A guideline for the distance measurement plans of site-directed spin labels for structural prediction of nucleic acids.

CONTEXT AND RESULTS: Site-directed spin labeling (SDSL) combined with electron paramagnetic resonance spectroscopy methods has been successfully used to predict the structures of nucleic acids. These methods measure the distances between spin labels yielding distance equations that are solved using numerical algorithms to provide one or several structural predictions. In this work, the minimum number of SDSL distance measurements and distance measurement types required to predict a unique nucleic acid structure were investigated. Our results indicate that at least six distance measurements should be obtained given that the distance measurements do not connect one SDSL on one arm with more than three SDSLs on the other arm. Moreover, there may be a preference for 1-to-1 SLs distance measurements rather than 1-to-many SLs as the latter was linked to undefined structures discussed in this study. METHODS: Pairs of double-helical arms of nucleic acid were simulated using the finite element software Pro/ENGINEER (PTC Inc., Boston, MA). In each simulation, a specific SDSL distance measurement plan was adopted and the resulting structure was tested for movability. Immovable structures indicate that this plan will potentially result in a unique structural prediction of the nucleic acid. All the possible plans for SDSL distance measurements were investigated either by direct measurement or by extrapolation.

A Scoring Framework and Apparatus for Epilepsy Seizure Detection Using a Wearable Belt.

To develop a wearable device that can detect epilepsy seizures. In particular, due to their prevalence, attention is focused on detecting the generalized tonic-clonic seizure (GTCS) type. When a seizure is detected, an alert phone call is initiated and an alarm SMS sent to the nearest health-care provider (and/or a predesignated family member), including the patient's location as global positioning system (GPS) coordinates. A wearable belt is developed including an Arduino processor that constantly acquires data from four different sensing modalities and monitors the acquired signal patterns for abnormalities. The sensors are a heart rate sensor, electromyography sensor, blood oxygen level (oxygen saturation) sensor, and an accelerometer to detect sudden falls. Higher-than-normal threshold levels are established for each sensor's signal. If two or more signal measurements exceed the corresponding threshold value for a predetermined time interval, then the seizure alarm is triggered. Clinical trials were not pursued in this study as this is the initial phase of system development (phase 0). Instead, the instrumented belt seizure detection prototype was tested on nine healthy individuals mimicking, to some degree, seizure symptoms. A total of eighteen trials took place of which half had <2 sensor thresholds exceeded and no alarm, whereas the other half resulted in activating the alarm when two or more sensor thresholds were exceeded for at least the predetermined time interval corresponding to each of the higher-than-normal sensor readings. For each trial that triggered the alarm when a seizure was detected, the on-board GPS and global system for mobile communication (GSM) units successfully initiated an alert phone call to a predesignated number in addition to sending an SMS message, including GPS location coordinates. Continuous real-time monitoring of signals from the four different sensors allows the developed wearable belt to detect GTCS while reducing false alarms. The proposed device produces an important alarm that may save a patient's life.

Measurement of serum prostate cancer markers using a nanopore thin film based optofluidic chip.

Currently used cancer marker for prostate adenocarcinoma (PC), serum prostate-specific antigen (PSA), greatly overestimates PC population. Patients with high PSA levels have to undergo unnecessary but physically painful and expensive procedure such as prostate biopsies repeatedly. The reliability of PC test can be greatly increased by finding a protein that is secreted selectively by malignant, but not normal, prostate cells. A recently discovered novel protein, referred as neuroendocrine marker (NEM), is secreted only by malignant prostate cells and released in blood circulation. Although NEM seems to be significantly more reliable based on the data obtained from a limited cohort, currently available NEM ELISA is not suitable for undertaking a large study. Therefore, the goal of the present study was to develop an alternative, label-free assay system that can reliably measure NEM and PSA in patient samples. Herein an optofluidic chip that can reliably detect PSA as well as NEM in patient samples has been developed. The optofluidic chip, which consists of arrayed nanopore-based sensors fabricated from anodic aluminum oxide (AAO) thin film, offers improved sensitivity upon the optimization of the concentration of the detector antibodies immobilized on the sensor surface. The results demonstrate that the chip is reliable, extremely sensitive and requires just 1 µl of patient serum (or even less) to measure PSA and NEM even in a non-cancer individual. Compared with the traditional ELISA for PSA, the nanopore-based sensor assay is 50-100 fold more sensitive, and offers many advantages such as elimination of labeled antigen, need for sophisticated equipment and highly trained individuals. These advantages, along with the low cost, should make the technology suitable for point-of-care application to screen elderly male populations for PC and to monitor the progress of patients undergoing PC treatment.