Transfer formalisms

We discuss some different ideas about the sort of formalism appropriate for translation (more specifically, transfer) that have been explored within Eurotra. The intention is not to evaluate these different ideas, but to outline the issues of general interest and relevance that they raise. Section 1 describes some common assumptions, section 2 describes the different ways they have been interpreted, and section 3 considers some further implications.     

Critical issues in the instruction of the learning disabled.

This article addresses several issues and trends relevant to the instruction of the learning disabled (LD). Although the concept of LD has received some support as a diagnostic category, limited data exist that demonstrate the effect of different instructional methods on the academic deficits of LD students. In this review, attempts to remediate LD are examined according to the adequacy of the theoretical context that guides the instruction and the efficacy and validity of the remediation procedures. Selected studies representative of medical, psychoeducational, neuropsychological, behavioral, linguistic, and cognitive treatment approaches are reviewed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Effectiveness of Early Head Start for 3-Year-Old Children and Their Parents: Lessons for Policy and Programs.

Early Head Start, a federal program begun in 1995 for low-income pregnant women and families with infants and toddlers, was evaluated through a randomized trial of 3,001 families in 17 programs. Interviews with primary caregivers, child assessments, and observations of parent-child interactions were completed when children were 3 years old. Caregivers were diverse in race-ethnicity, language, and other characteristics. Regression-adjusted impact analyses showed that 3-year-old program children performed better than did control children in cognitive and language development, displayed higher emotional engagement of the parent and sustained attention with play objects, and were lower in aggressive behavior. Compared with controls, Early Head Start parents were more emotionally supportive, provided more language and learning stimulation, read to their children more, and spanked less. The strongest and most numerous impacts were for programs that offered a mix of home-visiting and center-based services and that fully implemented the performance standards early. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physical and Sexual Intimate Partner Violence Among Women in Methadone Maintenance Treatment.

Although several studies have examined the relationship between intimate partner violence (IPV) and drug use among women in drug treatment programs, more information is needed to delineate differences, as a function of the specific drug used. Data from a random sample of 416 women attending methadone programs were analyzed to elucidate the differential associations between IPV and use of the following: marijuana only, cocaine only, heroin only, or cocaine and heroin. Prevalence of IPV among this sample far exceeded estimates from the general population. After adjusting for sociodemographic variables, use of cocaine only was significantly associated with an increased likelihood of experiencing IPV compared with no drug use. Similar results were found for women using both cocaine and heroin. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and in Vitro Characterisation of Ifenprodil‐Based Fluorescein Conjugates as GluN1/GluN2B N‐Methyl‐D‐aspartate Receptor Antagonists

GluN2B‐containing NMDA receptors are involved in many important physiological functions and play a pivotal role in mediating pain as well as in several neurodegenerative disorders. We aimed to develop fluorescent probes to target the GluN2B subunit selectively in order to allow better understanding of the relationships between receptor localisation and physiological importance. Ifenprodil, known as the GluNR2B antagonist of reference, was chosen as the template for the elaboration of probes. We had previously reported a fluorescein conjugate that was shown (by confocal microscopy imaging of DS‐red‐labelled cortical neurons) to bind specifically to GluN2B. To elaborate this probe, we explored the influence of both the nature and the attachment point of the spacer between the fluorophore and the parent compound, ifenprodil. We performed chemical modifications of ifenprodil at the benzylic position and on the phenol ring by introducing secondary amine or amide functions and evaluated alkyl chains from two to 20 bonds either including or not including secondary amide functions as spacers. The previously developed probe was found to display the greatest activity in the inhibition of NMDA‐induced Ca²⁺ influx by calcium imaging experiments on HEK293 cells transfected with the cDNA encoding for GluN1‐1A and GluN2B. Further investigations revealed that this probe had a neuroprotective effect equivalent to that of ifenprodil in a standard test for neurotoxicity. Despite effects of lesser amplitude with these probes relative to ifenprodil, we demonstrated that they displaced [³H]ifenprodil in mouse brain slices in a similar manner.     

Responses of Human Cells to PAH-Induced DNA Damage

Benzo[ a ]pyrene (B[ a ]P) and dibenzo[ a,l ]pyrene (DB[ a,l ]P) induce cytochrome P450 (CYP) CYP1A1 and CYP1B1, which metabolize these polycyclic aromatic hydrocarbons (PAHs) into DNA-binding species. In order to detail roles of CYP1A1 and CYP1B1 in activation of DB[ a,l ]P to the diol epoxide, we here report the inhibition of CYP1A1 in human MCF-7 cells with phosphorodiamidate morpholino antisense oligomers (morpholinos). PAH-DNA adduct formation was also determined after treatment with morpholinos and B[ a ]P or DB[ a,l ]P. p53 is involved in DNA repair, cell cycle arrest, and apoptosis. Cells with normal p53 protein arrest in the G1 phase of the cell cycle on exposure to DNA-damaging agents (presumably allowing the cell sufficient time to repair damaged DNA prior to replication). Previous studies in human MCF-7 cells indicate that cells with PAH-DNA adducts escape cell cycle arrest and accumulate in the S phase. In the present study the effect of PAH-DNA adducts on the cell cycle were observed in human diploid fibroblasts (HDF). We found that treatment of HDF with the diol epoxide of DB[ a,l ]P causes cell cycle arrest in G 1 . An increase in DNA adduct formation with increase in concentration of dibenzo[ a,l ]pyrene diol epoxide {( m )- anti -DB[ a,l ]PDE} was also observed.     

Identification of 4-Anilinoquin(az)oline as a Cell-Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype**

Deep annotation of a library of 4-anilinoquin(az)olines led to the identification of 7-iodo-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine 16 as a potent inhibitor (IC₅₀=14 nM) of Protein Kinase Novel 3 (PKN3) with micromolar activity in cells. Compound 16 is a potential tool compound to study the cell biology of PKN3 and its role in pancreatic and prostate cancer and T-cell acute lymphoblastic leukemia. These 4-anilinoquin(az)olines may also be useful tools to uncover the therapeutic potential of PKN3 inhibition in a broad range of diseases.     

Membrane reactor microstructure for polymer grade olefin production and hydrogen cogeneration

The current communication describes research work on effective membrane reactor nanostructures and nanoreaction-nanoseparation technology for polymer grade olefin production via catalytic paraffin dehydrogenation reactions. Emphasis is given in systems of permreactors and permeators to perform the described reactive and separative operations. We elaborate on new membrane microstructure designs for paraffin dehydrogenations including the design of experiments, operation, and best parameter selection and optimization of such systems. The described processes are of current significance in the area of new microreactor design and operation including hydrocarbon processing and conversion to valuable fuels and chemicals such as hydrogen, olefins, and polyolefins. These improved results are because of the unique design characteristics of the examined microreactor systems to perform accurate multiphase and heterogeneous functions into one unit operation. A number of membrane reactor configurations were made and tested on stream for the catalytic propane dehydrogenation reaction to propylene with successful results. Some of the results are discussed below which show the better performance of nanostructured membrane reactors for the specific dehydrogenation.     

The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.     

Sex differences in sensitivity of the hypothalamic-pituitary-adrenal axis.

Two studies examined sex differences in responsiveness of the hypothalamic-pituitary-adrenal cortical axis, a major component of the stress response. The first measured pituitary-adrenal responses to ovine corticotropin-releasing hormone (oCRH) in 24 healthy men and 19 healthy women. Plasma adrenocorticotropin hormone responses to oCRH were significantly greater among women than among men. In contrast, cortisol concentrations were similar in both groups, though elevations were more prolonged in women. Differences in corticotropin-releasing activity between men and women may help account for these findings; such differences in central components of the stress response might play a role in the known epidemiological differences in diseases of stress system dysregulation between men and women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)