Trans-disciplinary research approaches: integration of fluid mechanics with cell biology

At the level of the individual molecule, outstanding discoveries leading the the 2012 Nobel Prize in Chemistry clarified G-protein coupled receptors (GPCRs) crystallographic structures and functions. Nevertheless, a large number of such receptors cooperate to ultimately determine the cell response. Henceforth, understanding their group effects becomes crucial to predict the activity of the GPCRs populating the various cell aggregates

Priorities for Governing Large-scale Infrastructure in the Tropics

National governments, International Financial Institutions, and the G-20 have intensified investments of infrastructure to boost economic growth in the wake of economic recessions and the impacts of the COVID-19 pandemic. This infrastructure enables investments in large-scale agriculture, ranching, mining, and oil and gas extraction which tend to intensify the current inequalities. These activities is slated to occur in tropical forests and on lands historically occupied by Indigenous, Afro-Descendant, Traditional and other rural peoples. This has unprecedented negative impact on the ecosystem, the biodiversity as well as on the peoples. This article calls for a \u27three-leg\u27 agenda to align infrastructure, development, and sustainability. The first one deals for the stakeholders and society at large to rethink our understanding of the relationships between infrastructure and development. The second one involves with infrastructure planning and decision-making which must be based on territorially-based planning that includes all voices that are affected by these changes. Lastly, approaches to infrastructure planning must greatly expand the scope for public debate and oversight of what infrastructure is needed

Early detection and non-steroidal anti-inflammatory drug chemoprevention of colorectal cancer

Early detection and removal of pre-cancerous adenomas and polyps through endoscopic techniques remains the most effective method for reducing the morbidity and mortality associated with colorectal cancer (CRC). Aberrant crypt foci (ACF) are microscopic surface abnormalities that are putative precursors to adenomas and CRC. ACF exhibit similar histological and molecular abnormalities to adenomas and CRC and potentially represent useful biomarkers of cancer risk. We examined ACF from subjects undergoing screening colonoscopies. Notably, no patients included in the study had a concurrent colon cancer. Genomic DNA, isolated by laser capture microdissection, was prepared from ACF and adjacent normal colonic epithelium. We show that K-ras mutations, promoter hypermethylation of RASSF1A, hMLH1 and MGMT, and microsatellite instability (MSI) can all be detected in ACF in the absence of synchronous colon tumors and are not accompanied by field effects into the surrounding epithelium. Also, all ACF with MGMT hypermethylation displayed an MSI-low phenotype. These lesions may be precursors to MSI-low CRC, providing a potential early biomarker to assess the effects of cancer prevention strategies. ^ Chemoprevention has emerged as a complementary and even first-line strategy in high-risk subjects for the prevention of CRC, using agents that target cancer-associated pathways to delay, prevent or reverse the development of adenomas. Among the most promising chemopreventive approaches are non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit the COX-1 and -2 enzymes and can induce apoptosis in colon cancer cells through multiple mechanisms. We show that the NSAID sulindac significantly inhibits small intestinal tumors in ApcMin/+ mice, but actually increases colon tumor multiplicity. Importantly, p21WAF1/cip1 and PPARγ expression were absent in colon tumors from sulindac-treated mice, suggesting that loss of these proteins is necessary for drug resistance. These observations may be translatable to designing novel clinical therapies utilizing combinations of agents that target multiple molecular pathways to overcome sulindac resistance. We also show that the NSAID ibuprofen inhibits nuclear β-catenin expression in human sporadic colon adenomas as well as in colon cancer cell lines. These data demonstrate that this drug can target a key pathway associated with colon carcinogenesis and may be a good candidate for future clinical trials for CRC chemoprevention.

Community Consent Index 2015: Oil, gas, and mining company public positions on Free, Prior, and Informed Consent

As large-scale oil, gas, and mining projects move to increasingly remote areas, they threaten to generate adverse impacts for the local communities and indigenous peoples who inhabit these areas. For many project-affected communities, Free, Prior, and Informed Consent (FPIC) represents a critical tool for ensuring that they have a say in whether and how extractive industry projects move forward. This policy briefing examines publicly available corporate commitments regarding community rights and community engagement. The results suggest increasing commitments to FPIC in the mining sector but disappointing trends in relation to the oil and gas sector and women's participation in decision making.For the launch of the report, the United Nations Special Rapporteur on the Rights of Indigenous Peoples prepared a video address for Oxfam: Message of Victoria Tauli-Corpuz for the Save the Date for the Community Consent Index launch.At the Community Consent Index launch event in Washington, DC on 23 July 2015, Oxfam staff were joined by representatives from industry and civil society on a panel discussion

Forgive and Forget: Return to Obscurity

Traditionally, if someone did some act that required forgive-ness, there were social norms in place for such forgiveness to happen. Over time, the act is also typically forgotten. And, should the person not be forgiven and the social pressure become too great, he had the option of moving to a new location for a fresh start. Yet with the Internet, these op-tions are no longer available. Worse, activities which tradi-tionally did not even require forgiveness are now impacting lives in unexpected ways, and are never forgotten. There are, however, technical approaches that could be applied to the problem, such as (1) controlling dissemination through new access control models or cryptographic approaches, (2) flooding the web with contrary information, (3) leading users to believe the information applies to someone else, (4) chang-ing the semantics of what was written, and (5) finding a way to take advantage of the inconvenient information. In this paper we discuss the social act of forgiveness, and go into detail on the possible technical approaches to “forgetting” without deleting

Water Adsorption Isotherms on Fly Ash from Several Sources

In this study, horizontal attenuated total reflection (HATR) Fourier-transform infrared (FT-IR) spectroscopy was combined with quartz crystal microbalance (QCM) gravimetry to investigate the adsorption isotherms of water on fly ash, a byproduct of coal combustion in power plants. Because of composition variability with the source region, water uptake was studied at room temperature as a function of relative humidity (RH) on fly ash from several regions: United States, India, The Netherlands, and Germany. The FT-IR spectra show water features growth as a function of RH, with water absorbing on the particle surface in both an ordered (ice-like) and a disordered (liquid-like) structure. The QCM data was modeled using the Brunauer, Emmett, and Teller (BET) adsorption isotherm model. The BET model was found to describe the data well over the entire range of RH, showing that water uptake on fly ash takes place mostly on the surface of the particle, even for poorly combusted samples. In addition, the source region and power-plant efficiency play important roles in the water uptake and ice nucleation (IN) ability of fly ash. The difference in the observed water uptake and IN behavior between the four samples and mullite (3Al₂O₃·2SiO₂), the aluminosilicate main component of fly ash, is attributed to differences in composition and the density of OH binding sites on the surface of each sample. A discussion is presented on the RH required to reach monolayer coverage on each sample as well as a comparison between surface sites of fly ash samples and enthalpies of adsorption of water between the samples and mullite

En riktig pärla – framförställda adjektivattribut i resekataloger

Avhandlingen behandlar framförställda adjektivattribut i resekataloger. Ett adjektivattribut är en adjektivfras som fungerar som bestämning på satsens huvudord. Materialet är tre resekataloger publicerade av den svenska resebyrån BIG Travel: Australienkatalogen, Europakatalogen och Golfkatalogen. Totalt omfattar materialet 60 sidor. Avhandlingen betonar annonsering och marknadsföringskommunikation – syftet var att ta reda på hur och i vilken utsträckning man använder adjektivattribut i resespråket. Jag ville också utreda hur adjektivattribut fördelar sig statistiskt, hur man använder adjektivets böjningsformer (positiv, komparativ, superlativ) samt hurdana skillnader det finns mellan de tre katalogerna i bruket av adjektivattribut. Mina forskningsmetoder var kvalitativa och kvantitativa. Varje katalog är representerad med 20 sidor. Jag excerperade alla framförställda adjektivattribut och gjorde en lista för varje katalog. I slutet av listan angav jag antalet positiv-, komparativ- och superlativformer samt vilka som är de frekventaste attributen. I resespråket är det positivformen som är oftast i bruk: det beror troligen på att man vill hålla stilen neutral och inte skapa motsättning. Det finns en betydelsefull skillnad i attributantal mellan Australienkatalogen och Europakatalogen: resmål i Europa beskrivs med tydligt fler attribut jämfört med Australien. Det totala antalet adjektivattribut ligger på 1608 (Australienkatalogen 436, Golfkatalogen 561, Europakatalogen 610). Det finns alltså en enorm variation och bland denna variation är det få attribut som upprepas ofta. Den här trenden syns i alla kataloger. Slutsatsen är att reseskribenter försöker att uttrycka saker på nya, varierande sätt, vilket kan göras med olika adjektiv. På vissa adjektivattribut litar man mer än på andra och därför används dessa attribut oftare.Siirretty Doriast

Epigenetic Alterations in RASSF1A in Human Aberrant Crypt Foci

CpG island methylation (CIM) is an epigenetic mechanism for transcriptional silencing that occurs at various stages of colon tumorigenesis. CIM has been found in serrated adenomas and hyperplastic polyps. There is also evidence for hypermethylation in aberrant crypt foci (ACF) that are found in resected colons from cancer patients. Our study addresses promoter methylation of a tumor suppressor gene, RASSF1A, within the colonic epithelium of subjects undergoing screening colonoscopies in the absence of synchronous tumors. Patients included in this study were at elevated risk for colorectal cancer (CRC) based on family history, but without a previously occurring or synchronous colon carcinoma. ACF were identified using close-focus magnifying chromendoscopy and collected by biopsy in situ. We isolated ACF and adjacent normal colonic epithelium by laser capture microdissection (LCM) and studied methylation of the RASSF1A promoter region in ACF and in adjacent normal mucosa. Expression of RASSF1A was verified using quantitative real-time polymerase chain reaction (QRT–PCR). We found that 8.6% (3 out of 35) of ACF had K-ras mutations and 24% (6 out of 25) had RASSF1A hypermethylation. Our results demonstrate that RASSF1A hypermethylation and K-ras mutations are not mutually exclusive and are present in patients at elevated risk of CRC. Importantly, CIM of RASSF1A is an early epigenetic aberration, occurring in the absence of synchronous colon tumors and is not accompanied by field effects into the surrounding epithelium