Velocity of conduction between columns and layers in barrel cortex reported by parvalbumin interneurons.

Inhibitory interneurons expressing parvalbumin (PV) play critical roles throughout the brain. Their rapid spiking enables them to control circuit dynamics on a millisecond time scale, and the timing of their activation by different excitatory pathways is critical to these functions. We used a genetically encoded hybrid voltage sensor to image PV interneuron voltage changes with sub-millisecond precision in primary somatosensory barrel cortex (BC) of adult mice. Electrical stimulation evoked depolarizations with a latency that increased with distance from the stimulating electrode, allowing us to determine conduction velocity. Spread of responses between cortical layers yielded an interlaminar conduction velocity and spread within layers yielded intralaminar conduction velocities in different layers. Velocities ranged from 74 to 473 µm/ms depending on trajectory; interlaminar conduction was 71% faster than intralaminar conduction. Thus, computations within columns are more rapid than between columns. The BC integrates thalamic and intracortical input for functions such as texture discrimination and sensory tuning. Timing differences between intra- and interlaminar PV interneuron activation could impact these functions. Imaging of voltage in PV interneurons reveals differences in signaling dynamics within cortical circuitry. This approach offers a unique opportunity to investigate conduction in populations of axons based on their targeting specificity.

Dynamics of soundscape in a shallow water marine environment: a study of the habitat of the Indo-Pacific humpback dolphin.

The underwater acoustic field is an important ecological element for many aquatic animals. This research examines the soundscape of a critically endangered Indo-Pacific humpback dolphin population in the shallow water environment off the west coast of Taiwan. Underwater acoustic recordings were conducted between late spring and late fall in 2012 at Yunlin (YL), which is close to a shipping lane, and Waisanding (WS), which is relatively pristine. Site-specific analyses were performed on the dynamics of the temporal and spectral acoustic characteristics for both locations. The results highlight the dynamics of the soundscape in two major octave bands: 150-300 Hz and 1.2-2.4 kHz. The acoustic energy in the former frequency band is mainly associated with passing container vessels near YL, while the latter frequency band is from sonic fish chorus at nighttime in both recording sites. In addition, large variation of low frequency acoustic energy throughout the study period was noticed at WS, where the water depths ranged between 1.5 and 4.5 m depending on tidal cycle. This phenomenon suggests that besides certain sound sources in the environment, the coastal soundscape may also be influenced by its local bathymetry and the dynamics of the physical environment.

Airgun inter-pulse noise field during a seismic survey in an Arctic ultra shallow marine environment.

Offshore oil and gas exploration using seismic airguns generates intense underwater pulses that could cause marine mammal hearing impairment and/or behavioral disturbances. However, few studies have investigated the resulting multipath propagation and reverberation from airgun pulses. This research uses continuous acoustic recordings collected in the Arctic during a low-level open-water shallow marine seismic survey, to measure noise levels between airgun pulses. Two methods were used to quantify noise levels during these inter-pulse intervals. The first, based on calculating the root-mean-square sound pressure level in various sub-intervals, is referred to as the increment computation method, and the second, which employs the Hilbert transform to calculate instantaneous acoustic amplitudes, is referred to as the Hilbert transform method. Analyses using both methods yield similar results, showing that the inter-pulse sound field exceeds ambient noise levels by as much as 9 dB during relatively quiet conditions. Inter-pulse noise levels are also related to the source distance, probably due to the higher reverberant conditions of the very shallow water environment. These methods can be used to quantify acoustic environment impacts from anthropogenic transient noises (e.g., seismic pulses, impact pile driving, and sonar pings) and to address potential acoustic masking affecting marine mammals.

Optimal apparent damping as a function of the bandwidth of an array of vibration absorbers.

The transient response of a resonant structure can be altered by the attachment of one or more substantially smaller resonators. Considered here is a coupled array of damped harmonic oscillators whose resonant frequencies are distributed across a frequency band that encompasses the natural frequency of the primary structure. Vibration energy introduced to the primary structure, which has little to no intrinsic damping, is transferred into and trapped by the attached array. It is shown that, when the properties of the array are optimized to reduce the settling time of the primary structure's transient response, the apparent damping is approximately proportional to the bandwidth of the array (the span of resonant frequencies of the attached oscillators). Numerical simulations were conducted using an unconstrained nonlinear minimization algorithm to find system parameters that result in the fastest settling time. This minimization was conducted for a range of system characteristics including the overall bandwidth of the array, the ratio of the total array mass to that of the primary structure, and the distributions of mass, stiffness, and damping among the array elements. This paper reports optimal values of these parameters and demonstrates that the resulting minimum settling time decreases with increasing bandwidth.

Conformal scanning laser Doppler vibrometer measurement of tenor steelpan response to impulse excitation.

A conformal scanning laser Doppler vibrometer system is used in conjunction with a mechanical pannist to measure the surface normal vibration of the entire playing surface of a C-lead tenor steelpan. The mechanical pannist is a device designed to deliver controlled, repeatable strikes that mimic a mallet during authentic use. A description of the measurement system is followed by select examples of behavior common to the results from three different excitation notes. A summary of observed response shapes and associated frequencies demonstrates the concerted placement of note overtones by the craftsmen who manufacture and tune the instruments. The measurements provide a rich mechanical snapshot of the complex motion that generates the distinctive sound of a steelpan.

Shaping of a system's frequency response using an array of subordinate oscillators.

The frequency response of an oscillating structure can be tailored by attaching one or more subordinate oscillators. This paper shows how the magnitude and phase of the frequency response can be deliberately shaped by prescribing the distributions of the dynamic properties in an array of such subordinate oscillators. Exact analytic governing equations of motion are derived for the coupled system composed of the primary system and the subordinate array. For a relatively small number (<100) of attached oscillators whose total mass is small (<1%) relative to the primary structure, it is possible to engineer frequency-response functions of the primary oscillator to have, for example, nearly linear phase or constant amplitude over a frequency band of interest. The frequency range over which response shaping is achieved is determined by the band of the attached oscillators. It is shown that the common analytic methodology for designing a dynamic vibration absorber represents the limiting case of a single oscillator in the subordinate set. Moreover, increasing the number of subordinate oscillators (without increasing the total added mass) offers a number of advantages in reshaping the dominant system's frequency response.

Protective immunity against Toxoplasma challenge in mice by coadministration of T. gondii antigens and Eimeria profilin-like protein as an adjuvant.

Toll-like receptor (TLR) ligands are attractive adjuvant candidates in vaccine development. Eimeria tenella profilin-like protein has recently been shown to be a potent agonist of the innate immune system through its recognition by Toll-like receptor-11. In this report, we studied the systemic and mucosal adjuvant activity of Eimeria profilin-like protein within a vaccinal strategy against Toxoplasma gondii in mice. Using intraperitoneal (i.p.) immunization, we observed that coadministration of the recombinant Eimeria antigen (rEA) with T. gondii antigen (TAg) effectively elevates plasma levels of IL-12p70 and consequently induced both enhanced specific humoral and Th1 cellular immune responses. The co-administration of TAg plus rEA by i.p route significantly enhanced the protection against T. gondii infection (62% brain cyst reduction) in comparison with control mice and with mice immunized with TAg alone (only 36% brain cyst reduction). After intranasal immunization, humoral and cellular responses were weak. However mice immunized nasally with TAg plus rEA were significantly protected with 50% of brain cyst reduction, conversely TAg immunized mice did not present any brain cyst reduction.These results indicate that Eimeria profilin-like protein would serve as an efficacious systemic and mucosal adjuvant inducing protective immune response against chronical stage of T. gondii infection through TLR11 activation.

Immunoprophylaxis of Punta Toro virus (Phlebovirus, Bunyaviridae) infection in hamsters with recombinant Eimeria profilin-like antigen.

Recombinant Eimeria antigen (rEA) has been shown to have potent anticancer and antiviral activity in respective mouse disease models, presumably through robust immune stimulation that occurs via TLR11, a pattern recognition receptor that recognizes profilin-like proteins expressed on apicomplexan protozoans. Comparable immunostimulatory activity in other species has yet to be demonstrated. Since rEA is known to be highly effective in treating Punta Toro virus (PTV) infection in mice, its ability to elicit protective immunity in the hamster PTV infection model was investigated. rEA was given alone, or in combination with IL-18 or IL-2, and virally challenged hamsters were observed for mortality. Cytokine transcript profiles for IL-12p40, IL-21, IFN-gamma and TNF-alpha were assessed to evaluate the induction of these inflammatory mediators known to be induced in mice following exposure to rEA. A dose of 100 microg of rEA, given once 4 h prior to viral challenge, and a second time on day 3 of the infection, was found to be the most effective prophylactic therapy protecting 60% of treated hamsters from mortality, compared to only 5-10% observed in animals receiving placebo. Increased expression of IFN-gamma and IL-12p40 was evident following treatment with rEA. The data suggest that rEA does induce host antiviral responses in hamsters that result in significant protection from death, although determining the most appropriate dose for intervention in other species, including humans, will likely be challenging.

Prophylactic treatment with recombinant Eimeria protein, alone or in combination with an agonist cocktail, protects mice from Banzi virus infection.

A recombinant Eimeria protozoan protein antigen (rEA) has been shown to have antitumor and antiviral activity. The purpose of this study was to determine the effect of rEA treatment alone or in combination with an agonist cocktail consisting of granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin 4 (IL-4), and anti CD-40 antibody, in the treatment of Banzi virus (BV) disease in BALB/c mice. Treatment with rEA resulted in a significant increase in survival, weight gain, and mean day to death in BV-infected mice and resulted in a significant decrease in brain virus titer. Treatment with rEA, in combination with a 4-agonist cocktail, improved disease parameters to a greater degree than rEA treatment alone. The effect of treatment with a reduced concentration of agonist cocktail or fewer components of the agonist cocktail, in combination with rEA, on disease outcome in BV-infected mice was also investigated. Treatment with rEA, alone or in combination with agonist cocktail, 24h after virus challenge did not improve disease. Treatment with rEA, alone or in combination with an agonist cocktail, is efficacious for the prophylaxis of BV infection in mice.

Recombinant Eimeria protozoan protein elicits resistance to acute phlebovirus infection in mice but not hamsters.

A protein antigen from an Eimeria protozoan has recently been reported to induce antitumor activity in mice. This activity most likely results from the strong induction of interkeukin-12 (IL-12) and gamma interferon (IFN-gamma), which are also essential factors in the establishment of protective immunity against viral infection. We evaluated recombinant Eimeria antigen (rEA) as a potential immunotherapeutic agent in mouse and hamster models of acute phleboviral disease. Punta Toro virus (PTV) was highly sensitive to a single dose of nanogram quantities of rEA in the mouse infection model. Intraperitoneal treatment with rEA also reduced virus load and liver damage associated with PTV infection. IL-12 was elicited following exposure of uninfected mice to quantities of rEA of 10 ng or greater, and the levels peaked at between 3 and 8 h postexposure. IFN-gamma release was induced more slowly and required less rEA (1 ng) to produce a significant rise in systemic levels. The induction of IL-12 and IFN-gamma involved in the coordination of innate and adaptive immune responses to microbial pathogens required myeloid differentiation factor 88, a signaling adaptor shared by most members of the Toll-like receptor (TLR) family. Despite encouraging results in the murine system, rEA failed to protect hamsters challenged with PTV. Our findings suggest that hamsters may lack functional TLR11, which has recently been shown to recognize a profilin-like protein homologous to rEA from the protozoan Toxoplasma gondii. Further investigation into the immunostimulatory capacity of rEA in other mammalian systems is necessary.

Protein from intestinal Eimeria protozoan stimulates IL-12 release from dendritic cells, exhibits antitumor properties in vivo and is correlated with low intestinal tumorigenicity.

The small intestine (SI) of vertebrates exhibits low tumorigenesis and rarely supports metastatic growth from distant tumors. Many theories have been proposed to address this phenomenon, but none has been consistently supported. One candidate mechanism is that the vast immunologic compartment of the SI provides a heightened level of tumor immunosurveillance. Consistent with this, we have identified a molecule of low abundance from bovine SI that has the hallmarks of a potent immunostimulant and may be associated with the natural suppression of cancer in the intestinal tract. The protein originates from an endemic gut protozoan, Eimeria spp., and is homologous to the antigen 3-1E previously isolated from the avian apicomplexan E. acervulina. We show here that it is a very potent stimulator of IL-12 release from dendritic cells, upregulates inflammatory modulators in vivo (IL-12, MCP-1, IL-6, TNF-alpha and INF-gamma) and has antitumor properties in mice. In addition, it is synergistic in vitro with anti-CD40 antibody, IFN-gamma, IL-4 and GM-CSF; is active across species barriers in vivo; and has no observable toxicity. Based on these activities, we speculate that it is an inducer of protozoan-targeted innate immunity, which may explain its potential benefit to the intestinal tract and potency as an agent in cancer immunotherapy.