Approximating Exact Probabilities by χ2 and Continuity-Corrected χ2 in 2×2 Tables

Computations have been performed to find an adequate definition of exact two-sided probabilities in 2times2 contingency tables. It turns out, that both uncorrected χ² and Yates' correction for continuity give only unsatisfactory approximations to the exact probabilities of the hypergeometric distribution. The latter are therefore recommended for general use.     

HLA‐DQ7 β1 and β2 derived peptides as immunomodulators

Modulation of protein–protein interactions involved in the immune system by using small molecular mimics of the contact interfaces may lead to the blockage of the autoimmune response and the development of drugs for immunotherapy. The nonpolymorphic β‐regions, exposed to the microenvironment, of the modeled HLA‐DQ7, which is genetically linked to autoimmune diseases, were determined. Peptides 132–141 and 58–67, located at the β₁ and β₂ domains of HLA‐DQ7, respectively, were tested for their involvement in the interactions with CD4⁺ T lymphocytes. Linear, cyclic, and dimeric analogs that mimic the exposed surfaces of HLA‐DQ7 were designed and synthesized. Their immunosuppressory activities, found in the secondary, humoral immune response to sheep erythrocytes (SRBC) in mice in vitro, ranged from 11% to 53%. The significance of the total charge of the peptides, the pattern of the hydrogen bonding, and the presence of secondary structure were investigated in relation to the immunomodulatory effect of the peptides. Two dimeric analogs of the HLA‐DQ7 58–67 fragment, consisting of the two monomers covalently linked by a polyethylene glycol (PEG) spacer, able to mimic the superdimers, were also synthesized and studied. As the 58–67 segment is located at the β₁ region of HLA‐DQ7, close to the major histocompatibility complex (MHC) groove, one may assume that the 58–67 peptide could accommodate the association between T‐cell receptor (TCR) and human leukocyte antigen (HLA) by activating a co‐stimulatory molecule of the TCR/HLA interaction. This hypothesis is supported by the confocal laser image of the fluorescein‐labeled 58–67 peptide and by the fact that it is an immunostimulator at low concentration. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Syntheses of daidzein-7-yl β- -glucopyranosiduronic acid and daidzein-4′,7-yl di-β- -glucopyranosiduronic acid

Syntheses of the title compounds — commonly known as ‘daidzein 7-glucuronide’ and ‘daidzein 4′,7-diglucuronide’ — are described. Selective 7-deacetylation of 4′,7-di-O-acetyldaidzein is employed.     

Test Statistics for Three-Factor Interaction in 2 × 2 × 2 Contingency Tables

A Monte Carlo simulation was conducted in order to determine the size and power of two proposed tests (the covariance and correlation tests) for three-factor interaction in 2 × 2 × 2 contingency tables. Results were compared to the log-odds ratio test statistic. Simulation showed the correlation test to be more conservative than the covariance test, but less so than the log-odds ratio test. However, the correlation test was the most powerful among the three tests.     

Further crystallographic evidence of NH· · ·π (system) and CO· · ·π (system) interactions: The structures of bis(diarylhydrazonecarbonyl)methylene derivatives [{ArPhCNNH—C(O)}2CH2] (Ar = Ph, 2‐C5H4N, 2‐C4H3S)

In this study are reported the syntheses of three bis(diarylhydrazonecarbonyl)methylene derivatives [{ArPhCNNH C(O)}₂CH₂] [Ar = 2 C₅H₄N (5), C₆H₅ (6), and 2‐C₄H₃S (7)], obtained by condensation of corresponding hydrazones with carbon suboxide, C₃O₂. The solid‐state self‐assembly of these carbonyl derivatives, giving rise to polymeric and dimeric networks, is described. In the formation of these structural features, in addition to N—H· · ·OC intermolecular hydrogen bonds, stabilizing intramolecular NH· · · π (systems) and intermolecular CO· · ·π (systems) interactions also seem to play an important role. Solution ¹H‐nmr data of compounds 5–7 indicate that the polymeric and dimeric structures are not maintained in solution and show the occurrence of keto‐enolic equilibria. © 1999 John Wiley & Sons, Inc. Biopoly 49: 541–549, 1999     

Exact Test of Uniform Association in a 2 × 3 Table

In a similar approach to Fisher's exact test of independence (null association) for a 2 × 2 table, this note gives an exact test of uniform association for a 2 × 3 table.     

The Muscle-Specific Laminin Receptor α7β1 Integrin Negatively Regulates α5β1 Fibronectin Receptor Function

α7β1 is the major integrin complex expressed in differentiated muscle cells where it functions as a laminin receptor. In this work we have expressed the α7 integrin subunit in CHO cells to investigate the functional properties of this receptor. After transfection with α7 CHO cells acquired the ability to adhere and spread on laminin 1 consistent with the laminin receptor activity of the α7β1. α7 transfectants, however, showed a 70% reduction in the ability to adhere to fibronectin and were unable to assemble a fibronectin matrix. The degree of reduction was inversely related to the level of α7 expression. To define the mechanisms underlying this adhesive defect we analyzed surface expression and functional properties of the α5β1 fibronectin receptor. Although cell surface expression of α5β1 was reduced by a factor of 20–25% in α7 transfectants compared to control untransfected cells, this slight reduction was not sufficient to explain the dramatic reduction in cell adhesion (70%) and matrix assembly (close to 100%). Binding studies showed that the affinity of¹²⁵I-fibronectin for its surface receptor was decreased by 50% in α7 transfectants, indicating that the α5β1 integrin is partially inactivated in these cells. Inactivation can be reversed by Mn²⁺, a cation known to increase integrin affinity for their ligands. In fact, incubation of cells with Mn²⁺restored fibronectin binding affinity, adhesion to fibronectin, and assembly of fibronectin matrix in α7 transfectants. These data indicate that α7 expression leads to the functional down regulation of α5β1 integrin by decreasing ligand binding affinity and surface expression. In conclusion, the data reported establish the existence of anegative cooperativitybetween α7 and α5 integrins that may be important in determining functional regulation of integrins during myogenic differentiation.     

A Potential Role for 5‐Androstene‐3β,7β,17β‐triol in Obesity and Metabolic Syndrome

Metabolic syndrome is marked by perturbed glucocorticoid (GC) signaling, systemic inflammation, and altered immune status. Dehydroepiandrosterone (DHEA), a major circulating adrenal steroid and dietary supplement, demonstrates antiobesity, anti‐inflammatory, GC‐opposing and immune‐modulating activity when administered to rodents. However, plasma DHEA levels failed to correlate with metabolic syndrome and oral replacement therapy provided only mild benefits to patients. Androstene‐3β,7β,17β‐triol (β‐AET) an anti‐inflammatory metabolite of DHEA, also exhibits GC‐opposing and immune‐modulating activity when administered to rodents. We hypothesized a role for β‐AET in obesity. We now report that plasma levels of β‐AET positively correlate with BMI in healthy men and women. Together with previous studies, the observations reported here may suggest a compensatory role for β‐AET in preventing the development of metabolic syndrome. The β‐AET structural core may provide the basis for novel pharmaceuticals to treat this disease.     

Luminescence properties of a novel red phosphor 6LaPO4–3La3PO7–2La7P3O18:Eu3+

Eu³⁺‐doped 6LaPO₄–3La₃PO₇–2La₇P₃O₁₈ red luminescent phosphors were synthesized by co‐deposition and high‐temperature solid‐state methods and its polyphase state was confirmed by X‐ray diffraction analysis. Transmission electron microscopy showed the grain morphology as a mixture of rods and spheres. Luminescence properties of the phosphor were investigated and its red emission parameters were evaluated as a function of Eu³⁺ concentration (3.00–6.00 mol%). Excitation spectra of 6LaPO₄–3La₃PO₇–2La₇P₃O₁₈:Eu³⁺ showed strong absorption bands at 280, 395, and 466 nm, while the luminescence spectra exhibited prominent red emission peak centred at 615 nm (⁵D₀→⁷F₂) in the red region. CIE chromaticity coordinates of the 6LaPO₄–3La₃PO₇–2La₇P₃O₁₈:5%Eu³⁺ phosphor were (0.668, 0.313) in the red region, and defined its potential application as a red phosphor.     

Fracto‐mechanoluminescence and thermoluminescence properties of UV and γ‐irradiated Ca2Al2SiO7:Ce3+ phosphor

Ce³⁺‐doped calcium aluminosilicate phosphor was prepared by a combustion‐assisted method at an initiating temperature of 600°C. Structural characterization was carried out using X‐ray diffraction (XRD) and scanning electron microscopy (SEM). The absorption spectra of Ca₂Al₂SiO₇:Ce³⁺ showed an absorption edge at 230 nm. The optical characterization of Ca₂Al₂SiO₇:Ce³⁺ phosphor was investigated in a fracto‐mechanoluminescence (FML) and thermoluminescence (TL) study. The peak of ML intensity increased as the height of impact of the moving piston increased. The TL intensity of Ca₂Al₂SiO₇:Ce³⁺ was recorded for different exposure times of UV and γ‐irradiation and it was observed that TL intensity was maximum for a UV irradiation time of 30 min and for a γ‐dose of 1180 Gy. The TL intensity had three peaks for UV irradiation at temperatures 82°C, 125°C and 203°C. Also the TL intensity had a single peak at 152°C for γ‐irradiation. The TL and ML emission spectra of Ca₂Al₂SiO₇:Ce³⁺ phosphor showed maximum emission at 400 nm. The possible mechanisms involved in the TL and ML processes of the Ca₂Al₂SiO₇:Ce³⁺ phosphor are also explained. Copyright © 2015 John Wiley & Sons, Ltd.     

The role of calcium in apoptosis induced by 7β‐hydroxycholesterol and cholesterol‐5β,6β‐epoxide

Oxysterols, such as 7β‐hydroxy‐cholesterol (7β‐OH) and cholesterol‐5β,6β‐epoxide (β‐epoxide), may have a central role in promoting atherogenesis. This is thought to be predominantly due to their ability to induce apoptosis in cells of the vascular wall and in monocytes/macrophages. Although there has been extensive research regarding the mechanisms through which oxysterols induce apoptosis, much remains to be clarified. Given that experimental evidence has long associated alterations of calcium (Ca²⁺) homeostasis to apoptotic cell death, the aim of the present study was to determine the influence of intracellular Ca²⁺ changes on apoptosis induced by 7β‐OH and β‐epoxide. Ca²⁺ responses in differentiated U937 cells were assessed by epifluorescence video microscopy, using the ratiometric dye fura‐2. Over 15‐min exposure of differentiated U937 cells to 30 μM of 7β‐OH induced a slow but significant rise in fura‐2 ratio. The Ca²⁺ channel blocker nifedipine and the chelating agent EGTA blocked the increase in cytoplasmic Ca²⁺. Moreover, dihydropyridine (DHP) binding sites identified with BODIPY‐FLX‐DHP were blocked following pretreatment with nifedipine, indicating that the influx of Ca²⁺ occurred through L‐type channels. However, following long‐term incubation with 7β‐OH, elevated levels of cytoplasmic Ca²⁺ were not maintained and nifedipine did not provide protection against apoptotic cell death. Our results indicate that the increase in Ca²⁺ may be an initial trigger of 7β‐OH–induced apoptosis, but following chronic exposure to the oxysterol, the influence of Ca²⁺ on apoptotic cell death appears to be less significant. In contrast, Ca²⁺ did not appear to be involved in β‐epoxide–induced apoptosis. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:324–332, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20295     

Structural and biochemical insights into 7β‐hydroxysteroid dehydrogenase stereoselectivity

Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo‐ and regio‐selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7β‐hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active‐site accessibility, the bases of the specificity for NADP⁺, and the general architecture of the steroid binding site. Comparison with 7α‐hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C‐terminal extension reshapes the substrate site of the β‐selective enzyme, possibly leading to an inverted orientation of the bound substrate. Proteins 2016; 84:859–865. © 2016 Wiley Periodicals, Inc.     

Doping of [In2(phen)3Cl6]·CH3CN·2H2O Indium‐Based Metal–Organic Framework into Hole Transport Layer for Enhancing Perovskite Solar Cell Efficiencies

Perovskite solar cells (PSCs) have gained a promising position during the past few years. However, as far as it goes, there is rare combination of the merits of metal–organic framework with PSCs. In this work, a 3D metal–organic framework, namely, [In₂(phen)₃Cl₆]·CH₃CN·2H₂O (In2) is first introduced into hole transport material of PSCs through band alignment engineering. By this facile strategy, the pinholes in the hole transport layer are effectively reduced, and the migration of Au into the entire PSC structure can be alleviated simultaneously. Meanwhile, In2 also plays a role in enhancing the light absorption of perovskite, which is due to: (1) the large particles of In2 acting as light scattering centers; (2) the emission wavelength of In2 is almost the same as the excitation wavelength of perovskite. Consequently, short‐current density (J_sc), open circuit voltage (V_oc), and fill factor (FF) gain a significant increase from 19.53 to 21.03 mA cm^?2, 0.98 to 1.01 V, and 0.67 to 0.74, respectively. Thereby, the power conversion efficiency is remarkably enhanced from 12.8% to 15.8%. In the end, the stability of PSCs should also be improved.     

Synthesis and luminescent properties of Eu(TTA)3·3H2O nanocrystallines

Nanocrystallines of rare earth complex, Eu(TTA)₃·3H₂O, were synthesized by the chemical precipitation method and were characterized by elemental analysis, ultraviolet visible absorption spectroscopy (UV–vis), infrared spectroscopy (IR), differential thermal analysis–thermogravimetry (TG‐DTA), X‐ray diffraction (XRD) and transmission electron microscopy (TEM). The size of the nanocrystallines was tunable by selecting the proper buffer system, which was used to control the pH of the solution. A small polydispersity in particle size ranging from 70 to 250 nm was obtained when ammonia was used. The nanocrystallines showed the characteristic fluorescence of europium ions and energy transfer from the organic ligand to central ions was observed by fluorescence excitation and emission spectroscopy. These nanoparticles of rare earth complexes have potential application in luminescent materials due to their excellent fluorescence properties. Copyright © 2009 John Wiley & Sons, Ltd.     

Studies on the 5α-androstane-3β, 17β-diol-6α-hydroxylase and on the 5α-androstane-3β, 17β-diol-7α-hydroxylase in anterior hypophysis of male rats.

In anterior pituitaries from male rats, it appeared that 5α-androstane-3β, 17β-diol was quickly metabolized into 5α-androstane-3β,6α-17β-triol and 5α-androstane-3β,7α, 17β-triol by action of 6α- and 7α-hydroxylases. Hydroxysteroid hydroxylases were located in endoplasmic reticulum and were dependent on NADPH⁺. Their optimum pH was 8.0, optima temperature, 37°C, and their apparent Km was 2.7 μM. Hydroxylative reactions were not reversible and not modified by gonadectomy. Hydroxylation seemed an efficient control of the pituitary level of 5α-andros-tane-3β, 17β-diol.