Rationale:Acute otitis media is a common disease in early childhood,and is usually caused by Streptococcus pneumoniae(S.pneumoniae).Acute mastoiditis is a complication of acute otitis media and can involve not only th...Rationale:Acute otitis media is a common disease in early childhood,and is usually caused by Streptococcus pneumoniae(S.pneumoniae).Acute mastoiditis is a complication of acute otitis media and can involve not only the mucoperiosteum of the middle ear but can also spread to the periosteum by destroying the mastoid bone(acute coalescent mastoiditis).In addition,the infection can extend through the surrounding bones or the emissary veins beyond the mastoid’s air cells,leading to subperiosteal abscesses.Patient’s Concern:A 16-month-old female patient was hospitalized due to the purulent discharge of the left ear and the symptoms of right mastoiditis(swelling and redness of the skin).Diagnosis:Bilateral acute coalescent mastoiditis caused by S.pneumoniae infection.The computer tomography revealed bilateral bone destruction of the mastoid and abscesses found behind the auricle on both sides.Interventions:The patient underwent intravenous antibiotic therapy and surgical treatment.Outcomes:The patient was discharged 14 days after hospitalization with an improved condition.Lessons:Improperly treated acute coalescent mastoiditis can lead to extracranial and intracranial complications,sometimes serious and even life-threatening.Complications are prevalent in children under 2 years,in whom the disease progresses more rapidly and severely.The vaccination with a 13-valent vaccine may not result in sufficient immunity against S.pneumoniae,a predominant pathogen in children affected by acute coalescent mastoiditis.展开更多
Genetic variability plays a key role in the biology and medical treatment of RNA viruses. As an RNA virus, Hepatitis C virus (HCV) replicate as complex distributions of closely related genomes termed viral quasispecie...Genetic variability plays a key role in the biology and medical treatment of RNA viruses. As an RNA virus, Hepatitis C virus (HCV) replicate as complex distributions of closely related genomes termed viral quasispecies. The behavior of the evolving HCV quasispecies population is influenced by the ensemble of mutants that compose the viral population. One such influence is the presence of minority subpopulations, termed memory genomes, in the mutant spectra. Biologically relevant mutants have been previously observed to be present as memory genomes in RNA viral populations. For that reason, an in-depth analysis of HCV quasispecies populations is crucial for our understanding viral evolution, drug resistance and therapy outcome. Recently developed next-generation sequencing (NGS) platforms make it possible to investigate viral quasispecies at much greater detail. In order to gain insight into these matters, we have performed a Bayesian coalescent analysis of hypervariable region 1 (HVR1) sequences of a HCV quasispecies population circulating in a chronic patient, recently obtained by ultra-deep sequencing. The results of these studies revealed a mean rate of evolution of HCV HVR1 of the intra-host quasispecies population of 4.80 × 10-2 amino acid substitutions/site/year. A sharp and rapid diversification of the HCV quasispecies isolated from the patient in three different sub-populations was observed. The most abundant sequence in the quasispecies population was not found to be the center of a tight and complex network around this sequence, suggesting that the quasispecies population as a whole efficiently explore a wide sequence space. Co-evolution of relevant amino acid sites had been identified in the HVR1. This speaks of the possible roll of these residues in HVR1 to allow the virus to shift between combinations of residues to escape the immune system while retaining its structure and functions. The results of these studies highlight the importance of minority genomes in HCV population history and evolution, the mutant clouds as reservoirs of phenotypic and genetic variants for virus adaptability, as well as the roll of the mutant spectra to overcome selective constraints.展开更多
Conventional coalescent inferences of population history make the critical assumption that the population under examination is panmictic.However,most populations are structured.This complicates the prevailing coalesce...Conventional coalescent inferences of population history make the critical assumption that the population under examination is panmictic.However,most populations are structured.This complicates the prevailing coalescent analyses and sometimes leads to inaccurate estimates.To develop a coalescent method unhampered by population structure,we perform two analyses.First,we demonstrate that the coalescent probability of two randomly sampled alleles from the immediate preceding generation(one generation back)is independent of population structure.Second,motivated by this finding,we propose a new coalescent method:i-coalescent analysis.The i-coalescent analysis computes the instantaneous coalescent rate by using a phylogenetic tree of sampled alleles.Using simulated data,we broadly demonstrate the capability of i-coalescent analysis to accurately reconstruct population size dynamics of highly structured populations,although we find this method often requires larger sample sizes for structured populations than for panmictic populations.Overall,our results indicate i-coalescent analysis to be a useful tool,especially for the inference of population histories with intractable structure such as the developmental history of cell populations in the organs of complex organisms.展开更多
The transition of traits between genetically related lineages is a fascinating topic that provides clues to understanding the drivers of speciation and diversification.Much can be learned about this process from phylo...The transition of traits between genetically related lineages is a fascinating topic that provides clues to understanding the drivers of speciation and diversification.Much can be learned about this process from phylogeny-based trait evolution.However,such inference is often plagued by genome-wide gene-tree discordance(GTD),mostly due to incomplete lineage sorting(ILS)and/or introgressive hybridization,especially when the genes underlying the traits appear discordant.Here,by collecting transcriptomes,whole chloroplast genomes(cpDNA),and population genetic datasets,we used the coalescent model to turn GTD into a source of information for ILS and employed hemiplasy to explain specific cases of apparent“phylogenetic discordance”between different morphological traits and probable species phylogeny in the Allium subg.Cyathophora.Both concatenation and coalescence methods consistently showed the same phylogenetic topology for species tree inference based on single-copy genes(SCGs),as supported by the KS distribution.However,GTD was high across the genomes of subg.Cyathophora:~27%e38.9%of the SCG trees were in conflict with the species tree.Plasmid and nuclear incongruence was also present.Our coalescent simulations indicated that such GTD was mainly a product of ILS.Our hemiplasy risk factor calculations supported that random fixation of ancient polymorphisms in different populations during successive speciation events along the subg.Cyathophora phylogeny may have caused the character transition,as well as the anomalous cpDNA tree.Our study exemplifies how phylogenetic noise can be transformed into evolutionary information for understanding character state transitions along species phylogenies.展开更多
Direct shear tests were conducted on sandstone specimens under different constant normal stresses to study the coalescence of cracks between non-persistent flaws and the shear sliding characteristics of the shear-form...Direct shear tests were conducted on sandstone specimens under different constant normal stresses to study the coalescence of cracks between non-persistent flaws and the shear sliding characteristics of the shear-formed fault.Digital image correlation and acoustic emission(AE)techniques were used to monitor the evolution of shear bands at the rock bridge area and microcracking behaviors.The experimental results revealed that the shear stresses corresponding to the peak and sub-peak in the stressdisplacement curve are significantly affected by the normal stress.Strain localization bands emerged at both the tip of joints and the rock bridge,and their extension and interaction near the peak stress caused a surge in the AE hit rate and a significant decrease in the AE b value.Short and curvilinear strain bands were detected at low normal stress,while high normal stress generally led to more microcracking events and longer coplanar cracks at the rock bridge area.Furthermore,an increase in normal stress resulted in a higher AE count rate and more energetic AE events during friction sliding along the shearformed fault.It was observed that the elastic energy released during the crack coalescence at the prepeak stage was much greater than that released during friction sliding at the post-peak stage.More than 75%of AE events were located in the low-frequency band(0e100 kHz),and this proportion continued to rise with increasing normal stress.Moreover,more AE events of low AF value and high RA value were observed in specimens subjected to high normal stress,indicating that greater normal stress led to more microcracks of shear nature.展开更多
Froth flotation is a separation process widely used in the mineral processing industry that depends on differences in particle surface properties to separate valuable materials from undesired gangue. In froth flotatio...Froth flotation is a separation process widely used in the mineral processing industry that depends on differences in particle surface properties to separate valuable materials from undesired gangue. In froth flotation, an addition of a surfactant, acting as frother is usually needed. The basic function of the frother is to produce a swarm of air bubbles, which remain sufficiently stable for the hydrophobic mineral particles to be captured by them. This Paper presents a combination method of a foaming agent-surfactant composition with desirable selectivity and foaming properties. Wherein 1-butanol (C4H10O) is a main flotation foaming agent, which decides bubble sizes in a collecting area;and tetraethylene glycol (C8H18O5) is an auxiliary foaming agent, which affects a rising velocity of the bubbles in the collecting area and a foaming capability in a selected area. Set concentrations of the two components are respectively 60 ppm for the 1-butanol and 120 ppm for the tetraethylene glycol. An addition sequence is the 1-butanol followed by the tetraethylene glycol. The dual advantages of the selectivity and foaming properties of the foaming agent-surfactant composition in the present disclosure are verified through a series of tests, and desirable yields can be obtained in practice.展开更多
The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Au...The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.展开更多
Understanding speciation has long been a fundamental goal of evolutionary biology.It is widely accepted that speciation requires an interruption of gene flow to generate strong reproductive isolation between species.T...Understanding speciation has long been a fundamental goal of evolutionary biology.It is widely accepted that speciation requires an interruption of gene flow to generate strong reproductive isolation between species.The mechanism of how speciation in sexually dichromatic species operates in the face of gene flow remains an open question.Two species in the genus Chrysolophus,the Golden Pheasant(C.pictus)and Lady Amherst’s Pheasant(C.amherstiae),both of which exhibit significant plumage dichromatism,are currently parapatric in southwestern China with several hybrid recordings in field.In this study,we estimated the pattern of gene flow during the speciation of the two pheasants using the Approximate Bayesian Computation(ABC)method based on data from multiple genes.Using a newly assembled de novo genome of Lady Amherst’s Pheasant and resequencing of widely distributed individuals,we reconstructed the demographic history of the two pheasants by the PSMC(pairwise sequentially Markovian coalescent)method.The results provide clear evidence that the gene flow between the two pheasants was consistent with the predictions of the isolation with migration model during divergence,indicating that there was long-term gene flow after the initial divergence(ca.2.2 million years ago).The data further support the occurrence of secondary contact between the parapatric populations since around 30 kya with recurrent gene flow to the present,a pattern that may have been induced by the population expansion of the Golden Pheasant in the late Pleistocene.The results of the study support the scenario of speciation between the Golden Pheasant and Lady Amherst’s Pheasant with cycles of mixing-isolation-mixing,possibly due to the dynamics of geographical context in the late Pleistocene.The two species provide a good research system as an evolutionary model for testing reinforcement selection in speciation.展开更多
Background: Previous phylogenetic studies that include the four recognized species of Gallus have resulted in a number of distinct topologies, with little agreement. Several factors could lead to the failure to conver...Background: Previous phylogenetic studies that include the four recognized species of Gallus have resulted in a number of distinct topologies, with little agreement. Several factors could lead to the failure to converge on a consistent topology, including introgression, incomplete lineage sorting, different data types, or insufficient data.Methods: We generated three novel whole genome assemblies for Gallus species, which we combined with data from the published genomes of Gallus gallus and Bambusicola thoracicus(a member of the sister genus to Gallus). To determine why previous studies have failed to converge on a single topology, we extracted large numbers of orthologous exons, introns, ultra-conserved elements, and conserved non-exonic elements from the genome assemblies. This provided more than 32 million base pairs of data that we used for concatenated maximum likelihood and multispecies coalescent analyses of Gallus.Results: All of our analyses, regardless of data type, yielded a single, well-supported topology. We found some evidence for ancient introgression involving specific Gallus lineages as well as modest data type effects that had an impact on support and branch length estimates in specific analyses. However, the estimated gene tree spectra for all data types had a relatively good fit to their expectation given the multispecies coalescent.Conclusions: Overall, our data suggest that conflicts among previous studies probably reflect the use of smaller datasets(both in terms of number of sites and of loci) in those analyses. Our results demonstrate the importance of sampling large numbers of loci, each of which has a sufficient number of sites to provide robust estimates of gene trees. Low-coverage whole genome sequencing, as we did here, represents a cost-effective means to generate the very large data sets that include multiple data types that enabled us to obtain a robust estimate of Gallus phylogeny.展开更多
A novel method for breaking emulsions with microporous membranes is presented.A membrane would act as a coalescer if its pore size is smaller than the emulsion droplets and if the dispersed phase has great affinity to...A novel method for breaking emulsions with microporous membranes is presented.A membrane would act as a coalescer if its pore size is smaller than the emulsion droplets and if the dispersed phase has great affinity to the membrane.It was observed that a hydrophilic membrane is able to break water in oil emulsions with high separation efficiency.Effects of the membrane pore size,membrane thickness,transmembrane pressure and emulsion composition on demulsification performance were investigated.It was found that the membrane pore size and transmembrane pressure affect demulsification performance remarkably while other factors have slight or almost no effect.展开更多
Based on the axial stress-axial strain curves,the effect of fissure angle on the strength and deformation behavior of sandstone specimens containing combined flaws is analyzed.The mechanical parameters of sandstone sp...Based on the axial stress-axial strain curves,the effect of fissure angle on the strength and deformation behavior of sandstone specimens containing combined flaws is analyzed.The mechanical parameters of sandstone specimens containing combined flaws are all lower than that of intact specimen,but the reduction extent is distinctly related to the fissure angle.The results of sandstone specimens containing combined flaws are obtained by the acoustic emission,which can be used to monitor the crack initiation and propagation.The ultimate failure mode and crack coalescence behavior are evaluated for brittle sandstone specimens containing combined flaws.Nine different crack types are identified on the basis of their geometry and crack coalescence mechanism(tensile crack,hole collapse,far-field crack and surface spalling)for combined flaws.The photographic monitoring was also adopted for uniaxial compression test in order to confirm the sequence of crack coalescence in brittle sandstone specimens containing combined flaws,which recorded the real-time crack coalescence process during entire deformation.According to the monitored results,the effect of crack coalescence process on the strength and deformation behavior is investigated based on a detailed analysis for brittle sandstone specimens containing combined flaws by using digital photogrammetry.展开更多
The mechanism of cracks propagation and cracks coalescence due to compressive loading of the brittle substances containing pre-existing cracks (flaws) was modeled experimentally using specially made rock-like specim...The mechanism of cracks propagation and cracks coalescence due to compressive loading of the brittle substances containing pre-existing cracks (flaws) was modeled experimentally using specially made rock-like specimens from Portland Pozzolana Cement (PPC). The breakage process of the specimens was studied by inserting single and double flaws with different inclination angles at the center and applying uniaxial compressive stress at both ends of the specimen. The first crack was oriented at 50° from the horizontal direction and kept constant throughout the analysis while the orientation of the second crack was changed. It is experimentally observed that the wing cracks are produced at the first stage of loading and start their propagation toward the direction of uniaxial compressive loading. The secondary cracks may also be produced in form of quasi-coplanar and/or oblique cracks in a stable manner. The secondary cracks may eventually continue their propagation in the direction of maximum principle stress. These experimental works were also simulated numerically by a modified higher order displacement discontinuity method and the cracks propagation and cracks coalescence were studied based on Mode I and Mode II stress intensity factors (SIFs). It is concluded that the wing cracks initiation stresses for the specimens change from 11.3 to 14.1 MPain the case of numerical simulations and from 7.3 to 13.8 MPa in the case of experimental works. It is observed that cracks coalescence stresses change from 21.8 to 25.3 MPa and from 19.5 to 21.8 MPa in the numerical and experimental analyses, respectively. Comparing some of the numerical and experimental results with those recently cited in the literature validates the results obtained by the proposed study. Finally, a numerical simulation was accomplished to study the effect of confining pressure on the crack propagation process, showing that the SIFs increase and the crack initiation angles change in this case.展开更多
Hot-extruded magnesium alloy AZ31 bar was cut into hexagonal prisms and then compressed at room temperature with the loading direction parallel to the extrusion direction(ED)or perpendicular to ED.The effective stress...Hot-extruded magnesium alloy AZ31 bar was cut into hexagonal prisms and then compressed at room temperature with the loading direction parallel to the extrusion direction(ED)or perpendicular to ED.The effective stress and strain evolution at center and corner region of the hexagonal prisms was simulated by using DEFORM 3D,while microstructure evolution was characterized by electron backscatter diffraction(EBSD).Relationship between twinning behavior and stress-strain evolution during compression at room temperature was studied.The results indicated that the compressive stress and strain levels at central region of hexagonal prisms were lower than those at the corner parts.EBSD examination revealed that{10-12}twins activate during the compression and the volume fraction of twins at corner parts were less than that at the central parts,which was attributed to twin thickening and coalescence behaviors.Meanwhile,the EBSD map indicated that the arise of{10-11}contraction twins and{10-11}-{10-12}double twins in compressed samples,especially in the corner region with loading axis perpendicular to ED,which were considered to be related to the high stress level at corner region.The dislocation slips led to low-angle boundaries in LA⊥ED and LA//ED.展开更多
A series of laboratory experiments and PFC numerical simulations for rock-like material specimens containing two unparallel fissures were carried out.On the basis of experimental and numerical results,the stress-strai...A series of laboratory experiments and PFC numerical simulations for rock-like material specimens containing two unparallel fissures were carried out.On the basis of experimental and numerical results,the stress-strain curves,mechanical properties,AE events,cracking behavior and energy characteristics were analyzed to reveal the macro-mechanical behavior and meso-mechanism of pre-fissured specimens under different loading rates.Investigated results show that:1)When the loading rate is relatively low,the stress-strain curves show a brittle response.When the loading rate is relatively high,the curve shows a more ductile response.Both of the peak strength and elastic mudulus increase with the increase of loading rate,which can be expressed as power functions.2)Four crack types are identified,i.e.,tensile crack,shear crack,far-field crack and surface spalling.Moreover,the tensile crack,far-field crack and surface spalling are under tensile mechanism,while the shear crack is under shear mechanism.3)The drops of the stress-strain curves all correspond to the crack initiation or coalescence,which is also linked to a sudden increasing in the accumulated micro-crack curve.4)Both of the maximum bond force and energy have the similar trend with the increase of loading rate to peak strength,which indicates that the trend of peak strength can be explained by the meso-mechanics and energy.展开更多
Failure of rock mass that is subjected to compressive loads occurs from initiation, propagation, and linkage of new cracks from preexisting fissures. Our research investigates the cracking behaviour and coalescence pr...Failure of rock mass that is subjected to compressive loads occurs from initiation, propagation, and linkage of new cracks from preexisting fissures. Our research investigates the cracking behaviour and coalescence process in a brittle material with two non-parallel overlapping flaws using a high-speed camera. The coalescence tensile crack and tensile wing cracks were the first cracks to occur from the preexisting flaws. The initiation stresses of the primary cracks at the two tips of each flaw were simultaneous and decreased with reduced flaw inclination angle. The following types of coalescence cracks were identified between the flaws: primary tensile coalescence crack, tensile crack linkage, shear crack linkage, mixed tensile-shear crack, and indirect crack coalescence. Coalescence through tensile linkage occurred mostly at pre-peak stress. In contrast, coalescence through shear or mixed tensile-shear cracks occurred at higher stress. Overall, this study indicates that the geometry of preexisting flaws affect crack initiation and coalescence behaviour.展开更多
Effect of frothers in preventing bubble coalescence during flotation of minerals has long been investigated.To evaluate the performance of a frother,an apparatus to measure the bubble size is a basic necessity.McGill ...Effect of frothers in preventing bubble coalescence during flotation of minerals has long been investigated.To evaluate the performance of a frother,an apparatus to measure the bubble size is a basic necessity.McGill Bubble Size Analyzer(MBSA) or bubble viewer that has been developed and completed by McGill University's Mineral Processing Group during the last decade is a unique instrument to serve this purpose.Two parameters which are thought to influence the bubble size measurements by McGill bubble viewer include water quality and frother concentration in the chamber.Results show that there is no difference in Sauter mean(D32) when tap or de-ionized water was used instead of process water.However,the frother concentration,in this research DowFroth 250(DF250),inside the chamber exhibited a pronounced effect on bubble size.Frother concentration below a certain point can not prevent coalescence inside the chamber and therefore caution must be taken in plant applications.It was also noted that the frother concentration which has been so far practiced in plant measurements(CCC75-CCC95) is high enough to prevent coalescence with the bubble viewer.展开更多
Based on experimental restilts of brittle, intact sandstone under uniaxial compression, the micro-parameters were firstly confirmed by adopting particle flow code (PFC2D). Then, the validation of the simulated model...Based on experimental restilts of brittle, intact sandstone under uniaxial compression, the micro-parameters were firstly confirmed by adopting particle flow code (PFC2D). Then, the validation of the simulated models were cross checked with the experimental results of brittle sandstone containing three parallel fissures under uniaxial compression. The simulated results agreed very well with the experimental results, including the peak strength, peak axial strain, and ultimate failure mode. Using the same micro- parameters, the numerical models containing a new geometry of three fissures are constructed to investigate the fissure angle on the fracture mechanical behavior of brittle sandstone under uniaxial compression. The strength and deformation parameters of brittle sandstone containing new three fissures are dependent to the fissure angle. With the increase of the fis- sure angle, the elastic modulus, the crack damage threshold, and the peak strength of brittle sandstone containing three fissures firstly increase and secondly decrease. But the peak axial strain is nonlinearly related to the fissure angle. In the entire process of deformation, the crack initiation and propagation behavior of brittle sandstone containing three fissures under uniaxial compression are investigated with respect to the fissure angle. Six different crack coalescence modes are identified for brittle sandstone containing three fissures under uniaxial compression. The influence of the fissure angle on the length of crack propagation and crack coalescence stress is evaluated. These investigated conclusions are very important for ensuring the stability and safety of rock engineering with intermittent structures.展开更多
The mechanism of microdroplet coalescence is a fundamental issue for droplet-based microfluidics. We developed an asymmetric expansion (a rectangular groove) along one side of a microchannel to achieve multiple-microd...The mechanism of microdroplet coalescence is a fundamental issue for droplet-based microfluidics. We developed an asymmetric expansion (a rectangular groove) along one side of a microchannel to achieve multiple-microdroplet trapping, collision, and coalescence. Compared with reported symmetric expansions, this asymmetric groove could easily trap microdroplets and control two or three microdroplet coalescences precisely without a requirement for temporal and spatial synchronization. To reveal the mechanisms of multiple-droplet coalescences in a groove, we observed five different coalescence patterns under different flow conditions. Moreover, we characterized the flow behavior quantitatively by simulating the velocity vector fields in both the microdroplets and continuous phase, finding good agreement with experiments. Finally, a map of coalescence forms with different capillary numbers () and flow ratios () was obtained. The results could provide a useful guidance for the design and application of droplet-based microfluidic devices.展开更多
Joint probabilistic data association is an effective method for tracking multiple targets in clutter, but only the target kinematic information is used in measure-to-track association. If the kinematic likelihoods are...Joint probabilistic data association is an effective method for tracking multiple targets in clutter, but only the target kinematic information is used in measure-to-track association. If the kinematic likelihoods are similar for different closely spaced targets, there is ambiguity in using the kinematic information alone; the correct association probability will decrease in conventional joint probabilistic data association algorithm and track coalescence will occur easily. A modified algorithm of joint probabilistic data association with classification-aided is presented, which avoids track coalescence when tracking multiple neighboring targets. Firstly, an identification matrix is defined, which is used to simplify validation matrix to decrease computational complexity. Then, target class information is integrated into the data association process. Performance comparisons with and without the use of class information in JPDA are presented on multiple closely spaced maneuvering targets tracking problem. Simulation results quantify the benefits of classification-aided JPDA for improved multiple targets tracking, especially in the presence of association uncertainty in the kinematic measurement and target maneuvering. Simulation results indicate that the algorithm is valid.展开更多
文摘Rationale:Acute otitis media is a common disease in early childhood,and is usually caused by Streptococcus pneumoniae(S.pneumoniae).Acute mastoiditis is a complication of acute otitis media and can involve not only the mucoperiosteum of the middle ear but can also spread to the periosteum by destroying the mastoid bone(acute coalescent mastoiditis).In addition,the infection can extend through the surrounding bones or the emissary veins beyond the mastoid’s air cells,leading to subperiosteal abscesses.Patient’s Concern:A 16-month-old female patient was hospitalized due to the purulent discharge of the left ear and the symptoms of right mastoiditis(swelling and redness of the skin).Diagnosis:Bilateral acute coalescent mastoiditis caused by S.pneumoniae infection.The computer tomography revealed bilateral bone destruction of the mastoid and abscesses found behind the auricle on both sides.Interventions:The patient underwent intravenous antibiotic therapy and surgical treatment.Outcomes:The patient was discharged 14 days after hospitalization with an improved condition.Lessons:Improperly treated acute coalescent mastoiditis can lead to extracranial and intracranial complications,sometimes serious and even life-threatening.Complications are prevalent in children under 2 years,in whom the disease progresses more rapidly and severely.The vaccination with a 13-valent vaccine may not result in sufficient immunity against S.pneumoniae,a predominant pathogen in children affected by acute coalescent mastoiditis.
文摘Genetic variability plays a key role in the biology and medical treatment of RNA viruses. As an RNA virus, Hepatitis C virus (HCV) replicate as complex distributions of closely related genomes termed viral quasispecies. The behavior of the evolving HCV quasispecies population is influenced by the ensemble of mutants that compose the viral population. One such influence is the presence of minority subpopulations, termed memory genomes, in the mutant spectra. Biologically relevant mutants have been previously observed to be present as memory genomes in RNA viral populations. For that reason, an in-depth analysis of HCV quasispecies populations is crucial for our understanding viral evolution, drug resistance and therapy outcome. Recently developed next-generation sequencing (NGS) platforms make it possible to investigate viral quasispecies at much greater detail. In order to gain insight into these matters, we have performed a Bayesian coalescent analysis of hypervariable region 1 (HVR1) sequences of a HCV quasispecies population circulating in a chronic patient, recently obtained by ultra-deep sequencing. The results of these studies revealed a mean rate of evolution of HCV HVR1 of the intra-host quasispecies population of 4.80 × 10-2 amino acid substitutions/site/year. A sharp and rapid diversification of the HCV quasispecies isolated from the patient in three different sub-populations was observed. The most abundant sequence in the quasispecies population was not found to be the center of a tight and complex network around this sequence, suggesting that the quasispecies population as a whole efficiently explore a wide sequence space. Co-evolution of relevant amino acid sites had been identified in the HVR1. This speaks of the possible roll of these residues in HVR1 to allow the virus to shift between combinations of residues to escape the immune system while retaining its structure and functions. The results of these studies highlight the importance of minority genomes in HCV population history and evolution, the mutant clouds as reservoirs of phenotypic and genetic variants for virus adaptability, as well as the roll of the mutant spectra to overcome selective constraints.
基金supported by National Natural Science Foundation of China(31630042 and 31970570)Guangdong Special Support Program。
文摘Conventional coalescent inferences of population history make the critical assumption that the population under examination is panmictic.However,most populations are structured.This complicates the prevailing coalescent analyses and sometimes leads to inaccurate estimates.To develop a coalescent method unhampered by population structure,we perform two analyses.First,we demonstrate that the coalescent probability of two randomly sampled alleles from the immediate preceding generation(one generation back)is independent of population structure.Second,motivated by this finding,we propose a new coalescent method:i-coalescent analysis.The i-coalescent analysis computes the instantaneous coalescent rate by using a phylogenetic tree of sampled alleles.Using simulated data,we broadly demonstrate the capability of i-coalescent analysis to accurately reconstruct population size dynamics of highly structured populations,although we find this method often requires larger sample sizes for structured populations than for panmictic populations.Overall,our results indicate i-coalescent analysis to be a useful tool,especially for the inference of population histories with intractable structure such as the developmental history of cell populations in the organs of complex organisms.
基金supported by the Key Science & Technology Project of Gansu Province (22ZD6NA007)the National Key Research and Development Program of China (2021YFD2200202)Computing support was provided by the Supercomputing Center of Lanzhou University
文摘The transition of traits between genetically related lineages is a fascinating topic that provides clues to understanding the drivers of speciation and diversification.Much can be learned about this process from phylogeny-based trait evolution.However,such inference is often plagued by genome-wide gene-tree discordance(GTD),mostly due to incomplete lineage sorting(ILS)and/or introgressive hybridization,especially when the genes underlying the traits appear discordant.Here,by collecting transcriptomes,whole chloroplast genomes(cpDNA),and population genetic datasets,we used the coalescent model to turn GTD into a source of information for ILS and employed hemiplasy to explain specific cases of apparent“phylogenetic discordance”between different morphological traits and probable species phylogeny in the Allium subg.Cyathophora.Both concatenation and coalescence methods consistently showed the same phylogenetic topology for species tree inference based on single-copy genes(SCGs),as supported by the KS distribution.However,GTD was high across the genomes of subg.Cyathophora:~27%e38.9%of the SCG trees were in conflict with the species tree.Plasmid and nuclear incongruence was also present.Our coalescent simulations indicated that such GTD was mainly a product of ILS.Our hemiplasy risk factor calculations supported that random fixation of ancient polymorphisms in different populations during successive speciation events along the subg.Cyathophora phylogeny may have caused the character transition,as well as the anomalous cpDNA tree.Our study exemplifies how phylogenetic noise can be transformed into evolutionary information for understanding character state transitions along species phylogenies.
基金supported by the National Natural Science Foundation of China(Grant No.52125903).
文摘Direct shear tests were conducted on sandstone specimens under different constant normal stresses to study the coalescence of cracks between non-persistent flaws and the shear sliding characteristics of the shear-formed fault.Digital image correlation and acoustic emission(AE)techniques were used to monitor the evolution of shear bands at the rock bridge area and microcracking behaviors.The experimental results revealed that the shear stresses corresponding to the peak and sub-peak in the stressdisplacement curve are significantly affected by the normal stress.Strain localization bands emerged at both the tip of joints and the rock bridge,and their extension and interaction near the peak stress caused a surge in the AE hit rate and a significant decrease in the AE b value.Short and curvilinear strain bands were detected at low normal stress,while high normal stress generally led to more microcracking events and longer coplanar cracks at the rock bridge area.Furthermore,an increase in normal stress resulted in a higher AE count rate and more energetic AE events during friction sliding along the shearformed fault.It was observed that the elastic energy released during the crack coalescence at the prepeak stage was much greater than that released during friction sliding at the post-peak stage.More than 75%of AE events were located in the low-frequency band(0e100 kHz),and this proportion continued to rise with increasing normal stress.Moreover,more AE events of low AF value and high RA value were observed in specimens subjected to high normal stress,indicating that greater normal stress led to more microcracks of shear nature.
文摘Froth flotation is a separation process widely used in the mineral processing industry that depends on differences in particle surface properties to separate valuable materials from undesired gangue. In froth flotation, an addition of a surfactant, acting as frother is usually needed. The basic function of the frother is to produce a swarm of air bubbles, which remain sufficiently stable for the hydrophobic mineral particles to be captured by them. This Paper presents a combination method of a foaming agent-surfactant composition with desirable selectivity and foaming properties. Wherein 1-butanol (C4H10O) is a main flotation foaming agent, which decides bubble sizes in a collecting area;and tetraethylene glycol (C8H18O5) is an auxiliary foaming agent, which affects a rising velocity of the bubbles in the collecting area and a foaming capability in a selected area. Set concentrations of the two components are respectively 60 ppm for the 1-butanol and 120 ppm for the tetraethylene glycol. An addition sequence is the 1-butanol followed by the tetraethylene glycol. The dual advantages of the selectivity and foaming properties of the foaming agent-surfactant composition in the present disclosure are verified through a series of tests, and desirable yields can be obtained in practice.
基金the National Swedish Research Council(grants No.2015-04402,2019-04486)the Carl Trygger Foundation(CTS 20:6)+3 种基金the Jornvall FoundationJulian Francis for financial supportthe National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory,the Knut and Alice Wallenberg Foundationthe Research/Scientific Computing teams at The James Hutton Institute and NIAB for providing computational resources and technical support for the"UK's Crop Diversity Bioinformatics HPC"(BBSRC grant BB/S019669/1)。
文摘The family Alaudidae,larks,comprises 93-100 species(depending on taxonomy)that are widely distributed across Africa and Eurasia,with single species extending their ranges to North and northernmost South America and Australia.A decade-old molecular phylogeny,comprising~80%of the species,revealed multiple cases of parallel evolution and large variation in rates of morphological evolution,which had misled taxonomists into creating many non-monophyletic genera.Here,we reconstruct the phylogeny of the larks,using a dataset covering one mitochondrial and 16 nuclear loci and comprising all except one of the currently recognised species as well as several recently proposed new species(in total 133 taxa;not all loci available for all species).We provide additional support using genome-wide markers to infer a genus-level phylogeny based on near-complete generic sampling(in total 51 samples of 44 taxa across 40 species).Our results confirm the previous findings of rampant morphological convergence and divergence,and reveal new cases of paraphyletic genera.We propose a new subfamily classification,and also that the genus Mirafra is divided into four genera to produce a more balanced generic classification of the Alaudidae.Our study supports recently proposed species splits as well as some recent lumps,while also questioning some of the latter.This comprehensive phylogeny will form an important basis for future studies,such as comparative studies of lark natural history,ecology,evolution and conservation.
基金supported by the National Natural Science Foundation of China(No.31471987)approved by College of Life Sciences,Beijing Normal University:No.CLSEAW-2013-007。
文摘Understanding speciation has long been a fundamental goal of evolutionary biology.It is widely accepted that speciation requires an interruption of gene flow to generate strong reproductive isolation between species.The mechanism of how speciation in sexually dichromatic species operates in the face of gene flow remains an open question.Two species in the genus Chrysolophus,the Golden Pheasant(C.pictus)and Lady Amherst’s Pheasant(C.amherstiae),both of which exhibit significant plumage dichromatism,are currently parapatric in southwestern China with several hybrid recordings in field.In this study,we estimated the pattern of gene flow during the speciation of the two pheasants using the Approximate Bayesian Computation(ABC)method based on data from multiple genes.Using a newly assembled de novo genome of Lady Amherst’s Pheasant and resequencing of widely distributed individuals,we reconstructed the demographic history of the two pheasants by the PSMC(pairwise sequentially Markovian coalescent)method.The results provide clear evidence that the gene flow between the two pheasants was consistent with the predictions of the isolation with migration model during divergence,indicating that there was long-term gene flow after the initial divergence(ca.2.2 million years ago).The data further support the occurrence of secondary contact between the parapatric populations since around 30 kya with recurrent gene flow to the present,a pattern that may have been induced by the population expansion of the Golden Pheasant in the late Pleistocene.The results of the study support the scenario of speciation between the Golden Pheasant and Lady Amherst’s Pheasant with cycles of mixing-isolation-mixing,possibly due to the dynamics of geographical context in the late Pleistocene.The two species provide a good research system as an evolutionary model for testing reinforcement selection in speciation.
基金the Florida International University Tropics Program and the Susan S.Levine Trust.RTK and ELB also received support from the United States National Science Foundation(DEB-1118823 and DEB-1655683).
文摘Background: Previous phylogenetic studies that include the four recognized species of Gallus have resulted in a number of distinct topologies, with little agreement. Several factors could lead to the failure to converge on a consistent topology, including introgression, incomplete lineage sorting, different data types, or insufficient data.Methods: We generated three novel whole genome assemblies for Gallus species, which we combined with data from the published genomes of Gallus gallus and Bambusicola thoracicus(a member of the sister genus to Gallus). To determine why previous studies have failed to converge on a single topology, we extracted large numbers of orthologous exons, introns, ultra-conserved elements, and conserved non-exonic elements from the genome assemblies. This provided more than 32 million base pairs of data that we used for concatenated maximum likelihood and multispecies coalescent analyses of Gallus.Results: All of our analyses, regardless of data type, yielded a single, well-supported topology. We found some evidence for ancient introgression involving specific Gallus lineages as well as modest data type effects that had an impact on support and branch length estimates in specific analyses. However, the estimated gene tree spectra for all data types had a relatively good fit to their expectation given the multispecies coalescent.Conclusions: Overall, our data suggest that conflicts among previous studies probably reflect the use of smaller datasets(both in terms of number of sites and of loci) in those analyses. Our results demonstrate the importance of sampling large numbers of loci, each of which has a sufficient number of sites to provide robust estimates of gene trees. Low-coverage whole genome sequencing, as we did here, represents a cost-effective means to generate the very large data sets that include multiple data types that enabled us to obtain a robust estimate of Gallus phylogeny.
文摘A novel method for breaking emulsions with microporous membranes is presented.A membrane would act as a coalescer if its pore size is smaller than the emulsion droplets and if the dispersed phase has great affinity to the membrane.It was observed that a hydrophilic membrane is able to break water in oil emulsions with high separation efficiency.Effects of the membrane pore size,membrane thickness,transmembrane pressure and emulsion composition on demulsification performance were investigated.It was found that the membrane pore size and transmembrane pressure affect demulsification performance remarkably while other factors have slight or almost no effect.
基金Project(2014CB046905,2013CB36003)supported by the National Basic Research Program of ChinaProject(NCET-12-0961)supported by the Program for New Century Excellent Talents in University,China+1 种基金Projects(51179189,41272344)supported by the National Natural Science Foundation of ChinaProject(HBKLCIV201201)supported by the Open Research Fund Program of the Key Laboratory of Safety for Geotechnical and Structural Engineering of Hubei Province,China
文摘Based on the axial stress-axial strain curves,the effect of fissure angle on the strength and deformation behavior of sandstone specimens containing combined flaws is analyzed.The mechanical parameters of sandstone specimens containing combined flaws are all lower than that of intact specimen,but the reduction extent is distinctly related to the fissure angle.The results of sandstone specimens containing combined flaws are obtained by the acoustic emission,which can be used to monitor the crack initiation and propagation.The ultimate failure mode and crack coalescence behavior are evaluated for brittle sandstone specimens containing combined flaws.Nine different crack types are identified on the basis of their geometry and crack coalescence mechanism(tensile crack,hole collapse,far-field crack and surface spalling)for combined flaws.The photographic monitoring was also adopted for uniaxial compression test in order to confirm the sequence of crack coalescence in brittle sandstone specimens containing combined flaws,which recorded the real-time crack coalescence process during entire deformation.According to the monitored results,the effect of crack coalescence process on the strength and deformation behavior is investigated based on a detailed analysis for brittle sandstone specimens containing combined flaws by using digital photogrammetry.
文摘The mechanism of cracks propagation and cracks coalescence due to compressive loading of the brittle substances containing pre-existing cracks (flaws) was modeled experimentally using specially made rock-like specimens from Portland Pozzolana Cement (PPC). The breakage process of the specimens was studied by inserting single and double flaws with different inclination angles at the center and applying uniaxial compressive stress at both ends of the specimen. The first crack was oriented at 50° from the horizontal direction and kept constant throughout the analysis while the orientation of the second crack was changed. It is experimentally observed that the wing cracks are produced at the first stage of loading and start their propagation toward the direction of uniaxial compressive loading. The secondary cracks may also be produced in form of quasi-coplanar and/or oblique cracks in a stable manner. The secondary cracks may eventually continue their propagation in the direction of maximum principle stress. These experimental works were also simulated numerically by a modified higher order displacement discontinuity method and the cracks propagation and cracks coalescence were studied based on Mode I and Mode II stress intensity factors (SIFs). It is concluded that the wing cracks initiation stresses for the specimens change from 11.3 to 14.1 MPain the case of numerical simulations and from 7.3 to 13.8 MPa in the case of experimental works. It is observed that cracks coalescence stresses change from 21.8 to 25.3 MPa and from 19.5 to 21.8 MPa in the numerical and experimental analyses, respectively. Comparing some of the numerical and experimental results with those recently cited in the literature validates the results obtained by the proposed study. Finally, a numerical simulation was accomplished to study the effect of confining pressure on the crack propagation process, showing that the SIFs increase and the crack initiation angles change in this case.
基金The work was supported by the National Natural Science Foundation of China(No.5140115)the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province(No.BS2013CL034)+1 种基金Independent Inno-vation Foundation of Shandong University(No.GN2013001)partially by the Fundamental Research Funds of Shan-dong University(2016JC016).
文摘Hot-extruded magnesium alloy AZ31 bar was cut into hexagonal prisms and then compressed at room temperature with the loading direction parallel to the extrusion direction(ED)or perpendicular to ED.The effective stress and strain evolution at center and corner region of the hexagonal prisms was simulated by using DEFORM 3D,while microstructure evolution was characterized by electron backscatter diffraction(EBSD).Relationship between twinning behavior and stress-strain evolution during compression at room temperature was studied.The results indicated that the compressive stress and strain levels at central region of hexagonal prisms were lower than those at the corner parts.EBSD examination revealed that{10-12}twins activate during the compression and the volume fraction of twins at corner parts were less than that at the central parts,which was attributed to twin thickening and coalescence behaviors.Meanwhile,the EBSD map indicated that the arise of{10-11}contraction twins and{10-11}-{10-12}double twins in compressed samples,especially in the corner region with loading axis perpendicular to ED,which were considered to be related to the high stress level at corner region.The dislocation slips led to low-angle boundaries in LA⊥ED and LA//ED.
基金Project(BK20150005) supported by the Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars,ChinaProject(2014YC10) supported by the Fundamental Research Funds for the Central Universities,China
文摘A series of laboratory experiments and PFC numerical simulations for rock-like material specimens containing two unparallel fissures were carried out.On the basis of experimental and numerical results,the stress-strain curves,mechanical properties,AE events,cracking behavior and energy characteristics were analyzed to reveal the macro-mechanical behavior and meso-mechanism of pre-fissured specimens under different loading rates.Investigated results show that:1)When the loading rate is relatively low,the stress-strain curves show a brittle response.When the loading rate is relatively high,the curve shows a more ductile response.Both of the peak strength and elastic mudulus increase with the increase of loading rate,which can be expressed as power functions.2)Four crack types are identified,i.e.,tensile crack,shear crack,far-field crack and surface spalling.Moreover,the tensile crack,far-field crack and surface spalling are under tensile mechanism,while the shear crack is under shear mechanism.3)The drops of the stress-strain curves all correspond to the crack initiation or coalescence,which is also linked to a sudden increasing in the accumulated micro-crack curve.4)Both of the maximum bond force and energy have the similar trend with the increase of loading rate to peak strength,which indicates that the trend of peak strength can be explained by the meso-mechanics and energy.
基金supported by the National Natural Science Foundation of China (Grants 41572310, 41272351)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grants XDB10030301, XDB10030304)support provided by the CAS-TWAS Presidential Fellowship, University of Chinese Academy of Sciences, Beijing, China
文摘Failure of rock mass that is subjected to compressive loads occurs from initiation, propagation, and linkage of new cracks from preexisting fissures. Our research investigates the cracking behaviour and coalescence process in a brittle material with two non-parallel overlapping flaws using a high-speed camera. The coalescence tensile crack and tensile wing cracks were the first cracks to occur from the preexisting flaws. The initiation stresses of the primary cracks at the two tips of each flaw were simultaneous and decreased with reduced flaw inclination angle. The following types of coalescence cracks were identified between the flaws: primary tensile coalescence crack, tensile crack linkage, shear crack linkage, mixed tensile-shear crack, and indirect crack coalescence. Coalescence through tensile linkage occurred mostly at pre-peak stress. In contrast, coalescence through shear or mixed tensile-shear cracks occurred at higher stress. Overall, this study indicates that the geometry of preexisting flaws affect crack initiation and coalescence behaviour.
基金Project supported by the Chair in Mineral Processing at McGill University,under the Collaborative Research and Development Program of NSERC(Natural Sciences and Engineering Research Council of Canada)with industrial sponsorship from Vale,Teck Cominco,Xstrata Process Support,Agnico-Eagle,Shell Canada,Barrick Gold,COREM,SGS Lakefield Research and Flottec
文摘Effect of frothers in preventing bubble coalescence during flotation of minerals has long been investigated.To evaluate the performance of a frother,an apparatus to measure the bubble size is a basic necessity.McGill Bubble Size Analyzer(MBSA) or bubble viewer that has been developed and completed by McGill University's Mineral Processing Group during the last decade is a unique instrument to serve this purpose.Two parameters which are thought to influence the bubble size measurements by McGill bubble viewer include water quality and frother concentration in the chamber.Results show that there is no difference in Sauter mean(D32) when tap or de-ionized water was used instead of process water.However,the frother concentration,in this research DowFroth 250(DF250),inside the chamber exhibited a pronounced effect on bubble size.Frother concentration below a certain point can not prevent coalescence inside the chamber and therefore caution must be taken in plant applications.It was also noted that the frother concentration which has been so far practiced in plant measurements(CCC75-CCC95) is high enough to prevent coalescence with the bubble viewer.
基金supported by the Fundamental Research Funds for the Central Universities (China University of Mining and Technology) (Grant 2014YC10)the National Basic Research 973 Program of China (Grant 2014CB046905)
文摘Based on experimental restilts of brittle, intact sandstone under uniaxial compression, the micro-parameters were firstly confirmed by adopting particle flow code (PFC2D). Then, the validation of the simulated models were cross checked with the experimental results of brittle sandstone containing three parallel fissures under uniaxial compression. The simulated results agreed very well with the experimental results, including the peak strength, peak axial strain, and ultimate failure mode. Using the same micro- parameters, the numerical models containing a new geometry of three fissures are constructed to investigate the fissure angle on the fracture mechanical behavior of brittle sandstone under uniaxial compression. The strength and deformation parameters of brittle sandstone containing new three fissures are dependent to the fissure angle. With the increase of the fis- sure angle, the elastic modulus, the crack damage threshold, and the peak strength of brittle sandstone containing three fissures firstly increase and secondly decrease. But the peak axial strain is nonlinearly related to the fissure angle. In the entire process of deformation, the crack initiation and propagation behavior of brittle sandstone containing three fissures under uniaxial compression are investigated with respect to the fissure angle. Six different crack coalescence modes are identified for brittle sandstone containing three fissures under uniaxial compression. The influence of the fissure angle on the length of crack propagation and crack coalescence stress is evaluated. These investigated conclusions are very important for ensuring the stability and safety of rock engineering with intermittent structures.
基金supported by the Beijing Municipal Natural Science Foundation (Grant 7152012)the General Program of Science and Technology Development Project of the Beijing Municipal Education Commission (Grant KM201610005002)+2 种基金the National Natural Science Foundation of China (Grant 11572013)the China Scholarship Council (Grant 201406545031)the Training Plan of New Talent of Beijing University of Technology (Grant 2015-RX-L02)
文摘The mechanism of microdroplet coalescence is a fundamental issue for droplet-based microfluidics. We developed an asymmetric expansion (a rectangular groove) along one side of a microchannel to achieve multiple-microdroplet trapping, collision, and coalescence. Compared with reported symmetric expansions, this asymmetric groove could easily trap microdroplets and control two or three microdroplet coalescences precisely without a requirement for temporal and spatial synchronization. To reveal the mechanisms of multiple-droplet coalescences in a groove, we observed five different coalescence patterns under different flow conditions. Moreover, we characterized the flow behavior quantitatively by simulating the velocity vector fields in both the microdroplets and continuous phase, finding good agreement with experiments. Finally, a map of coalescence forms with different capillary numbers () and flow ratios () was obtained. The results could provide a useful guidance for the design and application of droplet-based microfluidic devices.
基金Defense Advanced Research Project "the Techniques of Information Integrated Processing and Fusion" in the Eleventh Five-Year Plan (513060302).
文摘Joint probabilistic data association is an effective method for tracking multiple targets in clutter, but only the target kinematic information is used in measure-to-track association. If the kinematic likelihoods are similar for different closely spaced targets, there is ambiguity in using the kinematic information alone; the correct association probability will decrease in conventional joint probabilistic data association algorithm and track coalescence will occur easily. A modified algorithm of joint probabilistic data association with classification-aided is presented, which avoids track coalescence when tracking multiple neighboring targets. Firstly, an identification matrix is defined, which is used to simplify validation matrix to decrease computational complexity. Then, target class information is integrated into the data association process. Performance comparisons with and without the use of class information in JPDA are presented on multiple closely spaced maneuvering targets tracking problem. Simulation results quantify the benefits of classification-aided JPDA for improved multiple targets tracking, especially in the presence of association uncertainty in the kinematic measurement and target maneuvering. Simulation results indicate that the algorithm is valid.