the larger cations tetramethylammonium, tetraethylammonium, or N-methyl-D-glucamine (Figure 1E). This size-selective permeability increase is characteristic of claudin-2 channel activity (14-16, 48-50), but does not exclude the possibility that other cation-selective pore-forming claudins, e.g., claudin-15 (10, 13, 22), contribute to IL-13-induced barrier loss in vivo. We therefore asked if claudin-2 was required for IL-13-induced barrier loss. Prior to IL-13 treatment, paracellular permeability was similar in Cldn2 +/+ and Cldn2-/mice, consistent with limited claudin-2 expression in adults. IL-13 treatment was not, however, able to increase paracellular permeability of small cations, including Na + and methylamine in Cldn2-/mice (Figure 1F). Claudin-2 is therefore necessary for IL-13-induced increases in intestinal pore pathway permeability. In order to determine if claudin-2 upregulation is sufficient to mediate the effects of IL-13 on intestinal cation permeability, transgenic mice expressing GFP-tagged mouse claudin-2 from the intestinal epithelium-specific villin (Vil1) promoter (Cldn2 Tg) were characterized (29). Total claudin-2 expression (the sum of endogenous and GFP-claudin-2) in these Cldn2 Tg mice was similar in distribution (Figure 1G) to that of IL-13-treated Cldn2 +/+ mice (Figure 1B) and increased 3.3-fold relative to Cldn2 +/+ mice that did not receive IL-13 (Figure 1, H and I). Moreover, transgenic GFPclaudin-2 expression selectively increased paracellular permeability of Na + , methylamine, and, to a lesser extent, ethylamine, in a manner that recapitulated the effect of IL-13 on Cldn2 +/+ mice (Figure 1J). Claudin-2 is, therefore, both necessary and sufficient to mediate IL-13-induced barrier loss in vivo. Transgenic claudin-2 expression exacerbates immune-mediated colitis. We have found that severity and duration of infectious colitis are reduced in these GFP-Cldn2 Tg mice (29). A study of similar transgenic mice expressing human claudin-2 from the same Vil1 promoter demonstrated that claudin-2 overexpression was also protective in DSS-induced, chemical colitis (41). Conversely, claudin-2 knockout exacerbated infectious and chemical colitis (29, 42). These data suggest that claudin-2-mediated pore pathway permeability increases may be adaptive, i.e., beneficial in IBD. To test this hypothesis, we compared severity of experimental IBD in immunodeficient Cldn2 Tg Rag1-/and Cldn2 +/+ Rag1-/mice using the well-established T cell transfer model (33, 51). Unexpectedly, disease was significantly more severe in Cldn2 Tg Rag1-/mice relative to Cldn2 +/+ Rag1-/mice. This was demonstrated by more extensive weight loss (Figure 2A) and greater disease activity (Figure 2B). Consistent with increased disease severity, leak (macromolecular) and unrestricted (epithelial damage) pathway permeabilities, measured as 4-kDa and 70-kDa dextran flux, respectively, were markedly greater in Cldn2 Tg Rag1-/mice relative to Cldn2 +/+ Rag1-/mice (Figure 2C and ref. 29). Colitis was associated with increased claudin-2 exp...

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[1] The interglacial Marine Isotope Stage (MIS) 11 received special attention due to its remarkable resemblance with present-day climate. Based on synchronicity of marine, ice sheet and terrestrial proxy responses, warm episodes with intervening cool phase(s) at MIS 11 are qualitatively established. Here we quantitatively evaluate 15 climate proxies during 368-552 kyr intervals adopting a novel long-range cross-correlation approach and information theory based similarity measures. We also estimate the information flow rate and dominant flow direction between these climate variables using transfer entropy and the related directionality index. Our results unequivocally establish that atmospheric CO 2 (p CO2 ) is the driving signal while all other proxies used in this study are the responses. The climate forcing greenhouse gas, the atmospheric CO 2 (p CO2 ) and the response signals like sea surface temperature (SST) and carbon isotope composition of total organic carbon (d 13 C TOC ) proxies are strongly correlated ($1 or À1) without significant observable time lag (less than 1 kyr). Various substages of MIS 11 are recognizable in the SST data alone based on normalized similarity measures. Additionally, eight more proxies from lacustrine sediments are identified as primary. During the cooler substages these proxies bear more similarity with ambient atmospheric p CO2 . Thus, the information theory-based similarity measures suggest that atmospheric CO 2 fluctuations are best captured by at least 9 climate proxies during cooler interglacial events. Based on the results related to interglacial MIS 11 and 13 obtained in this study, an important implication relevant to anthropogenic CO 2 input to the present-day atmosphere can be distilled. It is that sensitive and better-coupled response proxies such as SST and MAT, which already show an increasing trend, are likely to behave in a more dissimilar manner in future. That is, they tend to behave more independently in the near future ($0.75 kyr).Citation: Das Sharma, S., D. S. Ramesh, C. Bapanayya, and P. A. Raju (2012), Sea surface temperatures in cooler climate stages bear more similarity with atmospheric CO 2 forcing,

Applying the concept of cluster entropy, we demonstrate that the primary P-to-s (Ps) conversions originating from the well-recognized seismological boundaries (Moho, 410 km, and 660 km depth interfaces) in Earth's interior and multiple refl ections (reverberations) between the surface and the Moho-the prominent crust-mantle boundary of Earth-can be unambiguously identifi ed. Their attendant information dimension can act as a discriminant. Documentation of shallow mantle stratifi cation at depths ~150-300 km (L/X layers) using Ps signals is scarce and is sometimes attributed to their weak registration in the seismograms together with interference by reverberations from shallow structure. The slopes of best fi ts to mean cluster information dimension (as function of epicentral distance) of Ps signals from target boundaries such as the Moho, 410 km, and L/X discontinuities are consistently gentle with a slight negative character. In contrast, those related to multiples show a steep positive behavior. This opposite nature can potentially discriminate between reverberations and direct converted waves, even when they tend to arrive in overlapping time windows. Our approach thus enables unequivocal identifi cation of shallow mantle layering from Ps data recorded at diverse tectonic provenances of wide antiquity.

Mode conversions, such as the P-to-s (Ps) converted waves, are now employed in a routine manner to image the velocity boundaries in Earth's interior. However, there exists an ambiguity in establishing shallow-mantle velocity discontinuities in the depth range 100-300 km through the Ps receiver function approach. This primarily stems from overlap in the time windows of arrivals of direct converted phases from the target depth boundaries (~100-300 km depth) and reverberations originating from shallow structures (e.g., from crust and/or shallow lithosphere layers). Attempts have been made to address this problem. Classically, limited success has been achieved through methods such as the move-out, which are essentially performed in the measurement space. Recognizing this, we explore generic space-related information theory measures of similarity to extract diagnostics of discrimination between the primary converted waves and the multiply refl ected arrivals in Ps receiver functions. Various measures of similarity, such as the mutual information (MI), and associated normalized distance measures, like the normalized variation of information (NVI) and normalized information distance (NID), are successfully applied to receiver function data sampling regions of different tectonic regimes of wide antiquity. Our seismological stations are located in the Archean-Proterozoic craton-mobile belt regions of SE India, Canada, and Phanerozoic United States. Signifi cantly, at several locations in SE India, we interpret the unambiguous presence of midlithospheric discontinuities for the fi rst time. We also either reconfi rm or negate the presence of midlithospheric discontinuities beneath stations FFC (Flin Flon) and HRV (Harvard) located in North America. This study reinforces the presence of signifi cant velocity contrast features related to the Lehmann discontinuity depth beneath the Precambrian cratonic stations of India (Hyderabad and Cuddapah) and the Phanerozoic Pasadena station in the United States. Further, multiple deep discontinuities of opposing velocity contrasts are delineated at depths of ~275 km and ~320 km beneath station PAS (Pasadena). Our results therefore show tremendous potential to unambiguously detect and distinguish between direct converted seismological phases and multiple reverberations. These information theory approaches discriminate the seismic phases unequivocally. This new approach thus complements the S-to-p (Sp) receiver function technique, which is suitable for detection of shallow-mantle discontinuities (midlithospheric discontinuities, lithosphere-asthenosphere boundary, Lehmann, etc.).

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