3,780 research outputs found
港珠澳大橋-香港口岸國際概念設計大賽參賽作品
這是一個港澳珠跨海大橋香港口岸的概念設計,基地位於比鄰香港國際機場的填海人工島上,四下空曠,因為地處飛機起落的航線上,它有嚴格的高度限制。我們的初衷是創造一個地標光塔,它光彩斑斕、形態舞動,無論從陸地還是海上,空中還是山上,看上去它都會成為一個令人過目難忘的香港門戶。This entry to the Hong Kong Boundary Crossing Facilities (HKBCF) International Design Ideas Competition proposes an iconic beacon of dazzling light, colour and geometrical dynamics, visible as a gateway to Hong Kong, from the approach of both directions of the HKZM Bridge, from the air along the flight paths to HK airport, and the hills of Lantau Island and the New Territories.published_or_final_versio
A randomized clinical trial of the immunogenicity of 7-valent pneumococcal conjugate vaccine compared to 23-valent polysaccharide vaccine in frail, hospitalized elderly
Background: Elderly people do not mount strong immune responses to vaccines. We compared 23-valent capsular polysaccharide (23vPPV) alone versus 7-valent conjugate (PCV7) vaccine followed by 23vPPV 6 months later in hospitalized elderly. Methods: Participants were randomized to receive 23vPPV or PCV7-23vPPV. Antibodies against serotypes 3, 4, 6A, 6B, 9V, 14, 18C, 19A, 19F, 23F were measured by enzyme-linked immunosorbent (ELISA) and opsonophagocytic (OPA) assays at baseline, 6 months and 12 months. Results: Of 312 recruited, between 40% and 72% of subjects had undetectable OPA titres at baseline. After one dose, PCV7 recipients had significantly higher responses to serotypes 9V (both assays) and 23F (OPA only), and 23vPPV recipients had significantly higher responses to serotype 3 (ELISA), 19F and 19A (OPA only). In subjects with undetectable OPA titres at baseline, a proportionately greater rise in OPA titre (P<0.01) was seen for all serotypes after both vaccines. The GMT ratio of OPA was significantly higher at 12 months in the PCV7-23vPPV group for serotypes 6A, 9V, 18C and 23F. OPA titre levels for these serotypes increased moderately after 6 months, whereas immunity waned in the 23vPPV only arm. Conclusion: We did not show overwhelming benefit of one vaccine over the other. Low baseline immunity does not preclude a robust immune response, reiterating the importance of vaccinating the frail elderly. A schedule of PCV7-23vPPV prevents waning of antibody, suggesting that both vaccines could be useful in the elderly. Follow up studies are needed to determine persistence of immunity. Trial Registration: The Australian Clinical Trials Registry ACTRN12607000387426 © 2014 MacIntyre et al
Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.
Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC); Intramural program of the National Institutes of Health, National Heart, Lung and Blood Institute (to K.N.); Academy of Finland (to H.M.C.). Funding for open access charge: MRC
Shaping bursting by electrical coupling and noise
Gap-junctional coupling is an important way of communication between neurons
and other excitable cells. Strong electrical coupling synchronizes activity
across cell ensembles. Surprisingly, in the presence of noise synchronous
oscillations generated by an electrically coupled network may differ
qualitatively from the oscillations produced by uncoupled individual cells
forming the network. A prominent example of such behavior is the synchronized
bursting in islets of Langerhans formed by pancreatic \beta-cells, which in
isolation are known to exhibit irregular spiking. At the heart of this
intriguing phenomenon lies denoising, a remarkable ability of electrical
coupling to diminish the effects of noise acting on individual cells.
In this paper, we derive quantitative estimates characterizing denoising in
electrically coupled networks of conductance-based models of square wave
bursting cells. Our analysis reveals the interplay of the intrinsic properties
of the individual cells and network topology and their respective contributions
to this important effect. In particular, we show that networks on graphs with
large algebraic connectivity or small total effective resistance are better
equipped for implementing denoising. As a by-product of the analysis of
denoising, we analytically estimate the rate with which trajectories converge
to the synchronization subspace and the stability of the latter to random
perturbations. These estimates reveal the role of the network topology in
synchronization. The analysis is complemented by numerical simulations of
electrically coupled conductance-based networks. Taken together, these results
explain the mechanisms underlying synchronization and denoising in an important
class of biological models
Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial
Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI
Unsupervised Multi-Omic Data Fusion: the Neural Graph Learning Network
In recent years, due to the high availability of omic data, data-driven biology has greatly expanded. However, the analysis of different data sources is still an open challenge. A few multi-omics approaches have been proposed in the literature, none of which takes into consideration the intrinsic topology of each omic, though. In this work, an unsupervised learning method based on a deep neural network is proposed. Foreach omic, a separate network is trained, whose outputs are fused into a single graph; at this purpose, an innovative loss function has been designed to better represent the data cluster manifolds. The graph adjacency matrix is exploited to determine similarities among samples. With this approach, omics having a different number of features are merged into a unique representation. Quantitative and qualitative analyses show that the proposed method has comparable results to the state of the art. The method has great intrinsic flexibility as it can be customized according to the complexity of the tasks and it has a lot of room for future improvements compared to more fine-tuned methods, opening the way for future research
Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells
Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al
Large Anomalous Hall effect in a silicon-based magnetic semiconductor
Magnetic semiconductors are attracting high interest because of their
potential use for spintronics, a new technology which merges electronics and
manipulation of conduction electron spins. (GaMn)As and (GaMn)N have recently
emerged as the most popular materials for this new technology. While Curie
temperatures are rising towards room temperature, these materials can only be
fabricated in thin film form, are heavily defective, and are not obviously
compatible with Si. We show here that it is productive to consider transition
metal monosilicides as potential alternatives. In particular, we report the
discovery that the bulk metallic magnets derived from doping the narrow gap
insulator FeSi with Co share the very high anomalous Hall conductance of
(GaMn)As, while displaying Curie temperatures as high as 53 K. Our work opens
up a new arena for spintronics, involving a bulk material based only on
transition metals and Si, and which we have proven to display a variety of
large magnetic field effects on easily measured electrical properties.Comment: 19 pages with 5 figure
Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity
TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations
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