Materials informatics for the screening of multi-principal elements and high-entropy alloys.

The field of multi-principal element or (single-phase) high-entropy (HE) alloys has recently seen exponential growth as these systems represent a paradigm shift in alloy development, in some cases exhibiting unexpected structures and superior mechanical properties. However, the identification of promising HE alloys presents a daunting challenge given the associated vastness of the chemistry/composition space. We describe here a supervised learning strategy for the efficient screening of HE alloys that combines two complementary tools, namely: (1) a multiple regression analysis and its generalization, a canonical-correlation analysis (CCA) and (2) a genetic algorithm (GA) with a CCA-inspired fitness function. These tools permit the identification of promising multi-principal element alloys. We implement this procedure using a database for which mechanical property information exists and highlight new alloys having high hardnesses. Our methodology is validated by comparing predicted hardnesses with alloys fabricated by arc-melting, identifying alloys having very high measured hardnesses.

Efficient nitrogen-vacancy centers' fluorescence excitation and collection from micrometer-sized diamond by a tapered optical fiber in endoscope-type configuration.

Using an optical fiber to both excite the nitrogen-vacancy (NV) center in diamond and collect its fluorescence is essential to build NV-based endoscope-type sensor. Such endoscope-type sensor can reach inaccessible fields for traditional NV-based sensors built by bulky optical components and extend the application areas. Since single NV's fluorescence is weak and can easily be buried in fluorescence from optical fiber core's oxide defects excited by the green laser, fixing a micrometer size diamond containing high-density NVs rather than a nanodiamond containing single NV or several NVs on the apex of an optical fiber to build an endoscope-type sensor is more implementable. Unfortunately, due to small numerical aperture (NA), most of the optical fibers have a low fluorescence collection efficiency, which limits the sensitivity and spatial resolution of the NV-based endoscope-type sensor. Here, using a tapered optical fiber (TOF) tip, we significantly improve the efficiency of the laser excitation and fluorescence collection of the NV ensembles in diamond. This could potentially enhance the sensitivity and spatial resolution of the NV-based endoscope-type sensor. Numerical calculations show that the TOF tip delivers a high NA and has a high NV excitation and fluorescence collection efficiency. Experiments demonstrate that such TOF tip can obtain up to over 7-fold excitation efficiency and over 15-fold fluorescence collection efficiency of that from a flat-ended fiber (non-TOF) tip.

Swallow strength training exercise for elderly: A health maintenance need.

BACKGROUND: Recent studies have shown high prevalence of oropharyngeal dysphagia associated with frailty- and age-related muscle weakness. Strength training exercises have been advocated for locomotive health maintenance in the elderly and have shown positive outcomes. As muscles involved in oropharyngeal phase of swallowing are also comprised of striated muscles, the aim of this study was to determine biomechanical effect of a novel resistance exercise program, Swallowing Against Laryngeal Restriction (SALR), on pharyngeal phase swallowing in the healthy elderly. METHODS: A total of 28 volunteers (75 + 7 years; 17 females) with no complaint of dysphagia were studied using video fluoroscopy before and after 6 weeks of the swallow strength training exercise. Eighteen of these volunteers also underwent high-resolution pharyngeal manometry non-concurrent with fluoroscopy. Ten additional volunteers (81 + 6 years; 9 females) were studied by videofluoroscopy before and after 6 weeks of a sham exercise. KEY RESULTS: Swallow resistance exercise but not the sham exercise resulted in a significant increase in maximum upper esophageal sphincter opening (P < .01), superior and anterior laryngeal excursion (P < .01) as well as posterior pharyngeal wall thickness (P < .01). Resistance exercise but not sham exercise also resulted in a significant increase in deglutitive pharyngeal contractile integral (P < .01). CONCLUSIONS & INFERENCES: Strength training of muscles involved in the pharyngeal phase of swallowing using the swallowing against laryngeal restriction technique is feasible and significantly improves key physiologic features of the pharyngeal phase of swallowing. These findings provide the basis for consideration of developing an exercise-based swallow health maintenance program for the elderly swallow health maintenance program for the elderly.

Characterization of pharyngeal peristaltic pressure variability during volitional swallowing in healthy individuals.

BACKGROUND: Recent technological advances incorporated in high resolution manometry have justifiably heightened interest in manometric evaluation of the pharynx. Despite this interest, from both physiologic and clinical perspective there remain a number of unanswered questions regarding the magnitude of variability of pharyngeal pressure phenomena. Therefore, the aim of the present study was to characterize in healthy individuals the inter-subject and recording-site specific variability of pharyngeal peristaltic pressure phenomena. METHODS: We studied 32 healthy subjects (age: 21-83 years,20 under 35 years) during dry,5 and 10 mL water swallows ×3. Pharyngeal peristaltic pressures were recorded using a high resolution (HR) manometric system and a catheter assembly with 36 circumferential sensors spaced at 1 cm intervals positioned trans-nasally to traverse the pharynx, UES and proximal esophagus. KEY RESULTS: Both site-specific pressure data and the Pharyngeal contractile integral (PhCI) showed wide dispersion ranging between values under 50 mm Hg to over 300 mm Hg and 100-600 mm Hg/cm/s,respectively. There was also wide range of dispersion of data for both the standard deviations and the coefficient of variation for all sites (P=.001). The coefficient of variation for PhCI ranged between 0.02 and 0.25 representing data dispersion of 2-25 percent of the mean among subjects (P=.001). Position, age and volume of swallowed fluid did not influence the magnitude of variability. CONCLUSIONS: Deglutitive Pharyngeal peristalsis generates pressures with significant degree of site-related and inter-subject variability. This variability is not influenced by age, position and volume of swallowed fluid.

Antivenom activity of triterpenoid (C34H68O2) from Leucas aspera Linn. against Naja naja naja venom induced toxicity: antioxidant and histological study in mice.

The isolated and identified triterpenoid, 1-hydroxytetratriacontane-4-one (C34H68O2), obtained from the methanolic leaf extract of Leucas aspera Linn. was explored for the first time for antisnake venom activity. The plant (L. aspera Linn.) extract significantly antagonized the spectacled cobra (Naja naja naja) venom induced lethal activity in a mouse model. It was compared with commercial antiserum obtained from King Institute of Preventive Medicine (Chennai, Tamil Nadu, India). N. naja naja venom induced a significant decrease in antioxidant superoxide dismutase, glutathione (GSH) peroxidase, catalase, reduced GSH and glutathione-S-transferase activities and increased lipid peroxidase (LPO) activity in different organs such as heart, liver, kidney and lungs. The histological changes following the antivenom treatment were also evaluated in all these organs. There were significant alterations in the histology. Triterpenoid from methanol extract of L. aspera Linn. at a dose level of 75 mg per mouse significantly attenuated (neutralized) the venom-induced antioxidant status and also the LPO activity in different organs.

Detection and neutralization of cobra venom using rabbit antiserum in experimental envenomated mice.

A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect the venom of Indian cobra (Naja naja naja) in various tissues (brain, heart, lungs, liver, spleen, blood, kidneys, and tissue at the site of injection) of mice after cobra venom injected at different time intervals (0, 2, 4, 6, 8, and 12 h intervals up to 24 h). Whole venom antiserum or individual venom protein antiserum (14, 29, 65, 72, and 99 kDa) could recognize N. n. naja venom by Western blotting and ELISA, and antibody titer was also assayed by ELISA. Antiserum raised against cobra venom in rabbit significantly neutralized the toxicity of venom-injected mice at different time intervals after treatment. The assay could detect N. n. naja venom levels up to 2.5 ng/ml of tissue homogenate, and the venom was detected up to 24 h after venom injection. Venom was detected in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area, and blood. As observed in mice, tissue at the site of bite area showed the highest concentration of venom and the brain showed the least. Moderate amounts of venoms were found in liver, spleen, kidneys, heart, and lungs. Development of a simple, rapid, and species-specific diagnostic kit based on this ELISA technique useful to clinicians is discussed.

Magnetic spin imaging under ambient conditions with sub-cellular resolution.

The detection of small numbers of magnetic spins is a significant challenge in the life, physical and chemical sciences, especially when room temperature operation is required. Here we show that a proximal nitrogen-vacancy spin ensemble serves as a high precision sensing and imaging array. Monitoring its longitudinal relaxation enables sensing of freely diffusing, unperturbed magnetic ions and molecules in a microfluidic device without applying external magnetic fields. Multiplexed charge-coupled device acquisition and an optimized detection scheme permits direct spin noise imaging of magnetically labelled cellular structures under ambient conditions. Within 20 s we achieve spatial resolutions below 500 nm and experimental sensitivities down to 1,000 statistically polarized spins, of which only 32 ions contribute to a net magnetization. The results mark a major step towards versatile sub-cellular magnetic imaging and real-time spin sensing under physiological conditions providing a minimally invasive tool to monitor ion channels or haemoglobin trafficking inside live cells.

High sensitivity magnetic imaging using an array of spins in diamond.

We present a solid state magnetic field imaging technique using a two-dimensional array of spins in diamond. The magnetic sensing spin array is made of nitrogen vacancy (NV) centers created at shallow depths. Their optical response is used for measuring external magnetic fields in close proximity. Optically detected magnetic resonance is read out from a 60 x 60 microm(2) field of view in a multiplexed manner using a charge coupled device camera. We experimentally demonstrate full two-dimensional vector imaging of the magnetic field produced by a pair of current carrying microwires. The presented wide-field NV magnetometer offers, in addition to its high magnetic sensitivity and vector reconstruction, an unprecedented spatiotemporal resolution and functionality at room temperature.

Dynamic polarization of single nuclear spins by optical pumping of nitrogen-vacancy color centers in diamond at room temperature.

We report a versatile method to polarize single nuclear spins in diamond, based on optical pumping of a single nitrogen-vacancy (NV) defect and mediated by a level anticrossing in its excited state. A nuclear-spin polarization higher than 98% is achieved at room temperature for the 15N nuclear spin associated with the NV center, corresponding to microK effective nuclear-spin temperature. We then show simultaneous initialization of two nuclear spins in the vicinity of a NV defect. Such robust control of nuclear-spin states is a key ingredient for further scaling up of nuclear-spin based quantum registers in diamond.

Studies on the immunomodulatory effect of extract of Cyanodon dactylon in shrimp, Penaeus monodon, and its efficacy to protect the shrimp from white spot syndrome virus (WSSV).

The present study investigates the protection of shrimp Penaeus monodon against white spot syndrome virus (WSSV) using antiviral plant extract derived from Cyanodon dactylon and the modulation of the shrimp non-specific immunity. To determine the antiviral activity, the shrimp were treated by both in vitro (intramuscular injection) and in vivo (orally with feed) methods at the concentration of 2mg per animal and 2% of the plant extract incorporated with commercially available artificial pellet feed, respectively. The antiviral activity of C. dactylon plant extract was confirmed by PCR, bioassay and Western blot analysis. In the present study, anti-WSSV activity of C. dactylon plant extract by in vivo and in vitro methods showed strong antiviral activity and the immunological parameters such as proPO, O(2)(-), NO, THC and clotting time were all significantly (P<0.05) higher in the WSSV-infected shrimp treated with plant extract when compared to control groups. These results strongly indicate that in vivo and in vitro administration of C. dactylon plant extract enhances immunity of the shrimp. Based on the present data and the advantages of plant extract available at low price, we believe that oral administration of C. dactylon plant extract along with the pellet feed is a potential prophylactic agent against WSSV infection of shrimp.

Temporal coherence of photons emitted by single nitrogen-vacancy defect centers in diamond using optical Rabi-oscillations.

Photon interference among distant quantum emitters is a promising method to generate large scale quantum networks. Interference is best achieved when photons show long coherence times. For the nitrogen-vacancy defect center in diamond we measure the coherence times of photons via optically induced Rabi oscillations. Experiments reveal a close to Fourier-transform (i.e., lifetime) limited width of photons emitted even when averaged over minutes. The projected contrast of two-photon interference (0.8) is high enough to envisage applications in quantum information processing. We report 12 and 7.8 ns excited state lifetimes depending on the spin state of the defect.

Point mutations in membrane proteins reshape energy landscape and populate different unfolding pathways.

Using single-molecule force spectroscopy, we investigated the effect of single point mutations on the energy landscape and unfolding pathways of the transmembrane protein bacteriorhodopsin. We show that the unfolding energy barriers in the energy landscape of the membrane protein followed a simple two-state behavior and represent a manifestation of many converging unfolding pathways. Although the unfolding pathways of wild-type and mutant bacteriorhodopsin did not change, indicating the presence of same ensemble of structural unfolding intermediates, the free energies of the rate-limiting transition states of the bacteriorhodopsin mutants decreased as the distance of those transition states to the folded intermediate states decreased. Thus, all mutants exhibited Hammond behavior and a change in the free energies of the intermediates along the unfolding reaction coordinate and, consequently, their relative occupancies. This is the first experimental proof showing that point mutations can reshape the free energy landscape of a membrane protein and force single proteins to populate certain unfolding pathways over others.

Experimental transmission and tissue tropism of white spot syndrome virus (WSSV) in two species of lobsters, Panulirus homarus and Panulirus ornatus.

The susceptibility of two species of lobsters, Panulirus homarus and Panulirus ornatus to white spot syndrome virus (WSSV) was tested by oral route and intramuscular injection. The results revealed that these lobsters were as highly susceptible as marine shrimp when the WSSV was administered intramuscularly. The WSSV caused 100% mortality in both Panulirus homarus and Panulirus ornatus, at 168 and 120 h, respectively, after intramuscular injection and failed to cause mortality when given orally. The presence of WSSV in moribund lobsters was confirmed by single-step and nested PCR, Western blot, histology, and bioassay test. It was found in eyestalk, gill, head muscle, tail muscle, hemolymph, appendages, and stomach. In lobsters with oral route infection, all tested organs except stomach and head muscle was negative for WSSV by nested PCR at 120 h post-inoculation. The stomach and head muscle was positive by nested PCR at 120 h p.i., but negative at 168 h p.i. Western blot analysis was negative in all the tested organs of both species of lobster at 120 h post-inoculation by oral route.

Tumorigenicity assessments of Per.C6 cells and of an Ad5-vectored HIV-1 vaccine produced on this continuous cell line.

PER.C6, a cell line derived from human embryonic retinal cells transformed with the Adenovirus Type 5 (Ad5) E1A and E1B genes, is used to produce E1-deleted Ad5 vectors such as the MRKAd5 HIV-1 gag vaccine. While whole, live PER.C6 cells are capable of growing as tumours when transplanted subcutaneously into immunodeficient nude mice at a high dosage, the process for vaccine production includes filtration steps and other methods which effectively preclude contamination by intact viable substrate cells. However, because of the neoplastic nature of this cell line, we carried out a series of investigations to assess the tumorigenic risk posed by residuals from the cell substrate in a vaccine. To address concerns about transmission of oncogenic DNA, we demonstrated that purified PER.C6 cellular DNA does not induce tumours in newborn hamsters or nude mice. To address concerns about other potential residuals, including hypothetical adventitious tumour viruses, we demonstrated that a PER.C6 cell lysate and a MRKAd5 HIV-1 gag vaccine produced on PER.C6 cells do not induce tumours in newborn hamsters or newborn rats. These results, in conjunction with the wide panel of viral safety tests performed on these cells, support the safety of the PER.C6 as a cell substrate for vaccine production.

A self-learning coupled map lattice for vortex shedding in cable and cylinder wakes.

A coupled map lattice (CML) with self-learning features is developed to model flow over freely vibrating cables and stationary cylinders at low Reynolds numbers. Coupled map lattices that combine a series of low-dimensional circle maps with a diffusion model have been used previously to predict qualitative features of these flows. However, the simple nature of these CML models implies that there will be unmodeled wake features if a detailed, quantitative comparison is made with laboratory or simulated wake flows. Motivated by a desire to develop an improved CML model, we incorporate self-learning features into a new CML that is first trained to precisely estimate wake patterns from a target numerical simulation. A new convective-diffusive map that includes additional wake dynamics is developed. The new self-learning CML uses an adaptive estimation scheme (multivariable least-squares algorithm). Studies of this approach are conducted using wake patterns from a Navier-Stokes solution (spectral element-based NEKTAR simulation) of freely vibrating cable wakes at Reynolds numbers Re=100. It is shown that the self-learning model accurately and efficiently estimates the simulated wake patterns. The self-learning scheme is then successfully applied to vortex shedding patterns obtained from experiments on stationary cylinders. This constitutes a first step toward the use of the self-learning CML as a wake model in flow control studies of laboratory wake flows.

Experimental infection of twenty species of Indian marine crabs with white spot syndrome virus (WSSV).

Twenty species of Indian marine crabs were experimentally infected with white spot syndrome virus (WSSV), via the oral route and intramuscular injection, to determine their viral susceptibility. We determined that 16 species (Calappa philargius, Charybdis annulata, C. lucifera, Doclea hybrida, Grapsus albolineatus, Halimede ochtodes, Liagore rubronaculata, Lithodes maja, Matuta miersi, Paradorippe granulata, Parthenope prensor, Philyra syndactyla, Podophthalmus vigil, Portunus sanquinolentus, Scylla serrata and Thalamita danae) were susceptible and 4 (Atergatis integerrimus, Charybdis natator, Demania splendida or Menippe rumphii) were refractive at 50 d post-infection (p.i.). The presence of WSSV in these crabs was confirmed by PCR tests, histology and bioassay. WSSV was found in the gill, heart, eyestalks, striated muscle and cephalothoraxic tissue. The 4 WSSV-refractive species represent potential reservoirs or carriers of WSSV.

Ca(2+)-calmodulin antagonist chlorpromazine and poly(ADP-ribose) polymerase modulators 4-aminobenzamide and nicotinamide influence hepatic expression of BCL-XL and P53 and protect against acetaminophen-induced programmed and unprogrammed cell death in mice.

Acetaminophen (AAP), the analgesic hepatotoxicant, is a powerful inducer of oxidative stress, DNA fragmentation, and apoptosis. The anti-apoptotic oncogene bcl-XL, and the pro-apoptotic oncogene p53 are two key regulators of cell cycle progression and/or apoptosis subsequent to DNA damage in vitro and in vivo. This study investigated the effect of AAP on the expression of these oncogenes and whether agents that modulate DNA fragmentation (chlorpromazine, CPZ) and DNA repair through poly(ADP-Ribose) polymerase (PARP) activity (4-AB: 4-aminobenzamide) can protect against AAP-induced hepatotoxicity by inhibiting oxidative stress, DNA fragmentation, and/or by altering the expression of bcl-XL and p53. In addition, the protective effect of supplemental nicotinamide (NICO), known to be depleted in cells with high PARP activity during DNA repair, is similarly evaluated. Male ICR mice (3 months old) were administered vehicle alone; nontoxic doses of 4-AB (400 mg/kg, ip), NICO (250 mg/kg, ip) or CPZ (25 mg/kg, ip), hepatotoxic dose of AAP alone (500 mg/kg, ip), or AAP plus one of the protective agents 1 h later. All animals were sacrificed 24 h following AAP administration. Serum alanine aminotransferase activity (ALT), hepatic histopathology and lipid peroxidation, DNA damage, and expression of bcl-XL and p53 (western blot analysis) were compared in various groups. All of the three agents significantly prevented AAP-induced liver injury, lipid peroxidation, DNA damage, and associated apoptotic and necrotic cell deaths, 4-AB being the most effective and NICO the least. Compared to control, there was a considerable decrease in bcl-XL expression, and an increase in p53 expression in AAP-exposed livers. The effect of AAP on bcl-XL was antagonized and that on p53 was synergized by the PARP-modulator 4-AB as well as NICO, whereas the endonuclease inhibitor CPZ was without effect on either bcl-XL or p53 expression. These results suggest that the hepatotoxic effect of AAP involves multiple mechanisms including oxidative stress, upregulation of endonuclease (or caspase-activated DNAse) and alteration of pro- and anti-apoptotic oncogenes. The observed antagonism of AAP-induced hepatocellular apoptosis and/or necrosis by modulators of multiple processes including DNA repair suggests the likelihood that a more effective therapy against AAP intoxication should involve a combination of antidotes.