Laboratory Diagnosis of SARS

The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription–polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%–40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity

Superelasticity of Carbon Nanocoils from Atomistic Quantum Simulations

A structural model of carbon nanocoils (CNCs) on the basis of carbon nanotubes (CNTs) was proposed. The Young’s moduli and spring constants of CNCs were computed and compared with those of CNTs. Upon elongation and compression, CNCs exhibit superelastic properties that are manifested by the nearly invariant average bond lengths and the large maximum elastic strain limit. Analysis of bond angle distributions shows that the three-dimensional spiral structures of CNCs mainly account for their unique superelasticity

Orienting Attention Modulates Pain Perception: An ERP Study

2011-2012 > Academic research: refereed > Publication in refereed journalpublished_fina

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to search for astrophysical neutrino sources. It has so far provided compelling evidence for a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 was observed in coincidence with the high-energy neutrino IceCube-170922A detected by IceCube. The detection of very-high-energy gamma rays (VHE, E > 100 GeV) from this source helped establish the coincidence and constrained the modeling of the blazar emission at the time of the IceCube event. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) - FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program of target-of-opportunity observations of neutrino alerts sent by IceCube. This program has two main components. One are the observations of known gamma-ray sources around which a cluster of candidate neutrino events has been identified by IceCube (Gamma-ray Follow-Up, GFU). The second one is the follow-up of single high-energy neutrino candidate events of potential astrophysical origin such as IceCube-170922A. GFU has been recently upgraded by IceCube in collaboration with the IACT groups. We present here recent results from the IACT follow-up programs of IceCube neutrino alerts and a description of the upgraded IceCube GFU system

Flavonoid Dimers as Novel, Potent Antileishmanial Agents

The present study found that synthetic flavonoid dimers with either polyethylene glycol linker or amino ethyleneglycol linker have marked leishmanicidal activity. Compound <b>39</b> showed very consistent and promising leishmanicidal activity for both extracellular promastigotes (IC₅₀ ranging from 0.13 to 0.21 μM) and intracellular amastigotes (IC₅₀ = 0.63 μM) irrespective of the drug-sensitivity of parasites. Moreover, compound <b>39</b> displayed no toxicity toward macrophage RAW 264.7 cells (IC₅₀ > 100 μM) and primary mouse peritoneal elicited macrophages (IC₅₀ > 88 μM). Its high value of therapeutic index (>140) was better than other highly potent antileishmanials such as amphotericin B (therapeutic index = 119). Compound <b>39</b> is therefore a new, safe, and effective antileishmanial candidate compound which is even effective against drug-refractory parasites

Flavonoid Dimers as Bivalent Modulators for Pentamidine and Sodium Stiboglucanate Resistance in Leishmania

Drug resistance by overexpression of ATP-binding cassette (ABC) transporters is an impediment in the treatment of leishmaniasis. Flavonoids are known to reverse multidrug resistance (MDR) in Leishmania and mammalian cancers by inhibiting ABC transporters. Here, we found that synthetic flavonoid dimers with three (compound 9c) or four (compound 9d) ethylene glycol units exhibited a significantly higher reversing activity than other shorter or longer ethylene glycol-ligated dimers, with ∼3-fold sensitization of pentamidine and sodium stibogluconate (SSG) resistance in Leishmania, respectively. This modulatory effect was dosage dependent and not observed in apigenin monomers with the linker, suggesting that the modulatory effect is due to its bivalent nature. The mechanism of reversal activity was due to increased intracellular accumulation of pentamidine and total antimony in Leishmania. Compared to other MDR modulators such as verapamil, reserpine, quinine, quinacrine, and quinidine, compounds 9c and 9d were the only agents that can reverse SSG resistance. In terms of reversing pentamidine resistance, 9c and 9d have activities comparable to those of reserpine and quinacrine. Modulators 9c and 9d exhibited reversal activity on pentamidine resistance among LeMDR1(−/−), LeMDR1(+/+), and LeMDR1-overexpressed mutants, suggesting that these modulators are specific to a non-LeMDR1 pentamidine transporter. The LeMDR1 copy number is inversely related to pentamidine resistance, suggesting that it might be involved in importing pentamidine into the mitochondria. In summary, bivalency could be a useful strategy for the development of more potent ABC transporter modulators and flavonoid dimers represent a promising reversal agent for overcoming pentamidine and SSG resistance in parasite Leishmania

Electromechanical stability of compressible dielectric elastomer actuators

The constitutive relation and the electromechanical stability of Varga–Blatz–Ko-type compressible isotropic dielectric elastomers undergoing large deformation are investigated in this paper. Free energy in any form, which consists of elastic strain energy and electric field energy, can be applied to analyze the electromechanical stability of dielectric elastomers. The constitutive relation and the electromechanical stability are analyzed by applying a new kind of free energy model, which consists of elastic strain energy, composed of the Varga model as the volume conservative energy and the Blatz–Ko model as the volume non-conservative energy, and electric field energy with constant permittivity. The ratio between the principal planar stretches, the ratio between the thickness and length direction stretches, and the power exponent of the stretch are defined to characterize the mechanical loading behavior and compressible behavior of the dielectric elastomer. Along with the increase of these parameters, which determine the shape or volume of the elastomer, and the Poisson ratio, the critical nominal electric field is higher, which indicates a more stable dielectric elastomer electromechanical system. In contrast, with the decrease of the dimensionless material parameter α of the Varga elastic strain energy, the critical nominal electric field increases. The coupling system becomes more stable. We further demonstrate that the critical nominal electric field of the compressible dielectric elastomer electromechanical coupling system is significantly influenced by the ratio between the principal planar stretches

A new class of safe, potent, and specific P-gp modulator: flavonoid dimer FD18 reverses P-gp-mediated multidrug resistance in human breast xenograft in vivo

Flavonoid dimer FD18 is a new class of dimeric P-gp modulator that can reverse cancer drug resistance. FD18 is a potent (EC50 = 148 nM for paclitaxel), safe (selective index = 574), and selective P-glycoprotein (P-gp) modulator. FD18 can modulate multidrug resistance toward paclitaxel, vinblastine, vincristine, doxorubicin, daunorubicin, and mitoxantrone in human breast cancer LCC6MDR in vitro. FD18 (1 μM) can revert chemosensitivity of LCC6MDR back to parental LCC6 level. FD18 was 11- to 46-fold more potent than verapamil. FD18 (1 μM) can increase accumulation of doxorubicin by 2.7-fold, daunorubicin (2.1-fold), and rhodamine 123 (5.2-fold) in LCC6MDR. FD18 inhibited P-gp-mediated doxorubicin efflux and has no effect on influx. FD18 at 1 μM did not affect the protein expression level of P-gp. Pharmacokinetics studies indicated that intraperitoneal administration of 45 mg/kg FD18 was enough to maintain a plasma level above EC50 (148 nM) for more than 600 min. Toxicity studies with FD18 (90 mg/kg, i.p. for 12 times in 22 days) with paclitaxel (12 mg/kg, i.v. for 12 times in 22 days) revealed no obvious toxicity or death in mice. In vivo efficacy studies indicated that FD18 (45 mg/kg, i.p. for 12 times in 22 days) together with paclitaxel (12 mg/kg, i.v. for 12 times in 22 days) resulted in a 46% reduction in LCC6MDR xenograft volume (n = 11; 648 ± 84 mm3) compared to paclitaxel control (n = 8; 1201 ± 118 mm3). There were no animal deaths or significant drop in body weight and vital organ wet weight. FD18 can increase paclitaxel accumulation in LCC6MDR xenograft by 1.8- to 2.2-fold. The present study suggests that FD18 represents a new class of safe and potent P-gp modulator in vivo