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James Hicks

Publications and source records attributed to James Hicks.

7 recordsLinked to original sources

Space cycle: a human-powered centrifuge that can be used for hypergravity resistance training.

INTRODUCTION: This study represents the first step toward testing the hypothesis that hypergravity can be used as a unique resistance training modality for maintaining the health and function of skeletal muscle in microgravity. The primary objectives of this study were to use a human-powered short-arm centrifuge for the following: 1) to determine whether subjects could perform squats under hypergravity conditions without developing motion sickness or illusory motion; 2) to measure foot forces while performing squats under hypergravity conditions; and 3) to determine the mechanical power required to produce 1.5, 2.0, 2.5, and 3.0 Gz (head to foot) at the feet. METHODS: Subjects (22 males and 19 females) performed 10 squats each at 1.5, 2.0, 2.5, and 3.0 Gz on a human-powered short-arm centrifuge, the space cycle. Foot forces during each squat were monitored using insole force sensors, and normalized to foot forces measured at 1 Gz (relative foot forces). RESULTS: Illusory motion was minimized using a visual focal point, and did not affect the ability of subjects to perform squats. The mean standing relative foot forces at 3.0 Gz were 2.3 and 2.4 for the male and female subjects, respectively. The work rate required to power the space cycle was a linear function of Gz, and is well within the aerobic scope of untrained individuals. DISCUSSION: The findings of this study demonstrate that hypergravity can be used as an effective modality for loading skeletal muscle and that subjects can perform squat resistance exercise without developing motion sickness or illusory motion.

Adaptation, Physiological↗

Identification of alterations in DNA copy number in host stromal cells during tumor progression.

The interactions between cancer cells and the surrounding host stromal tissue play a critical role in tumor progression and metastasis, but the molecular nature of this relationship remains largely uncharacterized. Furthermore, although genetic changes of neoplastic cells in tumors contribute significantly to tumor progression, it is not known whether similar changes occur in the adjacent host stromal microenvironment and whether they contribute to or inhibit tumorigenesis. To address this question in an unbiased and genome-wide manner, we applied high-resolution DNA copy number analysis to murine stromal DNA isolated from human xenograft tumors that were formed in immunodeficient mice. We show that numerous amplifications and deletions are found within the host stromal microenvironment, suggesting that alterations in host DNA copy number can occur and may play a significant role in modifying tumor-stromal interactions.

Animals↗

Novel patterns of genome rearrangement and their association with survival in breast cancer.

Representational Oligonucleotide Microarray Analysis (ROMA) detects genomic amplifications and deletions with boundaries defined at a resolution of approximately 50 kb. We have used this technique to examine 243 breast tumors from two separate studies for which detailed clinical data were available. The very high resolution of this technology has enabled us to identify three characteristic patterns of genomic copy number variation in diploid tumors and to measure correlations with patient survival. One of these patterns is characterized by multiple closely spaced amplicons, or "firestorms," limited to single chromosome arms. These multiple amplifications are highly correlated with aggressive disease and poor survival even when the rest of the genome is relatively quiet. Analysis of a selected subset of clinical material suggests that a simple genomic calculation, based on the number and proximity of genomic alterations, correlates with life-table estimates of the probability of overall survival in patients with primary breast cancer. Based on this sample, we generate the working hypothesis that copy number profiling might provide information useful in making clinical decisions, especially regarding the use or not of systemic therapies (hormonal therapy, chemotherapy), in the management of operable primary breast cancer with ostensibly good prognosis, for example, small, node-negative, hormone-receptor-positive diploid cases.

Breast Neoplasms↗

Large-scale copy number polymorphism in the human genome.

The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.

Alleles↗

Hemodynamic and metabolic responses to hypergravity on a human-powered centrifuge.

INTRODUCTION: Microgravity causes the deconditioning of many physiological systems, and there is great interest in developing effective countermeasures. We recently developed a short-arm human-powered centrifuge, and the primary objective of this study was to assess the hemodynamic and metabolic responses to exercise under hypergravity conditions. METHODS: Phase I compared the hemodynamic and metabolic responses to 1 Gz (upright cycle ergometry) and 2 Gz conditions (Space Cycle) at the same work rate. Phase II contrasted the hemodynamic and metabolic responses at 2 and 3 Gz and at the same work rate. Phase III examined the BP and heart rate (HR) responses during passive and active centrifugation. Phase IV examined the relationship between work rate and oxygen uptake. RESULTS: In Phase I, the HR and BP responses were very similar between the two Gz conditions, with the exception that 2 Gz produced a lower diastolic BP in female subjects. In Phase II, both systolic and diastolic BPs were similar under the two different Gz conditions. However, there was a significant increase in HR at 3 Gz. In Phase III, the slope of the HR/Gz relationship was greater for passive conditions, suggesting that venous return is facilitated by the skeletal muscle pump. In Phase IV, it was found that there was a highly linear relationship between work rate and oxygen uptake. CONCLUSION: The results of this study demonstrate that exercise under low hypergravity conditions on the Space Cycle is well tolerated from a hemodynamic perspective.

Adult↗

Quantitation of seminal factor IX and factor IXa in fertile, nonfertile, and vasectomy subjects: a step closer toward identifying a functional clotting system in human semen.

Coagulation factor (F) IX is a zymogen of the plasma serine proteases, one that plays an essential role in the regulation of normal blood coagulation. Congenital defects of FIX synthesis or function cause hemophilia B (originally called hemophilia C). Factor IX is activated by Tissue Factor (TF):FVII/FVIIa complex and FXIa. Subsequent to its activation, FIXa combines with FVIIIa on the platelet surface and activates FX to FXa. Human semen forms a semi-solid gelatinous coagulum, which then liquefies within 5-20 minutes in vitro. In spite of evidence demonstrating the importance of the seminal coagulation and liquefaction process in terms of global fertility and despite the fact that the seminal coagulum is composed of fibrin-like material, it has always been addressed from the perspective of High Molecular Weight Seminal Vesicle (HMW-SV) proteins (Semenogelin I and II) and their cleavage by prostate-specific antigen rather than the conventional hemostatic factors. In this study and as part of our continuing investigation of human seminal clotting factors, we report here on seminal FIX and FIXa in normal, subfertile, and vasectomized subjects. Factors IX and FIXa were studied in a total of 119 semen specimens obtained from subfertile (n=18), normally fertile (n=34), and fertile sperm donors (n=27) and vasectomy subjects (n=40). Seminal FIX and FIXa levels were also measured in a group defined by normality in several parameters derived from the World Health Organization fertility criteria and termed "pooled normal semen parameters." Both FIX and FIXa were quantifiable in human semen. There was a wide individual variation in FIX and FIXa levels within groups. Despite the group size, statistically significant associations with fertility-related parameters were infrequent. There is a positive correlation between FIX and its activation product, FIXa (n=36; r=0.51; P <.05). Factor IXa elevation in the high sperm-clump group was significant (P <.05), and days of abstention correlated with FIXa levels (n=63; r=0.3; P <.05). The key finding of the present study is that both FIX and FIXa are present in concentrations that are not dissimilar to plasma levels and that are apparently functional, as the activated form is also present. This fact, taken with other reports of coagulation factors in semen, raises the likelihood that a functional set of hemostatic coagulation proteins exists in semen, potentially to interact with the HMW-SV proteins and the prostate-specific antigen system.

Adult↗