Laser facilitates vaccination

Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms

The interplay of single-particle and collective motions in the low-lying states of Λ21^{21}_\LambdaNe with quadrupole-octupole correlations

The beyond mean-field approach for low-lying hypernuclear states is extended by mixing the configurations associated with both single-particle and quadrupole-octupole collective excitations within the generator coordinate method based on a covariant density functional theory. The method is demonstrated in the application to the low-lying states of $^{21}_\Lambda$Ne, where the configurations with the $\Lambda$ hyperon occupying the first ($\Lambda_s$) and second ($\Lambda_p$) lowest-energy states are considered. The results indicate that the positive-parity states are dominated by the $\alpha+^{12}$C+$\alpha+\Lambda_s$ structure. In contrast, the low-lying negative-parity states are dominated by a strong admixture of $\alpha+^{16}$O+$\Lambda_s$ structure and $\alpha+^{12}$C+$\alpha+\Lambda_p$ structure due to the inclusion of octupole correlations. As a result, the low-lying negative-parity states become much lower than what is expected from the previous studies without the mixing, and the electric multipole transition strengths are significantly quenched.Comment: 9 pages with 5 figures and 2 table

Laser mimicking mosquito bites for skin delivery of malaria sporozoite vaccines

Immunization with radiation-attenuated sporozoites (RAS) via mosquito bites has been shown to induce sterile immunity against malaria in humans, but this route of vaccination is neither practical nor ethical. The importance of delivering RAS to the liver through circulation in eliciting immunity against this parasite has been recently verified by human studies showing that high-level protection was achieved only by intravenous (IV) administration of RAS, not by intradermal (ID) or subcutaneous (SC) vaccination. Here, we report in a murine model that ID inoculation of RAS into laser-illuminated skin confers immune protection against malarial infection almost as effectively as IV immunization. Brief illumination of the inoculation site with a low power 532 nm Nd:YAG laser enhanced the permeability of the capillary beneath the skin, owing to hemoglobin-specific absorbance of the light. The increased blood vessel permeability appeared to facilitate an association of RAS with blood vessel walls by an as-yet-unknown mechanism, ultimately promoting a 7-fold increase in RAS entering circulation and reaching the liver over ID administration. Accordingly, ID immunization of RAS at a laser-treated site stimulated much stronger sporozoite-specific antibody and CD8+IFN-γ+ T cell responses than ID vaccination and provided nearly full protection against malarial infection, whereas ID immunization alone was ineffective. This novel, safe, and convenient strategy to augment efficacy of ID sporozoite-based vaccines warrants further investigation in large animals and in humans

Distribution of Spectral Lags in Gamma Ray Bursts

Using the data acquired in the Time To Spill (TTS) mode for long gamma-ray bursts (GRBs) collected by the Burst and Transient Source Experiment on board the Compton Gamma Ray Observatory (BATSE/CGRO), we have carefully measured spectral lags in time between the low (25-55 keV) and high (110-320 keV) energy bands of individual pulses contained in 64 multi-peak GRBs. We find that the temporal lead by higher-energy gamma-ray photons (i.e., positive lags) is the norm in this selected sample set of long GRBs. While relatively few in number, some pulses of several long GRBs do show negative lags. This distribution of spectral lags in long GRBs is in contrast to that in short GRBs. This apparent difference poses challenges and constraints on the physical mechanism(s) of producing long and short GRBs. The relation between the pulse peak count rates and the spectral lags is also examined. Observationally, there seems to be no clear evidence for systematic spectral lag-luminosity connection for pulses within a given long GRB.Comment: 20 pages, 4 figure

Sustained epidermal powder drug delivery via skin microchannels

Transdermal delivery of hydrophilic drugs is challenging. This study presents a novel sustained epidermal powder delivery technology (sEPD) for safe, efficient, and sustained delivery of hydrophilic drugs across the skin. sEPD is based on coating powder drugs into high-aspect-ratio, micro-coating channels (MCCs) followed by topical application of powder drug-coated array patches onto ablative fractional laser-generated skin MCs to deliver drugs into the skin. We found sEPD could efficiently deliver chemical drugs without excipients and biologics drugs in the presence of sugar excipients into the skin with a duration of ~ 12 h. Interestingly the sEPD significantly improved zidovudine bioavailability by ~ 100% as compared to oral gavage delivery. sEPD of insulin was found to maintain blood glucose levels in normal range for at least 6 h in chemical-induced diabetes mice, while subcutaneous injection failed to maintain blood glucose levels in normal range. sEPD of anti-programmed death-1 antibody showed more potent anti-tumor efficacy than intraperitoneal injection in B16F10 melanoma models. Tiny skin MCs and ‘bulk’ drug powder inside relatively deep MCCs are crucial to induce the sustained drug release. The improved bioavailability and functionality warrants further development of the novel sEPD for clinical use

Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10

Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study