The statistical analysis of data from small groups.

The authors elaborate the complications and the opportunities inherent in the statistical analysis of small-group data. They begin by discussing nonindependence of group members' scores and then consider standard methods for the analysis of small-group data and determine that these methods do not take into account this nonindependence. A new method is proposed that uses multilevel modeling and allows for negative nonindependence and mutual influence. Finally, the complications of interactions, different group sizes, and differential effects are considered. The authors strongly urge that the analysis model of data from small-group studies should mirror the psychological processes that generate those data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

When similarity breeds content: Need for closure and the allure of homogeneous and self-resembling groups.

Four studies explored the relation between members' need for cognitive closure and their feelings toward groups. It was found that high (vs. low) need for closure individuals liked in-groups and out-groups more as function of the degree to which their membership was perceived as homogeneous (Studies 1-4), provided it was also self-similar (Studies 3 and 4). These results are discussed in terms of the relation between need for closure and homogeneous (vs. heterogeneous) groups' apparent potential as "closure providers." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Phosphoinositide 3‐Kinase Signaling Pathway is Involved in the Control of Modified Low‐Density Lipoprotein Uptake by Human Macrophages

The transformation of macrophages into lipid‐loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor‐mediated uptake of modified LDL, mediated primarily by scavenger receptors‐A (SR‐A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3‐kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR‐A, CD36 and LPL was attenuated by LY294002. The use of isoform‐selective PI3K inhibitors showed that PI3K‐β, ‐γ and ‐δ were all required for the expression of SR‐A and CD36 whereas only PI3K‐γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis.     

Identification of Aminoimidazole and Aminothiazole Derivatives as Src Family Kinase Inhibitors

Src family kinases (SFKs) are a family of non‐receptor tyrosine kinases (TKs) implicated in the regulation of many cellular processes. The aberrant activity of these TKs has been associated with the growth and progression of cancer. In particular, c‐Src is overexpressed or hyperactivated in a variety of solid tumors and is most likely a strong promoting factor for the development of metastasis. Herein, the synthesis of new 4‐aminoimidazole and 2‐aminothiazole derivatives and their in vitro biological evaluation are described for their potential use as SFK inhibitors. Initially, 2‐aminothiazole analogues of dasatinib and 4‐aminoimidazole derivatives were synthesized and tested against the SFKs Src, Fyn, Lyn, and Yes. Five hits were identified as the most promising compounds, with K_i values in the range of 90–480 nm . A combination of molecular docking, homology modeling, and molecular dynamics were then used to investigate the possible binding mode of such compounds within the ATP binding site of the SFKs. Finally, the antiproliferative activities of the best candidates were evaluated against SH‐SY5Y and K562 cell lines. Compound 3 b [2‐(4‐{2‐methyl‐6‐[(5‐phenylthiazol‐2‐yl)amino]pyrimidin‐4‐yl}piperazin‐1‐yl)ethanol] was found to be the most active inhibitor.     

Analgesic,Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete.     

Investigating the Role of Conformational Effects on Laccase Stability and Hyperactivation under Stress Conditions

Fungal laccase from Steccherinum ochraceum 1833 displays remarkable stability under different harsh conditions: organic/buffer mixtures, thermal treatment, and microwave radiation. The behavior is particularly significant in the light of the sharp inactivation observed for two different fungal laccases. Laccase from S. ochraceum 1833 also displays hyperactivation under mild thermal treatment (60 °C). Molecular dynamics simulations at 80 °C explained how this laccase retains the geometry of the electron transfer pathway, thereby assuring electron transfer through the copper ions and thus maintaining its catalytic activity at high temperature. Spectroscopic studies revealed that the thermal activation corresponds to specific conformational changes in the protein. The results indicate that this laccase is potentially applicable under denaturing conditions that might be beneficial for the biotransformation of recalcitrant substrates.     

Temperature-mediated control of the growth of an entangled carbon nanofiber layer on stainless steel micro-structured reactors

A well-adhered layer of carbon nanofibers (CNFs) was grown on stainless steel microreactors by decomposition of a hydrocarbon over microreactors previously coated with Ni dispersed on alumina. In a previous work, we reported that the growth temperature and hydrocarbon (methane or ethane) modulated the morphology and size of the grown carbon species. Using ethane, the carbon yield increased dramatically for temperatures exceeding 898 K. At these temperatures some carbon protrusions arise, which plug microreactor channels and render the microreactor unsuitable for use. For methane at all the tested temperatures or for ethane at the lowest temperatures (853 and 873 K), the microreactor channels were covered completely by a uniform mat of entangled CNFs ready for catalytic use. Here, we show that the growth temperature and hydrocarbon can also control the primary structure of CNFs, either rolled graphitic planes parallel to the axis (multi-wall carbon nanotubes) or graphitic planes forming an angle with respect to the axis (fishbone type).     

Analysis of Current–Voltage Measurements on Long-Wavelength HgCdTe Photodiodes Fabricated on Si Composite Substrates

We have performed a detailed study of dark current versus voltage to understand existing limitations in dark current and address the nonuniformity of dark current in devices fabricated on HgCdTe grown on silicon substrates. One interesting observation is that trap-assisted tunneling, g-r currents, are not found close to zero bias in certain devices. Devices from the low end of the R ₀ A distribution show heavy shunting paths close to zero bias. We believe that these shunting paths may be the limiting cause of tail distributions in fabricated focal plane array tail distributions. Possible causes for these shunting paths are surface charges associated with dislocation cores and impurity gettering at dislocation cores. The measured non-anti-reflection (AR)-coated quantum efficiency (QE) was 0.576 at 78 K and displays the classical response versus wavelength. The measured QE on isolated single devices is consistent with the 256 × 256 focal-plane array mean QE. Obtained average dark currents are on the order of mid 10⁻⁵ A cm^–2, which is one order of magnitude higher than dark currents obtained from arrays on lattice-matched substrates. On average, arrays on lattice-mismatched substrates show performance characteristics inferior to those of arrays fabricated on lattice-matched substrates. This inferior performance is due to array pixel operability, as can be seen from the tail of the distribution and the average dark currents, which are one order of magnitude higher than those obtained on lattice-matched substrates.     

Design and In vitro Evaluation of Branched Peptide Conjugates: Turning Nonspecific Cytotoxic Drugs into Tumor‐Selective Agents

The use of peptide receptors as targets for tumor‐selective therapies was envisaged years ago with the findings that receptors for different endogenous regulatory peptides are overexpressed in several primary and metastatic human tumors, and can be used as tumor antigens. Branched peptides can retain or even increase, through multivalent binding, the biological activity of a peptide and are very resistant to proteolysis, thus having a markedly higher in vivo activity compared with the corresponding monomeric peptides. Oligo‐branched peptides, containing the human regulatory peptide neurotensin (NT) sequence, have been used as tumor‐specific targeting agents. These peptides are able to selectively and specifically deliver effector units, for cell imaging or killing, to tumor cells that overexpress NT receptors. Results obtained with branched NT conjugated to different functional units for tumor imaging and therapy indicate that branched peptides are promising novel multifunctional targeting molecules. This study is focused on the role of the releasing pattern of drug‐conjugated branched NT peptides. We present results obtained with oligo‐branched neurotensin peptides conjugated to 6‐mercaptopurin (6‐MP), combretastain A‐4 (CA4) and monastrol (MON). Drugs were conjugated to oligo‐branched neurotensin through different linkers, and the mode‐of‐release, together with cytotoxicity, was studied in different human cancer cell lines. The results show that branched peptides are very promising pharmacodelivery options. Among our drug‐armed branched peptides, NT4–CA4 was identified as a candidate for further development and evaluation in preclinical pharmacokinetic and pharmacodynamic studies. This peptide–drug exhibits significant activity against pancreas and prostate human cancer cells. Consequently, this derivative is of considerable interest due to the high mortality rates of pancreas neuroendocrine tumors and the high incidence of prostate cancer.