The challenge of high temperatures in deep mining remains harmful to the health of workers and their production efficiency The addition of phase change materials (PCMs) to filling slurry and the use of the cold storag...The challenge of high temperatures in deep mining remains harmful to the health of workers and their production efficiency The addition of phase change materials (PCMs) to filling slurry and the use of the cold storage function of these materials to reduce downhole temperatures is an effective approach to alleviate the aforementioned problem.Paraffin–CaCl_(2)·6H_(2)O composite PCM was prepared in the laboratory.The composition,phase change latent heat,thermal conductivity,and cemented tailing backfill (CTB) compressive strength of the new material were studied.The heat transfer characteristics and endothermic effect of the PCM were simulated using Fluent software.The results showed the following:(1) The new paraffin–CaCl_(2)·6H_(2)O composite PCM improved the thermal conductivity of native paraffin while avoiding the water solubility of CaCl_(2)·6H_(2)O.(2) The calculation formula of the thermal conductivity of CaCl_(2)·6H_(2)O combined with paraffin was deduced,and the reasons were explained in principle.(3) The“enthalpy–mass scale model”was applied to calculate the phase change latent heat of nonreactive composite PCMs.(4)The addition of the paraffin–CaCl_(2)·6H_(2)O composite PCM reduced the CTB strength but increased its heat absorption capacity.This research can give a theoretical foundation for the use of heat storage backfill in green mines.展开更多
Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018...Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018;Yu et al., 2018). It is frequently mistaken for benign conditions or less aggressive malignancies such as basal cell carcinoma (Muqit et al., 2013), and the effects of delay in diagnosis can be devastating to patients. Aggressive surgical resection is the primary treatment of these tumors and often invoIves orbital exenteration with significant morbidity to patients, and these tumors frequently recur, with local recurrence rate as high as 18%. Importantly, this disease has a high metastatic potential, and there are very limited data guiding systemic treatment options;ultimately 6%—18% of patients diagnosed with SC of the eyelid succumb to metastatic disease (Zurcher et al., 1998;Shields et al., 2004).展开更多
Many cancer types reprogram their metabolism to become addicted to glutamine.One of the critical enzymes in the utilization of glutamine in these cells is glutaminase.CB-839(telaglenastat)is a drug that targets glutam...Many cancer types reprogram their metabolism to become addicted to glutamine.One of the critical enzymes in the utilization of glutamine in these cells is glutaminase.CB-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine metabolism.Despite its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical trials.Thus,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft tumors.Notably,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical trial.This assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.展开更多
The UNESCO label of World Heritage can attract a high number of tourists to heritage properties for their Outstanding Universal Values(OUV).Although international studies have demonstrated the World Heritage system ca...The UNESCO label of World Heritage can attract a high number of tourists to heritage properties for their Outstanding Universal Values(OUV).Although international studies have demonstrated the World Heritage system can contribute to stimulating cultural tourism and boosting the local economy,how this heritage-led development process promotes urban conservation and morphological changes in cities is yet to be explored adequately.This paper aims to explore the urban morphology of a historic Chinese city after its inscription on the UNESCO World Heritage List,taking the Old Town of Lijiang as case.The methods of spatial plan analysis and discourse analysis are used to analyse the data.The research findings have demonstrated that,theoretically,the Conzenian approach of urban morphology can be an effective framework for World Heritage OUV-monitoring.Methodologically,the analysis of spatial plans and multi-stakeholder interviews can reveal local urban morphology from macro to micro levels.Case-specifically in Lijiang,urban physical characteristics and building structures have been well maintained while traditional social fabric and neighbourhood networks have almost vanished.This research has incorporated the urban morphology approach into(world)heritage management in China,as well as worldwide,in order to maintain the balance between urban conservation and economic growth.展开更多
How PD-L1 expression is regulated in cancer is poorly understood.Here,we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers(CRCs).ERBB3 is one of the four ...How PD-L1 expression is regulated in cancer is poorly understood.Here,we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers(CRCs).ERBB3 is one of the four members of the EGF receptor family,all with protein tyrosine kinase domains.ERBB3 is a pseudokinase with a high binding affin-ity to ATP.We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines.The ERBB3 ATP-binding mutant cells dramatically reduce IFN-g-induced PD-L1 expres-sion.Mechanistically,ERBB3 regulates IFN-g-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis.CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells.Knockin of a tumor-derived ERBB3 mutation located in the ki-nase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy,suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune check-point therapy.展开更多
Tis fne book begins with a speech from French President Emmanuel Macron,who appeals for the returning of Africa cultural heritage from European museums to their places of origin,posing the long-standing question of wh...Tis fne book begins with a speech from French President Emmanuel Macron,who appeals for the returning of Africa cultural heritage from European museums to their places of origin,posing the long-standing question of who owns heritage.Tis is the tip of the iceberg of a broader discussion about the role of museums in critical heritage studies,which suggests to refect on their new defnition,bringing together a number of issues such as culture identity,cultural amnesia,cultural alienation and culture discourses for political goals.Against this backdrop,the fve chapters in this book address the distinction between cultural heritage and cultural property,illustrating diferent rationalities of government mobilising a number of global cases.展开更多
基金financial support provided by the National Natural Science Foundation of China (No. 52174106)the Key Technology Research and Development Program (No. 2022YFC2905102)。
文摘The challenge of high temperatures in deep mining remains harmful to the health of workers and their production efficiency The addition of phase change materials (PCMs) to filling slurry and the use of the cold storage function of these materials to reduce downhole temperatures is an effective approach to alleviate the aforementioned problem.Paraffin–CaCl_(2)·6H_(2)O composite PCM was prepared in the laboratory.The composition,phase change latent heat,thermal conductivity,and cemented tailing backfill (CTB) compressive strength of the new material were studied.The heat transfer characteristics and endothermic effect of the PCM were simulated using Fluent software.The results showed the following:(1) The new paraffin–CaCl_(2)·6H_(2)O composite PCM improved the thermal conductivity of native paraffin while avoiding the water solubility of CaCl_(2)·6H_(2)O.(2) The calculation formula of the thermal conductivity of CaCl_(2)·6H_(2)O combined with paraffin was deduced,and the reasons were explained in principle.(3) The“enthalpy–mass scale model”was applied to calculate the phase change latent heat of nonreactive composite PCMs.(4)The addition of the paraffin–CaCl_(2)·6H_(2)O composite PCM reduced the CTB strength but increased its heat absorption capacity.This research can give a theoretical foundation for the use of heat storage backfill in green mines.
基金supported by the merge funding 2016e17, the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicinesupported by the Harrington Physician Scientist Pathway at University Hospitals Cleveland Medical Centerthe Clinical Translational Science Training Program TL1 grant at Case Western Reserve University
文摘Sebaceous carcinoma (SC) of the eyelid is a rare but aggressive malignancy, accounting for 3%—5% of eyelid malignancies in the United States, and up to 35% in Asian populations (Deprez and Uffer, 2009;Xu et al., 2018;Yu et al., 2018). It is frequently mistaken for benign conditions or less aggressive malignancies such as basal cell carcinoma (Muqit et al., 2013), and the effects of delay in diagnosis can be devastating to patients. Aggressive surgical resection is the primary treatment of these tumors and often invoIves orbital exenteration with significant morbidity to patients, and these tumors frequently recur, with local recurrence rate as high as 18%. Importantly, this disease has a high metastatic potential, and there are very limited data guiding systemic treatment options;ultimately 6%—18% of patients diagnosed with SC of the eyelid succumb to metastatic disease (Zurcher et al., 1998;Shields et al., 2004).
基金the Case Comprehensive Cancer Center's K12 award(5K12CA076917-22)the Clinical and Translational Science Collaborative TL1 training grant(1TL1TRO02549-01)+1 种基金NIH grants RO1CA196643,UH2CA223670,P5OCA150964,and P30 CA043703a Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant(SU2C-AACR-DT22-17).Stand Up to Cancer is a program of the Entertainment Industry Foundation.
文摘Many cancer types reprogram their metabolism to become addicted to glutamine.One of the critical enzymes in the utilization of glutamine in these cells is glutaminase.CB-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine metabolism.Despite its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical trials.Thus,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft tumors.Notably,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical trial.This assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.
基金This work was supported by the Fundamental Research Funds for the Central Universities[2682022CX044]the China Postdoctoral Science Foundation[2021M702616].
文摘The UNESCO label of World Heritage can attract a high number of tourists to heritage properties for their Outstanding Universal Values(OUV).Although international studies have demonstrated the World Heritage system can contribute to stimulating cultural tourism and boosting the local economy,how this heritage-led development process promotes urban conservation and morphological changes in cities is yet to be explored adequately.This paper aims to explore the urban morphology of a historic Chinese city after its inscription on the UNESCO World Heritage List,taking the Old Town of Lijiang as case.The methods of spatial plan analysis and discourse analysis are used to analyse the data.The research findings have demonstrated that,theoretically,the Conzenian approach of urban morphology can be an effective framework for World Heritage OUV-monitoring.Methodologically,the analysis of spatial plans and multi-stakeholder interviews can reveal local urban morphology from macro to micro levels.Case-specifically in Lijiang,urban physical characteristics and building structures have been well maintained while traditional social fabric and neighbourhood networks have almost vanished.This research has incorporated the urban morphology approach into(world)heritage management in China,as well as worldwide,in order to maintain the balance between urban conservation and economic growth.
基金supported by the National Institutes of Health(NIH)grants(No.R01CA256791,R01CA264320,P50CA150964,P30CA043703).
文摘How PD-L1 expression is regulated in cancer is poorly understood.Here,we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers(CRCs).ERBB3 is one of the four members of the EGF receptor family,all with protein tyrosine kinase domains.ERBB3 is a pseudokinase with a high binding affin-ity to ATP.We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines.The ERBB3 ATP-binding mutant cells dramatically reduce IFN-g-induced PD-L1 expres-sion.Mechanistically,ERBB3 regulates IFN-g-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis.CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells.Knockin of a tumor-derived ERBB3 mutation located in the ki-nase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy,suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune check-point therapy.
文摘Tis fne book begins with a speech from French President Emmanuel Macron,who appeals for the returning of Africa cultural heritage from European museums to their places of origin,posing the long-standing question of who owns heritage.Tis is the tip of the iceberg of a broader discussion about the role of museums in critical heritage studies,which suggests to refect on their new defnition,bringing together a number of issues such as culture identity,cultural amnesia,cultural alienation and culture discourses for political goals.Against this backdrop,the fve chapters in this book address the distinction between cultural heritage and cultural property,illustrating diferent rationalities of government mobilising a number of global cases.
