3,323 research outputs found
The Competition for Shortest Paths on Sparse Graphs
Optimal paths connecting randomly selected network nodes and fixed routers
are studied analytically in the presence of non-linear overlap cost that
penalizes congestion. Routing becomes increasingly more difficult as the number
of selected nodes increases and exhibits ergodicity breaking in the case of
multiple routers. A distributed linearly-scalable routing algorithm is devised.
The ground state of such systems reveals non-monotonic complex behaviors in
both average path-length and algorithmic convergence, depending on the network
topology, and densities of communicating nodes and routers.Comment: 4 pages, 4 figure
Vowels of Hong Kong English: from an acoustic perspective
Thesis (B.Sc)--University of Hong Kong, 2007.A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2007.Also available in print.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science
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Characterisation and pharmacological regulation of GLP-1-mediated glucose homeostasis
Type 2 diabetes mellitus (T2DM) is characterised by the hormonal imbalance of insulin and glucagon, leading to dysfunctional glucose homeostasis. Glucagon-like peptide 1 (GLP-1), which is an incretin hormone, activates the predominantly Gαs-coupled glucagon-like peptide 1 receptor (GLP-1R), which is a class B G protein-coupled receptor (GPCR), to mediate glucose homeostasis. It does so by promoting glucose stimulated insulin secretion (GSIS) in the pancreatic β cells and inhibiting glucagon secretion in the pancreatic α cells. Given its proven clinical efficacy in reducing long term blood glucose level, GLP-1-based treatments, such as exenatide and liraglutide, have been widely used in T2DM patients.
However, in contrast to the well-studied phenomenon of how GLP-1 enhances GSIS, the mechanism of how GLP-1 regulates glucagon secretion is still unclear. Therefore, the aim of this work is to shed new lights on how GLP-1 mediates its glucagonostatic action. To do so, the signalling properties of GLP-1 and its closely-related peptide hormones, namely oxyntomodulin (OXM), glucagon (GCG), glucose-dependent insulinotropic polypeptide (GIP), and its metabolite, GLP-1(9-36)NH2, were examined in recombinant cell lines and rodent clonal α and β cell lines using cAMP functional assaying technique. It was demonstrated that these glucagon-like peptides, including GLP-1(9-36)NH2 yet except GIP, can activate both GLP-1R and glucagon receptor (GCGR), which is struc- turally analogous to GLP-1R. Furthermore, GLP-1R, despite its very low expression in the mouse αTC1.6 cell line detected through semi-quantitative RT-PCR studies, is found to play a critical role in directly inhibiting glucagon secretion upon GLP-1 activation through performing glucagon secretion antagonism studies. More importantly, the physiologically abundant GLP-1 metabolite is discovered to play a glucagonostatic role in the mouse glucagonoma cell line via the direct actions of GLP-1R and GCGR, an observation that has not yet been documented. Therefore, this thesis provides evidence of how GLP-1 and its metabolite are actively involved in their glucagonostatic actions via direct activations of GLP-1R and GCGR.
Another aim of this work is to identify viable pharmacological regulator of GLP-1- mediated glucose homeostasis through the action of positive allosteric modulator (PAM). Here, compound 249, which was identified previously as a small molecule GLP-1R PAM, was further pharmacologically validated using various signal transduction assaying techniques in recombinant cell lines. It was also demonstrated that compound 249 works independent of the cysteine-347 residue on the GLP-1R, an amino acid residue which has been previously shown to be instrumental for the actions of another GLP-1R agonist-PAMs. More importantly, compound 249 demonstrates robust potentiation of GLP-1 and OXM-augmented GSIS in the rat INS-1 832/3 insulinoma cell line and ex vivo isolated mouse islets, substantiating the potential of compound 249 to be further developed as a novel T2DM treatment.
Overall this thesis presents new evidence on the direct involvement of GLP-1R on GLP-1-regulated glucagon secretion in the pancreatic α cells and illustrates compound 249 as a PAM to promote GLP-1 mediated GSIS. The findings in this thesis will be used for future design of safer and more efficacious T2DM treatments
Capacity Analysis of Linear Operator Channels over Finite Fields
Motivated by communication through a network employing linear network coding,
capacities of linear operator channels (LOCs) with arbitrarily distributed
transfer matrices over finite fields are studied. Both the Shannon capacity
and the subspace coding capacity are analyzed. By establishing
and comparing lower bounds on and upper bounds on , various
necessary conditions and sufficient conditions such that are
obtained. A new class of LOCs such that is identified, which
includes LOCs with uniform-given-rank transfer matrices as special cases. It is
also demonstrated that is strictly less than for a broad
class of LOCs. In general, an optimal subspace coding scheme is difficult to
find because it requires to solve the maximization of a non-concave function.
However, for a LOC with a unique subspace degradation, can be
obtained by solving a convex optimization problem over rank distribution.
Classes of LOCs with a unique subspace degradation are characterized. Since
LOCs with uniform-given-rank transfer matrices have unique subspace
degradations, some existing results on LOCs with uniform-given-rank transfer
matrices are explained from a more general way.Comment: To appear in IEEE Transactions on Information Theor
Single Molecule Mechanics on Surface
This thesis explores the mechanics of single molecule machines on a surface, aiming to understand the principles underlying synthetic single molecular machines. The study utilizes scanning tunneling microscopy (STM) at ultra-low temperatures and high vacuum conditions to investigate individual small molecules adsorbed on a substrate. In the first part, the transmission of rotation between single molecule-gears is examined, employing a star-shaped pentaphenylcyclopentadiene molecule manipulated by STM. The second part focuses on a zwitterionic and chiral molecule's dual functionality as a molecule-rotor or a molecule-vehicle (nanocar), with motion driven by tunneling electrons. The third part explores the origin of unidirectional rotation in a single molecule-rotor, analyzing the effects of thermal and electronic excitations on rotation dynamics. Overall, this work contributes to the fundamental understanding of nanoscale mechanical molecular devices and their potential applications
Empirical studies on the network of social groups: the case of Tencent QQ
Participation in social groups are important but the collective behaviors of
human as a group are difficult to analyze due to the difficulties to quantify
ordinary social relation, group membership, and to collect a comprehensive
dataset. Such difficulties can be circumvented by analyzing online social
networks. In this paper, we analyze a comprehensive dataset obtained from
Tencent QQ, an instant messenger with the highest market share in China.
Specifically, we analyze three derivative networks involving groups and their
members -- the hypergraph of groups, the network of groups and the user network
-- to reveal social interactions at microscopic and mesoscopic level. Our
results uncover interesting behaviors on the growth of user groups, the
interactions between groups, and their relationship with member age and gender.
These findings lead to insights which are difficult to obtain in ordinary
social networks.Comment: 18 pages, 9 figure
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