Dynamic Volume Adjustment Module

The Dynamic Volume Adjuster Module is a piece of consumer audio hardware capable of automatically adjusting a sound system’s volume to remain louder than the noise of the environment. It accomplishes this by monitoring the sound in the environment and comparing the feedback from the sound system to the total sound level. The project focused on signal processing using a specialized DSP Microcontroller and a selection of peripheral components

Thresholds of Toxicological Concern for Endocrine Active Substances in the Aquatic Environment

The threshold of toxicological concern (TTC) concept proposes that an exposure threshold value can be derived for chemicals, below which no significant risk to human health or the environment is expected. This concept goes further than setting acceptable exposure levels for individual chemicals, because it attempts to set a de minimis value for chemicals, including those of unknown toxicity, by taking the chemical's structure or mode of action (MOA) into consideration. This paper examines the use of the TTC concept for endocrine active substances (EAS) with an estrogenic MOA. A case study formed the basis for a workshop of regulatory, industry and academic scientists held to discuss the use of the TTC in aquatic environmental risk assessment. The feasibility and acceptability, general advantages and disadvantages, and the specific issues that need to be considered when applying the TTC concept for EAS in risk assessment were addressed. Issues surrounding the statistical approaches used to derive TTCs were also discussed. This paper presents discussion points and consensus findings of the workshop.JRC.I.5-Systems Toxicolog

Using an engineered glutamate-gated chloride channel to silence sensory neurons and treat neuropathic pain at the source

Peripheral neuropathic pain arises as a consequence of injury to sensory neurons; the development of ectopic activity in these neurons is thought to be critical for the induction and maintenance of such pain. Local anaesthetics and anti-epileptic drugs can suppress hyper-excitability however these drugs are complicated by unwanted effects on motor, CNS and cardiac function and alternative more selective treatments to suppress hyper-excitability are therefore required. Here we show that a glutamate-gated chloride channel (GluCl) modified to be activated by low doses of Ivermectin (but not glutamate) is highly effective in silencing sensory neurons and reversing neuropathic pain related hypersensitivity. Activation of GluCl expressed in either rodent or human iPSC-derived sensory neurons in vitro potently inhibited their response to both electrical and algogenic stimuli. We have shown that silencing is achieved both at nerve terminals and the soma and is independent of membrane hyperpolarisation and instead likely mediated by lowering of the membrane resistance. Using intrathecal adeno-associated virus serotype-9 based delivery, GluCl was successfully targeted to mouse sensory neurons in vivo, resulting in high level and long lasting expression of GluCl selectively in sensory neurons. This enabled reproducible and reversible modulation of thermal and mechanical pain thresholds in vivo; analgesia was observed for three days after a single systemic dose of Ivermectin. We did not observe any motor or proprioceptive deficits and noted no reduction in cutaneous afferent innervation or up-regulation of the injury marker ATF-3 following prolonged GluCl expression. Established mechanical and cold pain related hypersensitivity generated by the spared nerve injury model of neuropathic pain was reversed by Ivermectin treatment. The efficacy of Ivermectin in ameliorating behavioural hypersensitivity was mirrored at the cellular level by a cessation of ectopic activity in sensory neurons. These findings demonstrate the importance of aberrant afferent input in the maintenance of neuropathic pain and the potential for targeted chemogenetic silencing as a new treatment modality in neuropathic pain

The Manatee [2016]

The Manatee is a literary journal run by the students of Southern New Hampshire Universit