The influence of a menthol and ethanol soaked garment on human temperature regulation and perception during exercise and rest in warm, humid conditions

This study assessed whether donning a garment saturated with menthol and ethanol (M/E) can improve evaporative cooling and thermal perceptions versus water (W) or nothing (CON) during low intensity exercise and rest in warm, humid conditions often encountered in recreational/occupational settings. It was hypothesised there would be no difference in rectal (Tre) and skin (Tsk) temperature, infra-red thermal imagery of the chest/back, thermal comfort (TC) and rating of perceived exertion (RPE) between M/E, W and CON, but participants would feel cooler in M/E versus W or CON. Methods - Six volunteers (mean [SD] 22 [4] years, 72.4 [7.4] kg and 173.6 [3.7] cm) completed (separate days) three, 60-min tests in 30 °C, 70%rh, in a balanced order. After 15-min of seated rest participants donned a dry (CON) or 80 mL soaked (M/E, W) long sleeve shirt appropriate to their intervention. They then undertook 30-min of low intensity stepping at a rate of 12 steps/min on a 22.5 cm box, followed by 15-min of seated rest. Measurements included heart rate (HR), Tre, Tsk (chest/back/forearm), thermal imaging (back/chest), thermal sensation (TS), TC and RPE. Data were reported every fifth minute as they changed from baseline and the area under the curves were compared by condition using one-way repeated measures ANOVA, with an alpha level of 0.05. Results - Tre differed by condition, with the largest heat storage response observed in M/E (p<0.05). Skin temperature at the chest/back/forearm, and thermal imaging of the chest all differed by condition, with the greatest rate of heat loss observed in W and M/E respectively (p<0.01). Thermal sensation differed by condition, with the coolest sensations observed in M/E (p<0.001). No other differences were observed. Conclusions - Both M/E and W enhanced evaporative cooling compared CON, but M/E causes cooler sensations and a heat storage response, both of which are likely mediated by menthol

A Study of Some Physical Properties of Concentrated Salt Solutions Using the Bubble Column Evaporator

The bubble column evaporator (BCE) was studied for novel applications in determining the enthalpy of vaporisation (ΔHvap) of concentrated salt solutions, decomposing solutes in salt solutions and controlling chemical precipitation. These BCE applications have potential uses in many industries, such as in desalination and water treatment. The project involved studies on the physical properties of various salt solutions by the main method of the BCE process. The BCE process offers a novel utilisation of the gas/liquid interface where the heat and mass transfer is efficiently carried out. Fine bubbles are produced through a porous sinter when a gas is sparged into column solutions. These bubbles, due to the inhibition effect of coalescence in some concentrated salt solutions, can be maintained at a small size to produce a high-density bubble column. The theoretical basis of the BCE process was also studied by modelling the energy balance in the column, the evaporation process and the solute decomposition process. ΔHvap values for concentrated salt solutions were accurately and precisely determined using a BCE system at room temperatures. It was established that the use of a vacuum space around the column and automatic-temperature-acquisition systems can enhance the accuracy and precision of these ΔHvap measurements. The accuracy was better than 1.0% compared to literature values. The BCE method typically gave high precision of ΔHvap data with a normal distribution. It was discovered that hot inlet air, at 150 C, can be used in the BCE to produce a continuous flow of hot surfaces, which can thermally decompose unstable solutes, such as NH₄HCO₃ and K₂S₂O₈. It was found that the BCE process was significantly more efficient than direct heating, for example, using a water bath at the same temperature. Lastly, it was discovered that chemical precipitation from supersaturated solutions was strongly inhibited by the BCE process. When CaCl₂ and Na₂SO₄ solutions were mixed to precipitate CaSO₄.2H₂O, the BCE process inhibited induction and growth of the precipitates, which were otherwise readily formed in a simple stirred system. These results suggest that the BCE process could be useful for the controlled production of nanometre and micrometre size particles

Thermal Modeling And Laser Beam Shaping For Microvias Drilling In High Density Packaging

Laser drilling of microvias for organic packaging applications is studied in present research. Thermal model is essential to understand the laser-materials interactions and to control laser drilling of blind micro holes through polymeric dielectrics in multilayer electronic substrates. In order to understand the profile of the drilling front irradiated with different laser beam profiles, a transient heat conduction model including vaporization parameters is constructed. The absorption length in the dielectric is also considered in this model. Therefore, the volumetric heating source criteria are applied in the model and the equations are solved analytically. The microvia drilling speed, temperature distribution in the dielectric and the thickness of the residue along the microvia walls and at the bottom of the microvia are studied for different laser irradiation conditions. An overheated metastable state of material is found to exist inside the workpiece. The overheating parameters are calculated for various laser drilling parameters and are used to predict the onset of thermal damage and to minimize the residue. As soon as a small cavity is formed during the drilling process, the concave curvature of the drilling front acts as a concave lens that diverges the incident laser beam. This self-defocusing effect can greatly reduce the drilling speed. This effect makes the refractive index of the substrate at different wavelengths an important parameter for laser drilling. A numerical thermal model is built to study the effect of self-defocusing for laser microvias drilling in multilayer electronic substrates with Nd:YAG and CO2 lasers.. The laser ablation thresholds was calculated with this model for the CO2 and Nd:YAG lasers respectively. Due to the expulsion of materials because of high internal pressures in the case of Nd:YAG laser microvia drilling, the ablation threshold may be far below the calculated value. A particular laser beam shape, such as pitch fork, was found to drill better holes than the Gaussian beam in terms of residue and tapering angle. Laser beam shaping technique is used to produce the desired pitchfork beam. Laser beam shaping allows redistribution of laser power and phase across the cross-section of the beam for drilling perfectly cylindrical holes. An optical system, which is comprised of three lenses, is designed to transform a Gaussian beam into a pitchfork beam. The first two lenses are the phase elements through which a Gaussian laser beam is transformed into a super Gaussian beam. The ray tracing technique of geometrical optics is used to design these phase elements. The third lens is the transform element which produces a pitchfork profile at the focal plane due to the diffraction effect. A pinhole scanning power meter is used to measure the laser beam profile at the focal plane to verify the existence of the pitchfork beam. To account for diffraction effect, the above mentioned laser beam shaping system was optimized by iterative method using Adaptive Additive algorithm. Fresnel diffraction is used in the iterative calculation. The optimization was target to reduce the energy contained in the first order diffraction ring and to increase the depth of focus for the system. Two diffractive optical elements were designed. The result of the optimization was found dependent on the relation between the diameter of the designed beam shape and the airy disk diameter. If the diameter of the designed beam is larger, the optimization can generate better result. Drilling experiment is performed with a Q-switched CO2 laser at wavelength of 9.3 μm. Comparison among the drilling results from Gaussian beam, Bessel beam and Pitchfork beam shows that the pitchfork beam can produce microvias with less tapering angle and less residue at the bottom of the via. Laser parameters were evaluated experimentally to study their influences on the via quality. Laser drilling process was optimized based on the evaluation to give high quality of the via and high throughput rate. Nd:YAG laser at wavelengths of 1.06 μm and 532 nm were also used in this research to do microvias drilling. Experimental result is compared with the model. Experimental results show the formation of convex surfaces during laser irradiation. These surfaces eventually rupture and the material is removed explosively due to high internal pressures. Due to the short wavelength, high power, high efficiency and high repetition rate, these lasers exhibit large potentials for microvias drilling

Influence of menthol on human temperature regulation and perception

When exercise is undertaken in warm, humid conditions, the thermal gradient between the skin and environment, and the capacity for evaporative heat loss, are reduced. These factors, along with an increase in metabolic heat production, lower work capacity and exercise performance. Thermoreceptors located within the skin and deep in the body convey information on this accumulation of thermal energy to higher brain structures and, if mean body temperature rises uncontrollably, the cumulative neuronal input is thought to produce inhibitory signals that lower work capacity, such that metabolic heat production decreases to protect the organism from heat injury. Lessening these inhibitory signals may enhance or help to maintain exercise performance in the heat. The inhibitory signals might be lessened by cooling the skin and deep body temperature prior to or during exercise, or perhaps by applying menthol on the skin, or some combination of these. Menthol is a chemical compound that activates cold receptors (TRPM8) in the skin to elicit cool sensations. These receptors are not otherwise activated unless cooled below 27 °C. Hence, menthol, when applied to the skin of heat stressed humans, may provide a “cool’’ neuronal input to higher brain structures in addition to the neuronal signals arising from warm thermoreceptors located within the body. But menthol may also induce a heat storage (cold defense) response that would then heighten the activity of warm receptors deep in the body. Therefore, it is not clear whether menthol might reduce, enhance or help to maintain exercise performance in heat stressed humans. Moreover, no studies have assessed the perceptual and thermoregulatory response to menthol during rest or exercise, or the consequence of its repeated use. Before it is recommended as a possible ergogenic aid, these studies should be undertaken. The early work presented in this thesis tested the hypotheses that a water-based spray, containing ethanol and/or menthol, would enhance evaporative cooling when sprayed on the skin, thereby lowering heat storage and improving thermal perception compared to an unsprayed Control condition; but menthol would also improve thermal perception independent of temperature by directly stimulating cold receptors, during rest and exercise in warm, humid conditions. The hypothesis that menthol-mediated cool sensations would not undergo any habituation after repeated exposures was also tested. The general approach to testing these hypotheses involved presenting human participants with a thermal challenge that would induce warm sensations and increase thermal discomfort, whilst encouraging a level of heat storage that could be compensated for by increasing heat loss through v sodilation and sweating. This was achieved by manipulating metabolic heat production through a combination of rest and fixed intensity exercise in warm (30 °C) and humid (70 %) conditions. The influence of a menthol solution spray was tested against the backdrop of this thermal challenge. The results supported the general hypothesis that a water-based upper-body spray containing menthol can increase sensations of coolth compared to no spraying or wateronly spraying during rest and exercise in warm, humid conditions, but menthol also influences body temperature regulation. The effect that menthol exerts over perception and thermoregulation differs by dose and fades with time. Specifically, 0.2 % menthol spraying encourages heat storage by enhancing vasoconstriction, and there is no habituation in these responses. 0.05 % menthol spraying did not encourage any additional heat storage compared to a Control spray. Menthol also influenced perception, with a 0.2 % menthol spray promoting cooler sensations and greater irritation than 0.05 % menthol and Control spraying. Compared to a Control spray, 0.2 % menthol reduced thermal comfort during rest and improved it during exercise, while 0.05 % menthol did not alter thermal comfort during rest, and may have improved it during exercise. Neither menthol spray influenced perceived exertion during exercise. Menthol-mediated cool sensations lasted 15 to 30 minutes. Both 0.2 % and 0.05 % menthol sprays underwent an habituation compared to the Control spray, with cool sensations diminishing after repeated daily exposures. It is concluded that a 0.05 % menthol spray, which induces cool sensations without a significant heat storage response, could be considered as a perceptual cooling intervention with some capacity to enhance evaporative heat loss when sprayed on the skin during rest and moderate fixed-intensity exercise in the heat. A 0.2 % menthol spray might be deployed later in exercise, but may increase heat storage and irritation. Further testing is required to identify whether menthol spraying improves maximal exercise performance.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Nutraceutical efficacy in experimental animal models of inflammatory bowel disease: \u3ci\u3eEchinacea angustifolia\u3c/i\u3e, \u3ci\u3ePrunella vulgaris\u3c/i\u3e and \u3ci\u3eHypericum gentianoides\u3c/i\u3e

Ulcerative colitis (UC) and Crohn\u27s disease (CD), collectively known as inflammatory bowel disease (IBD), are inflammatory diseases of the enteric mucosa whose etiology is currently undefined. While hypotheses for causation include genetic susceptibility, environmental risk factors, inappropriate and chronic immune responses to members of the intestinal microflora as well as failed immune regulatory mechanisms, many questions regarding IBD susceptibility, dysbiosis and immune dysfunction remain. Not surprisingly, current therapeutic targets are expensive, have questionable long term efficacy and are associated with risk of secondary bacterial and viral infections. As chronically ill patients substitute or supplement their treatments with alternative, nutraceutical remedies in ever greater numbers, more research is needed to ascertain the safety and efficacy of these products as therapeutics. Prunella vulgaris is a common `cure all\u27 which is popular in traditional Chinese medicine. P. vulgaris can be steeped in water and drank as a tea or ground into a salve, and is known for its anti-viral, anti-inflammatory and antioxidant benefits. P. vulgaris has never, until now, been studied in the context of colitic therapy and has yet to gain a foothold as a commonly utilized nutraceutical in western medicine. Hypericum gentianoides, akin to Hypericum perforatum/St. John\u27s Wort, is a unique and understudied species of Hypericum. H. gentianoides lacks the photoactive and cytotoxic compounds routinely found in other Hypericum species. While the bioactivity of this plant is not well characterized, it is known to have anti-inflammatory, immunomodulatory and antibacterial potential. This potential and the lack of cytotoxic, photoactive compounds make H. gentianoides a good candidate for study in colitis models. Echinacea angustifolia is well studied, commonly utilized world-wide as a preventative or remedy for the common cold, and has great potential as a therapeutic agent in many disease modalities. The roots of this plant contain several types of compounds known to be bioactive. Like other nutraceutical, E. angustifolia is documented anecdotally to cure or reduce symptoms related to countless maladies and diseases without sound scientific proof. E. angustifolia has never been studied as anti-colitic; however, pain suppressive and immunomodulatory capabilities of this plant lend credence to the potential for this type of study. In this study, the anti-colitic potential of P. vulgaris, H. gentianoides and E. angustifolia were determined in the mdr1a deficient (-/-) mouse model of spontaneous colitis or the chemically induced dextran sodium sulphate (DSS) mouse model of acute colitis. Extracts of E. angustifolia root or above ground sections of P. vulgaris or H. gentianoides were extracted using the Soxhlet method in 95% ethanol and were solubilized in a final concentration of 5% ethanol for use in studies. P. vulgaris and H. gentianoides were tested at daily doses of 2.4 mg (~ 100 mg/kg body weight) and 4.8 mg (~ 200 mg/kg body weight) respectively, while E. angustifolia was tested at daily doses of 100 mg/kg and 200 mg/kg body weight. In the DSS model of acute colitis, E. angustifolia was not found to be effective during the period of DSS treatment (in low dose 1.75% to high dose 2.5% DSS in male and female C57BL/6 mice), or during restitution. E. angustifolia was not found to be cytotoxic in vivo. Conversely, P. vulgaris was able to significantly (p \u3c 0.05) decrease weight loss and improve macroscopic indicators of severe colitic wasting. The disparity between E. angustifolia and P. vulgaris efficacies in this acute model of colitis could be due to the difference in the constituent types found in these two extracts. E. angustifolia is composed mostly of phenolics and alkylamides, while P. vulgaris contains phenolics, flavonoids and triterpinoids. Certain types of phenols have been shown to have efficacy in low dose DSS colitis; however, flavonoids have efficacy in models of colitis as well, and in combination with phenols may be synergistic. Since flavonoids have recently proven very effective in ameliorating spontaneous colitis, P. vulgaris was also evaluated in the mdr1a-/- model of spontaneous colitis. In the mdr1a-/- mouse model of spontaneous colitis, P. vulgaris extract treatment was compared to mdr1a-/- mice treated with 5% ethanol vehicle, metronidazole (an antibiotic and anti-colitic control) and FVBWT mice. It was discovered that P. vulgaris was able to delay onset of spontaneous colitis, significantly (p \u3c 0.05) decrease macroscopic typhlocolitic and microscopic cecal disease scores, prevent cecal neutrophil influx, and downregulate nuclear factor-kappaB (NF-kB) related cytokines/chemokines and gene targets. The downregulation of innate immune signals and function is hypothesized to contribute to the observed decrease in cecal tonsil CD4+ helper and CD8+ cytotoxic T cells as well as germinal center B cells. Adaptive immune function was also altered. Loss of immune tolerance to the microflora is a characteristic of chronic colitis. Unlike mdr1a-/- vehicle treated mice, which displayed antibody production to microflora antigens, P. vulgaris treated mice displayed little to no Ab response to the same microflora antigens. H. gentianoides contains flavonoids, phenolics and a unique antimicrobial compound called uliginosin A. As the mdr1a-/- mouse model of spontaneous colitis is driven by the host immune response to the microflora and Hypericum species are known to be immunomodulatory, this extract was of interest as a therapeutic anti-colitic in the mdr1a-/- model. Onset of spontaneous colitis was significantly delayed by H. gentianoides, but was not completely abolished. Macroscopic scores, microscopic scores, serum cytokine levels and myeloperoxidase production were all significantly (p \u3c 0.05) reduced by H. gentianoides gavage. While H. gentianoides has immunosuppressant potential, a surprising increase in intestinal plasma cell infiltrate and an increase in serum IL-6 correlated with H. gentianoides gavage in mdr1a-/- mice. To date, anti-microbial functions have not been ruled out as a contributing factor in the efficacy of anti-colitic activity of this extract. Together, these novel experiments have identified new candidates for anti-colitic therapy or therapeutic supplementation of current IBD treatment strategies. P. vulgaris, H. gentianoides and E. angustifolia merit further research as nutraceutical treatments of chronic inflammatory disorders, and these studies make it clear that synergy between phenolics, flavonoids and natural anti-bacterial compounds also warrant further research

Innovative Materials and Systems for Solid State Hydrogen Storage

The research presented in this doctoral thesis concerns with the development of novel materials and systems for solid state hydrogen storage. The first group of works presented is on alkaline and alkaline-earth borohydrides. The possibility to enhance their properties with the help of nanosupports has been widely explored. An attempt to improve the dehydrogenation kinetics of lithium borohydride has been made dispersing this material on the surface of modified nanotubes and graphite. The resulting nanoconfined material displayed a decreased decomposition temperature in comparison with pure material and further decreasing was observed when the surface area of the supports was increased. An analogous experiment was performed to investigate this effect in combination with the assets of a reactive hydride composite, where two materials are mixed to obtain a compound with a lower decomposition enthalpy. The effect of the mixture was beneficial in presence of the support, due to lower temperature melting. For calcium borohydride an ordered mesoporous carbon was used after chemical activation. The increased properties of this support resulted in lower decomposition temperature and improved reversibility for a number of cycles at different pressure values. The second research line is focused on magnesium hydride. To improve its kinetic properties a zirconium-nickel alloy was investigated to evaluate its influence on the reaction rate, both in absorption and desorption. The degradation observed in experimental reactors, of different magnesium hydride powders catalyzed with a transition metal oxide, motivated the fabrication of pellets with the addition of a binding agent, to obtain mechanical resistance, still allowing hydrogen diffusion. Each pellet was supposed to behave as an independent system, so they were also tested in a small reactor. Several hydrogen absorption/desorption cycles were performed to compare the behaviour of the small reactor with the laboratory data obtained on smaller quantity of powdered and pelletized specimens. Finally, the feasibility of a vehicular hydrogen tank system was investigated using an interstitial metal hydride as storage material. Apart from material basic characterization, two different kinds of experiment were performed. Static tests (measurements with automatic flow control and constant settings) were used to evaluate wether the requirements for desorption are met by the tank set-up. Then, dynamic tests were designed and applied on the tank, where the hydrogen flow was fluctuating following a hypothetical on-road trial. It was possible to underline the heat management issues of high-demanding performances and to analyze some solutions for that. Different cycles were carried out on the tank to find the ideal setting for high average and peak flows in a realistic experiment

Combinatorial design and development of biomaterials for use as drug delivery devices and immune adjuvants

There are several challenges associated with current strategies for drug and vaccine delivery. These include the need for multiple-dose administrations, which can hinder patience compliance, the requirements for specific storage conditions due to the fragile structure of protein-based molecules, and the need for additional excipients to enhance protein stability or adjuvant the immune response. This work has focused on the development of a high throughput, combinatorial approach to optimize degradable polymeric biomaterials, specifically polyanhydrides, to overcome these challenges associated with drug and vaccine delivery. We have developed high throughput techniques to rapidly fabricate polymer film and nanoparticle libraries to carry out detailed investigations of protein/biomaterial, cell/biomaterial, and host/biomaterial interactions. By developing and employing a highly sensitive fluorescence-based assay we rapidly identified that protein release kinetics are dictated by polymer chemistry, pH, and hydrophobicity, and thus can be tailored for the specific application to potentially eliminate the need for multiple-dose treatments. Further investigation of protein/biomaterial interactions identified polymer chemistry, pH, hydrophobicity, and temperature to be integral factors controlling protein stability during fabrication of the delivery device, storage, and delivery. Amphiphilic polymer chemistries were specifically identified to preserve the structure of both robust and fragile proteins from device fabrication to release. Our investigations of cell/biomaterial interactions revealed that all nanoparticle and polymer film chemistries studied were non-toxic at concentrations expected for human use. Furthermore, cellular activation studies were carried out with antigen presenting cells co-incubated with the polymer libraries which indicated that polymer films do not possess immune stimulating properties; however, the nanoparticles do, in a chemistry dependent manner. Combining these insights with informatics analysis, we discovered the molecular basis of the pathogen-mimicking behavior of amphiphilic polyanhydride nanoparticles. Specific molecular descriptors that were identified for this pathogen-mimicking behavior include alkyl ethers, % hydroxyl end groups, backbone oxygen content, and hydrophobicity. These findings demonstrated the stealth properties of polyanhydride films for tissue engineering and the pathogen-mimicking adjuvant properties of the nanoparticles for vaccine delivery. Finally, host/biomaterial interactions were studied, which indicated that polymer chemistry and administration route affect nanoparticle biodistribution and mucoadhesion. Amphiphilic nanoparticles were identified to reside longest at parenteral administration routes and adhere best to mucosal surfaces. These results point to their ability to provide a long-term antigen depot in vivo. In summary, the studies described in this thesis have created a rational design paradigm for materials selection and optimization for use as drug delivery vehicles and vaccine adjuvants, which will overcome the challenges associated with administration frequency, protein instability, and insufficient immune stimulation

Novel amphiphilic polyanhydrides for vaccine delivery

The rapid development of biopharmaceuticals suggests that many future vaccines will involve the delivery of peptide or protein sub units. The overall goal of this work is to design novel vaccine adjuvants based on biodegradable polymers that protect, stabilize, and enhance the immunogenicity of these protein antigens. Polyanhydrides, which are surface erodible polymers, have shown excellent performance as drug carriers. Their hydrophobic nature prevents water penetration into the bulk, thus eliminating water-induced covalent aggregation of proteins. Unfortunately, protein inactivation by non-covalent aggregation may still persist. It has been suggested that the use of carriers containing both hydrophobic and hydrophilic entities may provide a gentler environment for proteins. Hence, the synthesis and characterization of a novel amphiphilic polyanhydride system based on the anhydride monomers 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) was carried out. Subsequently, as most vaccines involve the delivery of peptides or protein subunits, protein stabilization in the CPTEG:CPH environment was analyzed. It was demonstrated that CPTEG:CPH system provides a gentle environment for proteins and sustained release from copolymer microspheres is attained. In order to evaluate the adjuvant characteristics of the CPTEG:CPH system, the activation of immune cells incubated with CPTEG:CPH microspheres and the implications for vaccine design were addressed. The promising adjuvant capabilities of CPTEG-content microspheres were evidenced by enhanced maturation of dendritic cells, the most potent antigen presenting cells of the immune system. Altogether, the studies presented in this thesis provide an excellent foundation for testing the viability of this system as an effective adjuvant for the development of vaccines. Development and application of this technology will facilitate the rational design of vaccines and the ability to appropriately redirect the immune response to develop protective immunity