Background: Fatigue is commonly reported by cancer patients. In some instances it can persist after treatment is completed. In order to develop effective treatment strategies it is important to understand the mechanis...Background: Fatigue is commonly reported by cancer patients. In some instances it can persist after treatment is completed. In order to develop effective treatment strategies it is important to understand the mechanisms underlying the development of fatigue and to be able to predict those that may be at greatest risk of experiencing fatigue during and following treatment. The current paper examines predisposing factors for fatigue including altered fatty acid homeostasis in a cohort of breast cancer radiotherapy patients. Methodology: Patients had undergone breast-conserving surgery and adjuvant breast irradiation. Prior to radiotherapy the patients were free from significant fatigue. Levels of fatigue were determined prior to and following radiotherapy using the Functional Assessment of Cancer Therapy fatigue subscale. Plasma fatty acid levels, urinary and plasma amino acid levels, blood biochemistry factors and general health and lifestyle characteristics were assessed. Results: Following radiotherapy, significant fatigue affected approximately one third of the 26 patients and these subjects were then assigned to the fatigued cohort. Univariate analysis revealed that higher levels of the fatty acids myristic acid and eicosadienoic acid were present for the fatigued cohort prior to radiotherapy. Multivariate analysis also revealed that fatty acid homeostasis was altered between the fatigued and non-fatigued groups at baseline. Orthogonal partial least squares discriminant analysis of the general health, lifestyle and metabolic data revealed that the fatigued and non-fatigued patients could be clustered into two clearly separate groups. Conclusions: The results supported the proposition that the fatigued patients had an underlying metabolic homeostasis which may predispose them to the development of fatigue. Biochemical and general health profiling of breast cancer patients has the potential to identify those at most risk of developing significant fatigue following radiotherapy.展开更多
The dissociation behavior of two dihydroxybenzoic acid isomers, 2,3-DHBA and 3,4-DHBA, at 281 K and 293 K was determined by potentiometric titrations in 0.01 M NaCl and 0.03 M NaCl. Results showed that the dissociatio...The dissociation behavior of two dihydroxybenzoic acid isomers, 2,3-DHBA and 3,4-DHBA, at 281 K and 293 K was determined by potentiometric titrations in 0.01 M NaCl and 0.03 M NaCl. Results showed that the dissociation enthalpy for the carboxylic group in DHBA is close to zero, resulting in dissociation constants that do not vary appreciably with temperature, whereas the dissociation constants for the first hydroxyl group vary significantly with temperature. Increasing ionic strength was found to result in increased values for the second dissociation constant, whereas the effect on the first dissociation constant was less clear.展开更多
Particle density is an important physical property of atmospheric particles. The information on high time-resolution size-resolved particle density is essential for understanding the atmospheric physical and chemical ...Particle density is an important physical property of atmospheric particles. The information on high time-resolution size-resolved particle density is essential for understanding the atmospheric physical and chemical aging processes of aerosols particles. In the present study, a centrifugal particle mass analyzer （CPMA） combined with a differential mobility analyzer （DMA） was deployed to determine the size-resolved effective density of 50 to 350 nm particles at a rural site of Beijing during summer 2016. The measured particle effective densities decreased with increasing particle sizes and ranged from 1.43 to 1.55 g/cm3, on average. The effective particle density distributions were dominated by a mode peaked at around 1.5 g/cm3 for 50 to 350 nm particles. Extra modes with peaks at 1.0, 0.8, and 0.6 g/cm3 for 150, 240, and 350 nm particles, which might be freshly emitted soot particles, were observed during intensive primary emissions episodes. The particle effective densities showed a diurnal variation pattern, with higher values during daytime. A case study showed that the effective density of Aitken mode particles during the new particle formation （NPF） event decreased considerably, indicating the significant contribution of organics to new particle growth.展开更多
Rechargeable Al batteries(RAB)are promising candidates for safe and environmentally sustainable battery systems with low-cost investments.However,the currently used aluminum chloridebased electrolytes present a signif...Rechargeable Al batteries(RAB)are promising candidates for safe and environmentally sustainable battery systems with low-cost investments.However,the currently used aluminum chloridebased electrolytes present a significant challenge to commercialization due to their corrosive nature.Here,we report for the first time,a novel electrolyte combination for RAB based on aluminum trifluoromethanesulfonate(Al(OTf)_(3))with tetrabutylammonium chloride(TBAC)additive in diglyme.The presence of a mere 0.1 M of TBAC in the Al(OTf)_(3) electrolyte generates the charge carrying electrochemical species,which forms the basis of reaction at the electrodes.TBAC reduces the charge transfer resistance and the surface activation energy at the anode surface and also augments the dissociation of Al(OTf)_(3) to generate the solid electrolyte interphase components.Our electrolyte’s superiority directly translates into reduced anodic overpotential for cells that ran for 1300 cycles in Al plating/stripping tests,the longest cycling life reported to date.This unique combination of salt and additive is non-corrosive,exhibits a high flash point and is cheaper than traditionally reported RAB electrolyte combinations,which makes it commercially promising.Through this report,we address a major roadblock in the commercialization of RAB and inspire equivalent electrolyte fabrication approaches for other metal anode batteries.展开更多
A method for analyzing the protein site similarity was devised aiming at understanding selectivity of homologous proteins and guiding the design of new drugs. The method is based on calculating Cα distances between s...A method for analyzing the protein site similarity was devised aiming at understanding selectivity of homologous proteins and guiding the design of new drugs. The method is based on calculating Cα distances between selected pocket residues and subsequent analysis by multivariate methods. Five closely related serine proteases, the coagulation factors II, VII, IX, X, and XI, were studied and their pocket similarity was illustrated by PCA clustering. OPLS-DA was then applied to identify the residues responsible for the variation. By combining these two multivariate methods, we could successfully cluster the different proteases according to class and identify the important residues responsible for the observed variation.展开更多
The K-Ras protein plays a key role in the signal transduction cascade. Certain mutations in K-Ras lead to a permanent “on” state which results in tumorigenesis due to failed interaction with the GTPase activating pr...The K-Ras protein plays a key role in the signal transduction cascade. Certain mutations in K-Ras lead to a permanent “on” state which results in tumorigenesis due to failed interaction with the GTPase activating protein (GAP). In this study, we examined the mutations E31N, D33N and D38N of K-Ras coupled and decoupled to wildtype GAP-334 and mutation K935N of GAP-334 coupled and decoupled to wildtype K-Ras, to illustrate the potential mechanism by which these mutants affect the interaction between the two proteins. We identify Tyr32 in the Ras Switch I region as a critical residue that acts as a gate to the GTP binding site and which needs to be “open” during Ras coupling with GAP to allow for insertion of GAP residue Arg789. This residue plays a vital role in stabilizing the transition state during GTP hydrolysis. The different mutations studied herein caused a reduced binding affinity, and the fluctuation of the Tyr32 side chain might hinder the insertion of Arg789. This may in turn be the cause of decreased GTP hydrolysis, and permanent “on” state of K-Ras, observed for these mutants.展开更多
Arsenic is a highly toxic and carcinogenic metalloid widely dispersed in the environment, contaminating water and soil and accumulating in crops. Paradoxically, arsenic is also part of modern therapy and employed in t...Arsenic is a highly toxic and carcinogenic metalloid widely dispersed in the environment, contaminating water and soil and accumulating in crops. Paradoxically, arsenic is also part of modern therapy and employed in treating numerous ailments and diseases. Hence, inventing strategies to tune cellular arsenic uptake based on purpose is striking. Here, we describe an approach in which the arsenite uptake can be increased using a MAPK inhibitor. Employing microfluidic flow chambers in combination with optical tweezers and fluorescent microscopy, we elevated the influx of arsenite into the yeast Saccharomyces cerevisiae cells following short-term treatment with a Hog1 kinase inhibitor. The increase in arsenite uptake was followed on arsenite triggered redistribution of a reporter protein, Hsp104-GFP, which was imaged over time. The effect was even more pronounced when the yeast mother and daughter cells were analyzed disjointedly, an opportunity provided owing to single-cell analysis. Our data firstly provide a strategy to increase arsenite uptake and secondly show that arsenite triggered aggregates, previously shown to be sites of damaged proteins, are distributed asymmetrically and less accumulated in daughter cells. Inventing approaches to tune arsenite uptake has a great value for its use in environmental as well as medical applications.展开更多
Long COVID,as currently defined by the World Health Organization(WHO)and other authorities,is a symptomatic condition that has been shown to affect an estimated 10%-30%of non-hospitalized patients after one infection....Long COVID,as currently defined by the World Health Organization(WHO)and other authorities,is a symptomatic condition that has been shown to affect an estimated 10%-30%of non-hospitalized patients after one infection.However,COVID-19 can also cause organ damage in individuals without symptoms,who would not fall under the current definition of Long COVID.This organ damage,whether symptomatic or not,can lead to various health impacts such as heart attacks and strokes.Given these observations,it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections.It is important to consider that many known adverse health outcomes,including heart conditions and cancers,can be asymptomatic until harm thresholds are reached.Many more medical conditions can be identified by testing than those that are recognized through reported symptoms.It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage,there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.展开更多
Herein,we use an oxidation flow reactor,Gothenburg:Potential Aerosol Mass(Go:PAM)reactor,to investigate the secondary organic aerosol(SOA)formation from wheat straw burning.Biomass burning emissions are exposed to hig...Herein,we use an oxidation flow reactor,Gothenburg:Potential Aerosol Mass(Go:PAM)reactor,to investigate the secondary organic aerosol(SOA)formation from wheat straw burning.Biomass burning emissions are exposed to high concentrations of hydroxyl radicals(OH)to simulate processes equivalent to atmospheric oxidation of 0-2.55 days.Primary volatile organic compounds(VOCs)were investigated,and particles were measured before and after the Go:PAM reactor.The influence of water content(i.e.5%and 11%)in wheat straw was also explored.Two burning stages,the flaming stage,and non-flaming stages,were identified.Primary particle emission factors(EFs)at a water content of 11%(~3.89 g/kg-fuel)are significantly higher than those at a water content of 5%(~2.26 g/kg-fuel)during the flaming stage.However,the water content showed no significant influence at the non-flaming stage.EFs of aromatics at a non-flaming stage(321.8±46.2 mg/kg-fuel)are larger than that at a flaming stage(130.9±37.1 mg/kg-fuel).The OA enhancement ratios increased with the increase in OH exposure at first and decreased with the additional increment of OH exposure.The maximum OA enhancement ratio is~12 during the non-flaming stages,which is much higher than~1.7 during the flaming stages.The mass spectrum of the primary wheat burning organic aerosols closely resembles that of resolved biomass burning organic aerosols(BBOA)based on measurements in ambient air.Our results show that large gap(0%-90%)still remains to estimate biomass burning SOA if only the oxidation of VOCs were included.展开更多
Bulk heterojunction(BHJ) solar cells based on small molecules have attracted potential attention due to their promise of conveniently defined structures, high absorption coefficients, solution process-ability and easy...Bulk heterojunction(BHJ) solar cells based on small molecules have attracted potential attention due to their promise of conveniently defined structures, high absorption coefficients, solution process-ability and easy fabrication. Three D—A—D—A type organic semiconductors(WS-31,WS-32 and WS-52) are synthesized, based on the indoline donor and benzotriazole auxiliary acceptor core, along with either bare thiophene or rigid cyclopentadithiophene as π bridge, rhodanine or carbonocyanidate as end-group. Their HOMO orbitals are delocalized throughout the whole molecules. Whereas the LUMOs are mainly localized on the acceptor part of structure, which reach up to benzothiadiazole, but no distribution on indoline donor. The first excitations for WS-31 and WS-32 are mainly originated by electron transition from HOMO to LUMO level, while for WS-52, partly related to transition between HOMO and LUMO+1 level. The small organic molecules are applied as donor components in bulk heterojunction(BHJ) organic solar cells, using PC_(61)BM as acceptor material to check their photovoltaic performances. The BHJ solar cells based on blended layer of WS-31:PC_(61)BM and WS-32:PC_(61)BM processed with chloroform show overall photoelectric conversion efficiency(PCE) of 0.56% and 1.02%, respectively. WS-32 based BHJ solar cells show a higher current density originated by its relatively larger driving force of photo-induced carrier in photo-active layer to LUMO of PC_(61)BM.展开更多
Valence and all electron correlation energies of a large set of atoms and molecules with structural motifs from amino acids and peptides at their equilibrium as well as non-equilibrium geometries are calculated at the...Valence and all electron correlation energies of a large set of atoms and molecules with structural motifs from amino acids and peptides at their equilibrium as well as non-equilibrium geometries are calculated at the levels of MP2, RI-MP2, and CCSD （T） with Dunnings sequential correlation consistent basis sets. A two point basis set extrapolation scheme for correlation energies to the complete basis set limit based on only DZ （double-zeta） and TZ （triple-zeta） results is presented and analyzed. We show that this basis set extrapolation scheme reduces the computational cost by two to three orders of magnitude to obtain the same accuracy as simpler extrapolations from higher order basis set computations.展开更多
The mechanisms of new particle formation(NPF)events that occurred under high aerosol loadings(“polluted”NPF)in the atmosphere have been unclear,which has inhibited the precision of particlepollution control.To deepe...The mechanisms of new particle formation(NPF)events that occurred under high aerosol loadings(“polluted”NPF)in the atmosphere have been unclear,which has inhibited the precision of particlepollution control.To deepen the understanding of how the“polluted”NPF events occur,a one-monthcomprehensive measurement was conducted in the atmosphere of Beijing during the summer of2016.The“clean”NPF events(frequency=22%)(condensation sink,CS<0.015 s^(-1))were found to becaused by local nucleation and growth.The“polluted”NPF events(frequency=28%)(CS>0.015 s^(-1))were influenced by both local nucleation-growth and regional transport,and the contributions from thetwo factors to 6e25 nm particle number concentration were 60%and 40%,respectively.This studyemphasized the importance of the transport for nanoparticles in relatively polluted atmospheres,and forthat the regional joint particle pollution control would be an essential policy.展开更多
Leveraging the biocatalytic machinery of living organisms for fabricating functional bioelectronic interfaces,in vivo,defines a new class of micro-biohybrids enabling the seamless integration of technology with living...Leveraging the biocatalytic machinery of living organisms for fabricating functional bioelectronic interfaces,in vivo,defines a new class of micro-biohybrids enabling the seamless integration of technology with living biological systems.Previously,we have demonstrated the in vivo polymerization of conjugated oligomers forming conductors within the structures of plants.Here,we expand this concept by reporting that Hydra,an invertebrate animal,polymerizes the conjugated oligomer ETE-S both within cells that expresses peroxidase activity and within the adhesive material that is secreted to promote underwater surface adhesion.The resulting conjugated polymer forms electronically conducting and electrochemically activeμm-sized domains,which are inter-connected resulting in percolative conduction pathways extending beyond 100μm,that are fully integrated within the Hydra tissue and the secreted mucus.Furthermore,the introduction and in vivo polymerization of ETE-S can be used as a biochemical marker to follow the dynamics of Hydra budding(reproduction)and regeneration.This work paves the way for well-defined self-organized electronics in animal tissue to modulate biological functions and in vivo biofabrication of hybrid functional materials and devices.展开更多
It is still generally assumed that interstellar travel will be possible after purely technical development and thus that mankind can move to some suitable exoplanet when needed.However,recent research indicates this n...It is still generally assumed that interstellar travel will be possible after purely technical development and thus that mankind can move to some suitable exoplanet when needed.However,recent research indicates this not to be the case,since interstellar space is filled with enough ultradense hydrogen H(0)as stable condensed dark matter(Holmlid,Astrophysical Journal 2018)to make interstellar space travel at the required and technically feasible relativistic velocities(Holmlid et al,Acta Astronautica 2020)almost impossible.H(0)can be observed to exist in space from the so-called extended red emission(ERE)features observed in space.A recent review(Holmlid et al.,Physica Scripta 2019)describes the properties of H(0).H(0)gives nuclear processes emitting kaons and other particles,with kinetic energies even above 100 MeV after induction for example by fast particle(spaceship)impact.These high particle energies give radiative temperatures of 12000 K in collisions against a solid surface and will rapidly destroy any spaceship structure moving into the H(0)clouds at relativistic velocity.The importance of preserving our ecosystem is pointed out,since travel to suitable exoplanets may be impossible.The possibilities of instead clearing interstellar space from H(0)are discussed,eventually providing tunnels suitable for relativistic interstellar transport.Finding regions with low intensity of ERE could even be a way to identify space-cleaning activities and thus to locate earlier spacetravelling civilizations.展开更多
Formic acid is one of the main weak acids in lignocellulosic hydrolysates that is known to be inhibitory to yeast growth even at low concentrations.In this study,we employed a CRISPR interference(CRISPRi)strain librar...Formic acid is one of the main weak acids in lignocellulosic hydrolysates that is known to be inhibitory to yeast growth even at low concentrations.In this study,we employed a CRISPR interference(CRISPRi)strain library comprising>9000 strains encompassing>98%of all essential and respiratory growth-essential genes,to study formic acid tolerance in Saccharomyces cerevisiae.To provide quantitative growth estimates on formic acid toler-ance,the strains were screened individually on solid medium supplemented with 140 mM formic acid using the Scan-o-Matic platform.Selected resistant and sensitive strains were characterized in liquid medium supplemented with formic acid and in synthetic hydrolysate medium containing a combination of inhibitors.Strains with gR-NAs targeting genes associated with chromatin remodeling were significantly enriched for strains showing formic acid tolerance.In line with earlier findings on acetic acid tolerance,we found genes encoding proteins involved in intracellular vesicle transport enriched among formic acid sensitive strains.The growth of the strains in syn-thetic hydrolysate medium followed the same trend as when screened in medium supplemented with formic acid.Strains sensitive to formic acid had decreased growth in the synthetic hydrolysate and all strains that had im-proved growth in the presence of formic acid also grew better in the hydrolysate medium.Systematic analysis of CRISPRi strains allowed identification of genes involved in tolerance mechanisms and provided novel engineering targets for bioengineering strains with increased resistance to inhibitors in lignocellulosic hydrolysates.展开更多
文摘Background: Fatigue is commonly reported by cancer patients. In some instances it can persist after treatment is completed. In order to develop effective treatment strategies it is important to understand the mechanisms underlying the development of fatigue and to be able to predict those that may be at greatest risk of experiencing fatigue during and following treatment. The current paper examines predisposing factors for fatigue including altered fatty acid homeostasis in a cohort of breast cancer radiotherapy patients. Methodology: Patients had undergone breast-conserving surgery and adjuvant breast irradiation. Prior to radiotherapy the patients were free from significant fatigue. Levels of fatigue were determined prior to and following radiotherapy using the Functional Assessment of Cancer Therapy fatigue subscale. Plasma fatty acid levels, urinary and plasma amino acid levels, blood biochemistry factors and general health and lifestyle characteristics were assessed. Results: Following radiotherapy, significant fatigue affected approximately one third of the 26 patients and these subjects were then assigned to the fatigued cohort. Univariate analysis revealed that higher levels of the fatty acids myristic acid and eicosadienoic acid were present for the fatigued cohort prior to radiotherapy. Multivariate analysis also revealed that fatty acid homeostasis was altered between the fatigued and non-fatigued groups at baseline. Orthogonal partial least squares discriminant analysis of the general health, lifestyle and metabolic data revealed that the fatigued and non-fatigued patients could be clustered into two clearly separate groups. Conclusions: The results supported the proposition that the fatigued patients had an underlying metabolic homeostasis which may predispose them to the development of fatigue. Biochemical and general health profiling of breast cancer patients has the potential to identify those at most risk of developing significant fatigue following radiotherapy.
基金The Swedish Foundation for Strategic Environmental Research(Mistra)for financial support through the Mistra Environmental Nanosafety Program.
文摘The dissociation behavior of two dihydroxybenzoic acid isomers, 2,3-DHBA and 3,4-DHBA, at 281 K and 293 K was determined by potentiometric titrations in 0.01 M NaCl and 0.03 M NaCl. Results showed that the dissociation enthalpy for the carboxylic group in DHBA is close to zero, resulting in dissociation constants that do not vary appreciably with temperature, whereas the dissociation constants for the first hydroxyl group vary significantly with temperature. Increasing ionic strength was found to result in increased values for the second dissociation constant, whereas the effect on the first dissociation constant was less clear.
基金supported by the following projects:the National Key R&D(Research and Development)Program of China(No.2016YFC0202800:Task 1)the National Natural Science Foundation of China(Nos.41475127,41571130021)the framework research program on ‘Photochemical smog in China’ financed by the Swedish Research Council(No.639-2013-6917)
文摘Particle density is an important physical property of atmospheric particles. The information on high time-resolution size-resolved particle density is essential for understanding the atmospheric physical and chemical aging processes of aerosols particles. In the present study, a centrifugal particle mass analyzer （CPMA） combined with a differential mobility analyzer （DMA） was deployed to determine the size-resolved effective density of 50 to 350 nm particles at a rural site of Beijing during summer 2016. The measured particle effective densities decreased with increasing particle sizes and ranged from 1.43 to 1.55 g/cm3, on average. The effective particle density distributions were dominated by a mode peaked at around 1.5 g/cm3 for 50 to 350 nm particles. Extra modes with peaks at 1.0, 0.8, and 0.6 g/cm3 for 150, 240, and 350 nm particles, which might be freshly emitted soot particles, were observed during intensive primary emissions episodes. The particle effective densities showed a diurnal variation pattern, with higher values during daytime. A case study showed that the effective density of Aitken mode particles during the new particle formation （NPF） event decreased considerably, indicating the significant contribution of organics to new particle growth.
基金the financial support from Agency for Science, Technology and Research (Central Research Fund Award)
文摘Rechargeable Al batteries(RAB)are promising candidates for safe and environmentally sustainable battery systems with low-cost investments.However,the currently used aluminum chloridebased electrolytes present a significant challenge to commercialization due to their corrosive nature.Here,we report for the first time,a novel electrolyte combination for RAB based on aluminum trifluoromethanesulfonate(Al(OTf)_(3))with tetrabutylammonium chloride(TBAC)additive in diglyme.The presence of a mere 0.1 M of TBAC in the Al(OTf)_(3) electrolyte generates the charge carrying electrochemical species,which forms the basis of reaction at the electrodes.TBAC reduces the charge transfer resistance and the surface activation energy at the anode surface and also augments the dissociation of Al(OTf)_(3) to generate the solid electrolyte interphase components.Our electrolyte’s superiority directly translates into reduced anodic overpotential for cells that ran for 1300 cycles in Al plating/stripping tests,the longest cycling life reported to date.This unique combination of salt and additive is non-corrosive,exhibits a high flash point and is cheaper than traditionally reported RAB electrolyte combinations,which makes it commercially promising.Through this report,we address a major roadblock in the commercialization of RAB and inspire equivalent electrolyte fabrication approaches for other metal anode batteries.
文摘A method for analyzing the protein site similarity was devised aiming at understanding selectivity of homologous proteins and guiding the design of new drugs. The method is based on calculating Cα distances between selected pocket residues and subsequent analysis by multivariate methods. Five closely related serine proteases, the coagulation factors II, VII, IX, X, and XI, were studied and their pocket similarity was illustrated by PCA clustering. OPLS-DA was then applied to identify the residues responsible for the variation. By combining these two multivariate methods, we could successfully cluster the different proteases according to class and identify the important residues responsible for the observed variation.
基金The Faculty of Science at the University of Gothenburg is gratefully acknowledged for financial support
文摘The K-Ras protein plays a key role in the signal transduction cascade. Certain mutations in K-Ras lead to a permanent “on” state which results in tumorigenesis due to failed interaction with the GTPase activating protein (GAP). In this study, we examined the mutations E31N, D33N and D38N of K-Ras coupled and decoupled to wildtype GAP-334 and mutation K935N of GAP-334 coupled and decoupled to wildtype K-Ras, to illustrate the potential mechanism by which these mutants affect the interaction between the two proteins. We identify Tyr32 in the Ras Switch I region as a critical residue that acts as a gate to the GTP binding site and which needs to be “open” during Ras coupling with GAP to allow for insertion of GAP residue Arg789. This residue plays a vital role in stabilizing the transition state during GTP hydrolysis. The different mutations studied herein caused a reduced binding affinity, and the fluctuation of the Tyr32 side chain might hinder the insertion of Arg789. This may in turn be the cause of decreased GTP hydrolysis, and permanent “on” state of K-Ras, observed for these mutants.
文摘Arsenic is a highly toxic and carcinogenic metalloid widely dispersed in the environment, contaminating water and soil and accumulating in crops. Paradoxically, arsenic is also part of modern therapy and employed in treating numerous ailments and diseases. Hence, inventing strategies to tune cellular arsenic uptake based on purpose is striking. Here, we describe an approach in which the arsenite uptake can be increased using a MAPK inhibitor. Employing microfluidic flow chambers in combination with optical tweezers and fluorescent microscopy, we elevated the influx of arsenite into the yeast Saccharomyces cerevisiae cells following short-term treatment with a Hog1 kinase inhibitor. The increase in arsenite uptake was followed on arsenite triggered redistribution of a reporter protein, Hsp104-GFP, which was imaged over time. The effect was even more pronounced when the yeast mother and daughter cells were analyzed disjointedly, an opportunity provided owing to single-cell analysis. Our data firstly provide a strategy to increase arsenite uptake and secondly show that arsenite triggered aggregates, previously shown to be sites of damaged proteins, are distributed asymmetrically and less accumulated in daughter cells. Inventing approaches to tune arsenite uptake has a great value for its use in environmental as well as medical applications.
文摘Long COVID,as currently defined by the World Health Organization(WHO)and other authorities,is a symptomatic condition that has been shown to affect an estimated 10%-30%of non-hospitalized patients after one infection.However,COVID-19 can also cause organ damage in individuals without symptoms,who would not fall under the current definition of Long COVID.This organ damage,whether symptomatic or not,can lead to various health impacts such as heart attacks and strokes.Given these observations,it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections.It is important to consider that many known adverse health outcomes,including heart conditions and cancers,can be asymptomatic until harm thresholds are reached.Many more medical conditions can be identified by testing than those that are recognized through reported symptoms.It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage,there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.
基金supported by National Natural Science Foundation of China(Nos.51636003,91844301,41977179)Beijing Municipal Science and Technology Commission(No.Z201100008220011)+2 种基金Natural Science Foundation of Beijing(No.8192022)China Postdoctoral Science Foundation(No.2020M680242)the Open Research Fund of State Key Laboratory of Multi-phase Complex Systems(No.MPCS-2021-D-12)
文摘Herein,we use an oxidation flow reactor,Gothenburg:Potential Aerosol Mass(Go:PAM)reactor,to investigate the secondary organic aerosol(SOA)formation from wheat straw burning.Biomass burning emissions are exposed to high concentrations of hydroxyl radicals(OH)to simulate processes equivalent to atmospheric oxidation of 0-2.55 days.Primary volatile organic compounds(VOCs)were investigated,and particles were measured before and after the Go:PAM reactor.The influence of water content(i.e.5%and 11%)in wheat straw was also explored.Two burning stages,the flaming stage,and non-flaming stages,were identified.Primary particle emission factors(EFs)at a water content of 11%(~3.89 g/kg-fuel)are significantly higher than those at a water content of 5%(~2.26 g/kg-fuel)during the flaming stage.However,the water content showed no significant influence at the non-flaming stage.EFs of aromatics at a non-flaming stage(321.8±46.2 mg/kg-fuel)are larger than that at a flaming stage(130.9±37.1 mg/kg-fuel).The OA enhancement ratios increased with the increase in OH exposure at first and decreased with the additional increment of OH exposure.The maximum OA enhancement ratio is~12 during the non-flaming stages,which is much higher than~1.7 during the flaming stages.The mass spectrum of the primary wheat burning organic aerosols closely resembles that of resolved biomass burning organic aerosols(BBOA)based on measurements in ambient air.Our results show that large gap(0%-90%)still remains to estimate biomass burning SOA if only the oxidation of VOCs were included.
基金supported by the NSFC for Creative Research Groups(21421004)Distinguished Young Scholars(21325625)+4 种基金NSFC/China,Science and Technology Commission of Shanghai Municipality(14YF1410500 and 15XD1501400)Shanghai Young Teacher Supporting Foundation(ZZEGD14011)Program for Professor of Special Appointment(Eastern Scholar)"Shu Guang" project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation(13SG55)Grants of computing timeat the C3SE supercomputing Center at Chalmers(Gteborg)
文摘Bulk heterojunction(BHJ) solar cells based on small molecules have attracted potential attention due to their promise of conveniently defined structures, high absorption coefficients, solution process-ability and easy fabrication. Three D—A—D—A type organic semiconductors(WS-31,WS-32 and WS-52) are synthesized, based on the indoline donor and benzotriazole auxiliary acceptor core, along with either bare thiophene or rigid cyclopentadithiophene as π bridge, rhodanine or carbonocyanidate as end-group. Their HOMO orbitals are delocalized throughout the whole molecules. Whereas the LUMOs are mainly localized on the acceptor part of structure, which reach up to benzothiadiazole, but no distribution on indoline donor. The first excitations for WS-31 and WS-32 are mainly originated by electron transition from HOMO to LUMO level, while for WS-52, partly related to transition between HOMO and LUMO+1 level. The small organic molecules are applied as donor components in bulk heterojunction(BHJ) organic solar cells, using PC_(61)BM as acceptor material to check their photovoltaic performances. The BHJ solar cells based on blended layer of WS-31:PC_(61)BM and WS-32:PC_(61)BM processed with chloroform show overall photoelectric conversion efficiency(PCE) of 0.56% and 1.02%, respectively. WS-32 based BHJ solar cells show a higher current density originated by its relatively larger driving force of photo-induced carrier in photo-active layer to LUMO of PC_(61)BM.
文摘Valence and all electron correlation energies of a large set of atoms and molecules with structural motifs from amino acids and peptides at their equilibrium as well as non-equilibrium geometries are calculated at the levels of MP2, RI-MP2, and CCSD （T） with Dunnings sequential correlation consistent basis sets. A two point basis set extrapolation scheme for correlation energies to the complete basis set limit based on only DZ （double-zeta） and TZ （triple-zeta） results is presented and analyzed. We show that this basis set extrapolation scheme reduces the computational cost by two to three orders of magnitude to obtain the same accuracy as simpler extrapolations from higher order basis set computations.
基金This study is funded by the National Natural Science Foundationof China(NSFC)(grant No.91844301)the NSFC e Creative ResearchGroup Fund(grant No.22221004)+1 种基金the National Key Research andDevelopment Program of China(grant No.2022YFC3701000,Task1)the bilateral SwedeneChina framework program“Photochemical smog in China:formation,transformation,impactand abatement strategies”(grant No.639-2013-6917).
文摘The mechanisms of new particle formation(NPF)events that occurred under high aerosol loadings(“polluted”NPF)in the atmosphere have been unclear,which has inhibited the precision of particlepollution control.To deepen the understanding of how the“polluted”NPF events occur,a one-monthcomprehensive measurement was conducted in the atmosphere of Beijing during the summer of2016.The“clean”NPF events(frequency=22%)(condensation sink,CS<0.015 s^(-1))were found to becaused by local nucleation and growth.The“polluted”NPF events(frequency=28%)(CS>0.015 s^(-1))were influenced by both local nucleation-growth and regional transport,and the contributions from thetwo factors to 6e25 nm particle number concentration were 60%and 40%,respectively.This studyemphasized the importance of the transport for nanoparticles in relatively polluted atmospheres,and forthat the regional joint particle pollution control would be an essential policy.
基金innovation programme under grant agreement No 800926(FET-OPEN-HyPhOE)by the Swedish Research Council(VR-2017-04910)+5 种基金Additional funding was provided by the Knut and Alice Wallenberg Foundationthe Swedish Foundation for Strategic Research(SSF)The European Research Council(ERC)project e-NeuroPharma 834677the Swedish Government Strategic Research Area in Materials Science on Advanced Functional Materials at Linkoping University(Faculty Grant SFO-Mat-LiU No.2009-00971)supported by MultiPark-A Strategic Research Area at Lund Universitythe MIUR project SHARID-ARS01-01270 for financial support.
文摘Leveraging the biocatalytic machinery of living organisms for fabricating functional bioelectronic interfaces,in vivo,defines a new class of micro-biohybrids enabling the seamless integration of technology with living biological systems.Previously,we have demonstrated the in vivo polymerization of conjugated oligomers forming conductors within the structures of plants.Here,we expand this concept by reporting that Hydra,an invertebrate animal,polymerizes the conjugated oligomer ETE-S both within cells that expresses peroxidase activity and within the adhesive material that is secreted to promote underwater surface adhesion.The resulting conjugated polymer forms electronically conducting and electrochemically activeμm-sized domains,which are inter-connected resulting in percolative conduction pathways extending beyond 100μm,that are fully integrated within the Hydra tissue and the secreted mucus.Furthermore,the introduction and in vivo polymerization of ETE-S can be used as a biochemical marker to follow the dynamics of Hydra budding(reproduction)and regeneration.This work paves the way for well-defined self-organized electronics in animal tissue to modulate biological functions and in vivo biofabrication of hybrid functional materials and devices.
文摘It is still generally assumed that interstellar travel will be possible after purely technical development and thus that mankind can move to some suitable exoplanet when needed.However,recent research indicates this not to be the case,since interstellar space is filled with enough ultradense hydrogen H(0)as stable condensed dark matter(Holmlid,Astrophysical Journal 2018)to make interstellar space travel at the required and technically feasible relativistic velocities(Holmlid et al,Acta Astronautica 2020)almost impossible.H(0)can be observed to exist in space from the so-called extended red emission(ERE)features observed in space.A recent review(Holmlid et al.,Physica Scripta 2019)describes the properties of H(0).H(0)gives nuclear processes emitting kaons and other particles,with kinetic energies even above 100 MeV after induction for example by fast particle(spaceship)impact.These high particle energies give radiative temperatures of 12000 K in collisions against a solid surface and will rapidly destroy any spaceship structure moving into the H(0)clouds at relativistic velocity.The importance of preserving our ecosystem is pointed out,since travel to suitable exoplanets may be impossible.The possibilities of instead clearing interstellar space from H(0)are discussed,eventually providing tunnels suitable for relativistic interstellar transport.Finding regions with low intensity of ERE could even be a way to identify space-cleaning activities and thus to locate earlier spacetravelling civilizations.
基金The authors would like to thank Cecilia Trivellin for providing the original R code for the analysis of the growth curves(available at https://github.com/cectri/Quantification-of-microbial-robustness.git)as well as Luca Torello Pianale for support in strain analysis.We acknowledge the Novo Nordisk Foundation(NF19OC0057685)The Swedish Research Council(Dnr 2018-04713)and the Hasselblad Foundation for financial support.
文摘Formic acid is one of the main weak acids in lignocellulosic hydrolysates that is known to be inhibitory to yeast growth even at low concentrations.In this study,we employed a CRISPR interference(CRISPRi)strain library comprising>9000 strains encompassing>98%of all essential and respiratory growth-essential genes,to study formic acid tolerance in Saccharomyces cerevisiae.To provide quantitative growth estimates on formic acid toler-ance,the strains were screened individually on solid medium supplemented with 140 mM formic acid using the Scan-o-Matic platform.Selected resistant and sensitive strains were characterized in liquid medium supplemented with formic acid and in synthetic hydrolysate medium containing a combination of inhibitors.Strains with gR-NAs targeting genes associated with chromatin remodeling were significantly enriched for strains showing formic acid tolerance.In line with earlier findings on acetic acid tolerance,we found genes encoding proteins involved in intracellular vesicle transport enriched among formic acid sensitive strains.The growth of the strains in syn-thetic hydrolysate medium followed the same trend as when screened in medium supplemented with formic acid.Strains sensitive to formic acid had decreased growth in the synthetic hydrolysate and all strains that had im-proved growth in the presence of formic acid also grew better in the hydrolysate medium.Systematic analysis of CRISPRi strains allowed identification of genes involved in tolerance mechanisms and provided novel engineering targets for bioengineering strains with increased resistance to inhibitors in lignocellulosic hydrolysates.
