The rockefeller university

As nanolithography becomes increasingly important in technology and daily life, a variety of inexpensive and creative methods toward communicating the concepts underpinning these processes in the classroom are necessary. An experiment is described that uses simple CD-Rs, C-clamps, an oven, and a freezer to provide concrete examples and insights into the chemistry and principles of nanolithography. The experiment also has flexibility, making it suitable for a range of classroom levels from high school to more advanced labs in college. Because CD-Rs are composed of grooves of polycarbonate, the experiment provides a basis for discussions and exploration into the chemistry and physics of polymers on the nanoscale.

P>From its inception in 1925 through the almost 30 years that it carried the title of Annals of Eugenics, this journal published numerous articles on the statistical aspects of genetic linkage analysis and its applications to family pedigree data. This overview discusses 40 papers on linkage analysis published in the Annals.

Regulatory T cells (Tregs) contribute significantly to the tolerogenic nature of the liver. The mechanisms, however, underlying liver-associated Treg induction are still elusive. We recently identified the vitamin A metabolite, retinoic acid (RA), as a key controller that promotes TGF-beta-dependent Foxp3(+) Treg induction but inhibits TGF-beta-driven Th17 differentiation. To investigate whether the RA producing hepatic stellate cells (HSC) are part of the liver tolerance mechanism, we investigated the ability of HSC to function as regulatory APC. Different from previous reports, we found that highly purified HSC did not express costimulatory molecules and only upregulated MHC class II after in vitro culture in the presence of exogenous IFN-gamma. Consistent with an insufficient APC function, HSC failed to stimulate naive OT-II TCR transgenic CD4(+)T cells and only moderately stimulated alpha-galactosylceramide-primed invariant NKT cells. In contrast, HSC functioned as regulatory bystanders and promoted enhanced Foxp3 induction by OT-II TCR transgenic T cells primed by spleen dendritic cells, whereas they greatly inhibited the Th17 differentiation. Furthermore, the regulatory bystander capacity of the HSC was completely dependent on their ability to produce RA. Our data thus suggest that HSC can function as regulatory bystanders, and therefore, by promoting Tregs and suppressing Th17 differentiation, they might represent key players in the mechanism that drives liver-induced tolerance. The Journal of Immunology, 2011, 186: 5549-5555.

The spectra of strange hadrons are measured in proton-proton collisions, recorded by the CMS experiment at the CERN LHC, at centre-of-mass energies of 0.9 and 7TeV. The K(S)(0), A, and Xi(-) particles and their antiparticles are reconstructed from their decay topologies and the production rates are measured as functions of rapidity and transverse momentum, p(T). The results are compared to other experiments and to predictions of the PYTHIA Monte Carlo program. The p(T) distributions are found to differ substantially from the PYTHIA results and the production rates exceed the predictions by up to a factor of three.

B cell-specific coactivator OCA-B, together with Oct-1/2, binds to octamer sites in promoters and enhancers to activate transcription of immunoglobulin (Ig) genes, although the mechanisms underlying their roles in enhancer-promoter communication are unknown. Here, we demonstrate a direct interaction of OCA-B with transcription factor TFII-I, which binds to DICE elements in Igh promoters, that affects transcription at two levels. First, OCA-B relieves HDAC3-mediated Igh promoter repression by competing with HDAC3 for binding to promoter-bound TFII-I. Second, and most importantly, Igh 3' enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. These and other results reveal an important function for OCA-B in Igh 3' enhancer function in vivo and strongly favor an enhancer mechanism involving looping and facilitated factor recruitment rather than a tracking mechanism.

Over the past decade, it has become increasingly clear that many tissues have regenerative capabilities. The challenge has been to find the stem cells or progenitors that are responsible for tissue renewal and repair. The revolution in technological advances that permit sophisticated spatial, temporal and kinetic analyses of stem cells has allowed stem cell hunters to ferret out where stem cells live, and to monitor when they come and go from these hiding places.

We present a search for a new particle T' decaying to top quark via T' -> t + X, where X is an invisible particle. In a data sample with 4.8 fb(-1) of integrated luminosity collected by the CDF II detector at Fermilab in p (p) over bar collisions with root s = 1.96 TeV, we search for pair production of T' in the lepton + jets channel, p (p) over bar -> t (t) over bar + X + X -> lvbqq'b + X + X. We interpret our results primarily in terms of a model where T' are exotic fourth generation quarks and X are dark matter particles. Current direct and indirect bounds on such exotic quarks restrict their masses to be between 300 and 600 GeV/c(2), the dark matter particle mass being anywhere below m(T'). The data are consistent with standard model expectations, and we set 95% confidence level limits on the generic production of T'(T) over bar -> t (t) over bar + X + X. For the dark matter model we exclude T' at 95% confidence level up to m(T)' = 360 GeV/c(2) for m(X) <= 100 GeV/c(2).

53BP1 is a DNA damage protein that forms phosphorylated H2AX (gamma-H2AX) dependent foci in a 1 Mb region surrounding DNA double-strand breaks (DSBs). In addition, 53BP1 promotes genomic stability by regulating the metabolism of DNA ends. We have compared the joining rates of paired DSBs separated by 1.2 kb to 27 Mb on chromosome 12 in the presence or absence of 53BP1. 53BP1 facilitates joining of intrachromosomal DSBs but only at distances corresponding to gamma-H2AX spreading. In contrast, DNA end protection by 53BP1 is distance independent. Furthermore, analysis of 53BP1 mutants shows that chromatin association, oligomerization, and N-terminal ATM phosphorylation are all required for DNA end protection and joining as measured by immunoglobulin class switch recombination. These data elucidate the molecular events that are required for 53BP1 to maintain genomic stability and point to a model wherein 53BP1 and H2AX cooperate to repress resection of DSBs.

We developed a general cell-based photocrosslinking approach to investigate the binding interfaces necessary for the formation of G protein-coupled receptor (GPCR) signaling complexes. The two photoactivatable unnatural amino acids p-benzoyl-l-phenylalanine and p-azido-l-phenylalanine were incorporated by amber codon suppression technology into CXC chemokine receptor 4 (CXCR4). We then probed the ligand-binding site for the HIV-1 coreceptor blocker, T140, using a fluorescein-labeled T140 analogue. Among eight amino acid positions tested, we found a unique UV-light-dependent crosslink specifically between residue 189 and T140. These results are evaluated with molecular modeling using the crystal structure of CXCR4 bound to CVX15.

Dijet angular distributions are measured over a wide range of dijet invariant masses in pp collisions at root s = 7 TeV, at the CERN LHC. The event sample, recorded with the CMS detector, corresponds to an integrated luminosity of 36 pb(-1). The data are found to be in good agreement with the predictions of perturbative QCD, and yield no evidence of quark compositeness. With a modified frequentist approach, a lower limit on the contact interaction scale for left-handed quarks of Lambda(+) = 5.6 TeV (Lambda(-) = 6.7 TeV) for destructive (constructive) interference is obtained at the 95% confidence level.