A molecular dynamics boundary condition for heat exchange between walls and a fluid

In molecular dynamics simulations of heat transfer in micro channels, a lot of computation time is used when the wall molecules are explicitly simulated. To save computation time, implicit boundary conditions, such as the Maxwell conditions, can be used. With these boundary conditions, heat transfer is still a problem. In this work, we derive a new boundary condition based on a vibrating potential wall. The heat-transfer properties of the new boundary condition are shown to be comparable with those of the explicit wall. The computation time needed for the implicit boundary condition is very small compared with that needed for the explicit simulation.     

New biotechnologies: spin-off on health and society

New biotechnologies and the new biology deriving from them are having a revolutionary impact on economy and society and are consequently transforming the role of researchers, which is changing continually to meet the competence required. The advances in human genetics on the other hand make it necessary to look for different approaches and new rules in bioethics. Comprehensive views and careful considerations are therefore needed in order that this new biology may have a positive impact on health, being respectful of the social and ethical principles of human beings.     

Genomes and genome projects of protozoan parasites

Protozoan parasites are causing some of the most devastating diseases world-wide. It has now been recognised that a major effort is needed to be able to control or eliminate these diseases. Genome projects for the most important protozoan parasites have been initiated in the hope that the read-out of these projects will help to understand the biology of the parasites and identify new targets for urgently needed drugs. Here, I will review the current status of protozoan parasite genome projects, present findings obtained as a result of the availability of genomic data and discuss the potential impact of genome information on disease control.     

Molecular population genetics.

Molecular population genetics is entering a new era dominated by studies of genomic polymorphism. Some of the theory that will be needed to analyze data generated by such studies is already available, but much more work is needed. Furthermore, population genetics is becoming increasingly relevant to other fields of biology, for example to genetic epidemiology, because of disease gene mapping in general populations.     

Intraspecific trait variation across scales: implications for understanding global change responses

Recognition of the importance of intraspecific variation in ecological processes has been growing, but empirical studies and models of global change have only begun to address this issue in detail. This review discusses sources and patterns of intraspecific trait variation and their consequences for understanding how ecological processes and patterns will respond to global change. We examine how current ecological models and theories incorporate intraspecific variation, review existing data sources that could help parameterize models that account for intraspecific variation in global change predictions, and discuss new data that may be needed. We provide guidelines on when it is most important to consider intraspecific variation, such as when trait variation is heritable or when nonlinear relationships are involved. We also highlight benefits and limitations of different model types and argue that many common modeling approaches such as matrix population models or global dynamic vegetation models can allow a stronger consideration of intraspecific trait variation if the necessary data are available. We recommend that existing data need to be made more accessible, though in some cases, new experiments are needed to disentangle causes of variation.     

A research agenda for malaria eradication: cross-cutting issues for eradication

Discipline-specific Malaria Eradication Research Agenda (malERA) Consultative Groups have recognized several cross-cutting issues that must be addressed to prevent repetition of some of the mistakes of past malaria elimination campaigns in future programs. Integrated research is required to develop a decision-making framework for the switch from malaria control to elimination. Similarly, a strong economic case is needed for the very long-term financial support that is essential for elimination. Another cross-cutting priority is the development of improved measures of intensity of transmission, especially at low and nonrandom levels. Because sustained malaria elimination is dependent on a functioning health system, a further key cross-cutting research question is to determine how inputs for malaria can strengthen health systems, information systems, and overall health outcomes. Implementation of elimination programs must also be accompanied by capacity building and training to allow the assessment of the impact of new combinations of interventions, new roles for different individuals, and the operational research that is needed to facilitate program expansion. Finally, because community engagement, knowledge management, communication, political, and multisectoral support are critical but poorly understood success factors for malaria elimination, integrated research into these issues is vital.     

The housing market in English cities after 1945

Race, Community and Conflict: A Study of Sparkbrook opened a new field of analysis. If it was to stimulate further growth of knowledge, it needed to be better related to the economic analysis of housing markets. Research to this end that was conducted in the Research Unit on Ethnic Relations after 1970 is described.     

“Macroscopic pattern analysis” based on formal analogies as a scientific methodology for complex systems

Bioprocess engineering at present concentrates on the enormous problems in the environment. What is therefore needed is a sound methodology, which should be based on the interactions between the physiology of biological reaction networks and physical processes in the environment and which should be an analogy to bioreactor performance. The conventional methodology is empirically oriented, using pilot plant data for the experimental estimates of process economics, where all further details are elucidated following the mechanistic approach on the microscopic level based on assumed mechanisms (causalities). According to the new view, the new systems-based methodology uses mathematical models as approximations and includes all the interactions. Pilot plant data are needed for model falsification, using analogies on the formal macroscopic level. Bioreactor scale-up as one application is a more rapid procedure of reasonable accuracy, where both the biokinetics as well as the fluid dynamics are quantified using formal macroscopic analogies. Model consistency and plausibility are the basic criteria when using model computer simulations as a decisive aid, while experiments lose their central role and are on longer the basis for evaluating the scientific work; they are simply the basis of the researcher's intuition. Another typical feature of complex systems is that model parameters are interdependent. The final decisive fact will be the mental experiment (“thinking” with the left and right side of the brain), which can be supported using computer simulations. This evolutionary interplay between the three realities of thinking, experimenting and simulating leads to a holistic progress towards the better understanding of highly complex systems. It offers the solution to the problems, which is needed in future.     

New insights into mechanisms of resistance to microtubule inhibitors

Mechanisms to explain tumor cell resistance to drugs that target the microtubule cytoskeleton have relied on the assumption that the drugs act either to suppress microtubule dynamics or to perturb the balance between assembled and nonassembled tubulin. Recently, however, it was found that these drugs also alter the stability of microtubule attachment to centrosomes, and do so at the same concentrations that are needed to inhibit cell division. Based on this new information, a new model is presented that explains resistance resulting from a variety of molecular changes that have been reported in the literature. The improved understanding of drug action and resistance has important implications for chemotherapy with these agents.     

Assembly and maturation of HIV-1--targets for new anti-HIV compounds

Much progress has been recently made in research of the final stages of the HIV-1 life cycle, i.e. of its assembly, gemmation and maturation. The virus was shown, in particular, to use widely cell mechanisms in its replication and assembly. The TSG 101 cellular endosomal sorting protein interacting with the p6 viral protein is necessary for gemmation. Cyclophilin and HP68 (cell proteins) needed for marphogenesis of the virus were identified. The recently obtained data on the interaction of Vif (a viral protein) and Apobec (a cell protein) showed that HIV-1 has an action mechanism overcoming the cell barriers. The "early" virus phenomenon, which is deprived of any mature structure or the ability to infect and does not contain mature Gag and Env proteins, illustrates that the proteolytic pressing of the Gag p55 precursor is not enough for the maturation of the virus and additional viral or cellular factors are needed for the virus to become infectious. Although the current antiviral therapy has been successful enough, it is far from being effective in all cases; one of the reasons is resistance to chemodrugs developing rapidly in patients. Fast mutations and exceptional plasticity of the viral genome (which helps the virus to develop rapidly resistance to drugs) belong to the major problems. The circulation of persistent virus variants has been quickly increasing. There is an urgent need in developing new antiviral drugs acting on new viral targets; progress in experimental virology would speed it up. Thus, new drugs can be created, which block the activity of Vif, that would make Apobec block the virus replication. Compounds can be developed, which block the interaction of cyclophilin and TSG101 with viral proteins. The recently described importance of cholesterol in the sexual transfer of viruses is expected to bring simple and inexpensive compounds destroying cholesterol in the mucous tunic of genitals into clinical use. The identification of additional factors needed for the maturation of the virus and for its becoming infectious can be a basis for the development of drugs blocking their packaging into virions. Future research is expected to define new targets for the chemotherapy of AIDS and to promote the designing of new chemodrugs.     

Mechanisms of Toxoplasma gondii persistence and latency

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes opportunistic disease, particularly in immunocompromised individuals. Central to its transmission and pathogenesis is the ability of the proliferative stage (tachyzoite) to convert into latent tissue cysts (bradyzoites). Encystment allows Toxoplasma to persist in the host and affords the parasite a unique opportunity to spread to new hosts without proceeding through its sexual stage, which is restricted to felids. Bradyzoite tissue cysts can cause reactivated toxoplasmosis if host immunity becomes impaired. A greater understanding of the molecular mechanisms orchestrating bradyzoite development is needed to better manage the disease. Here, we will review key studies that have contributed to our knowledge about this persistent form of the parasite and how to study it, with a focus on how cellular stress can signal for the reprogramming of gene expression needed during bradyzoite development.     

Plant Derived Antimalarial Agents: New Leads and Challenges

New treatments for malaria are urgently needed due to the increasing problem of drug-resistance in malaria parasites. The long-established use of quinine and the more recent introduction of artemisinin and its derivatives as highly effective antimalarials demonstrates that plant species are an important resource for the discovery of new antimalarial agents. Furthermore, many plant species continue to be used in traditional medicines for the treatment of malaria and many people depend on such remedies as they cannot afford and/or do not have access to effective antimalarial drugs. In this paper the potential of plant species to yield new leads to antimalarial drugs will be illustrated with reference to cryptolepine, the main alkaloid present in the species, Cryptolepis sanguinolenta. In addition to this approach, there is currently increasing interest in the use and development of traditional herbal remedies for the treatment of malaria as these may have the potential to provide affordable antimalarial treatment for many who cannot afford the drugs needed to treat chloroquine-resistant Plasmodium falciparum infections. However, little is known with respect to the efficacy and safety of traditional antimalarials and clinical studies are urgently needed to establish their value. Some of the issues pertinent to this area will be briefly reviewed and it is hoped that this will stimulate further discussion and research on this important topic.     

The invasion by the Yellow-legged hornet: A systematic review

The Yellow-legged hornet (Vespa velutina nigrithorax), native to regions of Southeast Asia, was accidentally introduced in Europe, South Korea, and Japan, where is has often become invasive. Due to its potential negative impacts at ecologic, economic and social levels, this hornet was included in the “Union list” of the EU legislation for invasive alien species. This means that measures are urgently needed to prevent further introductions, as well as to early-detect and control spread to avoid new populations. In this study we aim to identify the main reported drivers of distribution, ecological preferences, impacts, and methods for preventing introduction, controlling, and managing this invasive species. The supporting information was obtained from a comprehensive literature search. Then, a literature review was performed to classify the records gathered and to extract the relevant information following an adapted Drivers-Pressures-State-Impacts-Responses framework. The achieved results show a growing interest of researchers on V. velutina nigrithorax through time due to its quick spread and impacts on new ecosystems. They also revealed that there is much information on the State of invasions, whereas more knowledge is needed regarding the Drivers of those invasions. Biological traits such as life history traits, morphology, and the sting venom properties are some of the most studied topics regarding V. velutina nigrithorax. In the future, research should focus on the topics that lack information, analyse other Response solutions that meet the intended measures by the EU legislation, and use new methodology to study the impacts caused by this invader under new perspectives.     

The ecosystem-service chain and the biological diversity crisis

The losses that are being incurred of the Earth''s biological diversity, at all levels, are now staggering. The trend lines for future loss are steeply upward as new adverse drivers of change come into play. The political processes for matching this crisis are now inadequate and the science needs to address this issue are huge and slow to fulfil, even though strong advances have been made. A more integrated approach to evaluating biodiversity in terms that are meaningful to the larger community is needed that can provide understandable metrics of the consequences to society of the losses that are occurring. Greater attention is also needed in forecasting likely diversity-loss scenarios in the near term and strategies for alleviating detrimental consequences. At the international level, the Convention on Biological Diversity must be revisited to make it more powerful to meet the needs that originally motivated its creation. Similarly, at local and regional levels, an ecosystem-service approach to conservation can bring new understanding to the value, and hence the need for protection, of the existing natural capital.     

Long-lost relatives reappear: identification of new members of the tubulin superfamily

The identification and analysis of new members of the tubulin superfamily has advanced the belief that these tubulins play important roles in the duplication and assembly of centrioles and basal bodies. This idea is supported by their distribution in organisms with centrioles containing triplet microtubules and by recent functional analysis of the new tubulins. delta- and epsilon-tubulin are found in most organisms that assemble triplet microtubules. delta-tubulin is needed for maintaining triplet microtubules in Chlamydomonas and Paramecium. epsilon-tubulin is needed for centriole and basal body duplication and is an essential gene in Chlamydomonas. The distribution of eta-tubulin is more limited and has been found in only four organisms to date. Phylogenetic analysis suggests that it is most closely related to delta-tubulin, which suggests that delta- and eta-tubulin could have overlapping functions.     

Reflections on clinical research in sub-Saharan Africa

The urgent need for new, safe and sustainable interventions against diseases that disproportionally affect the poor is finally receiving global attention and the funding landscape for development projects has significantly improved during the past decade. For the development of new drug and vaccine candidates, clinical trials have become the most important tool to assess their safety and efficacy. Recently, there has been a seismic shift in the number of clinical trials conducted in resource-limited settings. We discuss the current framework of clinical research in sub-Saharan Africa, from building product pipelines to the capacities needed for the conduct of trials according the harmonised Good Clinical Practice (GCP) ICH E6 guideline. We place emphasis on clinical research in neglected tropical diseases which still frequently has to be conducted with limited financial, logistical and human resources. Given those short-comings we recommend minimum standards needed at the local, national and sponsor levels to provide GCP-compliant clinical research.     

The global pipeline of new medicines for the control and elimination of malaria

ABSTRACT: Over the past decade, there has been a transformation in the portfolio of medicines to combat malaria. New fixed-dose artemisinin combination therapy is available, with four different types having received approval from Stringent Regulatory Authorities or the World Health Organization (WHO). However, there is still scope for improvement. The Malaria Eradication Research agenda identified several gaps in the current portfolio. Simpler regimens, such as a single-dose cure are needed, compared with the current three-day treatment. In addition, new medicines that prevent transmission and also relapse are needed, but with better safety profiles than current medicines. There is also a big opportunity for new medicines to prevent reinfection and to provide chemoprotection. This study reviews the global portfolio of new medicines in development against malaria, as of the summer of 2012. Cell-based phenotypic screening, and 'fast followers' of clinically validated classes, mean that there are now many new classes of molecules starting in clinical development, especially for the blood stages of malaria. There remain significant gaps for medicines blocking transmission, preventing relapse, and long-duration molecules for chemoprotection. The nascent pipeline of new medicines is significantly stronger than five years ago. However, there are still risks ahead in clinical development and sustainable funding of clinical studies is vital if this early promise is going to be delivered.     

Immunotherapy for liver tumors: present status and future prospects

Increasing evidence suggests that immune responses are involved in the control of cancer and that the immune system can be manipulated in different ways to recognize and attack tumors. Progress in immune-based strategies has opened new therapeutic avenues using a number of techniques destined to eliminate malignant cells. In the present review, we overview current knowledge on the importance, successes and difficulties of immunotherapy in liver tumors, including preclinical data available in animal models and information from clinical trials carried out during the lasts years. This review shows that new options for the treatment of advanced liver tumors are urgently needed and that there is a ground for future advances in the field.     

Design of delay-dependent state estimator for discrete-time recurrent neural networks with interval discrete and infinite-distributed time-varying delays

The state estimation problem for discrete-time recurrent neural networks with both interval discrete and infinite-distributed time-varying delays is studied in this paper, where interval discrete time-varying delay is in a given range. The activation functions are assumed to be globally Lipschitz continuous. A delay-dependent condition for the existence of state estimators is proposed based on new bounding techniques. Via solutions to certain linear matrix inequalities, general full-order state estimators are designed that ensure globally asymptotic stability. The significant feature is that no inequality is needed for seeking upper bounds for the inner product between two vectors, which can reduce the conservatism of the criterion by employing the new bounding techniques. Two illustrative examples are given to demonstrate the effectiveness and applicability of the proposed approach.