The Cr, Zn, Cu, Cd, Pb contents were determined in Cyprinus carpio Linnaeus, Carassius auratus Linnaeus, Hypophthalmichthys molitrix and Aristichthys nobilis, which were caught from Meiliang Bay, Taihu Lake, a large, ...The Cr, Zn, Cu, Cd, Pb contents were determined in Cyprinus carpio Linnaeus, Carassius auratus Linnaeus, Hypophthalmichthys molitrix and Aristichthys nobilis, which were caught from Meiliang Bay, Taihu Lake, a large, shallow and eutrophic lake of China. The results showed that: (1) the Cr, Cu, Pb, Cd contents in the edible parts of the four fish species were much lower than Chinese Food Health Criterion (1994), but the Zn contents were higher than the Criterion; (2) Cd contents were the highest in the liver of fish, Pb contents were almost the same in all organs of fish, Cr contents mainly enriched in the skin and gonads, Zn contents were the highest in the gonad (♀), and Cu contents were the highest in the liver; (3) the total metal accumulation was the greatest in the liver and the lowest in the muscle. The total metal accumulation was the highest in C. auratus L. This investigation indicated that fish products in Taihu Lake were still safe for human consumption, but the amount consumed should be controlled under the Chinese Food Health Criterion to avoid excessive intake of Zn.展开更多
The Taihu Lake,a large shallow lake in the floodplain of the Changjiang(Yangtze) River in the eastern China,is faced with challenging ecological problems resulting from eutrophication,which has affected the regional f...The Taihu Lake,a large shallow lake in the floodplain of the Changjiang(Yangtze) River in the eastern China,is faced with challenging ecological problems resulting from eutrophication,which has affected the regional freshwater supply of a large population.Although efforts have been made to assess the nutrient evolution histories in the northern bays,little is known regarding nutrient histories in different parts across the entire lake basin.In this paper,we present nutrient histories for different parts of the lake based on chironomid transfer functions applied to four short cores obtained from the northern,western and eastern regions of the lake.The chironomid-inferred total phosphorus(CI-TP) concentrations were compared with the phosphorus concentrations obtained by using instrumental and sedimentary data.The results suggest that trophic evolution histories were asynchronous throughout the lake during the past decades in response to different ecological regimes controlled by the nutrient input,wind direction and shoreline topography.The restoration of aquatic plants may be an effective option for the management of lake rehabilitation to ′natural′ conditions.Given the multiple factors controlling the biotic communities in such a large and complex lake,combined analyses among the multi-proxies encountered in the sediments are necessary for comprehensive insight into paleolimnological studies.The spatial heterogeneity in the ecological trajectories within this complicated ecosystem suggests that different management practices should be undertaken for specific lake zones in the Taihu Lake.展开更多
Saccharomyces cerevisiae is a key component of beer brewing and a major by-product. The leftover, spent brewers’ yeast from large breweries has been used as a protein supplement in cattle;however the possible advanta...Saccharomyces cerevisiae is a key component of beer brewing and a major by-product. The leftover, spent brewers’ yeast from large breweries has been used as a protein supplement in cattle;however the possible advantages of spent yeast from smaller craft breweries, containing much higher levels of bioactive hop acids, have not been evaluated. Hops secondary metabolites from the hops (Humulus lupulus L.) used to make beer are concentrated in the yeast during brewing, and have antimicrobial activity against Gram-positive bacteria. Uncultivated suspensions of bovine rumen microorganisms produced less methane during fructose fermentation when exposed to inactivated, and freeze-dried spent craft brewers’ yeast than a bakers’ yeast control. The experiment was repeated with caprine rumen microorganisms and ground grass hay as the substrate. Likewise, in the presence of craft brewers’ yeast less methane was produced (2.7% vs. 6.9% CH<sub>4</sub>). Both experiments also revealed a decrease in acetic acid production, but not propionic acid production, when craft brewers’ yeast was included. These results indicated that spent yeast could represent a co-product for craft breweries, and a feed supplement for ruminants that has a favorable impact on methane production.展开更多
This study investigated loads among five fixation types (FT) [three cannulated screws (CS), dynamic hip screws with and without derotational screws (DHS-DS and DHS), and dynamic helical hip screws with and without der...This study investigated loads among five fixation types (FT) [three cannulated screws (CS), dynamic hip screws with and without derotational screws (DHS-DS and DHS), and dynamic helical hip screws with and without derotational screws (DHHS-DS and DHHS)] across three fracture moment lengths (ML) in Pauwels’ Type III fractures. Methods: Seventy-five sawbones were tested (5 FT × 5 trials × 3 ML). The study hypothesis was that significant differences in axial loading to failure would be demonstrated when CS was compared with the other four FT at the three MLs. Each construct was exposed to an axial compressive load to failure. Construct failure was defined as 5 mm of migration at the fracture site or fixation failure. Shapiro-Wilk was used to test for data normality. Subsequently, independent t-tests with Bonferroni correction was used for paired comparisons. Results: At fracture Moments A and B there were no statistical differences between CS and the other FT. At fracture Moment C all four FT yielded significantly higher (p ≤ 0.001) loads compared with CS. Conclusions: for basicervical fractures CS is a suboptimal form of fixation compared with DHS and DHHS both with and without derotation screws.展开更多
Tolpyralate is a new benzoylpyrazole herbicide for weed management in corn. It is recommended to be co-applied with atrazine along with the adjuvants methylated seed oil concentrate (MSO) plus an ammonium nitrogen fer...Tolpyralate is a new benzoylpyrazole herbicide for weed management in corn. It is recommended to be co-applied with atrazine along with the adjuvants methylated seed oil concentrate (MSO) plus an ammonium nitrogen fertilizer, such as urea ammonium nitrate (UAN). Two studies were conducted on glyphosate-resistant (GR) Canada fleabane and GR waterhemp to determine if an additional adjuvant is still required when tolpyralate plus atrazine are tankmixed with a commercial glyphosate formulation (Roundup WeatherMAX®) in corn. Trials were conducted over a two-year period (2018-19) on farms in south western Ontario with confirmed GR populations. When co-applied with Roundup WeatherMAX®, the addition of MSO to tolpyralate + atrazine increased control of GR waterhemp 9%;however, there was no increase in GR Canada fleabane control from the addition of additional adjuvants. At 8 WAA, all treatments provided > 91% and > 84% control of GR waterhemp and GR Canada fleabane, respectively. This study concludes that the addition of Roundup WeatherMAX®to tolpyralate plus atrazine improves the control of GR waterhemp and GR Canada fleabane in corn.展开更多
Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the ...Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor(ER) as the direct(for tamoxifen and fulvestrant) or indirect(for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant(pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogenregulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.展开更多
Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors(especially...Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors(especially HER1/EGFR and HER2/ERBB2) are involved in disease progression; hence, strategies to inhibit their action could prove advantageous in ovarian cancer patients,especially in patients resistant to first line therapy. Monoclonal antibodies and tyrosine kinase inhibitors are two classes of drugs that act on these receptors. They have demonstrated valuable antitumor activity in multiple cancers and their possible use in ovarian cancer continues to be studied. In this review, we discuss the human epidermal growth factor receptor family; review emerging clinical studies on monoclonal antibodies and tyrosine kinase inhibitors targeting these receptors in ovarian cancer patients; and propose future research possibilities in this area.展开更多
Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s population.The most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human VEGFA.Alth...Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s population.The most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human VEGFA.Although bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in mice.Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(CD64)and c-Cbl,impairing macrophage migration.Other approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized mice.This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated signaling.Furthermore,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice.Finally,mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis.These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.展开更多
We consider scattering of a time harmonic incident plane wave by a convex polygon with piecewise constant impedance boundary conditions.Standard finite or boundary element methods require the number of degrees of free...We consider scattering of a time harmonic incident plane wave by a convex polygon with piecewise constant impedance boundary conditions.Standard finite or boundary element methods require the number of degrees of freedom to grow at least linearly with respect to the frequency of the incident wave in order to maintain accuracy.Extending earlier work by Chandler-Wilde and Langdon for the sound soft problem,we propose a novel Galerkin boundary element method,with the approximation space consisting of the products of plane waves with piecewise polynomials supported on a graded mesh with smaller elements closer to the corners of the polygon.Theoretical analysis and numerical results suggest that the number of degrees of freedom required to achieve a prescribed level of accuracy grows only logarithmically with respect to the frequency of the incident wave.展开更多
Tolpyralate is a new HPPD-inhibiting herbicide that is efficacious on annual grass and broadleaf weed species in corn. For maximum herbicide performance of tolpyralate, it is recommended that atrazine is tank mixed wi...Tolpyralate is a new HPPD-inhibiting herbicide that is efficacious on annual grass and broadleaf weed species in corn. For maximum herbicide performance of tolpyralate, it is recommended that atrazine is tank mixed with tolpyralate along with the adjuvants methylated seed oil concentrate (MSO) plus urea ammonia nitrate (UAN). A common use pattern of tolpyralate plus atrazine will be in a tank mix with Roundup WeatherMAX®due to the high proportion of corn acres that are seeded to Roundup Ready®hybrids in Eastern Canada. There is no information in the peer-reviewed literature if the adjuvant system in Roundup WeatherMAX®is adequate for optimal herbicide performance of tolpyralate plus atrazine, or if MSO and UAN are still required. Six field trials were conducted over two years near Ridgetown and Exeter, ON, Canada to determine if adjuvants are still required when tolpyralate plus atrazine is tank mixed with Roundup WeatherMAX®in corn. Tolpyralate plus atrazine plus MSO and Roundup WeatherMAX®plus tolpyralate plus atrazine provided excellent control of velvetleaf, pigweed spp, common ragweed, lambsquarters, ladysthumb, wild mustard, flower-of-an-hour, barnyardgrass and green foxtail in this study. Results of this study show that in the absence of Roundup WeatherMAX®, weed control with tolpyralate plus atrazine was improved substantially with the addition of MSO;however, there was little to no increase in weed control with the addition of UAN. When tolpyralate plus atrazine was co-applied with Roundup WeatherMAX®, there was no improvement in weed control with the addition of MSO and/or UAN.展开更多
Tolpyralate is a benzoylpyrazole, 4-hydroxyphenyl-pyruvate dioxygenase inhibitor, and a herbicide registered for use in corn. The efficacy of tolpyralate plus atrazine to provide full-season residual control of glypho...Tolpyralate is a benzoylpyrazole, 4-hydroxyphenyl-pyruvate dioxygenase inhibitor, and a herbicide registered for use in corn. The efficacy of tolpyralate plus atrazine to provide full-season residual control of glyphosate-resistant (GR) Canada fleabane in corn is not known under Ontario environmental conditions. Five field trials were completed over a two-year period (2018-19) in south-western Ontario on farms with confirmed GR Canada fleabane [Conyza canadensis (L.) Cronq.] populations to determine if tolpyralate + atrazine provides full-season residual control of GR Canada fleabane in corn. Corn injury was less than 10% with all treatments. At 4 weeks after application (WAA), tolpyralate (30 g·ai·ha−1), tolpyralate (40 g·ai·ha−1), and atrazine (560 g·ai·ha−1) controlled GR Canada fleabane 64, 78 and 72%, respectively. A tank mix of tolpyralate + atrazine at both rates improved GR Canada fleabane control to 94%. Saflufenacil/dimethenamid-p, mesotrione + atrazine, and dicamba/atrazine controlled GR Canada fleabane 99, 95 and 92%, respectively. At 8 WAA, tolpyralate (30 g·ai·ha−1), tolpyralate (40 g·ai·ha−1) and atrazine (560 g·ai·ha−1) controlled GR Canada fleabane 83, 88, and 83%, respectively (Table 2). The tank mixes of tolpyralate (30 g·ai·ha−1) + atrazine (560 g·ai·ha−1) and tolpyralate (40 g·ai·ha−1) + atrazine (560 g·ai·ha−1) controlled GR Canada fleabane 94, and 97%, respectively, 8 WAA which was similar to saflufenacil/dimethenamid-p, mesotrione + atrazine and dicamba/atrazine. There was no treatment difference for corn yield. Based on these results, tolpyralate (40 g·ha−1), tolpyralate (30 g·ha−1) + atrazine and tolpyralate (40 g·ha−1) + atrazine, applied PRE, provided similar control of GR Canada fleabane as current industry standards at 8 WAA.展开更多
AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was adminis...AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was administered to rats chronically treated with either△^(9)-tetrahydrocannabinol(THC)or vehicle.Subjects were then injected with either SR141716A or vehicle and behavior was observed for 1 h.RESULTS:Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al(1995)produced a profound withdrawal syndrome.Treatment with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the syndrome.CONCLUSION:It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome.展开更多
Dear Editor,Time-lapse videography of human embryos allows for the easy visualization of the embryos without removing them from the protective environment of the incubator[1],the measurement of various morphokinetic(q...Dear Editor,Time-lapse videography of human embryos allows for the easy visualization of the embryos without removing them from the protective environment of the incubator[1],the measurement of various morphokinetic(quantitative)parameters[2],and the identification of abnormalities of growth(qualitative parameters)such as direct cleavage[3],reverse cleavage[4]and intercellular contact of blastomeres[5].展开更多
Magnesium alloys are of considerable current interest for use as degradable implants due to their unique properties including biodegrad-ability,biocompatibility,low density and adequate mechanical properties.Neverthel...Magnesium alloys are of considerable current interest for use as degradable implants due to their unique properties including biodegrad-ability,biocompatibility,low density and adequate mechanical properties.Nevertheless,there is a need to further improve these properties either by alloying or through the use of appropriate processing.Among the different biodegradable Mg alloys now in use,the Mg-Zn series are of special interest and have been the subject of many research investigations.This is primarily because Zn is an essential element for the human body in addition to its positive effects in improving the mechanical strength and lowering the degradation rate of the implant.The properties of Mg-Zn alloys may be further improved both through the addition of third and fourth alloying elements such as Ca,Ag,Sn or Sr and/or by thermo-mechanical processing where the latter is more environmentally and economically favorable.In practice,procedures based on the application of severe plastic deformation(SPD)are especially suited to produce fine-grained microstructures with improved mechanical,degradation and cell behavior.Equal-channel angular pressing(ECAP)is a popular SPD technique that has the capability of pro-ducing bulk materials that are sufficiently large for use as typical implants.Accordingly,this review is designed to provide a comprehensive summary of the research that has been undertaken on ECAP-processed biodegradable Mg-Zn alloys.展开更多
Nanoscale metallic multilayers(NMMs)have attracted significant attention owing to their enhanced me-chanical properties and excellent thermal stability.However,the underlying deformation mechanisms of the high-tempera...Nanoscale metallic multilayers(NMMs)have attracted significant attention owing to their enhanced me-chanical properties and excellent thermal stability.However,the underlying deformation mechanisms of the high-temperature annealed microstructures have not been well clarified.In this study,the effect of annealing temperatures(500,600,700,800,and 1000℃)on the microstructural evolution and mechan-ical properties of Cu/Nb NMMs was investigated systematically.The results show that when the anneal-ing temperature is lower than 800℃the Cu/Nb NMMs maintain their initial continuous nanolayered structure.As the annealing temperature reaches 1000℃,a thermal instability,driven by thermal grain boundary grooving and a Rayleigh instability,leads to the pinching offof the nanolayered structure and even a complete disintegration into an equiaxed grain structure.Uniaxial tensile tests show that 1000℃annealed samples exhibit an enhanced strain hardening capability compared to as-rolled NMMs and this imparts superior ultimate tensile strength(∼492 MPa)and a high elongation(∼20%).TEM observations demonstrate that high-density entangled dislocations exist in the Cu-Nb interface and layers after tensile testing of the high-temperature annealed samples.The dislocation tangles lead to stable and progres-sive strain hardening which is the dominant factor in determining the superior combination of strength and ductility of the high-temperature annealed samples.Thus,this study offers a promising strategy for evading the strength-ductility dilemma and instead promotes a more in-depth understanding of the de-formation mechanisms of heterostructured materials.展开更多
基金Projects supported by the National Natural Science Foundation of China(No.40673078,40203007).
文摘The Cr, Zn, Cu, Cd, Pb contents were determined in Cyprinus carpio Linnaeus, Carassius auratus Linnaeus, Hypophthalmichthys molitrix and Aristichthys nobilis, which were caught from Meiliang Bay, Taihu Lake, a large, shallow and eutrophic lake of China. The results showed that: (1) the Cr, Cu, Pb, Cd contents in the edible parts of the four fish species were much lower than Chinese Food Health Criterion (1994), but the Zn contents were higher than the Criterion; (2) Cd contents were the highest in the liver of fish, Pb contents were almost the same in all organs of fish, Cr contents mainly enriched in the skin and gonads, Zn contents were the highest in the gonad (♀), and Cu contents were the highest in the liver; (3) the total metal accumulation was the greatest in the liver and the lowest in the muscle. The total metal accumulation was the highest in C. auratus L. This investigation indicated that fish products in Taihu Lake were still safe for human consumption, but the amount consumed should be controlled under the Chinese Food Health Criterion to avoid excessive intake of Zn.
基金Under the auspices of National Basic Research Program of China(No.2012CB9561002008CB418103)National Natural Science Foundation of China(No.41072267)
文摘The Taihu Lake,a large shallow lake in the floodplain of the Changjiang(Yangtze) River in the eastern China,is faced with challenging ecological problems resulting from eutrophication,which has affected the regional freshwater supply of a large population.Although efforts have been made to assess the nutrient evolution histories in the northern bays,little is known regarding nutrient histories in different parts across the entire lake basin.In this paper,we present nutrient histories for different parts of the lake based on chironomid transfer functions applied to four short cores obtained from the northern,western and eastern regions of the lake.The chironomid-inferred total phosphorus(CI-TP) concentrations were compared with the phosphorus concentrations obtained by using instrumental and sedimentary data.The results suggest that trophic evolution histories were asynchronous throughout the lake during the past decades in response to different ecological regimes controlled by the nutrient input,wind direction and shoreline topography.The restoration of aquatic plants may be an effective option for the management of lake rehabilitation to ′natural′ conditions.Given the multiple factors controlling the biotic communities in such a large and complex lake,combined analyses among the multi-proxies encountered in the sediments are necessary for comprehensive insight into paleolimnological studies.The spatial heterogeneity in the ecological trajectories within this complicated ecosystem suggests that different management practices should be undertaken for specific lake zones in the Taihu Lake.
文摘Saccharomyces cerevisiae is a key component of beer brewing and a major by-product. The leftover, spent brewers’ yeast from large breweries has been used as a protein supplement in cattle;however the possible advantages of spent yeast from smaller craft breweries, containing much higher levels of bioactive hop acids, have not been evaluated. Hops secondary metabolites from the hops (Humulus lupulus L.) used to make beer are concentrated in the yeast during brewing, and have antimicrobial activity against Gram-positive bacteria. Uncultivated suspensions of bovine rumen microorganisms produced less methane during fructose fermentation when exposed to inactivated, and freeze-dried spent craft brewers’ yeast than a bakers’ yeast control. The experiment was repeated with caprine rumen microorganisms and ground grass hay as the substrate. Likewise, in the presence of craft brewers’ yeast less methane was produced (2.7% vs. 6.9% CH<sub>4</sub>). Both experiments also revealed a decrease in acetic acid production, but not propionic acid production, when craft brewers’ yeast was included. These results indicated that spent yeast could represent a co-product for craft breweries, and a feed supplement for ruminants that has a favorable impact on methane production.
文摘This study investigated loads among five fixation types (FT) [three cannulated screws (CS), dynamic hip screws with and without derotational screws (DHS-DS and DHS), and dynamic helical hip screws with and without derotational screws (DHHS-DS and DHHS)] across three fracture moment lengths (ML) in Pauwels’ Type III fractures. Methods: Seventy-five sawbones were tested (5 FT × 5 trials × 3 ML). The study hypothesis was that significant differences in axial loading to failure would be demonstrated when CS was compared with the other four FT at the three MLs. Each construct was exposed to an axial compressive load to failure. Construct failure was defined as 5 mm of migration at the fracture site or fixation failure. Shapiro-Wilk was used to test for data normality. Subsequently, independent t-tests with Bonferroni correction was used for paired comparisons. Results: At fracture Moments A and B there were no statistical differences between CS and the other FT. At fracture Moment C all four FT yielded significantly higher (p ≤ 0.001) loads compared with CS. Conclusions: for basicervical fractures CS is a suboptimal form of fixation compared with DHS and DHHS both with and without derotation screws.
文摘Tolpyralate is a new benzoylpyrazole herbicide for weed management in corn. It is recommended to be co-applied with atrazine along with the adjuvants methylated seed oil concentrate (MSO) plus an ammonium nitrogen fertilizer, such as urea ammonium nitrate (UAN). Two studies were conducted on glyphosate-resistant (GR) Canada fleabane and GR waterhemp to determine if an additional adjuvant is still required when tolpyralate plus atrazine are tankmixed with a commercial glyphosate formulation (Roundup WeatherMAX®) in corn. Trials were conducted over a two-year period (2018-19) on farms in south western Ontario with confirmed GR populations. When co-applied with Roundup WeatherMAX®, the addition of MSO to tolpyralate + atrazine increased control of GR waterhemp 9%;however, there was no increase in GR Canada fleabane control from the addition of additional adjuvants. At 8 WAA, all treatments provided > 91% and > 84% control of GR waterhemp and GR Canada fleabane, respectively. This study concludes that the addition of Roundup WeatherMAX®to tolpyralate plus atrazine improves the control of GR waterhemp and GR Canada fleabane in corn.
文摘Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor(ER) as the direct(for tamoxifen and fulvestrant) or indirect(for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant(pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogenregulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.
基金The work disclosed in this publication is partially funded by the Endeavour Scholarship Scheme (Malta) Scholarships are part-financed by the European Union–European Social Fund (ESF)–Operational Program II–Cohesion Policy 2014–2020 "Investing in human capital to create more opportunities and promote the well-being of society"
文摘Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors(especially HER1/EGFR and HER2/ERBB2) are involved in disease progression; hence, strategies to inhibit their action could prove advantageous in ovarian cancer patients,especially in patients resistant to first line therapy. Monoclonal antibodies and tyrosine kinase inhibitors are two classes of drugs that act on these receptors. They have demonstrated valuable antitumor activity in multiple cancers and their possible use in ovarian cancer continues to be studied. In this review, we discuss the human epidermal growth factor receptor family; review emerging clinical studies on monoclonal antibodies and tyrosine kinase inhibitors targeting these receptors in ovarian cancer patients; and propose future research possibilities in this area.
文摘Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s population.The most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human VEGFA.Although bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in mice.Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(CD64)and c-Cbl,impairing macrophage migration.Other approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized mice.This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated signaling.Furthermore,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice.Finally,mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis.These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.
文摘We consider scattering of a time harmonic incident plane wave by a convex polygon with piecewise constant impedance boundary conditions.Standard finite or boundary element methods require the number of degrees of freedom to grow at least linearly with respect to the frequency of the incident wave in order to maintain accuracy.Extending earlier work by Chandler-Wilde and Langdon for the sound soft problem,we propose a novel Galerkin boundary element method,with the approximation space consisting of the products of plane waves with piecewise polynomials supported on a graded mesh with smaller elements closer to the corners of the polygon.Theoretical analysis and numerical results suggest that the number of degrees of freedom required to achieve a prescribed level of accuracy grows only logarithmically with respect to the frequency of the incident wave.
文摘Tolpyralate is a new HPPD-inhibiting herbicide that is efficacious on annual grass and broadleaf weed species in corn. For maximum herbicide performance of tolpyralate, it is recommended that atrazine is tank mixed with tolpyralate along with the adjuvants methylated seed oil concentrate (MSO) plus urea ammonia nitrate (UAN). A common use pattern of tolpyralate plus atrazine will be in a tank mix with Roundup WeatherMAX®due to the high proportion of corn acres that are seeded to Roundup Ready®hybrids in Eastern Canada. There is no information in the peer-reviewed literature if the adjuvant system in Roundup WeatherMAX®is adequate for optimal herbicide performance of tolpyralate plus atrazine, or if MSO and UAN are still required. Six field trials were conducted over two years near Ridgetown and Exeter, ON, Canada to determine if adjuvants are still required when tolpyralate plus atrazine is tank mixed with Roundup WeatherMAX®in corn. Tolpyralate plus atrazine plus MSO and Roundup WeatherMAX®plus tolpyralate plus atrazine provided excellent control of velvetleaf, pigweed spp, common ragweed, lambsquarters, ladysthumb, wild mustard, flower-of-an-hour, barnyardgrass and green foxtail in this study. Results of this study show that in the absence of Roundup WeatherMAX®, weed control with tolpyralate plus atrazine was improved substantially with the addition of MSO;however, there was little to no increase in weed control with the addition of UAN. When tolpyralate plus atrazine was co-applied with Roundup WeatherMAX®, there was no improvement in weed control with the addition of MSO and/or UAN.
文摘Tolpyralate is a benzoylpyrazole, 4-hydroxyphenyl-pyruvate dioxygenase inhibitor, and a herbicide registered for use in corn. The efficacy of tolpyralate plus atrazine to provide full-season residual control of glyphosate-resistant (GR) Canada fleabane in corn is not known under Ontario environmental conditions. Five field trials were completed over a two-year period (2018-19) in south-western Ontario on farms with confirmed GR Canada fleabane [Conyza canadensis (L.) Cronq.] populations to determine if tolpyralate + atrazine provides full-season residual control of GR Canada fleabane in corn. Corn injury was less than 10% with all treatments. At 4 weeks after application (WAA), tolpyralate (30 g·ai·ha−1), tolpyralate (40 g·ai·ha−1), and atrazine (560 g·ai·ha−1) controlled GR Canada fleabane 64, 78 and 72%, respectively. A tank mix of tolpyralate + atrazine at both rates improved GR Canada fleabane control to 94%. Saflufenacil/dimethenamid-p, mesotrione + atrazine, and dicamba/atrazine controlled GR Canada fleabane 99, 95 and 92%, respectively. At 8 WAA, tolpyralate (30 g·ai·ha−1), tolpyralate (40 g·ai·ha−1) and atrazine (560 g·ai·ha−1) controlled GR Canada fleabane 83, 88, and 83%, respectively (Table 2). The tank mixes of tolpyralate (30 g·ai·ha−1) + atrazine (560 g·ai·ha−1) and tolpyralate (40 g·ai·ha−1) + atrazine (560 g·ai·ha−1) controlled GR Canada fleabane 94, and 97%, respectively, 8 WAA which was similar to saflufenacil/dimethenamid-p, mesotrione + atrazine and dicamba/atrazine. There was no treatment difference for corn yield. Based on these results, tolpyralate (40 g·ha−1), tolpyralate (30 g·ha−1) + atrazine and tolpyralate (40 g·ha−1) + atrazine, applied PRE, provided similar control of GR Canada fleabane as current industry standards at 8 WAA.
文摘AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was administered to rats chronically treated with either△^(9)-tetrahydrocannabinol(THC)or vehicle.Subjects were then injected with either SR141716A or vehicle and behavior was observed for 1 h.RESULTS:Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al(1995)produced a profound withdrawal syndrome.Treatment with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the syndrome.CONCLUSION:It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome.
文摘Dear Editor,Time-lapse videography of human embryos allows for the easy visualization of the embryos without removing them from the protective environment of the incubator[1],the measurement of various morphokinetic(quantitative)parameters[2],and the identification of abnormalities of growth(qualitative parameters)such as direct cleavage[3],reverse cleavage[4]and intercellular contact of blastomeres[5].
基金supported by the European Research Council under Grant Agreement No.267464-SPDMETALS(TGL).
文摘Magnesium alloys are of considerable current interest for use as degradable implants due to their unique properties including biodegrad-ability,biocompatibility,low density and adequate mechanical properties.Nevertheless,there is a need to further improve these properties either by alloying or through the use of appropriate processing.Among the different biodegradable Mg alloys now in use,the Mg-Zn series are of special interest and have been the subject of many research investigations.This is primarily because Zn is an essential element for the human body in addition to its positive effects in improving the mechanical strength and lowering the degradation rate of the implant.The properties of Mg-Zn alloys may be further improved both through the addition of third and fourth alloying elements such as Ca,Ag,Sn or Sr and/or by thermo-mechanical processing where the latter is more environmentally and economically favorable.In practice,procedures based on the application of severe plastic deformation(SPD)are especially suited to produce fine-grained microstructures with improved mechanical,degradation and cell behavior.Equal-channel angular pressing(ECAP)is a popular SPD technique that has the capability of pro-ducing bulk materials that are sufficiently large for use as typical implants.Accordingly,this review is designed to provide a comprehensive summary of the research that has been undertaken on ECAP-processed biodegradable Mg-Zn alloys.
基金supported by the National Natural Science Foun-dation of China under Grant No.51635005the Program of Introducing Talents of Discipline to Universities under grant num-ber B18017Partial support was provided by the European Research Council underERC GrantAgreementNo.267464-SPDMETALS(TGL).
文摘Nanoscale metallic multilayers(NMMs)have attracted significant attention owing to their enhanced me-chanical properties and excellent thermal stability.However,the underlying deformation mechanisms of the high-temperature annealed microstructures have not been well clarified.In this study,the effect of annealing temperatures(500,600,700,800,and 1000℃)on the microstructural evolution and mechan-ical properties of Cu/Nb NMMs was investigated systematically.The results show that when the anneal-ing temperature is lower than 800℃the Cu/Nb NMMs maintain their initial continuous nanolayered structure.As the annealing temperature reaches 1000℃,a thermal instability,driven by thermal grain boundary grooving and a Rayleigh instability,leads to the pinching offof the nanolayered structure and even a complete disintegration into an equiaxed grain structure.Uniaxial tensile tests show that 1000℃annealed samples exhibit an enhanced strain hardening capability compared to as-rolled NMMs and this imparts superior ultimate tensile strength(∼492 MPa)and a high elongation(∼20%).TEM observations demonstrate that high-density entangled dislocations exist in the Cu-Nb interface and layers after tensile testing of the high-temperature annealed samples.The dislocation tangles lead to stable and progres-sive strain hardening which is the dominant factor in determining the superior combination of strength and ductility of the high-temperature annealed samples.Thus,this study offers a promising strategy for evading the strength-ductility dilemma and instead promotes a more in-depth understanding of the de-formation mechanisms of heterostructured materials.