alpha-Aminoisobutyric acid modified protected analogues of beta-amyloid residue 17-20: a change from sheet to helix

The strong intermolecular interactions mediated by short hydrophobic sequences (e.g., 17-20, -L-Leu-L-Val-L-Phe-L-Phe-) in the middle of A beta are known to play a crucial role in the neuropathology of Alzheimer's disease. FTIR, TEM and Congo red binding studies indicated that a series of L-Ala substituted terminally protected peptides related to the sequence 17-20 of the beta-amyloid peptide, adopted D-sheet conformations. However, the Aib-modified analogues disrupt the D-sheet structure and switch over to a 310 helix with increasing number of Aib residues. X-ray crystallography shed some light on the change from sheet to helix at atomic resolution. (c) 2006 Elsevier Ltd. All rights reserved.

Design of supramolecular beta-sheet forming beta-turns containing aromatic rings and non-coded alpha-aminoisobutyric acid and the formation of flat fibrillar structures through self-assembly

Single crystal X-ray diffraction studies show that the three designed tripeptides Boc-Leu-Aib-m-NA-NO2 (I), Boc-Phe-Aib-m-NA-NO2 (II) and Boc-Pro-Aib-m-ABA-OMe (III) (Aib, -aminoisobutyric acid; m-NA, m-nitroaniline; m-ABA, m-aminobenzoic acid; Boc, t-butyloxycarbonyl) containing aromatic rings in the backbones adopt -turn structures that are self-assembled through intermolecular hydrogen bonds and van der Waals interactions to create layers of -sheets. Solvent-dependent NMR titration and CD studies show that the -turn structures of the peptides also exist in the solution phase. The field emission scanning electron microscopic and transmission electron microscopic images of the peptides in the solid state reveal fibrillar structures of flat morphology that are formed through -sheet mediated self-assembly of the preorganised -turn building blocks.

Supramolecular beta-sheet and nanofibril formation by self-assembling tripeptides containing an N-terminally located gamma-aminobutyric acid residue

Three terminally protected tripeptides Boc-gamma-Abu-Val-Leu-OMe 1, Boc-gamma-Abu-Leu-Phe-OMe 2 and Boc-gamma-Abu-Val-Tyr-OMe 3 (gamma-Abu = gamma-aminobutyric acid) each containing an N-terminally positioned gamma-aminobutyric acid residue have been synthesized, purified and studied. FT-IR studies of all these peptides revealed that these peptides form intermolecularly hydrogen bonded supramolecular beta-sheet structures. Peptides 1, 2 and 3 adopt extended backbone beta-strand molecular structures in crystals. Crystal packing of all these peptides demonstrates that these beta-strand structures self-assemble to form intermolecularly H-bonded parallel beta-sheet structures. Peptide 3 uses a side chain tyrosyl -OH group as an additional hydrogen bonding functionality in addition to the backbone CONH groups to pack in crystals. Transmission electron microscopic studies of all peptides indicate that they self-assemble to form nanofibrillar structures of an average diameter of 65 nm. These peptide fibrils exhibit amyloid-like behavior as they bind to a physiological dye Congo red and show a characteristic green-gold birefringence under polarizing microscope.

Mode I fracture of sheet metal

The perceived wisdom about thin sheet fracture is that (i) the crack propagates under mixed mode I & III giving rise to a slant through-thickness fracture profile and (ii) the fracture toughness remains constant at low thickness and eventually decreases with increasing thickness. In the present study, fracture tests performed on thin DENT plates of various thicknesses made of stainless steel, mild steel, 6082-O and NS4 aluminium alloys, brass, bronze, lead, and zinc systematically exhibit (i) mode I “bath-tub”, i.e. “cup & cup”, fracture profiles with limited shear lips and significant localized necking (more than 50% thickness reduction), (ii) a fracture toughness that linearly increases with increasing thickness (in the range of 0.5–5 mm). The different contributions to the work expended during fracture of these materials are separated based on dimensional considerations. The paper emphasises the two parts of the work spent in the fracture process zone: the necking work and the “fracture” work. Experiments show that, as expected, the work of necking per unit area linearly increases with thickness. For a typical thickness of 1 mm, both fracture and necking contributions have the same order of magnitude in most of the metals investigated. A model is developed in order to independently evaluate the work of necking, which successfully predicts the experimental values. Furthermore, it enables the fracture energy to be derived from tests performed with only one specimen thickness. In a second modelling step, the work of fracture is computed using an enhanced void growth model valid in the quasi plane stress regime. The fracture energy varies linearly with the yield stress and void spacing and is a strong function of the hardening exponent and initial void volume fraction. The coupling of the two models allows the relative contributions of necking versus fracture to be quantified with respect to (i) the two length scales involved in this problem, i.e. the void spacing and the plate thickness, and (ii) the flow properties of the material. Each term can dominate depending on the properties of the material which explains the different behaviours reported in the literature about thin plate fracture toughness and its dependence with thickness.

Construction of supramolecular helices and breaking the helicity by forming supramolecular β-sheet structures using suitable self-assembling pseudopeptide building blocks

Bis-valine derivatives or malonamide (Guha,S.; Drew, M.G.B. Small 2008, 4, 1993-2005) and a bis-valine derivative of 1,1-cyclopropone dicarboxamide were used as building blocks for the construction of supramolecular helical structures. The six-membered intramolecular hydrogen-bonded scaffold is formed, and this acts as a unique supramolecular synthon for the construction of a pseudopeptide-based supramolecular helical structure. However, in absence of this intramolecular hydrogen bond. intermolecular hydrogen bonds are formed among the peptide strands. This leads to a supramolecular beta-sheet structure. Proper selection of the supramolecular synthon (six-membered intramolecular hydrogenbonded scaffold) promotes supramolecular helix formation, and a deviation from this molecular structure dictates the disruption of supramolecular helicity. In this study, six crystal structures have been used to demonstrate that a change in the central angle and/or the central core structure of dicarboxamides can be used to design either a supramolecular helix or a beta-sheet.

Fibrils and nanotubes assembled from a modified amyloid-β peptide fragment differ in the packing of the same β-sheet building blocks

The peptide AAKLVFF assembles into fibrils in water and nanotubes in methanol. Solid-state NMR data are consistent with fibrils constructed from β-sheet bilayers and nanotubes bounded by a wall of offset β-sheet monolayers. Remarkably distinct morphologies are thus traced to subtle differences in the arrangement of the same fundamental building blocks.

Cyclic loss of open solar flux since 1868: the link to heliospheric current sheet tilt and implications for the Maunder Minimum

Open solar flux (OSF) variations can be described by the imbalance between source and loss terms. We use spacecraft and geomagnetic observations of OSF from 1868 to present and assume the OSF source, S, varies with the observed sunspot number, R. Computing the required fractional OSF loss, χ, reveals a clear solar cycle variation, in approximate phase with R. While peak R varies significantly from cycle to cycle, χ is surprisingly constant in both amplitude and waveform. Comparisons of χ with measures of heliospheric current sheet (HCS) orientation reveal a strong correlation. The cyclic nature of χ is exploited to reconstruct OSF back to the start of sunspot records in 1610. This agrees well with the available spacecraft, geomagnetic, and cosmogenic isotope observations. Assuming S is proportional to R yields near-zero OSF throughout the Maunder Minimum. However, χ becomes negative during periods of low R, particularly the most recent solar minimum, meaning OSF production is underestimated. This is related to continued coronal mass ejection (CME) activity, and therefore OSF production, throughout solar minimum, despite R falling to zero. Correcting S for this produces a better match to the recent solar minimum OSF observations. It also results in a cycling, nonzero OSF during the Maunder Minimum, in agreement with cosmogenic isotope observations. These results suggest that during the Maunder Minimum, HCS tilt cycled as over recent solar cycles, and the CME rate was roughly constant at the levels measured during the most recent two solar minima.

The impact of 21st century Arctic sea ice decline on the climate and mass balance of the Greenland ice sheet and Svalbard’s glaciers and ice caps

The Arctic is a region particularly susceptible to rapid climate change. General circulation models (GCMs) suggest a polar amplification of any global warming signal by a factor of about 1.5 due, in part, to sea ice feedbacks. The dramatic recent decline in multi-year sea ice cover lies outside the standard deviation of the CMIP3 ensemble GCM predictions. Sea ice acts as a barrier between cold air and warmer oceans during winter, as well as inhibiting evaporation from the ocean surface water during the summer. An ice free Arctic would likely have an altered hydrological cycle with more evaporation from the ocean surface leading to changes in precipitation distribution and amount. Using the U.K. Met Office Regional Climate Model (RCM), HadRM3, the atmospheric effects of the observed and projected reduction in Arctic sea ice are investigated. The RCM is driven by the atmospheric GCM HadAM3. Both models are forced with sea surface temperature and sea ice for the period 2061-2090 from the CMIP3 HadGEM1 experiments. Here we use an RCM at 50km resolution over the Arctic and 25km over Svalbard, which captures well the present-day pattern of precipitation and provides a detailed picture of the projected changes in the behaviour of the oceanic-atmosphere moisture fluxes and how they affect precipitation. These experiments show that the projected 21stCentury sea ice decline alone causes large impacts to the surface mass balance (SMB) on Svalbard. However Greenland’s SMB is not significantly affected by sea ice decline alone, but responds with a strongly negative shift in SMB when changes to SST are incorporated into the experiments. This is the first study to characterise the impact of changes in future sea ice to Arctic terrestrial cryosphere mass balance.

The Greenland Ice Sheet's surface mass balance in a seasonally sea-ice free Arctic

General circulation models predict a rapid decrease in sea ice extent with concurrent increases in near surface air temperature and precipitation in the Arctic over the 21st century. This has led to suggestions that some Arctic land ice masses may experience an increase in accumulation due to enhanced evaporation from a seasonally sea ice free Arctic Ocean. To investigate the impact of this phenomenon on Greenland ice sheet climate and surface mass balance (SMB) a regional climate model, HadRM3, was used to force an insolation-temperature melt SMB model. A set of experiments designed to investigate the role of sea ice independently from sea surface temperature (SST) forcing are described. In the warmer and wetter SI + SST simulation Greenland experiences a 23% increase in winter SMB but 65% reduced summer SMB, resulting in a net decrease in the annual value. This study shows that sea ice decline contributes to the increased winter balance, causing 25% of the increase in winter accumulation; this is largest in eastern Greenland as the result of increased evaporation in the Greenland Sea. These results indicate that the seasonal cycle of Greenland's SMB will increase dramatically as global temperatures increase, with the largest changes in temperature and precipitation occurring in winter. This demonstrates that the accurate prediction of changes in sea ice cover is important for predicting Greenland SMB and ice sheet evolution.

High-latitude climate sensitivity to ice-sheet forcing over the last 120kyr

Interpretation of ice-core records is currently limited by paucity of modelling at adequate temporal and spatial resolutions. Several key questions relate to mechanisms of polar amplification and inter-hemispheric coupling on glacial/interglacial timescales. Here, we present the first results from a large set of global ocean–atmosphere climate model ‘snap-shot’ simulations covering the last 120 000 years using the Hadley Centre climate model (HadCM3) at up to 1 kyr temporal resolution. Two sets of simulations were performed in order to examine the roles of orbit and greenhouse gases versus ice-sheet forcing of orbital-scale climate change. A series of idealised Heinrich events were also simulated, but no changes to aerosols or vegetation were prescribed. This paper focuses on high latitudes and inter-hemispheric linkages. The simulations reproduce polar temperature trends well compared to ice-core reconstructions, although the magnitude is underestimated. Polar amplification varies with obliquity, but this variability is dampened by including variations in land ice coverage, while the overall amplification factor increases. The relatively constant amplification of Antarctic temperatures (with ice-sheet forcing included) suggests it is possible to use Antarctic temperature reconstructions to estimate global changes (which are roughly half the magnitude). Atlantic Ocean overturning circulation varies considerably only with the introduction of Northern Hemisphere ice sheets, but only weakens in the North Atlantic in the deep glacial, when ocean–sea-ice feedbacks result in the movement of the region of deep convection to lower latitudes and with the introduction of freshwater to the surface North Atlantic in order to simulate Heinrich events.

Interhemispheric coupling, the West Antarctic Ice Sheet and warm Antarctic interglacials

Ice core evidence indicates that even though atmospheric CO2 concentrations did not exceed ~300 ppm at any point during the last 800 000 years, East Antarctica was at least ~3–4 °C warmer than preindustrial (CO2~280 ppm) in each of the last four interglacials. During the previous three interglacials, this anomalous warming was short lived (~3000 years) and apparently occurred before the completion of Northern Hemisphere deglaciation. Hereafter, we refer to these periods as "Warmer than Present Transients" (WPTs). We present a series of experiments to investigate the impact of deglacial meltwater on the Atlantic Meridional Overturning Circulation (AMOC) and Antarctic temperature. It is well known that a slowed AMOC would increase southern sea surface temperature (SST) through the bipolar seesaw and observational data suggests that the AMOC remained weak throughout the terminations preceding WPTs, strengthening rapidly at a time which coincides closely with peak Antarctic temperature. We present two 800 kyr transient simulations using the Intermediate Complexity model GENIE-1 which demonstrate that meltwater forcing generates transient southern warming that is consistent with the timing of WPTs, but is not sufficient (in this single parameterisation) to reproduce the magnitude of observed warmth. In order to investigate model and boundary condition uncertainty, we present three ensembles of transient GENIE-1 simulations across Termination II (135 000 to 124 000 BP) and three snapshot HadCM3 simulations at 130 000 BP. Only with consideration of the possible feedback of West Antarctic Ice Sheet (WAIS) retreat does it become possible to simulate the magnitude of observed warming.

The Mid-Brunhes Event and West Antarctic ice sheet stability

The complex cyclical nature of Pleistocene climate, driven by the evolving orbital configuration of the Earth, is well known but not well understood. A major climatic transition took place at the Mid-Brunhes Event (MBE), ca. 430 ka ago after which the amplitude of the ca.100 ka climate oscillations increased, with substantially warmer interglacials, including periods warmer than present. Recent modelling has indicated that while the timing of these warmer-than-present transient (WPT) events is consistent with southern warming due to a deglaciation-forced slowdown of the Atlantic Meridional Overturning Circulation, the magnitude of warming requires a local amplification, for which a candidate is the feedback of significant West Antarctic Ice Sheet (WAIS) retreat. We here extend this argument, based on the absence of WPTs in the early ice core record (450–800 ka ago), to hypothesize that the MBE could be a manifestation of decreased WAIS stability, triggered by ongoing subglacial erosion.

Stability of an ice sheet on an elastic bed

The stability of stationary flow of a two-dimensional ice sheet is studied when the ice obeys a power flow law (Glen's flow law). The mass accumulation rate at the top is assumed to depend on elevation and span and the bed supporting the ice sheet consists of an elastic layer lying on a rigid surface. The normal perturbation of the free surface of the ice sheet is a singular eigenvalue problem. The singularity of the perturbation at the front of the ice sheet is considered using matched asymptotic expansions, and the eigenvalue problem is seen to reduce to that with fixed ice front. Numerical solution of the perturbation eigenvalue problem shows that the dependence of accumulation rate on elevation permits the existence of unstable solutions when the equilibrium line is higher than the bed at the ice divide. Alternatively, when the equilibrium line is lower than the bed, there are only stable solutions. Softening of the bed, expressed through a decrease of its elastic modulus, has a stabilising effect on the ice sheet.

Glaciodynamics of the central sector of the last British–Irish ice sheet in Northern England

The central sector of the last British–Irish Ice Sheet (BIIS) was characterised by considerable complexity, both in terms of its glacial stratigraphy and geomorphological signature. This complexity is reflected by the large number and long history of papers that have attempted to decipher the glaciodynamic history of the region. Despite significant advances in our understanding, reconstructions remain hotly debated and relatively local, thereby hindering attempts to piece together BIIS dynamics. This paper seeks to address these issues by reviewing geomorphological mapping evidence of palimpsest flow signatures and providing an up-to-date stratigraphy of the region. Reconciling geomorphological and sedimentological evidence with relative and absolute dating constraints has allowed us to develop a new six-stage glacial model of ice-flow history and behaviour in the central sector of the last BIIS, with three major phases of glacial advance. This includes: I. Eastwards ice flow through prominent topographic corridors of the north Pennines; II. Cessation of the Stainmore ice flow pathway and northwards migration of the North Irish Sea Basin ice divide; III. Stagnation and retreat of the Tyne Gap Ice Stream; IV. Blackhall Wood–Gosforth Oscillation; V. Deglaciation of the Solway Lowlands; and VI. Scottish Re-advance and subsequent final retreat of ice out of the central sector of the last BIIS. The ice sheet was characterised by considerable dynamism, with flow switches, initiation (and termination) of ice streams, draw-down of ice into marine ice streams, repeated ice-marginal fluctuations and the production of large volumes of meltwater, locally impounded to form ice-dammed glacial lakes. Significantly, we tie this reconstruction to work carried out and models developed for the entire ice sheet. This therefore situates research in the central sector within contemporary understanding of how the last BIIS evolved over time.

Landscape evolution and ice-sheet behaviour in a semi-arid polar environment: James Ross Island, NE Antarctic Peninsula

This study of landscape evolution presents both new modern and palaeo process-landform data, and analyses the behaviour of the Antarctic Peninsula Ice Sheet through the Last Glacial Maximum (LGM), the Holocene and to the present day. Six sediment-landform assemblages are described and interpreted for Ulu Peninsula, James Ross Island, NE Antarctic Peninsula: (1) the Glacier Ice and Snow Assemblage; (2) the Glacigenic Assemblage, which relates to LGM sediments and comprises both erratic-poor and erratic-rich drift, deposited by cold-based and wet-based ice and ice streams respectively; (3) the Boulder Train Assemblage, deposited during a Mid-Holocene glacier readvance; (4) the Ice-cored Moraine Assemblage, found in front of small cirque glaciers; (5) the Paraglacial Assemblage including scree, pebble-boulder lags, and littoral and fluvial processes; and (6) the Periglacial Assemblage including rock glaciers, protalus ramparts, blockfields, solifluction lobes and extensive patterned ground. The interplay between glacial, paraglacial and periglacial processes in this semi-arid polar environment is important in understanding polygenetic landforms. Crucially, cold-based ice was capable of sediment and landform genesis and modification. This landsystem model can aid the interpretation of past environments, but also provides new data to aid the reconstruction of the last ice sheet to overrun James Ross Island.