92nd Annual Meeting of the Virginia Academy of Science: Proceedings

Full proceedings of the 92nd Annual Meeting of the Virginia Academy of Science, May 13-15, 2014, Virginia Commonwealth University, Richmond, Virgini

Peer production of Open Hardware: Unfinished artifacts and architectures in the hackerspaces

The dissertation adopts the theoretical framework of peer production to investigate the phenomena of open collaboration in hacker clubs through two case studies of small scale electronic artefacts. A critique of current theories of peer production is developed from a Science and Technology Studies point of view, arguing for the primacy of social constructivism over technological determinist narratives about the role of ICTs in late capitalism in general and hacker culture in particular. Properties of disruptive novelty and spontaneous emergence routinely attributed to ICTs – and by extension to the peer production practices of hackers – are approached sceptically with a historically informed ethnographic method that concentrates on continuities and contexts.La tesis adopta el marco teórico de la producción entre iguales para investigar los fenómenos de colaboración abierta en los clubs de hackers, a través de dos estudios de caso sobre artefactos electrónicos de pequeña escala. Se desarrolla una crítica de las teorías actuales sobre la producción entre iguales desde el punto de vista de los Estudios de Ciencia y Tecnología, defendiendo la primacía de la visión constructivista social por encima de las narrativas deterministas tecnológicas en el papel de las TIC en el capitalismo tardío, en general, y en la cultura hacker en particular. Nociones como la novedad perturbadora y la aparición espontánea, atribuidas habitualmente a las TIC y, por extensión, a las prácticas de producción entre iguales de los hackers, se tratan con escepticismo mediante un método etnográfico históricamente informado, que se concentra en las continuidades y contextos.La tesi adopta el marc teòric de la producció entre iguals per investigar els fenòmens de col·laboració oberta als clubs de hackers, a través de dos estudis de cas sobre artefactes electrònics de petita escala. S’hi desenvolupa una crítica de les teories actuals sobre la producció entre iguals des del punt de vista dels Estudis de Ciència i Tecnologia, defensant la primacia de la visió constructivista social per sobre de les narratives deterministes tecnològiques en el paper de les TIC en el capitalisme tardà, en general, i en la cultura hacker en particular. Nocions com la novetat pertorbadora i l’aparició espontània, atribuïdes habitualment a les TIC i, per extensió, a les pràctiques de producció entre iguals dels hackers, es tracten amb escepticisme mitjançant un mètode etnogràfic històricament informat, que es concentra en les continuïtats i els contextos.Societat de la informació i el coneixemen

Das MYCN-Onkogen als Marker für minimale Resterkrankung und therapeutisches Ziel beim Neuroblastom

Neuroblastoma, the most common extracranial solid childhood cancer, arises from precursors of the developing sympathetic nervous system. MYCN oncogene amplification is a determinant of high risk and occurs in ~25% of neuroblastomas. Despite intensive treatment, more than half these patients succumb to their disease, implying persistence of therapy-resistant MYCN-amplified minimal residual neuroblastoma cells. This thesis proposes a comprehensive concept for the specific diagnostic detection of the MYCN amplicon and evaluates new treatment options for MYCN-amplified neuroblastoma. Disease-relevant nucleotide changes, structural gene rearrangements and copy number alterations were detected in tumor material by next-generation sequencing of a customized hybrid capture-based targeted panel. Unique MYCN amplicon breakpoints in the rearranged gene constitute a target sequence for a personalized minimal residual disease (MRD) PCR diagnostic. MYCN amplicon breakpoints in neuroblastoma cell lines and tumors were identified and recovered by individual, semi-quantitative PCR assays and Sanger sequencing. The assay was further developed for highly sensitive, real-time quantitative and droplet digital PCR detection for selected MYCN breakpoints in cell lines. MRD level detected in bone marrow aspirates collected during therapy outlined different disease courses in patients, including MRD persistence until relapse and good response to the first treatment course. Combining multi-agent chemotherapy in current high-risk protocols with indirect MYCN inhibitors provides a potential route to improve poor cure rates for MYCN-amplified neuroblastomas. Different hyperactive biological networks in MYCN-amplified neuroblastoma were tackled using small molecule inhibitors of the bromodomain and extra-terminal (BET) domain-containing protein BRD4, phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (PLK1). BET (JQ1, OTX015 and TEN-010) and kinase (alpelisib, volasertib and rigosertib) inhibitors demonstrated anti-cancer activity by diminishing viability in cell line-based drug screens at nanomolar to low micromolar concentrations. Rigosertib treatment altered PLK1 and PI3K signaling and strongly impaired the cellular ability for wound healing and colony formation. In line with in vitro observations, rigosertib reduced tumor growth in patient-derived neuroblastoma xenografts in mice. Combining OTX015 and volasertib produced synergistic anti-tumor responses in two MYCN-amplified neuroblastoma cell lines. To prevent MYCN-driven proliferation of tumor cells, further indirect MYCN targets are also being considered. This is exemplified by a substrate of PLK1, ASPM, which is elevated in MYCN-amplified primary neuroblastomas. Knockdown of ASPM, a microtubule-associated protein involved in mitotic spindle assembly, in MYCN-amplified neuroblastoma cell lines reduced viability and proliferation, accompanying a neuronal differentiation phenotype with neurite-like outgrowth, cytoskeletal changes and increased expression of differentiation markers. This study presents clinical implementable molecular diagnostics to pinpoint unique MYCN-amplified neuroblastoma cells within non-invasively accessible biopsy material, and proposes indirect small molecule-based MYCN therapies and potentially new drug targets for a personalized treatment.Das Neuroblastom, der häufigste extrakranielle solide Krebs im Kindesalter, entsteht aus Vorläuferzellen des sich entwickelnden sympathischen Nervensystems. Eine Amplifikation des MYCN-Onkogens ist ein bestimmender Faktor für ein hohes Risiko und tritt bei ~25% der Neuroblastome auf. Trotz intensiver Behandlung erliegt mehr als die Hälfte dieser Patienten ihrer Krankheit, was die Persistenz therapieresistenter, MYCN-amplifizierter minimaler Restneuroblastomzellen impliziert. Diese Arbeit stellt ein umfassendes Konzept für den spezifischen, diagnostischen Nachweis des MYCN-Amplikons vor und evaluiert neue Behandlungsoptionen für MYCN-amplifizierte Neuroblastome. Krankheitsrelevante Nukleotidveränderungen, strukturelle Genrearrangements und Kopienzahl-veränderungen wurden im Tumormaterial mit Hilfe eines maßgeschneiderten, zielgerichteten hybrid-capture-basierten Next Generation Sequencing (NGS) Assays nachgewiesen. Einzigartige MYCN-Amplikon-Bruchpunkte im rearrangierten Gen stellen eine Zielsequenz für eine personalisierte PCR-Diagnostik der minimalen Resterkrankung (MRD) dar. MYCN-Amplikon-Bruchpunkte in Neuroblastom-Zelllinien und Tumoren wurden durch individuelle, semi-quantitative PCR-Assays und Sanger Sequenzierung identifiziert und wiedererkannt. Der Assay wurde für den hochsensitiven, quantitativen Echtzeit- und digitalen Tröpfchen-PCR-Nachweis für ausgewählte MYCN-Bruchpunkte in Zelllinien weiterentwickelt. Die MRD Level, die in den während der Therapie gesammelten Knochenmarkaspiraten nachgewiesen wurden, skizzierten die verschiedenen Krankheitsverläufe bei den Patienten, einschließlich der MRD-Persistenz bis zum Rezidiv und des guten Ansprechens auf den ersten Behandlungsabschnitt. Die Kombination der Multi-Wirkstoff-Chemotherapie in den aktuellen Hochrisikoprotokollen mit indirekten MYCN-Inhibitoren stellt einen möglichen Weg dar, die schlechten Heilungsraten für MYCN-amplifizierte Neuroblastome zu verbessern. Verschiedene, hyperaktive biologische Netzwerke in MYCN-amplifizierten Neuroblastomen wurden mit niedermolekularen Inhibitoren der Bromdomäne und des extra-terminalen (BET) domänenhaltigen Proteins BRD4, der Phosphoinositid-3-Kinase (PI3K) und der polo-ähnlichen Kinase 1 (PLK1) behandelt. BET (JQ1, OTX015 und TEN-010) und Kinase-Inhibitoren (Alpelisib, Volasertib und Rigosertib) zeigten eine krebshemmende Wirkung, indem sie die Viabilität in zelllinienbasierten Wirkstoff-Screens bei nanomolaren bis niedrigen mikromolaren Konzentrationen verminderten. Die Behandlung mit Rigosertib veränderte die PLK1- und PI3K-Signalübertragung und beeinträchtigte die zelluläre Fähigkeit zur Wundheilung und Koloniebildung stark. In Übereinstimmung mit In-vitro-Beobachtungen reduzierte Rigosertib das Tumorwachstum in von Patienten stammenden Neuroblastom-Xenografts bei Mäusen. Die Kombination von OTX015 und Rigosertib erzeugte synergistische antitumorale Aktivität in zwei MYCN-amplifizierten Neuroblastom-Zelllinien. Um die MYCN-gesteuerte Proliferation von Tumorzellen zu verhindern, werden weitere indirekte MYCN-Targets in Betracht gezogen. Ein Beispiel hierfür ist ein Substrat von PLK1, ASPM, das in MYCN-amplifizierten, primären Neuroblastomen erhöht ist. Das Herunterregulieren von ASPM, einem Mikrotubuli-assoziierten Protein, das an der mitotischen Spindelanordnung beteiligt ist, führte in MYCN-amplifizierten Neuroblastom-Zelllinien zu einer verminderten Viabilität und Proliferation, was mit einem neuronalen Differenzierungsphänotyp mit neuritenartigem Auswuchs, zytoskelettalen Veränderungen und erhöhter Expression von Differenzierungsmarkern einherging. Diese Studie stellt eine klinisch umsetzbare, molekulare Diagnostik vor, um einzigartige MYCN-amplifizierte Neuroblastomzellen in nicht-invasiv zugänglichem Biopsiematerial zu detektieren, und schlägt indirekte, niedermolekular-basierende MYCN-Therapien und potenziell neue Zielmoleküle für eine personalisierte Krebsbehandlung vor

Longitudinal locomotion assessment to study neurodegeneration in C. elegans models of tauopathies

Tauopathies are a group of neurodegenerative diseases defined by the aggregation of abnormally phosphorylated protein tau. The cause for neurodegeneration observed in tauopathies is not known. The discovery of mutations in the gene encoding for tau in familial cases of FTDP-17, a hereditary tauopathy, emphasized the importance of tau in these diseases. This led to the creation of animal models expressing human tau containing mutations found in FTDP-17, recapitulating some of the aspects of the disease, including neurodegeneration and tau aggregation. Reports on the consequences of human tau expression in the neurons of C. elegans are partially contradictory, especially with regard to their locomotor phenotype. In this work, we replicated C. elegans models of tauopathies and performed immunohistochemical and locomotion assessments. We created 23 genomically integrated strains pan-neuronally expressing either wild type or mutated human tau. In agreement with published reports, immunohistochemistry revealed no difference between wild type or mutated human tau with regard to phosphorylation status. To obtain lifelong, longitudinal recordings of several hundred worms, we developed a novel worm tracking system which we termed Robot-Assisted Plate Imaging Device (RAPID). Using RAPID, we recorded the stimulated locomotor performance of human tau-expressing worms, exceeding the number of all reported observations combined by two orders of magnitude. Our data indicate no pronounced locomotor phenotype in those transgenic worms, arguing against the reported neurotoxic effect of tau in C. elegans

Graduate course catalog (Florida International University). [2020-2021]

This catalog contains a description of the various policies, graduate programs, degree requirements, and course offerings at Florida International University during the 2020-2021 academic year.https://digitalcommons.fiu.edu/catalogs/1080/thumbnail.jp

Graduate course catalog (Florida International University). [2021-2022]

This catalog contains a description of the various policies, graduate programs, degree requirements, and course offerings at Florida International University during the 2021-2022 academic year.https://digitalcommons.fiu.edu/catalogs/1082/thumbnail.jp

Life in the Cold

Preface; First and Corresponding Author Contact Information; An Evolutionary Framework for Studies of Hibernation and Short-term Torpor -- Gordon C. Grigg; Was Adaptive Hypothermia a Prerequisite for the Colonization of Madagascar By Mammals? -- Barry G. Lovegrove; No Evidence for Torpor in a Small African Mainland Primate: The Lesser Bushbaby, Galago moholi -- Nomakwezi Mzilikazi, Barry G. Lovegrove, and Judith C. Masters; The Origin of Mammalian Heterothermy: A Case for Perpetual Youth? -- Michael B. Harris, Link E. Olson, and William K. Milsom; Passive Rewarming from Torpor in Mammals and Birds: Energetic, Ecological and Evolutionary Implications -- Fritz Geiser, Rebecca L. Drury, Gerhard Kortner, Christopher Turbill, Chris R. Pavey, and R. Mark Brigham; Solar Radiation and the Energetic Cost of Rewarming from Torpor -- Andrew M. McKechnie and Blair O. Wolf; The Role of α-Linolenic Acid (18:3) in Mammalian Torpor -- Craig L. Frank, Wendy R. Hood, and Mary C. Donnelly; Heat Transfer in Humans: Lessons from Large Hibernators -- Dennis Grahn and H. Craig Heller; Factors Influencing the Timing of Dormancy in the Pocket Mouse,Perognathus longimembris -- Alan R. French; The Energetic State-dependency of Autumn Immergence in Eastern Chipmunks -- Murray M. Humphries and Brandon Rodgers; Seasonal Timing of Reproduction and Hibernation in the Edible Dormouse (Glis glis) -- Claudia Bieber and Thomas Ruf; Reproduction and Hibernation in Females: A Comparison of Two Sympatric Ground-Dwelling Rodents -- Eva Millesi, Ilse E. Hoffmann, Anna Aschauer, and Claudia Franceschini; How the Photoperiod Times the Annual Reproductive and Hibernation Cycles -- P. Pevet, M. Saboureau, and P. Klosen; Behaviour, Body Temperature, and Hibernation in Tasmanian Echidnas (Tachyglossus aculeatus) -- Stewart Nicol, Christina Vedel-Smith, and Niels A. Andersen; Metabolic Diversity in Yellow-Bellied Marmots -- Kenneth B. Armitage; Metabolic Rate Reduction During Hibernation and Daily Torpor -- Fritz Geiser; How to Enter Torpor: Thermodynamic and Physiological Mechanisms of Metabolic Depression -- Gerhard Heldmaier and Ralf Elvert; Slow Loss of Protein Integrity During Torpor: A Cause for Arousal? -- Sandra L. Martin, Timothy Dahl, and L. Elaine Epperson; A Technique for Modelling Thermoregulatory Energy Expenditure in Free-ranging Endotherms -- Craig K. R. Willis, Jeffery E. Lane, Eric T. Liknes, David L. Swanson, and R. Mark Brigham; Sex Differences in the Response of Torpor to Exogenous Corticosterone During the Onset of the Migratory Season in Rufous Hummingbirds -- Sara M. Hiebert, John C. Wingfield, Marilyn Ramenofsky, Leah Deni, and Antoinette Grafin zu Elz; The Avian Enigma: “Hibernation” by Common Poorwills (Phalaenoptilus nuttalli) -- Christopher P. Woods and R. Mark Brigham; Shivering Thermogenesis in Birds and Mammals -- Esa Hohtola; The Impact of Social Interactions on Torpor Use in Hummingbirds -- Donald Powers; The Energetics of the Rewarming Phase of Avian Torpor -- Andrew E. McKechnie and Blair O. Wolf; Insect Cold-Hardiness: New Advances Using Gene Screening Technology -- Kenneth B. Storey and David C. McMullen; Advantages and Disadvantages of Freeze-Tolerance and Freeze-Avoidance Overwintering Strategies -- Karl Erick Zachariassen, Sindre Andre Pedersen, and Erlend Kristiansen; Live and Let Diapause: Cell Cycle Regulation During Insect Overwintering -- Savvas c. Pavlides, Kenneth A. Weir, and Steven P. Tammariello; Vertebrate Freeze Tolerance: Role of Freeze-Responsive Gene Expression -- Kenneth B. Storey; Ice, Antifreeze Proteins, and Antifreeze Genes in Polar Fishes -- Arthur L. DeVries; Overwintering in Submerged Turtles -- Donald C. Jackson; Environmental Physiology of Terrestrial Hibernation in Hatchling Turtles -- Patrick J. Baker, Jon P. Costanzo, and Richard E. Lee, Jr.; Overwintering in Tegu Lizards -- Denis V. Andrade, Colin Sanders, William K. Milsom, and Augusto S. Abe; Overwintering in Cold-Submerged Frogs -- Glenn J. Tattersall; Effect of Temperature on Regular and Modified Circannual Rhythms in the European Ground Squirrel Under Free-Running Conditions -- Radoslav K. Andjus, Marina Marjanovic, and Dragoslava Zivadinovic; The Role of the Suprachiasmatic Pacemaker (SCN) in Energy Expenditure During Hibernation of Golden-mantled Ground Squirrels -- Patricia J. DeCoursey; Does Hibernation Violate Biological Laws? -- Andre Malan; The Suprachiasmatic Nucleus Influences Energy Balance of Golden-mantled Ground Squirrels During Hibernation -- Norman E. Ruby; Pesticide Effects on Body Temperature of Torpid/Hibernating Rodents (Peromyscus leucopus and Spermophilus tridecemlineatus) -- Thomas E. Tomasi, Peta Elsken-Lacy, Jean A. Perry, and Kerry Withers; Steroidogenesis and the HPA Axis During Hibernation: Differential Expression of the StAR Protein -- Matthew T. Andrews, Meaghan M. Tredrea, and Aubie K. Shaw; A Quest for the Origin of Mammalian Uncoupling Proteins -- Marton Jastroch, Sigrid Stohr, Kerry Withers, and Martine Klingenspor; Brown-Fat-Derived and Thyroid-Hormone Thermogenesis: Mechanisms and Interactions -- Jan Nedergaard, Valeria Golozoubova, and Barbara Cannon; Alterations in Localization of Hippocampal Protein Kinase Cγ (PKCγ), but Not PKCα, -β1, or –β2, in European Ground Squirrels During Hibernation -- Eddy A. Van der Zee, Jens Stieler, Roelof A. Hut, Martin de Wilde, and Arjen M. Strijkstra; The Role of the Medial Septum in the Control of Hibernation -- Irina Yu. Popova and Yurii M. Kokoz; Proteolysis in Hibernators -- Frank can Breukelen; Post-genomic Approaches to the Mechanisms of Cold Response in Fish and Hibernating Small Mammals -- Daryl Williams, L. Elaine Epperson, Andrew R. Cossins, Jane Fraser, Weizhong Li, Sandra Martin, and Andrew Y. Gracey; Use of Suppression Subtractive Hybridization to Elucidate Novel Gene Products Related to Physiological Events in a Hibernator -- Gregory L. Florant, Chris Pittman, and Scott A. Summers; Clinical Applications and Limitations of Hypothermia -- Philip E. bickler; Hibernation in Mammals: A Model for Alzheimer-type Phosphorylation of the Microtubule-associated Protein Tau -- Thomas Arendt, Jens Stieler, Arjen M. Strijkstriam Roelof A. Hut, Eddy A. Van der Zee, max Holzer, and Woldfgang Hartig; Resistance of Livers to Cold Ischemia/Reperfusion Injury During Hibernation: Involvement of Matrix Metalloproteinase and Nitric Oxide Synthase -- Hannah V. Carey, Timothy M. Piazza, Sarah E. Davis, Susanne L. Lindell, Anna Durranis, Kieran Clarke, and James H. Southard; Anti-Proliferative Effects of Plasma from Hibernating Rodents -- Donna G. Sieckmann, Decheng Cai, Howard Jaffe, John Hallenbeck, and Richard M. McCarron; Antifreeze Proteins in Terrestrial Arthropods -- John G. Duman, Valerie A. Bennett, N. Li, L. Wang, L. Huang, T. Sformo, and B.M. Barnes; Cardiac Conduction and Resistance to Ventricular Fibrillation in Siberian Hibernator Ground Squirrel Citellus undulatus -- Vadim V. Fedorov, Rubin R. Aliev, Alexey V. Glukhov, Andrey V. Resnik, Andrey Anufriev, Irina A. Ivanova, Olga V. Nakipova, Stella G. Kolaeva, Leonid V. Rosenshtraukh, and Igor R. Efimov; The Correlation Between Akt Activity and Hibernation -- Decheng Cai, Richard M. McCarron, Donna Sieckmann, and John M. Hallenbeck; Protection from Traumatic Brain Injury During Hibernation -- Kelly L. Drew, Fang Zhou, Xiongwei Zhu, Rudy J. Castellani, and Mark A. Smith; δ-Opioid Agonists Protect the Rat Liver From Cold Storage and Ischemia/Reperfusion Injury -- Thomas L. Husted, Wen-Jian Chang, Alex B. Lentsch, Steven M. Rudich;Animal Adaptability to Oxidative Stress: Gastropod Estivation and Mammalian Hibernation -- Marcelo Hermes-Lima, Gabriella R. Ramos-Vasconcelos, Luciano A. Cardoso, Adrienne l. Orr, Patricia M. Rivera, and Kelly L. Drew

Graduate course catalog (Florida International University). [2023-2024]

This catalog contains a description of the various policies, graduate programs, degree requirements, and course offerings at Florida International University during the 2023-2024 academic year.https://digitalcommons.fiu.edu/catalogs/1086/thumbnail.jp

Graduate course catalog (Florida International University). [2022-2023]

This catalog contains a description of the various policies, graduate programs, degree requirements, and course offerings at Florida International University during the 2022-2023 academic year.https://digitalcommons.fiu.edu/catalogs/1084/thumbnail.jp