Advanced source and drain contact engineering for low parasitic series resistance

Master'sMASTER OF ENGINEERIN

Open Learning in Singapore

Although Open Learning is not a concept that is widely used in Singapore public education institutions, we shares that Open Learning is of strategic importance to Singapore education as the country prepares to meet the challenges of a knowledge-driven economy. We propose three principles that form the wheel of Open Learning, which can be “turned” by ICT as a driver. The three principles are the ‘minimising of constraints to access to learning’, ‘Learner-Centred’ learning that include the recognition of ‘prior learning and experience’ and ‘flexible learning’. We shares that there are already examples of Singapore public educational institutions implementing aspects of Open Learning. These institutions have already a good ICT infrastructure in place to minimise access constraints to learning beyond the physical “classroom” boundaries. The challenge ahead for the Singapore public educational institutions in Open Learning is to be able to more fully articulate the latter two principles of Learner-Centred” learning and flexible learning

Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells

10.1186/1749-8546-6-4Chinese Medicine6

Interactions of Dopamine D1 and N-methyl-D-Aspartate Receptors are Required for Acute Cocaine-Evoked Nitric Oxide Efflux in the Dorsal Striatum

Alterations in nitric oxide (NO) release in response to psychostimulants in the striatum cause a plastic change contributing to the development and expression of addiction. In this study, regulation of NO efflux evoked by acute cocaine in the dorsal striatum was investigated using real-time detection of NO in vivo. We found that acute systemic injection of cocaine (20 mg/kg) increased NO efflux, which was reduced by the intrastriatal infusion of the dopamine D1 receptor antagonist, SCH23390 (7.5 nmol), and the dopamine D2 receptor agonist, quinpirole (5 nmol). Increased levels of NO efflux by acute cocaine were also reduced by the intrastriatal infusion of the N-methyl-D-aspartate (NMDA) receptor antagonists, MK801 (2 nmol) and AP5 (2 nmol). These findings suggest that interactions of dopamine D1 receptors and NMDA receptors after acute exposure to cocaine participate in the upregulation of NO efflux in the dorsal striatum

Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide

Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN. Here, we determined the crystal structure of an amino-terminal peptide of SALL4(1-12) complexed to RBBp4, the chaperone subunit of NuRD, at 2.7 Å, and subsequent design of a potent therapeutic SALL4 peptide (FFW) capable of antagonizing the SALL4-NURD interaction using systematic truncation and amino acid substitution studies. FFW peptide disruption of the SALL4-NuRD complex resulted in unidirectional up-regulation of transcripts, turning SALL4 from a dual transcription repressor-activator mode to singular transcription activator mode. We demonstrate that FFW has a target affinity of 23 nM, and displays significant antitumor effects, inhibiting tumor growth by 85% in xenograft mouse models. Using transcriptome and survival analysis, we discovered that the peptide inhibits the transcription-repressor function of SALL4 and causes massive up-regulation of transcripts that are beneficial to patient survival. This study supports the SALL4-NuRD complex as a drug target and FFW as a viable drug candidate, showcasing an effective strategy to accurately target oncogenes previously considered undruggable

An Early-warning System for Electromagnetic Follow-up of Gravitational-wave Events

Binary neutron stars (BNSs) will spend ≃10–15 minutes in the band of Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo detectors at design sensitivity. Matched-filtering of gravitational-wave (GW) data could in principle accumulate enough signal-to-noise ratio (S/N) to identify a forthcoming event tens of seconds before the companions collide and merge. Here we report on the design and testing of an early-warning GW detection pipeline. Early-warning alerts can be produced for sources that are at low enough redshift so that a large enough S/N accumulates ~10–60 s before merger. We find that about 7% (49%) of the total detectable BNS mergers will be detected 60 s (10 s) before the merger. About 2% of the total detectable BNS mergers will be detected before merger and localized to within 100 deg² (90% credible interval). Coordinated observing by several wide-field telescopes could capture the event seconds before or after the merger. LIGO–Virgo detectors at design sensitivity could facilitate observing at least one event at the onset of merger