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Critical transitions between ecosystem states can be triggered by relatively small external forces or internal perturbations and may show time-lagged or hysteretic recovery. Understanding the precise mechanisms of a transition is important for ecosystem management, but it is hampered by a lack of information about the preceding interactions and associated feedback between different components in an ecosystem. This paper employs a range of data, including paleolimnological, environmental monitoring and documentary sources from lake Erhai and its catchment, to investigate the ecosystem structure and dynamics across multiple trophic levels through the process of eutrophication. A long-term perspective shows the growth and decline of two distinct, but coupled, positive feedback loops: a macrophyte-loop and a phosphorus-recycling-loop. The macrophyte-loop became weaker, and the phosphorus-recycling-loop became stronger during the process of lake eutrophication, indicating that the critical transition was propelled by the interaction of two positive feedback loops with different strengths. For lake restoration, future weakening of the phosphorus-recycling loop or a reduction in external pressures is expected to trigger macrophyte growth and eventually produce clear water conditions, but the speed of recovery will probably depend on the rates of feedback loops and the strength of their coupling.

An austenitic low-density steel was processed by dynamic plastic deformation (DPD) over the strain range from 0.25 to 0.75 followed by aging at 450°C and then it was subjected to compressive testing at strain rates of 1.0 × 10-3 − 2.0 × 103 s-1. The results show that fine grain structures with high density dislocations are achieved after DPD processing. After aging, the grain size increased slightly together and there was an additional marginal decrease in the dislocation density. κ-carbides only appeared in the samples after DPD processing at the strain of 0.75 and after subsequent aging. Submicron-sized (Nb, Mo)C particles existed in the matrix before DPD and there was no change in size and distribution during DPD processing and post-DPD aging. The yield strengths of the steels after DPD at different strain rates increased significantly by ~120-190% compared with the as-received sample, where this is mainly due to a combination of dislocation strengthening and grain boundary strengthening. For the steel processed by DPD at strain of 0.75, there was an additional precipitation strengthening of κ-carbides besides the dislocation strengthening and grain boundary strengthening, and this produced an increase of over ~900 MPa in yield strength by comparison with the as-received steel. After aging, the yield strength decreased slightly due to a reduction in the dislocation density and a slight coarsening of the grains, except for samples after DPD at a strain of 0.75 which showed a slight increase in strength due to further κ precipitation. The strain rate strengthening effect and strain hardening ability were also analyzed.

An Al-7075 aluminum alloy and a ZK60 magnesium alloy were processed by a combination of equal-channel angular pressing (ECAP) for 4 passes and high-pressure torsion (HPT) through total numbers of up to 20 turns. Processing by ECAP and HPT were performed at 473 K and room temperature, respectively. Mechanical testing showed an increase in the hardness value of the Al-7075 alloy after a combination of ECAP and HPT whereas in the ZK60 alloy the hardness was reduced. Microstructural images of the Al-7075 alloy revealed very significant grain refinement after a combination of ECAP + HPT compared to the individual processing techniques. By contrast, and consistent with the hardness measurements, the average grain size of the ZK60 alloy was larger after processing by the two-step SPD technique. These results are examined and an explanation is presented based on the available microstructural evidence.

Superplasticity refers to the ability of some materials to exhibit exceptionally high elongations when pulled in tension. This phenomenon forms the background for the use of superplastic forming in which complex curved parts may be fabricated through relatively simple forming operations. At the present time, this type of forming is important in manufacturing products for a wide range of industrial applications. An important development in this field occurred in 1985 when Professor Oscar Kaibyshev established the Institute of Problems of Superplasticity of Metals (IPSM) under the auspices of the Russian Academy of Scienc-es in Ufa in the Ural Mountains region of Russia. At that time, this institute was, and remains to this day, the first and only in-stitute devoted exclusively to the development of research in superplasticity. In practice, the establishment of this institute came at an appropriate time because it marked the beginning of the availability of new and sophisticated tools which permitted detailed microstructural observations which surpassed the techniques available in earlier decades. In this special issue of the journal devoted to “Superplasticity and Related Phenomena” it is appropriate, therefore, to examine some of the developments in superplasticity that have occurred over the last three decades with an emphasis on research conducted by scientists from Ufa..

An investigation was conducted to examine the microstructure and mechanical properties of an Al-5483 aluminium alloy subjected to a hybrid severe plastic deformation (SPD) process consisting of hydrostatic extrusion (HE) followed by high-pressure torsion (HPT) for up to 10 revolutions. The results are compared with those for samples processed separately by HE or by HPT. Microhardness measurements were taken on cross-sectional planes of the HE billets and on the HPT disks and in addition the microstructures were examined using transmission electron microscopy. The results demonstrate that the hybrid process of HE+HPT induces additional grain refinement when compared with HPT with average grain sizes of ~ 60 and 90 nm, respectively. Also, a significantly higher fraction of high-angle grain boundaries (HAGBs) was present after HE+HPT and the beneficial role of HE pre-processing was also apparent in the microhardness measurements. After the hybrid process, the microhardness saturated at Hv ≈ 255 which is higher than after either HPT (Hv ≈ 235) or HE (Hv ≈ 160). A linear Hall-Petch relationship was maintained for coarse-grained and SPD-processed samples with high fractions of HAGBs (above 70%) while samples with higher fractions of low-angle grain boundaries showed a significant deviation from linearity.

A ZK60 magnesium alloy was processed through 5 turns of high-pressure torsion (HPT) at room temperature under an applied pressure of 2.0 GPa to produce a reasonably homogeneous ultrafine microstructure with a grain size of ~ 700 nm. The potential superplastic behavior of this alloy was investigated by measuring the strain rate sensitivity using two different procedures of miniature tensile testing and miniature shear punch testing (SPT). The tensile experiments were conducted at initial strain rates of 3.0 × 10−5 to 1.0 × 10−1 s−1 and the SPT was performed at shear strain rates from 3.3 × 10−3 to 3.3 × 10−1 s−1 at temperatures of 473 and 523 K. It is shown that the strain rate sensitivity index, m, has a maximum value of ~ 0.5 at intermediate strain rates in both tensile testing and SPT and there was a maximum elongation to failure of 940% in the tensile testing. The results demonstrate that tensile testing and SPT are both effective procedures in indicating the potential for achieving superplasticity.

Oxygen-free copper of 99.95Â wt.% purity was severely deformed at room temperature by two modes of severe plastic deformation, equal-channel angular pressing (ECAP) and high-pressure torsion (HPT). ECAP was performed using 4, 16 and 24 passes, and HPT was performed using 1/2, 1 and 10 turns. The results show that while recovery occurs during both ECAP and HPT processing, copper shows a faster recovery rate with HPT processing than ECAP. The occurrence of recovery was observed at an equivalent strain exceeding â¼12 that led to an enhancement in the uniform plastic deformation. The influence of recovery behaviour on the mechanical properties was investigated using X-ray diffraction, microhardness and tensile testing. Keywords: Ductility, Equal-channel angular pressing, High-pressure torsion, Recovery, Strain rate sensitivity, Work hardening

High pressure torsion provides an opportunity to process materials with low formability such as magnesium at room temperature. The present work shows the microstructure evolution in commercially pure magnesium processed using a pressure of 6.0 GPa up to 10 turns of rotation. The microstructure evolution is evaluated using electron microscopy and the hardness is determined using dynamic hardness testing. The results show that the grain refinement mechanism in this material differs from materials with b.c.c. and f.c.c. structures. The mechanism of grain refinement observed at high temperatures also applies at room temperature. The hardness distribution is heterogeneous along the longitudinal section of the discs and is not affected by the amount of deformation imposed to the material.

The sequence and kinetics of pre-precipitation in an Mg-1.43Nd (wt.%) alloy was investigated after severe plastic deformation by high-pressure torsion (HPT) at room temperature using in situ synchrotron X-ray diffraction and differential scanning calorimetry (DSC). In situ aging at 250 °C up to 5 h led to precipitation of the β1-Mg3Nd and β-Mg12Nd phases but without any evidence for the metastable β‴ (undifferentiated β’’-DO19 and β′-Mg7Nd) or equilibrium βe-Mg41Nd5 phases. The β1-Mg3Nd and β-Mg12Nd phases appeared rapidly after HPT processing and their amounts were relatively large compared to the non-deformed sample. The Avrami time exponent of the β-Mg12Nd phase had a value near unity indicating a mechanism of nucleation after saturation and growth of the particles in 2 dimensions. DSC analysis revealed all metastable phases as well as the equilibrium phase. The activation energies associated with the pre-precipitation phases ranged between ∼126 and ∼235 kJ mol−1.

The Al-Mg-Sc alloys have become important materials in research conducted on superplasticity in aluminum-based alloys. Many results are now available and this provides an opportunity to examine the consistency of these data and also to make a direct comparison with the predicted rate of flow in conventional superplasticity. Accordingly, all available data were tabulated with divisions according to whether the samples were prepared without processing using severe plastic deformation (SPD) techniques or they were processed using the SPD procedures of equal-channel angular pressing or high-pressure torsion or they were obtained from friction stir processing. It is shown that all results are mutually consistent, the measured superplastic strain rates have no clear dependence on the precise chemical compositions of the alloys and there is general agreement, to within less than one order of magnitude of strain rate, with the theoretical prediction for superplastic flow in conventional materials.

High-pressure torsion (HPT) deformation of multiphase metallic systems produces a high density of interfaces and leads to atomic mixing between the constituent phases. Here we present a study of the interphase boundary structure, grain size evolution and intermetallic phase formation during HPT deformation of a nano-crystalline Al/Ti composite. High-resolution transmission electron microscopy was used to study the structural features of the interphase boundaries. The Al/Ti interphase boundaries were found to significantly promote the generation of dislocations during deformation. After HPT deformation to a shear strain of 87, the average grain sizes of Al and Ti are 22 and 31 nm, respectively. The chemical mixing between the Al and Ti phases was enhanced by defect-mediated short circuit diffusion and dislocation shuffle-controlled plastic deformation at the interphase boundaries. The intermetallic phases formed during HPT deformation are associated with the strain energy stored by the high density of dislocations at the interphase boundaries.

Pancreatic adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death in the United States. PDAC is difficult to manage effectively, with a five-year survival rate of only 5%. PDAC is largely driven by activating KRAS mutations, and as such, cannot be directly targeted with therapeutic agents that affect the activated protein. Instead, inhibition of downstream signaling and other targets will be necessary to effectively manage PDAC. Here, we describe a tiered single-agent and combination compound screen to identify targeted agents that impair growth of a panel of PDAC cell lines. Several of the combinations identified from the screen were further validated for efficacy and mechanism. Combination of the bromodomain inhibitor JQ1 and the neddylation inhibitor MLN4294 altered the production of reactive oxygen species in PDAC cells, ultimately leading to defects in the DNA damage response. Dual bromodomain/neddylation blockade inhibited in vivo growth of PDAC cell line xenografts. Overall, this work revealed novel combinatorial regimens, including JQ1 plus MLN4294, which show promise for the treatment of RAS-driven PDAC. Mol Cancer Ther; 16(6); 1041–53. ©2017 AACR.

Chironomid based calibration training sets comprised of 100 lakes from southwestern China and a subset of 47 lakes from Yunnan Province were established. Multivariate ordination analyses were used to investigate the relationship between the distribution of chironomid species and 15 environmental variables from these lakes. Canonical correspondence analyses (CCAs) and partial CCAs showed that mean July temperature is the sole independent and significant (p < 0.05) variable that explains 16 % of the variance in the chironomid data from the 47 Yunnan lakes. Mean July temperature remains one of the independent and significant variables explaining the second largest amount of variance after potassium ions (K+) in the 100 south-western Chinese lakes. Quantitative transfer functions were created using the chironomid assemblages for both calibration data sets. The first component of the weighted average partial least square (WA-PLS) model based on the 47 lakes training set produced a coefficient of determination (r2jack) of 0.83, maximum bias (jackknifed) of 3.15 and root mean squared error of prediction (RMSEP) of 1.72 °C. The two-component WA-PLS model for the 100 lakes training set produced an r2bootstrap of 0.63, maximum bias (bootstrapped) of 5.16 and RMSEP of 2.31 °C. We applied both transfer functions to a 150-year chironomid record from Tiancai Lake (26°38′3.8 N, 99°43’E, 3898 m a.s.l), Yunnan, China to obtain mean July temperature inferences. The reconstructed results based on both models showed remarkable similarity to each other in terms of pattern. We validated these results by applying several reconstruction diagnostics and comparing them to a 50-year instrumental record from the nearest weather station (26°51'29.22"N, 100°14'2.34"E, 2390 m a.s.l). Both transfer functions perform well in this comparison. We argue that the large training set is also suitable for reconstruction work despite the low explanatory power of MJT because it contains a more complete range of modern temperature and environmental data for the chironomid taxa observed and is therefore more robust.

Oxygen-free copper was processed by equal-channel angular pressing (ECAP) at room temperature for 1, 4 and 8 passes and then the ECAP specimens were further deformed by dynamic testing at 298 K using a strain rate of 10 s−1. Experiments were conducted to investigate the influence of the initial microstructures induced by ECAP on the subsequent grain refinement and mechanical properties after dynamic testing. The results show the strength of copper increased with increasing numbers of ECAP passes and a significant additional grain refinement was produced in the ECAP specimens through the dynamic testing. Thus, the initial grain sizes after ECAP for 1, 4 and 8 passes were ~16, ~4.4 and ~2.9 μm, respectively, and these values were reduced to ~400, ~330 and ~300 nm by dynamic testing, The grains were refined by conventional dislocation processes in the 1-pass specimen but there was evidence for dynamic recrystallization in the specimen processed by 8 passes.

Herein the microstructure evolution and microhardness variations in a peak‐aged Al–Zn–Mg alloy after equal‐channel angular pressing (ECAP) for 1–8 passes followed by heat treatments at temperatures of 393–473 K for 5–20 h are examined. The results show that ECAP processing hardens the alloy, and the hardness increases with each pass due to grain refinement, the formation of large numbers of fine precipitates, and the introduction of a high dislocation density. Post‐ECAP annealing at 393 K up to 20 h after 1 and 4 passes of ECAP leads to a further increase in microhardness and this increase is substantial for an annealing time of 20 h after 1 pass due primarily to the extensive formation of a nano‐sized η′ phase. After ECAP for 8 passes, post‐ECAP annealing at 393 K for 5 h or more leads to softening due to the occurrence of recrystallization and the transformation of fine η′ to coarse η. Post‐ECAP anneals at the higher temperatures of 423 and 473 K are not capable of producing high hardness values.

Axis specification of the zebrafish embryo begins during oogenesis and relies on proper formation of well-defined cytoplasmic domains within the oocyte. Upon fertilization, maternally-regulated cytoplasmic flow and repositioning of dorsal determinants establish the coordinate system that will build the structure and developmental body plan of the embryo. Failure of specific genes that regulate the embryonic coordinate system leads to catastrophic loss of body structures. Here, we review the genetic principles of axis formation and discuss how maternal factors orchestrate axis patterning during zebrafish early embryogenesis. We focus on the molecular identity and functional contribution of genes controlling critical aspects of oogenesis, egg activation, blastula, and gastrula stages. We examine how polarized cytoplasmic domains form in the oocyte, which set off downstream events such as animal-vegetal polarity and germ line development. After gametes interact and form the zygote, cytoplasmic segregation drives the animal-directed reorganization of maternal determinants through calcium- and cell cycle-dependent signals. We also summarize how maternal genes control dorsoventral, anterior-posterior, mesendodermal, and left-right cell fate specification and how signaling pathways pattern these axes and tissues during early development to instruct the three-dimensional body plan. Advances in reverse genetics and phenotyping approaches in the zebrafish model are revealing positional patterning signatures at the single-cell level, thus enhancing our understanding of genotype-phenotype interactions in axis formation. Our emphasis is on the genetic interrogation of novel and specific maternal regulatory mechanisms of axis specification in the zebrafish.

Differential scanning calorimetry (DSC) was used to evaluate the recrystallization temperature and activation energy for an Mg-1.43Nd (wt.%) alloy after severe plastic deformation by high-pressure torsion (HPT) at room temperature up to 10 turns. The recrystallization kinetics were determined from DSC analysis. The results show that the recrystallization temperature increases with increasing heating rate and decreases with increasing numbers of HPT turns. Severe plastic deformation by HPT significantly reduces the recrystallization temperature. The estimated activation energy for recrystallization was in the range of ∼ 84−89 kJ mol−1.

The low ductility of magnesium at room temperature is usually attributed to an insufficient number of independent slip systems. Recent research has shown that refining the grain structure of pure magnesium promotes a breakdown in the Hall‐Petch relationship at low strain rates and may lead to the development of exceptional ductilities. This report describes the evolution of microstructure and the mechanical behaviour of pure magnesium using different amounts of imposed plastic deformation by high‐pressure torsion (HPT). It is shown that the initial coarse grains undergo twinning followed by a gradual grain refinement. The flow stress at low strain rates decreases as the grain size is reduced, thereby confirming an inverse Hall‐Petch behaviour. The elongation to failure increases with grain refinement and elongations over 300% are achieved after 1/2 turn of HPT. These experimental data agree with a model for the low temperature deformation behaviour of fine‐grained pure magnesium.

Eutrophication and sedimentation are affecting global Marine Protected Area (MPA) ecosystems, such as estuaries, as catchments are developed and sea levels rise. Managers are often faced with short term datasets and modelling evidence with which to undertake management of these complex open systems. Longer term datasets which monitor environmental change can be used to improve understanding of estuary biogeochemistry and the resulting ecological response. In this paper we use the case study of Holes Bay, Poole Harbour to explore how palaeoenvironmental archives can be used to extend the evidence base for sediment, nutrient and ecological management within a coastal MPA.

The effect of the chemical inhomogeneities on the local mechanical behavior was studied in a CoCrFeMnNi high-entropy alloy. Micropillar compression revealed that, despite the difference in the chemical composition, the stress-strain behaviors in the two regions were almost identical. The size effect was negligible in the micropillar compression experiments.

The effect of the increase in crystalline defects in the structure generated by high-pressure torsion (HPT) on the corrosion behavior of metallic materials is not well understood. This report evaluates the influence of HPT on the corrosion behavior of a solution treated Al-3wt% Mg-0.2wt% Sc alloy in a 3.5 wt./v.% NaCl solution. The electrochemical behavior of the alloy was evaluated using cyclic polarization, electrochemical impedance spectroscopy (EIS), Mott Schottky, X-ray photoelectron spectroscopy, and chronoamperometry testing. The passive current density decreased after HPT processing, indicating a more protective oxide layer was formed on the surface of the HPT-processed alloy. Mott Schottky analysis confirmed the higher protection efficiency of the passive layer on the HPT-processed alloy. The film formed in the solution-treated alloy was a p-type and an n-type semiconductor while the alloy processed by HPT exhibited only an n-type semiconductor behavior. EIS showed that corrosion resistance in a saline medium increased with HPT processing.

Climate warming and human impacts are thought to be causing peatlands to dry,\ud potentially converting them from sinks to sources of carbon. However, it is unclear\ud whether the hydrological status of peatlands has moved beyond their natural envelope.\ud Here we show that European peatlands have undergone substantial, widespread drying\ud during the last ~300 years. We analyse testate amoeba-derived hydrological\ud reconstructions from 31 peatlands across Britain, Ireland, Scandinavia and continental\ud Europe to examine changes in peatland surface wetness during the last 2000 years.\ud 60% of our study sites were drier during the period CE 1800-2000 than they have been\ud for the last 600 years; 40% of sites were drier than they have been for 1000 years; and\ud 24% of sites were drier than they have been for 2000 years. This marked recent\ud transition in the hydrology of European peatlands is concurrent with compound\ud pressures including climatic drying, warming and direct human impacts on peatlands,\ud although these factors vary between regions and individual sites. Our results suggest\ud that the wetness of many European peatlands may now be moving away from natural\ud baselines. Our findings highlight the need for effective management and restoration of\ud European peatlands.

International audience; The evolution of microstructure, texture, and mechanical properties of an Mg-1.43Nd (wt%) alloy is investigated after processing by high-pressure torsion at room temperature through five turns and isochronal annealing for 1 h at 150, 250, 350, and 450 C using electron backscatter diffraction and Vickers microhardness. The alloy exhibits a good thermal stability up to annealing at 250 C, with mean grain size of %0.65 μm. The microhardness shows an initial hardening after annealing at 150 C and then a subsequent softening. The deformation texture, a basal texture shifted 60 away from the shear direction (SD), is retained during annealing up to 250 C. In contrast, a basal texture with symmetrical splitting toward SD is developed after annealing at 350 C. The precipitation sequence and their pinning effects are responsible for the age-hardening, stabilization of grain size, and the texture modification. The kinetics of grain growth in the Mg-1.43Nd alloy follows two stages depending on the temperature annealing range, with an activation energy of %26 kJ mol À1 in the low temperature range of 150-250 C and %147 kJ mol À1 in the high temperature range of 250-450 C.

Hydroxyapatite and bioactive glass particles were added to pure magnesium and an AZ91 magnesium alloy and then consolidated into disc-shaped samples at room temperature using high-pressure torsion (HPT). The bioactive particles appeared well-dispersed in the metal matrix after multiple turns of HPT. Full consolidation was attained using pure magnesium, but the center of the AZ91 disc failed to fully consolidate even after 50 turns. The magnesium-hydroxyapatite composite displayed an ultimate tensile strength above 150 MPa, high cell viability, and a decreasing rate of corrosion during immersion in Hank&rsquo, s solution. The composites produced with bioactive glass particles exhibited the formation of calcium phosphate after 2 h of immersion in Hank&rsquo, s solution and there was rapid corrosion in these materials.

It is well-known that processing by severe plastic deformation using high-pressure torsion (HPT) promotes grain refinement and increases the strength of magnesium and its alloys. The present research is conducted to evaluate the effect of such processing on cytotoxicity and corrosion behavior in Hank's solution by using samples of commercial purity magnesium and AZ31, AZ91, and ZK60 magnesium alloys. All samples are subjected to electrochemical testing and hydrogen evolution testing before and after processing by HPT and the results show that this processing improves the corrosion resistance of pure magnesium, has no significant effect on the AZ31 and AZ91 alloys but reduces the corrosion resistance of the ZK60 alloy. The observations support the conclusion that grain refinement improves the corrosion resistance of metals with a tendency for passivation but impedes the resistance of metals without passivation. In addition, in vitro cytotoxicity tests are performed on the processed materials and show cell viability in all samples. The results demonstrate that HPT processing may be used to improve the performance of magnesium and its alloys as biodegradable implants.

OBJECTIVES: To evaluate the use of fluorescent tagging for environmental surface cleaning surveillance in a small animal veterinary hospital and identify factors associated with tag removal. MATERIALS AND METHODS: Over 5.5 weeks, a commercial fluorescent dye (Glo Germ) was used to tag (mark) surfaces in a small animal veterinary teaching hospital. Twenty‐four hours after tagging, cleaning was assessed with a black light (UV‐A source). Surfaces were recorded as cleaned based on complete removal of fluorescent tagging at assessment. Proportions cleaned were calculated overall and by predictors (i.e. surface location/type, primary nature of surface contact – animal/human, week of study). RESULTS: A total of 4984 surfaces were tagged and assessed. Overall cleaning was 50%. Cleaning varied by surface/object (range: 2 to 100%) and hospital location (4 to 78%). Surfaces designated as having primarily animal contact were cleaned more frequently than those with primarily human contact (75%, 42%; P

Tests are conducted to evaluate the effect of long-term storage on the microstructure and microhardness of an oxygen-free high conductivity (OFHC) copper after processing by high-pressure torsion (HPT) for various numbers of revolutions at ambient temperature. Results are presented for samples subjected to storage at room temperature through periods of either 1.25 or 7 years. The results show that an increase in storage time leads to a coarsening of the ultrafine-grained structure produced by HPT processing and a corresponding decrease in the microhardess where this is associated with the occurrence of recrystallization and grain growth. Plots of hardness against equivalent strain reveal a three-stage behavior with much lower hardness values over a range of equivalent strains of ~2-8. This behavior is similar after both storage periods but the hardness values are lower and the grain sizes are larger after storage for the longer time. The results demonstrate that long-term storage has a significantly detrimental effect on the microstructure and hardness of ultrafine-grained OFHC Cu

Oxygen isotope (δ18O) measurements on the exoskeletons of aquatic insects can be used to reconstruct changes in the δ18O of ambient water and, indirectly, to infer the climate and environmental conditions at the time of tissue synthesis. Prior to stable isotope analysis, it is often necessary to chemically pretreat insect remains to remove allochthonous organic and inorganic compounds without altering the δ18O signature. We tested the effectiveness and impact of duration of exposure to a buffered 2 M ammonium chloride (NH4Cl) solution for removing carbonates at neutral pH from chironomid head capsules, water beetle sclerites and marine crab remains prior to stable isotope analysis. Immersion in NH4Cl for 24 h efficiently removed the effect of carbonates with no long-term effects of prolonged exposure observed. Furthermore, we assessed the variability in δ18O values within and between individual sclerites (exoskeleton parts) of both modern and fossil water beetle remains. Both modern and fossil specimens had similar intra-sclerite variability in δ18O values (~ 2‰ range). In contrast, modern specimens had much smaller inter-sclerite variability (18O records.

The composition of Chironomidae communities and the ecological significance of such assemblages in peatlands have received little attention, especially in subtropical alpine regions. We report on the spatial distribution of subfossil chironomids and environmental controls on the insects in three subalpine peatlands from subtropical, central China. We found 44 genera and 62 morphotypes in 41 surficial peat samples from three peatlands in subtropical China. The taxa are different from those found in shallow freshwater lakes in the same region, as terrestrial/semi-terrestrial taxa are common in the peatland chironomid communities. Dissimilarities were observed among the three investigated peatlands, and spatially heterogeneous microhabitats also showed notable differences in particular species abundances, even within the same peatland. Important taxa that are associated with specific peatlands, and/or illustrate within-peatland community differences, include Tanytarsus pallidicornis-type2, which is related to lower conductivity, and Neozavrelia, which is associated with greater redox potential and pH. Multivariate statistical analysis revealed significant relationships between chironomid community composition and three environmental factors (conductivity, redox potential and pH). Anthropogenic influences and autogenic processes in peatlands likely modify the biotic communities, either through direct or indirect changes in peatland hydrology and chemistry. Low chironomid concentrations and diversity in Erxianyan Peatland may reflect ecological degradation caused by intense human activities, including the harvest of Sphagnum. This study provides information about subtropical peatland biodiversity and illustrates the utility of subfossil chironomids as proxies for past hydro-chemical changes in peatlands.

Rhabdomyosarcoma (RMS) is an embryonal tumor resembling developing skeletal muscle and the most common pediatric soft-tissue sarcoma. RMS is molecularly defined by the presence or absence of a fusion oncoprotein corresponding with the histological subtypes alveolar and embryonal RMS, respectively. Embryonal, or fusion-negative, RMS (FN-RMS) is heterogeneous in its molecular alteration profile; the major exception is the near universal PTEN promoter hypermethylation found in FN-RMS corresponding with decreased PTEN expression. PTEN's functional role in FN-RMS remains unclear as does PTEN's role in defining tumor fate decisions. Organismal cancer models can help elucidate these decisions by defining the potential tumor fate landscape that can occur in transformed multipotent progenitor cells. Our laboratory leverages a highly penetrant, early onset model of FN-RMS driven by the transdifferentiation of endothelial progenitors into skeletal muscle-like RMS cells by Hedgehog pathway activation. Therefore, our model is uniquely primed to empirically determine the core regulatory factors critical in FN-RMS initiation. Here, we conditionally deleted Pten in these cells (ASPcKO). ASPcKO tumors presented earlier than wild-type tumors and more closely resemble human FN-RMS with a less differentiated skeletal muscle state. These were unique characteristics of ASPcKO tumors as mice with homozygous loss of other tumor suppressors - Cdkn2a, Trp53, and Rb1 - did not recapitulate these phenotypes. We further probed the downstream transcriptional outputs of ASPcKO tumors revealing a profound increase in expression of the neural developmental transcription factors Dbx1 and Pax7. These outputs are functionally important as human FN-RMS patient-derived xenografts are dependent on both DBX1 and PAX7. Subsequently, we also show that DBX1 is a downstream transcriptional target of PAX7 highlighting how Pten loss engages a unique transcriptional program for tumor maintenance. PAX7 is also a core FN-RMS regulatory circuit component. To further interrogate the role of PAX7 on tumor initiation, we concomitantly deleted Pten and Pax7 in our FN-RMS model and found not only that Pax7 loss rescues the survival kinetics observed when Pten is lost, but also alters the developmental trajectory of the tumors that do develop. Instead of Smoothened trans-differentiating our aP2-Cre expressing primordial endothelial cell into a skeletal-muscle like FN-RMS, Pten and Pax7 loss dictates these endothelial cells to give rise to tumors with smooth muscle-like differentiation, including human-like leiomyosarcoma. Together, this synthetic essential interaction between Pten and Pax7 in FN-RMS stresses the importance of the bifunctional role of PAX7 in tumor initiation and maintenance and how specific tumor suppressor loss can engage developmental transcriptional programs to alter tumor fate. Citation Format: Casey G. Langdon, Katherine E. Gadek, Matthew R. Garcia, Kristin B. Reed, Madeline Bush, Jason A. Hanna, Catherine J. Drummond, Matthew C. Maguire, Patrick J. Leavey, David Finkelstein, Hongjian Jin, Jerold E. Rehg, Mark E. Hatley. Synthetic essentiality between PTEN and core dependency factor PAX7 dictates rhabdomyosarcoma indentity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3022.

Ultrafine-grained materials have a strong tendency to transform into coarse-grained materials due to the high density of grain boundaries at elevated temperature. In this study, pure titanium was processed by high-pressure torsion for 10 turns to give an ultrafine-grained (UFG) structure with an average grain size of ~96 nm. The recrystallization behavior of the UFG Ti was investigated by in-situ transmission electron microscopy (TEM). It is found that the gradient microstructures with average grain size ranging from ~129 nm to ~655 nm are formed under in-situ TEM heating up to 800 °C for 30 min. The Kossel-Mollenstedt (K-M) fringes in a convergent-beam electron diffraction (CBED) pattern were used to provide an accurate measure of the sample thicknesses. The results demonstrate that grain growth is significantly suppressed in the UFG pure Ti thin film compared to bulk material. Mechanism analysis shows the combined effects of driving force and drag force on grain boundary migration is the primary cause of the grain growth inhibition in the UFG pure Ti thin film.

The lattice defect structure developed during plastic deformation in a High-Entropy Alloy (HEA) with the composition of Ti35Zr27.5Hf27.5Nb5Ta5 was investigated. The crystallite size as well as the density and types of dislocations in a disk processed by High-Pressure Torsion (HPT) were determined by X-ray profile line analysis (XLPA). Additional transmission electron microscopy (TEM) investigations were carried out to monitor the grain size evolution during deformation. It was found that the dislocation density in the HPT-processed sample was very high compared to conventional materials. In addition, in Ti35Zr27.5Hf27.5Nb5Ta5 HEA the initial body-centered cubic structure transformed into a martensitic phase during HPT. The hardness of this HEA was investigated along the HPT-processed disk radius and correlated to the microstructure.

The effect of different plastic deformation methods on the phase composition, lattice defect structure and hardness in 316L stainless steel was studied. The initial coarse-grained γ-austenite was deformed by cold rolling (CR) or high-pressure torsion (HPT). It was found that the two methods yielded very different phase compositions and microstructures. Martensitic phase transformation was not observed during CR with a thickness reduction of 20%. In γ-austenite phase in addition to the high dislocation density (~10 × 1014 m-2) a significant amount of twin-faults was detected due to the low stacking fault energy. On the other hand, γ-austenite was gradually transformed into ε and α’-martensites with transformation sequences γ→ε→α’ during HPT deformation. A large dislocation density (~133 × 1014 m-2) was detected in the main phase (α’-martensite) at the periphery of the disk after 10 turns of HPT. The high defect density is accompanied by a very small grain size of ~45 nm in the HPT-processed sample, resulting in an very large hardness of 6130 MPa.

Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity, and were validated in low-throughput experiments. Principal component analysis revealed that a fraction of all upregulated or downregulated genes of a particular targeted pathway could partly explain cell sensitivity toward agents targeting that pathway. Combination therapies deemed immediately tractable to translation included ABT-263/crizotinib, ABT-263/paclitaxel, paclitaxel/JQ1, ABT-263/XL-184, and paclitaxel/nutlin-3, all of which exhibited synergistic antiproliferative and apoptotic activity in multiple TNBC backgrounds. Mechanistic investigations of the ABT-263/crizotinib combination offering a potentially rapid path to clinic demonstrated RTK blockade, inhibition of mitogenic signaling, and proapoptotic signal induction in basal and mesenchymal stem–like TNBC. Our findings provide preclinical proof of concept for several combination treatments of TNBC, which offer near-term prospects for clinical translation. Cancer Res; 77(2); 566–78. ©2016 AACR.

An artificially aged Al-Zn-Mg alloy with a grain size of ~ 1.3 µm was processed by equal-channel angular pressing (ECAP) and then subjected to dynamic compression at a strain rate of 4000 s-1 in the range from room temperature to 673 K. The results show the n' phase is refined and a n phase is formed during the first pass of ECAP and after further processing 8 passes the GP zones are removed. An ultrafine-grained (UFG) structure with an average grain size of ~200 nm was obtained after 4 passes. It is shown that dynamic compressive deformation assists the precipitation process through precipitate coalescence and by changing the precipitate orientations. The dynamic compressive yield strengths and flow stresses decrease gradually to different degrees with increasing temperature except after ECAP processing for 4 passes where there is thermal stability up to 473 K. The ECAP processing significantly improves the strength of the alloy at elevated temperatures by comparison with the as-received material.

Mg–Gd–Y–Zr alloys have attracted much attention recently due to their ability to exhibit stable fine-grained microstructures and their potential superplastic behavior. However, the microstructure and superplasticity of these alloys processed by severe plastic deformation (SPD) methods remain less understood. In this work, the microstructure and superplastic behavior of an Mg–5Gd–4Y–0.4Zr (GW54) alloy were investigated after processing using extrusion and the SPD processes of equal-channel angular pressing (ECAP) and high-pressure torsion (HPT). Microstructural characterization by transmission electron microscopy and electron backscattered diffraction showed that nano-sized grains of ~72±5 nm were obtained after 8 HPT turns whereas the grain sizes were about ~4.6±0.2 and ~2.2±0.2 µm after extrusion and 4 ECAP passes, respectively. Shear punch tests revealed that the optimum temperature for superplasticity is 623 K for the HPT samples and 723 K for the ECAP and extrusion samples, at which the strain rate sensitivities were measured as about 0.42±0.05, 0.46±0.05 and 0.50±0.05 for the extrusion, ECAP and HPT samples, respectively, and the corresponding activation energies were about 117, 101 and 110 kJ/mol for these three processing conditions. These results suggest that grain boundary sliding controlled by grain boundary diffusion is the dominant mechanism of deformation at the optimum temperatures for superplastic flow.

Differential scanning calorimetry (DSC) was used to study the thermal stability of the microstructure and the phase composition in nanocrystalline 316L stainless steel processed by high-pressure torsion (HPT) for ¼ and 10 turns. The DSC thermograms showed two characteristic peaks which were investigated by examining the dislocation densities, grain sizes and phase compositions after annealing at different temperatures. The first DSC peak was exothermic and was related to recovery of the dislocation structure without changing the phase composition and grain size. The activation energies for recovery after processing by ¼ and 10 turns were ~163 and ~106 kJ/mol., respectively, suggesting control by diffusion along grain boundaries and dislocations. The second DSC peak was endothermic and was caused by a reverse transformation of α’-martensite to γ-austenite. The hardness of annealed samples was determined primarily by the grain size and followed the Hall–Petch relationship. Nanocrystalline 316L steel processed by HPT exhibited good thermal stability with a grain size of ~200 nm after annealing at 1000 K and a very high hardness of ~4900 MPa.

An investigation was conducted to examine the mechanical behavior and microstructure evolution during deformation of ultrafine-grained pure magnesium at low temperatures within the temperature range of 296–373 K. Discs were processed by high-pressure torsion until saturation in grain refinement. Dynamic hardness testing revealed a gradual increase in strain rate sensitivity up to m ? 0.2. High ductility was observed in the ultrafine-grained magnesium including an exceptional elongation of ?360% in tension at room temperature and stable deformation in micropillar compression. Grain coarsening and an increase in frequency of grain boundaries with misorientations in the range 15°–45° occurred during deformation in tension. The experimental evidence, when combined with an analysis of the deformation behavior, suggests that grain boundary sliding plays a key role in low strain rate deformation of pure magnesium when the grain sizes are at and below ?5 ?m.

Experiments were conducted on an AZ80 magnesium alloy by processing by high-pressure torsion (HPT) at room temperature (296 K) for up to 10 turns under an imposed pressure of 6.0 GPa. Measurements of the Vickers microhardness along diameters and through the disk thicknesses were recorded after HPT to evaluate the evolution towards homogeneity. The results show hardness increases up to a factor of approximately 2 and the deformation is more homogeneous along the disc diameter than through the thickness.

The processing of metals through the application of high-pressure torsion (HPT) provides the potential for achieving exceptional grain refinement in bulk metal solids. These ultrafine grains in the bulk metals usually show superior mechanical and physical properties. Especially, the development of micro-mechanical behavior is observed after significant changes in microstructure through processing and it is of great importance for obtaining practical future applications of these ultrafine-grained metals. Accordingly, this presentation demonstrates the evolution of small-scale deformation behavior through nanoindentation experiments after HPT on various metallic alloys including a ZK60 magnesium alloy, a Zn-22% Al eutectoid alloy and a high entropy alloy. Special emphasis is placed on demonstrating the essential microstructural changes of these materials with increased straining by HPT and the evolution of the micro-mechanical responses in these materials by measuring the strain rate sensitivity.

Ultrafine-grained (UFG) materials produced by severe plastic deformation (SPD) may show both enhanced ductility and strength and hence resolve the so-called strength-ductility paradox. To gain mechanistic insights into such resolution, the effect of high-pressure torsion (HPT) on the microstructure and mechanical behavior was studied using a cast Al-7 wt. % Si alloy. As expected, the grain size decreased while the fraction of high-angle grain boundaries and microhardness increased due to HPT processing. However, tensile testing at room temperature revealed a simultaneous increase in strength and ductility compared to the as-cast sample. The samples showing simultaneous increase in strength and ductility also showed an increased contribution from grain boundary sliding (GBS), even at room temperature, which is attributed to the existence of a high fraction of high-angle and high-energy grain boundaries. It is proposed that the occurrence of moderate GBS, providing ductility, in very small size grains provides Hall-Petch strengthening and this suggests a potential combination for simultaneously achieving high strength and high ductility in SPD-processed UFG materials.

The evolution of phase composition, microstructure and hardness in 316L austenitic stainless steel processed by high-pressure torsion (HPT) was studied up to 20 turns. It was revealed that simultaneous grain refinement and phase transformation occur during HPT-processing. The γ-austenite in the initial material transformed gradually to ɛ-and α’-martensites due to deformation. After 20 turns of HPT the main phase was α’-martensite. The initial grain size of ~42 μm was refined to ~48 nm while the dislocation density increased to ~143 × 1014 m-2 in the α’-martensite phase at the disk periphery processed by 20 turns. The microstructure and hardness along the disk radius became more homogeneous with increasing numbers of turns. An approximately homogeneous hardness distribution with a saturation value of ~6140 MPa was achieved in 20 turns.

The Al-1% Mg and Al-0.1% Mg alloys were both processed by high-pressure torsion (HPT) at room temperature. In the Al-1% Mg alloy, the hardness values in the disc centre area are lower than in the disc edge area after 1/2 and 1 turn, and the area of lower hardness values in the disc centre decreases as the number of turns increases from 1/2 to 1 turn. Finally, the hardness values are reasonably homogenous along the disc diameter as the number of turns increases to 5 and 10 turns. The Al-0.1% Mg alloy displays a different hardness evolution behavior: the hardness values in the disc centre are higher than at the disc edge 1/2 and 1 turn, and the area of higher hardness values decreases as the numbers of turn increases from 1/2 to 1 turn. The hardness values evolve towards homogeneity along the disc diameter after 5 and 10 turns. EBSD microstructure investigations in the Al-0.1% Mg alloy reveal that a few low-angle boundaries exist at the disc edge after 1/2 turn. It is suggested that the higher hardness values in the disc centre in the Al-0.1% Mg alloy are related to rapid recovery at the disc edge where the material is subjected to heavy straining.

High-pressure torsion (HPT) is one of the major severe plastic deformation (SPD) procedures where disk metals generally achieve exceptional grain refinement at ambient temperatures. HPT has been applied for the consolidation of metallic powders and bonding of machining chips whereas very limited reports examined the application of HPT for the fabrication of nanocomposites. An investigation was initiated to evaluate the potential for the formation of a metal matrix nanocomposite (MMNC) by processing two commercial metal disks of Al-1050 and ZK60 magnesium alloy through HPT at room temperature. Evolutions in microstructure and mechanical properties including hardness and plasticity were examined in the processed disks with increasing numbers of HPT turns up to 5. This study demonstrates the promising possibility for using HPT to fabricate a wide range of hybrid MMNCs from simple metals.

An Al-3% Mg-0.2% Sc alloy was subjected to annealing or solution treatment and further processed by HPT at room temperature. Microhardness measurements were taken along the middle-sections of the discs and they demonstrated that a very substantial hardening is achieved during HPT processing regardless of the initial heat treatment. Hardness values of ~200 Hv were recorded at the edge of the samples although the microhardness distribution remained inhomogeneous along the diameters of the discs after 20 turns of high-pressure torsion. In addition, the microhardness of the solution treated Al-Mg-Sc samples continued to increase with the equivalent strain imposed by the anvils even after 30 turns of HPT processing whereas the hardness at the edges of the annealed discs saturated after 10 turns. These differences in the hardness evolution are attributed to the higher Mg content in solid solution in the case of the solution treated samples and its influence on delaying the recovery rate of this aluminium alloy.

The annealing-induced phase transformation was investigated in coarse-grained and severely deformed nanocrystalline face-centered cubic (FCC) high entropy alloys (HEA). Increasing temperature leads to phase transformations from the FCC phase to an L12 phase and finally to a B2 phase in the coarse-grained HEA. By contrast, direct transformation from the FCC phase to the B2 phase was observed in the nanocrystalline HEA at a lower temperature. Keywords: High entropy alloy, Nanocrystalline, Annealing, Phase transformation