Columnar and highly oriented (100) BaTiO3 and SrTiO3 thin films were prepared by a chelate‐type chemical solution deposition (CSD) process by manipulation of film deposition conditions and seeded growth techniques. Randomly oriented columnar films were prepared on platinum‐coated Si substrates by a multilayering process in which nucleation of the perovskite phase was restricted to the substrate or underlying layers by control of layer thickness. The columnar films displayed improvements in dielectric constant and dielectric loss compared to the fine‐grain equiaxed films that typically result from CSD methods. Highly oriented BaTiO3 and SrTiO3 thin films were fabricated on LaAlO3 by a seeded growth process that appeared to follow a standard “two‐step” growth mechanism that has been previously reported. The film transformation process involved the bulk nucleation of BaTiO3 throughout the film, followed by the consumption of this matrix by an epitaxial overgrowth process originating at the seed layer. Both BaTiO3 and PbTiO3 seed layers were effective in promoting the growth of highly oriented (100) BaTiO3 films. Based on the various processing factors that can influence thin film microstructure, the decomposition pathway involving the formation of BaCO3 and TiO2 appeared to dictate thin film microstructural evolution.

T helper-2 (T H 2)-bias, the propensity of naive CD4 + T cells to differentiate into interleukin 4 (IL-4) secreting T H 2 cells, is a genetic trait impacting infectious, autoimmune and allergic disease susceptibility. T H 2-bias correlates with the amount of IL-4 initially secreted by newly activated T H cells that feeds back positively through the IL-4R-STAT6-GATA3 pathway to drive T H 2 development. Here, we identify Mina, a JmjC family member, as a genetic determinant of T H 2-bias. Mina specifically bound to and repressed the Il4 promoter. Mina overexpression in transgenic mice impaired Il4 expression, while its knockdown in primary CD4 + T cells led to Il4 derepression. Together, these findings provide mechanistic insight into an Il4 regulatory pathway controlling T H differentiation and genetic variation in T H 2-bias. Naive CD4 + T cells are multipotent sentinels of the immune system, poised to respond to instructive signals from antigen-presenting cells by differentiating into distinct effector cell lineages. These include T helper (T H ) 1 and T H 2 cells, differentially adapted for the control, respectively, of intra-and extracellular pathogens, in part via developmentally acquired potential for high expression of distinct cytokine genes 1 . Dysregulated CD4 + T cell development can promote susceptibility to infectious, autoimmune and allergic disease [2][3][4][5][6][7][8][9] .Interleukin 4 (IL-4) [http://www.signaling-gateway.org/molecule/query?afcsid=A001262], the canonical T H 2 effector cytokine, is also a critical developmental determinant, promoting Accession codesThe microarray data are deposited in RCAI RefDIC (URL: http://refdic.rcai.riken.jp/welcome.cgi) 50 under the following accession codes: RMSPTB007001 and RMSPTB008001. 11,12 to promote the differentiation of T H 2 cells possessing the capacity to secrete copious amounts of IL-4 10, 13-18 . Thus, regulation of autocrine IL-4 expression by activated T H cells is a key control point in T helper cell lineage commitment. Nonetheless, the molecular mechanism underlying this regulation is incompletely understood. Author contributions NIH Public AccessT H 2-bias is a complex genetic trait characterizing variation in the propensity of naive T H cells to differentiate into T H 2 (as opposed to T H 1) cells. T H 2-bias, measured experimentally as the amount of IL-4 produced by effector CD4 + T cells differentiated in vitro from naive T H cells activated under 'neutral' conditions (no exogenous cytokines added, except IL-2, and cultured without cytokine-specific antibodies), varies over 50-fold from the highproducer phenotype of BALB/c mice to the low-producer phenotype of B10.D2 mice and correlates with susceptibility to T H 2-dependent diseases such as bronchial asthma and leishmaniasis [14][15][16][19][20][21][22] . Various cellular mechanisms have been suggested as the basis for T H 2-bias, including variation in the sensitivity to prostaglandin 2 (PGE 2 )-dependent inhibition of interferon-γ (IFN-γ) production 23 , the timing of IL-1...

Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFR␣ or PDGFR␤ is embryonic lethal. In Xenopus embryos, disruption of PDGFR␣ signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFR␣ function in this process, we have analyzed all known effectorbinding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFR␣s, we have identified a role for phospholipase C␥ (PLC␥) in protecting cells from death. PDGFR␣-mediated cell survival requires PLC␥ and phosphatidylinositol 3-kinase signaling, and that PDGFR␣ with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFR␣ signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFR␣ signaling through PLC␥ and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos.apoptosis ͉ gastrulation ͉ phospholipase C␥ ͉ Xenopus

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students' learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our "formative frustration" hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of "formative frustration" is an important aspect for a successful CURE.