Developing the next "wow" fitness product

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2007.Includes bibliographical references (p. 79-80).The fitness industry has not seen a commercially successful revolution since the elliptical trainer in the mid 1990s. Newer products such as the Cybex Arc Trainer are vying to replicate this success, but are only slowly gaining acceptance. Most companies that have tried to succeed with unique products or heavy telemarketing, have failed in leaving any lasting or notable mark. In an attempt to do what others have failed in doing, the goal of this project was to develop the next revolutionary product in the industry. In the footsteps of the elliptical trainer and Bowflex, the aim is to design a brand new fitness product to create industry buzz and become a household name. The work done has gone through the usual design process, beginning with extensive research and continuing to problem selection, solution brainstorming, quantity conceptualization, quality narrowing, and concept development ...by Jorge F. Renjifo.S.B

Short and long term surface chemistry and wetting behaviour of stainless steel with 1D and 2D periodic structures induced by bursts of femtosecond laser pulses

We investigate the short and long term wettability of laser textured stainless steel samples in order to better understand the interplay between surface topography and chemistry. Very different 1D and 2D periodic as well as non-periodic surface patterns were produced by exploiting the extreme flexibility of a setup consisting of five rotating birefringent crystals, which allows generating bursts of up to 32 femtosecond laser pulses with fixed intra-burst delay of 1.5 ps. The change of the surface morphology as a function of the pulse splitting, the burst polarization state and the fluence was systematically studied. The surface topography was characterized by SEM and AFM microscopy. The laser textured samples exhibited, initially, superhydrophilic behaviour which, during exposure to ambient air, turned into superhydrophobic with an exponential growth of the static contact angle. The dynamic contact angle measurements revealed a water adhesive character which was explained by XPS analyses of the surfaces that showed an increase of hydrocarbons and more oxidized metal species with the aging. The characteristic water adhesiveness and superhydrophobicity of laser textured surfaces can be exploited for no loss droplet reversible transportation or harvesting

Development and Validation of “Hazard O’Clock”: A Home Hazard and Disaster Awareness Game

The Philippines is the fourth most disaster-prone country in the world due to its location in the Pacific Ring of Fire and Pacific Typhoon Belt. When it comes to these disasters, children below the age of 18 are considered to be among the most vulnerable. This study aimed to develop a mobile game about Disaster Risk Reduction and Management (DRRM) in the home setting that can be used as a teaching aid for children. The information integrated into the game was from different resources made by various government agencies. The Analysis, Design, Development, Implementation, and Evaluation (ADDIE) model was used in the development of the game, and game development educators and STEM educators evaluated it. Using a 5-point Likert scale survey, the game’s quality and appropriateness were evaluated for the following categories: Instructional Content, Functional Suitability, Performance Efficiency, and Usability. For each category, the mean score ratings were 4.43, 4.43, 4.80, and 4.60 respectively. Overall, the game received a rating of 4.52 indicating that it is Very Appropriate for its purpose. The research findings have shown that the game, Hazard O’Clock, could be used as a teaching aid for DRRM

Burkitt lymphoma beyond MYC translocation: N-MYC and DNA methyltransferases dysregulation

Background: The oncogenic transcription factor MYC is pathologically activated in many human malignancies. A paradigm for MYC dysregulation is offered by Burkitt lymphoma, where chromosomal translocations leading to Immunoglobulin gene-MYC fusion are the crucial initiating oncogenic events. However, Burkitt lymphoma cases with no detectable MYC rearrangement but maintaining MYC expression have been identified and alternative mechanisms can be involved in MYC dysregulation in these cases. Methods: We studied the microRNA profile of MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases in order to uncover possible differences at the molecular level. Data was validated at the mRNA and protein level by quantitative Real-Time polymerase chain reaction and immunohistochemistry, respectively. Results: We identified four microRNAs differentially expressed between the two groups. The impact of these microRNAs on the expression of selected genes was then investigated. Interestingly, in MYC translocation-negative cases we found over-expression of DNA-methyl transferase family members, consistent to hypo-expression of the hsa-miR-29 family. This finding suggests an alternative way for the activation of lymphomagenesis in these cases, based on global changes in methylation landscape, aberrant DNA hypermethylation, lack of epigenetic control on transcription of targeted genes, and increase of genomic instability. In addition, we observed an over-expression of another MYC family gene member, MYCN that may therefore represent a cooperating mechanism of MYC in driving the malignant transformation in those cases lacking an identifiable MYC translocation but expressing the gene at the mRNA and protein levels. Conclusions: Collectively, our results showed that MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases are slightly different in terms of microRNA and gene expression. MYC translocation-negative Burkitt lymphoma, similarly to other aggressive B-cell non Hodgkin's lymphomas, may represent a model to understand the intricate molecular pathway responsible for MYC dysregulation in cancer

The Origin of X-ray Emission in the Gamma-ray emitting Narrow-Line Seyfert 1 1H 0323+342

We present the results of X-ray spectral and timing analyses of the closest gamma-ray emitting narrow-line Seyfert 1 ($\gamma$-NLS1) galaxy, 1H 0323+342. We use observations from a recent, simultaneous XMM-Newton/NuSTAR campaign. As in radio-quiet NLS1s, the spectrum reveals a soft excess at low energies ($\lesssim2$ keV) and reflection features such as a broad iron K emission line. We also find evidence of a hard excess at energies above $\sim35$ keV that is likely a consequence of jet emission. Our analysis shows that relativistic reflection is statistically required, and using a combination of models that includes the reflection model relxill for the broadband spectrum, we find an inclination of $i=63^{+7}_{-5}$ degrees, which is in tension with much lower values inferred by superluminal motion in radio observations. We also find a flat ($q=2.2\pm0.3$) emissivity profile, implying that there is more reflected flux than usual being emitted from the outer regions of the disk, which in turn suggests a deviation from the thin disk model assumption. We discuss possible reasons for this, such as reflection off of a thick accretion disk geometry.Comment: Accepted for publication in MNRAS. 11 pages, 9 figures; references adde

Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development

Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein–Barr virus (EBV) infection with malaria and environmental carcinogens exposure, such as the food contaminant aflatoxin B1 (AFB1), the molecular determinants underlying the pathogenesis are not fully understood. Consistent with the role of epigenetic mechanisms at the interface between the genome and environment, AFB1 and EBV impact the methylome of respectively leukocytes and B cells specifically. Here, we conducted a thorough investigation of common epigenomic changes following EBV or AFB1 exposure in B cells. Genome-wide DNA methylation profiling identified an EBV–AFB1 common signature within the TGFBI locus, which encodes for a putative tumor suppressor often altered in cancer. Subsequent mechanistic analyses confirmed a DNA-methylation-dependent transcriptional silencing of TGFBI involving the recruitment of DNMT1 methyltransferase that is associated with an activation of the NF-κB pathway. Our results reveal a potential common mechanism of B cell transformation shared by the main risk factors of endemic BL (EBV and AFB1), suggesting a key determinant of disease that could allow the development of more efficient targeted therapeutic strategies

Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study [ISRCTN83050762]

BACKGROUND: Although serotonin reuptake inhibitors are effective in the treatment of OCD, many patients fail to respond to these agents. Growing evidence from open-label and placebo-controlled trials suggests a role for augmentation of SRIs with atypical antipsychotics in OCD. Quetiapine is generally well tolerated and previous open-label data has produced mixed results in OCD and additional controlled data is needed. METHODS: We undertook a double-blind, randomised, parallel-group, flexible-dose, placebo-controlled study of quetiapine augmentation in subjects who had responded inadequately to open-label treatment with an SRI for 12 weeks. Following informed consent and screening, forty-two subjects were randomised to either placebo or quetiapine for six weeks. RESULTS: There was significant improvement from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale in both the quetiapine and placebo groups (quetiapine, n = 20, p < 0.0001; placebo, n = 21, p = 0.001) with 40% (n = 8) of quetiapine and 47.6% (n = 10) of placebo treated subjects being classified as responders. Quetiapine did not demonstrate a significant benefit over placebo at the end of the six-week treatment period (p = .636). Similarly quetiapine failed to separate from placebo in the subgroup of subjects (n = 10) with co-morbid tics. Quetiapine was generally well tolerated. CONCLUSIONS: In this study, quetiapine augmentation was no more effective than placebo augmentation of SRIs. A number of limitations in study design make comparisons with previous studies in this area difficult and probably contributed to our negative findings. Future work in this important clinical area should address these limitations

Burkitt lymphoma with a granulomatous reaction: an M1/Th1-polarised microenvironment is associated with controlled growth and spontaneous regression

Aims: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. Methods and results: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein–Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. Conclusions: Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy

Burkitt lymphoma with granulomatous reaction: A M1/TH1‐polarized microenvironment associates with controlled growth and spontaneous regression

AIMS: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, which in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four of such cases, two of which regressed spontaneously. METHODS AND RESULTS: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV) positive with type I latency. The investigation of the tumour microenvironment (TME) showed similar features in all four cases. The analysis revealed a pro-inflammatory response triggered by Th1 lymphocytes and M1 polarized macrophages encircling the neoplastic cells with a peculiar topographic distribution. CONCLUSIONS: Our data provide an in vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights to explore new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy

The Reactome pathway knowledgebase

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation