An Investigation into the Physical Properties Governing the​ Coupled Harmonic Oscillator​

The coupled harmonic oscillator is an extremely important model in physics - especially in the field of solid state physics where the forces that tie atoms to their equilibrium positions are much stronger than their inter-atomic coupling forces. Given a coupled spring-mass system, we want to theoretically determine and then experimentally verify the normal frequencies involved in coupled harmonic oscillation. To do so, a coupled spring-mass system was built using an air track, carts, and PASCO motion detectors, the normal frequencies were theoretically calculated, and then we experimentally verified these normal frequencies with 4 trials: Symmetric, Antisymmetric, and two Mixed Modes

A Deep-Time Socioecosystem Framework to Understand Social Vulnerability on a Tropical Island

Archaeological research has the potential to contribute to our understanding of social vulnerability to environmental change by providing examples of change in the deep and recent past. Here we argue that human activity and historical processes deeply transform tropical environments through time, and that these changes accumulate on the landscape affecting social vulnerability. These changes, however, are not always evident due to rapid vegetation growth obscuring past human impact. Our research investigates the northernmost 25 km of the Manatí Hydrological Basin in Puerto Rico, focusing on evidence of human activity and environmental characteristics including topography, sediments and vegetation cover. The data collected, which articulates archaeological and ethnographic records, covers the span of pre-Columbian occupation of the region, through the colonial periods, and into the twentieth century. Results show that human activity through time has deeply altered the forests. The accumulation of long-term histories of biotic, abiotic and cultural dynamics affects social sensitivity and exposure. Human ingenuity can widen resilience thresholds, making long-term practices particularly important components of adaptive strategies. Deep-time socioecological perspectives can contribute to current vulnerability assessments by enhancing local and historical records that can feed predictive models and inform decision-making in the present

Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I

Umbilical cord blood (UCB) is a promising source of stem cells to use in early haematopoietic stem cell transplantation (HSCT) approaches for several genetic diseases that can be diagnosed at birth. Mucopolysaccharidosis type I (MPS-I) is a progressive multi-system disorder caused by deficiency of lysosomal enzyme α-L-iduronidase, and patients treated with allogeneic HSCT at the onset have improved outcome, suggesting to administer such therapy as early as possible. Given that the best characterized MPS-I murine model is an immunocompetent mouse, we here developed a transplantation system based on murine UCB. With the final aim of testing the therapeutic efficacy of UCB in MPS-I mice transplanted at birth, we first defined the features of murine UCB cells and demonstrated that they are capable of multi-lineage haematopoietic repopulation of myeloablated adult mice similarly to bone marrow cells. We then assessed the effectiveness of murine UCB cells transplantation in busulfan-conditioned newborn MPS-I mice. Twenty weeks after treatment, iduronidase activity was increased in visceral organs of MPS-I animals, glycosaminoglycans storage was reduced, and skeletal phenotype was ameliorated. This study explores a potential therapy for MPS-I at a very early stage in life and represents a novel model to test UCB-based transplantation approaches for various diseases

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Temperature Modulation of Electric Fields in Biological Matter

Pulsed electric fields (PEF) have become an important minimally invasive surgical technology for various applications including genetic engineering, electrochemotherapy and tissue ablation. This study explores the hypothesis that temperature dependent electrical parameters of tissue can be used to modulate the outcome of PEF protocols, providing a new means for controlling and optimizing this minimally invasive surgical procedure. This study investigates two different applications of cooling temperatures applied during PEF. The first case utilizes an electrode which simultaneously delivers pulsed electric fields and cooling temperatures. The subsequent results demonstrate that changes in electrical properties due to temperature produced by this configuration can substantially magnify and confine the electric fields in the cooled regions while almost eliminating electric fields in surrounding regions. This method can be used to increase precision in the PEF procedure, and eliminate muscle contractions and damage to adjacent tissues. The second configuration considered introduces a third probe that is not electrically active and only applies cooling boundary conditions. This second study demonstrates that in this probe configuration the temperature induced changes in electrical properties of tissue substantially reduce the electric fields in the cooled regions. This novel treatment can potentially be used to protect sensitive tissues from the effect of the PEF. Perhaps the most important conclusion of this investigation is that temperature is a powerful and accessible mechanism to modulate and control electric fields in biological tissues and can therefore be used to optimize and control PEF treatments

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Protocol for the detection and nutritional management of high-output stomas

Introduction: An issue of recent research interest is excessive stoma output and its relation to electrolyte abnormalities. Some studies have identified this as a precursor of dehydration and renal dysfunction. A prospective study was performed of the complications associated with high-output stomas, to identify their causes, consequences and management.Materials and methods: This study was carried out by a multidisciplinary team of surgeons, gastroenterologists, nutritionists and hospital pharmacists. High-output stoma (HOS) was defined as output ≥1500 ml for two consecutive days. The subjects included in the study population, 43 patients with a new permanent or temporary stoma, were classified according to the time of HOS onset as early HOS (<3 weeks after initial surgery) or late HOS (≥3 weeks after surgery). Circumstances permitting, a specific protocol for response to HOS was applied. Each patient was followed up until the fourth month after surgery.Results: Early HOS was observed in 7 (16 %) of the sample population of 43 hospital patients, and late HOS, in 6 of the 37 (16 %) non-early HOS population. By type of stoma, nearly all HOS cases affected ileostomy, rather than colostomy, patients. The patients with early HOS remained in hospital for 18 days post surgery, significantly longer than those with no HOS (12 days). The protocol was applied to the majority of EHOS patients and achieved 100 % effectiveness. 50 % of readmissions were due to altered electrolyte balance. Hypomagnesaemia was observed in 33 % of the late HOS patients.Conclusion: The protocol developed at our hospital for the detection and management of HOS effectively addresses possible long-term complications arising from poor nutritional status and chronic electrolyte alteration

Simultaneous Inhibition of mTOR-Containing Complex 1 (mTORC1) and MNK Induces Apoptosis of Cutaneous T-Cell Lymphoma (CTCL) Cells

BACKGROUND: mTOR kinase forms the mTORC1 complex by associating with raptor and other proteins and affects a number of key cell functions. mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1). In turn, p70S6K1 phosphorylates a S6 protein of the 40S ribosomal subunit (S6rp) and 4E-BP1, with the latter negatively regulating eukaryotic initiation factor 4E (eIF-4E). MNK1 and MNK2 kinases phosphorylate and augment activity of eIF4E. Rapamycin and its analogs are highly specific, potent, and relatively non-toxic inhibitors of mTORC1. Although mTORC1 activation is present in many types of malignancies, rapamycin-type inhibitors shows relatively limited clinical efficacy as single agents. Initially usually indolent, CTCL displays a tendency to progress to the aggressive forms with limited response to therapy and poor prognosis. Our previous study (M. Marzec et al. 2008) has demonstrated that CTCL cells display mTORC1 activation and short-term treatment of CTCL-derived cells with rapamycin suppressed their proliferation and had little effect on the cell survival. METHODS: Cells derived from CTCL were treated with mTORC1 inhibitor rapamycin and MNK inhibitor and evaluated for inhibition of the mTORC1 signaling pathway and cell growth and survival. RESULTS: Whereas the treatment with rapamycin persistently inhibited mTORC1 signaling, it suppressed only partially the cell growth. MNK kinase mediated the eIF4E phosphorylation and inhibition or depletion of MNK markedly suppressed proliferation of the CTCL cells when combined with the rapamycin-mediated inhibition of mTORC1. While MNK inhibition alone mildly suppressed the CTCL cell growth, the combined MNK and mTORC1 inhibition totally abrogated the growth. Similarly, MNK inhibitor alone displayed a minimal pro-apoptotic effect; in combination with rapamycin it triggered profound cell apoptosis. CONCLUSIONS: These findings indicate that the combined inhibition of mTORC1 and MNK may prove beneficial in the treatment of CTCL and other malignancies