A hierarchical approach to formal modeling and verification of asynchronous circuits

The self-timed (or asynchronous) approach to circuit design has demonstrated benefits in a number of different areas for its low energy consumption, high operating speed, composability, and modularity. Nonetheless, the asynchronous paradigm exposes challenges that are not found in the synchronous (or clock-driven) paradigm. For the verification task, a challenge emerges from the large number of potential operational interleavings exhibited in the asynchronous paradigm. Simply exploring all interleavings is, in general, intractable because the number of interleavings can grow exponentially. This dissertation focuses on developing scalable methods that are capable of reasoning effectively about the interleaving problem exhibited in self-timed systems. We specify and verify finite-state-machine representations of self-timed circuit designs using the DE system, a formal hardware description language defined using the ACL2 theorem-proving system. We apply a link-joint paradigm to model self-timed circuits as networks of channels that communicate with each other locally via handshake protocols. This link-joint model has been shown to be a universal model for various self-timed circuit families. In addition, this model has a clean formalization in the ACL2 logic and provides a protocol level that abstracts away timing constraints at the circuit level. Unlike many efforts for validating timing and communication properties of self-timed systems, we are interested in verifying functional properties. Specifically, we verify the functional correctness of self-timed systems in terms of relationships between their input and output sequences. To mitigate the consideration of all interleavings simultaneously, we address the verification problem hierarchically and avoid exploring the internal structures of verified submodules as well as their operational interleavings. The input-output relationship of a verified submodule is determined based on the communication signals at the submodule's input and output ports, while abstracting away all execution paths internal to that submodule.Computer Science

Saponins isolated from the Vietnamese sea cucumber Stichopus chloronotus.

Using various chromatographic methods, three triterpene saponins neothyonidioside (1), stichoposide D (2), and holothurin B (3), were isolated from the methanol extract of the sea cucumber Stichopus chloronotus. Their structures were elucidated by 1D and 2D-NMR experiments and comparison of their NMR data with reported values. Compound 1 was isolated from S. chloronotus for the first time

Sterols isolated from the soft coral sinularia dissecta

Using various chromatographic methods, five sterols, gorgost-4-ene-3-one (1), ergost-4-ene-3-one (2), 24-methyleneergost-4-ene-3-one (3), ergost-4-ene-3,6-dione (4), and 24-methylenecholest-4-ene-3,6-dione (5), were isolated from the methanol extract of the soft coral Sinularia dissecta. Their structures were elucidated by 1D and 2D-NMR experiments and comparison of their NMR data with reported values. These compounds were isolated from S. dissecta for the first time

Polyhydroxylated sterols from the soft coral sarcophyton pauciplicatum

The methanol extract of the soft coral Sarcophyton pauciplicatum afforded four sterols as (24S)-ergostane-3β,5α,6β,25-tetraol 25-monoacetate (1), (24S)-ergostane-3β,5α,6β,25-tetraol (2), (24S)-ergostane-1β,3β,5α,6β,25-pentaol 25-monoacetate (3), and (24S)-ergost-25-ene-1β,3β,5α,6β-tetraol (4) after subjecting it to various chromatographic experiments. The structures of isolated compounds were elucidated by 1D and 2D-NMR experiments and comparison of their NMR data with reported values. This is the first report of these compounds from                       S. pauciplicatum

Spatiotemporal evolution of SARS-CoV-2 Alpha and Delta variants during large nationwide outbreak of COVID-19, Vietnam, 2021

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Isoprenoids from the sponge Gellius varius living in Vietnamese sea

Five isoprenoids, cholest-7-ene-3β,5α,6β-triol (1), 6β-methoxycholest-7-ene-3β,5α-diol (2), 5,8-epidioxycholest-6-en-3-ol (3), cholesterol (4) and trans-phytol (5) were isolated from chloroform extract of the sponge Gellius varius collected in Vietnam. Their structures were determined on the basis of the physicochemical and spectroscopic data. This is the first report of compounds 1, 2 and 3 from this species.Keywords: Gellius varius, cholest-7-ene-3β,5α,6β-triol, 6β-methoxycholest-7-ene-3β,5α-diol

Anti-inflammatory components of the Vietnamese starfish Protoreaster nodosus

BACKGROUND: In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ±0.01 to 26.19 ±0.64 μg/mL. Four highly pure steroid derivatives (1-4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S)5α-cholestane-3β,6α,7α,8β,15α,16β,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 μM), and for (25S)5α-cholestane-3β, 6α,8β, 15α,16β, 26-hexol (1) and (25S)5α-cholestane-3β,6α,7α,8β,15α,16β,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ±0.00 and and 1.02 ± 0.01 μM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production. CONCLUSION: This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases

New Derivatives of Lupeol and Their Biological Activity

The natural product lupeol (1) was isolated from Bombax ceiba leaves, which were used as starting material in the semisynthetic approach. Three new derivatives (2a, 2b, and 3) were synthesized using oxidation and aldolization. Their chemical structures were elucidated by spectroscopic analyses (HRESIMS and NMR). Compounds 3 showed significant &alpha;-glucosidase inhibition with an IC50 value of 202 &micro;M, whereas 2a and 2b were inactive