Here, we report on six unrelated individuals, all presenting with early-onset global developmental delay, associated with impaired motor, speech and cognitive development, partly with developmental epileptic encephalopathy and physical dysmorphisms. All individuals carry heterozygous missense variants of KCND2, which encodes the voltage-gated potassium (Kv) channel α-subunit Kv4.2. The amino acid substitutions associated with the variants, p.(Glu323Lys) (E323K), p.(Pro403Ala) (P403A), p.(Val404Leu) (V404L) and p.(Val404Met) (V404M), affect sites known to be critical for channel gating. To unravel their likely pathogenicity, recombinant mutant channels were studied in the absence and presence of auxiliary β-subunits under two-electrode voltage-clamp in Xenopus oocytes. All channel mutants exhibited slowed and incomplete macroscopic inactivation, and the P403A variant in addition slowed activation. Co-expression of KChIP2 or DPP6 augmented the functional expression of both wild-type and mutant channels, however, the auxiliary β-subunit-mediated gating modifications differed from wild-type and among mutants. To simulate the putative setting in the affected individuals, heteromeric Kv4.2 channels (wild-type + mutant) were studied as ternary complexes (containing both KChIP2 and DPP6). In the heteromeric ternary configuration, the E323K variant exhibited only marginal functional alterations compared to homomeric wild-type ternary, compatible with mild loss-of-function. By contrast, the P403A, V404L and V404M variants displayed strong gating impairment in the heteromeric ternary configuration, compatible with loss or gain-of-function. Our results support the etiological involvement of Kv4.2 channel gating impairment in early-onset monogenic global developmental delay. In addition, they suggest that gain-of-function mechanisms associated with a substitution of V404 increase epileptic seizure susceptibility.

These results indicated that this porous Mg-based alloy fabricated by infiltration casting shows great mechanical properties and biocompatibilities, and it has potential as an ideal bone tissue engineering scaffold material for bone regeneration.

Heterogeneous wireless networks will be dominant in the next-generation wireless networks with the integration of various wireless access networks. Wireless mesh networks will become to a key technology as an economically viable solution for wide deployment of high speed, scalable and ubiquitous wireless Internet services.In this thesis, we consider an interworking architecture of wireless mesh backbone and propose an effective vertical handoff scheme between 802.11 and 802.16 wireless access networks. The proposed vertical handoff scheme aims at reducing handoff signaling overhead on the wireless backbone and providing a low handoff delay to mobile nodes. The handoff signaling procedure in different scenarios is discussed. iii Acknowledgements First and foremost, I would like to express my deep gratitude and appreciation to my supervisor, Professor Weihua Zhuang, for her continuous guidance, encouragement, and patience, and for giving me the opportunity to do this work. Without her advice and support not only in academic matters but also in personal matters,

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BackgroundA structured motif allows variable length gaps between several components, where each component is a simple motif, which allows either no gaps or only fixed length gaps. The motif can either be represented as a pattern or a profile (also called positional weight matrix). We propose an efficient algorithm, called SMOTIF, to solve the structured motif search problem, i.e., given one or more sequences and a structured motif, SMOTIF searches the sequences for all occurrences of the motif. Potential applications include searching for long terminal repeat (LTR) retrotransposons and composite regulatory binding sites in DNA sequences.ResultsSMOTIF can search for both pattern and profile motifs, and it is efficient in terms of both time and space; it outperforms SMARTFINDER, a state-of-the-art algorithm for structured motif search. Experimental results show that SMOTIF is about 7 times faster and consumes 100 times less memory than SMARTFINDER. It can effectively search for LTR retrotransposons and is well suited to searching for motifs with long range gaps. It is also successful in finding potential composite transcription factor binding sites.ConclusionSMOTIF is a useful and efficient tool in searching for structured pattern and profile motifs. The algorithm is available as open-source at: .

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Carbon fiber-reinforced polymer (CFRP) has the advantages of a high strength-weight ratio and excellent fatigue resistance and has been widely used in aerospace, automotive, civil infrastructure, and other fields. The properties of CFRP materials under high temperatures are a key design issue. This paper presents the quasi-static tensile mechanical properties of unidirectional CFRP plates at temperatures ranging from 20 to 600 °C experimentally. The laser displacement transducer was adopted to capture the in situ displacement of the tested specimen. The results showed that the tensile strength of the CFRP specimen was affected by the high-temperature effect significantly, which dropped 68% and 16% for the 200 and 600 °C, respectively, compared with that of the room temperature. The degradation measured by the laser transducer system was more intensive compared with previous studies. The elastic modulus decreased to about 29% of the room temperature value at 200 °C. With the evaporation of the resin, the failure modes of the CFRP experienced brittle fracture to pullout of the fiber tow. The study provides accurate tensile performance of the CFRP plate under high-temperature exposure, which is helpful for the engineering application.