The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in ...The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in arterial blood.P(v-a) CO_2 depends on the cardiac output and the global CO_2 production,and on the complex relationship between PCO_2 and CO_2 content.Experimental and clinical studies support the evidence that P(v-a) CO_2 cannot serve as an indicator of tissue hypoxia,and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO_2generated by the peripheral tissues.P(v-a) CO_2 can be replaced by the central venous-to-arterial CO_2 difference(△PCO_2),which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and,therefore,more easy to obtain at the bedside.Determining the △PCO_2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation(SCVO_2) > 70%associated with elevated blood lactate levels.Because high blood lactate levels is not a discriminatory factor in determining the source of that stress,an increased △PCO_2(> 6 mmHg)could be used to identify patients who still remain inadequately resuscitated.Monitoring the △PCO_2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and,thus,guiding the therapy.In this respect,it can aid to titrate inotropes to adjust oxygen delivery to CO_2 production,or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO_2 related to metabolic demand.The combination of P(v-a) CO_2 or △PCO_2 with oxygen-derived parameters through the calculation of the P(v-a) CO_2 or △PCO_2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.展开更多
Litter size and birth weights are limited by uterine capacity, defined as the ability of the uterus to maintain the appropriate development of some number of conceptuses. Uterine capacity is the result of the combined...Litter size and birth weights are limited by uterine capacity, defined as the ability of the uterus to maintain the appropriate development of some number of conceptuses. Uterine capacity is the result of the combined effects of uterine, placental and embryo/fetal function. The number of living conceptuses that the uterus is capable of supporting is greater during early gestation compared to later gestation. Plots of log fetal weight versus log placental weight also indicate that fetal weights are less sensitive to reduced placental weight （and therefore reduced intrauterine space） in early gestation compared to late gestation. However, even in late gestation, mechanisms still exist that maintain fetal growth when the size of the placenta is reduced. One such mechanism is likely to be improved development of the folded placental-epithelial/maternal-epithelial bilayer. Fold depth, and therefore the maternal fetal interactive surface, increases as gestation advances and is greater in placenta from smal fetuses. On the fetal side of the placenta, the epithelial bilayer is embedded in stromal tissue. Glycosaminoglycans are major components of stroma, including hyaluronan and heparan sulfate. Hyaluronidases and heparanases are present within placental tissues, and likely play roles in modification of stromal components to facilitate fold development. Glycosaminoglycans are polymers of forms of glucose （glucosamine, glucuronic acid, iduronic acid） suggesting that glycosaminoglycan synthesis may compete with the glucose needs of the developing fetus. Pig conceptuses are fructogenic, such that a substantial portion of glucose transferred from mother to fetus is converted to fructose. Fructose is an intermediate product in the synthesis of glucosamine from glucose, and glucosamine is linked to regulation of trophoblast cell proliferation through regulation of mTOR. These findings suggest a link between glucose, fructose, glucosamine synthesis, GAG production, and placental morphogenesis, but the details of these i展开更多
The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The...The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The re- sulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the pre- dictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic suc- cess. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antivi- ral therapy in patients infected by the same HCV geno- type. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Inter- feron pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity. Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non- structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.展开更多
Current deep learning approaches are cutting-edge methods for solving classification tasks.Arising transfer learning techniques allows applying large generic model to simple tasks whereas simpler models could be used....Current deep learning approaches are cutting-edge methods for solving classification tasks.Arising transfer learning techniques allows applying large generic model to simple tasks whereas simpler models could be used.Large models raise the major problem of their memory consumption and processor usage and lead to a prohibitive ecological footprint.In that paper,we present a novel visual analytics approach to interactively prune those networks and thus limit that issue.Our technique leverages a novel sparkline matrix visualization technique as well as a novel local metric which evaluates the discriminatory power of a filter to guide the pruning process and make it interpretable.We assess the well-founded of our approach through two realistic case studies and a user study.For both of them,the interactive refinement of the model led to a significantly smaller model having similar prediction accuracy than the original one.展开更多
Visualizing social networks,especially an overview emphasizing their structure,i.e.,communities and their interconnections,is known to be a challenging problem.In this paper,we present a set of design rationales to bu...Visualizing social networks,especially an overview emphasizing their structure,i.e.,communities and their interconnections,is known to be a challenging problem.In this paper,we present a set of design rationales to build such overview visualizations of social networks and our solution called Jasper.We evaluate its performances against two of the most wide-spread visualization techniques(matrix and node-link diagram)in a human–computer controlled experiment based on community-related tasks.While none of the techniques emerge as the overwhelming winner,Jasper appears to be one of the best methods for each task;a fact sustained by the marks given by the users.Overall,Jasper can be seen as an all-encompassing solution for quickly producing legible and compact overviews of large social networks on a single modern computer.展开更多
This paper is devoted to the existence and the uniqueness of the entropy solution for a general scalar conservation law associated with a forced bilateral obstacle condition in a bounded domain of Rp, p>= 1. The me...This paper is devoted to the existence and the uniqueness of the entropy solution for a general scalar conservation law associated with a forced bilateral obstacle condition in a bounded domain of Rp, p>= 1. The method of penalization is used with a view to obtaining an existence result. However, the former only gives uniform L -estimates and so leads in fact to look for an Entropy Measure-Valued Solution, according to the specific properties of bounded sequences in L . The uniqueness of this EMVS is proved. Classically, it first ensures the existence of a bounded and measurable function U entropy solution and then the strong convergence in Lq of approximate solutions to U.展开更多
Transcription factor TFIIA is controlled by complex regulatory networks including proteolysis by the protease Taspase 1, though the full impact of cleavage remains elusive. Here, we demonstrate that in contrast to the...Transcription factor TFIIA is controlled by complex regulatory networks including proteolysis by the protease Taspase 1, though the full impact of cleavage remains elusive. Here, we demonstrate that in contrast to the general assumption, de novo produced TFIIA is rapidly confined to the cytoplasm via an evolutionary conserved nuclear export signal （NES, amino acids ^21VINDVRDIFL^30）, interacting with the nuclear export receptor Exportin-1/chromosomal region maintenance 1 （Crml）. Chemical export inhibition or genetic inactivation of the NES not only promotes TFIIA＇s nuclear localization but also affects its transcrip- tional activity. Notably, Taspase 1 processing promotes TFIIA＇s nuclear accumulation by NES masking, and modulates its tran- scriptional activity. Moreover, TFIIA complex formation with the TATA box binding protein （TBP） is cooperatively enhanced by inhibition of proteolysis and nuclear export, leading to an increase of the ceil cycle inhibitor p16INK, which is counteracted by pre- vention of TBP binding. We here identified a novel mechanism how proteolysis and nuclear transport cooperatively fine-tune tran- scriptional programs.展开更多
Spray drift has become an important issue in pesticide application. Vineyard spraying is particularly interesting to consider, as pesticide droplets are not directed towards the ground but rather towards the targeted ...Spray drift has become an important issue in pesticide application. Vineyard spraying is particularly interesting to consider, as pesticide droplets are not directed towards the ground but rather towards the targeted crop. The aim of this study was to investigate the influence of nozzle orientation on droplet size and droplet velocity using three different nozzles （IDK, TVI and TXA） used in vineyards. Two series of measurement were performed in order to assess the effect of the gravity on sprays. Droplet size and one-dimensional droplet velocity characteristics were measured using a phase Doppler particle analyser （PDPA）. Two planes, i.e., one horizontal and one vertical, were considered. Results suggest that the nozzle orientation slightly affects the size distribution, which is shifted towards larger droplets when nozzles spray horizontally compared to vertically spray, However, droplet axial velocity distribution is shifted towards lower values. Supposing that the only droplets which can reach the crop are those with an axial velocity greater than 1 m/s and a diameter larger than 100 lain, results showed significant differences according to the nozzle and orientation. More than 98.6% of the spray volume would reach the target whatever the orientation of the IDK nozzle, 78.8% of the spray volume would reach the crop when the TVI nozzle sprays horizontally, while only 16.0% of the spray volume would reach the crop when TXA nozzle sprays horizontally. This paper offers new perspectives in the comprehension and the optimization of the deposition process into the vegetation based from droplet size and velocity profiles from horizontally oriented sprays from flat fan or hollow cone nozzles.展开更多
Transmission of cytomegalovirus (CMV) infection frommothers to preterm infants during breastfeeding may be symptomatic and long term consequences are unknown. This study evaluated the kinetics of CMV load in breast mi...Transmission of cytomegalovirus (CMV) infection frommothers to preterm infants during breastfeeding may be symptomatic and long term consequences are unknown. This study evaluated the kinetics of CMV load in breast milk and the rate of postnatal CMV transmission via breastmilk from mothers to their preterm infants. Methods: Prospective study of mother child pairs after preterm delivery before 33 weeks. Exclusion of donor breast milk and of CMV-seropositive blood products.Material used was maternal CMV serostatus, ear swab of the infant at birth, weekly screened breast milk and children’s urine by rapid viral culture. Results: During a 5-month period 28 mother-infantpairs with 34 preterm infants were studied.Eighteen women (64.3%)were CMV-seronegative at birth;breast milk samples and the infants’ urine remained CMV-negative.Eight of the 10 seropositive mothers, who had 11 preterm infants, excreted CMV into breast milk (80%). CMV excretion into breast milk was detected during the first week after delivery in 66%cases and was at its peaked between 3 to 5 weeks after delivery.Out of the 7 CMV-exposed infants, CMV transmission was confirmed in only one asymptomatic case. Total quantity of breast milk intake did not seem discriminative for CMV transmission.Conclusion: In CMV-seropositive mothers of preterm infants a high incidence of CMV excretion into breast milk was detected. Despite this high rate, symptomatic infection did not occur. However, potential risk and severity of infection may be difficult to establish. Because breastfeeding is beneficial, new procedures for gentle virus inactivation of seropositive breast milk should be assessed.展开更多
During pesticide spraying, some of the smallest or slowest droplets do not reach the target and may contribute to spray drift. Therefore, it is important to characterize droplet size and velocity close to the nozzle e...During pesticide spraying, some of the smallest or slowest droplets do not reach the target and may contribute to spray drift. Therefore, it is important to characterize droplet size and velocity close to the nozzle exit. The aim of this study was to contribute to the comprehension of spray formation. Surfactant influence on spray characteristics was studied by comparing water spray with sprays containing three different surfactants, Two nozzles including a classical hollow cone nozzle ATR （Albuz, France） and an air-induced hollow cone nozzle TVI which is a low-drift nozzle （Albuz, France） were chosen. Radial profiles of the axial velocity component and Sauter mean diameter at two axial distances from the nozzle exit were measured using a Phase Doppler Particle Analyzer （PDPA）. Results showed that sprays issued from ATR and TVI nozzles were very different, even when water was sprayed. Effect of adding surfactant depended on the nozzle type. Sheet thickness was reduced by adding Elton and Heliosol regardless of the nozzle type. They reduced spray angle of ATR nozzle spray but did not affect that of YVI nozzle. Break-Thru has a slight effect when sprayed through the ATR nozzle, but it has the most pronounced effect on the SMD when sprayed through the TVI nozzle.展开更多
In plants, resistance to necrotrophic pathogens depends on the interplay between different hormone systems, such as those regulated by salicylic acid （SA）, jasmonic acid （JA）, ethylene, and abscisic acid. Repressi...In plants, resistance to necrotrophic pathogens depends on the interplay between different hormone systems, such as those regulated by salicylic acid （SA）, jasmonic acid （JA）, ethylene, and abscisic acid. Repression of auxin signaling by the SA pathway was recently shown to contribute to antibacterial resistance. Here, we demonstrate that Arabidopsis auxin signaling mutants axrl, axr2, and axr6 that have defects in the auxin-stimulated SCF （Skpl-Cullin- F-box） ubiquitination pathway exhibit increased susceptibility to the necrotrophic fungi Plectosphaerella cucumerina and Botrytis cinerea. Also, stabilization of the auxin transcriptional repressor AXR3 that is normally targeted for removal by the SCF-ubiquitin/proteasome machinery occurs upon P. cucumerina infection. Pharmacological inhibition of auxin transport or proteasome function each compromise necrotroph resistance of wild-type plants to a similar extent as in non-treated auxin response mutants. These results suggest that auxin signaling is important for resistance to the necrotro- phic fungi P. cucumerina and B. cinerea. SGTlb （one of two Arabidopsis SGT1 genes encoding HSP90/HSC70 co-chaperones） promotes the functions of SCF E3-ubiquitin ligase complexes in auxin and JA responses and resistance conditioned by certain Resistance （R） genes to biotrophic pathogens. We find that sgtlb mutants are as resistant to P. cucumerina as wild-type plants. Conversely, auxin/SCF signaling mutants are uncompromised in RPP4-triggered resistance to the obligate biotrophic oomycete, Hyaloperonospora parasitica. Thus, the predominant action of SGTlb in R gene-conditioned resis- tance to oomycetes appears to be at a site other than assisting SCF E3-ubiquitin ligases. However, genetic additivity of sgtlb axrl double mutants in susceptibility to H. parasitica suggests that SCF-mediated ubiquitination contributes to lim- iting biotrophic pathogen colonization once plant-pathogen compatibility is established.展开更多
The Arabidopsis heterotrimeric G-protein controls defense responses to necrotrophic and vascular fungi. The agbl mutant impaired in the Gβ subunit displays enhanced susceptibility to these pathogens. Gβ/AGB1 forms a...The Arabidopsis heterotrimeric G-protein controls defense responses to necrotrophic and vascular fungi. The agbl mutant impaired in the Gβ subunit displays enhanced susceptibility to these pathogens. Gβ/AGB1 forms an obligate dimer with either one of the Arabidopsis Gγsubunits （γ1/AGG1 and γ2/AGG2）. Accordingly, we now demonstrate that the aggl agg2 double mutant is as susceptible as agbl plants to the necrotrophic fungus Plectosphaerella cucumerina. To elucidate the molecular basis of heterotrimeric G-protein-mediated resistance, we performed a comparative transcriptomic analysis of agbl-1 mutant and wild-type plants upon inoculation with P cucumerina. This analysis, together with metab- olomic studies, demonstrated that G-protein-mediated resistance was independent of defensive pathways required for resistance to necrotrophic fungi, such as the salicylic acid, jasmonic acid, ethylene, abscisic acid, and tryptophan-derived metabolites signaling, as these pathways were not impaired in agbl and aggl agg2 mutants. Notably, many mis-reguiated genes in agbl plants were related with cell wall functions, which was also the case in aggl agg2 mutant. Biochemical analyses and Fourier Transform InfraRed （FTIR） spectroscopy of cell walls from G-protein mutants revealed that the xylose content was lower in agbl and aggl agg2 mutants than in wild-type plants, and that mutant walls had similar FTIR spec-tratypes, which differed from that of wild-type plants. The data presented here suggest a canonical functionality of the Gβ and Gγ1/γ2 subunits in the control of Arabidopsis immune responses and the regulation of cell wall composition.展开更多
MYB34, MYB51, and MYB122 transcription factors are known as decisive regulators of indolic glucosinolate （IG） biosynthesis with a strong impact on expression of genes encoding CYP79B2 and CYP79B3 enzymes that redund...MYB34, MYB51, and MYB122 transcription factors are known as decisive regulators of indolic glucosinolate （IG） biosynthesis with a strong impact on expression of genes encoding CYP79B2 and CYP79B3 enzymes that redundantly convert tryptophan to indole-3-acetaldoxime （IAOx）. This intermediate represents a branching point for IG biosynthesis, and pathways leading to camalexin and indole-carboxylic acids （ICA）. Here we investigate how these MYBs affect the pathogen-triggered Trp metabolism. Our experiments indicated that these three MYBs affect not only IG production but also constitutive biosynthesis of other IAOx- derived metabolites. Strikingly, the PENETRATION 2 （PEN2）-dependent IG-metabolism products, which are absent in myb34/51/122 and pen2 mutants, were indispensable for full flg22-mediated induction of other IAOx-dedved compounds. However, germ induction and accumulation of ICAs and camalexin upon path- ogen infection was not compromised in myb34/51/122 plants, despite strongly reduced IG levels. Hence, in comparison with cyp79B2/B3, which lacks all IAOx-derived metabolites, we found myb34/51/122 an ideal tool to analyze IG contribution to resistance against the necrotrophic fungal pathogen Plectosphaerella cucumerina. The susceptibility of myb34/51/122 was similar to that of pen2, but much lower than susceptibility of cyp79B2/B3, indicating that MYB34/51/122 contribute to resistance toward P. cucumerina exclu- sively through IG biosynthesis, and that PEN2 is the main leaf myrosinase activating IGs in response to microbial pathogens.展开更多
In this study,we analyze new ways of conceptualizing improvements in firms'innovation by implementing the"right-factors configuration,"illustrated through an analog of a recipe and its ingredients.Specif...In this study,we analyze new ways of conceptualizing improvements in firms'innovation by implementing the"right-factors configuration,"illustrated through an analog of a recipe and its ingredients.Specifically,we research the multiple combinations of three ingredients(creativity,innovation networks,and resources)required to accomplish the innovation recipe.Using a sample of firms from a Spanish science and technology park,we apply qualitative comparative analysis(QCA)-specifically,fuzzy-set QCA(fsQCA)-to test the importance of each component in technological and non-technological innovation.First,the results suggest a map of combinations of innovative ingredients with eight possible patterns.Second,they show that the only ingredient needed is the combination of a creative climate and creative intensity.Finally,the methods of obtaining technological and non-technological innovations differ.The implications for management and policymakers are discussed,and directions for future research are highlighted.展开更多
Background： During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesize...Background： During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized that supplementing gestating dams with glucosamine during this time would support placental folded-epithelial-bilayer development and increase litter size. In Exp. 1, gilts were unilaterally hysterectomizedovariectomized（UHO）. UHO gilts were mated and then supplemented daily with 10 g glucosamine（n = 16） or glucose（control, n = 17） from d 85 of gestation until slaughter（d 105）. At slaughter, the number of live fetuses was recorded and each live fetus and its placenta was weighed. Uterine wall samples adjacent to the largest and smallest fetuses within each litter were processed for histology. In Exp. 2, pregnant sows in a commercial sow farm were supplemented with either 10 g glucosamine or glucose daily from d 85 of gestation to farrowing. Total piglets born and born alive were recorded for each litter. In Exp. 3, the same commercial farm and same protocol were used except that the dose of glucosamine and glucose was doubled to 20 g/d.Results： In Exp. 1, the number of live fetuses tended to be greater in glucosamine-treated UHO gilts（P = 0.098）.Placental morphometry indicated that the width of the folded bilayer was greater（P = 0.05） in glucosamine-treated gilts. In Exp. 2, litter size did not differ between glucosamine-and glucose-treated sows. However in Exp. 3, the increased dose of glucosamine resulted in a significant treatment by parity interaction（P ≤ 0.01）, in which total piglets born and born alive were greater in glucosamine treated sows of later parity（5 and 6）.Conclusions： These results indicated that glucosamine supplementation increased the width of the folds of the placental bilayer and increased litter size in later parity, intact pregnant commercial sows.展开更多
AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients wi...AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCVRNA were included. Markers of fibrosis progression were assessed. RESULTS： Median duration of infection and time between paired biopsies was 13 （95% CI： 1-28） and 4 （95% CI： 2-16） years respectively. Alaninetransaminase （ALT） activity was normal in 43.4% of cases. 50% demonstrated progression of the necroinflammation and 34% of fibrosis after a median time evolution of 4 years （95% CI： 2-16）. The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression （P = 0.03） was observed in patients with body mass index （BMI） 〉 25. Fibrosis progression correlated with the time interval between biopsies （P = 0.01）. A significant progression of activity （1.7 vs 0.4, P 〈 0.05） or fibrosis （0.9 vs 0.0, P 〈 0.01） was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression（P = 0.003）. Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI 〉 25 and the time interval between 2 biopsies. CONCLUSION： There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI 〉 25.展开更多
文摘The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in arterial blood.P(v-a) CO_2 depends on the cardiac output and the global CO_2 production,and on the complex relationship between PCO_2 and CO_2 content.Experimental and clinical studies support the evidence that P(v-a) CO_2 cannot serve as an indicator of tissue hypoxia,and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO_2generated by the peripheral tissues.P(v-a) CO_2 can be replaced by the central venous-to-arterial CO_2 difference(△PCO_2),which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and,therefore,more easy to obtain at the bedside.Determining the △PCO_2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation(SCVO_2) > 70%associated with elevated blood lactate levels.Because high blood lactate levels is not a discriminatory factor in determining the source of that stress,an increased △PCO_2(> 6 mmHg)could be used to identify patients who still remain inadequately resuscitated.Monitoring the △PCO_2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and,thus,guiding the therapy.In this respect,it can aid to titrate inotropes to adjust oxygen delivery to CO_2 production,or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO_2 related to metabolic demand.The combination of P(v-a) CO_2 or △PCO_2 with oxygen-derived parameters through the calculation of the P(v-a) CO_2 or △PCO_2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.
文摘Litter size and birth weights are limited by uterine capacity, defined as the ability of the uterus to maintain the appropriate development of some number of conceptuses. Uterine capacity is the result of the combined effects of uterine, placental and embryo/fetal function. The number of living conceptuses that the uterus is capable of supporting is greater during early gestation compared to later gestation. Plots of log fetal weight versus log placental weight also indicate that fetal weights are less sensitive to reduced placental weight （and therefore reduced intrauterine space） in early gestation compared to late gestation. However, even in late gestation, mechanisms still exist that maintain fetal growth when the size of the placenta is reduced. One such mechanism is likely to be improved development of the folded placental-epithelial/maternal-epithelial bilayer. Fold depth, and therefore the maternal fetal interactive surface, increases as gestation advances and is greater in placenta from smal fetuses. On the fetal side of the placenta, the epithelial bilayer is embedded in stromal tissue. Glycosaminoglycans are major components of stroma, including hyaluronan and heparan sulfate. Hyaluronidases and heparanases are present within placental tissues, and likely play roles in modification of stromal components to facilitate fold development. Glycosaminoglycans are polymers of forms of glucose （glucosamine, glucuronic acid, iduronic acid） suggesting that glycosaminoglycan synthesis may compete with the glucose needs of the developing fetus. Pig conceptuses are fructogenic, such that a substantial portion of glucose transferred from mother to fetus is converted to fructose. Fructose is an intermediate product in the synthesis of glucosamine from glucose, and glucosamine is linked to regulation of trophoblast cell proliferation through regulation of mTOR. These findings suggest a link between glucose, fructose, glucosamine synthesis, GAG production, and placental morphogenesis, but the details of these i
文摘The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The re- sulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the pre- dictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic suc- cess. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antivi- ral therapy in patients infected by the same HCV geno- type. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Inter- feron pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity. Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non- structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.
基金We acknowledge the Nouvelle-Aquitaine Region,Bordeaux Métropole and SUEZ,le LyRE for mainly funding and supporting this work through the Convention N°AAPR2020-2019-8171810。
文摘Current deep learning approaches are cutting-edge methods for solving classification tasks.Arising transfer learning techniques allows applying large generic model to simple tasks whereas simpler models could be used.Large models raise the major problem of their memory consumption and processor usage and lead to a prohibitive ecological footprint.In that paper,we present a novel visual analytics approach to interactively prune those networks and thus limit that issue.Our technique leverages a novel sparkline matrix visualization technique as well as a novel local metric which evaluates the discriminatory power of a filter to guide the pruning process and make it interpretable.We assess the well-founded of our approach through two realistic case studies and a user study.For both of them,the interactive refinement of the model led to a significantly smaller model having similar prediction accuracy than the original one.
文摘Visualizing social networks,especially an overview emphasizing their structure,i.e.,communities and their interconnections,is known to be a challenging problem.In this paper,we present a set of design rationales to build such overview visualizations of social networks and our solution called Jasper.We evaluate its performances against two of the most wide-spread visualization techniques(matrix and node-link diagram)in a human–computer controlled experiment based on community-related tasks.While none of the techniques emerge as the overwhelming winner,Jasper appears to be one of the best methods for each task;a fact sustained by the marks given by the users.Overall,Jasper can be seen as an all-encompassing solution for quickly producing legible and compact overviews of large social networks on a single modern computer.
文摘This paper is devoted to the existence and the uniqueness of the entropy solution for a general scalar conservation law associated with a forced bilateral obstacle condition in a bounded domain of Rp, p>= 1. The method of penalization is used with a view to obtaining an existence result. However, the former only gives uniform L -estimates and so leads in fact to look for an Entropy Measure-Valued Solution, according to the specific properties of bounded sequences in L . The uniqueness of this EMVS is proved. Classically, it first ensures the existence of a bounded and measurable function U entropy solution and then the strong convergence in Lq of approximate solutions to U.
文摘Transcription factor TFIIA is controlled by complex regulatory networks including proteolysis by the protease Taspase 1, though the full impact of cleavage remains elusive. Here, we demonstrate that in contrast to the general assumption, de novo produced TFIIA is rapidly confined to the cytoplasm via an evolutionary conserved nuclear export signal （NES, amino acids ^21VINDVRDIFL^30）, interacting with the nuclear export receptor Exportin-1/chromosomal region maintenance 1 （Crml）. Chemical export inhibition or genetic inactivation of the NES not only promotes TFIIA＇s nuclear localization but also affects its transcrip- tional activity. Notably, Taspase 1 processing promotes TFIIA＇s nuclear accumulation by NES masking, and modulates its tran- scriptional activity. Moreover, TFIIA complex formation with the TATA box binding protein （TBP） is cooperatively enhanced by inhibition of proteolysis and nuclear export, leading to an increase of the ceil cycle inhibitor p16INK, which is counteracted by pre- vention of TBP binding. We here identified a novel mechanism how proteolysis and nuclear transport cooperatively fine-tune tran- scriptional programs.
文摘Spray drift has become an important issue in pesticide application. Vineyard spraying is particularly interesting to consider, as pesticide droplets are not directed towards the ground but rather towards the targeted crop. The aim of this study was to investigate the influence of nozzle orientation on droplet size and droplet velocity using three different nozzles （IDK, TVI and TXA） used in vineyards. Two series of measurement were performed in order to assess the effect of the gravity on sprays. Droplet size and one-dimensional droplet velocity characteristics were measured using a phase Doppler particle analyser （PDPA）. Two planes, i.e., one horizontal and one vertical, were considered. Results suggest that the nozzle orientation slightly affects the size distribution, which is shifted towards larger droplets when nozzles spray horizontally compared to vertically spray, However, droplet axial velocity distribution is shifted towards lower values. Supposing that the only droplets which can reach the crop are those with an axial velocity greater than 1 m/s and a diameter larger than 100 lain, results showed significant differences according to the nozzle and orientation. More than 98.6% of the spray volume would reach the target whatever the orientation of the IDK nozzle, 78.8% of the spray volume would reach the crop when the TVI nozzle sprays horizontally, while only 16.0% of the spray volume would reach the crop when TXA nozzle sprays horizontally. This paper offers new perspectives in the comprehension and the optimization of the deposition process into the vegetation based from droplet size and velocity profiles from horizontally oriented sprays from flat fan or hollow cone nozzles.
文摘Transmission of cytomegalovirus (CMV) infection frommothers to preterm infants during breastfeeding may be symptomatic and long term consequences are unknown. This study evaluated the kinetics of CMV load in breast milk and the rate of postnatal CMV transmission via breastmilk from mothers to their preterm infants. Methods: Prospective study of mother child pairs after preterm delivery before 33 weeks. Exclusion of donor breast milk and of CMV-seropositive blood products.Material used was maternal CMV serostatus, ear swab of the infant at birth, weekly screened breast milk and children’s urine by rapid viral culture. Results: During a 5-month period 28 mother-infantpairs with 34 preterm infants were studied.Eighteen women (64.3%)were CMV-seronegative at birth;breast milk samples and the infants’ urine remained CMV-negative.Eight of the 10 seropositive mothers, who had 11 preterm infants, excreted CMV into breast milk (80%). CMV excretion into breast milk was detected during the first week after delivery in 66%cases and was at its peaked between 3 to 5 weeks after delivery.Out of the 7 CMV-exposed infants, CMV transmission was confirmed in only one asymptomatic case. Total quantity of breast milk intake did not seem discriminative for CMV transmission.Conclusion: In CMV-seropositive mothers of preterm infants a high incidence of CMV excretion into breast milk was detected. Despite this high rate, symptomatic infection did not occur. However, potential risk and severity of infection may be difficult to establish. Because breastfeeding is beneficial, new procedures for gentle virus inactivation of seropositive breast milk should be assessed.
文摘During pesticide spraying, some of the smallest or slowest droplets do not reach the target and may contribute to spray drift. Therefore, it is important to characterize droplet size and velocity close to the nozzle exit. The aim of this study was to contribute to the comprehension of spray formation. Surfactant influence on spray characteristics was studied by comparing water spray with sprays containing three different surfactants, Two nozzles including a classical hollow cone nozzle ATR （Albuz, France） and an air-induced hollow cone nozzle TVI which is a low-drift nozzle （Albuz, France） were chosen. Radial profiles of the axial velocity component and Sauter mean diameter at two axial distances from the nozzle exit were measured using a Phase Doppler Particle Analyzer （PDPA）. Results showed that sprays issued from ATR and TVI nozzles were very different, even when water was sprayed. Effect of adding surfactant depended on the nozzle type. Sheet thickness was reduced by adding Elton and Heliosol regardless of the nozzle type. They reduced spray angle of ATR nozzle spray but did not affect that of YVI nozzle. Break-Thru has a slight effect when sprayed through the ATR nozzle, but it has the most pronounced effect on the SMD when sprayed through the TVI nozzle.
文摘In plants, resistance to necrotrophic pathogens depends on the interplay between different hormone systems, such as those regulated by salicylic acid （SA）, jasmonic acid （JA）, ethylene, and abscisic acid. Repression of auxin signaling by the SA pathway was recently shown to contribute to antibacterial resistance. Here, we demonstrate that Arabidopsis auxin signaling mutants axrl, axr2, and axr6 that have defects in the auxin-stimulated SCF （Skpl-Cullin- F-box） ubiquitination pathway exhibit increased susceptibility to the necrotrophic fungi Plectosphaerella cucumerina and Botrytis cinerea. Also, stabilization of the auxin transcriptional repressor AXR3 that is normally targeted for removal by the SCF-ubiquitin/proteasome machinery occurs upon P. cucumerina infection. Pharmacological inhibition of auxin transport or proteasome function each compromise necrotroph resistance of wild-type plants to a similar extent as in non-treated auxin response mutants. These results suggest that auxin signaling is important for resistance to the necrotro- phic fungi P. cucumerina and B. cinerea. SGTlb （one of two Arabidopsis SGT1 genes encoding HSP90/HSC70 co-chaperones） promotes the functions of SCF E3-ubiquitin ligase complexes in auxin and JA responses and resistance conditioned by certain Resistance （R） genes to biotrophic pathogens. We find that sgtlb mutants are as resistant to P. cucumerina as wild-type plants. Conversely, auxin/SCF signaling mutants are uncompromised in RPP4-triggered resistance to the obligate biotrophic oomycete, Hyaloperonospora parasitica. Thus, the predominant action of SGTlb in R gene-conditioned resis- tance to oomycetes appears to be at a site other than assisting SCF E3-ubiquitin ligases. However, genetic additivity of sgtlb axrl double mutants in susceptibility to H. parasitica suggests that SCF-mediated ubiquitination contributes to lim- iting biotrophic pathogen colonization once plant-pathogen compatibility is established.
文摘The Arabidopsis heterotrimeric G-protein controls defense responses to necrotrophic and vascular fungi. The agbl mutant impaired in the Gβ subunit displays enhanced susceptibility to these pathogens. Gβ/AGB1 forms an obligate dimer with either one of the Arabidopsis Gγsubunits （γ1/AGG1 and γ2/AGG2）. Accordingly, we now demonstrate that the aggl agg2 double mutant is as susceptible as agbl plants to the necrotrophic fungus Plectosphaerella cucumerina. To elucidate the molecular basis of heterotrimeric G-protein-mediated resistance, we performed a comparative transcriptomic analysis of agbl-1 mutant and wild-type plants upon inoculation with P cucumerina. This analysis, together with metab- olomic studies, demonstrated that G-protein-mediated resistance was independent of defensive pathways required for resistance to necrotrophic fungi, such as the salicylic acid, jasmonic acid, ethylene, abscisic acid, and tryptophan-derived metabolites signaling, as these pathways were not impaired in agbl and aggl agg2 mutants. Notably, many mis-reguiated genes in agbl plants were related with cell wall functions, which was also the case in aggl agg2 mutant. Biochemical analyses and Fourier Transform InfraRed （FTIR） spectroscopy of cell walls from G-protein mutants revealed that the xylose content was lower in agbl and aggl agg2 mutants than in wild-type plants, and that mutant walls had similar FTIR spec-tratypes, which differed from that of wild-type plants. The data presented here suggest a canonical functionality of the Gβ and Gγ1/γ2 subunits in the control of Arabidopsis immune responses and the regulation of cell wall composition.
文摘MYB34, MYB51, and MYB122 transcription factors are known as decisive regulators of indolic glucosinolate （IG） biosynthesis with a strong impact on expression of genes encoding CYP79B2 and CYP79B3 enzymes that redundantly convert tryptophan to indole-3-acetaldoxime （IAOx）. This intermediate represents a branching point for IG biosynthesis, and pathways leading to camalexin and indole-carboxylic acids （ICA）. Here we investigate how these MYBs affect the pathogen-triggered Trp metabolism. Our experiments indicated that these three MYBs affect not only IG production but also constitutive biosynthesis of other IAOx- derived metabolites. Strikingly, the PENETRATION 2 （PEN2）-dependent IG-metabolism products, which are absent in myb34/51/122 and pen2 mutants, were indispensable for full flg22-mediated induction of other IAOx-dedved compounds. However, germ induction and accumulation of ICAs and camalexin upon path- ogen infection was not compromised in myb34/51/122 plants, despite strongly reduced IG levels. Hence, in comparison with cyp79B2/B3, which lacks all IAOx-derived metabolites, we found myb34/51/122 an ideal tool to analyze IG contribution to resistance against the necrotrophic fungal pathogen Plectosphaerella cucumerina. The susceptibility of myb34/51/122 was similar to that of pen2, but much lower than susceptibility of cyp79B2/B3, indicating that MYB34/51/122 contribute to resistance toward P. cucumerina exclu- sively through IG biosynthesis, and that PEN2 is the main leaf myrosinase activating IGs in response to microbial pathogens.
基金support provided by the PID2021-126516NB-I00 project funded by MCIN/AEI/10.13039/501100011033/FEDER,UE.
文摘In this study,we analyze new ways of conceptualizing improvements in firms'innovation by implementing the"right-factors configuration,"illustrated through an analog of a recipe and its ingredients.Specifically,we research the multiple combinations of three ingredients(creativity,innovation networks,and resources)required to accomplish the innovation recipe.Using a sample of firms from a Spanish science and technology park,we apply qualitative comparative analysis(QCA)-specifically,fuzzy-set QCA(fsQCA)-to test the importance of each component in technological and non-technological innovation.First,the results suggest a map of combinations of innovative ingredients with eight possible patterns.Second,they show that the only ingredient needed is the combination of a creative climate and creative intensity.Finally,the methods of obtaining technological and non-technological innovations differ.The implications for management and policymakers are discussed,and directions for future research are highlighted.
基金partially supported by the Nebraska Pork Producers Council[grant number 14–238]
文摘Background： During late gestation the placental epithelial interface becomes highly folded, which involves changes in stromal hyaluronan. Hyaluronan is composed of glucoronate and N-acetyl-glucosamine. We hypothesized that supplementing gestating dams with glucosamine during this time would support placental folded-epithelial-bilayer development and increase litter size. In Exp. 1, gilts were unilaterally hysterectomizedovariectomized（UHO）. UHO gilts were mated and then supplemented daily with 10 g glucosamine（n = 16） or glucose（control, n = 17） from d 85 of gestation until slaughter（d 105）. At slaughter, the number of live fetuses was recorded and each live fetus and its placenta was weighed. Uterine wall samples adjacent to the largest and smallest fetuses within each litter were processed for histology. In Exp. 2, pregnant sows in a commercial sow farm were supplemented with either 10 g glucosamine or glucose daily from d 85 of gestation to farrowing. Total piglets born and born alive were recorded for each litter. In Exp. 3, the same commercial farm and same protocol were used except that the dose of glucosamine and glucose was doubled to 20 g/d.Results： In Exp. 1, the number of live fetuses tended to be greater in glucosamine-treated UHO gilts（P = 0.098）.Placental morphometry indicated that the width of the folded bilayer was greater（P = 0.05） in glucosamine-treated gilts. In Exp. 2, litter size did not differ between glucosamine-and glucose-treated sows. However in Exp. 3, the increased dose of glucosamine resulted in a significant treatment by parity interaction（P ≤ 0.01）, in which total piglets born and born alive were greater in glucosamine treated sows of later parity（5 and 6）.Conclusions： These results indicated that glucosamine supplementation increased the width of the folds of the placental bilayer and increased litter size in later parity, intact pregnant commercial sows.
文摘AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCVRNA were included. Markers of fibrosis progression were assessed. RESULTS： Median duration of infection and time between paired biopsies was 13 （95% CI： 1-28） and 4 （95% CI： 2-16） years respectively. Alaninetransaminase （ALT） activity was normal in 43.4% of cases. 50% demonstrated progression of the necroinflammation and 34% of fibrosis after a median time evolution of 4 years （95% CI： 2-16）. The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression （P = 0.03） was observed in patients with body mass index （BMI） 〉 25. Fibrosis progression correlated with the time interval between biopsies （P = 0.01）. A significant progression of activity （1.7 vs 0.4, P 〈 0.05） or fibrosis （0.9 vs 0.0, P 〈 0.01） was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression（P = 0.003）. Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI 〉 25 and the time interval between 2 biopsies. CONCLUSION： There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI 〉 25.
