Cooperativity among Short Amyloid Stretches in Long Amyloidogenic Sequences

Amyloid fibrillar aggregates of polypeptides are associated with many neurodegenerative diseases. Short peptide segments in protein sequences may trigger aggregation. Identifying these stretches and examining their behavior in longer protein segments is critical for understanding these diseases and obtaining potential therapies. In this study, we combined machine learning and structure-based energy evaluation to examine and predict amyloidogenic segments. Our feature selection method discovered that windows consisting of long amino acid segments of ∼30 residues, instead of the commonly used short hexapeptides, provided the highest accuracy. Weighted contributions of an amino acid at each position in a 27 residue window revealed three cooperative regions of short stretch, resemble the β-strand-turn-β-strand motif in A-βpeptide amyloid and β-solenoid structure of HET-s(218–289) prion (C). Using an in-house energy evaluation algorithm, the interaction energy between two short stretches in long segment is computed and incorporated as an additional feature. The algorithm successfully predicted and classified amyloid segments with an overall accuracy of 75%. Our study revealed that genome-wide amyloid segments are not only dependent on short high propensity stretches, but also on nearby residues

Growth in China's rural enterprises: impacts on urban-rural relations

China's rural enterprises are economic units established by local government in the countryside or by the peasants and they operate outside the planning system. Rural enterprises have grown twice as fast as the rest of the economy since 1984. The rural enterprise sector has so far challenged the urban economy, in both product markets and markets for raw materials. What are the prospects for their relationship - competition or cooperation? To answer the question, we develop a well-specified but simple model of the rural and urban economies. The rural enterprise boom was caused in this model by the presence of barriers to factor mobility within China, price distortions and the pool of available labour in the countryside. The origins of the boom imply that rural enterprise exports tend to be relatively labour intensive. The complementarities between rural and urban enterprises are likely to dominate their future economic relationship and lead to further growth in the rural enterprise sector.Zhang Xiaohe, Christopher Findlay & Andrew Watso

Fiber-Optic Array Scanning Technology (FAST) for Detection and Molecular Characterization of Circulating Tumor Cells.

Circulating tumor cell (CTC) as an important component in "liquid biopsy" holds crucial clinical relevance in cancer prognosis, treatment efficiency evaluation, prediction and potentially early detection. Here, we present a Fiber-optic Array Scanning Technology (FAST) that enables antigen-agnostic, size-agnostic detection of CTC. By immunofluorescence staining detection of a combination of a panel of markers, FAST technology can be applied to detect rare CTC in non-small cell lung cancer (NSCLC) setting with high sensitivity and specificity. In combination with Automated Digital Microscopy (ADM) platform, companion markers on CTC such as Vimentin and Programmed death-ligand 1 (PD-L1) can also be analyzed to further characterize these CTCs. FAST data output is also compatible with downstream single cell picking platforms. Single cell can be isolated post ADM confirmation and used for "actionable" genetic mutations analysis