Coupling and Elastic Loading Affect the Active Response by the Inner Ear Hair Cell Bundles

Active hair bundle motility has been proposed to underlie the amplification mechanism in the auditory endorgans of non-mammals and in the vestibular systems of all vertebrates, and to constitute a crucial component of cochlear amplification in mammals. We used semi-intact in vitro preparations of the bullfrog sacculus to study the effects of elastic mechanical loading on both natively coupled and freely oscillating hair bundles. For the latter, we attached glass fibers of different stiffness to the stereocilia and observed the induced changes in the spontaneous bundle movement. When driven with sinusoidal deflections, hair bundles displayed phase-locked response indicative of an Arnold Tongue, with the frequency selectivity highest at low amplitudes and decreasing under stronger stimulation. A striking broadening of the mode-locked response was seen with increasing stiffness of the load, until approximate impedance matching, where the phase-locked response remained flat over the physiological range of frequencies. When the otolithic membrane was left intact atop the preparation, the natural loading of the bundles likewise decreased their frequency selectivity with respect to that observed in freely oscillating bundles. To probe for signatures of the active process under natural loading and coupling conditions, we applied transient mechanical stimuli to the otolithic membrane. Following the pulses, the underlying bundles displayed active movement in the opposite direction, analogous to the twitches observed in individual cells. Tracking features in the otolithic membrane indicated that it moved in phase with the bundles. Hence, synchronous active motility evoked in the system of coupled hair bundles by external input is sufficient to displace large overlying structures

A Comparative Study of Defeasible Argumentation and Non-monotonic Fuzzy Reasoning for Elderly Survival Prediction Using Biomarkers

Computational argumentation has been gaining momentum as a solid theoretical research discipline for inference under uncertainty with incomplete and contradicting knowledge. However, its practical counterpart is underdeveloped, with a lack of studies focused on the investigation of its impact in real-world settings and with real knowledge. In this study, computational argumentation is compared against non-monotonic fuzzy reasoning and evaluated in the domain of biological markers for the prediction of mortality in an elderly population. Different non-monotonic argument-based models and fuzzy reasoning models have been designed using an extensive knowledge base gathered from an expert in the field. An analysis of the true positive and false positive rate of the inferences of such models has been performed. Findings indicate a superior inferential capacity of the designed argument-based models

Integrating removal actions and remedial actions: Soil and debris management at the Fernald Environmental Management Project

Since 1991, excess soil and debris generated at the Fernald Environmental management Project (FEMP) have been managed in accordance with the principles contained in a programmatic Removal Action (RvA) Work Plan (WP). This plan provides a sitewide management concept and implementation strategy for improved storage and management of excess soil and debris over the period required to design and construct improved storage facilities. These management principles, however, are no longer consistent with the directions in approved and draft Records of Decision (RODs) and anticipated in draft RODs other decision documents. A new approach has been taken to foster improved management techniques for soil and debris that can be readily incorporated into remedial design/remedial action plans. Response, Compensation and Liability Act (CERCLA) process. This paper describes the methods that were applied to address the issues associated with keeping the components of the new work plan field implementable and flexible; this is especially important as remedial design is either in its initial stages or has not been started and final remediation options could not be precluded

A Novel Approach to Molecular Recognition Surface of Magnetic Nanoparticles Based on Host–Guest Effect

A novel route has been developed to prepared β-cyclodextrin (β-CD) functionalized magnetic nanoparticles (MNPs). The MNPs were first modified with monotosyl-poly(ethylene glycol) (PEG) silane and then tosyl units were displaced by amino-β-CD through the nucleophilic substitution reaction. The monotosyl-PEG silane was synthesized by modifying a PEG diol to form the corresponding monotosyl-PEG, followed by a reaction with 3-isocyanatopropyltriethoxysilane (IPTS). The success of the synthesis of the monotosyl-PEG silane was confirmed with1H NMR and Fourier transform infrared (FTIR) spectroscopy. The analysis of FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS) confirmed the immobilization of β-CD onto MNPs. Transmission electron microscopy (TEM) indicated that the β-CD functionalized MNPs were mostly present as individual nonclustered units in water. The number of β-CD molecules immobilized on each MNP was about 240 according to the thermogravimetric analysis (TGA) results. The as-prepared β-CD functionalized MNPs were used to detect dopamine with the assistance of a magnet

Biomarkers of Multiple Sclerosis

The search for an ideal multiple sclerosis biomarker with good diagnostic value, prognostic reference and an impact on clinical outcome has yet to be realized and is still ongoing. The aim of this review is to establish an overview of the frequent biomarkers for multiple sclerosis that exist to date. The review summarizes the results obtained from electronic databases, as well as thorough manual searches. In this review the sources and methods of biomarkers extraction are described; in addition to the description of each biomarker, determination of the prognostic, diagnostic, disease monitoring and treatment response values besides clinical impact they might possess. We divided the biomarkers into three categories according to the achievement method: laboratory markers, genetic-immunogenetic markers and imaging markers. We have found two biomarkers at the time being considered the gold standard for MS diagnostics. Unfortunately, there does not exist a single solitary marker being able to present reliable diagnostic value, prognostic value, high sensitivity and specificity as well as clinical impact. We need more studies to find the best biomarker for MS.publishersversionPeer reviewe

predictive precision medicine towards the computational challenge

The emerging fields of predictive and precision medicine are changing the traditional medical approach to disease and patient. Current discoveries in medicine enable to deepen the comprehension of diseases, whereas the adoption of high-quality methods such as novel imaging techniques (e.g. MRI, PET) and computational approaches (i.e. machine learning) to analyse data allows researchers to have meaningful clinical and statistical information. Indeed, applications of radiology techniques and machine learning algorithms rose in the last years to study neurology, cardiology and oncology conditions. In this chapter, we will provide an overview on predictive precision medicine that uses artificial intelligence to analyse medical images to enhance diagnosis, prognosis and treatment of diseases. In particular, the chapter will focus on neurodegenerative disorders that are one of the main fields of application. Despite some critical issues of this new approach, adopting a patient-centred approach could bring remarkable improvement on individual, social and business level

Approved CAMU equals faster, better, cheaper remediation at the Fernald Environmental Management Project

A 1,050 acre Corrective Action Management Unit (CAMU) was approved for the Fernald Protection Agency Environmental Management Project (FEMP) by the US Environmental Protection Agency (USEPA) to manage environmental media remediation waste in the Operable Unit 5 Record of Decision, 1995. Debris is also proposed for management as remediation waste under the CAMU Rule in the Operable Unit 3 Remedial Investigation/Feasibility Study (RI/FS) Report, as of December 1995. Application of the CAMU Rule at the FEMP will allow consolidation of low-level mixed waste and hazardous waste that presents minimal threat from these two operable units in an on-property engineered disposal facility without triggering land disposal restrictions (LDRs). The waste acceptance criteria for the on property disposal facility are based on a combination of site-specific risk-based concentration standards, as opposed to non-site-specific requirements imposed by regulatory classifications