as fractional polynomials and others are very useful to obtain dose‐response curves or for confounder adjustment. Different methods have their specific merits making it difficult to give general recommendations. The application of some of the methods is demonstrated with real data examples from epidemiological studies. Some suggestions for practical strategies in analysing continuous covariables are given.     

Standard reporting requirements for biological samples in metabolomics experiments: microbial and in vitro biology experiments

With the increasing use of metabolomics as a means to study a large number of different biological research questions, there is a need for a minimal set of reporting standards that allow the scientific community to evaluate, understand, repeat, compare and re-investigate metabolomics studies. Here we propose, a first draft of minimal requirements to effectively describe the biological context of metabolomics studies that involve microbial or in vitro biological subjects. This recommendation has been produced by the microbiology and in vitro biology working subgroup of the Metabolomics Standards Initiative in collaboration with the yeast systems biology network as part of a wider standardization initiative led by the Metabolomics Society. Microbial and in vitro biology metabolomics is defined by this sub-working group as studies with any cell or organism that require a defined external medium to facilitate growth and propagation. Both a minimal set and a best practice set of reporting standards for metabolomics experiments have been defined. The minimal set of reporting standards for microbial or in vitro biology metabolomics experiments includes those factors that are specific for metabolomics experiments and that critically determine the outcome of the experiments. The best practice set of reporting standards contains both the factors that are specific for metabolomics experiments and general aspects that critically determine the outcome of any microbial or in vitro biological experiment.     

Role of modelling in improving nutrient efficiency in cropping systems

The applicability of models in addressing resource management issues in agriculture has been widely promoted by the research community, yet examples of real impacts of such modelling efforts on current farming practices are rare. Nevertheless, simulation models can compliment traditional field experimentation in researching alternative management options. The first objective of this paper is, therefore, to provide four case study examples of where models were used to help research issues relating to improved nutrient efficiency in low-input cropping systems. The first two cases addressed strategies of augmenting traditional farming practices with small applications of chemical fertilizer (N and P). The latter two cases explicitly addressed the question of what plant genetic traits can be beneficial in low-nutrient farming systems. In each of these case studies, the APSIM (Agricultural Production Systems Simulator) systems model was used to simulate the impacts of alternative crop management systems.The question of whether simulation models can assist the research community in contributing to purposeful change in farming practice is also addressed. Recent experiences in Australia are reported where simulation models have contributed to practice change by farmers. Finally, current initiatives aimed at testing whether models can also contribute to improving the nutrient efficiency of smallholder farmers in the SAT are discussed.     

Careers in academic general practice: problems,constraints, and opportunities.

Changing priorities in the NHS have underlined the crucial importance of academic general practice in providing quality training and research to underpin developments in general practice. Unfortunately, several problems and constraints mean that the full potential of general practitioners to make a contribution to teaching and research has not been realised. These issues are examined and recommendations for improvements are made. Obstacles to career development for academics in general practice should be removed. The funding of academic general practice should be the same as for other medical disciplines. Vocational training for general practice should be extended to include research and audit methods, particularly for doctors interested in an academic career. Above all, the long term objective should be to integrate undergraduate and post-graduate general practice to increase the overall effectiveness of teaching and research and hence the quality of service general practice.     

Management of myocardial infarction in a rural area

In an attempt to determine the most appropriate type of facility for the treatment of myocardial infarction in a rural community, the five-year experience of a practice serving 10,000 people is reviewed. This population is found to have a low incidence of myocardial infarction, a low death rate from the condition both in hospitalized patients and in the general population, and a low incidence of complications in the survivors. None of the deaths either in or out of hospital would likely have been prevented through the use of specialized facilities. It is concluded that no such facilities are necessary in this community and that other areas considering their acquisition should justify the need on the basis of their own experience and not on accounts in the literature.     

Metabolic and evolutionary engineering research in Turkey and beyond

This review discusses metabolic engineering research with an emphasis on evolutionary (whole cell and protein) engineering, which is an inverse metabolic engineering approach. For each section on metabolic, inverse metabolic and evolutionary engineering research, a general review of the major global studies in the literature is made and research examples from Turkey are given and discussed. It is expected that with the rapid development in systems biology and the novel powerful analytical technologies to identify the genetic basis of cellular phenotypes, metabolic and evolutionary engineering research will become widespread and increasingly important in Turkey, following global scientific trends.     

鼎湖山森林群落演替之研究(英文)

鼎湖山森林群落在自然状态下遵循一定的客观规律向更优化的气候顶极群落演变。本文分析其1955年至1989年(35年)来的演替结果,总结出鼎湖山森林群落演替的进程和模式,进一步应用植物群落演替系统的线性模型和非线性模型对演替进程进行定量研究,并做出相应的演替进程的数量预测。     

DNA damage in humans exposed to environmental and dietary polycyclic aromatic hydrocarbons

The paper describes recent research on human DNA damage related to environmental and dietary polycyclic aromatic hydrocarbon (PAH) exposures. The study populations either represent general populations of large geographical regions, or their exposure situation may have relevance to the general population. In Silesia, Poland, and Northern Bohemia, Czech Republic, where coal-based industry and domestic heating are the major sources of PAHs, significant differences have been observed in white blood cell DNA adducts and cytogenetic biomarkers between environmentally exposed and rural control populations, and significant seasonal variations of DNA damage have been detected. Bus drivers, traffic policemen and local residents have been involved in biomarker studies in Copenhagen, Athens, Genoa and Cairo, and differences have been measured in the level of DNA damage of urban and rural populations. Burning of smoky coal in unvented homes in Xuan Wei region, China, causes high PAH exposure of residents, which has been reflected in DNA adduct levels in different tissues. Indoor wood burning in open fireplaces did not increase human DNA adduct levels. Oil-well fires left burning in Kuwait after the Persian Gulf war created an unprecedented environmental pollution. However, insignificant environmental PAH levels were measured several miles from these fires. Aromatic and PAH-DNA adduct levels in white blood cells of US Army soldiers were lower during their deployment in Kuwait, than in Fulda, Germany, where they were stationed before and after serving in Kuwait. The contribution of dietary PAH exposure to blood cell DNA adduct levels had been demonstrated in studies in which volunteers consumed heavily charbroiled beef. Environmental tobacco smoke did not cause detectable changes, as measured by 32P-postlabelling, in DNA adduct levels in non-smokers. In the reviewed studies, observed DNA adduct levels were generally in the range of 1 to 10 adducts, and not higher than 40 adducts in 108 nucleotides. Typically, 1.5 to 3-fold differences have been detected in DNA adduct levels between the exposed and control groups.     

Funding options for research: facing the market as well as government.

Parasitology is a challenge. At one level, the structural and genetic complexities of parasites provide ample technical challenges in regard to an understanding of parasite variability and adaptability, epidemiological diversity, drug resistance, etc. The intricacies of host parasite relationships including the immunology of parasitism will continually surprise yet frustrate the vaccine developer and keep the bravest immunoparasitologist busy and creative for decades. As if the technical considerations were not challenging enough, we see difficulties arising in sustaining a research endeavour and preserving a critical mass of researchers through the generation of high-level, long-term funding support. Contributing to this situation is the fact that most parasitic diseases of major impact in humans are largely centred around the rural poor in tropical, less industrially-developed countries and therefore of little or of fickle interest to the strictly commercially oriented. Moreover, the focus in the rural industries has moved away from aspects of on-farm production with lower priority given to studies on even the 'economically-important' parasites of livestock. It is contended that this may change again with pressures and clear marketing advantages to preserving a 'clean and green' image for Australia's primary industries. Overall, the extraordinary technical and conceptual advances in recent times have been tempered by uncertainties in research funding and severe cuts from some traditional sources for both fundamental and strategic/applied research in Parasitology. Several have highlighted the fact that deliverables in terms of new methods of disease control have been sparse and some claims made in the past have certainly been exaggerated. Yet the prospects and achievements at the front end of the long R&D pathway have never been brighter. In this article we examine the merits of a 'portfolio approach' to generating research funds in Parasitology and Science and Technology in Australia more generally, with an emphasis on strategies that, through welding good science with clear, medium-term product objectives, increase research funding opportunities.     

The implementation of tissue banking experiences for setting up a cGMP cell manufacturing facility

Cell manufacturing for clinical applications is a unique form of biologics manufacturing that relies on maintenance of stringent work practices designed to ensure product consistency and prevent contamination by microorganisms or by another patient's cells. More extensive, prolonged laboratory processes involve greater risk of complications and possibly adverse events for the recipient, and so the need for control is correspondingly greater. To minimize the associate risks of cell manufacturing adhering to international quality standards is critical. Current good tissue practice (cGTP) and current good manufacturing practice (cGMP) are examples of general standards that draw a baseline for cell manufacturing facilities. In recent years, stem cell researches have found great public interest in Iran and different cell therapy projects have been started in country. In this review we described the role of our tissue banking experiences in establishing a new cGMP cell manufacturing facility. The authors concluded that, tissue banks and tissue banking experts can broaden their roles from preparing tissue grafts to manufacturing cell and tissue engineered products for translational researches and phase I clinical trials. Also they can collaborate with cell processing laboratories to develop SOPs, implement quality management system, and design cGMP facilities.     

Gene Therapy for ALS: progress and prospects

Amyotrophic lateral sclerosis (ALS) is a devastating disease for which there are no effective drug treatments to date. Recent advances in Gene Therapy open up the possibility of developing an effective treatment aiming at halting or delaying the degeneration of motor neurons. Viral vectors such as lentiviral vectors and adeno-associated virus can transfer genes into many different types of primary neurons from a broad range of species including man and the resulting gene expression is long-term. Numerous animal studies have now been undertaken with these vectors and correction of disease models has been obtained. These vectors have been refined to a very high level and can be produced safely for the clinic. However, we believe that there are some major issues that need to be addressed in order to see a Gene Therapy approach with viral vectors proceed to the clinic for ALS patients. This review will describe the general features of lentiviral vectors. It will then describe some key examples of gene transfer and genetic correction in animal models of motor neuron disease. The prospects for the clinical evaluation of lentiviral vectors for the treatment of human motor neuron disease will be outlined.     

Palearctic passerines in Afrotropical environments: a review

Previous ecological studies of Palearctic passerine migrants in Africa have claimed to reveal some general features with respect to habitat use, foraging ecology and interspecific relationships with Afrotropical residents. In this review we discuss apparent contradictions between earlier generalisations and more recent results from more detailed field studies and explore in which areas our ecological knowledge and theoretical understanding remain poor and have given rise to misconceptions. For example, it has been claimed that migrants use structurally more diverse and open habitats and that they forage higher and in more peripheral parts of the vegetation than their ecologically similar Afrotropical counterparts, yet in the past these characteristics were often not clearly defined and not always correlated in practice. It has also been stated that migrants are more flexible in habitat use, occupying a wider range of habitat types and employing a higher diversity of foraging techniques, both of which were assumed to be adaptations to permit coexistence with Afrotropical residents by using untapped resources that are only seasonally available. Yet results from studies of the role of competition in shaping migrant-resident communities remain largely unconvincing. While flexibility may facilitate migrant-resident coexistence, it may also favour the evolution of migration because specialists are less able to use their advantages in different environments. We note that definitions of flexibility and specialisation may themselves depend on the ecological or evolutionary approach adopted by researchers. We conclude that few generalisations can safely be made about the ecology of Palearctic migrants in Africa and that adaptive explanations for the behaviours observed are largely lacking, as are studies of the fitness consequences of different migrant strategies such as have been conducted in the Nearctic-Neotropical migration system.