Needleless Vaccine Delivery Using Micro-Shock Waves

Shock waves are one of the most efficient mechanisms of energy dissipation observed in nature. In this study, utilizing the instantaneous mechanical impulse generated behind a micro-shock wave during a controlled explosion, a novel nonintrusive needleless vaccine delivery system has been developed. It is well-known that antigens in the epidermis are efficiently presented by resident Langerhans cells, eliciting the requisite immune response, making them a good target for vaccine delivery. Unfortunately, needle-free devices for epidermal delivery have inherent problems from the perspective of the safety and comfort of the patient. The penetration depth of less than 100 mu m in the skin can elicit higher immune response without any pain. Here we show the efficient utilization of our needleless device (that uses micro-shock waves) for vaccination. The production of liquid jet was confirmed by high-speed microscopy, and the penetration in acrylamide gel and mouse skin was observed by confocal microscopy. Salmonella enterica serovar Typhimurium vaccine strain pmrG-HM-D (DV-STM-07) was delivered using our device in the murine salmonellosis model, and the effectiveness of the delivery system for vaccination was compared with other routes of vaccination. Vaccination using our device elicits better protection and an IgG response even at a lower vaccine dose (10-fold less) compared to other routes of vaccination. We anticipate that our novel method can be utilized for effective, cheap, and safe vaccination in the near future.

Review of hypersonic research investigations in IISc shock tunnel (HST1)

Real gas effects dominate the hypersonic flow fields encountered by modem day hypersonic space vehicles. Measurement of aerodynamic data for the design applications of such aerospace vehicles calls for special kinds of wind tunnels capable of faithfully simulating real gas effects. A shock tunnel is an established facility commonly used along with special instrumentation for acquiring the data for this purpose within a short time period. The hypersonic shock tunnel (HST1), established at the Indian Institute of Science (IISc) in the early 1970s, has been extensively used to measure the aerodynamic data of various bodies of interest at hypersonic Mach numbers in the range 4 to 13. Details of some important measurements made during the period 1975-1995 along with the performance capabilities of the HST1 are presented in this review. In view of the re-emergence of interest in hypersonics across the globe in recent times, the present review highlights the Suitability of the hypersonic shock tunnel at the IISc for future space application studies in India.

Primary Sequence That Determines the Functional Overlap between Mitochondrial Heat Shock Protein 70 Ssc1 and Ssc3 of Saccharomyces cerevisiae

The evolutionary diversity of the HSP70 gene family at the genetic level has generated complex structural variations leading to altered functional specificity and mode of regulation in different cellular compartments. By utilizing Saccharomyces cerevisiae as a model system for better understanding the global functional cooperativity between Hsp70 paralogs, we have dissected the differences in functional properties at the biochemical level between mitochondrial heat shock protein 70 (mtHsp70) Ssc1 and an uncharacterized Ssc3 paralog. Based on the evolutionary origin of Ssc3 and a high degree of sequence homology with Ssc1, it has been proposed that both have a close functional overlap in the mitochondrial matrix. Surprisingly, our results demonstrate that there is no functional cross-talk between Ssc1 and Ssc3 paralogs. The lack of in vivo functional overlap is due to altered conformation and significant lower stability associated with Ssc3. The substrate-binding domain of Ssc3 showed poor affinity toward mitochondrial client proteins and Tim44 due to the open conformation in ADP-bound state. In addition to that, the nucleotide-binding domain of Ssc3 showed an altered regulation by the Mge1 co-chaperone due to a high degree of conformational plasticity, which strongly promotes aggregation. Besides, Ssc3 possesses a dysfunctional inter-domain interface thus rendering it unable to perform functions similar to generic Hsp70s. Moreover, we have identified the critical amino acid sequence of Ssc1 and Ssc3 that can ``make or break'' mtHsp70 chaperone function. Together, our analysis provides the first evidence to show that the nucleotide-binding domain of mtHsp70s plays a critical role in determining the functional specificity among paralogs and orthologs across kingdoms.

Strong shock approximation in the new theory of shock dynamics

This paper investigates the propagation of a strong shock into an inhomogeneous medium using the new theory of shock dynamics. The equations are simple to solve and involve no trial-and-error method commonly used in this case. The results compare favourably with earlier results obtained in the case of self-similar flows, which arise as a special case of this theory.

Diaphragmless shock wave generators for industrial applications of shock waves

The prime focus of this study is to design a 50 mm internal diameter diaphragmless shock tube that can be used in an industrial facility for repeated loading of shock waves. The instantaneous rise in pressure and temperature of a medium can be used in a variety of industrial applications. We designed, fabricated and tested three different shock wave generators of which one system employs a highly elastic rubber membrane and the other systems use a fast acting pneumatic valve instead of conventional metal diaphragms. The valve opening speed is obtained with the help of a high speed camera. For shock generation systems with a pneumatic cylinder, it ranges from 0.325 to 1.15 m/s while it is around 8.3 m/s for the rubber membrane. Experiments are conducted using the three diaphragmless systems and the results obtained are analyzed carefully to obtain a relation between the opening speed of the valve and the amount of gas that is actually utilized in the generation of the shock wave for each system. The rubber membrane is not suitable for industrial applications because it needs to be replaced regularly and cannot withstand high driver pressures. The maximum shock Mach number obtained using the new diaphragmless system that uses the pneumatic valve is 2.125 +/- 0.2%. This system shows much promise for automation in an industrial environment.

Shock tunnel study of spiked aerodynamic bodies flying at hypersonic Mach numbers

A three-component accelerometer balance system is used to study the drag reduction effect of an aerodisc on large angle blunt cones flying at hypersonic Mach numbers. Measurements in a hypersonic shock tunnel at a freestream Mach number of 5.75 indicate more than 50% reduction in the drag coefficient for a 120degrees apex angle blunt cone with a forward facing aerospike having a flat faced aerodisc at moderate angles of attack. Enhancement of drag has been observed for higher angles of attack due to the impingement of the flow separation shock on the windward side of the cone. The flowfields around the large angle blunt cone with aerospike assembly flying at hypersonic Mach numbers are also simulated numerically using a commercial CFD code. The pressure and density levels on the model surface, which is under the aerodynamic shadow of the flat disc tipped spike, are found very low and a drag reduction of 64.34% has been deduced numerically.

Unimolecular HCl elimination from 1,2-dichloroethane: A single pulse shock tube and ab initio study

Thermal decomposition of 1,2-dichloroethane (1,2-DCE) has been studied in the temperature range of 10501175 K behind reflected shock waves in a single pulse shock tube. The unimolecular elimination of HCl is found to be the major channel through which 1,2-DCE decomposes under these conditions. The rate constant for the unimolecular elimination of HCl from 1,2-dichloroethane is found to be 10(13.98+/-0.80) exp(-57.8+/-2.0/RT) s(-1), where the activation energy is given in kcal mol(-1) and is very close to that value for CH3CH2Cl (EC). Ab initio (HF and MP2) and DFT calculations have been carried out to find the activation barrier and the structure of the transition state for this reaction channel from both EC and 1,2-DCE. The preexponential factors calculated at various levels of theory (BF/6-311++G**, MP2/6-311++G**, and B3LYP/6-311++G**) are (approximate to10(15) s(-1)) significantly larger than the experimental results. If the torsional mode in the ground state is treated as free internal rotation the preexponential factors reduce significantly, giving excellent agreement with experimental values. The DFT results are in excellent (fortuitous?) agreement with the experimental value for activation energy for 1,2-DCE while the MP2 and HF results seem to overestimate the barrier. However, DFT results for EC is 4.5 kcal mol(-1) less than the previously reported experimental values. At all levels, theory predicts an increase in HCI elimination barrier on beta-Cl substitution on EC.

A study of shock wave interaction with a rotating cylinder

Shock wave reflection over a rotating circular cylinder is numerically and experimentally investigated. It is shown that the transition from the regular reflection to the Mach reflection is promoted on the cylinder surface which rotates in the same direction of the incident shock motion, whereas it is retarded on the surface that rotates to the reverse direction. Numerical calculations solving the Navier-Stokes equations using extremely fine grids also reveal that the reflected shock transition from RRdouble right arrowMR is either advanced or retarded depending on whether or not the surface motion favors the incident shock wave. The interpretation of viscous effects on the reflected shock transition is given by the dimensional analysis and from the viewpoint of signal propagation.

Minimum error solutions of the Boltzmann equation for shock structure

‘Best’ solutions for the shock-structure problem are obtained by solving the Boltzmann equation for a rigid sphere gas by applying minimum error criteria on the Mott-Smith ansatz. The use of two such criteria minimizing respectively the local and total errors, as well as independent computations of the remaining error, establish the high accuracy of the solutions, although it is shown that the Mott-Smith distribution is not an exact solution of the Boltzmann equation even at infinite Mach number. The minimum local error method is found to be particularly simple and efficient. Adopting the present solutions as the standard of comparison, it is found that the widely used v2x-moment solutions can be as much as a third in error, but that results based on Rosen's method provide good approximations. Finally, it is shown that if the Maxwell mean free path on the hot side of the shock is chosen as the scaling length, the value of the density-slope shock thickness is relatively insensitive to the intermolecular potential. A comparison is made on this basis of present results with experiment, and very satisfactory quantitative agreement is obtained.

Heat shock protein 70 as a biomarker of heat stress in a simulated hot cockpit

Background: Fighter pilots are frequently exposed to high temperatures during high-speed low-level flight. Heat strain can result in temporary impairment of cognitive functions and when severe, loss of consciousness and consequent loss of life and equipment. Induction of stress proteins is a highly conserved stress response mechanism from bacteria to humans. induced stress protein levels are known to be cytoprotective and have been correlated with stress tolerance. Although many studies on the heat shock response mechanisms have been performed in cell culture and animal model systems, there is very limited information on stress protein induction in human subjects. Hypothesis: Heat shock proteins (Hsp), especially Hsp70, may be induced in human subjects exposed to high temperatures in a hot cockpit designed to simulate heat stress experienced in low flying sorties. Methods: Six healthy volunteers were subjected to heat stress at 55degreesC in a high temperature cockpit simulator for a period of 1 h at 30% humidity. Physiological parameters such as oral and skin temperatures, heart rate, and sweat rate were monitored regularly during this time. The level of Hsp70 in leukocytes was examined before and after the heat exposure in each subject. Conclusions: Hsp70 was found to be significantly induced in all the six subjects exposed to heat stress. The level of induced Hsp70 appears to correlate with other strain indicators such as accumulative circulatory strain and Craig's modified index. The usefulness of Hsp70 as a molecular marker of heat stress in humans is discussed.