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Spatial spectral analyses of topography and strain rate magnitude across the western United States reveal the presence of at least two separable spectral peaks, representative of characteristic length scales, one short (~10–50 km) and one long (~150–250 km). Less spectral power at intermediate wavelengths aside from that expected for a red, or power law, spectrum occurs in either data set. These results quantify previous qualitative observations that the topography of western North America contains both short and long characteristic wavelength features. Comparing the spectral results to simplified bounding solutions for elastic, viscous, and layered models under tension shows that multiple spectral peaks of comparable power can be reproduced only by mechanical models with more than one layer. Therefore, the simplest model of lithospheric architecture capable of generating the observed dominant characteristic length scales is an elastoplastic lid over a viscous layer. We analyze patterns in topography and strain rate magnitude. Comparing them to one another and to theoretical predictions for the size of features under different assumptions about the physical properties of earth materials allows us to draw conclusions about how tectonics works in continental settings. Two characteristic length scales occur in the tectonic deformation of the western United StatesThese scales suggest that the North American lithosphere includes at least two distinct rheological materialsSpectral tools can be used to evaluate characteristic scaling and hence provide novel constraints on continental rheology and architecture

In the arid region of northern Chile the environmental conditions are favorable for measuring tectonic and climatic influences on catchment denudation rates in the absence of vegetation. Previous studies of denudation rates from cosmogenic 10Be and 26Al concentrations are limited to single drainages. In this study, we examine catchment‐ to orogen‐scale spatial variation in denudation rates between 18 and 23°S in the Coastal and Western Cordilleras of northern Chile. 10Be and 26Al data were obtained from 33 catchments to examine the relative roles of tectonics and climate on catchment‐averaged denudation rates. At broader scales, we examine whether denudation rates and orogen topography reflect the 3‐D plate geometry of the region. Cosmogenic nuclide‐derived denudation rates range from 0.4 ± 0.5 to 20.6 ± 1.5 m/Myr in the Coastal Cordillera and from 1.4 ± 0.7 to 168.0 ± 19.8 m/Myr in the Western Cordillera. The controls on the denudation rates are evaluated using a statistical factor analysis of 10 selected catchment parameters. Denudation rates indicate a strong linear relationship with channel steepness indices but insignificant correlations and covariation with mean annual precipitation rates, drainage area, stream order, mean elevation, mean local relief, mean basin slope, and grain size of the sampled sediments. Moreover, denudation rates are better correlated with tectonic controls at catchment scale than orogen‐scale plate tectonics in the Western and Coastal Cordillera. Analyzing tectonic and climatic influences on 10Be‐and 26Al‐derived denudation rates in a syntaxial orogenSignificant correlation and covariation of denudation rates and channel steepness indicesCatchment‐scale tectonic processes rather than orogen‐scale topographic trends control denudation rates in this arid setting

The long‐term extent of the Earth system response to anthropogenic interference remains uncertain. However, the geologic record offers insights into this problem as Earth has previously cycled between warm and cold intervals during the Phanerozoic. We present an updated compilation of surface temperature proxies for several key time intervals to reconstruct global temperature changes during the Cenozoic. Our data synthesis indicates that Earth’s surface slowly cooled by ca. 9°C during the early Paleogene to late Neogene and that continent‐scale ice sheets developed after global temperature dropped to less than 10°C above preindustrial conditions. Slow cooling contrasts with the steep decrease in combined radiative forcing from past CO2concentrations, solar luminosity, and ocean area, which was close to preindustrial levels even as Earth remained in a much warmer state. From this, we infer that the Earth system was less sensitive to greenhouse gas forcing for most of the Cenozoic and that sensitivity must have increased by at least a factor of 2 during the Plio‐Pleistocene. Our results imply that slow feedbacks will raise global surface temperatures by more than 3°C in the coming millennia, even if anthropogenic forcing is stabilized at the present‐day value (2 W/m2), and that their impact will diminish with further warming. It is not well known how much Earth’s surface temperature will change over the next few millennia as a result of increasing atmospheric CO2concentrations. This is because we still have a limited understanding of many slow climate feedback mechanisms activated by climate change that will become important in the future. Most climate models project eventual global warming of 3–4°C for doubled CO2concentration but exclude many slow climate feedbacks, such as shrinking ice sheets. The distant (geologic) past provides additional clues about the future because the climate system and all of its feedbacks were in equilibrium with naturally elevated CO2. Using up‐to‐date geologic information of the last 50 million years, we find that Earth’s climate history is best described by a switch from a moderate sensitivity, close to that found in climate models, to a much higher sensitivity in the last 3 million years. If Earth behaves the same way today as it has done in the past, melting ice sheets, natural aerosols, and shifting vegetation patterns will slowly continue to raise global warming above the 2°C target during the next few thousand years even if the human contribution does not increase any further. Large compilation of Cenozoic paleoclimate proxies was analyzedPaleogene and Neogene were dominated by Earth system sensitivity of 4°C but sensitivity must have increased in the Plio‐PleistoceneHigh Earth system sensitivity stresses the importance of climate change mitigation over adaptation Large compilation of Cenozoic paleoclimate proxies was analyzed Paleogene and Neogene were dominated by Earth system sensitivity of 4°C but sensitivity must have increased in the Plio‐Pleistocene High Earth system sensitivity stresses the importance of climate change mitigation over adaptation

BACKGROUND:Attention Deficit Hyperactivity Disorder (ADHD) is one of the most frequently reported neuropsychiatric disorders in childhood. However, there is limited data on the biological basis for this disorder. Disturbances in neurotransmitters have been suggested to play a pathophysiologic role. Phenotypically an increased prevalence of obesity has been reported. OBJECTIVE:To investigate resting energy expenditure (REE) and diet-induced thermogenesis in stimulant medication-naïve children with ADHD. DESIGN:Case control study of 12 pre-pubertal boys with ADHD of the hyperactive-impulsive type and 12 control boys without ADHD. Anthropometric testing and indirect calorimetry were performed before and after a standardized meal. REE and thermogenesis were measured in each subject at 2 time points. In an independent group of 60 boys with ADHD, BMI standard deviation scores (BMI-SDS) were compared to age-adapted reference values. RESULTS:REE was on average 6.5 kcal/kg fat free mass/day higher in the ADHD compared to the control group (p<0.01). In contrast, the thermogenic effect of food was not different between the two groups (average increase by 16%, p=n.s.). The repeat measurements, an average of 5±1 months apart, were highly reproducible in all subjects. Age and restlessness did not explain the differences in REE. Boys with ADHD had similar BMI-SDS values (mean BMI-SDS -0.10±0.98) as reference groups. CONCLUSIONS:REE, in contrast to diet-induced thermogenesis, is higher in medication-naïve boys with ADHD. The normal BMI levels suggest increased energy intake in these children.

Tidal modulation of ice streams and their adjacent ice shelves is a real‐world experiment to understand ice‐dynamic processes. We observe the dynamics of Priestley Glacier, Antarctica, using Terrestrial Radar Interferometry (TRI) and GNSS. Ocean tides are predominantly diurnal but horizontal GNSS displacements also oscillate semi‐diurnally. The oscillations are strongest in the ice shelf and tidal signatures decay near‐linearly in the TRI data over >10 km upstream of the grounding line. Tidal flexing is observed >6 km upstream of the grounding line including cm‐scale uplift. Tidal grounding line migration is small and <40% of the ice thickness. The frequency doubling of horizontal displacements relative to the ocean tides is consistent with variable ice‐shelf buttressing demonstrated with a visco‐elastic Maxwell model. Taken together, this supports previously hypothesized flexural ice softening in the grounding‐zone through tides and offers new observational constraints for the role of ice rheology in ice‐shelf buttressing. Temperatures in Antarctica's interior are below zero, so that ice continuously accumulates through snowfall. This mass gain is balanced by ice transport from the interior toward the coast. There, floating ice shelves form on the ocean and ice is eventually lost through iceberg calving and ocean induced melting. Small changes in any of these processes impact global ocean circulation and mean sea level. The speed of the ice varies with ocean tides. We use a specialized instrument that detects this variability and tidal flexing area‐wide and every few hours. We find that although low‐ and high‐tide only occur once a day in this area, ice flow is largest twice a day. This can be explained because ice softens when it is flexed by the ocean tides so that it can flow episodically faster. This is important because the deformation of ice shelves determines to an extent the stability of the entire ice sheet. Terrestrial radar interferometry and GNSS identify dynamic changes at Priestley Glacier, Antarctica, forced by diurnal ocean tidesHorizontal displacements vary semi‐diurnally, are strongest in the shelf and decay near‐linearly >10 km upstream of the grounding lineGrounding line migration is small and flexural softening in ice‐shelf shear margins can explain the semi‐diurnal ice flow component Terrestrial radar interferometry and GNSS identify dynamic changes at Priestley Glacier, Antarctica, forced by diurnal ocean tides Horizontal displacements vary semi‐diurnally, are strongest in the shelf and decay near‐linearly >10 km upstream of the grounding line Grounding line migration is small and flexural softening in ice‐shelf shear margins can explain the semi‐diurnal ice flow component

Alpine glacial erosion exerts a first‐order control on mountain topography and sediment production, but its mechanisms are poorly understood. Observational data capable of testing glacial erosion and transport laws in glacial models are mostly lacking. New insights, however, can be gained from detrital tracer thermochronology. Detrital tracer thermochronology works on the premise that thermochronometer bedrock ages vary systematically with elevation, and that detrital downstream samples can be used to infer the source elevation sectors of sediments. We analyze six new detrital samples of different grain sizes (sand and pebbles) from glacial deposits and the modern river channel integrated with data from 18 previously analyzed bedrock samples from an elevation transect in the Leones Valley, Northern Patagonian Icefield, Chile (46.7°S). We present 622 new detrital zircon (U‐Th)/He (ZHe) single‐grain analyses and 22 new bedrock ZHe analyses for two of the bedrock samples to determine age reproducibility. Results suggest that glacial erosion was focused at and below the Last Glacial Maximum and neoglacial equilibrium line altitudes, supporting previous modeling studies. Furthermore, grain age distributions from different grain sizes (sand, pebbles) might indicate differences in erosion mechanisms, including mass movements at steep glacial valley walls. Finally, our results highlight complications and opportunities in assessing glacigenic environments, such as dynamics of sediment production, transport, transient storage, and final deposition, that arise from settings with large glacio‐fluvial catchments. Mountain glaciers flow down valleys and erode the underlying rocks. Furthermore, rivers that are fed by glaciers, rock falls, and hillslope processes contribute to the erosion of glaciated landscapes. Understanding these processes and where erosion occurs in a catchment is important because these factors affect how landscapes evolve over time and under changing climate conditions. It is difficult to directly study processes that occur under glaciers because these regions are inaccessible. As a result, computer models of glacier erosion are often used to predict where and how erosion occurs. One technique to test these models is to trace where sediments, that were deposited in a glacial moraine or that are being transported by a river from a glacier, originated from within the catchment. We applied this technique to moraine and river samples from the Northern Patagonian Icefield, Chile, to determine at what elevation most erosion occurred during neoglacial times, 2.5 thousand years ago, and to better understand the influence of sediment size and sampling location along a river on study results. Our main finding confirms previous computer models and observational studies that erosion during glacial times is focused in a narrow elevation sector, where glacier sliding velocity is highest. Integration of bedrock, detrital moraine, and fluvial thermochronometer samples documents spatial variations in catchment erosionApproximately 2.5 ka (or earlier) glacial erosion is focused at the Last Glacial Maximum equilibrium line altitude and limited at higher elevationsA well‐constrained bedrock map of cooling ages is essential for quantifying erosion and sediment routing within catchments Integration of bedrock, detrital moraine, and fluvial thermochronometer samples documents spatial variations in catchment erosion Approximately 2.5 ka (or earlier) glacial erosion is focused at the Last Glacial Maximum equilibrium line altitude and limited at higher elevations A well‐constrained bedrock map of cooling ages is essential for quantifying erosion and sediment routing within catchments

Cancer is a general term used to describe many disease states, each of which are characterized by abnormal cell proliferation. The causes which bring about this abnormal cellular behavior are specific to each type of cancer. The success of tumor-targeted therapy is limited by this diversity. One common denominator for all types of cancer is the requirement of a suitable blood supply. Therefore, tumor vasculature has emerged as a potential target for therapeutic intervention. New blood vessel growth from preexisting vasculature stimulated by biochemical signals is termed angiogenesis. Tumor masses require a constant supply of oxygen and nutrients, and a means of efficient waste removal to ensure sustained development. Diffusion from nearby capillaries can supply adequate nutrition for tumors less than 2 mm in size, but for continued growth the tumors must develop their own blood supply. Alteration of the delicate balance of angiogenic stimulating factors and angiogenic inhibitors results in the phenotypic change from quiescence to active endothelial proliferation. To date, this angiogenic switch is not completely understood. The goal of antiangiogenic therapy is to interfere with these mechanisms and prevent tumor cells from developing a viable blood supply. Fumagillin is a naturally occurring antifungal agent. Curcumin is a natural product isolated from the spice turmeric. Both compounds have been shown to have antiangiogenic properties in vitro and in vivo. This paper describes efforts to design and prepare fumagillin and curcumin analogs and evaluate their corresponding antiangiogenic activities.

Ice shelves around Antarctica can provide back stress for outlet glaciers and control ice sheet mass loss. They often contain narrow bands of thin ice termed ice shelf channels. Ice shelf channel morphology can be interpreted through surface depressions and exhibits junctions and deflections from flowlines. Using ice flow modeling and radar, we investigate ice shelf channels in the Roi Baudouin Ice Shelf. These are aligned obliquely to the prevailing easterly winds. In the shallow radar stratigraphy, syncline and anticline stacks occur beneath the upwind and downwind side, respectively. The structures are horizontally and vertically coherent, except near an ice shelf channel junction where patterns change structurally with depth. Deeper layers truncate near basal incisions. Using ice flow modeling, we show that the stratigraphy is ∼9 times more sensitive to atmospheric variability than to oceanic variability. This is due to the continual adjustment toward flotation. We propose that syncline‐anticline pairs in the shallow stratigraphy are caused by preferential snow deposition on the windward side and wind erosion at the downwind side. This drives downwind deflection of ice shelf channels of several meters per year. The depth variable structures indicate formation of an ice shelf channel junction by basal melting. We conclude that many ice shelf channels are seeded at the grounding line. Their morphology farther seaward is shaped on different length scales by ice dynamics, the ocean, and the atmosphere. These processes act on finer (subkilometer) scales than are captured by most ice, atmosphere, and ocean models, yet the dynamics of ice shelf channels may have broader implications for ice shelf stability. Ice flows from Antarctica's interior toward the coast. At the contact point between ice and ocean, the ice becomes afloat and forms fast‐flowing ice shelves. Snowfall continuously accumulates at the ice shelf surface, and at the ice shelf bottom the relatively warm ocean water can melt ice from below. Ice shelves sometimes exhibit a network of surface depressions resembling a river network. At the base, the depressions are accompanied by large incisions termed ice shelf channels. Using radar as a tool for echolocation, we investigate how the shape of this network is formed. We find that snow preferentially collects in the upwind side of the surface depressions. This makes ice shelf channels move to the downwind side. We also find that ice shelf channels can form junctions through localized ocean melting. This is important because it helps us to better understand how the Antarctic ice sheet interacts with the surrounding ocean. The radar stratigraphy in ice shelves is 9 times more sensitive to variability in snow deposition than to variability in basal meltingSome ice shelf channels at Roi Baudouin Ice Shelf deflect from flowlines; the radar stratigraphy reflects related processesVariable snow deposition causes slow deflection, and basal melting can form ice shelf channel junctions far from the grounding line

Many stable isotope paleoaltimetry studies have focused on paleoelevation reconstructions of orogenic plateaus such as the Tibetan or Andean Plateaus. We address the opportunities and challenges of applying stable isotope paleoaltimetry to “smaller” orogens. We do this using a high‐resolution isotope tracking general circulation model (ECHAM5‐wiso) and explore the precipitation δ18O (δ18Op) signal of Cenozoic paleoclimate and topographic change in the European Alps. Results predict a maximum δ18Opchange of 4–5‰ (relative to present day) during topographic development of the Alps. This signal of topographic change has the same magnitude as changes in δ18Opvalues resulting from Pliocene and Last Glacial Maximum global climatic change. Despite the similar magnitude of the isotopic signals resulting from topographic and paleoclimate changes, their spatial patterns across central Europe differ. Our results suggest that an integration of paleoclimate modeling, multiproxy approaches, and low‐elevation reference proxy records distal from an orogen improve topographic reconstructions. Here we use a climate model with water isotopes implemented to explore the maximum precipitation isotopic signal of Cenozoic topographic and paleoclimate change in the European Alps. Our results show that the impact of topography change has the same magnitude as changes in the isotopic composition of local precipitation resulting from Pliocene and Last Glacial Maximum global climatic change. High‐resolution isotope tracking general circulation model (ECHAM5‐wiso) is used to explore changes in past oxygen isotope ratios in precipitation in the AlpsModel‐simulated isotopic signals of topographic change and difference between glacials and interglacials show the same magnitudeLow‐elevation proxy records improve reconstructions of paleotopography by reducing long‐term climate change bias