Small area estimation of general parameters with application to poverty indicators: A hierarchical Bayes approach

Poverty maps are used to aid important political decisions such as allocation of development funds by governments and international organizations. Those decisions should be based on the most accurate poverty figures. However, often reliable poverty figures are not available at fine geographical levels or for particular risk population subgroups due to the sample size limitation of current national surveys. These surveys cannot cover adequately all the desired areas or population subgroups and, therefore, models relating the different areas are needed to 'borrow strength" from area to area. In particular, the Spanish Survey on Income and Living Conditions (SILC) produces national poverty estimates but cannot provide poverty estimates by Spanish provinces due to the poor precision of direct estimates, which use only the province specific data. It also raises the ethical question of whether poverty is more severe for women than for men in a given province. We develop a hierarchical Bayes (HB) approach for poverty mapping in Spanish provinces by gender that overcomes the small province sample size problem of the SILC. The proposed approach has a wide scope of application because it can be used to estimate general nonlinear parameters. We use a Bayesian version of the nested error regression model in which Markov chain Monte Carlo procedures and the convergence monitoring therein are avoided. A simulation study reveals good frequentist properties of the HB approach. The resulting poverty maps indicate that poverty, both in frequency and intensity, is localized mostly in the southern and western provinces and it is more acute for women than for men in most of the provinces.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS702 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

hTID-1 defines a novel regulator of c-Met Receptor signaling in renal cell carcinomas

The c-Met receptor tyrosine kinase (MetR) is frequently overexpressed and constitutively phosphorylated in a number of human malignancies. Activation of the receptor by its ligand, hepatocyte growth factor (HGF), leads to increased cell proliferation, motility, survival and disruption of adherens junctions. In this study, we show that hTid-1, a DNAJ/Hsp40 chaperone, represents a novel modulator of the MetR signaling pathway. hTid-1 is a co-chaperone of the Hsp70 family of proteins, and has been shown to regulate a number of cellular signaling proteins including several involved in tumorigenic and apoptotic pathways. In this study we demonstrate that hTid-1 binds to unphosphorylated MetR and becomes dissociated from the receptor upon HGF stimulation. Overexpression of the short form of hTid-1 (hTid-1S) in 786-0 renal clear cell carcinomas (RCCs) enhances MetR kinase activity leading to an increase in HGF-mediated cell migration with no discernible effect on cell proliferation. By contrast, knockdown of hTid-1 markedly impairs both the onset and amplitude of MetR phosphorylation in response to HGF without altering receptor protein levels. hTid-1-depleted cells display defective migratory properties, coincident with inhibition of ERK/MAP kinase and STAT3 pathways. Taken together, our findings denote hTid-1S as an essential regulatory component of MetR signaling. We propose that the binding of hTid-1S to MetR may stabilize the receptor in a ligand-competent state and this stabilizing function may influence conformational changes that take place during the catalytic cycle that promote kinase activation. Given the prevalence of HGF/MetR pathway activation in human cancers, targeted inhibition of hTid-1 may be a useful therapeutic in the management of MetR-dependent malignancies

Lariat formation in splicing of pre-messenger RNA : conformation and base stacking at the lariat branch point studied using 500-MHz proton NMR and CD spectroscopy

A conformational-analysis study based on 500-MHz 1H NMR and circular dichroism (CD) has been performed on the branched trinucleotide U-5'-3'-A-2'-5'-G (1) which models the branch point in the lariat structure of Group-II excised introns. The NMR and CD results are in agreement with previous work in which it was shown that adenine 2'-5' guanine base stacking essentially determines the molecular conformation of compound 1. The ribose ring of the A residue shows a preference for the S conformation, while the riboses of U and G are highly flexible, i.e. no clear preference for N or S is observed. CD spectroscopy of 1 showed that ethylene glycol leads to disruption of adenine 2'-5' guanine stacking. Furthermore, we studied the unnatural branched trinucleotide G-5'-3'-A-2'-5'-U (2) in which U and G are reversed in comparison with compound 1. The molecular conformation of 2 is far more rigid in comparison with 1, as a result of very strong adenine 2'-5' uracil stacking. Ethylene glycol was apparently unable to facilitate de-stacking of adenine and uracil in 2. The present results show that guanosine as the 2'linked nucleotide corresponds with a clear molecular flexibility. This may be of relevance in understanding why guanosine, as the 2'-5' nucleotide, is a prerequisite for the occurrence of the second step in group-II splicing

Why do all lariat RNA introns have adenosine as the branch-point nucleotide? Conformational study of naturally-occurring branched trinucleotides and its eleven analogs by proton, phosphorus-31 NMR and CD spectroscopy

H-NMR conformational studies of six branched triribonucleotides where the branch-point nucleotide was either U, C or G (4–9) have been carried out by assigning 1H resonances through 2D NMR and then observing the temperature-dependent (i) chemical shifts of the aromatic and the anomeric protons, and (ii) shifts of the equilibrium of N and S pseudorometer popolations of each sugar moiety. The data have been compared with those of 2' ¿ 5' dimers (1–3) and other branched trimers (10–16). It emerged that all the branched trimers (4–16) adopt a conformational state closer to the corresponding 2' ¿ 5' dimers than the corresponding 3' ¿ 5' dimers. A temperature-dependent 31P chemical shift study confirmed that the conformational constraint is mainly associated with the 2' ¿ 5' phosphate linkage. Although, it appeared with the CD data that when C or especially when U is at the branch-point the overall constraint is weak. This suggests that even if these trimers adopt a 2' ¿ 5' dimer geometry, there is a lack of stabilization of strong stackings within the molecule. This is in sharp contrast with the results found for A (10–16) and to a smaller extent for G (8–9) at the branch-point

Protection of 5′‐Hydroxy Functions of Nucleosides

The 5‐hydroxy group is the primary hydroxy group of nucleosides. It is mandatory to protect 5‐hydroxyls in all methods of oligonucleotide synthesis that require nucleoside synthons. This unit discusses a wide variety of acid‐labile and base‐labile protecting groups, as well as enzymatic methods for 5‐protection and deprotection.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143732/1/cpnc0203.pd