4,294 research outputs found

    Civilized settlement & nomadic dominion: Inter-tribal treaties and grand councils between the Cherokee and Osage Indians, 1817-1828

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    The inter-tribal councils and treaties of 1818 and 1822 between the Cherokee and Osage tribes in the Missouri and Arkansas territories are the focus of the thesis. The tribes that migrated into western territories fled warfare and American pressure for tribal lands and found the landscapes populated by vastly different tribes. Inter-tribal diplomacy is one potentially vital factor for Cherokee relocation into Osage country. Cherokee survival within Osage country hinged on councils and diplomacy that attempted to stop the violence that arose due to the use of hunting grounds and retaliatory murders. Cherokee and Osage diplomacy in the western territories of Missouri and Arkansas Territory occurred as migrant Native Americans headed into the western regions. The growing pressures for resources called attention to the need for creating diplomatic meetings to quell inter-tribal violence and misunderstandings between tribes. The thesis examines Cherokee and Osage inter-tribal diplomacy by tracing how the Cherokee in the western territories dealt with the issues of violence and warfare with the Osage Nation. The thesis concludes with the Cherokees and Osages having attempted inter-tribal diplomacy and the failures of the peace accords. The Cherokee-Osage inter-tribal warfare provided American settlers with examples used to justify greater United States military occupation in the western territories. The Cherokee and Osage councils and treaties of 1818 and 1822 are crucial years for inter-tribal diplomacy between the two nations and highlight the history of Native peoples in the territories created by the United States

    Imatinib administration in two patients with liver metastases from GIST and severe jaundice

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    Imatinib is the only effective and approved systemic therapy for the treatment of patients with advanced gastrointestinal stromal tumours (GISTs). Although metastases from GISTs most commonly involve the liver, yielding hyperbilirubinaemia, very few data on imatinib administration in subjects with jaundice are available. We provide evidence that imatinib tolerability was not adversely affected by jaundice in two patients with advanced GIST

    Contribution of Matrix Metalloproteinase-9 to Cerebral Edema and Functional Outcome following Experimental Subarachnoid Hemorrhage

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    Background: Cerebral edema is an important risk factor for death and poor outcome following subarachnoid hemorrhage (SAH). However, underlying mechanisms are still poorly understood. Matrix metalloproteinase (MMP)-9 is held responsible for the degradation of microvascular basal lamina proteins leading to blood-brain barrier dysfunction and, thus, formation of vasogenic cerebral edema. The current study was conducted to clarify the role of MMP-9 for the development of cerebral edema and for functional outcome after SAH. Methods: SAH was induced in FVB/N wild-type (WT) or MMP-9 knockout (MMP-9(-/-)) mice by endovascular puncture. Intracranial pressure (ICP), regional cerebral blood flow (rCBF), and mean arterial blood pressure (MABP) were continuously monitored up to 30 min after SAH. Mortality was quantified for 7 days after SAH. In an additional series neurological function and body weight were assessed for 3 days after SAH. Subsequently, ICP and brain water content were quantified. Results: Acute ICP, rCBF, and MABP did not differ between WT and MMP-9(-/-) mice, while 7 days' mortality was lower in MMP-9(-/-) mice (p = 0.03; 20 vs. 60%). MMP-9(-/-) mice also exhibited better neurological recovery, less brain edema formation, and lower chronic ICP. Conclusions: The results of the current study suggest that MMP-9 contributes to the development of early brain damage after SAH by promoting cerebral edema formation. Hence, MMP-9 may represent a novel molecular target for the treatment of SAH. Copyright (C) 2011 S. Karger AG, Base

    An Augmented Interface to Display Industrial Robot Faults

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    Technology advancement is changing the way industrial factories have to face an increasingly complex and competitive market. The fourth industrial revolution (known as industry 4.0) is also changing how human workers have to carry out tasks and actions. In fact, it is no longer impossible to think of a scenario in which human operators and industrial robots work side-by-side, sharing the same environment and tools. To realize a safe work environment, workers should trust robots as well as they trust human operators. Such goal is indeed complex to achieve, especially when workers are under stress conditions, such as when a fault occurs and the human operators are no longer able to understand what is happening in the industrial manipulator. Indeed, Augmented Reality (AR) can help workers to visualize in real-time robots’ faults. This paper proposes an augmented system that assists human workers to recognize and visualize errors, improving their awareness of the system. The system has been tested using both an AR see-through device and a smartphone

    Incoherent non-Fermi liquid scattering in a Kondo lattice

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    One of the most notorious non-Fermi liquid properties of both archetypal heavy-fermion systems [1-4] and the high-Tc copper oxide superconductors [5] is an electrical resistivity that evolves linearly with temperature, T. In the heavy-fermion superconductor CeCoIn5 [5], this linear behaviour was one of the first indications of the presence of a zero-temperature instability, or quantum critical point. Here, we report the observation of a unique control parameter of T-linear scattering in CeCoIn5, found through systematic chemical substitutions of both magnetic and non-magnetic rare-earth, R, ions into the Ce sub-lattice. We find that the evolution of inelastic scattering in Ce1-xRxCoIn5 is strongly dependent on the f-electron configuration of the R ion, whereas two other key properties -- Cooper-pair breaking and Kondo-lattice coherence -- are not. Thus, T-linear resistivity in CeCoIn5 is intimately related to the nature of incoherent scattering centers in the Kondo lattice, which provides insight into the anomalous scattering rate synonymous with quantum criticality [7].Comment: 4 pages, 3 figures (published version

    Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

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    Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

    A pilot randomised controlled trial investigating a mindfulness-based stress reduction (MBSR) intervention in individuals with pulmonary arterial hypertension (PAH): the PATHWAYS study

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    Background: Pulmonary arterial hypertension (PAH) is an uncommon condition with progressive heart failure and premature death. Treatment costs up to £120,000 per patient per year, and the psychological burden of PAH is substantial. Mindfulness-based stress reduction (MBSR) is an intervention with the potential to reduce this burden, but to date, it has not been applied to people with pulmonary hypertension. We wished to determine whether a trial of MBSR for people with PAH would be feasible. Methods: A customised gentle MBSR programme of eight sessions was developed for people with physical disability due to PAH, and they were randomised to group-based MBSR or treatment as usual. The completeness of outcome measures including Beck Anxiety Index, Beck Depression Inventory and standard physical assessment at 3 months after randomisation were recorded. Health care utilisation was measured. Attendance at the sessions and the costs involved in delivering the intervention were assessed. Semi-structured interviews were conducted to explore the acceptability of the MBSR intervention and when appropriate the reasons for trial non-participation. Results: Fifty-two patients were recruited, but only 34 were randomised due to patients finding it difficult to travel to sessions. Twenty-two completed all questionnaires and attended all clinics, both routine and additional in order to collect outcomes measures. The MSBR sessions were delivered in Bristol, Cardiff and London, costing, on average, between £2234 (Cardiff) and £4128 (London) per patient to deliver. Attendance at each session averaged between two patients in Bristol and Cardiff and three in London. For those receiving treatment as usual, clinician blinding was achievable. Interviews revealed that people who attended MBSR found it interesting and helpful in managing their symptoms and minimising the psychological component of their disease. Conclusions: We found that attendance at group MBSR was poor in people with chronic PAH within the context of a trial. Achieving better MBSR intervention attendance or use of an Internet-based programme might maximise the benefit of MBSR

    Structure and mechanism of human DNA polymerase η

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    The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

    Thermodynamic analysis of the Quantum Critical behavior of Ce-lattice compounds

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    A systematic analysis of low temperature magnetic phase diagrams of Ce compounds is performed in order to recognize the thermodynamic conditions to be fulfilled by those systems to reach a quantum critical regime and, alternatively, to identify other kinds of low temperature behaviors. Based on specific heat (CmC_m) and entropy (SmS_m) results, three different types of phase diagrams are recognized: i) with the entropy involved into the ordered phase (SMOS_{MO}) decreasing proportionally to the ordering temperature (TMOT_{MO}), ii) those showing a transference of degrees of freedom from the ordered phase to a non-magnetic component, with their Cm(TMO)C_m(T_{MO}) jump (ΔCm\Delta C_m) vanishing at finite temperature, and iii) those ending in a critical point at finite temperature because their ΔCm\Delta C_m do not decrease with TMOT_{MO} producing an entropy accumulation at low temperature. Only those systems belonging to the first case, i.e. with SMO0S_{MO}\to 0 as TMO0T_{MO}\to 0, can be regarded as candidates for quantum critical behavior. Their magnetic phase boundaries deviate from the classical negative curvature below T2.5T\approx 2.5\,K, denouncing frequent misleading extrapolations down to T=0. Different characteristic concentrations are recognized and analyzed for Ce-ligand alloyed systems. Particularly, a pre-critical region is identified, where the nature of the magnetic transition undergoes significant modifications, with its Cm/T\partial C_m/\partial T discontinuity strongly affected by magnetic field and showing an increasing remnant entropy at T0T\to 0. Physical constraints arising from the third law at T0T\to 0 are discussed and recognized from experimental results
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