As the most successful neural prosthesis, cochlear implants have provided partial hearing to more than 120,000 persons worldwide; half of which being pediatric users who are able to develop nearly normal language. Biomedical engineers have played a central role in the design, integration and evaluation of the cochlear implant system, but the overall success is a result of collaborative work with physiologists, psychologists, physicians, educators, and entrepreneurs. This review presents broad yet in-depth academic and industrial perspectives on the underlying research and ongoing development of cochlear implants. The introduction accounts for major events and advances in cochlear implants, including dynamic interplays among engineers, scientists, physicians, and policy makers. The review takes a system approach to address critical issues from design and specifications to integration and evaluation. First, the cochlear implant system design and specifications are laid out. Second, the design goals, principles, and methods of the subsystem components are identified from the external speech processor and radio frequency transmission link to the internal receiver, stimulator and electrode arrays. Third, system integration and functional evaluation are presented with respect to safety, reliability, and challenges facing the present and future cochlear implant designers and users. Finally, issues beyond cochlear implants are discussed to address treatment options for the entire spectrum of hearing impairment as well as to use the cochlear implant as a model to design and evaluate other similar neural prostheses such as vestibular and retinal implants.

The “dry gets drier, wet gets wetter” (DGDWGW) paradigm is widely accepted in global moisture change. However, Greve et al.1 have declared that this paradigm has been overestimated. This controversy leaves a large gap in the understanding of the evolution of water-related processes. Here, we examine the global moisture trends using satellite soil moisture for the past 35 years (1979–2013). Our results support those of Greve et al., although there are quantitative differences. Generally, approximately 30% of global land has experienced robust moisture trends (22.16% have become drier, and 7.14% have become wetter). Only 15.12% of the land areas have followed the DGDWGW paradigm, whereas 7.77% have experienced the opposite trend. A new finding is that there is a significant “drier in dry, wetter in wet” (DIDWIW) trend paradigm; 52.69% of the drying trend occurred in arid regions, and 48.34% of the wetter trend occurred in the humid regions. Overall, 51.63% of the trends followed the DIDWIW paradigm, and 26.93% followed the opposite trend. We also identified the DGDWGW and DIDWIW paradigms in low precipitation-induced arid regions in which the dry soil led to an increasing sensible heat flux and temperature and subsequently potential evapotranspiration.

BackgroundThe specific interaction between hepatitis B virus (HBV) polymerase (P protein) and the ε RNA stem-loop on pregenomic (pg) RNA is crucial for viral replication. It triggers both pgRNA packaging and reverse transcription and thus represents an attractive antiviral target. RNA decoys mimicking ε in P protein binding but not supporting replication might represent novel HBV inhibitors. However, because generation of recombinant enzymatically active HBV polymerase is notoriously difficult, such decoys have as yet not been identified.Methodology/Principal FindingsHere we used a SELEX approach, based on a new in vitro reconstitution system exploiting a recombinant truncated HBV P protein (miniP), to identify potential ε decoys in two large ε RNA pools with randomized upper stem. Selection of strongly P protein binding RNAs correlated with an unexpected strong enrichment of A residues. Two aptamers, S6 and S9, displayed particularly high affinity and specificity for miniP in vitro, yet did not support viral replication when part of a complete HBV genome. Introducing S9 RNA into transiently HBV producing HepG2 cells strongly suppressed pgRNA packaging and DNA synthesis, indicating the S9 RNA can indeed act as an ε decoy that competitively inhibits P protein binding to the authentic ε signal on pgRNA.Conclusions/SignificanceThis study demonstrates the first successful identification of human HBV ε aptamers by an in vitro SELEX approach. Effective suppression of HBV replication by the S9 aptamer provides proof-of-principle for the ability of ε decoy RNAs to interfere with viral P-ε complex formation and suggests that S9-like RNAs may further be developed into useful therapeutics against chronic hepatitis B.