Aptamer-targeted oligonucleotide theranostics: a smarter approach for brain delivery and the treatment of neurological diseases

Aptamers represent the novel class of oligonucleotides holding multiple applications in the area of biomedicine. The advancements introduced with the Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach further eased the scope of producing modified aptamers within a short span yet retaining the properties of stability and applicability. In the recent times, aptamers were identified to have the potential for penetrating into the deep human crevices and thus can be utilized in addressing the issues of complex neurological disorders. Considering the specificity and stability enhancement by chemical modifications, aptamer-based nanotechnologies may have great potential for future therapeutics and diagnostics (theranostics). The research community has already witnessed success with the approval of macugen (an anti-vascular endothelial growth factor aptamer) for treating degenerating eye disease, and hopefully those that are in the clinical trials will soon be translated for human application. Herein, we have summarized the aptamer chemistry, aptamer-nanoconjugates and their applications against neurological diseases.

Nucleic acid-based aptamers: applications, development and clinical trials

Short single-stranded oligonucleotides called aptamers, often termed as chemical antibodies, have been developed as powerful alternatives to traditional antibodies with respect to their obvious advantages like high specificity and affinity, longer shelf-life, easier manufacturing protocol, freedom to introduce chemical modifications for further improvement, etc. Reiterative selection process of aptamers over 10-15 cycles starting from a large initial pool of random nucleotide sequences renders them with high binding affinity, thereby making them extremely specific for their targets. Aptamer-based detection systems are well investigated and likely to displace primitive detection systems. Aptamer chimeras (combination of aptamers with another aptamer or biomacromolecule or chemical moiety) have the potential activity of both the parent molecules, and thus hold the capability to perform diverse functions at the same time. Owing to their extremely high specificity and lack of immunogenicity or pathogenicity, a number of other aptamers have recently entered clinical trials and have garnered favorable attention from pharmaceutical companies. Promising results from the clinical trials provide new hope to change the conventional style of therapy. Aptamers have attained high therapeutic relevance in a short time as compared to synthetic drugs and/or other modes of therapy. This review follows the various trends in aptamer technology including production, selection, modifications and success in clinical fields. It focusses largely on the various applications of aptamers which mainly depend upon their selection procedures. The review also sheds light on various modifications and chimerizations that have been implemented in order to improve the stability and functioning of the aptamers, including introduction of locked nucleic acids (LNAs). The application of various aptamers in detection systems has been discussed elaborately in order to stress on their role as efficient diagnostic agents. The key aspect of this review is focused on success of aptamers on the basis of their performance in clinical trials for various diseases.

An Instrument Design for Space-Based Optical Observation of Space Debris

Currently, observations of space debris are primarily performed with ground-based sensors. These sensors have a detection limit at some centimetres diameter for objects in Low Earth Orbit (LEO) and at about two decimetres diameter for objects in Geostationary Orbit (GEO). The few space-based debris observations stem mainly from in-situ measurements and from the analysis of returned spacecraft surfaces. Both provide information about mostly sub-millimetre-sized debris particles. As a consequence the population of centimetre- and millimetre-sized debris objects remains poorly understood. The development, validation and improvement of debris reference models drive the need for measurements covering the whole diameter range. In 2003 the European Space Agency (ESA) initiated a study entitled “Space-Based Optical Observation of Space Debris”. The first tasks of the study were to define user requirements and to develop an observation strategy for a space-based instrument capable of observing uncatalogued millimetre-sized debris objects. Only passive optical observations were considered, focussing on mission concepts for the LEO, and GEO regions respectively. Starting from the requirements and the observation strategy, an instrument system architecture and an associated operations concept have been elaborated. The instrument system architecture covers the telescope, camera and onboard processing electronics. The proposed telescope is a folded Schmidt design, characterised by a 20 cm aperture and a large field of view of 6°. The camera design is based on the use of either a frame-transfer charge coupled device (CCD), or on a cooled hybrid sensor with fast read-out. A four megapixel sensor is foreseen. For the onboard processing, a scalable architecture has been selected. Performance simulations have been executed for the system as designed, focussing on the orbit determination of observed debris particles, and on the analysis of the object detection algorithms. In this paper we present some of the main results of the study. A short overview of the user requirements and observation strategy is given. The architectural design of the instrument is discussed, and the main tradeoffs are outlined. An insight into the results of the performance simulations is provided.

Capability of a space-based space surveillance system to detect and track objects in GEO, MEO and LEO orbits

In this paper we present the results from the coverage and the orbit determination accuracy simulations performed within the recently completed ESA study “Assessment Study for Space Based Space Surveillance (SBSS) Demonstration System” (Airbus Defence and Space consortium). This study consisted in investigating the capability of a space based optical sensor (SBSS) orbiting in low Earth orbit (LEO) to detect and track objects in GEO (geosynchronous orbit), MEO (medium Earth orbit) and LEO and to determinate and improve initial orbits from such observations. Space based systems may achieve better observation conditions than ground based sensors in terms of astrometric accuracy, detection coverage, and timeliness. The primary observation mode of the proposed SBSS demonstrator is GEO surveillance, i.e. the systematic search and detection of unknown and known objects. GEO orbits are specific and unique orbits from dynamical point of view. A space-based sensor may scan the whole GEO ring within one sidereal day if the orbit and pointing directions are chosen properly. For an efficient survey, our goal was to develop a leak-proof GEO fence strategy. Collaterally, we show that also MEO, LEO and other (GTO,Molniya, etc.) objects would be possible to observe by the system and for a considerable number of LEO objects to down to size of 1 cm we can obtain meaningful statistical data for improvement and validation of space debris environment models

Control of a solar dryer through using a fuzzy logic and low-cost model-based sensor

Solar drying is one of the important processes used for extending the shelf life of agricultural products. Regarding consumer requirements, solar drying should be more suitable in terms of curtailing total drying time and preserving product quality. Therefore, the objective of this study was to develop a fuzzy logic-based control system, which performs a ?human-operator-like? control approach through using the previously developed low-cost model-based sensors. Fuzzy logic toolbox of MatLab and Borland C++ Builder tool were utilized to develop a required control system. An experimental solar dryer, constructed by CONA SOLAR (Austria) was used during the development of the control system. Sensirion sensors were used to characterize the drying air at different positions in the dryer, and also the smart sensor SMART-1 was applied to be able to include the rate of wood water extraction into the control system (the difference of absolute humidity of the air between the outlet and the inlet of solar dryer is considered by SMART-1 to be the extracted water). A comprehensive test over a 3 week period for different fuzzy control models has been performed, and data, obtained from these experiments, were analyzed. Findings from this study would suggest that the developed fuzzy logic-based control system is able to tackle difficulties, related to the control of solar dryer process.

Toward a new generation of photonic humidity sensors

This review offers new perspectives on the subject and highlights an area in need of further research. It includes an analysis of current scientific literature mainly covering the last decade and examines the trends in the development of electronic, acoustic and optical-fiber humidity sensors over this period. The major findings indicate that a new generation of sensor technology based on optical fibers is emerging. The current trends suggest that electronic humidity sensors could soon be replaced by sensors that are based on photonic structures. Recent scientific advances are expected to allow dedicated systems to avoid the relatively high price of interrogation modules that is currently a major disadvantage of fiber-based sensors.

Perspective work on optical fibre sensors

Optical fibre based sensors are transforming industry by permitting monitoring in hitherto inaccessible environments or measurement approaches that cannot be reproduced using conventional electronic sensors. A multitude of techniques have been developed to render the fibres sensitive to a wide range of parameters including: temperature, strain, pressure (static and dynamic), acceleration, rotation, gas type, and specific biochemical species. Constructed entirely of glass or polymer material, optical fibre devices like fibre gratings offer the properties: low loss, dielectric construction, small size, multiplexing, and so on [1-3]. In this paper, the authors will show the latest developing industrial applications, using polymer optical fibre (POF) devices, and comparing their performance with silica optical fibre devices. The authors address two pressing commercial requirements. The first concerns the monitoring of fuel level in civil aircraft. There is a strong motivation in the aerospace industry to move away from electrical sensors, especially in the fuel system. This is driven by the need to eliminate potential ignition hazards, the desire to reduce cabling weight and the need to mitigate the effects of lightning strikes in aircraft where the conventional metallic skin is increasingly being replaced by composite materials. In this case, the authors have developed pressure sensors based on a diaphragm in which a polymer fibre Bragg grating (POFBG) has been embedded [3]. These devices provide high pressure sensitivity enabling level measurement in the mm range. Also, it has developed an approach incorporating several such sensors which can compensate for temperature drifts and is insensitive to fluid density. Compared with silica fibre-based sensors, their performance is highly enhanced. Initial results have attracted the interest of Airbus from UK, who is keen to explore the potential of optical technology in commercial aircraft. The second concerns the monitoring of acoustic signals and vibration in the subsea environment, for applications in geophysical surveying and security (detection of unwanted craft or personnel). There is strong motivation to move away from electrical sensors due to the bulk of the sensor and associated cabling and the impossibility of monitoring over large distances without electrical amplification. Optical approaches like optical hydrophones [5] offer a means of overcoming these difficulties. In collaboration with Kongsberg from Norway, the authors will exploit the sensitivity improvements possible by using POF instead of silica fibre. These improvements will arise as a result of the much more compliant nature of POF compared to silica fibre (3 GPa vs 72 GPa, respectively). Essentially, and despite the strain sensitivity of silica and POFBGs being very similar, this renders the POF much more sensitive to the applied stress resulting from acoustic signals or vibration. An alternative way of viewing this is that the POF is better impedance-matched to the surrounding environment (water for the intended applications), because although its impedance is higher than that of water, it is nearly an order of magnitude smaller than that of silica. Finally, other future industrial applications will be presented and discussed, showing the vast range of the optical fiber devices in sensing applications.

Performance analysis of polymer optical fibre based Fabry-Perot sensor formed by two uniform Bragg gratings

The stress sensitivity of polymer optical fibre (POF) based Fabry-Perot sensors formed by two uniform Bragg gratings with finite dimensions is investigated. POF has received high interest in recent years due to its different material properties compared to its silica counterpart. Biocompatibility, a higher failure strain and the highly elastic nature of POF are some of the main advantages. The much lower Young’s modulus of polymer materials compared to silica offers enhanced stress sensitivity to POF based sensors which renders them great candidates for acoustic wave receivers and any kind of force detection. The main drawback in POF technology is perhaps the high fibre loss. In a lossless fibre the sensitivity of an interferometer is proportional to its cavity length. However, the presence of the attenuation along the optical path can significantly reduce the finesse of the Fabry-Perot interferometer and it can negatively affect its sensitivity at some point. The reflectivity of the two gratings used to form the interferometer can be also reduced as the fibre loss increases. In this work, a numerical model is developed to study the performance of POF based Fabry-Perot sensors formed by two uniform Bragg gratings with finite dimensions. Various optical and physical properties are considered such as grating physical length, grating effective length which indicates the point where the light is effectively reflected, refractive index modulation of the grating, cavity length of the interferometer, attenuation and operating wavelength. Using this model, we are able to identify the regimes in which the PMMA based sensor offer enhanced stress sensitivity compared to silica based one.

Wearable sensors in Huntington disease:a pilot study

Background: The Unified Huntington’s Disease Rating Scale (UHDRS) is the principal means of assessing motor impairment in Huntington disease but is subjective and generally limited to in-clinic assessments. Objective: To evaluate the feasibility and ability of wearable sensors to measure motor impairment in individuals with Huntington disease in the clinic and at home. Methods: Participants with Huntington disease and controls were asked to wear five accelerometer-based sensors attached to the chest and each limb for standardized, in-clinic assessments and for one day at home. A secondchest sensor was worn for six additional days at home. Gait measures were compared between controls, participants with Huntington disease, and participants with Huntington disease grouped by UHDRS total motor score using Cohen’s d values. Results: Fifteen individuals with Huntington disease and five controls completed the study. Sensor data were successfully captured from 18 of the 20 participants at home. In the clinic, the standard deviation of step time (timebetween consecutive steps) was increased in Huntington disease (p<0.0001; Cohen’s d=2.61) compared to controls. At home with additional observations, significant differences were observed in seven additional gait measures. The gait of individuals with higher total motor scores (50 or more) differed significantly from those with lower total motor scores (below 50) on multiple measures at home. Conclusions: In this pilot study, the use of wearable sensors in clinic and at home was feasible and demonstrated gait differences between controls, participants with Huntington disease, and participants with Huntington diseasegrouped by motor impairment.

Wireless video-based sensor networks for surveillance of residential districts

Compared to traditional wired video sensor networks to supervise a residential district, Wireless Video-based Sensor Networks (WVSN) can provide more detail and precise information while reduce the cost. However, state-of-the-art low cost wireless video-based sensors have very constrained resources such as low bandwidth, small storage, limited processing capability, and limited energy resource. Also, due to the special sensing range of video-based sensors, cluster-based routing is not as effective as it apply to traditional sensor networks. This paper provides a novel real-time change mining algorithm based on an extracted profile model of moving objects learnt from frog's eyes. Example analysis shows the extracted profile would not miss any important semantic images to send to the Base Station for further hazards detection, while efficiently reducing futile video stream data to the degree that nowadays wireless video sensor can realize. Thus it makes WVSN available to surveillance of residential districts.

Targeting cancer cells using LNA-modified aptamer-siRNA chimeras

Aptamers are chimerized with drug or antisense oligos or nanoparticles to generate targeted therapeutics for cancer. Aptamer chimerized siRNA rescues nonspecific delivery and, thereby, enhances the availability of siRNA to target cells. EpCAM RNA aptamer (EpApt or Ep) has potential for siRNA chimerization due to its secondary structure. Stathmin and survivin proteins are reported to aid oncogenicity in retinoblastoma (RB), breast cancer and other cancers. Thus, chimerization of EpCAM Apt with siRNA against survivin and stathmin, respectively, was performed by incorporating Locked Nucleic Acid (LNA) modification. The LNA-modified chimeric aptamers were stable until 96 h and got internalized into RB, WERI-Rb1 and breast cancer, MDAMB453 cell lines. The constructs were studied using the recombinant dicer enzyme for the siRNA generation. Quantitative polymerase chain reaction and immunofluorescence by microscopic analysis of chimeras in vitro exhibited silencing of stathmin and survivin in the RB and breast cancer model. The chimeric constructs showed significant inhibition of cell proliferation of breast cancer cells. Thus, LNA-modified aptamer-based siRNA delivery aids in cell targeting and necessitates further studies in animal models.

Object grasping and safe manipulation using friction-based sensing.

This project provides a solution for slippage prevention in industrial robotic grippers for the purpose of safe object manipulation. Slippage sensing is performed using novel friction-based sensors, with customisable slippage sensitivity and complemented by an effective slippage prediction strategy. The outcome is a reliable and affordable slippage prevention technology.

Monitoring animal behaviour and environmental interactions : GPS collars and satellite remote sensing within a satellite remote sensing context

Remote monitoring of animal behaviour in the environment can assist in managing both the animal and its environmental impact. GPS collars which record animal locations with high temporal frequency allow researchers to monitor both animal behaviour and interactions with the environment. These ground-based sensors can be combined with remotely-sensed satellite images to understand animal-landscape interactions. The key to combining these technologies is communication methods such as wireless sensor networks (WSNs). We explore this concept using a case-study from an extensive cattle enterprise in northern Australia and demonstrate the potential for combining GPS collars and satellite images in a WSN to monitor behavioural preferences and social behaviour of cattle.

Monitoring animal behaviour and environmental interactions using wireless sensor networks, GPS collars and satellite remote sensing

Remote monitoring of animal behaviour in the environment can assist in managing both the animal and its environmental impact. GPS collars which record animal locations with high temporal frequency allow researchers to monitor both animal behaviour and interactions with the environment. These ground-based sensors can be combined with remotely-sensed satellite images to understand animal-landscape interactions. The key to combining these technologies is communication methods such as wireless sensor networks (WSNs). We explore this concept using a case-study from an extensive cattle enterprise in northern Australia and demonstrate the potential for combining GPS collars and satellite images in a WSN to monitor behavioural preferences and social behaviour of cattle.

Non-invasive method for detecting changes in soil moisture using wireless sensor networks

There are several popular soil moisture measurement methods today such as time domain reflectometry, electromagnetic (EM) wave, electrical and acoustic methods. Significant studies have been dedicated in developing method of measurements using those concepts, especially to achieve the characteristics of noninvasiveness. EM wave method provides an advantage because it is non-invasive to the soil and does not need to utilise probes to penetrate or bury in the soil. But some EM methods are also too complex, expensive, and not portable for the application of Wireless Sensor Networks; for example satellites or UAV (Unmanned Aerial Vehicle) based sensors. This research proposes a method in detecting changes in soil moisture using soil-reflected electromagnetic (SREM) wave from Wireless Sensor Networks (WSNs). Studies have shown that different levels of soil moisture will affects soil’s dielectric properties, such as relative permittivity and conductivity, and in turns change its reflection coefficients. The SREM wave method uses a transmitter adjacent to a WSNs node with purpose exclusively to transmit wireless signals that will be reflected by the soil. The strength from the reflected signal that is determined by the soil’s reflection coefficients is used to differentiate the level of soil moisture. The novel nature of this method comes from using WSNs communication signals to perform soil moisture estimation without the need of external sensors or invasive equipment. This innovative method is non-invasive, low cost and simple to set up. There are three locations at Brisbane, Australia chosen as the experiment’s location. The soil type in these locations contains 10–20% clay according to the Australian Soil Resource Information System. Six approximate levels of soil moisture (8, 10, 13, 15, 18 and 20%) are measured at each location; with each measurement consisting of 200 data. In total 3600 measurements are completed in this research, which is sufficient to achieve the research objective, assessing and proving the concept of SREM wave method. These results are compared with reference data from similar soil type to prove the concept. A fourth degree polynomial analysis is used to generate an equation to estimate soil moisture from received signal strength as recorded by using the SREM wave method.