We present a free-form model of SMACS0723, the first cluster observed with JWST. This model does not make any strong assumptions on the distribution of mass (mostly made up of dark matter) in the ...cluster and we use it to study the possible correlation between dark matter with the intracluster light and distribution of globular clusters (GCs). To explore the uncertainty in mass modeling, we derived three lens models based on spectroscopically confirmed systems and new candidate systems with redshifts predicted by the lens model derived from the spectroscopic systems. We find that beyond the radius of influence for the brightest cluster galaxy (BCG), the total mass does not trace the intracluster light (ICL), implying the need for a dark component (dark matter). Two loop-like structures observed in the intracluster light do not have any obvious correspondence with the total mass (of mostly dark matter) distribution. The radial profiles of the ICL and the distribution of GCs are similar to each other, but they are steeper than the profile of the lens model. More specifically, we find that the total mass is shallower by 1 dex in log scale than both ICL and GC profiles. This is in excellent agreement with current
N
-body simulations of cold dark matter.
We present a new compilation of Type Ia supernovae (SNe Ia), a new data set of low-redshift nearby-Hubble-flow SNe, and new analysis procedures to work with these heterogeneous compilations. This ...'Union' compilation of 414 SNe Ia, which reduces to 307 SNe after selection cuts, includes the recent large samples of SNe Ia from the Supernova Legacy Survey and ESSENCE Survey, the older data sets, as well as the recently extended data set of distant supernovae observed with the Hubble Space Telescope (HST). A single, consistent, and blind analysis procedure is used for all the various SN Ia subsamples, and a new procedure is implemented that consistently weights the heterogeneous data sets and rejects outliers. We present the latest results from this Union compilation and discuss the cosmological constraints from this new compilation and its combination with other cosmological measurements (CMB and BAO). The constraint we obtain from supernovae on the dark energy density is image, for a flat, Lambda CDM universe. Assuming a constant equation of state parameter, w, the combined constraints from SNe, BAO, and CMB give image. While our results are consistent with a cosmological constant, we obtain only relatively weak constraints on a w that varies with redshift. In particular, the current SN data do not yet significantly constrain w at image. With the addition of our new nearby Hubble-flow SNe Ia, these resulting cosmological constraints are currently the tightest available.
Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing ...turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.
Ghrelin is directly involved with short-term regulation of energy balance. Although circulating levels of ghrelin are elevated in anorexia nervosa and reduced in obesity, the role of ghrelin in ...regulating long-term energy balance in healthy women has not been investigated. We examined the effects of a 3-month energy deficit-imposing diet and exercise intervention on circulating ghrelin in normal-weight, healthy women. Body composition, resting metabolic rate, and serum ghrelin were measured at pre-, mid-, and postintervention in controls (n = 7), who performed no exercise, and exercising women who remained weight stable (n = 5) or lost weight (n = 10). Exercise training occurred five times per week, and subjects were fed a specific diet. Ghrelin significantly increased over time (770 ± 296 to 1322 ± 664 pmol/liter) in the weight-loss group compared with the controls and the weight-stable group (P < 0.05). Changes in ghrelin were negatively correlated with changes in body weight (r = −0.61; P < 0.05). Body fat, body weight, and resting metabolic rate significantly decreased in the weight-loss group before the increase in ghrelin. These findings suggest that ghrelin responds in a compensatory manner to changes in energy homeostasis in healthy young women, and that ghrelin exhibits particular sensitivity to changes in body weight.
Turmeric (Curcuma longa L., Zingiberaceae) rhizomes contain two classes of secondary metabolites, curcuminoids and the less well-studied essential oils. Having previously identified potent ...anti-arthritic effects of the curcuminoids in turmeric extracts in an animal model of rheumatoid arthritis (RA), studies were undertaken to determine whether the turmeric essential oils (TEO) were also joint protective using the same experimental model. Crude or refined TEO extracts dramatically inhibited joint swelling (90−100% inhibition) in female rats with streptococcal cell wall (SCW)-induced arthritis when extracts were administered via intraperitoneal injection to maximize uniform delivery. However, this anti-arthritic effect was accompanied by significant morbidity and mortality. Oral administration of a 20-fold higher dose TEO was nontoxic, but only mildly joint-protective (20% inhibition). These results do not support the isolated use of TEO for arthritis treatment but, instead, identify potential safety concerns in vertebrates exposed to TEO.
We examine whether firms utilize governance systems and increased monitoring mechanisms when information asymmetry and managerial discretion are limited. Given that such monitoring is costly, we ...expect regulated firms to use less monitoring if regulation substitutes for governance. Using data from initial public offerings, we document that regulated firms have greater proportions of monitoring directors and larger boards as well as use similar amounts of equity-based compensation as non-regulated firms. Further, regulated and unregulated firms are analogous in terms of observed trade-offs between traditional monitoring mechanisms and insider ownership. Finally, regulated firms appear to decrease monitoring following a period of deregulation. These findings support the hypothesis that regulation and governance are complements and are consistent with the notion that regulators pressure firms to adopt effective monitoring structures.
While tumoral Smad-mediated transforming growth factor β (TGFβ) signaling drives osteolytic estrogen receptor α-negative (ER-) breast cancer bone metastases (BMETs) in preclinical models, its role in ...ER+ BMETs, representing the majority of clinical BMETs, has not been documented. Experiments were undertaken to examine Smad-mediated TGFβ signaling in human ER+ cells and bone-tropic behavior following intracardiac inoculation of estrogen (E
)-supplemented female nude mice. While all ER+ tumor cells tested (ZR-75-1, T47D, and MCF-7-derived) expressed TGFβ receptors II and I, only cells with TGFβ-inducible Smad signaling (MCF-7) formed osteolytic BMETs in vivo. Regulated secretion of PTHrP, an osteolytic factor expressed in >90% of clinical BMETs, also tracked with osteolytic potential; TGFβ and E
each induced PTHrP in bone-tropic or BMET-derived MCF-7 cells, with the combination yielding additive effects, while in cells not forming BMETs, PTHrP was not induced. In vivo treatment with 1D11, a pan-TGFβ neutralizing antibody, significantly decreased osteolytic ER+ BMETs in association with a decrease in bone-resorbing osteoclasts at the tumor-bone interface. Thus, TGFβ may also be a driver of ER+ BMET osteolysis. Moreover, additive pro-osteolytic effects of tumoral E
and TGFβ signaling could at least partially explain the greater propensity for ER+ tumors to form BMETs, which are primarily osteolytic.
The first
James Webb
Space Telescope (JWST) data on the massive colliding cluster
El Gordo
allow for 23 known families of multiply lensed images to be confirmed and for eight new members of these ...families to be identified. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and nine were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range 2 <
z
< 6. The derived dark-matter distribution confirms the double-peak configuration of mass found by earlier work with the southern and northern clumps having similar masses. We confirm that El Gordo is the most massive known cluster at
z
> 0.8 and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at
z
= 0.87 and has an estimated mass of 3.8 × 10
9
M
⊙
, making it the smallest substructure found at
z
> 0.5. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at
z
= 2.1878. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at
z
> 6, making more of them visible than in blank fields of a similar size, but there appears to be a deficiency of such objects.
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scarring and matrix deposition. Recent reports highlight an autoimmune component in IPF ...pathogenesis. We have reported anti-col(V) immunity in IPF patients. The objective of our study was to determine the specificity of col(V) expression profile and anti-col(V) immunity relative to col(I) in clinical IPF and the efficacy of nebulized col(V) in pre-clinical IPF models.
Col(V) and col(I) expression profile was analyzed in normal human and IPF tissues. C57-BL6 mice were intratracheally instilled with bleomycin (0.025 U) followed by col(V) nebulization at pre-/post-fibrotic stage and analyzed for systemic and local responses.
Compared to normal lungs, IPF lungs had higher protein and transcript expression of the alpha 1 chain of col(V) and col(I). Systemic anti-col(V) antibody concentrations, but not of anti-col(I), were higher in IPF patients. Nebulized col(V), but not col(I), prevented bleomycin-induced fibrosis, collagen deposition, and myofibroblast differentiation. Col(V) treatment suppressed systemic levels of anti-col(V) antibodies, IL-6 and TNF-α; and local Il-17a transcripts. Compared to controls, nebulized col(V)-induced tolerance abrogated antigen-specific proliferation in mediastinal lymphocytes and production of IL-17A, IL-6, TNF-α and IFN-γ. In a clinically relevant established fibrosis model, nebulized col(V) decreased collagen deposition. mRNA array revealed downregulation of genes specific to fibrosis (Tgf-β, Il-1β, Pdgfb), matrix (Acta2, Col1a2, Col3a1, Lox, Itgb1/6, Itga2/3) and members of the TGF-β superfamily (Tgfbr1/2, Smad2/3, Ltbp1, Serpine1, Nfkb/Sp1/Cebpb).
Anti-col(V) immunity is pathogenic in IPF, and col(V)-induced tolerance abrogates bleomycin-induced fibrogenesis and down regulates TGF- β-related signaling pathways.
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•While anti-inflammatory effects of ginger are often attributed to its gingerols, each of its secondary metabolites, the essential oils and the gingerols, are joint protective in an ...experimental arthritis model.•Both of ginger’s secondary metabolites (essential oils and gingerols) have anti-arthritic effects in an experimental model.•Anti-arthritic effects of ginger essential oils (GEO) mirrored those of 17-β estradiol.•However, GEO had no effect on classic estrogen-responsive organs.•GEO were well tolerated.•GEO and gingerols may have additive joint protective effects in arthritis.
Ginger and its extracts have been used traditionally as anti-inflammatory remedies, with a particular focus on the medicinal properties of its phenolic secondary metabolites, the gingerols. Consistent with these uses, potent anti-arthritic effects of gingerol-containing extracts were previously demonstrated by our laboratory using an experimental model of rheumatoid arthritis, streptococcal cell wall (SCW)-induced arthritis. In this study, anti-inflammatory effects of ginger’s other secondary metabolites, the essential oils (GEO), which contain terpenes with reported phytoestrogenic activity, were assessed in female Lewis rats with SCW-induced arthritis. GEO (28mg/kg/d ip) prevented chronic joint inflammation, but altered neither the initial acute phase of joint swelling nor granuloma formation at sites of SCW deposition in liver. Pharmacologic doses of 17-β estradiol (200 or 600μg/kg/d sc) elicited the same pattern of anti-inflammatory activity, suggesting that GEO could be acting as a phytoestrogen. However, contrary to this hypothesis, GEO had no in vivo effect on classic estrogen target organs, such as uterus or bone. En toto, these results suggest that ginger’s anti-inflammatory properties are not limited to the frequently studied phenolics, but may be attributable to the combined effects of both secondary metabolites, the pungent-tasting gingerols and as well as its aromatic essential oils.
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