Why a Particle Physicist is Interested in DNA Branch Migration

We describe an explicitly discrete model of the process of DNA branch migration. The model matches the existing data well, but we find that branch migration along long strands of DNA (N \simge 40~bp) is also well modeled by continuum diffusion. The discrete model is still useful for guiding future experiments.Comment: Talk presented at LATTICE96(theoretical developments); 3 pages, TeXsis w/ LAT96.txs (available from ftp://lifshitz.ph.utexas.edu/texsis/styles/LAT96.txs and will be a part of the next Elsevier.txs) and TXSdcol.te

Toward an International Fourth Amendment: Rethinking Searches and Seizures Abroad After Verdugo-Urquidez

Should the Fourth Amendment reach abroad to protect noncitizens when United States law enforcement agents conduct searches and seizures in a foreign state? The courts have assumed this to be a closed question since 1990, when the Supreme Court, in a broadly worded plurality opinion by Chief Justice Rehnquist, asserted that the Amendment protects only citizens and other members of the national community. However, as this Article points out, the Chief Justice\u27s plurality opinion in United States v. Verdugo-Urquidez did not represent the judgment of a majority of the Court and therefore does not foreclose continued consideration of the scope of the Fourth Amendment abroad. This Article addresses the principal questions that the Verdugo decision and subsequent scholarship have left unresolved: Does the Fourth Amendment\u27s command that searches and seizures be reasonable apply to searches of noncitizens abroad? And if so, what does it mean for a search to be reasonable in a foreign state? The author argues that the alternatives proposed by the Supreme Court in Verdugo--either confining the Amendment to the water\u27s edge or applying it in full force whenever the United States acts abroad--do not take proper account of the transnational nature of extraterritorial searches. The author proposes instead that any determination of the reasonableness of foreign searches take into account their transnational nature by reconciling United States search-and-seizure standards with either international law or the laws of the states with which the United States acts jointly abroad

Development of Feeding Cues During Infancy and Toddlerhood

To enhance responsive feeding, this study aimed to characterize the development of feeding cues during infancy and toddlerhood

A Passion for video: 25 stories about making, translating, sharing and using videos on farmer innovation

Since 2013, Access Agriculture has been training young professionals from various organisations in six African countries to make farmer-to-farmer videos. The videos are a way of moving ideas faster, and more clearly, beyond borders. The Access Agriculture website hosts the videos by these young professionals, and by other agencies, if the videos meet Access Agriculture’s quality and style standards. Access Agriculture encourages all organisations working in developing countries to invest in translating videos available on the website into any language. Access Agriculture offers a fee-based translation service to anyone interested in using quality videos in their own farmer training programmes. The stories in this volume were gathered as part of a Writeshop held in Nairobi on 9–10 November, in the context of the Access Agriculture Week 9–13 November, 201

A passion for video

Since 2013, Access Agriculture has been training young professionals from various organisations in six African countries to make farmer-to-farmer videos. The videos are a way of moving ideas faster, and more clearly, beyond borders. The Access Agriculture website hosts the videos by these young professionals, and by other agencies, if the videos meet Access Agriculture’s quality and style standards. Access Agriculture encourages all organisations working in developing countries to invest in translating videos available on the website into any language. Access Agriculture offers a fee-based translation service to anyone interested in using quality videos in their own farmer training programmes. The stories in this volume were gathered as part of a Writeshop held in Nairobi on 9–10 November, in the context of the Access Agriculture Week 9–13 November, 201

Context-Dependent Cell Cycle Checkpoint Abrogation by a Novel Kinase Inhibitor

Checkpoint kinase 1 and 2 (Chk1/Chk2), and the Aurora kinases play a critical role in the activation of the DNA damage response and mitotic spindle checkpoints. We have identified a novel inhibitor of these kinases and utilized this molecule to probe the functional interplay between these two checkpoints.Fragment screening, structure guided design, and kinase cross screening resulted in the identification of a novel, potent small molecule kinase inhibitor (VER-150548) of Chk1 and Chk2 kinases with IC(50)s of 35 and 34 nM as well as the Aurora A and Aurora B kinases with IC(50)s of 101 and 38 nM. The structural rationale for this kinase specificity could be clearly elucidated through the X-ray crystal structure. In human carcinoma cells, VER-150548 induced reduplication and the accumulation of cells with >4N DNA content, inhibited histone H3 phosphorylation and ultimately gave way to cell death after 120 hour exposure; a phenotype consistent with cellular Aurora inhibition. In the presence of DNA damage induced by cytotoxic chemotherapeutic drugs, VER-150548 abrogated DNA damage induced cell cycle checkpoints. Abrogation of these checkpoints correlated with increased DNA damage and rapid cell death in p53 defective HT29 cells. In the presence of DNA damage, reduplication could not be observed. These observations are consistent with the Chk1 and Chk2 inhibitory activity of this molecule.In the presence of DNA damage, we suggest that VER-150548 abrogates the DNA damage induced checkpoints forcing cells to undergo a lethal mitosis. The timing of this premature cell death induced by Chk1 inhibition negates Aurora inhibition thereby preventing re-entry into the cell cycle and subsequent DNA reduplication. This novel kinase inhibitor therefore serves as a useful chemical probe to further understand the temporal relationship between cell cycle checkpoint pathways, chemotherapeutic agent induced DNA damage and cell death