Strategies for resource exploitation

In a mixed strategy, game-theoretical scenario mimicking the behaviour of fishing vessels competing for a limited renewable resource, agents following either a Collective Intelligence or a purely selfish strategy quickly outperform fully cooperative teams as well as agents not planning for future action by acting randomly. The stable balance between fully selfish agents and the Collective Intelligence depends subtly on the ratio of instantaneous demand to instantaneously available resource as well as on the dynamics of the resource itself. This suggests use of ratio of strategies as an indicator of the level of resource exploitation. The Collective Intelligence performance proves to be extremely robust to uncertain information, especially when longer records of historical catch are accounted for.     

多部门联动推行抗菌药物合理应用的精细化管控

探讨抗菌药物临床合理应用中存在的问题,列举了多部门联动实行抗菌药物精细化管控的具体做法和取得的成效,进而提出多部门联动精细化管控是实现抗菌药物临床合理应用的有效策略。     

Water-soluble polymer–drug conjugates for combination chemotherapy against visceral leishmaniasis

There is a need for new safe, effective and short-course treatments for leishmaniasis; one strategy is to use combination chemotherapy. Polymer–drug conjugates have shown promise for the delivery of anti-leishmanial agents such as amphotericin B. In this paper, we report on the preparation and biological evaluation of polymer–drug conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA), amphotericin B and alendronic acid. The combinatorial polymer–drug conjugates were effective anti-leishmanial agents in vitro and in vivo, but offered no advantage over the single poly(HPMA)–amphotericin B conjugates.     

Tumor angiogenesis factor. Speculations on an approach to cancer chemotherapy

Tumor angiogenesis factor (TAF) and its importance in determining a strategy for cancer chemotherapy are discussed. It is suggested that inhibition of RNA synthesis or increased RNA catabolism might interfere with the metabolism of solid tumor cells more so than in normal cells, and thus hinder angiogenesis and pursuant tumor growth by preventing the synthesis of the RNA component of TAF. An attempt is made to indicate potential models for anti-angiogenesis agents of this type. The drugs offered as initial prototypes for investigations along these lines are actinomycin D (which likely has antimetabolite and anti-angiogenesis activities), polyriboinosinic-polyribocytidylic acid (which likely has adjuvant and anti-angiogenesis activities) and ribonuclease (which in theory might be a purely anti-angiogenetic agent). It is noted that these models may turn out to be less than ideal as therapeutic agents due to problems of toxicity, metabolism, potency, or distribution, but nonetheless might serve to yield insights into the design of new cancer chemotherapeutic drugs. In addition, some evidence is cited suggesting that actinomycin D may be more effective against certain tumors when employed in lower, chronic dosages rather than its present use in “loading” dosages.The concept of anti-angiogenesis agents as fundamentally “tumoristatic” therapies is discussed, and the likelihood that such agents might be effectively “tumoricidal” in immunocompetent hosts is mentioned. The main promise of an anti-angiogenetic strategy is efficacy against presently intractable slowly growing human cancers when used in combination with other treatment modalities. In summary, a strategy of cancer chemotherapy predicated upon interference with RNA synthesis or increase in RNA catabolism is offered as a potential mechanism for establishing anti-angiogenesis, and as a promising alternative and adjunct to present methods.     

Evolving robots able to integrate sensory-motor information over time

Summary We will discuss in which conditions we can expect the emergence of agents able to integrate sensory-motor information over time and later use this information to modulate their behavior accordingly. In doing so we will illustrate the problems that these agents should be able to solve and the processes that might lead to a transition from simple agents that only rely on sensory information or on their internal dynamic to agents that are also able to integrate information over time. The analysis of evolved individuals revealed that: (1) individuals able to integrate information over time rely on mixed strategy in which basic sensory-motor mechanisms are complemented and enhanced with additional internal mechanisms; (2) evolved individuals tend to rely on partial, action-oriented, and action-mediated representations of the external environment.     

Chemopreventive agent-induced modulation of death receptors

The goals of chemoprevention of cancer are to inhibit the initiation or suppress the promotion and progression of preneoplastic lesions to invasive cancer through the use specific natural or synthetic agents. Therefore, a more desirable and aggressive approach is to eliminate aberrant clones by inducing apoptosis rather than merely slowing down their proliferation. The increased understanding of apoptosis pathways has directed attention to components of these pathways as potential targets not only for chemotherapeutic but also for chemopreventive agents. Activation of death receptors triggers an extrinsic apoptotic pathway, which plays a critical role in tumor immunosurveillance. An increasing number of previously identified chemopreventive agents were found to induce apoptosis in a variety of premalignant and malignant cell types in vitro and in a few animal models in vivo. Some chemopreventive agents such as non-steroidal anti-inflammatory drugs, tritepenoids, and retinoids increase the expression of death receptors. Thus, understanding the modulation of death receptors by chemopreventive agents and their implications in chemoprevention may provide a rational approach for using such agents alone or in combination with other agents to enhance death receptor-mediated apoptosis as a strategy for effective chemoprevention of cancer.     

The scarlet letter of alkylation: a mini review of selective alkylating agents

If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to "tame" the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association.     

Strategies in managing asthma.

The management of adult asthma involves a concerted effort to identify and remove or mollify inciting or triggering stimuli such as respiratory tract infections, gastric reflux, aspirin, beta-antagonists, and environmental agents; educate patients, using written treatment plans and pulmonary function monitoring; and properly use the antiasthmatic medications including beta-agonists, theophylline, anticholinergics, and corticosteroids, with an emphasis on aerosol delivery and the use of corticosteroids during exacerbations. This strategy is summarized with suggestions on therapy in emergency departments, during the transition from hospital to ambulatory care, before exercise, and during pregnancy.     

Can an a priori strategy be developed for biological control? The case of Onopordum spp. thistles in Australia

Abstract  Between 1992 and 2000, seven insect agents were released in Australia for the biological control of Onopordum spp. thistles. This paper describes the protocol used for the selection of these agents, starting with the development of a preliminary strategy, based on the ecology and population dynamics of the target weed. The strategy informed the surveys for natural enemies in the native range of Onopordum , targeting insects that attacked key transitional stages of the weed's life cycle. Ongoing studies of Onopordum populations in both Australia and Europe, plus experimental studies on the ecology, potential impact and preliminary host specificity of the agents, led to the refinement of the strategy and the selection and prioritisation of the agents. It is argued that development of an explicit strategy prior to release should be encouraged, as it forces researchers to revisit the rationale for and aims of particular biological control projects, ensuring that the process of agent selection remains focused. It also provides a tool to improve the process of agent selection, as subsequent results can be measured against the strategy and agent success or failure evaluated against the a priori expectations.     

纳米酶的抗菌作用及其机制研究进展

抗生素类药物的发现和使用给人类提供了抗击细菌感染的强大武器。但是,抗生素长期使用导致的细菌耐药问题限制了其在临床上的应用。开发新型的基于纳米酶(Nano-Enzyme)的新型抗菌剂为解决上述问题提供了新思路。将纳米酶可以归为两大类:一类是酶和纳米材料的复合材料;另一类是纳米材料本身具有类酶活性。因为银(Ag)纳米粒子是历史最悠久且研究最广泛的纳米抗菌剂,而且其抗菌机制多样化,因此将Ag纳米粒子的抗菌机制和最新进展单独论述。纳米抗菌剂可以组合多种抗菌机制协同抗菌,从而提高其抗菌性能。因此,在这篇综述中系统介绍了Ag纳米粒子和上述2种类型纳米抗菌剂的最新研究进展和抗菌机制,重点介绍了纳米材料的物理性质对抗菌活性和生物安全性的影响。最后,该综述还强调了该领域目前面临的问题和挑战,并对该领域的发展前景进行了展望。     

The big dilemma: the chemotherapy of non-small cell lung carcinoma

The most problematic area in pulmonary oncology is the chemotherapy of non-small cell lung carcinoma and its place in the therapeutic strategy. Chemotherapy based on the earlier alkylating agents worsened survival of NSCLC patients. That was the reason for the nihilistic approach by many colleagues toward chemotherapy in NSCLC. Today this question has been resolved. Platinum based combined chemotherapy significantly prolongs survival and improves quality of life. Other possibilities are to incorporate the new chemotherapeutic agents (taxanes, Gemcitabine, Vinorelbine, Irinotecan) into the chemotherapeutic regimens. These agents improve the response rate and the quality of life and can be safely administered in outpatient bases, although in comparison to the earlier agents the survival gain is moderate. In early stages the role of adjuvant chemotherapy is questionable. Chemotherapy, surgery and postoperative irradiation may all have a role in the case of N2 disease.In locally advanced disease the use of radiochemotherapy is recommended. In advanced NSCLC chemotherapy is suggested in good performance status. The author summarises the role of chemotherapy in NSCLC, based on literature and on his own experience.     

TRAIL: a potential agent for cancer therapy

Induction of apoptosis in cancer cells with chemotherapy and radiation treatment is a major strategy in cancer therapy at present. Nevertheless, innate or acquired resistance has been an obstacle for conventional clinical therapy. TNF-related apoptosis inducing ligand (TRAIL/Apo-2L) is a typical member of the TNF ligand family that induces apoptosis through activating the death receptors. In recent years, considerable attention has been focused on the potential benefits of TRAIL in cancer therapy, as the majority of cancer cells are sensitive to TRAIL-induced apoptosis, while most normal cells are TRAIL-resistant. Furthermore, the use of TRAIL in combination with chemotherapeutic agents or irradiation strengthens its apoptotic effects. In this review, we will discuss the regulation mechanism of TRAIL-induced apoptosis and the molecular basis of the synergies created by its use in combination with chemotherapeutic agents and irradiation. We also analyze in detail that TRAIL may be cytotoxic, as this is a potential obstacle to its development for being used in cancer therapy.     

Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells

The development of multidrug resistance (MDR) of tumors is a major cause of failure in antitumor chemotherapy. This type of cross-resistance is due to the expression of ABC transporter glycoproteins actively effluxing the drug from the cells against the concentration gradient at the expense of metabolic energy, thus preventing the accumulation in cells of therapeutic concentration of active agents. In this review strategies for overcoming this adverse phenomenon are discussed. They comprise the control of expression of MDR glycoprotein transporters and control of the functioning of the expressed transporter proteins. The latter approach is discussed in more detail, comprising the following general strategies: (i) development of compounds that are not substrates of efflux pump(s), (ii) use of agents that inactivate (inhibit) MDR proteins, (iii) design of cytostatics characterized by fast cellular uptake, surpassing their mediated efflux, (iv) use of compounds competing with the drug for the MDR protein-mediated efflux. Positive and negative aspects of these strategies are analysed, with special attention put on strategy based on the use of MDR modulators in combination therapy, allowing the restoration of cytotoxic activity of clinical cytostatics towards resistant tumor cells.     

Learning and stabilization of altruistic behaviors in multi-agent systems by reciprocity

Optimization of performance in collective systems often requires altruism. The emergence and stabilization of altruistic behaviors are difficult to achieve because the agents incur a cost when behaving altruistically. In this paper, we propose a biologically inspired strategy to learn stable altruistic behaviors in artificial multi-agent systems, namely reciprocal altruism. This strategy in conjunction with learning capabilities make altruistic agents cooperate only between themselves, thus preventing their exploitation by selfish agents, if future benefits are greater than the current cost of altruistic acts. Our multi-agent system is made up of agents with a behavior-based architecture. Agents learn the most suitable cooperative strategy for different environments by means of a reinforcement learning algorithm. Each agent receives a reinforcement signal that only measures its individual performance. Simulation results show how the multi-agent system learns stable altruistic behaviors, so achieving optimal (or near-to-optimal) performances in unknown and changing environments. Received: 1 August 1997 / Accepted in revised form: 28 November 1997     

Biocontrol of Pests of Apples and Pears in Northern and Central Europe - 3. Predators

Predators of apple and pear pests in northern and central Europe and their use as biological control agents are reviewed. Many natural enemy species are specialized feeders and are able to respond to the population dynamics of particular pest species. The most oustandingly successful example of this is the use of phytoseiid mites, particularly Typhlodromus pyri , against phytophagous pest mites in apple. This mite management strategy is now widespread throughout European apple growing regions. Another example is the use of Anthocoris nemoralis against pear psyllids, Cacopsylla pyricola and C. pyri . Several groups of naturally occurring polyphagous predators, such as chrysopids, coccinellids, syrphids and spiders, also prey on a number of pest species in orchards, contributing generally to the reduction in pest populations. However, they are unlikely alone to prevent pest damage fully and reliably. In seeking biological control opportunities for a particular pest, these polyphagous natural enemies are unlikely to be a high priority. An exception, due to its abundance in orchards, is the common earwig, Forficula auricularia , although this predator may also cause some fruit injury. Another option to consider when reviewing possibilities for biological control in orchards is the introduction of biological control agents. The success rate of this approach, using arthropod predators to control pests of field crops, has been generally poor. Furthermore, mass production methods for predators are likely to be difficult and very costly. The biological supplies industry is constantly seeking culture techniques, largely for arthropod biological control agents of pests of protected crops. It is possible that some future advance may be relevant to orchards, though currently available predators do not appear promising. A careful economic appraisal of the feasibility of use of any potential biological control agent would be prudent before embarking on research.     

Natural selection of memory-one strategies for the iterated prisoner's dilemma

In the iterated Prisoner's Dilemma, mutually cooperative behavior can become established through Darwinian natural selection. In simulated interactions of stochastic memory-one strategies for the Iterated Prisoner's Dilemma, Nowak and Sigmund discovered that cooperative agents using a Pavlov (Win-Stay Lose-Switch) type strategy eventually dominate a random population. This emergence follows more directly from a deterministic dynamical system based on differential reproductive success or natural selection. When restricted to an environment of memory-one agents interacting in iterated Prisoner's Dilemma games with a 1% noise level, the Pavlov agent is the only cooperative strategy and one of very few others that cannot be invaded by a similar strategy. Pavlov agents are trusting but no suckers. They will exploit weakness but repent if punished for cheating.     

Optimization of labile esters for esterase-assisted accumulation of nitroxides into cells: a model for in vivo EPR imaging

Nitroxide-based electron paramagnetic resonance (EPR) imaging agents are useful quantitative probes of O2 concentration in vivo in real time. Lipophilic, labile alkanoyloxymethyl esters of nitroxides can cross the blood-brain barrier, and after hydrolysis, the corresponding anionic nitroxide is intracellularly entrapped at levels sufficient to permit O2 measurements. The utility of nitroxides as EPR imaging agents depends critically on their ability to accumulate in the brain to high levels. In this study, we systematically investigated the relationship between the structure of the alkanoyl moiety and the ability of the corresponding labile ester to deliver nitroxide intracellularly. We demonstrate, in a cultured cell model, that for nitroxide labile esters with unbranched alkanoyl chains, increasing the chain length improves intracellular loading. Moreover, by studying an isomeric series of labile esters, we conclude that branching of the alkanoyl chain drastically reduces intracellular loading. These structural insights improve our general ability to use labile esters to deliver carboxylates intracellularly, and suggest a strategy for enhancing delivery of nitroxide imaging agents across the blood-brain barrier in a living animal.     

Emergent Group Level Navigation: An Agent-Based Evaluation of Movement Patterns in a Folivorous Primate

The foraging activity of many organisms reveal strategic movement patterns, showing efficient use of spatially distributed resources. The underlying mechanisms behind these movement patterns, such as the use of spatial memory, are topics of considerable debate. To augment existing evidence of spatial memory use in primates, we generated movement patterns from simulated primate agents with simple sensory and behavioral capabilities. We developed agents representing various hypotheses of memory use, and compared the movement patterns of simulated groups to those of an observed group of red colobus monkeys (Procolobus rufomitratus), testing for: the effects of memory type (Euclidian or landmark based), amount of memory retention, and the effects of social rules in making foraging choices at the scale of the group (independent or leader led). Our results indicate that red colobus movement patterns fit best with simulated groups that have landmark based memory and a follow the leader foraging strategy. Comparisons between simulated agents revealed that social rules had the greatest impact on a group’s step length, whereas the type of memory had the highest impact on a group’s path tortuosity and cohesion. Using simulation studies as experimental trials to test theories of spatial memory use allows the development of insight into the behavioral mechanisms behind animal movement, developing case-specific results, as well as general results informing how changes to perception and behavior influence movement patterns.     

Chitosan-based delivery systems for curcumin: A review of pharmacodynamic and pharmacokinetic aspects

Effective drug delivery is one of the most important issues associated with the administration of therapeutic agents that have low oral bioavailability. Curcumin is an active ingredient in the turmeric plant, which has low oral bioavailability due to its poor aqueous solubility. One strategy that has been considered for enhancing the aqueous solubility, and, thus, its oral bioavailability, is the use of chitosan as a carrier for curcumin. Chitosan is a biodegradable and biocompatible polymer that is relatively water-soluble. Therefore, various studies have sought to improve the aqueous solubility of chitosan. The use of different pharmaceutical excipients and formulation strategies has the potential to improve aqueous solubility, formulation processing, and the overall delivery of hydrophobic drugs. This review focuses on various methods utilized for chitosan-based delivery of curcumin.     

SNAP-tag technology mediates site specific conjugation of antibody fragments with a photosensitizer and improves target specific phototoxicity in tumor cells

Cancer cells can be killed by photosensitizing agents that induce toxic effects when exposed to nonhazardous light, but this also causes significant damage to surrounding healthy cells. The specificity of photodynamic therapy can be increased by conjugating photosensitizing agents to antibodies and antibody fragments that bind specifically to tumor cell antigens. However, standard conjugation reactions produce heterogeneous products whose targeting specificity and spectroscopic properties can be compromised. In this study, we used an antibody fragment (scFv-425) that binds to the epidermal growth factor receptor (EGFR) as a model to investigate the use of SNAP-tag fusions as an improved conjugation strategy. The scFv-425-SNAP-tag fusion protein allowed the specific conjugation of a chlorin e6 photosensitizer modified with O(6)-benzylguanine, generating a homogeneous product that was delivered specifically to EGFR(+) cancer cells and resulted in significant, tumor cell-specific cytotoxicity. The impact of our results on the development of photodynamic therapy is discussed.