Numerical analysis of TIROS radiation observations

June 1965.Includes bibliographical references.Sponsored by the CSU project on the Meterology of the Southeast Asia Summer Monsoon DA 28-043-AMC-01303 (E)

Tumor cell migration in complex microenvironments

Tumor cell migration is essential for invasion and dissemination from primary solid tumors and for the establishment of lethal secondary metastases at distant organs. In vivo and in vitro models enabled identification of different factors in the tumor microenvironment that regulate tumor progression and metastasis. However, the mechanisms by which tumor cells integrate these chemical and mechanical signals from multiple sources to navigate the complex microenvironment remain poorly understood. In this review, we discuss the factors that influence tumor cell migration with a focus on the migration of transformed carcinoma cells. We provide an overview of the experimental and computational methods that allow the investigation of tumor cell migration, and we highlight the benefits and shortcomings of the various assays. We emphasize that the chemical and mechanical stimulus paradigms are not independent and that crosstalk between them motivates the development of new assays capable of applying multiple, simultaneous stimuli and imaging the cellular migratory response in real-time. These next-generation assays will more closely mimic the in vivo microenvironment to provide new insights into tumor progression, inform techniques to control tumor cell migration, and render cancer more treatable.National Science Foundation (U.S.) (Graduate Research Fellowship)Charles Stark Draper Laboratory (Research and Development Program (N.DL-H-550151))National Cancer Institute (U.S.) (R21CA140096

The Relationship Between Participation in Service-learning Projects and Youth Leadership Life Skills Development Among Middle Grade Students in Selected Private Schools

Middle grades are a time of transition and development. It is during this time, as students move through grades 6, 7, and 8, that the development of life skills, especially for those who have leadership potential become increasingly important. Within these few years engaged learning and the pedagogical tool of service-learning enhances the meaning and impact of traditional course content and offers potential in helping to develop leadership skills in middle grade students. The purpose of this study was to provide evidence of the effectiveness of a community service-learning project as related to the specific development of leadership skills. The sample consisted of fifty-five eighth grade students divided into one test group and two control groups, based upon the Solomon Three Group Design. The pretest and posttest assessments made use of the four sub scales of leadership, self-confidence, cooperation, and citizenship from the Leadership and Personal Development Inventory developed by Carter (1989). Through a one-way ANOVA , no significant difference among the posttest scores of the three groups was shown at the .05 significance level. Thus, the null hypothesis, which stated that there was no significant difference in perceived self-assessed leadership potential among middle grade students who participated in a community service-learning project from those who did not participate, was accepted

Engineering of In Vitro 3D Capillary Beds by Self-Directed Angiogenic Sprouting

In recent years, microfluidic systems have been used to study fundamental aspects of angiogenesis through the patterning of single-layered, linear or geometric vascular channels. In vivo, however, capillaries exist in complex, three-dimensional (3D) networks, and angiogenic sprouting occurs with a degree of unpredictability in all x,y,z planes. The ability to generate capillary beds in vitro that can support thick, biological tissues remains a key challenge to the regeneration of vital organs. Here, we report the engineering of 3D capillary beds in an in vitro microfluidic platform that is comprised of a biocompatible collagen I gel supported by a mechanical framework of alginate beads. The engineered vessels have patent lumens, form robust ~1.5 mm capillary networks across the devices, and support the perfusion of 1 µm fluorescent beads through them. In addition, the alginate beads offer a modular method to encapsulate and co-culture cells that either promote angiogenesis or require perfusion for cell viability in engineered tissue constructs. This laboratory-constructed vascular supply may be clinically significant for the engineering of capillary beds and higher order biological tissues in a scalable and modular manner.Singapore-MIT Alliance for Research and Technolog

Prevalence of mental health disorders in inflammatory bowel disease: an Australian outpatient cohort

BACKGROUND: This study aimed to characterize prevalence of anxiety and depressive conditions and uptake of mental health services in an Australian inflammatory bowel disease (IBD) outpatient setting. METHODS: Eighty-one IBD patients (39 males, mean age 35 years) attending a tertiary hospital IBD outpatient clinic participated in this study. Disease severity was evaluated according to the Manitoba Index. Diagnosis of an anxiety or depressive condition was based upon the Mini-International Neuropsychiatric Interview and the Hospital Anxiety and Depression Scale. RESULTS: Based on Hospital Anxiety and Depression Scale subscale scores >8 and meeting Mini-International Neuropsychiatric Interview criteria, 16 (19.8%) participants had at least one anxiety condition, while nine (11.1%) had a depressive disorder present. Active IBD status was associated with higher prevalence rates across all anxiety and depressive conditions. Generalized anxiety was the most common (12 participants, 14.8%) anxiety condition, and major depressive disorder (recurrent) was the most common depressive condition reported (five participants, 6.2%). Seventeen participants (21%) reported currently seeking help for mental health issues while 12.4% were identified has having at least one psychological condition but not seeking treatment. CONCLUSION: We conclude that rates of anxiety and depression are high in this cohort, and that IBD-focused psychological services should be a key component of any holistic IBD service, especially for those identified as having active IBD

Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells

Here we describe a strategy to model blood vessel development using a well-defined induced pluripotent stem cell-derived endothelial cell type (iPSC-EC) cultured within engineered platforms that mimic the 3D microenvironment. The iPSC-ECs used here were first characterized by expression of endothelial markers and functional properties that included VEGF responsiveness, TNF-α-induced upregulation of cell adhesion molecules (MCAM/CD146; ICAM1/CD54), thrombin-dependent barrier function, shear stress-induced alignment, and 2D and 3D capillary-like network formation in Matrigel. The iPSC-ECs also formed 3D vascular networks in a variety of engineering contexts, yielded perfusable, interconnected lumen when co-cultured with primary human fibroblasts, and aligned with flow in microfluidics devices. iPSC-EC function during tubule network formation, barrier formation, and sprouting was consistent with that of primary ECs, and the results suggest a VEGF-independent mechanism for sprouting, which is relevant to therapeutic anti-angiogenesis strategies. Our combined results demonstrate the feasibility of using a well-defined, stable source of iPSC-ECs to model blood vessel formation within a variety of contexts using standard in vitro formats.National Institutes of Health (U.S.) (NIH 1UH2 TR000506-01)National Institutes of Health (U.S.) (3UH2 TR000506-02S1)National Institutes of Health (U.S.) (T32 HL007936-12)National Institutes of Health (U.S.) (RO1 HL093282)National Institutes of Health (U.S.) (R21 EB016381-01

Effects of numerical methods on comparisons between experiments and simulations of shock-accelerated mixing.

We consider the detailed structures of mixing flows for Richtmyer-Meshkov experiments of Prestridge et al. [PRE 00] and Tomkins et al. [TOM 01] and examine the most recent measurements from the experimental apparatus. Numerical simulations of these experiments are performed with three different versions of high resolution finite volume Godunov methods. We compare experimental data with simulations for configurations of one and two diffuse cylinders of SF{sub 6} in air using integral measures as well as fractal analysis and continuous wavelet transforms. The details of the initial conditions have a significant effect on the computed results, especially in the case of the double cylinder. Additionally, these comparisons reveal sensitive dependence of the computed solution on the numerical method

Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

BACKGROUND: 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. METHODS: Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg/m(2) was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg/m(2). Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg/m(2). This constituted a cycle of therapy and was repeated every 2 weeks until progression. RESULTS: The median age was 64 yrs (34–84) and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. CONCLUSIONS: This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress and may prove encouraging