Effect of low extracellular pH on NF-κB activation in macrophages

Objective: Many diseases, including atherosclerosis, involve chronic inflammation. The master transcription factor for inflammation is NF-κB. Inflammatory sites have a low extracellular pH. Our objective was to demonstrate the effect of pH on NF-κB activation and cytokine secretion. Methods: Mouse J774 macrophages or human THP-1 or monocyte-derived macrophages were incubated at pH 7.0–7.4 and inflammatory cytokine secretion and NF-κB activity were measured. Results: A pH of 7.0 greatly decreased pro-inflammatory cytokine secretion (TNF or IL-6) by J774 macrophages, but not THP-1 or human monocyte-derived macrophages. Upon stimulation of mouse macrophages, the levels of IκB��, which inhibits NF-κB, fell but low pH prevented its later increase, which normally restores the baseline activity of NF-κB, even though the levels of mRNA for IκB�� were increased. pH 7.0 greatly increased and prolonged NF-κB binding to its consensus promoter sequence, especially the anti-inflammatory p50:p50 homodimers. Human p50 was overexpressed using adenovirus in THP-1 macrophages and monocyte-derived macrophages to see if it would confer pH sensitivity to NF-κB activity in human cells. Overexpression of p50 increased p50:p50 DNA-binding and in THP-1 macrophages inhibited considerably TNF and IL-6 secretion, but there was still no effect of pH on p50:p50 DNA binding or cytokine secretion. Conclusion: A modest decrease in pH can sometimes have marked effects on NF-κB activation and cytokine secretion and might be one reason to explain why mice normally develop less atherosclerosis than do humans.

Of tropics, prisons and bicycles: a conversation with David Arnold

David Arnold who retired this year as the Professor of Asian and Global History at the University of Warwick remains one of the most prolific historians of colonial medicine and modern South Asia. A founding member of the subaltern studies collective, he is considered widely as a pioneer in the histories of colonial medicine, environment, penology, hunger and famines within South Asian studies and beyond. In this interview he recalls his formative inspirations, ideological motivations and reflects critically on his earlier works, explaining various shifts as well as map- ping the possible course of future work. He talks at length about his forthcoming works on everyday technology, food and monsoon Asia. Finally, he shares with us his desire of initiating work on an ambitious project about the twin themes of poison and poverty in South Asian his- tory, beginning with the Bengal famine in the late eighteenth century and ending with the Bhopal gas tragedy of the early 1980s. This conversation provides insights into the ways in which the field of medical history in modern South Asia has been shaped over the past three decades through interactions with broader discussions on agency, resistance, power, everydayness, subal- tern studies, global and spatial histories. It hints further at the newer directions which are being opened up by such persisting intellectual entanglements.

The COnvective Precipitation Experiment (COPE): investigating the origins of heavy precipitation in the southwestern UK

A recent field campaign in southwest England used numerical modeling integrated with aircraft and radar observations to investigate the dynamic and microphysical interactions that can result in heavy convective precipitation. The COnvective Precipitation Experiment (COPE) was a joint UK-US field campaign held during the summer of 2013 in the southwest peninsula of England, designed to study convective clouds that produce heavy rain leading to flash floods. The clouds form along convergence lines that develop regularly due to the topography. Major flash floods have occurred in the past, most famously at Boscastle in 2004. It has been suggested that much of the rain was produced by warm rain processes, similar to some flash floods that have occurred in the US. The overarching goal of COPE is to improve quantitative convective precipitation forecasting by understanding the interactions of the cloud microphysics and dynamics and thereby to improve NWP model skill for forecasts of flash floods. Two research aircraft, the University of Wyoming King Air and the UK BAe 146, obtained detailed in situ and remote sensing measurements in, around, and below storms on several days. A new fast-scanning X-band dual-polarization Doppler radar made 360-deg volume scans over 10 elevation angles approximately every 5 minutes, and was augmented by two UK Met Office C-band radars and the Chilbolton S-band radar. Detailed aerosol measurements were made on the aircraft and on the ground. This paper: (i) provides an overview of the COPE field campaign and the resulting dataset; (ii) presents examples of heavy convective rainfall in clouds containing ice and also in relatively shallow clouds through the warm rain process alone; and (iii) explains how COPE data will be used to improve high-resolution NWP models for operational use.

The effectiveness of protected areas in the conservation of species with changing geographical ranges

A cornerstone of conservation is the designation and management of protected areas (PAs): locations often under conservation management containing species of conservation concern, where some development and other detrimental influences are prevented or mitigated. However, the value of PAs for conserving biodiversity in the long term has been questioned given that species are changing their distributions in response to climatic change. There is a concern that PAs may become climatically unsuitable for those species that they were designated to protect, and may not be located appropriately to receive newly-colonizing species for which the climate is improving. In the present study, we analyze fine-scale distribution data from detailed resurveys of seven butterfly and 11 bird species in Great Britain aiming to examine any effect of PA designation in preventing extinctions and promoting colonizations. We found a positive effect of PA designation on species' persistence at trailing-edge warm range margins, although with a decreased magnitude at higher latitudes and altitudes. In addition, colonizations by range expanding species were more likely to occur on PAs even after altitude and latitude were taken into account. PAs will therefore remain an important strategy for conservation. The potential for PA management to mitigate the effects of climatic change for retracting species deserves further investigation.

Utveckling av en SMS-tjänst med David Siegels modell

Det satsas allt mer på mobiltelefontjänster idag och snabbt växande är sådana tjänster som involverar SMS. Högskolans Bibliotek på Campus Borlänge har ett intresse av att kunna erbjuda sina låntagare en påminnelsetjänst för försenade eller reserverade b��cker.Vi fick i uppgift att under vårt examensarbete ta fram en prototyp av en SMS-tjänst åt biblioteket. Den skall påminna låntagare om att en bok är försenad och/eller att en reserverad bok har inkommit. Denna tjänst skall hjälpa biblioteket att nå ut med informationen till låntagaren via ett SMS till mobiltelefonen.Denna rapport är en undersökning av vilka delkomponenter i David Siegels modell som anses lämpade respektive inte lämpade för utveckling av ny funktionalitet som innefattar SMS till en befintlig webbplats. En förklaring finns varför vissa är lämpade och andra inte.I rapporten förklaras också att SMS-funktionen är en IT-tjänst, närmare bestämt en SMS-tjänst. Tjänsten utvecklas utifrån David Siegels modell och genom en prövning mot empirin har vi kommit fram till vilka delkomponenter som är lämpliga respektive inte lämpliga för utveckling av en SMS- tjänst.Vid utvecklingen av denna SMS-tjänst fungerade Siegels modell tillfredsställande. Om man använder de dokument vi anser vara viktiga för denna typ av utveckling kan vi rekommendera denna modell för framtida tilläggstjänster som innefattar SMS.

Professor David Firmage, Department of Biology and Environmental Studies

Professor Emeritus David Firmage, Department of Biology and Environmental Studies. Reading Looking for Alaska by Peter Jenkins

A Reading by David Wojhan

A Reading by David Wojhan on January 1, 1983.

A Reading by David Ray

A reading delivered at Colby College in 1976.

New York Trade School Graduates David J. Stevens and Ernest Fitzgerald

David J. Stevens and Ernest Fitzgerald were 1948 graduates of the Plumbing Department at the New York Trade School and are pictured with a truck from their successful D.H. Stevens Company in Washington, DC. Original caption reads, "David J. Stevens - Plumbing 1948, is shown here with Ernest Fitzgerald - Plumbing 1948, with two of their thirteen pieces of equipment necessary to satisfy 650 calls per month. David Stevens is the third generation to have graduated from Plumbing." Black and white photograph with caption adhered to reverse.

Graduate of the Sheet Metal Sheet Metal Department David Harning

David Harning graduated from the Sheet Metal Department in 1957 and is shown in his position as Sheet Metal Cutter at the Triangle Sheet Metal Works Inc. Original caption reads, "David Harning - Sheet Metal 1957, is shown at his bench where he lays out all types of Sheet Metal pieces. These pieces will be constructed by other Sheet Metal Workers." Black and white photograph with captioned adhered to reverse.

Point of View: The Lesson of David Kato

Gay activist from Uganda had applied for an Oak Fellowship at Colby; his murder should serve as a warning of the sometimes dangerous power of Americans abroad. Ellen Morris ’11 on “knowing” slain gay-rights activist David Kato.

Spring 2010: David vs. Goliath

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