Multiagent cooperation for solving global optimization problems: an extendible framework with example cooperation strategies

This paper proposes the use of multiagent cooperation for solving global optimization problems through the introduction of a new multiagent environment, MANGO. The strength of the environment lays in itsflexible structure based on communicating software agents that attempt to solve a problem cooperatively. This structure allows the execution of a wide range of global optimization algorithms described as a set of interacting operations. At one extreme, MANGO welcomes an individual non-cooperating agent, which is basically the traditional way of solving a global optimization problem. At the other extreme, autonomous agents existing in the environment cooperate as they see fit during run time. We explain the development and communication tools provided in the environment as well as examples of agent realizations and cooperation scenarios. We also show how the multiagent structure is more effective than having a single nonlinear optimization algorithm with randomly selected initial points

IKAP/Elp1 Is Required In Vivo for Neurogenesis and Neuronal Survival, but Not for Neural Crest Migration

Familial Dysautonomia (FD; Hereditary Sensory Autonomic Neuropathy; HSAN III) manifests from a failure in development of the peripheral sensory and autonomic nervous systems. The disease results from a point mutation in the IKBKAP gene, which encodes the IKAP protein, whose function is still unresolved in the developing nervous system. Since the neurons most severely depleted in the disease derive from the neural crest, and in light of data identifying a role for IKAP in cell motility and migration, it has been suggested that FD results from a disruption in neural crest migration. To determine the function of IKAP during development of the nervous system, we (1) first determined the spatial-temporal pattern of IKAP expression in the developing peripheral nervous system, from the onset of neural crest migration through the period of programmed cell death in the dorsal root ganglia, and (2) using RNAi, reduced expression of IKBKAP mRNA in the neural crest lineage throughout the process of dorsal root ganglia (DRG) development in chick embryos in ovo. Here we demonstrate that IKAP is not expressed by neural crest cells and instead is expressed as neurons differentiate both in the CNS and PNS, thus the devastation of the PNS in FD could not be due to disruptions in neural crest motility or migration. In addition, we show that alterations in the levels of IKAP, through both gain and loss of function studies, perturbs neuronal polarity, neuronal differentiation and survival. Thus IKAP plays pleiotropic roles in both the peripheral and central nervous systems

Small molecule activators of the Trk receptors for neuroprotection

The neurotophin signaling network is critical to the development and survival of many neuronal populations. Especially sensitive to imbalances in the neurotrophin system, cholinergic neurons in the basal forebrain are progressively lost in Alzheimer's disease. Therapeutic use of neurotrophins to prevent this loss is hampered, however, by a number of pharmacological challenges. These include a lack of transport across the blood-brain barrier, rapid degradation in the circulation, and difficulty in production. In this review we discuss the evidence supporting the neurotrophin system's role in preventing neurodegeneration and survey some of the pharmacological strategies being pursued to develop effective therapeutics targeting neurotrophin function

Common practices in botulinum toxin injection for spasmodic dysphonia treatment: A national survey

Objectives/Hypothesis Although no clear guidelines exist, protocols in the treatment of spasmodic dysphonia (SD) vary among physicians. Previously published work comes from relatively few centers. Study Design A descriptive survey among experts (laryngologists who practice Botulinum toxin injections for SD). Methods An online 58‐item survey was sent to all otolaryngologists who self‐identify as laryngologists on the American Academy of Otolaryngology–Head and Neck Surgery website. Items surveyed included botulinum toxin injection technique, laterality, and dosage. Results An 80% response rate was achieved (70 completed the survey). Participants collectively reported treating >4,000 SD patients in the past year (mean, 71 ± 68 patients/laryngologist). Eighty‐seven percent perform injections exclusively in the office; the remainder both in the office and operating room. For adductor SD injections, 88% use electromyographic (EMG) guidance alone via cricothyroid approach. The remainder use anatomical landmarks alone (9%) or EMG with endoscopic guidance (3%). Sitting is the preferred patient position (70%; supine, 30%). A substantial majority (87%) begin with bilateral injections (starting dosage mode, 1.25 units/side). For abductor SD injections, 67% use EMG guidance alone and 31% use endoscopic guidance with or without EMG. Sitting is the preferred patient position (84%; supine, 16%). The preferred approach is anterior‐translaryngeal (51%), followed by lateral‐retrolaryngeal with rotation (34%). A considerable majority (79%) begin with unilateral injections (starting dosage mode, 5 units). When deciding on initial dosage, the most influential factor was balancing patients' desire/needs, followed by patients' frailty and risk of aspiration. The typical planned interval between injections is 3 to 4 months. Conclusions Laryngologists follow fairly uniform protocols in the treatment of SD with some important and previously unpublished differences. This study documents areas of agreement and discordance among laryngologists in the United States for the treatment of SD. Level of Evidence 4 Laryngoscope, 129:1650–1656, 201