254 resultados para Intellectual property systems Australia


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The purpose of this research is to investigate potential methods to produce an ion-exchange membrane that can be integrated directly into a polydimethylsiloxane Lab-on-a-Chip or Micro-Total-Analysis-System. The majority of microfluidic membranes are based on creating microporous structures, because it allows flexibility in the choice of material such that it can match the material of the microfluidic chip. This cohesion between the material of the microfluidic chip and membrane is an important feature to prevent bonding difficulties which can lead to leaking and other practical problems. However, of the materials commonly used to manufacture microfluidic chips, there are none that provide the ion-exchange capability. The DuPont product Nafion{TM} is chosen as the ion-exchange membrane, a copolymer with high conductivity and selectivity to cations and suitable for many applications such as electrolysis of water and the chlor-alkali process. The use of such an ion-exchange membrane in microfluidics could have multiple advantages, but there is no reversible/irreversible bonding that occurs between PDMS and Nafion{TM}. In this project multiple methods of physical entrapment of the ion-exchange material inside a film of PDMS are attempted. Through the use of the inherent properties of PDMS, very inexpensive sugar granulate can be used to make an inexpensive membrane mould which does not interfere with the PDMS crosslinking process. After dissolving away this sacrificial mould material, Nafion{TM} is solidified in the irregular granulate holes. Nafion{TM} in this membrane is confined in the irregular shape of the PDMS openings. The outer structure of the membrane is all PDMS and can be attached easily and securely to any PDMS-based microfluidic device through reversible or irreversible PDMS/PDMS bonding. Through impedance measurement, the effectiveness of these integrated membranes are compared against plain Nafion{TM} films in simple sodium chloride solutions.

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The heat transfer from a hot primary flow stream passing over the outside of an airfoil shaped strut to a cool secondary flow stream passing through the inside of that strut was studied experimentally and numerically. The results showed that the heat transfer on the inside of the strut could be reliably modeled as a developing flow and described using a power law model. The heat transfer on the outside of the strut was complicated by flow separation and stall on the suction side of the strut at high angles of attack. This separation was quite sensitive to the condition of the turbulence in the flow passing over the strut, with the size of the separated wake changing significantly as the mean magnitude and levels of anisotropy were varied. The point of first stall moved by as much as 15% of the chord, while average heat transfer levels changed by 2-5% as the inlet condition was varied. This dependence on inlet conditions meant that comparisons between experiment and steady RANS based CFD were quite poor. Differences between the CFD and experiment were attributed to anisotropic and unsteady effects. The coupling between the two flows was shown to be quite low - that is to say, heat transfer coefficients on both the inner and outer surfaces of the strut were relatively unaffected by the temperature of the strut, and it was possible to predict the temperature on the strut surface quite reliably using heat transfer data from decoupled tests, especially for CFD simulations.

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GM2 gangliosidoses is a family of severe, neurodegenerative disorders resulting from a deficiency in the β-hexosaminidase A (Hex A) enzyme. This disorder is typically caused by a mutation to either the HEXA gene, causing Tay Sachs disease, or a mutation to the HEXB gene, causing Sandhoff disease. The HEXA and HEXB genes are required to produce the α and β subunits of the Hex A enzyme respectively. Using a Sandhoff disease (SD) mouse model (Hexb-/-) we tested the potential of a low dose of systemically delivered single stranded adeno-associated virus 9 (ssAAV9) expressing human HEXB and human HEXA cDNA under the control of a single promoter through the use of a bicistronic vector design with a P2A linker to correct the neurological phenotype. Neonatal mice were injected with either this ssAAV9-HexB-P2A-HexA vector (HexB-HexA) or a vehicle solution via the superficial temporal vein. HexB-HexA treatment alone conferred an increase in survival of 56% compared to vehicle-injected controls and biochemical analysis of the brain tissue and serum revealed an increase in HexA activity and a decrease in brain GM2 ganglioside buildup. Additionally, treatments with the non-steroidal anti-inflammatory drug indomethacin (Indo), the histone deactylase inhibitor ITF2357 (ITF) and the pharmacological chaperone pyrimethamine (Pyr) were tested. The anti-inflammatory treatments of Indo and ITF conferred an increase in survival of 12% and 8% respectively while causing no alteration in the HexA activity or GM2 ganglioside buildup. Pyr had no observable effect on disease progression. Lastly HexB-HexA treatment was tested in conjunction with Indo, ITF and Pyr individually. Additive increases in survival and behavioural testing results were observed with Indo and ITF treatments while no additional benefit to HexA activity or GM2 ganglioside levels in the brain tissue was observed. This indicates the two treatments slowed the progression of the disease through a different mechanism than the reduction of the GM2 ganglioside substrate. Pyr treatment was shown to have no effect when combined with HexB-HexA treatment. This study demonstrates the potential amelioration of SD with a novel AAV9 gene therapy approach as well as helped to identify the additive potential of anti-inflammatory treatments in gene therapy of GM2 gangliosidoses.

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Breast cancer is the most frequently diagnosed cancer in women, accounting for over 25% of cancer diagnoses and 13% of cancer-related deaths in Canadian women. There are many types of therapies for treatment or management of breast cancer, with chemotherapy being one of the most widely used. Taxol (paclitaxel) is one of the most extensively used chemotherapeutic agents for treating cancers of the breast and numerous other sites. Taxol stabilizes microtubules during mitosis, causing the cell cycle to arrest until eventually the cell undergoes apoptosis. Although Taxol has had significant benefits in many patients, response rates range from only 25-69%, and over half of Taxol-treated patients eventually acquire resistance to the drug. Drug resistance remains one of the greatest barriers to effective cancer treatment, yet little has been discerned regarding resistance to Taxol, despite its widespread clinical use. Kinases are known to be heavily involved in cancer development and progression, and several kinases have been linked to resistance of Taxol and other chemotherapeutic agents. However, a systematic screen for kinases regulating Taxol resistance is lacking. Thus, in this study, a set of kinome-wide screens was conducted to interrogate the involvement of kinases in the Taxol response. Positive-selection and negative-selection CRISPR-Cas9 screens were conducted, whereby a pooled library of 5070 sgRNAs targeted 507 kinase-encoding genes in MCF-7 breast cancer cells that were Taxol-sensitive (WT) or Taxol-resistant (TxR) which were then treated with Taxol. Next generation sequencing (NGS) was performed on cells that survived Taxol treatment, allowing identification and quantitation of sgRNAs. STK38, Blk, FASTK and Nek3 stand out as potentially critical kinases for Taxol-induced apoptosis to occur. Furthermore, kinases CDKL1 and FRK may have a role in Taxol resistance. Further validation of these candidate kinases will provide novel pre-clinical data about potential predictive biomarkers or therapeutic targets for breast cancer patients in the future.

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The photochemistry of the polar regions of Earth, as well as the interstellar medium, is driven by the effect of ultraviolet radiation on ice surfaces and on the materials trapped within them. While the area of ice photochemistry is vast and much research has been completed, it has only recently been possible to study the dynamics of these processes on a microscopic level. One of the leading techniques for studying photoreaction dynamics is Velocity Map Imaging (VMI). This technique has been used extensively to study several types of reaction dynamics processes. Although the majority of these studies have utilized molecular beams as the main medium for reactants, new studies showed the versatility of the technique when applied to molecular dynamics of molecules adsorbed on metal surfaces. Herein the development of a velocity map imaging apparatus capable of studying the photochemistry of condensed phase materials is described. The apparatus is used to study of the photo-reactivity of NO2 condensed within argon matrices to illustrate its capabilities. A doped ice surface is formed by condensing Ar and NO2 gas onto a sapphire rod which is cooled using a helium compressor to 20 K. The matrix is irradiated using an Nd:YAG laser at 355 nm, and the resulting NO fragment is state-selectively ionized using an excimer-pumped dye laser. In all, we are able to detect transient photochemically generated species and can collect information on their quantum state and kinetic energy distribution. It is found that the REMPI spectra changes as different sections of the dissociating cloud are probed. The rotational and translational energy populations are found to be bimodal with a low temperature component roughly at the temperature of the matrix, and a second component with much higher temperature, the rotational temperature showing a possible population inversion, and the translational temperature of 100-200 K. The low temperature translational component is found to dominate at long delay times between dissociation and ionization, while at short time delays the high temperature component plays a larger role. The velocity map imaging technique allows for the detection of both the axial and radial components of the translational energy. The distribution of excess energy over the rotational, electronic and translational states of the NO photofragments provides evidence for collisional quenching of the fragments in the Ar-matrix prior to their desorption.

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ABSTRACT The purpose of this study was to examine the technical adequacy of the Developmental Reading Assessment (Beaver & Carter, 2004). Internal consistency analysis, factor analysis, and linear regression analyses were used to test whether the DRA is a statistically reliable measuring of reading comprehension for Grades 7 and 8 students. Correlational analyses, decision consistency analyses, and a focus group of experienced Intermediate (Grades 7 and 8) teachers examined whether there is evidence that the results from the DRA provide valid interpretations regarding students’ reading skills and comprehension. Results indicated that, as currently scored, internal consistency is low and skewness of distribution is high. Factor analyses did not replicate those cited by the DRA developers to prove construct validity. Two-way contingency analyses determined that decision consistency did not vary greatly between the DRA, EQAO, scores and report card marks. Views expressed during the focus group echoed many of the challenges to validity found in the statistical analysis. The teachers found that the DRA was somewhat useful, as there were limited alternative reading assessments available for the classroom, but did not endorse it strongly. The study found little evidence that the DRA provides valid interpretations regarding Intermediate students’ reading skills. Indicated changes to the structure and administration procedures of the DRA may ameliorate some of these issues.

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Water remains a predominant vector for human enteric pathogens not just for developing countries but also developed nations, where numerous infectious disease outbreaks, linked to the contamination of drinking water have been documented. Private drinking water wells are a source of drinking water that is largely unstudied even though a significant percentage of the population in Ontario relies on wells as their primary water source. As there exists little to no systematic surveillance for enteric infections or outbreaks related to well water sources, these individuals may be at higher risk of waterborne infectious diseases. The relationships between various fecal indicators in the water of private drinking water wells, including E. coli, Total Coliforms (TC) and Bacteroides, and enteric pathogens, including Campylobacter jejuni, Salmonella spp., and Shiga toxin producing E. coli, were studied. Convenience private well water samples collected from various regions of interest during the summer of 2014 underwent membrane filtration and culture to determine quantities of E. coli and TC colony forming units. 289 E. coli positive and 230 TC-only waters were successfully analyzed by individual qPCR assays for the aforementioned enteric pathogens. Microbial source tracking methods targeted to specific Bacteroides were used to determine the source of fecal contamination as either human or bovine. The source of fecal contamination varied by geographic region and is thought to be due to such things as differences in septic tank density and underlying geology, among others. Fecal indicators, E. coli and Bacteroides, were significantly correlated. E. coli as measured by qPCR was more strongly correlated to both total and human-specific Bacteroides genetic markers than culturable E. coli. Lastly, 1.9% of samples showed molecular evidence of contamination with enteric pathogens. Although low, this finding is significant given the limited volume of water available for testing, and suggests a potential health risk to consumers. Knowing the extent of contamination, as well as the biologic source, can better inform risk assessment and the development of potential intervention strategies for private well water in specific regions of Ontario.

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We present an extensive photometric catalog for 548 CALIFA galaxies observed as of the summer of 2015. CALIFA is currently lacking photometry matching the scale and diversity of its spectroscopy; this work is intended to meet all photometric needs for CALIFA galaxies while also identifying best photometric practices for upcoming integral field spectroscopy surveys such as SAMI and MaNGA. This catalog comprises gri surface brightness profiles derived from Sloan Digital Sky Survey (SDSS) imaging, a variety of non-parametric quantities extracted from these pro files, and parametric models fitted to the i-band pro files (1D) and original galaxy images (2D). To compliment our photometric analysis, we contrast the relative performance of our 1D and 2D modelling approaches. The ability of each measurement to characterize the global properties of galaxies is quantitatively assessed, in the context of constructing the tightest scaling relations. Where possible, we compare our photometry with existing photometrically or spectroscopically obtained measurements from the literature. Close agreement is found with Walcher et al. (2014), the current source of basic photometry and classifications of CALIFA galaxies, while comparisons with spectroscopically derived quantities reveals the effect of CALIFA's limited field of view compared to broadband imaging surveys such as the SDSS. The colour-magnitude diagram, star formation main sequence, and Tully-Fisher relation of CALIFA galaxies are studied, to give a small example of the investigations possible with this rich catalog. We conclude with a discussion of points of concern for ongoing integral field spectroscopy surveys and directions for future expansion and exploitation of this work.

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The transition of epithelial-like tumour cells to those exhibiting mesenchymal characteristics (Epithelial-to-mesenchymal Transition; EMT) is an integral process in breast cancer metastasis. EMT can be promoted by Transforming growth factor-beta (TGF-β) which can be found at high levels in the tumour stroma. Tumour-associated macrophages (TAMs) can also induce EMT in breast cancer cells, which is one way that they promote breast cancer metastasis. Vitamin D signalling has been implicated in EMT suppression and plays a role in modulating macrophage differentiation and stimulating their anti-inflammatory functions. This project had two major aims. First, we aimed to create and verify a unique fluorescent reporter gene construct designed to evaluate the dynamics of EMT in real-time and at the single-cell level. While some components of this reporter system were successfully validated, work to complete the final reporter construct is ongoing. The second and main aspect of this project focused on exploring the ability of 1,25-dihydroxyvitamin D3 (1,25D3) to modulate the interaction between mesenchymal mammary tumour cells and TAMs. Unexpectedly, in short-term treatment (48 hours) studies of 4T1 murine mammary tumour cells, we observed that 1,25D3 and TGF-β signalling work together to increase expression of the mesenchymal markers, Snai1, Fn1, and Col1a1. 1,25D3 and TGF-β also synergistically activate transcription of the gene encoding the 1,25D3-catabolizing enzyme, Cyp24a1. The ability of 1,25D3 and TGF-β to enhance expression of these genes was diminished in a long-term treatment (14 days) of 4T1 cells, and this effect was accompanied by a decrease in cell proliferation. 1,25D3 may also cooperate with cytokines produced by normal macrophages and macrophages considered to be TAM-like. Conditioned media experiments revealed that in the presence of factors from normal macrophages, 1,25D3 enhanced expression of Fn1, and in the presence of factors from TAM-like macrophages, 1,25D3 enhanced expression of Fn1 and Cyp24a1. Rather than mitigating the interaction as hypothesized, 1,25D3 may exacerbate the tumour-promoting effects of the EMT-TAM relationship. Also, signalling pathways involved in the EMT-TAM relationship may synergize with 1,25D3 to upregulate Cyp24a1 expression. These findings are important for understanding the potential of vitamin D compounds to be used in the treatment of breast cancer.

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Several determinants of fear of falling (FoF) and low balance confidence overlap with the consequences/complications of diabetes mellitus (DM). FoF is strongly associated with low balance confidence, and balance confidence mediates the relationship between FoF and balance and physical function. The purpose of this thesis was two-fold: (1) to examine the prevalence, severity and determinants of FoF in older adults (aged≥65) with DM, and (2) to evaluate the validity of the short version of the Activities-specific Balance Confidence scale (ABC-6) and its association with balance and postural control in older adults with DM. Three separate studies were conducted of older adults with DM (DM-group) and without DM (noDM-group). Study I revealed that although FoF prevalence adjusted for age and sex was not different between-groups, the DM-group had 8.8% fewer participants in the low and 8.4% more in the high Falls-Efficacy Scale International categories when compared to the noDM-group. Higher FoF severity in the DM-group was associated with poor physical performance, being female, fall history and clinical depressive symptoms. Study II provided evidence of convergent, discriminant and concurrent validity of the ABC-6 for use in older adults with DM with and without diabetic peripheral neuropathy (DPN). Notably, the ABC-6 was more sensitive in detecting subtle differences in balance confidence between the DM-group and noDM-group when compared to the original ABC scale (ABC-16), and can be administered in less time. Study III explored balance confidence (ABC-6) and its association with balance and postural control in older adults with DM. Subtle differences in axial segmental control (i.e., lower trunk roll velocity and higher head-trunk correlations) while walking and lower balance confidence were apparent in the DM-group, even in the absence of DPN, when compared to the noDM-group. Balance confidence partially explained the variance in head-trunk stiffening between-groups, and consequently low balance confidence in older adults with DM may contribute to the dependence on postural control strategies that are normally only utilized in high-risk situations. Findings from this thesis will help to guide the development of protocols for screening and intervention recommendations of patient education and targeted rehabilitation programs for older adults with DM.

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The advent of next-generation sequencing has significantly reduced the cost of obtaining large-scale genetic resources, opening the door for genomic studies of non-model but ecologically interesting species. The shift in mating system, from outcrossing to selfing, has occurred thousands of times in angiosperms and is accompanied by profound changes in the population genetics and ecology of a species. A large body of work has been devoted to understanding why the shift occurs and the impact of the shift on the genetics of the resulting selfing populations, however, the causes and consequences of the transition to selfing involve a complicated interaction of genetic and demographic factors which are difficult to untangle. Abronia umbellata is a Pacific coastal dune endemic which displays a striking shift in mating system across its geographic range, with large-flowered outcrossing populations south of San Francisco and small-flowered selfing populations to the north. Abronia umbellata is an attractive model system for the study of mating system transitions because the shift appears to be recent and therefore less obscured by post-shift processes, it has a near one-dimensional geographic range which simplifies analysis and interpretation, and demographic data has been collected for many of the populations. In this study, we generated transcriptome-level data for 12 plants including individuals from both subspecies, along with a resequencing study of 48 individuals from populations across the range. The genetic analysis revealed a recent transition to selfing involving a drastic reduction in genetic diversity in the selfing lineage, potentially indicative of a recent population bottleneck and a transition to selfing due to reproductive assurance. Interestingly, the genetic structure of the populations was not coincident with the current subspecies demarcation, and two large-flowered populations were classified with the selfing subspecies, suggesting a potential need for re-evaluation of the current subspecies classification. Our finding of low diversity in selfing populations may also have implications for the conservation value of the threatened selfing subspecies.

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Background: Mechanisms underlying the effect of estrogen exposure on breast cancer risk remain unclear. Insulin-like growth factor-1 (IGF-1) levels have been positively associated with breast cancer and are a potential mechanism. Objectives: The objectives of this thesis are: 1) to explore whether the reproductive risk factors and the lifetime cumulative number of menstrual cycles (LCMC), as measures for long-term estrogen exposure, are associated with IGF-1 levels, and 2) to examine the effect of an aromatase inhibitor (AI) on IGF-1 levels, and the potential interaction with BMI. Methods: A cross sectional study and a randomized controlled trial nested with the MAP.3 chemoprevention trial were used to address objective 1 and 2, respectively. 567 postmenopausal women were selected. Anthropometric measurements, lifestyle factors, reproductive characteristics and serum IGF-1 concentrations were collected at baseline and one year. Objective 1. The LCMC was computed as a composite measure of the reproductive characteristics. Multivariable linear regression models were used to assess the association between IGF-1 levels and LCMC and the hormonal risk factors, while adjusting for potential covariates. Objective 2. Changes in IGF-1 were compared between the exemestane and placebo, and effect modification by BMI was tested with an interaction term. Results: Objective 1. Women aged 55 years or older at menopause had 16.26 ng/mL (95% CI: 1.76, 30.75) higher IGF-1 compared to women aged less than 50 years at menopause. Women in the highest category of menstrual cycles (≥500 cycles) had an average 19.00 ng/mL (95%CI: 5.86, 32.14) higher concentration of IGF-1 compared to women in the lowest category (<350). Exogenous hormones had no effect on postmenopausal IGF-1 levels. Objective 2. Exemestane significantly increased IGF-1 levels by 18% (95% CI: 14%-22%); while, placebo had no effect on IGF-1. The changes in IGF-1 were significantly different between the treatment arms (P<0.0001) and no significant interaction was observed between treatment and BMI on IGF-1 changes (P=0.1327). Conclusion: Objective 1. Larger number of menstrual cycles and a later age at menopause are positively associated with IGF-1. IGF-1 may be one mechanism by which prolonged estrogen exposure increases cancer risk. Objective 2. We conclude that the reduced cancer risk observed with AI therapy likely occurs in an IGF-1 independent mechanism. Further studies exploring the clinical consequences of increased IGF-1 on AI therapy are needed.

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The human ether-a-go-go-related gene (hERG) encodes the voltage-gated K+ channel, hERG (Kv11.1). This channel passes the rapidly-activating delayed rectifier K+ current (IKr), which is important for cardiac repolarization. A reduction in IKr due to loss-of-function mutations or drug interactions causes long QT syndrome (LQTS), which can lead to cardiac arrhythmias and sudden cardiac death. The density of hERG channels in the plasma membrane is a key determinant of normal physiological function, and is balanced by trafficking to and from the cell surface. Many LQTS-associated hERG mutations result in a trafficking deficiency of otherwise functional channels. Thus, elucidating mechanisms of hERG regulation at the plasma membrane is useful for the prevention and treatment of LQTS. We previously demonstrated that M3 muscarinic receptor activation increases mature hERG expression through a Gq protein-dependent protein kinase C (PKC) pathway. In addition to conventional Gq protein-coupling, M3 receptors recruit β-arrestins upon agonist binding. Traditionally known for their role in receptor desensitization and internalization, β-arrestins also act as adaptor proteins to facilitate G protein-independent signaling. In the present work, I investigated the exclusive effect of β-arrestin signaling on hERG expression by utilizing an arrestin-biased M3 designer receptor (M3D-arr) exclusively activated by clozapine-N-oxide (CNO). By expressing M3D-arr in hERG-HEK cells and treating with CNO under various conditions, I found that M3D-arr activation increased mature hERG expression and current. Within this paradigm, M3D-arr recruited β-arrestin to the plasma membrane, and promoted the PI3K-dependent activation of Akt. I further found that the activated Akt acted through phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) and Rab11 to facilitate endosomal recycling of hERG channels to the plasma membrane.

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Knot/knotting Practice in Craft and Space is a three part research-creation project that used a study of knotting techniques to locate craft in an expanded field of spatial practice. The first part consisted of practical, studio based exercises in which I worked with various natural and synthetic fibres to learn common knotting techniques. The second part was an art historical study that combined craft and architecture history with critical theory related to the social production of space. The third part was an exhibition of drawing and knotted objects titled Opening Closures. This document unifies the lines inquiry that define my project. The first chapter presents the art historical justification for knotting to be understood as a spatial practice. Nineteenth-century German architect and theorist Gottfried Semper’s idea that architectural form is derived from four basic material practices allies craft and architecture in my project and is the point of departure from which I make my argument. In the second chapter, to consider the methodological concerns of research-creation as a form of knowledge production and dissemination, I adopt the format of an instruction manual to conduct an analysis of knot types and to provide instructions for the production of several common knots. In the third chapter, I address the formal and conceptual underpinnings of each artwork presented in my exhibition. I conclude with a proposal for an expanded field of spatial practice by adapting art critic and theorist Rosalind Krauss’s well-known framework for assessing sculpture in 1960s.

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Measuring and tracking athletic performance is crucial to an athlete’s development and the countermovement vertical jump is often used to measure athletic performance, particularly lower limb power. The linear power developed in the lower limb is estimated through jump height. However, the relationship between angular power, produced by the joints of the lower limb, and jump height is not well understood. This study examined the contributions of the kinetic value of angular power, and its kinematic component, angular velocity, of the lower limb joints to jump height in the countermovement vertical jump. Kinematic and kinetic data were gathered from twenty varsity-level basketball and volleyball athletes as they performed six maximal effort jumps in four arm swing conditions: no-arm involvement, single-non-dominant arm swing, single-dominant arm swing, and two-arm swing. The displacement of the whole body centre of mass, peak joint powers, peak angular velocity, and locations of the peaks as a percentage of the jump’s takeoff period, were computed. Linear regressions assessed the relationship of the variables to jump height. Results demonstrated that knee peak power (p = 0.001, ß = 0.363, r = 0.363), its location within takeoff period (p = 0.023, ß = -0.256, r = 0.256), and peak knee peak angular velocity (p = 0.005, ß = 0.310, r = 0.310) were moderately linked to increased jump height. Additionally, the location, within the takeoff period, of the peak angular velocities of the hip (p = 0.003, ß = -0.318, r = 0.419) and ankle (p = 0.011, ß = 0.270, r = 0.419) were positively linked to jump height. These results highlight the importance of training the velocity and timing of joint motion beyond traditional power training protocols as well as the importance of further investigation into appropriate testing protocol that is sensitive to the contributions by individual joints in maximal effort jumping.