Mapping the human cortical surface by combining quantitative T(1) with retinotopy

We combined quantitative relaxation rate (R1= 1/T1) mapping-to measure local myelination-with fMRI-based retinotopy. Gray-white and pial surfaces were reconstructed and used to sample R1 at different cortical depths. Like myelination, R1 decreased from deeper to superficial layers. R1 decreased passing from V1 and MT, to immediately surrounding areas, then to the angular gyrus. High R1 was correlated across the cortex with convex local curvature so the data was first "de-curved". By overlaying R1 and retinotopic maps, we found that many visual area borders were associated with significant R1 increases including V1, V3A, MT, V6, V6A, V8/VO1, FST, and VIP. Surprisingly, retinotopic MT occupied only the posterior portion of an oval-shaped lateral occipital R1 maximum. R1 maps were reproducible within individuals and comparable between subjects without intensity normalization, enabling multi-center studies of development, aging, and disease progression, and structure/function mapping in other modalities

It's Time to End Single-Family Zoning

Local planning in the United States is unique in the amount of land it reserves for detached single-family homes. This privileging of single-family homes, normally called R1 zoning, exacerbates inequality and undermines efficiency. R1’s origins are unpleasant: Stained by explicitly classist and implicitly racist motivations, R1 today continues to promote exclusion. It makes it harder for people to access high-opportunity places, and in expensive regions it contributes to shortages of housing, thereby benefiting homeowners at the expense of renters and forcing many housing consumers to spend more on housing. Stacked against these drawbacks, moreover, are a series of only weak arguments in R1’s favor about preferences, aesthetics, and a single-family way of life. We demonstrate that these pro-R1 concerns are either specious, or can be addressed in ways less socially harmful than R1. Given the strong arguments against R1 and the weak arguments for it, we contend planners should work to abolish R1 single-family zoning

A modified R1 X R1 method for helioseismic rotation inversions

We present an efficient method for two dimensional inversions for the solar rotation rate using the Subtractive Optimally Localized Averages (SOLA) method and a modification of the R1 X R1 technique proposed by Sekii (1993). The SOLA method is based on explicit construction of averaging kernels similar to the Backus-Gilbert method. The versatility and reliability of the SOLA method in reproducing a target form for the averaging kernel, in combination with the idea of the R1 X R1 decomposition, results in a computationally very efficient inversion algorithm. This is particularly important for full 2-D inversions of helioseismic data in which the number of modes runs into at least tens of thousands.Comment: 12 pages, Plain TeX + epsf.tex + mn.te

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium : putative role of interleukin-1ß

CRH targets the human myometrium during pregnancy. The efficiency of CRH actions is determined by expression of functional receptors (CRH-R), which are dynamically regulated. Studies in myometrial tissue biopsies using quantitative RT-PCR demonstrated that the onset of labor, term or preterm, is associated with a significant 2- to 3-fold increase in CRH-R1 mRNA levels. Detailed analysis of myometrial CRH-R1 mRNA variants showed a decline of the pro-CRH-R1 mRNA encoding the CRH-R1ß variant during labor and increased mRNA levels of CRH-R1d mRNA. Studies in myometrial cells identified IL-1ß as an important regulator of myometrial CRH-R1 gene expression because prolonged treatment of myometrial cells with IL-1ß (1 ng/ml) for 18 h induced expression of CRH-R1 mRNA levels by 1.5- to 2-fold but significantly attenuated CRH-R1ß mRNA expression by 70%. In contrast, IL-1ß had no effect on CRH-R1d mRNA expression. Studies using specific inhibitors suggest that ERK1/2, p38 MAPK, and downstream nuclear translocation of nuclear factor-B mediate IL-1ß effects on myometrial CRH-R1 gene. However, the increased CRH-R1 mRNA expression was associated with a dampening of the receptor efficacy to activate the adenylyl cyclase/cAMP signaling cascade. Thus, our findings suggest that IL-1ß is an important regulator of CRH-R1 expression and functional activity, and this interaction might play a role in the transition of the uterus from quiescence to active contractions necessary for the onset of parturition

Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI.

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). delta R1 was repeatedly measured over 30 min. Gd-BOPTA caused greater delta R1 for blood and myocardium than did Gd-DTPA; clearance of both agents from normal- and infarcted myocardium was similar to blood clearance; plots of delta R1 myocardium/delta R1 blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTPA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater delta R1 than Gd-DTPA in regions which contain serum albumin

Facile synthesis of isoxazoles and pyrazoles from ß-diketohydrazones

Indexación: ScieloNew 3,5-dimethyl-4-[(E)-4-(R1-phenyl)diazenyl]isoxazoles and 3,5-dimethyl-1-(R2-phenyl)-4-[(E)-(R1-phenyl)diazenyl]-1H-pyrazoles may be obtained by reaction of 3-[2-(R1-phenyl)hydrazono)]pentane-2,4-dione with H2NOH-HCl and R2-4-C6H4-NHNH2, respectively. The reactions were performed in ethanol as solvent and catalyzed by glacial acetic acid.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072009000300013&nrm=is

<i>N,N</i>-bis-(dimethylfluorosilylmethyl)amides of <i>N</i>-organosulfonylproline and sarcosine: synthesis, structure, stereodynamic behaviour and <i>in silico</i> studies

(O→Si)-Chelate difluorides R3R2NCH(R1)C(O)N(CH2SiMe2F)2 (9a–c, R1R2 = (CH2)3, R3 = Ms (a), Ts (b); R1 = H, R2 = Me, R3 = Ms (c)), containing one penta- and one tetracoordinate silicon atoms were synthesized by silylmethylation of amides R3R2NCH(R1)C(O)NH2, subsequent hydrolysis of unstable intermediates R3R2NCH(R1)C(O)N(CH2SiMe2Cl)2 (7a–c) into 4-acyl-2,6-disilamorpholines R3R2NCH(R1)C(O)N(CH2SiMe2O)2 (8a–c) and the reaction of the latter compounds with BF3·Et2O. The structures of disilamorpholines 8a,c and difluoride 9a were confirmed by an X-ray diffraction study. According to the IR and NMR data, the O→Si coordination in solutions of these compounds was weaker than that in the solid state due to effective solvation of the Si–F bond. A permutational isomerisation involving an exchange of equatorial Me groups at the pentacoordinate Si atom in complexes 9a–c was detected, and its activational parameters were determined by 1H DNMR. In silico estimation of possible pharmacological effects and acute rat toxicity by PASS Online and GUSAR Online services showed a potential for their further pharmacological study