A strategy for determining arterial blood gases on the summit of Mt. Everest

BACKGROUND: Climbers on the summit of Mt. Everest are exposed to extreme hypoxia, and the physiological implications are of great interest. Inferences have been made from alveolar gas samples collected on the summit, but arterial blood samples would give critical information. We propose a plan to insert an arterial catheter at an altitude of 8000 m, take blood samples above this using an automatic sampler, store the samples in glass syringes in an ice-water slurry, and analyze them lower on the mountain 4 to 6 hours later. RESULTS: A preliminary design of the automatic sampler was successfully tested at the White Mountain Research Station (altitude 3800 m – 4300 m). To determine how much the blood gases changed over a long period, rabbit blood was tonometered to give a gas composition close to that expected on the summit (PO(2 )4.0 kPa (30 mmHg), PCO(2 )1.3 kPa (10 mmHg), pH 7.7) and the blood gases were measured every 2 hours for 8 hours both at sea level and 3800 m. The mean changes were PO(2 )+0.3 to +0.4 kPa (+2 to +3 mmHg), PCO(2 )0 to +0.13 kPa (+1 mmHg), pH -0.02 to -0.04, base excess -0.7 to -1.2 mM. In practice the delay before analysis should not exceed 4 to 6 hours. The small paradoxical rise in PO(2 )is presumably caused mainly by contamination of the blood with air. CONCLUSION: We conclude that automatic arterial blood sampling at high altitude is technically feasible and that the changes in the blood gases over a period of several hours are acceptably small

Baby Pigs Have a Sweet Tooth!

Early gains are the cheapest. And you can get faster early gains by feeding a good pig starter. In this article, the others tell how pig starters can be made more palatable and also what should go into a good pig starter

Renminbi Internationalisation: Precedents and Implications

While it is commonly assumed that there are no known precedents against which to benchmark the internationalisation of the Renminbi (RMB), this paper argues that the PRCs own development experience provides a useful perspective on the internationalisation debate. In particular it indicates that lessons can be learnt from both the successes and the shortcomings of efforts to internationalise the RMB in the 1970s. During this period state-owned banks in Hong Kong played a central role in mobilising finance for foreign trade. Access to Hong Kong’s developed financial institutions allowed the PRC to maximise receipts from foreign trade as well as minimise the risks of undue swings in capital flows. The paper shows that although China no longer faces foreign exchange scarcity, economic reforms have not yet resolved vulnerabilities in China’s financial institutions and as such Hong Kong’s role in mitigating the risk of undue capital swings remains

Three-Nucleon Force Effects in Nucleon Induced Deuteron Breakup: Predictions of Current Models (I)

An extensive study of three-nucleon force effects in the entire phase space of the nucleon-deuteron breakup process, for energies from above the deuteron breakup threshold up to 200 MeV, has been performed. 3N Faddeev equations have been solved rigorously using the modern high precision nucleon-nucleon potentials AV18, CD Bonn, Nijm I, II and Nijm 93, and also adding 3N forces. We compare predictions for cross sections and various polarization observables when NN forces are used alone or when the two pion-exchange Tucson-Melbourne 3NF was combined with each of them. In addition AV18 was combined with the Urbana IX 3NF and CD Bonn with the TM' 3NF, which is a modified version of the TM 3NF, more consistent with chiral symmetry. Large but generally model dependent 3NF effects have been found in certain breakup configurations, especially at the higher energies, both for cross sections and spin observables. These results demonstrate the usefulness of the kinematically complete breakup reaction in testing the proper structure of 3N forces.Comment: 42 pages, 20 ps figures, 2 gif figure

Robust Antigen Specific Th17 T Cell Response to Group A Streptococcus Is Dependent on IL-6 and Intranasal Route of Infection

Group A streptococcus (GAS, Streptococcus pyogenes) is the cause of a variety of clinical conditions, ranging from pharyngitis to autoimmune disease. Peptide-major histocompatibility complex class II (pMHCII) tetramers have recently emerged as a highly sensitive means to quantify pMHCII-specific CD4+ helper T cells and evaluate their contribution to both protective immunity and autoimmune complications induced by specific bacterial pathogens. In lieu of identifying an immunodominant peptide expressed by GAS, a surrogate peptide (2W) was fused to the highly expressed M1 protein on the surface of GAS to allow in-depth analysis of the CD4+ helper T cell response in C57BL/6 mice that express the I-Ab MHCII molecule. Following intranasal inoculation with GAS-2W, antigen-experienced 2W:I-Ab-specific CD4+ T cells were identified in the nasal-associated lymphoid tissue (NALT) that produced IL-17A or IL-17A and IFN-γ if infection was recurrent. The dominant Th17 response was also dependent on the intranasal route of inoculation; intravenous or subcutaneous inoculations produced primarily IFN-γ+ 2W:I-Ab+ CD4+ T cells. The acquisition of IL-17A production by 2W:I-Ab-specific T cells and the capacity of mice to survive infection depended on the innate cytokine IL-6. IL-6-deficient mice that survived infection became long-term carriers despite the presence of abundant IFN-γ-producing 2W:I-Ab-specific CD4+ T cells. Our results suggest that an imbalance between IL-17- and IFN-γ-producing CD4+ T cells could contribute to GAS carriage in humans

Fantastically reasonable: ambivalence in the representation of science and technology in super-hero comics

A long-standing contrast in academic discussions of science concerns its perceived disenchanting or enchanting public impact. In one image, science displaces magical belief in unknowable entities with belief in knowable forces and processes and reduces all things to a single technical measure. In the other, science is itself magically transcendent, expressed in technological adulation and an image of scientists as wizards or priests. This paper shows that these contrasting images are also found in representations of science in super-hero comics, which, given their lowly status in Anglo-American culture, would seem an unlikely place to find such commonality with academic discourse. It is argued that this is evidence that the contrast constitutes an ambivalence arising from the dilemmas that science poses; they are shared rhetorics arising from and reflexively feeding a set of broad cultural concerns. This is explored through consideration of representations of science at a number of levels in the comics, with particular focus on the science-magic constellation, and enchanted and disenchanted imagery in representations of technology and scientists. It is concluded that super-hero comics are one cultural arena where the public meaning of science is actively worked out, an activity that unites “expert” and “non-expert” alike

NK-like homeodomain proteins activate NOTCH3-signaling in leukemic T-cells

<p>Abstract</p> <p>Background</p> <p>Homeodomain proteins control fundamental cellular processes in development and in cancer if deregulated. Three members of the NK-like subfamily of homeobox genes (NKLs), TLX1, TLX3 and NKX2-5, are implicated in T-cell acute lymphoblastic leukemia (T-ALL). They are activated by particular chromosomal aberrations. However, their precise function in leukemogenesis is still unclear. Here we screened further NKLs in 24 T-ALL cell lines and identified the common expression of MSX2. The subsequent aim of this study was to analyze the role of MSX2 in T-cell differentiation which may be disturbed by oncogenic NKLs.</p> <p>Methods</p> <p>Specific gene activity was examined by quantitative real-time PCR, and globally by expression profiling. Proteins were analyzed by western blot, immuno-cytology and immuno-precipitation. For overexpression studies cell lines were transduced by lentiviruses.</p> <p>Results</p> <p>Quantification of MSX2 mRNA in primary hematopoietic cells demonstrated higher levels in CD34+ stem cells as compared to peripheral blood cells and mature CD3+ T-cells. Furthermore, analysis of MSX2 expression levels in T-cell lines after treatment with core thymic factors confirmed their involvement in regulation. These results indicated that MSX2 represents an hematopoietic NKL family member which is downregulated during T-cell development and may functionally substituted by oncogenic NKLs. For functional analysis JURKAT cells were lentivirally transduced, overexpressing either MSX2 or oncogenic TLX1 and NKX2-5, respectively. These cells displayed transcriptional activation of NOTCH3-signaling, including NOTCH3 and HEY1 as analyzed by gene expression profiling and quantitative RT-PCR, and consistently attenuated sensitivity to gamma-secretase inhibitor as analyzed by MTT-assays. Furthermore, in addition to MSX2, both TLX1 and NKX2-5 proteins interacted with NOTCH-pathway repressors, SPEN/MINT/SHARP and TLE1/GRG1, representing a potential mechanism for (de)regulation. Finally, elevated expression of NOTCH3 and HEY1 was detected in primary TLX1/3 positive T-ALL cells corresponding to the cell line data.</p> <p>Conclusion</p> <p>Identification and analysis of MSX2 in hematopoietic cells implicates a modulatory role via NOTCH3-signaling in early T-cell differentiation. Our data suggest that reduction of NOTCH3-signaling by physiological downregulation of MSX2 expression during T-cell development is abrogated by ectopic expression of oncogenic NKLs, substituting MSX2 function.</p

A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12

Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales

A strategy for determining arterial blood gases on the summit of Mt. Everest.

BackgroundClimbers on the summit of Mt. Everest are exposed to extreme hypoxia, and the physiological implications are of great interest. Inferences have been made from alveolar gas samples collected on the summit, but arterial blood samples would give critical information. We propose a plan to insert an arterial catheter at an altitude of 8000 m, take blood samples above this using an automatic sampler, store the samples in glass syringes in an ice-water slurry, and analyze them lower on the mountain 4 to 6 hours later.ResultsA preliminary design of the automatic sampler was successfully tested at the White Mountain Research Station (altitude 3800 m-4300 m). To determine how much the blood gases changed over a long period, rabbit blood was tonometered to give a gas composition close to that expected on the summit (PO2 4.0 kPa (30 mmHg), PCO2 1.3 kPa (10 mmHg), pH 7.7) and the blood gases were measured every 2 hours for 8 hours both at sea level and 3800 m. The mean changes were PO2 +0.3 to +0.4 kPa (+2 to +3 mmHg), PCO2 0 to +0.13 kPa (+1 mmHg), pH -0.02 to +0.04, base excess -0.7 to +1.2 mM. In practice the delay before analysis should not exceed 4 to 6 hours. The small paradoxical rise in PO2 is presumably caused mainly by contamination of the blood with air.ConclusionWe conclude that automatic arterial blood sampling at high altitude is technically feasible and that the changes in the blood gases over a period of several hours are acceptably small