The Chimp Challenge: Working memory in chimps and humans

Matsuzawa (2012) presented work at Evolang demonstrating the working memory abilities of chimpanzees. (Inoue & Matsuzawa, 2007) found that chimpanzees can correctly remember the location of 9 randomly arranged numerals displayed for 210ms - shorter than an average human eye saccade. Humans, however, perform poorly at this task. Matsuzawa suggests a semantic link hypothesis: while chimps have good visual, eidetic memory, humans are good at symbolic associations. The extra information in the semantic, linguistic links that humans possess increase the load on working memory and make this task difficult for them. We were interested to see if a wider search could find humans that matched the performance of the chimpanzees. We created an online version of the experiment and challenged people to play. We also attempted to run a non-semantic version of the task to see if this made the task easier. We found that, while humans can perform better than Inoue and Matsuzawa (2007) suggest, chimpanzees can perform better still. We also found no evidence to support the semantic link hypothesis

Multiplex serum protein analysis reveals potential mechanisms and markers of response to hyperimmune caprine serum in systemic sclerosis

BACKGROUND: Hyperimmune caprine serum (HICS) is a novel biological therapy with potential benefit for skin in established diffuse cutaneous systemic sclerosis. Here we report multiplex protein analysis of blood samples from a placebo-controlled phase II clinical trial and explore mechanisms of action and markers of response. METHODS: Patients were treated with HICS (n = 10) or placebo (n = 10) over 26 weeks, with follow-up open-label treatment to 52 weeks in 14 patients. Serum or plasma samples at baseline, 26 and 52 weeks were analysed using multiplex or individual immunoassays for 41 proteins. Patterns of change were analysed by clustering using Netwalker 1.0, Pearson coefficient and significance analysis of microarrays (SAM) correction. RESULTS: Cluster analysis, SAM multiplex testing and paired comparison of individual analytes identified proteins that were upregulated or downregulated during treatment with HICS. There was upregulation of the hypothalamo-pituitary-adrenal axis after HICS treatment evidenced by increases in α-MSH and ACTH in cases treated with HICS. Interestingly, significant increase in PIIINP was associated with HICS treatment and improved MRSS suggesting that this may be a marker of extracellular matrix turnover. Other relevant factors reduced in HICS-treated patients compared with controls, although not reaching statistical significance included COMP, CCL2, IL6, TIMP2, Fractalkine and TGFβ1 levels. CONCLUSIONS: Our results suggest mechanisms of action for HICS, including upregulation of α-MSH, that has been shown to be anti-fibrotic in preclinical models, and possible markers to be included in future trials targeting skin in diffuse cutaneous systemic sclerosis. TRIAL REGISTRATION: Eudract, No. 2007-003122-24. ClinTrials.gov, No. NCT00769028 . Registered 7 October 2008

Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths

Balancing Organizational Regulation and Agent Autonomy: An MDE-Based Approach

The deployment of agent societies —as complex systems— in dynamic and unpredictable settings brings forth critical issues concerning their design. Organizational models have been advocated to specify open systems in dynamic environments in order to accomplish the need to represent regulating structures explicitly and independently from acting components (or agents). Despite the fact that several frameworks have been proposed for the specification of organizational models, it is still a matter of design choice how to balance between regulative design and component flexibility. We propose a design framework, discussing the advantages of having different degrees of abstraction at organizational level in the development of agent societies. That is, we illustrate how the design properties impact the flexibility of run-time systems to cope with context changes. We adopt the OperA software engineering methodology to deal with the organizational model specification, and the Model Driven Engineering (MDE) mechanisms to map concepts between different design models

Strategies for avoiding preference profiling in agent-based e-commerce environments

Agent-based electronic commerce is known to offer many advantages to users. However, very few studies have been devoted to deal with privacy issues in this domain. Nowadays, privacy is of great concern and preserving users' privacy plays a crucial role to promote their trust in agent-based technologies. In this paper, we focus on preference profiling, which is a well-known threat to users' privacy. Specifically, we review strategies for customers' agents to prevent seller agents from obtaining accurate preference proles of the former group by using data mining techniques. We experimentally show the efficacy of each of these strategies and discuss their suitability in different situations. Our experimental results show that customers can improve their privacy notably with these strategies

Proinflammatory action of the antiinflammatory drug infliximab in tumor necrosis factor receptor-associated periodic syndrome

Objective. Tumor necrosis factor receptor (TNFR) -associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory condition caused by mutations in the TNFRSFIA gene. Unlike other autoinflammatory diseases in which anti-TNF therapy is largely a successful treatment option, therapy with the anti-TNF drug infliximab is often ineffective in patients with TRAPS. Moreover, in certain cases, infliximab actually triggers severe episodes of inflammation. The aim of this study was to elucidate the mechanisms underlying such a reaction. Methods. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with TRAPS. Both caspase 3 activity and NF-kappa B subunit activity were determined by enzyme-linked immunosorbent assay. Cytokine secretion was assessed using a specific customized human multiplex bead immunoassay kit. Results. Unlike findings in controls, cells from a family of 9 patients, all of whom carried the T50M mutation in TNFRSFIA, failed to respond to infliximab through proapoptotic induction of caspase 3 activity. Instead, we observed enhanced antiapoptotic c-Rel subunit activity, accompanied by a significant increase in secretion of the proinflammatory cytokines interleukin-1 beta (IL-1 beta), IL-1 receptor, IL-6, IL-8, and IL-12. Conclusion. Altered extracellular conformation of TNFRI, resulting from the T50M mutation in TNFRSFIA, results in failure of PBMCs to induce an apoptotic response to infliximab. We hypothesize that failure to shed infliximab-bound TNF/TNFRI from the cell surface of cells from patients with the T50M mutation triggers c-Rel activation, and that this leads to a marked increase in cytokine secretion and an increased proinflammatory response. In light of these findings, we strongly advise caution when prescribing infliximab as anti-TNF therapy to patients with TRAPS

Autonomous CaMKII Activity as a Drug Target for Histological and Functional Neuroprotection after Resuscitation from Cardiac Arrest

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of physiological glutamate signaling, but its role in pathological glutamate signaling (excitotoxicity) remains less clear, with indications for both neuro-toxic and neuro-protective functions. Here, the role of CaMKII in ischemic injury is assessed utilizing our mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR). CaMKII inhibition (with tatCN21 or tatCN19o) at clinically relevant time points (30 min after resuscitation) greatly reduces neuronal injury. Importantly, CaMKII inhibition also works in combination with mild hypothermia, the current standard of care. The relevant drug target is specifically Ca2+-independent “autonomous” CaMKII activity generated by T286 autophosphorylation, as indicated by substantial reduction in injury in autonomy-incompetent T286A mutant mice. In addition to reducing cell death, tatCN19o also protects the surviving neurons from functional plasticity impairments and prevents behavioral learning deficits, even at extremely low doses (0.01 mg/kg), further highlighting the clinical potential of our findings

Governance of Services: A Natural Function for Agents (extended abstract)

Multi Actor SystemsTechnology, Policy and Managemen