Sclerosteosis,an ultra-rare disorder characterised by high bone mass(HBM)and skeletal overgrowth,leads to facial paralysis,hearing loss and raised intracranial pressure,which is currently managed only through high-ris...Sclerosteosis,an ultra-rare disorder characterised by high bone mass(HBM)and skeletal overgrowth,leads to facial paralysis,hearing loss and raised intracranial pressure,which is currently managed only through high-risk surgery.Sclerosteosis is caused by SOST mutations and loss of functional sclerostin,a protein that suppresses osteogenesis by antagonising Wnt/β-catenin signalling.Herein,using in vitro and in vivo approaches,we explore whether LGK974,another potent Wnt inhibitor that targets porcupine(PORCN,Wnt-specific acyltransferase),is a promising sclerosteosis therapeutic.In vitro assays showed that 100 nmol/L LGK974 significantly reduced osteoblast alkaline phosphatase(ALP)activity/mineralisation,decreased Wnt/osteoblast marker(Axin2,Runx2 and Ocn)expression,and downregulated ossification and the Wnt signalling pathway,without affecting osteoclast numbers/resorption.To assess in vivo effects,6-week-old male and female Sost deficient(Sost-/-)mice received LGK974 for 4 weeks and right hindlimbs were subjected to 20 N peak loading to assess mechanoadaptive interactions.µCT revealed significant reductions in vertebral trabecular number and lower cortical bone volume in loaded and non-loaded tibiae in male and female LGK974-treated Sost-/-mice.Interestingly,the target engagement biomarker Axin2 was only significantly reduced in male vertebrae,which may indicate differences in male and female response to LGK974.This study also shows that PORCN inhibition may effectively limit characteristic HBM and skeletal overgrowth in sclerosteosis patients at sites with severe pathology.展开更多
Autism spectrum disorder(ASD)is a multifaceted neurological developmental condition that manifests in several ways.Nearly all autistic children remain undiagnosed before the age of three.Developmental problems affecti...Autism spectrum disorder(ASD)is a multifaceted neurological developmental condition that manifests in several ways.Nearly all autistic children remain undiagnosed before the age of three.Developmental problems affecting face features are often associated with fundamental brain disorders.The facial evolution of newborns with ASD is quite different from that of typically developing children.Early recognition is very significant to aid families and parents in superstition and denial.Distinguishing facial features from typically developing children is an evident manner to detect children analyzed with ASD.Presently,artificial intelligence(AI)significantly contributes to the emerging computer-aided diagnosis(CAD)of autism and to the evolving interactivemethods that aid in the treatment and reintegration of autistic patients.This study introduces an Ensemble of deep learning models based on the autism spectrum disorder detection in facial images(EDLM-ASDDFI)model.The overarching goal of the EDLM-ASDDFI model is to recognize the difference between facial images of individuals with ASD and normal controls.In the EDLM-ASDDFI method,the primary level of data pre-processing is involved by Gabor filtering(GF).Besides,the EDLM-ASDDFI technique applies the MobileNetV2 model to learn complex features from the pre-processed data.For the ASD detection process,the EDLM-ASDDFI method uses ensemble techniques for classification procedure that encompasses long short-term memory(LSTM),deep belief network(DBN),and hybrid kernel extreme learning machine(HKELM).Finally,the hyperparameter selection of the three deep learning(DL)models can be implemented by the design of the crested porcupine optimizer(CPO)technique.An extensive experiment was conducted to emphasize the improved ASD detection performance of the EDLM-ASDDFI method.The simulation outcomes indicated that the EDLM-ASDDFI technique highlighted betterment over other existing models in terms of numerous performance measures.展开更多
Written by Julian Barnes,a well-known contemporary British writer,The Porcupine is a novel with a touch on Bulgaria’s social realities in the early 1990s.However,it is not a realistic novel in a conventional sense.It...Written by Julian Barnes,a well-known contemporary British writer,The Porcupine is a novel with a touch on Bulgaria’s social realities in the early 1990s.However,it is not a realistic novel in a conventional sense.It is composed of forty-three sections,long or short,fragmented in form and laid out by means of montage strategies.In the novel,Barnes used“continuous montage”and“parallel montage”strategies to unveil the plot and tell the story and employed“psychological montage”and“contrast montage”strategies to showcase characters’consciousness and personalities.The ingenious use of different montage strategies in the novel challenges the linear narrative paradigm in traditionally realistic novels,enriches its narrative structures and textual dimensions,and highlights its dramatic conflict,hence reflecting the narrative innovation in Barnes’s fictional writing and providing new space for the studies of his novels from the viewpoint of narratology and/or postmodernism.展开更多
This research study evaluated the effect of different additives on the bait consumption by Indian crested porcupine,a serious forest and agricultural pest,under field conditions.Different additives(saccharin,common sa...This research study evaluated the effect of different additives on the bait consumption by Indian crested porcupine,a serious forest and agricultural pest,under field conditions.Different additives(saccharin,common salt,bone meal,fish meal,peanut butter,egg yolk,egg shell powder,yeast powder,mineral oil and coconut oil)at 2 and 5%each were tested for their relative preference,using groundnut-maize(1:1)as basic bait.All the additives were tested under a no-choice test pattern.For control tests,no additive was mixed with the basic bait.Saccharin at 5%concentration significantly enhanced the consumption of bait over the basic bait,while 2%saccharin supplemented bait resulted in a non-significant bait consumption.All other additives did not enhance the consumption of the bait material;rather,these worked as repellents.However,the repellency was lowest with the common salt,followed by egg yolk,egg shell powder,bone meal,peanut butter,mineral oil,fish meal and yeast powder,while coconut remained the most repellent compound.The present study suggested that groundnut-maize(1:1)supplemented with 5%saccharin was the preferred bait combination,and can be used with different rodenticides for the management of Indian crested porcupine.展开更多
Biogenic opal and calcium carbonate contents in the Quaternary fine-grained sediments in the deep sea coral mound area (Hole U1317E and Hole U1318B drilled by IODP Expedition 307) in Porcupine Seabight, southwest off ...Biogenic opal and calcium carbonate contents in the Quaternary fine-grained sediments in the deep sea coral mound area (Hole U1317E and Hole U1318B drilled by IODP Expedition 307) in Porcupine Seabight, southwest off Ireland, were measured to estimate the primary productivity (Pp) of the surface seawater in NE Atlantic. The results from the two holes commonly show relatively high Pp values of 10-30 g cm-2 ky-1, having stratigraphic cyclicity reversely correlated with the δ13C profile. The high Pp could be attributed to the oceanic setting controlled by the Eastern North Atlantic (Central) Water and Shelf Edge Current, which have been strongly influenced by the obliquity forcing of the Milankovitch cycle. A positive covariance was observed between high Pp and the mound development in U1317E, implying that the organic matter was the principal food source for the mound coral community. It is proposed that the pelagic marl matrix of the mound sediments provides information of the surface water productivity that is useful for reconstructing the paleoceanography and the paleoclimate in the NW Atlantic.展开更多
Objective:To study nematode parasites morphology of Hystrix javanica(H.javanica),both through the feces and internal organs.Methods:Feces were observed by direct smear method,internal organs were observed after dissec...Objective:To study nematode parasites morphology of Hystrix javanica(H.javanica),both through the feces and internal organs.Methods:Feces were observed by direct smear method,internal organs were observed after dissecting the host.Specimens for light microscopy examination were fixed with 70%warm alcohol,cleared and mounted in lactophenol for wet mounting.Specimens for SEM examination were postfixed in cacodylate buffer and glutaraldehyde,dehydrated through a graded series of alcohol and freeze dried.The specimens were attached to stubs with double cello-tape,coated with gold and observed with a JSM5310LV electron microscope.Figures were made with the aid of a drawiug tube attached to Olympus compound microscope,other figures were photographs of scanning electron microscope images.Measurements were given in micrometers as the mean followed by the range in parentheses,unless otherwise stated.Results:The nematode species found in the intestine of H.javanica are Gireterakis girardi and a new species,Trihuris landak.The new species differs with previously reported species from Hystrix because of having stylet and short cervical alae.The pattern of bacillary band is closed to Trichuris trichiurus,the species that infect human,but differs because the surface of its vulva is not covered with densely spine.Conclusions:The species of nematodes found on H.javanica were Gireterakis girardi and a new species Trichuris landak n.sp.Those two species are newly recorded in Indonesia.展开更多
文摘Sclerosteosis,an ultra-rare disorder characterised by high bone mass(HBM)and skeletal overgrowth,leads to facial paralysis,hearing loss and raised intracranial pressure,which is currently managed only through high-risk surgery.Sclerosteosis is caused by SOST mutations and loss of functional sclerostin,a protein that suppresses osteogenesis by antagonising Wnt/β-catenin signalling.Herein,using in vitro and in vivo approaches,we explore whether LGK974,another potent Wnt inhibitor that targets porcupine(PORCN,Wnt-specific acyltransferase),is a promising sclerosteosis therapeutic.In vitro assays showed that 100 nmol/L LGK974 significantly reduced osteoblast alkaline phosphatase(ALP)activity/mineralisation,decreased Wnt/osteoblast marker(Axin2,Runx2 and Ocn)expression,and downregulated ossification and the Wnt signalling pathway,without affecting osteoclast numbers/resorption.To assess in vivo effects,6-week-old male and female Sost deficient(Sost-/-)mice received LGK974 for 4 weeks and right hindlimbs were subjected to 20 N peak loading to assess mechanoadaptive interactions.µCT revealed significant reductions in vertebral trabecular number and lower cortical bone volume in loaded and non-loaded tibiae in male and female LGK974-treated Sost-/-mice.Interestingly,the target engagement biomarker Axin2 was only significantly reduced in male vertebrae,which may indicate differences in male and female response to LGK974.This study also shows that PORCN inhibition may effectively limit characteristic HBM and skeletal overgrowth in sclerosteosis patients at sites with severe pathology.
基金Researchers supporting Project number(RSPD2025R1107),King Saud University,Riyadh,Saudi Arabia.
文摘Autism spectrum disorder(ASD)is a multifaceted neurological developmental condition that manifests in several ways.Nearly all autistic children remain undiagnosed before the age of three.Developmental problems affecting face features are often associated with fundamental brain disorders.The facial evolution of newborns with ASD is quite different from that of typically developing children.Early recognition is very significant to aid families and parents in superstition and denial.Distinguishing facial features from typically developing children is an evident manner to detect children analyzed with ASD.Presently,artificial intelligence(AI)significantly contributes to the emerging computer-aided diagnosis(CAD)of autism and to the evolving interactivemethods that aid in the treatment and reintegration of autistic patients.This study introduces an Ensemble of deep learning models based on the autism spectrum disorder detection in facial images(EDLM-ASDDFI)model.The overarching goal of the EDLM-ASDDFI model is to recognize the difference between facial images of individuals with ASD and normal controls.In the EDLM-ASDDFI method,the primary level of data pre-processing is involved by Gabor filtering(GF).Besides,the EDLM-ASDDFI technique applies the MobileNetV2 model to learn complex features from the pre-processed data.For the ASD detection process,the EDLM-ASDDFI method uses ensemble techniques for classification procedure that encompasses long short-term memory(LSTM),deep belief network(DBN),and hybrid kernel extreme learning machine(HKELM).Finally,the hyperparameter selection of the three deep learning(DL)models can be implemented by the design of the crested porcupine optimizer(CPO)technique.An extensive experiment was conducted to emphasize the improved ASD detection performance of the EDLM-ASDDFI method.The simulation outcomes indicated that the EDLM-ASDDFI technique highlighted betterment over other existing models in terms of numerous performance measures.
文摘Written by Julian Barnes,a well-known contemporary British writer,The Porcupine is a novel with a touch on Bulgaria’s social realities in the early 1990s.However,it is not a realistic novel in a conventional sense.It is composed of forty-three sections,long or short,fragmented in form and laid out by means of montage strategies.In the novel,Barnes used“continuous montage”and“parallel montage”strategies to unveil the plot and tell the story and employed“psychological montage”and“contrast montage”strategies to showcase characters’consciousness and personalities.The ingenious use of different montage strategies in the novel challenges the linear narrative paradigm in traditionally realistic novels,enriches its narrative structures and textual dimensions,and highlights its dramatic conflict,hence reflecting the narrative innovation in Barnes’s fictional writing and providing new space for the studies of his novels from the viewpoint of narratology and/or postmodernism.
基金supported by Higher Education Commission of Pakistanthrough a financial support provided under its Indigenous PhD Fellowship Programme to Muhammad Mushtaq.
文摘This research study evaluated the effect of different additives on the bait consumption by Indian crested porcupine,a serious forest and agricultural pest,under field conditions.Different additives(saccharin,common salt,bone meal,fish meal,peanut butter,egg yolk,egg shell powder,yeast powder,mineral oil and coconut oil)at 2 and 5%each were tested for their relative preference,using groundnut-maize(1:1)as basic bait.All the additives were tested under a no-choice test pattern.For control tests,no additive was mixed with the basic bait.Saccharin at 5%concentration significantly enhanced the consumption of bait over the basic bait,while 2%saccharin supplemented bait resulted in a non-significant bait consumption.All other additives did not enhance the consumption of the bait material;rather,these worked as repellents.However,the repellency was lowest with the common salt,followed by egg yolk,egg shell powder,bone meal,peanut butter,mineral oil,fish meal and yeast powder,while coconut remained the most repellent compound.The present study suggested that groundnut-maize(1:1)supplemented with 5%saccharin was the preferred bait combination,and can be used with different rodenticides for the management of Indian crested porcupine.
基金supported by National Natural Science Foundation of China (Grant Nos. 40772074, 40643017)the Japan Agency for Marine-Earth Science and Technologypartly by the Center for Advanced Marine Core Research, Kochi University
文摘Biogenic opal and calcium carbonate contents in the Quaternary fine-grained sediments in the deep sea coral mound area (Hole U1317E and Hole U1318B drilled by IODP Expedition 307) in Porcupine Seabight, southwest off Ireland, were measured to estimate the primary productivity (Pp) of the surface seawater in NE Atlantic. The results from the two holes commonly show relatively high Pp values of 10-30 g cm-2 ky-1, having stratigraphic cyclicity reversely correlated with the δ13C profile. The high Pp could be attributed to the oceanic setting controlled by the Eastern North Atlantic (Central) Water and Shelf Edge Current, which have been strongly influenced by the obliquity forcing of the Milankovitch cycle. A positive covariance was observed between high Pp and the mound development in U1317E, implying that the organic matter was the principal food source for the mound coral community. It is proposed that the pelagic marl matrix of the mound sediments provides information of the surface water productivity that is useful for reconstructing the paleoceanography and the paleoclimate in the NW Atlantic.
文摘Objective:To study nematode parasites morphology of Hystrix javanica(H.javanica),both through the feces and internal organs.Methods:Feces were observed by direct smear method,internal organs were observed after dissecting the host.Specimens for light microscopy examination were fixed with 70%warm alcohol,cleared and mounted in lactophenol for wet mounting.Specimens for SEM examination were postfixed in cacodylate buffer and glutaraldehyde,dehydrated through a graded series of alcohol and freeze dried.The specimens were attached to stubs with double cello-tape,coated with gold and observed with a JSM5310LV electron microscope.Figures were made with the aid of a drawiug tube attached to Olympus compound microscope,other figures were photographs of scanning electron microscope images.Measurements were given in micrometers as the mean followed by the range in parentheses,unless otherwise stated.Results:The nematode species found in the intestine of H.javanica are Gireterakis girardi and a new species,Trihuris landak.The new species differs with previously reported species from Hystrix because of having stylet and short cervical alae.The pattern of bacillary band is closed to Trichuris trichiurus,the species that infect human,but differs because the surface of its vulva is not covered with densely spine.Conclusions:The species of nematodes found on H.javanica were Gireterakis girardi and a new species Trichuris landak n.sp.Those two species are newly recorded in Indonesia.
