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Intensification of northern hemisphere glaciation (iNHG), ~2.7 million years ago (Ma), led to establishment of the Pleistocene to present-day bipolar icehouse state. Here we document evolution of orbital- and millennial-scale Asian winter monsoon (AWM) variability across the iNHG using a palaeomagnetically dated centennial-resolution grain size record between 3.6 and 1.9 Ma from a previously undescribed loess-palaeosol/red clay section on the central Chinese Loess Plateau. We find that the late Pliocene–early Pleistocene AWM was characterized by combined 41-kyr and ~100-kyr cycles, in response to ice volume and atmospheric CO2 forcing. Northern hemisphere ice sheet expansion, which was accompanied by an atmospheric CO2 concentration decline, substantially increased glacial AWM intensity and its orbitally oscillating amplitudes across the iNHG. Superposed on orbital variability, we find that millennial AWM intensity fluctuations persisted during both the warmer (higher-CO2) late Pliocene and colder (lower-CO2) early Pleistocene, in response to both external astronomical forcing and internal climate dynamics. Persistent millennial Asian winter monsoon variability is shown to be superposed on orbital 41-kyr and 100-kyr cycles across the Pliocene–Pleistocene glacial intensification using a paleomagnetically dated high-resolution Chinese Loess Plateau grain size record. [ABSTRACT FROM AUTHOR]

The focus here is on a thin solid body passing through a channel flow and interacting with the flow. Unsteady two-dimensional interactive properties from modelling, analysis and computation are presented along with comparisons. These include the effects of a finite dilation or constriction, as the body travels through, and the effects of a continuing expansion of the vessel. Finite-time clashing of the body with the channel walls is investigated as well as the means to avoid clashing. Sustained oscillations are found to be possible. Wake properties behind the body are obtained, and broad agreement in trends between full-system and reduced-system responses is found for increased body mass. [ABSTRACT FROM AUTHOR]

Fluorosis can induce neurotoxicity. Sodium butyrate (SB), a histone deacetylase inhibitor, has important research potential in correcting glucose metabolism disorders and is widely used in a variety of neurological diseases and metabolic diseases, but it is not yet known whether it plays a role in combating fluoride-induced neurotoxicity. This study aims to evaluate the effect of SB on fluoride neurotoxicity and the possible associated mechanisms. The results of HE staining and Morris water maze showed that, in mice exposed to 100 mg/L fluoride for 3 months, the hippocampal cells arranged in loosely with large cell gaps and diminished in number. One thousand milligram per kilogram per day SB treatment improved fluoride-induced neuronal cell damage and spatial learning memory impairment. Western blot results showed that the abundance of malate dehydrogenase 2 (MDH2) and pyruvate dehydrogenase (PDH) in the hippocampus of fluorosis mice was increased, the abundance of pyruvate kinase M (PKM), lactate dehydrogenase (LDH), hexokinase (HK), phosphatidylinositol 3-kinase (PI3K), phosphorylated Akt (P-AKT), and hypoxia-inducible factor 1α (HIF-1α) was inhibited, and the content of lactate and ATP was decreased. SB treatment reversed the decreased glycolysis in the hippocampus of fluorosis mice. These results suggested that SB could ameliorate fluorosis-induced neurotoxicity, which might be linked with its function in regulating glycolysis as well as inhibition of the PI3K/AKT/HIF-1α pathway. Sodium butyrate ameliorates fluorosis-induced neurotoxicity by regulating hippocampal glycolysis in vivo (created with MedPeer (www.medpeer.cn)) [ABSTRACT FROM AUTHOR]

This paper is concerned with the input delay compensation problem for neutral-type systems with both state and input delays. Single/various cascaded-observers based output feedback controllers are designed to predict the future states such that the input delay that can be arbitrarily large yet exactly known is compensated completely. Compared with the existing techniques, some more simple necessary and sufficient conditions guaranteeing the stability of the closed-loop systems are offered in terms of the stability of retarded-type time-delay systems referred to as observer-error systems. Finally, the lossless transmission line control system is worked out to illustrate the effectiveness of the proposed controllers. [ABSTRACT FROM AUTHOR]

The functional behaviors and service performances of aeronautic gears are significantly determined by its surface integrity. Vibratory polishing, as one of the most promising ultra-high-precision finishing approaches for free-form surfaces, shows strong capability to improve the surface integrity of aeronautic gears. In order to gain a scientific insight into the surface generation, a three-dimensional predictive model is proposed in this study for the vibratory polishing surfaces of aeronautic gear considering the initial workpiece topography. The single abrasive particle is regarded as a micro-tool and the removed material is quantitatively determined based on the calculation of Brinell hardness. Then, the predictive model of the surface micro-topography can be developed on the basis of the initial workpiece topography and the interaction between workpiece and abrasive particles. The vibratory polishing tests are further carried out to verify the validity of the proposed surface topography prediction model. The results indicate that the predicted three-dimensional surface roughness agrees well with that of the measured data with an average error of 6.35%. Finally, parametric analysis is conducted to investigate the influence of polishing time, surface hardness, and abrasive particle diameter on the surface parameters. The preliminary work presented in this study is not only helpful to lay a scientific foundation for the more in-depth understanding of the surface generation and material removal mechanism in vibratory polishing, but also meaningful to provide an engineering guidance for the prediction of surface quality and optimization of machining parameters. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic, potentially cancerous disease with limited treatment options. Quercetin may be a novel treatment for IBD. However, its efficacy and safety are unknown. Our goal was to conduct a systematic evaluation to summarize the preclinical effects of quercetin, which may help guide future studies. Methods: The literature was drawn from three English databases (PubMed, Embase, and Web of Science), and the quality of the included literature was assessed using the SYRCLE list (10 items). The meta-analysis was performed using STATA 15.1 software. Results: A total of 11 animal studies with 199 animals were involved. The current meta-analysis showed that quercetin could reduce histological score (HS), Disease Activity Index (DAI), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide(NO), malondialdehyde (MDA), myeloperoxidase (MPO) activity and increase colon length (CL), weight change degree (WCD), interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase (SOD) activity and catalase (CAT) activity, which may involve anti-inflammatory, anti-oxidative stress, cytoprotective, barrier protection, flora regulation. Conclusions: In conclusion, preclinical evidence suggests that quercetin is an ideal agent for IBD treatment. However, the validity of the findings may be compromised by the low methodological quality and the small number of studies included. There may be some discrepancies between the results of the current analysis and the real situation. More rigorous experimental designs and more comprehensive studies are needed to test the protection of quercetin against IBD. [ABSTRACT FROM AUTHOR]

By increasing the activity and specific properties of the catalyst during oxygen reduction reactions (ORR), we hope to improve fuel cell performance and energy conversion efficiency. Using a single microwave step, the graphene oxide-decorated iron phthalate catalyst (FePcNs@GO) nanocomposites were synthesised. Some analytical techniques were used to validate the morphology and composition of Fe catalyst/graphene (FePcGO) and FePcNs@GO. In an oxygen-saturated environment, we conducted the ORR electrocatalytic studies on the prepared materials. The results demonstrate that when FePcNs@GO is combined with graphene oxide, it exhibits excellent electrochemical properties. In comparison to commercial FePc and 20% Pt/C, the overpotential is significantly lower. Under nitrogen-saturated conditions, the Fe2+/3+ redox form potential in FePcNs@GO exhibits a more positive behaviour, which favours strong interactions between Fe2+ and O2. In this work, we demonstrate that platinum-free catalysts have potential applications in ORR. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (AdCC) of the breast is a rare indolent carcinoma of salivary gland-type tumors, frequently associated with MYB genetic alteration. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a sparse variant of AdCC. This study sought to search for clinicopathological and genomic features in SB-AdCC. Registered clinicopathological data on a cohort of 13 AdCC of the breast cases, including six conventional adenoid cystic carcinoma (C-AdCC) cases and seven SB-AdCC cases, were collected. MYB gene rearrangement via fluorescent in situ hybridization was investigated and MYB protein expression was evaluated by immunohistochemistry. Compared with C-AdCC, we found that the distribution of SB-AdCC cases were shifted to older age and were more frequently distant metastasis. Moreover, metastasis cases also showed a high (exceed 30%) Ki-67 index. Both groups showed MYB rearrangements and MYB protein expression, but they were less frequent in SB-AdCC than C-AdCC. To conclude, our results suggest that SB-AdCC is an aggressive variant of mammary AdCC with a higher incidence of distant metastases compared with C-AdCC, though they share common molecular features. A high Ki-67 index may be an adverse prognostic factor for metastasis. [ABSTRACT FROM AUTHOR]

In the design of the hypersonic airliner which can greatly shorten the flight time and conduct space travel, it is of great significance for a Riemann solver to accurately simulate hypersonic flows. In this survey, the research process on the Riemann solver for hypersonic flows is reviewed, including the constructions of the traditional Riemann solvers, improvements of the traditional Riemann solvers for the shock anomaly, and the importance of the all-speed Riemann solver for hypersonic flows. Moreover, constructions and applications of the all-speed Riemann solvers are presented. It is obvious that the Riemann solver should be capable of obtaining physical solutions at low speeds and be robust against shock anomaly near strong shocks at the same time in simulating hypersonic flows. [ABSTRACT FROM AUTHOR]

Across the Miocene–Pliocene boundary (MPB; 5.3 million years ago, Ma), late Miocene cooling gave way to the early-to-middle Pliocene Warm Period. This transition, across which atmospheric CO2 concentrations increased to levels similar to present, holds potential for deciphering regional climate responses in Asia—currently home to more than half of the world's population— to global climate change. Here we find that CO2-induced MPB warming both increased summer monsoon moisture transport over East Asia, and enhanced aridification over large parts of Central Asia by increasing evaporation, based on integration of our ~1–2-thousand-year (kyr) resolution summer monsoon records from the Chinese Loess Plateau aeolian red clay with existing terrestrial records, land-sea correlations, and climate model simulations. Our results offer palaeoclimate-based support for 'wet-gets-wetter and dry-gets-drier' projections of future regional hydroclimate responses to sustained anthropogenic forcing. Moreover, our high-resolution monsoon records reveal a dynamic response to eccentricity modulation of solar insolation, with predominant 405-kyr and ~100-kyr periodicities between 8.1 and 3.4 Ma. Global warming drove 'wet gets wetter and dry gets drier' climate shifts in Asia ~5.3 million years ago with monsoon pacing by ~400,000 and ~ 100,000 year cycles. This could be a template for future Asian climate response to anthropogenic warming. [ABSTRACT FROM AUTHOR]

Normally, when different species of herbivorous arthropods feed on the same plant this leads to fitness-reducing competition. We found this to be different for two of Asia's most destructive rice pests, the brown planthopper and the rice striped stem borer. Both insects directly and indirectly benefit from jointly attacking the same host plant. Double infestation improved host plant quality, particularly for the stemborer because the planthopper fully suppresses caterpillar-induced production of proteinase inhibitors. It also reduced the risk of egg parasitism, due to diminished parasitoid attraction. Females of both pests have adapted their oviposition behaviour accordingly. Their strong preference for plants infested by the other species even overrides their avoidance of plants already attacked by conspecifics. This cooperation between herbivores is telling of adaptations resulting from the evolution of plant-insect interactions, and points out mechanistic vulnerabilities that can be targeted to control these major pests. Herbivore cooperation between insect pests can result in substantially greater damage to crops but also constitutes a good target for improved pest control. Liu et al. reveal how the brown plant-hopper and the rice striped stem-borer obtain mutual benefits when feeding on the same rice plant. [ABSTRACT FROM AUTHOR]

Thellier-type paleointensity experiments associated with partial thermal remanent magnetization checks have been widely used to determine paleointensity values from volcanic and archaeological media. However, previous studies have revealed that a substantial portion of paleointensity results with positive checks for historical lava samples largely fails to predict known Earth magnetic field intensity values. To determine the fidelity of paleointensity values, conventional Thellier-type paleointensity experiments were performed on Kilauea lava flows that erupted in 1960. The positive partial thermal remanent magnetization checks for our results range from 30.28 ± 1.38 µT to 52.94 ± 1.89 µT. This strongly indicates that conventional paleointensity checks cannot guarantee the fidelity of paleointensity results, especially when the unblocking temperatures for the newly formed magnetic particles are higher than the treatment temperature. Therefore, in this study, to check for thermal alteration during heating, the temperature dependence of the hysteresis parameter measured at room temperature for the thermally treated samples was also measured. Our new results show that nearly all biased paleointensity values correspond to a ratio of the coercivity of remanence to the magnetic coercivity of > 3 and a chemical alteration index > ~ 10%, which indicates the strong effect of the domain state and thermal alteration on the fidelity of the paleointensity results. Our study provides feasible criteria to further improve the fidelity of paleointensity estimations. [ABSTRACT FROM AUTHOR]

Background: Tetrapyrroles play indispensable roles in various biological processes. In higher plants, glutamate 1-semialdehyde 2,1-aminomutase (GSAM) converts glutamate 1-semialdehyde (GSA) to 5-aminolevulinic acid (ALA), which is the rate-limiting step of tetrapyrrole biosynthesis. Up to now, GSAM genes have been successively identified from many species. Besides, it was found that GSAM could form a dimeric protein with itself by x-ray crystallography. However, no mutant of GSAM has been identified in monocotyledonous plants, and no experiment on interaction of GSAM protein with itself has been reported so far. Result: We isolated a yellow leaf mutant, ys53, in rice (Oryza sativa). The mutant showed decreased photosynthetic pigment contents, suppressed chloroplast development, and reduced photosynthetic capacity. In consequence, its major agronomic traits were significantly affected. Map-based cloning revealed that the candidate gene was LOC_Os08g41990 encoding GSAM protein. In ys53 mutant, a single nucleotide substitution in this gene caused an amino acid change in the encoded protein, so its ALA-synthesis ability was significantly reduced and GSA was massively accumulated. Complementation assays suggested the mutant phenotype of ys53 could be rescued by introducing wild-type OsGSAM gene, confirming that the point mutation in OsGSAM is the cause of the mutant phenotype. OsGSAM is mainly expressed in green tissues, and its encoded protein is localized to chloroplast. qRT-PCR analysis indicated that the mutation of OsGSAM not only affected the expressions of tetrapyrrole biosynthetic genes, but also influenced those of photosynthetic genes in rice. In addition, the yeast two-hybrid experiment showed that OsGSAM protein could interact with itself, which could largely depend on the two specific regions containing the 81th–160th and the 321th–400th amino acid residues at its N- and C-terminals, respectively. Conclusions: We successfully characterized rice GSAM gene by a yellow leaf mutant and map-based cloning approach. Meanwhile, we verified that OsGSAM protein could interact with itself mainly by means of the two specific regions of amino acid residues at its N- and C-terminals, respectively. [ABSTRACT FROM AUTHOR]

An artificial intelligence (AI) processor is a promising solution for energy-efficient data processing, including health monitoring and image/voice recognition. However, data movements between compute part and memory induce memory wall and power wall challenges to the conventional computing architecture. Recently, the memory-centric architecture has been revised to solve the data movement issue, where the memory is equipped with the compute-capable memory technique, namely, computing-in-memory (CIM). In this paper, we analyze the requirement of AI algorithms on the data movement and low power requirement of AI processors. In addition, we introduce the story of CIM and implementation methodologies of CIM architecture. Furthermore, we present several novel solutions beyond traditional analog-digital mixed static random-access memory (SRAM)-based CIM architecture. Finally, recent CIM tape-out studies are listed and discussed. [ABSTRACT FROM AUTHOR]

The secondary explosive welding process promotes the diffusion of the carbon element and accumulation of chromium carbide, which leads to a decrease of tensile properties and toughness of the material. In this work, the average shear strength value increased from 400 to 421 MPa. The crack of the fatigue specimens started from the inclusions rich in alumina near the surface, and the harmful hard-phase inclusions were exposed because of stress concentration. The maximum load limit of 10CrNi3MoV steel undergoing secondary explosive welding was between 590 and 605 MPa. [ABSTRACT FROM AUTHOR]

In the present study, composite bimetallic plates of 10CrNi3MoV steel—304L stainless steel were butt welded by shielded metal arc welding (SMAW). A transition layer was designed to compensate for the dilution of Cr and Ni in stainless steel layer during the welding of dissimilar metals. From the results, it was seen that the lowest hardness of fusion weld was located in transition layer, followed by 304L stainless steel side, and the highest hardness occurred at 10CrNi3MoV steel area. The minimum hardness was related to high Cr and Ni in transition layer welded by E309L welding rod, and a uniform dendritic austenite structure was formed in the fusion weld. The formation of high-hardness carbides and vanadium-containing phases enhanced the hardness of the fusion weld. Butt welded joints had excellent tensile strength and toughness. The maximum tensile strength of the joint was about 694 MPa, and the tensile specimens fractured in ductile at matrix of the bimetallic plates. The impact energy of the weld joint was about 98 J at − 20 °C. When the number of loading cycles was set to 2 × 106 times, the maximum load limit of the bimetallic plate welded joint in 10CrNi3MoV steel was between 600 MPa and 625 MPa. [ABSTRACT FROM AUTHOR]

The first major build-up of Antarctic glaciation occurred in two consecutive stages across the Eocene–Oligocene transition (EOT): the EOT-1 cooling event at ~34.1–33.9 Ma and the Oi-1 glaciation event at ~33.8–33.6 Ma. Detailed orbital-scale terrestrial environmental responses to these events remain poorly known. Here we present magnetic and geochemical climate records from the northeastern Tibetan Plateau margin that are dated precisely from ~35.5 to 31 Ma by combined magneto- and astro-chronology. These records suggest a hydroclimate transition at ~33.7 Ma from eccentricity dominated cycles to oscillations paced by a combination of eccentricity, obliquity, and precession, and confirm that major Asian aridification and cooling occurred at Oi-1. We conclude that this terrestrial orbital response transition coincided with a similar transition in the marine benthic δ18O record for global ice volume and deep-sea temperature variations. The dramatic reorganization of the Asian climate system coincident with Oi-1 was, thus, a response to coeval atmospheric CO2 decline and continental-scale Antarctic glaciation. Marine records indicate a greenhouse to icehouse climate transition at ~34 million years ago, but how the climate changed within continental interiors at this time is less well known. Here, the authors show an orbital climate response shift with aridification on the northeastern Tibetan Plateau during this time. [ABSTRACT FROM AUTHOR]

Summary: Acute myeloid leukemia (AML) is reported to be vulnerable to transcription disruption due to transcriptional addiction. Cyclin-dependent kinase 9 (CDK9), which regulates transcriptional elongation, has attracted extensive attention as a drug target. Although several inhibitors, such as alvocidib and dinaciclib, have shown potent therapeutic effects in clinical trials on AML, the lack of high selectivity for CDK9 and other CDKs has limited their optimal clinical efficacy. Therefore, developing highly selective CDK9 inhibitors is still imperative for the efficacy and safety profile in treating AML. Here, we report a novel highly selective CDK9 inhibitor, JSH-009, which exhibited high potency against CDK9 and displayed great selectivity over 468 kinases/mutants. It also demonstrates impressive in vitro and in vivo antileukemic efficacy in preclinical models of AML, which makes JSH-009 a useful pharmacological tool for elucidating CDK9-mediated transcription and a novel therapeutic candidate for AML. [ABSTRACT FROM AUTHOR]

Heavy metals, one of the most toxic classes of pollutants, are resistant to degradation and harmful to the biological environment. The lakes that have developed on the Tibetan Plateau are ideal regions to investigate historic heavy metal pollution, particularly through the use of the reliable 210Pb dating technique. Environmental magnetism has been successfully applied to estimate heavy metal pollution in different environmental systems due to its characteristics of simple processing steps, good sensitivity, and non-destructibility. However, it has not yet been applied to assess heavy metal pollution in lake sediments on the Tibetan Plateau. A series of environmental magnetic investigations of Qiangyong Co Lake sediments (southern Tibetan Plateau) was therefore conducted to explore the relationship between magnetic minerals and mercury (Hg) concentrations. The results showed that the magnetic mineral species in lake sediments remained stable, with similar levels of four different components from 1899 to 2011. However, the proportion of component 1 (C1, hematite) increased continuously with the corresponding decrease in the proportion of C2 (goethite), while the proportions of C3 and C4 (magnetite) did not change significantly. As a result, the bulk magnetic signals (e.g., SIRM and χlf) were unsuitable for the evaluation of the Hg concentration; however, the proportion of hematite had a strong positive correlation with the Hg concentration. It is possible that the Qiangyong Glacier (the main water supply for Qiangyong Co Lake) has experienced faster melting with global and local warming, and the Hg trapped in cryoconite and ice was released. Hematite, with a large specific surface area, has a strong capacity for absorbing Hg, and both materials are ultimately transported to Qiangyong Co Lake. The proportion of hematite in a sample is therefore a suitable semi-quantitative proxy that can be used to evaluate the Hg concentration in Qiangyong Co Lake sediments. This study confirmed that the variation of magnetic minerals can provide a new method to estimate the variation of Hg concentrations and to study the process of Hg deposition in lakes in the southern Tibetan Plateau on the basis of a detailed environmental magnetic analysis. [ABSTRACT FROM AUTHOR]

High strength low alloy (HSLA) steel 10CrNi3MoV and stainless steel 304L (SS304L) were used to manufacture bimetallic plates by explosive welding. The quality and overall performance of the bimetallic plates were evaluated in terms of microstructure and mechanical properties. Its microstructure, elemental distribution, and phase analysis of the bonding interface were investigated by means of OM, SEM, EDS, and XRD. The mechanical properties of the bimetallic plates were studied by experimental measurements, including tensile tests, shear tests, Charpy impact tests, hardness tests, and then evaluated based on the standards. Experimental evaluation showed out that HSLA 10CrNi3MoV steel and SS304L could be cladded with a good quality of bonding properties by explosive welding. The base material 10CrNi3MoV steel still maintained its inherent excellent mechanical performance, even after undergoing explosive welding process. The functional flyer layer SS304L maintained its corrosion resistance even after undergoing a process of post-weld heat treatment at high temperature 645 °C for 240 min. Shear strength of the bimetallic plates was about 432 MPa more than twice the value required by the standard. The maximum hardness value was obtained near the joint on the side of SS304L, and the minimum one appeared in the middle of the explosive welding interface. [ABSTRACT FROM AUTHOR]

Single-crystal cathode materials for lithium-ion batteries have attracted increasing interest in providing greater capacity retention than their polycrystalline counterparts. However, after being cycled at high voltages, these single-crystal materials exhibit severe structural instability and capacity fade. Understanding how the surface structural changes determine the performance degradation over cycling is crucial, but remains elusive. Here, we investigate the correlation of the surface structure, internal strain, and capacity deterioration by using operando X-ray spectroscopy imaging and nano-tomography. We directly observe a close correlation between surface chemistry and phase distribution from homogeneity to heterogeneity, which induces heterogeneous internal strain within the particle and the resulting structural/performance degradation during cycling. We also discover that surface chemistry can significantly enhance the cyclic performance. Our modified process effectively regulates the performance fade issue of single-crystal cathode and provides new insights for improved design of high-capacity battery materials. Performance improvement of cathode materials represents one of the most critical technological challenges for lithium-ion batteries. Here the authors show a close correlation between surface chemistry and phase distribution from homogeneity to heterogeneity, and its impact on the cyclic performance. [ABSTRACT FROM AUTHOR]

Determination of hematite contributions to sedimentary magnetizations is an important but difficult task in quantitative environmental studies. The poorly crystalline and fine-grained nature of hematite nanoparticles makes quantification of their concentrations in natural environments challenging using mineralogical and spectroscopic methods, while the weak magnetization of hematite and often significant superparamagnetic nanoparticle concentrations make quantification difficult using magnetic remanence measurements. We demonstrate here that much-used magnetic parameters, such as the S-ratio and 'hard' isothermal remanent magnetization (HIRM), tend to significantly underestimate relative and absolute hematite contents, respectively. Unmixing of isothermal remanent magnetization (IRM) acquisition curves is among the more suitable approaches for defining magnetic mineral contributions, although it has under-appreciated uncertainties that limit hematite quantification. Diffuse reflectance spectroscopy and other methods can enable relative hematite and goethite content quantification under some conditions. Combined use of magnetic, mineralogical, and spectroscopic approaches provides valuable cross-checks on estimated hematite contents; such an integrated approach is recommended here. Further work is also needed to rise to the challenge of developing improved methods for hematite quantification. [ABSTRACT FROM AUTHOR]

MS-222 (tricaine methanesulfonate) and eugenol are the two frequently used fish anesthetics. This study intends to analyze the regulation of these anesthetics in Chinese sea bass, Lateolabrax maculatus, through transcriptomic analysis. L. maculatus were exposed to MS-222 or eugenol, and those without any treatments were regarded as controls. Gills and livers were extracted for transcriptomic analysis after recovery in fresh water for 6 h. Identified genes were assigned to NR, COG, SWISS, GO, and KEGG database for predicting gene functions. A FDR ≤ 0.05 and |log2(FC)| ≥ 1 were applied to determined differentially expressed gene (DEG). A total of 45,626 unigenes were annotated using at least one database. The eugenol-treated liver group presented less DEGs compared with that treated by MS-222. Both the MS-222- and eugenol-treated liver groups presented notable DEGs that participated in human disease and metabolism pathways. The eugenol group showed more pathways related to detoxification activity and xenobiotics biodegradation, and those from the MS-222 group were related to organismal system such as reproduction. By comparing gill and liver samples using the same drug, the enriched pathways were generally consistent among the three comparisons. In conclusion, eugenol and MS-222 could change the pathways related to metabolism and immunity in L. maculatus. MS-222 may trigger more damages on the fish liver and reproduction. [ABSTRACT FROM AUTHOR]

Teprenone (geranylgeranylacetone) is one kind of safe and effective agent in gastrointestinal mucosa, which have been widely used in human and veterinary, but rarely used in aquaculture animals. In this study, Lateolabrax maculatus, an important economic fish species in southern China, was taken as the object of study to investigate the protective effect of teprenone on intestinal stress. The present study was designed to investigate the potential mechanism underlying the protection offered by teprenone to protect the gastrointestinal tract against hypoxia and reoxygenation injury of L. maculatus. (a) For oxidative stress parameters, SOD, CAT, and T-AOC in control group were higher than those in teprenone group. MDA content was significantly higher than that in teprenone group at N and 12h time points in intestine (P < 0.05), and at 12, 24, and 48 h time points in stomach. (b) For immune-associated proteins, LZM activity in the control group was lower than that in the teprenone group, and the difference between the two groups in stomach and intestine was significant at 12.48 h and 6.48 h time points, respectively (P < 0.05). Compared with time point N, the content of HSP70 in the control group increased at 0 h in intestine. At 0–48 h, intestine HSP70 content in the control group showed a gradually decreasing trend, which was higher than that in the teprenone group. (c) For apoptosis-related factors, the activity of Cyt-C, caspase9, and caspase3 increased first and then decreased in both groups. The content of Cyt-C in the control group was significantly higher than that in the teprenone group at N-3.6 h, and 3.48 h time points in stomach and intestine, respectively (P<0.05). The activity of caspase9 and caspase3 was higher than that in the teprenone group at N-48 h. Results indicated that acute hypoxia and reoxygenation cause the expression levels of oxidative stress and apoptosis-related factors in the stomach and intestine increased first and then decreased within 0–48 h. Acute hypoxia and reoxygenation also that causes the level of nonspecific immunity decreased first and then increased. A total of 400-mg/kg treatment of teprenone can protect stomach and intestinal tissues to a certain extent. It can effectively protect oxidative stress and apoptosis within 0–48 h after acute hypoxia and reoxygenation and enhance non-specific immunity. [ABSTRACT FROM AUTHOR]

Transition metal phosphides have been regarded as reliable supercapacitor electrode materials and extensively researched. In this work, a facile three-step way has been taken to synthesize NiCoP@NiCoP core–shell nanoarrays directly grown on carbon cloth, which was used as a high-performance supercapacitor electrode. Compared with the NiCo-LDH precursor and NiCoP nanowire and NiCoP nanosheet, NiCoP@NiCoP core–shell composite shows higher electrochemical performance owing to the integration of the advantages of phosphides and core–shell structure. To be specific, the as-fabricated NiCoP C–S electrode exhibits great electrochemical performance with high specific capacitance (1492.5 F g−1 at 1 A g−1), good rate performance (68.82% of the initial specific capacitance at 15 A g−1) and outstanding cycling stability (maintains 80.9% of the initial capacitances after 5000 cycles at 10 A g−1). Moreover, the assembled NiCoP C–S//rGO asymmetric supercapacitor device delivers a high energy density of 48.13 Wh kg−1 at the power density of 1125 W kg−1 and it still retains 20.94 Wh kg−1 at a high power density of 11250 W kg−1, indicating its great possibility of practical application. [ABSTRACT FROM AUTHOR]

Transition metal phosphides (TMPs) are regarded as reliable supercapacitor electrode materials due to its high conductivity and excellent chemical activity. In this work, NiCo-LDH was synthesized via electrode position techniques, followed by one-step phosphating to convert the hydroxide into a phosphide. The obtained NiCoP shows 3D porous nanosheet stack structure, which provides a larger specific surface area and more active sites. The as-fabricated electrode exhibits good electrochemical performance with high specific capacitance (1142.84 F g−1 at 1 A g−1), good rate capabilities (62.07% of the initial specific capacitance at 10 A g−1), and outstanding cycle stability (maintains 74.5% of initial capacitances after 5000 cycles at 10 A g−1). Owning to superior electrical conductivity and excellent redox activity of phosphide, its voltage window and cycle stability are significantly improved compared with NiCo-LDH. In addition, NiCoP was used as the positive electrode and rGO as the negative electrode to fabricate the NiCoP//rGO asymmetric supercapacitor, which delivers a voltage window of 1.5 V and a high energy density of 14.7 Wh kg−1 at a power density of 753.6 W kg−1. [ABSTRACT FROM AUTHOR]

Forkhead box O (FoxO) is a downstream transcription factor of the insulin-signaling pathway, which plays vital roles in the growth and metabolism of organisms. In this study, BmFoxO was overexpressed in BmE cells, in which proliferation was inhibited and apoptosis was increased. The transgenic vector overexpressing BmFoxO was constructed, and the transgenic silkworm line A4FoxO was generated via embryonic microinjection. The body size of A4FoxO silkworm was smaller than that of non-transgenic silkworm (WT). The quantitative polymerase chain reaction results revealed that the insulin pathway was enhanced and the growth-related TOR pathway was suppressed. Furthermore, the translation of proteins in the fat body of A4FoxO silkworm was inhibited. The expression level of genes involved in the glucose synthesis and lipolysis pathways was increased, whereas that of genes involved in fat synthesis was decreased. Oil red O staining revealed that the amount of lipid droplets was reduced in A4FoxO silkworms compared with WT. Further analysis showed that the content of triglyceride and glycogen was significantly decreased in fat body, but the content of glucose and trehalose was increased in the hemolymph of A4FoxO silkworms. These results suggest that the enhanced expression of BmFoxO disturbs glycolipid metabolism and affects silkworm growth. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: High-energy diets are among the main causes of the global epidemic of metabolic disorders, including obesity and type 2 diabetes. The mechanisms of high-energy-diet-induced metabolic disorders are complex and largely unknown. The non-receptor tyrosine kinase c-Abl plays an important role in adipogenesis in vitro but its role in vivo in the regulation of metabolism is still elusive. Hence, we sought to address the role of c-Abl in diet-induced obesity and obesity-associated insulin resistance. Methods: The expression of c-Abl in different fat tissues from obese humans or mice fed a high-fat diet (HFD) were first analysed by western blotting and quantitative PCR. We employed conditional deletion of the c-Abl gene (also known as Abl1) in adipose tissue using Fabp4-Cre and 6-week-old mice were fed with either a chow diet (CD) or an HFD. Age-matched wild-type mice were treated with the c-Abl inhibitor nilotinib or with vehicle and exposed to either CD or HFD, followed by analysis of body mass, fat mass, glucose and insulin tolerance. Histological staining, ELISA and biochemical analysis were used to clarify details of changes in physiology and molecular signalling. Results: c-Abl was highly expressed in subcutaneous fat from obese humans and HFD-induced obese mice. Conditional knockout of c-Abl in adipose tissue improved insulin sensitivity and mitigated HFD-induced body mass gain, hyperglycaemia and hyperinsulinaemia. Consistently, treatment with nilotinib significantly reduced fat mass and improved insulin sensitivity in HFD-fed mice. Further biochemical analyses suggested that c-Abl inhibition improved whole-body insulin sensitivity by reducing HFD-triggered insulin resistance and increasing adiponectin in subcutaneous fat. Conclusions/interpretation: Our findings define a new biological role for c-Abl in the regulation of diet-induced obesity through improving insulin sensitivity of subcutaneous fat. This suggests it may become a novel therapeutic target in the treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

The Upper Permian Changxing dolomite reservoirs serves as one of the most important gas and oil reservoirs in the NE Sichuan Basin. Determining the dolomitizing fluid's pathway is regarded as the key to solve the 'dolomite problem' and further petroleum exploration. Outcrop samples from Upper Permian Changhsingian Panlongdong Section were studied using oxygen isotopic analysis, cathodoluminescence (CL) and major element analysis, in an attempt to determine the migration path way and properties of the dolomitizing fluid. Of the Changxing dolomite, the δ O values ranged from -3.494‰ to -5.481‰, which decreased from the top layer to the bottom in the section; the MgO contents varied from 9.24% to 21.43%, CaO contents from 28.65% to 39.87%, the CaO/MgO ratio from 1.40 to 4.31 and the MnO contents from 0.004% to 0.009 8%. The MgO contents showed a downwardly decreasing trend in the section, while the CaO/MgO showed an opposite rule. All of the dolomites looked dull or dark when they were exposed to the electron beam of the cathodoluminescence device. None of the fine- to medium grained dolomite showed a banded structure. Given that dolomitizing fluid's salinity decreased during the dolomitization process in its pathway, we concluded that the dolomitizing fluid migrated downwardly in Changxing Formation after excluding the possibility of deep burial or meteoric-marine mixing-water influences. As the dolomitizing fluid's pathway has always been difficult to be determined in highly dolomitized Formation, this study showed an important application of oxygen isotope values in resolving this problem. [ABSTRACT FROM AUTHOR]

Scanning tunneling microscopy (STM) can be used to image individual biological molecules, such as proteins, in vacuum or air. This requires sample dehydration and thus may not reflect the native state of the molecule. Extensive efforts have been made to image single proteins in solution using STM; however, the images have revealed only round or oval shapes with no sub-molecular details. Here, we present the sub-molecular features of streptavidin proteins under physiological conditions using a homebuilt low-leakage-current and highstability liquid phase STM. The N-lobe, C-lobe, and C-terminal tail of the epidermal growth factor receptor kinase domains were also resolved in solution. Our results demonstrate that the structure, morphology, and dynamics of a protein molecule can be examined under physiological conditions by the STM. [ABSTRACT FROM AUTHOR]

Serpentinites have great implications for the oceanic crust, subduction zones, island arc magmatism activity, and the formation of nickel ore deposits. To further determine the mechanism of magnetic property changes of serpentinites, samples from ODP Holes 897D and 1070A were investigated by integrating both magnetic and non-magnetic methods. Detailed rock magnetic results demonstrate that magnetite prevails in the entire serpentinite section, while maghemite is present in the upper and altered parts. The concentration of Fe in the fresh peridotite is inhomogeneous; nonetheless, the magnetic properties are generally determined by the serpentinization process. The formation and state of the magnetite depend on the fracture conditioning and fluid activities which are controlled by the serpentinization process. By comparing these two holes, we found that the production of magnetite is consistent with the serpentinization process; serpentinization is a multi-stage process which involves early high-temperature serpentinization and later low-temperature oxidation. As the serpentinization continues, the fine magnetic particles become coarser, combined with the formation of new SP particles, and the later low-temperature oxidation leads to the maghemitization of the magnetites. The duration of oxidation also contributes to the differences of remanent magnetization between these two holes. These results greatly improve our understanding of the magnetic enhancement during the serpentinization process, and provide constraints on the interpretation of the paleomagnetic and aeromagnetic anomalies in this area. [ABSTRACT FROM AUTHOR]

Magnetite is the most important magnetic mineral in paleomagnetism. Its magnetic properties are controlled by many factors, such as grain size distribution, shape and interactions. Traditional rock magnetic experiments, however, have great difficulty in decoupling the effects of these parameters. In this study, we attempted to investigate the effects of grain size distribution on magnetic properties of magnetite powders by using a micromagnetic method. The particle geometries used in the micromagnetic model were based on the grain size distribution observed in a synthetic magnetite powder. The simulated hysteresis parameters agree well with the experimental measurements and provide clear microstructures of the magnetic remanence. Our results show that grain size plays a more important role in affecting hysteresis parameters of magnetite assemblages than shape under effects of interactions. Uniform or vortex superstates formed by two or more particles are found and display different stabilities of magnetic recording in assemblages. Some domain structures of single-domain (SD) particles are reversed as the applied field decreases to zero. Small pseudo-single-domain particles behave as SD structures and may dominate the magnetic recordings. In all, micromagnetic modeling of grain size distributions provide a better understanding of magnetic assemblages consisting of nanoscale particles. [ABSTRACT FROM AUTHOR]

Magnetic minerals in sediments of the continental shelf are sensitive to environmental changes. Therefore, to determine the exact phases of magnetic minerals is the prerequisite to investigate the paleoenvironmental significances. In this study, a comprehensive rock magnetic investigation, coupled with mineralogical studies, was carried out on the long core NHH01 (with a length of 125.64 m) from the central continental shelf of the South Yellow Sea. Single-domain greigite was identified as the dominant magnetic carrier in sediments between 44.90 and 51.80 m, and terrigenous magnetite is the major magnetic phase in the adjacent layers. The existence of greigite unambiguously indicates an anoxic environment. We tentatively interpreted that such an environment could be formed by the fast sea level changes, long-existing of the cold eddies during warm stages, or in a lake which might be related to locally tectonic uplifting. Therefore, the occurrence of the thick-layer greigite could supply a new perspective to paleoenvironmental or even tectonic studies. [ABSTRACT FROM AUTHOR]

The physical and chemical properties of soils are closely controlled by the climate factors and thus are significant for paleoclimate reconstruction. In this study, two adjacent soil profiles (LP and LPM) with different slopes from Yan'an, Shaanxi Province, were investigated using magnetic methods to determine the impact of topography on magnetic properties of soil. Our results show that although LP and LPM have similar magnetic minerals and grain size distribution, both the average and maximum magnetic susceptibility ( χ) of LP are almost doubled compared to those of LPM. In addition, the ratios of susceptibility enhancement to the background ( E) for LP and LPM are 2.27 and 2.04, respectively; the ratios of saturation isothermal remnant magnetization (SIRM) enhancement ( E) for these two profiles are 1.80 and 1.86, respectively. The slopes of the linear regression trends between frequency-dependent susceptibility ( χ) and 'hard' isothermal remnant magnetization (HIRM) ( χ/HIRM), Anhysteretic remnant magnetization (ARM) and HIRM (ARM/HIRM), are almost free from the effect of parent material. χ/HIRMs for LP and LPM are 28.7×10 and 28.9×10 A m, respectively; ARM/HIRMs are 0.35 and 0.33 for LP and LPM, respectively. These results demonstrate that parameters, χ/HIRM, ARM/HIRM, E and E, are affected less by parent material and topography, which are better than the χ for bulk samples to indicate the paleoclimatic conditions (e.g., the paleorainfall) in a large-scale region. [ABSTRACT FROM AUTHOR]

To assess the potential effects of Cry2Aa-expressing insect-resistant Bt rice on Chrysoperla sinica larvae, we conducted two tritrophic bioassays using a non-target ( Laodelphax striatellus) and a target herbivore ( Chilo suppressalis) as prey. None of the tested life-table parameters of C. sinica did differ when fed with L. striatellus nymphs reared on either Bt or control rice plants. Similarly, C. sinica larval survival and development were not affected when fed C. suppressalis larvae that were reared on Cry2Aa-contained artificial diet compared to those fed control diet. However, the 7-day larval weight was significantly decreased in the Bt treatment and none of the C. sinica larvae developed to the adult stage. To clarify whether the observed effects were due to the direct toxicity of Cry2Aa or prey-quality mediated, we conducted a dietary exposure assay in which the toxicity of Cry2Aa to C. sinica larvae was tested. Potassium arsenate (PA) was included as a positive control. None of the tested life-table parameters of C. sinica was adversely affected when fed Cry2Aa at 500 μg/ml sucrose solution. In contrast, C. sinica larvae were adversely affected by feeding on sucrose solution containing PA. In the feeding assays, exposure of C. sinica larvae to Cry2Aa was confirmed by ELISA. Our results demonstrate that C. sinica larvae are not sensitive to Cry2Aa at concentrations exceeding the levels that the larvae may encounter in Bt rice fields. Consequently the detrimental effects observed in the tritrophic studies using Bt rice-fed C. suppressalis as prey can be attributed to the decreased prey quality due to the sensitivity of C. suppressalis larvae to Cry2Aa. [ABSTRACT FROM AUTHOR]

The interaction between the HSP90 chaperone and its client kinases is sensitive to the conformational status of the kinase, and stabilization of the kinase fold by small molecules strongly decreases chaperone interaction. Here we exploit this observation and assay small-molecule binding to kinases in living cells, using chaperones as 'thermodynamic sensors'. The method allows determination of target specificities of both ATP-competitive and allosteric inhibitors in the kinases' native cellular context in high throughput. We profile target specificities of 30 diverse kinase inhibitors against >300 kinases. Demonstrating the value of the assay, we identify ETV6-NTRK3 as a target of the FDA-approved drug crizotinib (Xalkori). Crizotinib inhibits proliferation of ETV6-NTRK3-dependent tumor cells with nanomolar potency and induces the regression of established tumor xenografts in mice. Finally, we show that our approach is applicable to other chaperone and target classes by assaying HSP70/steroid hormone receptor and CDC37/kinase interactions, suggesting that chaperone interactions will have broad application in detecting drug-target interactions in vivo. [ABSTRACT FROM AUTHOR]

High-resolution environmental records from the Tibetan Plateau are essential to understand past global climatic and environmental changes. Magnetic minerals in lake sediments are important proxies to reconstruct environmental and climatic changes. Nam Co (lake) is a typical great lake in the transitional region of southwest monsoon in the Tibetan Plateau. Previous studies have extensively focused on geochemistry, microfossils, sedimentology and biochemistry analysis of Nam Co, which provides sound interpretation of paleoclimatic and paleoenvironmental changes. However, up to now, no systematic environmental magnetic studies have been carried out. Therefore, high-resolution and systematic magnetic studies combined with geochemical parameters were carried on lake sediments of core NC 08/01 from Nam Co for the Holocene period (11.3 cal ka BP) in order to explore how magnetic properties of the sediments respond to climatic changes. Based on variations of magnetic proxies, the sequence can be separated into 3 units. Unit 1 (236-199 cm, 11.3-7.8 cal ka BP) contains dominantly coarse-grained magnetite with homogeneous grain size. A positive correlation between magnetite and Ti strongly suggests that these coarse-grained detrital magnetites reflect detrital input signals due to insignificant effects of postdepositional dissolution processes on these coarse-grained magnetite particles. For Unit 2 (198-102 cm, 7.8-2.1 cal ka BP), magnetic grain size is finer and the corresponding concentration of magnetite is also reduced. This is mainly due to significant dissolution of these fine-grained detrital magnetite particles, which were transported under reduced water flow conditions during this period. For Unit 3 (101-0 cm, 2.1-0 cal ka BP), the bulk magnetic properties are dominated by a mixture of single domain biogenic magnetite and detrital magnetite. The concentration of magnetic minerals is not correlated with the Ti content. In conclusion, the preservation of magnetic minerals in the lake sediment and thus the corresponding magnetic properties are related to the initial grain size. Combination of magnetic properties (including variation of grain size and concentration) and other proxies of detrital inputs (e.g. Ti) can be used to infer the variation of redox conditions in Nam Co. These results provide a viable framework for reconstructing the paleoenvironmental changes of this lake. [ABSTRACT FROM AUTHOR]

Environmental magnetic studies were conducted on a 9.42-m-long sediment core from Gonghai Lake, North China. Radiocarbon dating indicates that the record spans the last 15,000 cal year BP. The principal magnetic mineral in the sediments is pseudo-single domain magnetite of detrital origin with minimal post-depositional alteration. Although the variations in the concentration of detrital magnetic minerals and their grain size throughout the core reflect inputs from both soil erosion and eolian dust, it is shown that their climatic and environmental significance changes with time. In the lowermost part of the core, ~15,000-11,500 cal year BP, the magnetic minerals were supplied mainly by bedrock erosion, soil erosion and dust input when climate ameliorated after the cold and dusty last glacial maximum. The increasing magnetic susceptibility (χ) in this interval may indicate a combination of changes in the lake environment together with catchment-surface stabilization and a decreasing proportion of dust input. In the central part of the core, ~11,500-1,000 cal year BP, the detrital magnetic minerals mainly originated from dust inputs from outside the catchment when the lake catchment was covered by forest, and catchment-derived sediment supply (and thus the lake sediment accumulation rate) were minimal. The generally low concentration of magnetic minerals in this part of the core reflects the highest degree of soil stability and the strongest summer monsoon during the Holocene. In the uppermost part of the core, the last ~1,000 years, detrital magnetic minerals mainly originated from erosion of catchment soils when the vegetation cover was sparse and the sediment accumulation rates were high. Within this part of the core the high magnetic susceptibility reflects strong pedogenesis in the lake catchment, and thus a strong summer monsoon. This scenario is similar to that recorded in loess profiles. Overall, the results document three main stages of summer monsoon history with abrupt shifts from one stage to another: an increasing and variable summer monsoon during the last deglacial, a generally strong summer monsoon in the early and middle Holocene and a weak summer monsoon in the late Holocene. The results also suggest that different interpretational models may need to be applied to lake sediment magnetic mineral assemblages corresponding to different stages of environmental evolution. [ABSTRACT FROM AUTHOR]

This paper studies magnetic properties and composition of granulite-facies rocks of both the Neogene and Archean continental lower crust in the Neogene xenolith-bearing Hannuoba(汉诺坝) alkaline basalt and the exposed lower crustal section in the Archean Huai'an(淮安) terrain (Wayaokou (瓦窑口)-Manjinggou(蔓菁沟 profile), the northern North China Craton. It provides a unique opportunity for a comparative study of magnetic properties and composition of both the Archean and Neogene continental lower crust. We measure magnetic parameters (susceptibility κ and magnetic hysteresis parameters, such as saturation magnetization J, saturation isothermal remanent magnetization J, and intrinsic coercivity H) of eleven Hannuoba lower crustal xenoliths and nine terrain granulites from the Archean Huai'an terrain. Results indicate that the average values of κ, J and J of Archean granulites are 4 122×10 SI, 523.1 A/m and 74.9 A/m, respectively, which are generally higher than those of granulite-facies xenoliths (1 657×10 SI, 163.9 A/m and 41.9 A/m, respectively). These two types of granulites contain ilmenite, (titano) magnetite, minor hematite and some 'magnetic silicates' (clinopyroxene, plagioclase and biotite). The Mg-rich ilmenite in granulite-facies xenolith is relatively higher than that in terrain granulites. We observe a more evolved character as higher magnetic as well as lower Sr/Nd, Cr/Nd, Ni/Nd, Co/Nd and V/Nd ratios in terrain granulites. These differences in magnetic characteristics reflect their different origins and evolutions. The high magnetization of granulites in the Huai'an terrain represents magnetic properties of the Archean continental lower crust, and low magnetization of granulite-facies xenoliths represents magnetic properties of the Cenozoic lower crusts in the northern North China Craton. [ABSTRACT FROM AUTHOR]

The magnetic properties of loess, lake, and ocean sediments are often used as indicators for paleoclimatic/paleoenvironmental changes. Thermomagnetic analysis is a conventional approach for identifying magnetic phases and thermal alteration of samples. Magnetic concentration parameters are often enhanced after thermal treatment. In this study, the role of clay minerals in magnetic enhancement at elevated temperatures is systematically investigated. The results indicate that the clay minerals (saponite, Ca-montmorillonite, kaolinite, and chlorite) are dominated by paramagnetic behaviour and that the magnetic properties remain relatively stable after heating to 700°C in argon. In contrast, mixtures of hematite and chlorite have a high degree of magnetic enhancement after heating in argon, which indicates that clay minerals play important role in magnetic enhancement. These results improve our understanding of the processes involved in complicated mineral transformations, which is important for retrieving paleoclimatic/paleoenvironemntal signals from magnetic proxies. [ABSTRACT FROM AUTHOR]

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines-which represent much of the tissue-type and genetic diversity of human cancers-with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies. [ABSTRACT FROM AUTHOR]

Aeolian dust, a primary terrigenous component of ocean sediments, has been widely used to reconstruct the paleoclimatic evolution because its transported distance, grain size and concentration are sensitive to climate changes. To further characterize the aeolian dust, the deposits at site Ocean Drilling Program (ODP) 882A in northwestern Pacific Ocean are divided into four grain-size fractions (<8, 8-16, 16-64, >64 μm) using the gravitative differentiation method. Detailed rock magnetism results show that magnetite and hematite are dominant magnetic minerals for the dust components. In addition, the aeolian dust (<8 μm) represented by the concentration of magnetic minerals increases sharply at 2.73 Ma, which corresponds to the onset of major glaciation in the Northern Hemisphere. In contrast, the ice-rafted detritus (IRD) (>64 μm) contributes little to the magnetic enhancement of the sediments at 2.73 Ma. These new results greatly improve our understanding of paleoenvironmental evolution during late Pliocene-early Pleistocene in this area. [ABSTRACT FROM AUTHOR]

Insoluble microparticles in ice cores are related closely to the transportation of eolian dust, and thus are important natural media to reconstruct climate change. In this study, we conducted a systematic mineral-magnetic investigation of insoluble microparticles in the Nojingkangsang ice core (29°2.1′N, 90°11.88′E, 5950 m) from the Southern Tibetan Plateau. Results indicate that the dominant magnetic mineral is magnetite, and its concentration has grown significantly since the 1980s, which coincides with trends in climate warming of the Tibetan Plateau. Influenced by regional warming, the glacial recession around Nojingkangsang shortens the distance between the dust source and glacial areas and thus increases the concentration of coarse-grained magnetic minerals in ice cores. However, the frequency of dust storms, associated with annual precipitation, could play only a regulatory role on the magnetic content over yearly (or seasonal) time scales. Therefore, using a new approach, the magnetic index of insoluble microparticles in ice cores of this region is seen as mainly reflecting trends in climate warming. [ABSTRACT FROM AUTHOR]