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Nuclear Receptor Research
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Vol. 2 (2015), Article ID 101163, 9 pages
doi:10.11131/2015/101163
Activation of Nuclear Receptors RAR, RXR, and LXR Does Not Reduce Cuprizone-Induced Demyelination in Mice
Davina Kruczek1, Tim Clarner2, Cordian Beyer2, Markus Kipp2,3, and Jörg Mey1,4,5
1Institut für Biologie II, RWTH Aachen, Germany
2Institut für Neuroanatomie, Universitätsklinikum Aachen, Germany
3Lehrstuhl II – Neuroanatomie, Ludwig-Maximilians-Universität München, Germany
4Laboratorio Regeneración Nerviosa, Hospital Nacional de Parapléjicos, Toledo, Spain
5EURON Graduate School of Neuroscience, Maastricht University, Netherlands
Received 26 March 2015; Accepted 15 May 2015
Editor: Xiaoying Li
Copyright © 2015 Davina Kruczek et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Experiments with animal models of multiple sclerosis have shown that the expression of retinoid X receptors (RXR) increases during demyelination and that RXR is involved in the regulation of remyelination. After ligand binding RXRs form heterodimeric transcription factors with other nuclear receptor (NR) families including the retinoic acid receptors (RAR) and liver X receptors (LXR). We tested whether activation of these nuclear receptor complexes reduces pathological demyelination using the cuprizone mouse model. Cuprizone, which causes oligodendrocyte degeneration, was given for three weeks as a food additive. For the activation of nuclear receptors mice were treated with daily i.p. injections of agonists for RXR (9-cis RA), RAR (all-trans RA), and LXR (T0901317). Myelin status, oligodendrocyte survival, astrogliosis, microglial activation, and axon density were monitored with immunohistochemistry and evaluated quantitatively. Three weeks of cuprizone feeding caused severe demyelination and significantly raised the number of Iba1 immunoreactive microglia cells in the caudal corpus callosum. This increase of microglia activity was reduced with 9-cis RA treatment but was enhanced with all-trans RA and was not affected by T0901317. Nuclear receptor activation did not influence the degree of demyelination, oligodendrocyte survival, astrogliosis, or axonal preservation. We conclude that RXR activation, although affecting Iba1-positive microglia, does not protect oligodendrocytes from cuprizone toxicity and does not induce compensatory mechanisms in the initial phase of demyelination.
Recently, ligand activated transcription factors of the retinoid X receptor family (RXR) have been shown to be involved in the endogenous responses to toxin induced demyelination [1,2]. The RXRs form heterodimers with other nuclear receptor (NR) families, including retinoic acid receptors (RAR) and liver X receptors (LXR). Experimental administration of agonists of these receptors was suggested as a potential treatment option for Alzheimer's disease, multiple sclerosis, ischemia, and spinal cord injury [3]. Anti-inflammatory functions of retinoic acid (RA), the natural ligand of RAR/RXR, have been described for astrocytes [4,5,6] and microglia [7,8].In three animal models of multiple sclerosis, that is, experimental allergic encephalomyelitis (EAE), systemic treatment with cuprizone, and focal application of lysolecithin, the oral administration of ligands of RAR [9-11], PPAR [12,13], or n-3 polyunsaturated fatty acids (which activate RXR) [14] resulted in therapeutic benefits. The studies evaluated T-cell function, pro- and anti-inflammatory cytokines, histological signs of demyelination, and clinical scores of disease progression. Since LXR/RXR signaling regulates cholesterol homeostasis in oligodendrocytes [15] and modulates the activity of macrophages [16] and T-cells [17], their ligands are likely to be involved in the physiological processes during remyelination as well.
Figure 1: Myelination of central fiber tracts shown with immunohistochemistry of PLP. Parasagittal sections of the Cc area are shown three weeks after cuprizone treatment. (a) Control section of a mouse fed normal chow; (b) effect of cuprizone feeding; (c) of cuprizone and daily intraperitoneal injections of all-trans RA; (d) of cuprizone and 9-cis RA; (e) of cuprizone and T0901317. Reduced myelin staining in all cuprizone treated animals is visible as is dark granular myelin debris. The caudal end of the Cc is in the upper right corner of the photographs; co: cerebral cortex, cc: corpus callosum; spl: splenium; hc: hippocampus; fo: fornix. (f) Quantitative evaluation of myelin status in the Cc, based on PLP immunohistochemistry; myelin scale converted to % of control. Bars indicate means and standard error of the mean (SEM). Nonparametric H-test of treatment effect was significant and post hoc U-tests demonstrated a significant effect of cuprizone feeding compared to control (*P< 0.05, **P < 0.01) and no influence of the NR agonists.
Figure 2: Examples of immunohistochemical staining illustrate the effect of cuprizone and NR agonists on oligodendrocytes. Shown are sections of the caudal Cc following treatments; (a) control condition, normal chow; (b) after three weeks of cuprizone feeding; (c) combined cuprizone feeding with injection of all-trans RA; (d) combined treatment of cuprizone with 9-cis RA; and (e) combined treatment of cuprizone with T0901317. Oligodendrocytes were marked with an antibody against adenomatous polyposis coli (APC). Scale bar 100 µm in panel e is valid for all photographs.
Using acute demyelination combined with laser capture microdissection the groups of Franklin, ffrench-Constant, and Chambon demonstrated that RXRγ controls the differentiation of oligodendrocyte precursor cells and promotes remyelination in vivo [1]. The involvement of RXRγ in the process of demyelination was demonstrated by us using the copper chelator cuprizone [2]. In this model 0.2% cuprizone is fed to young male mice. The treatment causes apoptosis of mature oligodendrocytes, which is closely followed by microglia and astrocyte activation. The blood-brain barrier remains intact and a hematogenic immune response with cerebral T-cell infiltration is not elicited [18]. In the present work we investigated whether activation with ligands of RAR (all-trans RA), RXR (9-cis RA), and LXR (T0901317) affected the process of demyelination in this animal model. Since we observed that three weeks of cuprizone treatment led to a strong degree of demyelination of the Corpus callosum (Cc) this treatment period and fiber tract were selected in the present study.
Figure 3: Quantification of the effect of cuprizone and NR agonists on cell numbers of oligodendrocytes, microglia, and astrocytes. (a) After three weeks of cuprizone feeding APC positive cell counts were significantly reduced in all regions of the Cc while treatment with the NR agonists had no mitigating or aggravating effect. (b) Quantification of microglia activation and (c) of GFAP positive cell numbers. Bars indicate means ± SEM. Following ANOVA, Dunnett's test comparisons vs. control condition are marked with asterisks (*P< 0.05, **P< 0.01, ***P< 0.001), comparison vs. cuprizone condition with the pound symbol (#P < 0.05). Regions of the Cc are abbreviated r: rostral, f: central near fornix, and c: caudal.
2.1. The cuprizone animal model
To induce demyelination of central fiber tracts, 8-week-old male C57BL/6 mice, 20–25 g body weight (Charles River, Germany), were treated with the copper chelator cuprizone (Sigma-Aldrich, Germany). Demyelination was induced by feeding a diet containing 0.2% cuprizone mixed into a ground of standard rodent chow for three weeks. Animals were maintained in a pathogen-free environment, underwent routine cage maintenance once a week and microbiological monitoring. Food and water were available ad libitum. Research and animal care procedures were in accordance with national regulations and guidelines for the care and use of laboratory animals and were approved by the Review Board for the Care of Animal Subjects of the district government in Nordrhein-Westfalen, Germany.
2.2. Nuclear receptor activation in vivo
To activate RAR, RXR, or LXR transcription factors, mice received daily intraperitoneal (i.p.) injections of either 20 µg all-trans RA (Sigma-Aldrich), 20 µg 9-cis RA (Sigma-Aldrich) diluted in 100 µl of 50/50 DMSO/PBS, or 0.5 mg T0901317 (Cayman Chemicals) dissolved in 100 µl of 10/90 DMSO/PBS. Animals in the cuprizone-treated control group received daily i.p. injections of 100 µl 50/50 DMSO/PBS. The efficacy of NR activation with i.p. application of these listed agonists had been established in previous studies [19,20,21]. Following an accommodation period and the three weeks of experimental drug application, all animals were sacrificed and further processed.
2.3. Tissue preparation and demyelination scoring
For the histological evaluation, mice were transcardially perfused with 4% paraformaldehyde containing saturated picric acid. After decapitation and post fixation overnight, brains were dissected and embedded in paraffin. Best staining results were achieved with dehydration for seven days in 70% ethanol followed by 96%, 100% ethanol, acetone, and paraffin embedding. Parasagittal sections of 5 µm covered the lateral 0.48 mm–0.72 mm area according to the stereotaxic atlas [22]. The degree of demyelination was evaluated immunohistochemically and by staining with Luxol fast blue/cresyl violet following the protocol previously described [18]. The myelin status was staged independently by three blinded investigators using a scale between 0 and 100, where a score of 100 was given to the myelin status of reference mice, not treated with cuprizone, whereas zero corresponded to a totally demyelinated corpus callosum.
2.4. Analysis of nuclear receptor expression
The expression of nuclear receptors under conditions of cuprizone induced demyelination was assessed with the GeneChip Mouse Gene 1.0 ST Array (Affymetrix, USA) using the Agilent 2100 Bioanalyzer (Agilent, USA). The detailed procedure and treatment regimen have been published before [18]. Effects on nuclear receptors that are likely to mediate RA signaling were confirmed with quantitative RT-PCR using iQ5 real-time PCR detection (BioRad) using the same primers as listed previously [2].
Figure 4: Examples of immunohistochemical staining illustrate the effect of cuprizone and NR agonists on microglia cells. Shown are sections of Cc following treatments; (a), (b) control condition, normal chow; (c), (d) after three weeks of cuprizone feeding; (e), (f) combined cuprizone feeding with injection of all-trans RA; (g), (h) combined treatment of cuprizone with 9-cis RA; and (i), (j) combined treatment of cuprizone with T0901317. Panels (a), (c), (e), (g), and (i) represent areas in the caudal, panels (b), (d), (f), (h), and (j) in the rostral Cc. Microglia cells were marked with an antiserum against ionized calcium binding adapter molecule-1 (Iba1). Scale bar 50 µm in panel j is valid for all photographs.
2.5. Immunohistochemistry
Paraffin-embedded sections on silane-coated slides were rehydrated, heat-unmasked in citric acid buffer (pH 6.0; 20 min, microwave 180 W), and then processed using the Vectastain Elite ABC-Kit (avidin-biotinylated enzyme complex, Vector Laboratories, PK4010). Sections were blocked with 2% normal serum and incubated overnight with mouse monoclonal antibodies against myelin proteolipid protein (PLP; 1/500; Abd Serotec, Germany, catalogue number: MCA839G), adenomatous polyposis coli (APC; 1/250; Calbiochem, Germany, OP80), and pan-axonal neurofilament (smi312, 1/1000; Covance, UK, SMI312-R), with rabbit polyclonal sera against glial fibrillary acidic protein (GFAP; 1/1000; EnCor, USA, RPCA-GFAP) and against ionized calcium binding adaptor molecule-1 (Iba1; 1/200; Wako, Germany, 019-19741). In Iba1 labeling experiments, counterstaining with hematoxylin/eosin was used. Biotinylated secondary antibodies, included in the Vectastain kit, were goat anti-rabbit IgG and horse anti-mouse IgG (both from Vector Laboratories, BA-1000, BA-2000). For visualization of peroxidase labeling a substrate kit with aminoethyl carbazole and a chromophore was used (Zymed, AEC Red Substrate Kit, 00-2007; Invitrogen). Sections were viewed and documented using a Nikon Eclipse 80i microscope equipped with a Nikon Y-TV55 camera.
2.6. Quantification and statistical analysis
Microphotographs were captured and evaluated with Nikon NIS Element D program and NIH ImageJ. Immunoreactive cells were manually selected and counted automatically. Three regions of the Corpus callosum (Cc), caudal (splenium), central (adjacent to fornix), and rostral Cc, were assessed independently. Cell densities were normalized to 0.1 mm2 tissue area. Using a 40x objective (Iba1) or 20x objective (GFAP, APC) the numbers of positive cells were counted by two blinded observers in four animals per condition except for the group treated with cuprizone only, which contained eight animals. Two sections per mouse were averaged.
Non-parametric data of myelin staging were evaluated with the H-Test after Kruskal and Wallis followed by Wilcoxon/Mann/Whitney post hoc U-test with correction for ties. Cell density data were evaluated with ANOVA and post hoc Dunnett's test. Statistical tests were done using GraphPad Prism 5.01, the U-test manually with Excel. In all graphs means ± standard error of the mean are shown.
3.1. Cuprizone-induced demyelination is not affected by retinoic acid or T0901317
Three weeks of oral cuprizone treatment caused severe demyelination of the Cc, as shown with histological staining (Luxol fast blue) and PLP immunohistochemistry (Figure 1(a), 1(b)). In addition to the reduced staining, dark granular myelin debris was visible, as illustrated in the Cc and adjacent cingulum. In contrast to these fiber tracts, myelination of the fornix was not affected. To test whether pharmacological activation of NR influences demyelination, the cuprizone treatment was combined with daily i.p. injections of ligands for RARs (all-trans RA), RXRs (9-cis RA), and LXRs (T0901317; Figure 1(c)–1(e)). Previous studies have established that this treatment alters gene expression in the CNS [19,20,21]. Immunoreactivity of RARα and RXRβ is present in the corpus callosum [2]. The cuprizone-induced demyelination was not affected by any of the NR agonists (LFB staining). Quantification of PLP immunoreactivity corroborated the signal reduction due to cuprizone administration (Figure 1(a), 1(b)). Although myelin degradation appeared to be somewhat attenuated after treatment with all-trans RA (Figure 1(c)) and T0901317 (Figure 1(e)), the quantification showed no significant effect of any of the NR ligands (Figure 1(f)).
Mature oligodendrocyte cell bodies were marked with an antibody against APC (Figure 2). Numerous oligodendrocytes were homogeneously distributed in the Cc of control mice, and no difference was apparent between caudal, middle, and rostral parts of the Cc. In cuprizone-treated animals the numbers were strongly reduced. After three weeks we found the decline to be most pronounced in the caudal area, where the APC positive cell population was reduced to 24% (Figure 2(a), 2(b)). The administration of all-trans RA, 9-cis RA, or T0901317 did not affect oligodendrocytes (Figure 2(b)–2(e)), as demonstrated by the quantification of cell numbers (Figure 3(a), no statistical differences between cuprizone-treated animals and the groups that received additional injections of NR ligands). Across the rostrocaudal extent of the Cc and treatment conditions the decline in oligodendrocytes paralleled demyelination.
Figure 5: Examples of immunohistochemical staining illustrate the effect of cuprizone and NR agonists on astrocytes. Shown are sections of caudal Cc following treatments; (a) control condition, normal chow; (b) after three weeks of cuprizone feeding; (c) combined cuprizone feeding with injection of all-trans RA; (d) combined treatment of cuprizone with 9-cis RA; and (e) combined treatment of cuprizone with T0901317. Astrocytes were marked with an antiserum against glial fibrillary acidic protein (GFAP). Scale bar 100 µm in panel (e) is valid for all photographs.
Figure 6: Gene expression analysis RARs and RXRs in the murine corpus callosum. (a) Agarose gels with RT-PCR products under control conditions, and after 2 and 5 weeks cuprizone feeding. (b) Quantification with qRT-PCR was normalized to the expression of hypoxanthine phosphoribosyltransferase (HPRT). Error bars indicate SEM, controls n = 4–8 animals/group; t-test: *P< 0.05.
At three weeks of continued cuprizone treatment the density of nerve fibers, quantified with smi312 immunohistochemistry, was not yet affected. Compared to the neurofilament signal intensity in the Cc of control animals (normalized mean 100 ± SEM 1.7), cuprizone treatment caused no change (100 ± 2.6), and none of the NR agonists affected fiber density either (cuprizone with all-trans RA: 99 ± 1.5; cuprizone with 9-cis RA: 99 ± 3.6; cuprizone with T0901317: 96 ± 1.0). These are data from the rostral Cc, and similar results were obtained from the central and caudal areas of the fiber tract.
Table 1: Effect of cuprizone treatment on the expression of nuclear receptors in the murine corpus callosum (Affimetrix gene chip).
3.2. Effect of NR agonists on microglial activation and astrogliosis
Although the cuprizone-induced demyelination differs from the EAE model by not activating the immune system systemically, the tissue damage caused a local inflammatory reaction. In cuprizone treated mice we noted the appearance of a large population of Iba1 expressing microglia (Figure 4), which was particularly strong in the caudal Cc. The quantification is shown in Figure 3(b). Additional treatment with 9-cis RA reduced this increase (Figure 4(g), 4(h)), such that the difference with respect to the control condition without cuprizone was no longer significant; however the comparison between 9-cis RA treated and non-treated animals under conditions of demyelination fell short of the required level of significance (0.05 <P< 0.1). On the other hand, injections of all-trans-RA caused a significantly stronger Iba1 immunoreactivity than cuprizone feeding alone (P< 0.05). The LXR agonist T0901317 did not modify the response (Figures 3(b) and 4(c)–4(j)).
Cuprizone-induced damage was accompanied with mild signs of local astrogliosis. Immunohistochemical staining against GFAP revealed a moderate increase in the size and staining intensity of astrocytes in the Cc (Figure 5(a), 5(b)). The strongest signal was apparent in the caudal area, although it reached significance only in the rostral Cc (Figure 3(c)). The quantitative evaluation revealed no influence of all-trans RA, 9-cis RA and T0901317 under conditions of demyelination (P> 0.05 in all cases; Figures 3(c) and 5(b)–5(e)).
3.3. Nuclear receptors of the RAR, RXR, and LXR families are expressed in the murine corpus callosum under conditions of demyelination
The expression of nuclear receptors that form functional dimers with RXR and would provide the basis for physiological effects of the investigated ligands was detected in the Cc of untreated and cuprizone-fed mice. An Affymetrix GeneChip screen indicated high levels of expression of RARβ, RXRγ, RORα, LXRα and PPARβ and a cuprizone-induce increase of the transcripts for RXRβ and RORβ (Table 1). The observed effects of RA on microglia are likely to be mediated by RAR/RXR heterodimers.
Their expression was confirmed with RT-PCR (Figure 6). During demyelination we measured a significant increase of RXRγ (t-test, P< 0.05) and a tendency to increase for RXRβ (P = 0.059).
After three weeks of cuprizone feeding we found that activation of RAR, RXR, or LXR had no effect on the degree of demyelination, oligodendrocyte survival, or astrogliosis. Cuprizone feeding raised the number of activated microglia cells in the Cc, as shown with Iba1 IR. This increase was reduced with 9-cis RA treatment. On the other hand, after exposure to all-trans RA microglia activity was enhanced, whereas T0901317 had no effect above the toxin-induced changes.
Previous experiments suggested that tissue damage in the nervous system causes local production of all-trans RA, and we hypothesized that this constitutes a neuroprotective feedback via activation of RAR/RXR [23]. Recent experiments based on RXRγ knockdown and the application of RXRγ agonists provide convincing data that this receptor is an endogenous regulator of remyelination [1]. In another organ system, cholesterol homeostasis was disrupted in Sertoli cells of RXRβ deficient mice [24]. Therefore, we speculated that the regulation of lipid turnover is one of the functions of this receptor in the brain, at least under pathological circumstances with an effect on myelin [2]. In light of the results with RXRγ the absence of a treatment effect in the present experiments is surprising. Different experimental models were employed in the two approaches with RA treatment, focal demyelination with lysolecithin in one study [1] versus long-term systemic exposure to cuprizone in the other. While this divergence may explain some difference in the outcome, the more likely explanation is that RXRγ activation controls differentiation of oligodendrocytes but does not affect primary demyelination. Using the time period of three weeks we were able to disentangle demyelination from the compensatory processes regulated by RXRγ.
A second interesting observation is the opposite effect of 9-cis RA and all-trans RA on macrophage activation. So far, mainly anti-inflammatory activity of both isomers has been reported [4,5,8,23,25]. In the EAE mouse model, LXR activation reduced pathological symptoms via a reduction of Th17 mediated autoimmunity [17]. Thus, the lower number of Iba1 positive cells following injections with 9-cis RA was to be expected. However, Iba1 immunoreactivity was elevated in the caudal Cc when we combined cuprizone treatment with all-trans RA. In the brain, Iba1 is a specific marker of microglia which upregulate that gene during inflammation and when they assume a phagocytotic phenotype [26]. Although most studies focus on the destructive aspect of excessive microglia activation, it is crucial to bear in mind that different physiological phenotypes of microglia are not adequately described with a linear scale from resting state to inflammation [27]. In experimental models of demyelination, the role of macrophages is controversial [28]. Many studies suggest that the proinflammatory cytokines released by these cells are detrimental. Suppression of macrophages prevented the development of EAE. On the other hand, experiments with monocyte depletion indicate that microglia/macrophages have the potential to clear myelin debris, promote the recruitment of OPC, and release neurotrophic factors. A detailed discussion of these aspects is provided in a recent review [29]. The differential regulation of Iba1 described hereafter prolonged exposure to all-trans and 9-cis RA indicates that RAR and RXR modulate the activity of microglia cells. Stimulation by all-trans RA might foster phagocytosis and clearance of myelin debris and by this mechanism facilitate remyelination. It will be important in the future to study the differential effects of RXR-binding NR families with respect to the multiple physiological functions of microglia cells.
Experimental activation of the transcription factors RAR, RXR, and LXR does not directly affect toxin-induced demyelination. Ligands of these three NR families have differential effects on microglia activation.
The study was financed by intramural funding of the Institutes of Neuroanatomy and Biology II, RWTH Aachen. MK was supported by the Hertie-Foundation. We declare no conflict of interests. We thank Katherine Nelissen, University of Hasselt, Belgium, for providing the T0901317, Bernd Denecke for help with the GeneChip analysis, and the anonymous reviewers for helpful suggestions.
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Amazon Prime Day is LIVE NOW! Check out these deals on Coleman Products where you can save an extra 20% off select items!
I found this deal on this Coleman 9-Can Soft Cooler With Hard Liner for ONLY $11.19 after you apply the extra 20% off for Amazon Prime Members!


"Overlord II is a 2009 third-person action-adventure game and sequel to the 2007 video game Overlord, developed by Triumph Studios and published by Codemasters for Microsoft Windows, Xbox 360, and PlayStation 3. All versions were released in North America on June 23, 2009, then later in Europe on June 26 and Australia on July 9, 2009, alongside two spin-offs: Overlord: Dark Legend and Overlord: Minions for the Wii and the Nintendo DS respectively.
Continuing the style of the series, the game is set in a fantasy realm where players take the role of the Overlord, a mysterious warrior whose goal is to destroy or conquer the land by commanding hordes of small gremlin-like creatures known as "Minions". The story directly follows the events of the first Overlord game, with the succeeding Overlord rising to power opposing a Roman-styled military power known as the "Glorious Empire". The story was written by Rhianna Pratchett and maintains a satirical tone and dark humor towards the fantasy setting and genre."
Source: Wikipedia, "Overlord_II," available under the CC-BY-SA License.


The Ward Melville High School Linguistics class took a look into current research on endangered languages in the indigenous areas of South America during a recent guest lecture presentation by Dr. Elias-Ulloa, an associate professor of linguistics at Stony Brook University.
Linguistics is a new class at Ward Melville High School and is taught by Cynthia Porter. During the guest workshop, students learned about Arabela, a language with only four remaining speakers left in the world, as well as the languages and cultures of the Konibo and the Shipibo. The Konibo ("Deer People") and Shipibo ("Snake People") live along the Ucayali River in the Amazon rainforest in Peru. The Shipibo people are talented artists who produce beautifully intricate and vibrant works of art that honor their natural surroundings.
Dr. Elias-Ulloa shared a Shipibo myth about animals cooperating and working together to escape the belly of an anaconda.


ST. PETERSBURG — Behind the dugout, Don Semento heard the sound of balls being smashed off a hitting tee.
Jonathan Lucroy, who had just been yanked from a summer-league game by the former Umatilla coach for not hustling, was frustrated at himself.
And he responded, not by sitting on the bench and sulking or assigning blame elsewhere. Lucroy, now the Milwaukee Brewers' all-star catcher, went back to work.
"I grew up as part of a hard-working family," said Lucroy, 28. "I don't want to be one of those guys who ever quits working to get better."
Born in Eustis and raised in neighboring Umatilla, Lucroy has been a low-key leader on a team that surprisingly has led the National League Central for most of this season. With the Brewers at Tropicana Field on Wednesday afternoon to conclude a three-game series against the Tampa Bay Rays, Lucroy entered Tuesday night's game with a .307 batting average, 12 home runs and 50 RBIs.
Teammate Ryan Braun, the 2011 National League MVP, told mlb.com that Lucroy should be in the running for that honor this year.
"It's a lot of fun when you are winning," said Lucroy, in his fifth major-league season. "We have a lot of teammates who are playing well right now. For me, it's easier to play well when there are other guys around me also playing well."
Despite his success this season, including doubling twice and driving in two runs in the All-Star Game this month in Minneapolis, Lucroy enjoys a degree of anonymity.
Sure, chants of "Luc" are heard frequently at Miller Park in Milwaukee and sometimes on the road, but when Lucroy met a group of relatives and friends at a sports bar after Monday night's game, nobody else recognized him.
"Ever since we were small, we were around baseball," said Jeremy Lucroy, Jonathan's cousin. "It was always a part of us."
Said Semento: "One way I would motivate him is to say the catcher on the opposing team was better than him, and I knew he would go have a great game. He always was driven to be the best."
More than 30 of Lucroy's relatives and friends were at Monday night's game, which the Rays won 2-1, but he no longer lives in Lake County. Lucroy, his wife, Sarah, and their 3-year-old daughter, Ellia, split their time between a house on the outskirts of Milwaukee during the season and living in Louisiana in the offseason. He met his wife when they were college students at Louisiana Lafayette.
Carter Clements, Lucroy's best friend, said they spent much of their time playing baseball, but they also went hunting and fishing. They still enjoy those activities.
"He doesn't forget where he came from," Clements said. "The best way to describe him might be that he is a down-to-earth person who isn't going to let any amount of success change him."
Or get in the way of Lucroy's working to improve.


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text:
Q: how to display multiple google maps per page I have a problem when I try to show two maps in more than a view. I hope you can help me.
I have this HTML code:

            <meta charset="UTF-8">
            <meta name="viewport" content="width=device-width, initial-scale=1">
            <link rel="stylesheet" href="http://maxcdn.bootstrapcdn.com/bootstrap/3.3.6/css/bootstrap.min.css">

        ........

    ........

            <form class="form" role="form">

                    <input type="text" class="form-control" placeholder="Direccion" ng-model="address"/>

                                                        Latitud: {{latitud}}

                                                        Logitud: {{longitud}}

                                                <button ng-click="sacarDir(address)" type="submit" class="btn btn-primary btn-block">Buscar</button>

                                            </form>

.................

CONTROLLER JS:
angular.module('userManager',[],function($locationProvider){
    $locationProvider.html5Mode(true);
});

var map;
var map2;

.................

function initMap() {
    map = new google.maps.Map(document.getElementById('map_canvas'), {
        center: {lat: 40.46366700000001, lng: -3.7492200000000366},
        zoom: 6
    });

    map2 = new google.maps.Map(document.getElementById('map_canvas2'), {
        center: {lat: 40.46366700000001, lng: -3.7492200000000366},
        zoom: 6
    });

    $.get('/pois', function(res){
        var message=res.message;
        if(!res.error){
            for(i=0;i<message.length;i++){
                var marker = new google.maps.Marker({
                    position: {lat: message[i].latitud, lng: message[i].longitud},
                    map: map,
                    animation: google.maps.Animation.DROP,
                    title: message[i].nombre
                });
                // Push marker to markers array
                markers.push(marker);
            }
        }
    });
    setMarkers(markers);
}

The problem is that the first map (map_canvas) works perfectly, but when I change to the search tab the map doesn't show, only a grey square. Then if I resize the window of explorer I can see the map (map_canvas2) but the other map (map_canvas) stops working. What can I do?
Thanks!!

redpajama_set_name: RedPajamaStackExchange


text:
South Africa: post-Mangaung the ANC talks the talk but can it walk the walk? – By Renee Horne
By Uncategorised
Cyril Ramaphosa - saviour in a business suit for the ANC?
"In the Wise words of Nelson Mandela, there is no easy walk to freedom there will certainly be no easy walk socio-economic freedom". Impressive words from President Jacob Zuma at the closing day of the Mangaung Conference in the Free State. Jacob Zuma has the top job in the African National Congress (ANC) and likely to serve a second term as South Africa's president. President Zuma said this conference is a decisive moment for the party and transforming society. Indeed, there was decisive action regarding ANC comrades' misbehaviour. Expelled ANC Youth League leader, Julius Malema hoped that delegates would review his expulsion, but this was not the case. There was a great deal of talk about the ruling party's organisational renewal, yet divisions have been reaffirmed within the ANC.
Zuma also consolidated his grip on the ANC – the National Executive Committee (NEC) is dominated by his backers such as disgraced former Gauteng housing MEC Humphrey Mmemezi and former national police commissioner Bheki Cele. Those who were part of the Anti Zuma camp, such as multimillionaire, Tokyo Sexwale and Mathews Phosa were purged.
In a surprise move, super-rich Cyril Ramaphosa is now ANC deputy president. So, what happens to outgoing ANC deputy president, Kgalema Motlanthe? He will be redeployed to lead the ANC political education programme which focuses on organisational development. Whispers are that he is likely to step down as Deputy President of the country, but the ANC top brass vehemently rejected this statement.
That begs the question: will Zuma and Ramaphosa be the formidable pair that leads South Africa into the so called next phase of socio-economic transformation in the country?
One wonders how long Ramaphosa will be prepared to wait in the wings for the top job or is Zuma merely a figurehead with Ramaphosa charged to make the tough decisions? ANC secretary general, Gwede Mantashe, said that Zuma will still be in charge of the big picture, but Ramaphosa will be expected to act in much the same way as Mbeki did when he was deputy to former president Nelson Mandela after 1994. "One thing that is quite important is the deputy president is the head of government business. To me that is powerful enough. The president is not an MP but the head of government is the deputy president "" how he uses that power is up to the individual" said Mantashe in a recent business report.
Business optimism or pessimism
There is renewed optimism from business that Ramaphosa is now the second in command of the ANC. Economists have interpreted the former trade union leader's appointment as favourable to investment and the economy. It appears that Ramaphosa is taking his position seriously. He's called for a review of his business dealings. The multimillionaire owns Shanduka Holdings and is chairman of the Bidvest Group and MTN, as well as the owner of the South African franchise of McDonalds. Ramaphosa is also on the board of Lonmin, the mining company whose 34 workers were killed during an illegal protest over low pay and miserable living conditions. "This is necessary to address any potential conflicts of interest and to ensure that I can adequately perform the responsibilities of this position," stated Ramaphosa. The tycoon is envied by the poor due to making millions from Black Economic Empowerment (BEE). Appeasing, both the poor and business will be a difficult hurdle to overcome for the ANC's newest flavour of the month.
Optimism from business also stems from the fact that the ANC has squashed its alliance partners (COSATU and the SACP) calls' to broaden the central bank's mandate to include jobs and growth, but will stick to its current inflation-targeting regime. However, government will contemplate tax breaks for employers who hire young job-seekers to tackle the unemployment crisis in the country.
Nationalisation also appears to have been dealt with once and for all. ANC economic transformation policy commission head, Malusi Gigaba, said the conference had resolved that wholesale nationalisation was "off the table". There would be "strategic nationalisation" in the form of a "resource rent" tax on mining firms, which is a windfall levy of 50 percent that will kick in after investors have seen returns. On the part of investors, there is pessimism and uncertainty as they would like to see how this policy will be implemented before they invest in the country.
Broad sweeping policies
The resolutions at Mangaung are deemed as a Christmas tree of gifts to appease both business and the masses, but it's short on real specifics. The broad sweeping policies to resolve the myriad of socio-economic problems will be vested in the National Development Plan (NDP). "Our first main strategic task is the comprehensive implementation of the NDP by 2030. We will attain full employment for our people consequently reduce poverty and inequality," said Zuma. While this might raise optimism among the masses, are these realistic objectives?
Zuma added, "Comrades, we have had very robust and constructive debates in the plenary and commissions. We have taken several other resolutions. Our priority is to draw up a clear plan of action to implement the policies. Early in the year the programme of action will be done and concluded. We have got to get working on implementing our policies." Policies such as Broad-Based Black Economic Empowerment (BBBEE) which is currently being reviewed, will continue to be part of the ANC's initiative to change the racial demographic of South African business which is predominantly white.
"Over the next 5 years the ANC will take decisive action to overcome poverty and unemployment at the heart of South Africa's challenges. This will be through industrialisation, BBBEE, strengthening and expanding the role of the state embraced in the National Development Plan to build a prosperous society," said Zuma. Broad sweeping statements came from Zuma and the conference resolutions, but will this affectively appease the masses that have persevered with lack of service delivery since the ANC took office in 1994. The masses have been optimistic about the ANC's mantra, "˜A better life for all'. Only the 2014 elections will seal the fate of the ANC, already the predictions are that the party could experience the worse ever showing at the polls.
Dr Renee Horne is the Head of the BBBEE Unit at the Gordon Institute of Business Science (GIBS), South Africa
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South Africa: post-Mangaung the ANC talks the talk but can it walk the walk? – By Renee Horne | Fkthis 2 January, 2013 at 11:40
[…] Original article found at: https://africanarguments.org/2012/12/21/south-africa-post-mangaung-the-anc-talks-the-talk-but-can-it-… […]
South Africa: post-Mangaung the ANC talks the talk but can it walk the walk? – By Renee Horne | WordPress Directory 21 January, 2013 at 08:00
South Continent: post-Mangaung the ANC talks the talk but can it walk the walk? – By Renee Horne | Pvt0.com 5 February, 2013 at 20:42
South Continent: post-Mangaung the ANC talks the talk but can it walk the walk? – By Renee Horne | Google PageRank 12 February, 2013 at 17:08
What Price Justice?
Electoral Code of Conduct Adopted in Juba
AU Panel in Zalingei: "It Went Well. We Told Them."

redpajama_set_name: RedPajamaCommonCrawl


Immaculate in presentation and luxurious in design comes the stunning 8 Anchorage Avenue in the heart of Martha Cove.
This two-storey town residence comprises of 3 large bedrooms (master with WIR, full ensuite and private balcony), 2 bathrooms with main featuring spa-bath, separate shower and skylight), main open plan living area with feature gas fire-place plus upstairs rumpus room - both with beautiful floorboards.
The entertainers kitchen is the epitome of style and class with stone bench-tops, soft-closing drawers, extendable tap fitting, huge walk-in-pantry, breakfast bar plus "Neff" appliances including cooktop, dishwasher and pyrolitic & self-cleaning oven.
The master bedroom suite is simply luxurious and will beckon you to relax on its large balcony with your favourite beverage whilst you take in the surrounding views of the marina and Arthurs Seat. Boasting large walk-in-robe with ample hanging and storage space, that leads through to the sparkling ensuite. A further two large bedrooms are to the rear of the home and feature mirrored robes, plantation shutters and are serviced by the stunning main bathroom nearby complete with spa bath and separate shower.
A perfect extension of your living zone is found in the rear deck that is accessed via sliding doors from the dining room and kept in comfort with electric louvers on the pergola.
This property will have the ultimate in lifestyle access to the future shopping precinct, but without the wait to move in and enjoy your new serene & nautical chapter.
Call Jarod or Sally - the Martha Cove Specialists - today to book your private inspection!


Download the CatMan_EWS.zip file and extract it to a folder on any 64 bit computer or server that will not be shut down while Exchange server is being used. You can copy it to the Exchange server itself but that is not a requirement.
Select ApplicationImpersonation", click "add ->" and then click OK.
Open CatAdmin console if you closed it and click the "Test Credentials" button. At the bottom of the screen you will see how it tries to connect to the Exchange server Autodiscovery service. When you don't get an error here read on at #6 otherwise here are some tips.
In case of errors at "test credentials" and a local exchange server.
In exchange server admin centre, open the mailbox of your CatManAdmin service account. Click the "Account" tab and check the domain value in the drop down list. Click the "Email Addresses" tab and make sure that the Email address part behind the '@' matches that value. When you adjust the email address make sure to adjust it in the credentials field of the CatAdmin.exe too.
Click the "Test SCP in AD" button in the CatManAdmin console. It will show you a URL like https://computer.domain.com/Autodiscover/Autodiscover.xml. If the "domain.com" section in this url is different from the domain in the CatManAdmin email address, adjust the email address. Also make sure that the domain is selected in the "Account" tab of the CatManAdmin mailbox. If you can not select the domain in the list there then you must add it to that list with the"Active Directory domains and trusts"- tool. (right click the top tree object in that tool, Properties, add a "Alternative UPN Suffix"). Reopen the mailbox properties to find the UPN listed in the drop down list in the "Accounts" tab. If the credentials still don't pass click the "Chat" button on the website and we can do a remote session. There are some other less frequent occurring issues that we can quickly identify and fix for you.
Enter the email address of a user in the field behind the green plus sign and press Enter on your keyboard or click the "Add User email". Notice the "Group Number" indicator on the left hand side. You can add the next user to the same group or change the group number to add the next user to another group number.
Once you configured some groups of users, select a group and enter the list of categories and colors for that group. When you check the box under the list it will delete all categories that the user already has.
Adjust the slider so it processes more often (to the left) or less often (to the right). The uttermost left position is a interval of a minute, the uttermost right position is once a day. A full progress bar indicates processing start. It will however only start processing after installation of the processing component of the software. Read on to configure that.
Run InstallService.bat to install the processing service. You will see a log file appear. It creates up to 10 log files of 1 mb, overwriting the oldest. Check the log file for errors. Hit the Chat button on the website when you see a error that you don't understand or can't fix.
- It may take a while before the categories appear in outlook after you started the service. In the catman console is a slider and under it a yellow bar. When the yellow bar is full, the processing starts. Set the ruler to the left to make it start quicker or to the right to make it process later.


I am recently married with a lovely wife. However, i have an issue.
I had a 15K credit debt because of our spending and i lied to her about it. I did not tell her about it. She found out eventually and was really upset and disappointed with me. I had them since paid off that debt. This was before the marriage.
I married my current wife on the 19th July 2014. I am having another 18K credit dedt due to our our spending (Piled up before our marriage) and I am really looking to have a reset button to have the credit issue constantly pressing on my mind. I have a lump sum that will be coming in in Oct that will pay off the debt. But the constant disappointment that se will discover my lies a second time is really concerning to me.
I would like to hear your opinions on the above issue on how to resolve this. I welcome all advices.
I know i am really despicable in writing this but I want to resolve this to embark on a new life with her, but i am afraid it will cause her too much heartache if i were to tell her this now after we remarried.
(PS: I am an avid gundam collector and i am looking to hear the opinion of liked-minded brothers.
If you're going to pay it off in October, just tell her that you as a unit need to cut back on spending for a few months. Maybe let her see the finances in the future so you two can keep each others spending in check.
Well the marriage is supposed to be a union of two people. What will be worse, you coming out with it or her finding about it eventually on her own?
It already happened once so I think you should just let her know. Then make darn sure that it never happens again by discussing that she will be informed of any and all spending. She has to be a part of the financial status, period. Yeah, she'll probably be worried more often that way, but at least she's aware of what's going on.
What these guys said. It's better to come clean and be honest about your spending problem then for her to find out on her own later. Honesty is the best policy.
By ChapelMkII in forum Modeling How-To, Tips, and Tricks.


text:
Treasurer and RBA too close for comfort
The RBA governor and Treasurer met in Melbourne on Thursday. Credit:David Geraghty
Treasurer Josh Frydenberg is taking some extraordinary steps to try to convince Australians that everything is all right with the economy, but it will take more than spin. In an unprecedented move on Thursday, the Treasurer invited Reserve Bank of Australia Governor Philip Lowe to his office and orchestrated a joint mini-press conference about the economy. Dr Lowe said he and the Treasurer were ''100 per cent in agreement'' that the economy was growing.
Treasurers and the RBA have always collaborated behind the scenes, but this was the first time in many decades that the RBA governor and the Treasurer have spoken from the same podium, however briefly. The event creates a worrying precedent. Excessive closeness with the government could compromise the RBA's hard-won independence since the early 1990s to set monetary policy.
The fact that the RBA is able to raise and lower interest rates in the long-term interests of the economy without political interference has been crucial for Australia's record 28 years of uninterrupted growth. Former RBA governor Glenn Stevens famously made the point in the 2007 election when he raised interest rates weeks after John Howard promised to keep them low.
Mr Frydenberg has form in trying to co-opt independent regulators for his political ends. The meeting with Dr Lowe was reminiscent of the photo opportunity last February when he prevailed on Kenneth Hayne to sit by his side when the former judge handed over his report after the royal commission into the banks. Mr Hayne's discomfort on that occasion was excruciating.
Dr Lowe has shown more good humour about the latest stunt but it was still not a good look. Australia must not follow US president Donald Trump, who has tried to bully the US Federal Reserve into cutting rates.
The fact that Mr Frydenberg organised this unusual public meeting with the RBA is not necessarily a good sign. It could suggest he is worried that consumer and business confidence are flagging.
At the meeting on Thursday, Dr Lowe pointed to three causes for optimism: house prices seem to have stopped falling; tax cuts will soon be hitting the accounts of middle-income earners; and the 0.5-percentage-point reduction in the official cash rate by the RBA is reducing mortgage repayments.
At the same time, the bad news is that household debts are increasing and incomes are stagnating.
Indeed, the RBA released research this week showing that the growth in debt has households worried and is making all households, not just those on low-incomes, cut their spending.
That could frustrate Mr Frydenberg's hopes that consumers will rush out and spend their tax refunds. If they do not, the government and the RBA will come under pressure to do more to stimulate the economy to prevent unemployment rising. Yet further spending, such as a cash splash of cheques or emergency infrastructure projects, could be seen as a sign of panic.
Given the complexity of the levers that can be pulled to control the economy, it seems extraordinary that Dr Lowe and Mr Frydenberg could truly be in ''100 per cent agreement''. Australian needs more than spin from those running the economy.
A note from the editor – Subscribers can have Age editor Alex Lavelle's exclusive weekly newsletter delivered to their inbox by signing up here: www.theage.com.au/editornote


text:
Big Brother USA Season 22 All-Stars - Episode Recaps
Big Brother USA Archives
Big Brother 22 Archives
Big Brother Season 22 All-Stars-HOH comp and Nominations week 6
By IndyMom78,
September 14, 2020 in Big Brother USA Season 22 All-Stars - Episode Recaps
IndyMom78
Location:Indiana, USA
Previously, on Big Brother All-Stars, a new twist sent the HG looking for secret powers in the BB basement and David walked away with The Disruptor. The powerful committee alliance of Dani, Christmas, Tyler, Nicole, Memphis, and Cody was running the game so HOH Christmas went after two people not in her squad.
Dani had been after Bayleigh and Da for weeks and Tyler played both sides of the conflict. But after Dani and Da exchanged notes, Tyler was firmly on their radar. At the live eviction, Bayleigh's game came to an end. With the power back up for grabs the HG were hanging on for dear life. The first three off will be have nots and the last player standing will be the HOH. Who will win and who will be nominated? Find out now on Big Brother!
We pick up on day 37 at the HOH competition. Da says her ride or die and she was put on the block that she thought she was close to. This is a brand new game for her and a brand new game brings a brand new strategy. The rain starts and the HG are complaining about their calves. Tyler needs to win this HOH because last week was a tough week and he has to get his stuff together. He feels like this is a second chance for him to re-focus.
Christmas says she's conflicted about her HOH. Game wise she was successful, but personally it was tough. Tensions got elevated between her and Da and she apologized to Da 23 hours before eviction. Christmas asks her a favor and she asks Da if she wins HOH If she's safe. Da says this is pure strategic and it's not real at all. She doesn't want America to think she's dumb enough to play nice with someone who just nominated her. First chance, Christmas is hers.
David is visualizing he's on a real billboard and if he falls the game is really over. The wall tips forward and Dani says she doesn't want to win this HOH. She feels like she's in a good spot with everyone in the house. The one person she doesn't want to win is Tyler because he broke her trust. Ian thinks it's time to win because he wants to leverage that to find out who has powers and then find a way to make them benefit his game.
Kevin says everyone sees him as expendable and winning power loops you into important conversations so he needs to win this HOH. Christmas is telling them to control their breath and not hold it. Da says she's been kept in the house because she can't win comps. So she's going to use that and she falls after 12 minutes. She starts crying and says she's tired of sucking at the competitions. Then she says the tears are fake and she's using them. Da will be a have-not for the week.
The rain is falling again and Dani says she's so cold she's convulsing. She says she doesn't know where the water comes from. There's cold water, freezing water, snow cold water, and then BB water. Nicole says Enzo is being goofy and shouting things at the wall. Cody says this is classic Enzo. He's not taking it serious and Enzo is making it difficult for him to stay locked in. Enzo shouts again and Dani asks if she can change places.
The billboard is leaning forward again and Christmas tells them to hold on and lock in their breathing. Memphis asks what he did wrong in his life to end up here. He says he's barely hanging on and he's getting pelted in the face with water. Nicole's arms are shaking and her hands are getting blisters and her whole body is trembling and she's holding on for dear life. Enzo kind of likes the water and Dani says she will push him off.
David says this is by far the toughest competition he's ever done. He can't find a comfortable position, his arms and biceps are blowing up and he can't move his fingers. It's tough. David falls after 48 minutes and he's so disappointed. He wanted to do better. David will be a have-not. Kevin is shaking and Ian says he's leaning out more than everyone else and that's very frustrating. Ian falls after 53 minutes and he is the final have-not for the week.
Memphis says as soon as Ian falls and he knows he's not a have-not he pulls the cord and let's go after 53 minutes. Tyler says his knees are shaking and Enzo says this is the hardest comp they've had so far. He says his arms are feeling good but the wall is starting to tilt and he tries to readjust and he tries to get cute and go lower on the grips and falls after 1 hour and 2 minutes. The lower grips put too much weight on his arms. He wants Cody or Tyler to win so he knows he's safe for sure if they win.
It's down to Kevin, Dani, Nicole, Tyler, and Cody. Kevin says this competition is difficult and this is what Big Brother is all about, pushing yourself and making it count. Kevin is grunting and hanging on and the rain starts again. Kevin is shaking and he can't hold himself any longer. Kevin falls after 1 hour and 7 minutes. He says it's another week of survival. He says there is no one in this house he trusts except himself.
Tyler says it's down to himself, Cody, Nicole, and Dani and even though they are in an alliance he knows he wronged Dani. He says you don't get too many chances to make things right so hopefully he can win and can make things right. Dani says she is going to do everything she can to outlast Tyler. You are going to have to peel her body off the wall in order for her to fall before Tyler.
It's down to Dani, Nicole, Cody, and Tyler. Dani is chanting Tennessee and she says the only thing that cannot happen is for Tyler to win this HOH. Cody is readjusting and Tyler asks how it's hanging everybody. The rain is pouring again. Tyler says he's hunched off the wall like a gargoyle and he has these evil spirits coming out of his mouth. He's holding on with all his might but his fingers are slipping and his arms are shaking. He does a sommersault and falls off after 1 hour and 16 minutes.
Dani says words cannot express how happy she is. She's ready to throw the competition but she doesn't want to fall right away because she doesn't want to make it obvious she was waiting for Tyler. Cody doesn't want to win because the girls have won nothing and he thinks it's time they get some blood on their hands. Dani is squealing. Nicole says as much as she wants to win and she sees Dani and Cody and she trusts them and she doesn't want to nominate anyone this week. Nicole falls and that's Cody's cue and he lets go right away. Dani has won HOH!
Dani is so flooded with emotions. The first thing she thinks of is her daughter and she's so overwhelmed with joy. She really doesn't know what happened. She wanted to throw it but then she beat everybody. Obviously, she still has it. Tyler says his mind didn't give out his body did. He's excited Dani won on one hand, but on the other hand Dani might want to get revenge on him. Not many have wronged her in the game, but she knows he's someone who has.
The HG head inside from the HOH competition. Dani says she didn't really want this but she's the HOH this week. She's super excited she's finally going to get pictures and a letter from home. She's aligned with everyone in the house and she's going to make some people really mad this week. Tyler says with Dani being the new HOH and he did kind of throw her under the bus a couple of weeks ago.
Nicole winning Dani winning this HOH is great for her. She trusts Dani and she thinks Dani trusts her so she shouldn't see the block this week. But she knows Dani didn't want it. Dani hugs and Da and Da tells us her and Dani compared notes and bonded over it so she's going to get back in her ear about Tyler being a target. Da is talking to David and he thinks Dani is close with Christmas, Memphis, and Tyler. David doesn't feel safe, but he has his power and he can keep himself safe this week. He hasn't told anyone about his power and he doesn't intend to.
Ian and Kevin are talking. They both feel ok but Kevin says we'll see. He doesn't have an agreement with her and he has no idea who she'd put up. Kevin says out of everyone in the house, he genuinely likes Dani but she's stone faced. He's talked very little strategy with her and he's a little worried. Ian says he used to be a lot better at those comps and Kevin said that was torture.
Dani and Da are in the HOH room. Dani says she's used to hating everyone in the house and being eager to get them out, but this season is different. Da says she needs to sprinkle some magic and keep Dani from saying her name. Da pitches Christmas as pawn next to Tyler. Dani says she's scared. She says last time she played too hard too fast and it came back to bite her.
Dani is talking to Cody and Cody suggests putting up Kevin and David. Cody says he and Dani have an alliance with almost everyone but them. He says they are the easiest targets. Cody says she has to put Kevin up. Dani says she doesn't think he's coming after her ever. Cody asks who she thinks is coming after her and she says Tyler. Cody says put him on the block. Then says just kidding because he'll win the veto. Cody says she can't put him up and blow up their alliance two straight weeks. Cody says keeping Tyler around is important for him because he'll win a lot of competitions and he will be a bigger target. Cody says he doesn't like Tyler going this week means the others numbers won't be clipped. He doesn't want anyone to come down this week because it would just be chaos.
Dani is talking to Da and Kevin and they are laughing about Dani planning to pop out and scare Cody. Da goes to get Cody after Dani hides and she jumps out and screams and Cody says that was the biggest betrayal of all time. Dani says the ultimate betrayal and they are laughing. Dani says he's so mad.
Kevin is talking to Enzo, Dani, and David and Kevin is hoping he's doing the LGBT community proud. He says sometimes there is criticism too. He's a firm believer that representation matters. He became a part of the show because of the representation BB offers and he hopes his community is proud of the way he's representing them. He was criticized last time because of the way he acted because he was "too feminine". He's putting his face out there for little Kevin's of the world to know it's ok for them to be who they are.
Dani is in the WA and Tyler comes in and says she killed that comp. He asks if she knows what she's doing and she says I guess, it's tough. Tyler says he wouldn't blame her if she backdoored him, he deserves it. Tyler says he wants to be honest with Dani but he feels it would be too early and they have other fish to fry. Dani says Tyler put himself on her radar. She's in a position where she could come after him but he could seriously hurt her game. So does she go after him or not.
Nicole is talking to Dani and she asks what she's going to do. Dani says Kevin and David. She says Kevin is going to hate her. She wants to tell him to trust her. She feels horrible. She's trying to decide. She's scared to upset Christmas. Nicole says are talking about backdooring her? Dani says not her, Tyler. Dani tells her about the conversation she had with Tyler. Dani says she doesn't trust him at all. Nicole doesn't want this to happen. Even if Tyler is a threat to Dani's game, that will not be good. If she swings and misses it will get ugly and The Committee will be shattered. Dani says she knows she has to take a shot but she needs it to be the right time. Nicole says she'll support whatever she wants to do.
Kevin comes in to the HOH to talk to Dani. Kevin says he would like to keep working with her and she says she's on the same page. He asks if he's in trouble this week. Dani says she's scared of the powers and she wants to name people to be pawns. She totally trusts him and she hopes he trusts her. She says if she can guarantee the votes to stay how would he feel. Kevin is not trying to be a pawn again. What can he say to convince her? He tells her that people can see him as expendable. Dani says she would never want him out of the house. Dani says he has herself and Da. Kevin doesn't want to fee completely and utterly played. He'd be salty if he had to celebrate his birthday alone in jury. Dani doesn't think he or David is coming after her but she's in The Committee.
Tyler is in the HOH and Dani offers him a donut. She says if Tyler is going to stay then she needs to cover her butt and make sure he won't come after her. Tyler says if she doesn't put him he will be indebted to her. Dani wants to make a verbal agreement that they won't go after each until F6 with The Committee. Tyler says he'll go one step further and says he won't go after her until F4. He says if the week goes by and he doesn't end up on the block then he knows he mended things. Tyler says if she puts him or backdoors him he deserves it, but if she doesn't then he is hers. Dani says she might not get this opportunity again, but Tyler is one of those people if you swing, then you better not miss.
It's time for nominations! Dani's first nominee is…Kevin. Dani's second nominee is…David. Dani has nominated them because winning HOH was catch 22. She doesn't want to crush anyone's dreams of being here but she just doesn't talk game with David or Kevin. Dani says they are the only two she doesn't talk game with. She's trying to dodge powers and she needs to play the game she wants to play.
Kevin says he is a pawn again. He's disposable to these people. He must have zero persuasive skills. He just needs to go for that veto. David says he's going to be safe. He has a power and no one knows and he will not only take himself off but he'll be safe for the week. What will Dani do when The Disruptor power is used? And who will win the Power of Veto? Find out Tuesday!


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This easy salsa recipe is going to be your go-to for any time you are having company or bringing an appetizer to a party. Just wait until you taste the way these flavors mingle!
If you have sailed on a Carnival ship and eaten at the Blue Iguana, you probably remember the Watermelon Jicama Salsa. It's kind of unforgettable, to the point that I had to make it as soon as I got home.
A couple of weeks ago my sister and I went on a girls getaway spending three days on the Carnival Liberty sailing to Nassau in the Bahamas. We had such a blast hanging out at the pool, spending the day on a private island in Nassau, and eating at several of the fabulous restaurants onboard the ship.
One of my favorite places to eat was the Blue Iguana. I love Mexican food, largely in part because I adore salsa. If there is a party where salsa and chips are served, you will find me hanging out near the bowl. Truth.
Now that I have this easy salsa recipe and know how truly simple it is to prepare, this will be my go-to recipe. The jicama gives the salsa a crunch that doesn't get soggy, and the watermelon gives it just the right amount of sweetness.
You will see that I did not add jalapenos as my younger daughter can't take the heat. Unless you have a family member that is opposed, I would definitely include the jalapenos.
Place first 4 ingredients in a medium-sized bowl. Pour lime juice over all and add lime zest.
Gently fold together being careful not to smash the watermelon. Add salt and taste to your preference.
Chill before serving. This salsa kept really well in the fridge. We had it on chicken tacos one night, and shrimp tacos the next. It would also be wonderful served with chips or as a topping for fish. The possibilities are endless!
Be sure to check out the Blue Iguana the next time you are sailing with Carnival!
You are going to love this easy salsa recipe from Carnival Cruise Lines!
If you have sailed on a Carnival ship and eaten at the Blue Iguana, you probably remember the Watermelon Jicama Salsa. It's kind of unforgettable, to the point that I had to make it as soon as I got home. Just wait until you taste it!
Place first 4 ingredients in a medium sized bowl.
Pour lime juice over all and add lime zest.
Add salt and taste for your preference.
This salsa kept really well in the fridge. We had it on chicken tacos one night, and shrimp tacos the next. It would also be wonderful served with chips or as a topping for fish. The possibilities are endless!
It is SO good and stays crunchy for days, Lynsey! I'm planning dinner around what goes with it because I have some left!
Sounds so good! I've never had jicama before.
It's not a very strong flavor but the crunch is amazing, Sherry. It's the perfect addition to the watermelon!
I love salsa and I love watermelon. Never would have thought of putting them together. Can't wait to make this.
PS: your pictures look great!
Thank you, Linda! I've had it before, but not this good! Carnival's recipe is the best I've ever tasted! You will love it!
Yum. That sounds so good. Maybe as a garnish rolled in a tortilla too. But I think I'd go the salsa and chips route!
So glad you have this recipe. I just returned from a Carnival cruise aboard the PRIDE (May 14-21, 2017). I had this everyday!!!! It is unbelievable how GOOD this is! Hope this recipe holds up to original – looks like it should – the cilantro is the key I think….
I agree, Kristen! And I like extra cilantro!
Exactly like on the ship! Delicious!
Thank you so much for sharing this recreation! I adored the salsa on my last Carnival trip . I had it most days, particularly in the morning with the huervos rancheros (sp?). Looking forward to making.
Thanks, Jim! I love it in the morning with eggs, too. I think the crunch makes it extra delicious. Enjoy!


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The 1991–92 Washington State Cougars men's basketball team represented Washington State University for the 1991–92 NCAA Division I men's basketball season. Led by fifth-year head coach Kelvin Sampson, the Cougars were members of the Pacific-10 Conference and played their home games on campus at Beasley Coliseum in Pullman, Washington.

The Cougars were  overall in the regular season and  in conference play, tied for fifth in the standings. There was no conference tournament this season; last played in 1990, it resumed in 2002.

For the first time, Washington State played in the National Invitation Tournament, and advanced to the

Postseason results

|-
!colspan=5 style=| National Invitation Tournament

References

External links
Sports Reference – Washington State Cougars: 1991–92 basketball season

Washington State Cougars men's basketball seasons
Washington State Cougars
Washington State Cougars
Washington State
Washington State

redpajama_set_name: RedPajamaWikipedia


How the bicep tenses is no longer a secret. In every muscle cell there are so-called myofibrils, which contract at the same time. They are responsible for muscle movement. Each of these fibrils represents an exact pattern of hundreds of identical units consisting of different protein molecules. However, it is not yet understood how these individual building blocks arrange themselves into highly regular patterns during embryonic development or healing processes. An interdisciplinary team involving the physicist Dr. Benjamin Friedrich (Center for Advancing Electronics Dresden – cfaed, TU Dresden) has now acquired a research contract from the "Human Frontier Science Program" to investigate this question.
However, how the individual building blocks of myofibrils arrange themselves into such highly regular patterns during embryonic development or during healing processes (e.g. after sports injuries) is still a matter of controversy in science. In order to uncover this secret, cooperation between different scientific disciplines is required. An interdisciplinary team led by biologist Frank Schnorrer (Developmental Biology Institute of Marseille – IBDM), the physician Olivier Pourquie (Harvard Medical School) and the physicist Benjamin Friedrich (Center for Advancing Electronics Dresden – cfaed, TU Dresden) has now been awarded a research grant by the international "Human Frontier Science Program" to investigate this question. The grant has a volume of over one million US dollars and a term of three years.
Frank Schnorrer's group will use high-resolution video microscopy to follow the individual stages of pattern formation in the fruit fly model organism. The flies are genetically modified so that individual molecules can be made visible or turned off. The researchers also hope to use novel biomolecules that light up when they are subjected to mechanical stress and thus enable the precise measurement of minute forces. For the first time, it is now possible to investigate how the formation of regular structures and the generation of mechanical forces go hand in hand during the self-assembly of myofibrils.
Oliver Pourquie's team uses human stem cells that are differentiated into muscle cells in the Petri dish. This enables to test the findings obtained from fruit flies directly on mammalian cells without the need for animal experiments.
The Dresden-based project partner Benjamin Friedrich is research group leader in the "Cluster of Excellence" cfaed at TU Dresden. Among other things, he investigates the question of how biomolecules spontaneously assemble into functional structures and how these processes function robustly even in the event of disturbances and fluctuations. Of particular interest is the transfer of biological principles to engineering problems, such as the self-organised dynamics of stochastic components. Conversely, dealing with technical applications gives a completely new view of the fundamental biological question of how biological systems function reliably, despite various interferences. Here, Dresden is an ideal location for interdisciplinary research with the University of Excellence TU Dresden with the Cluster of Excellence cfaed, but also the proposed Cluster of Excellence "Physics of Life", and the many partner institutes, such as the Max Planck Institute for Molecular Cell Biology and Genetics, or the Biotechnology Centre.
cfaed is a "Cluster of Excellence" within the Excellence Initiative of the German federal and state governments. The interdisciplinary research center for advancing electronics is based as a Central Academic Unit at TU Dresden, and also integrates TU Chemnitz as well as nine non-university research institutions in Saxony as participating institutions. The Cluster brings together 300 scientists from around 30 nations. It is engaged in the development of completely new solutions for the transmission and processing of information. With its vision, the Cluster aims to shape the future of electronics and initiate revolutionary new applications, such as electronics featuring zero-boot time that are capable of THz imaging, or support complex biosensors. In order to achieve its goals, cfaed combines the thirst for knowledge of the natural sciences with the innovative power of the engineering sciences. Novel materials such as 2D materials, silicon nanowires, carbon nanotubes or polymers as well as completely new concepts such as self-assembling structures from DNA originals are investigated. The DFG-funded Cluster is in its first funding period, which runs from 2012 to 2018. A proposal for a further seven-years funding period has been submitted.


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Home Biography Paula Throckmorton
Paula Throckmorton
Paula Throckmorton is famous for being the es wife of journalist and author, Fareed Zakaria. Fareed is well known in the public for being the host of his own show on CNN, Fareed Zakaria GPS.
Don't Miss: Courtney Reagan
Paula is a MBA graduate from Harvard university. She used to be a jewelry maker and managed her own business. Now, she works as a writer and meditation teacher. She recently published her first novel. She used to write for Wall Street Journal and Slate.
She was interested in meditation since she was nineteen years old and appreciated the fact that she was eventually able to become a meditation teacher.. She teaches meditation to various groups of people including women undergoing chemotherapy.
The popular online news site Huffington Post asked Paula to speak on motherhood. On the topic of newborns, she said "What is it about newborns? How can someone the size of a bread loaf contain so much soul that she completely changes the energy in a room? We are all drawn to newborns, even the loud uncle who flashes his new gadgets and back slaps too hard. We whisper around a baby, keep the lights low, look into the little person's eyes. We forget about multi-tasking and emails. We are our best selves: calm, loving and present. We listen more than we talk and want to help in any way possible. We feel a pure love. Somehow newborns remind us of the most beautiful and quiet feeling inside us. They remind us of who we are."
She wanted to give new mothers a reality check and tell them about what they should expect, "But then the relentless physical duties of motherhood begin -- the feeding, the burping, the pooping, the diapers, the sleep deprivation, not to mention hosting the pesky aunt who insists that the baby's nose closely resembles hers. The first trip in a car is a herculean challenge. Packing the bag with the wipes, the diapers, the extra clothes, the bottle, the barf cloth. And then the car seat. You might have read the manual and adjusted the straps before your baby's birth, but who knew that a human being could be so small?"
Married to a Famous Journalist
Paula got married to the love of her life, Fareed in 1997. The relationship between Paula and Fareed started with a blind date that was set up by their mutual friend. She ended up having three children with him. The couple has a son named Omar and two daughters Lila and Sofia. When she married him, she knew that she would want to start a family with him. He was everything that she wanted in a husband and father to her children. She felt safe around him because he was always confident and knew what he wanted out of life. She was attracted to him because he was very articulate and able to speak to her on a level that she never experienced with other men before in her life.
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Paula was never married before meeting Fareed. Her past boyfriends and old dating life are not known to the media. She came into public limelight after being married to Fareed. Fareed is also famous because his father, who is a political figure in India. His father Rafiq, was an Islamic scholar and a politician associated with the Indian National Congress. His father joined the Indian movement for freedom.
She is now living in New York with her husband and three children. They have tried to keep their best to keep their personal lives and their children far away from the clutches of the media. Though Paula is not a celebrity herself like her husband, she is quite popular and active in her social media profiles. She likes to give her fans and followers updates on her life. She is well aware that a lot of her fan base on social media comes from the fact that she has a popular celebrity husband. That fact does not bother her, she is not petty or jealous of her husband's success. She is very supportive of her husband and sees her activity on social media as an extension of the family and a way to help promote her husband's career.
Reports began to surface that claimed Zakaria and his wife Paula were not in a comfortable married zone. Some sources said that Fareed has an affair with one of his female colleagues which brought tension to the marriage. Fareed and Paula started to live individually, until they found the time to work out their differences. They wanted to make things right so they can avoid having a divorce.
When he was temporarily fired by CNN and Times Magazine, his personal life took a hit just like his career. It was reported that for a period of three years, the couple had been trying to make their marriage work out. Initially, the couple refused to confirm to the public that there was a dispute. But, in the last years of their marriage, they have admitted that they were temporarily separated for a few years before getting back together. They were seen together in many public events indicating that that they had patch things up.
One source revealed that the separation was due to a shirtless picture of Fareed that went viral on social media sites. The couple began to fight over the picture and even when the picture was proved to be not Fareed, the disputes continued because of the tension and doubt that it caused.
Unfortunately, in July of 2018, it was announced that Paula asked for a divorce from Fareed. After 21 long years of marriage, she was done and wanted out of the marriage. Fareed publicly announced Paula's request for the divorce and confirmed that the two had been living apart for a while. Fareed took the divorce very hard but the only person he had to blame was himself because of his infidelity. Paula was not a part of any extra marital affair rumors, all of those rumors were tied to Fareed only.
After the news of divorce went public, it was revealed that the problems in their marriage were due to his lack of attention to family life because of his career problems. He was being stressed out at work and was working hard to fix his career. While he was focused on journalism, he lost sight of wife and children.
Courtney Reagan
Shara Grylls
Juju Chang
Joanna Going
Rick Mahorn


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Former Tennessee star Jay Graham again returning to Vols as running backs coach
by Gene Henley
Jay Graham is shown in this 2012 file photo. (Amy Smotherman Burgess/News Sentinel)
KNOXVILLE - According to multiple reports, Tennessee has hired former Volunteer Jay Graham to be its running backs coach.
Graham held that position the last two seasons at Texas A&M.
It will be his third stint in Knoxville as a coach, as he served as a graduate assistant in 2005 and coached running backs in 2012 in Derek Dooley's final season as head coach.
In between there was a stint at the University of Tennessee at Chattanooga, where his backs averaged 177.6 rushing yards per game and Eldra Buckley was a 2006 first-team All-Southern Conference selection. Buckley would go on to spend five seasons on NFL rosters, rushing for 111 yards and one touchdown, scored while with the Philadelphia Eagles in 2009.
Tennessee running back Rajion Neal drills with running backs coach Jay Graham during practice Monday, August 6, 2012, at the University of Tennessee in Knoxville. (Saul Young/Knoxville News Sentinel)
Graham also coached at UT-Martin (2008), South Carolina (2009-11) and Florida State (2014-17), where he was instrumental in the recruitment and development of some of the top players in the country.
With the Vols he replaces David Johnson, who left recently to become the running backs coach at Florida State.
Graham rushed for 2,609 yards and 25 touchdowns during his Tennessee playing career, the yardage ranking sixth all-time. In 1995, he ran for 1,438 yards and 12 scores and caught a touchdown pass.
He was drafted by the Baltimore Ravens in 1997 and spent five years in the NFL before closing out his pro career in 2003 with the Montreal Alouettes of the Canadian Football League. In the NFL he had 454 yards rushing and two scores, both in his rookie season in Baltimore.
Contact Gene Henley at ghenley@timesfreepress.com. Follow him on Twitter @genehenley3 or at Facebook.com/VolsUpdate.