Cancer immunotherapy has greatly advanced in recent years,and PD-1/PD-L1 blocking therapy has become a major pillar of immunotherapy.Successful clinical trials of PD-1/PD-L1 blocking therapies in cancer treatments hav...Cancer immunotherapy has greatly advanced in recent years,and PD-1/PD-L1 blocking therapy has become a major pillar of immunotherapy.Successful clinical trials of PD-1/PD-L1 blocking therapies in cancer treatments have benefited many patients,which promoted the Food and Drug Administration(FDA)approval of PD-1/PD-L1 blocking drugs.In this review,we provide a detailed introduction of five PD-1/PD-L1 blocking drugs,with indications and studies,as a valuable reference for doctors and medical investigators.Moreover,the characteristics of PD-1/PD-L1 blocking therapies,including their universality and sustainability,are discussed in this review.Furthermore,we also discuss and predict the possibility of PD-L1 as an indication marker of PD-1/PD-L1 blocking therapy for pan-cancer treatment,and the current status of combination therapies.展开更多
The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agent...The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro RNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.展开更多
Rigid blocking masses are located in the typical base structure of a power cabin based on the impedance mismatch principle.By combining the acoustic-structural coupling method and statistical energy analysis,the full-...Rigid blocking masses are located in the typical base structure of a power cabin based on the impedance mismatch principle.By combining the acoustic-structural coupling method and statistical energy analysis,the full-band vibration and sound radiation reduction effect of vibration isolation masses located in a base structure was researched.The influence of the blocking mass’ cross-section size and shape parameters and the layout location of the base isolation performance was discussed.Furthermore,the effectiveness of rigid vibration isolation design of the base structure was validated.The results show that the medium and high frequency vibration and sound radiation of a power cabin are effectively reduced by a blocking mass.Concerning weight increment and section requirement,suitably increasing the blocking mass size and section height and reducing section width can result in an efficiency-cost ratio.展开更多
The impact on temperature and precipitation anomalies over the European continent of the different action centers of blocking events in the Euro-Atlantic sector was investigated. It was found that the position of the ...The impact on temperature and precipitation anomalies over the European continent of the different action centers of blocking events in the Euro-Atlantic sector was investigated. It was found that the position of the blocking action center in the Euro-Atlantic region seems to dominate European climates. When the center of the blocking action is in the Greenland region, there is a strong negative temperature anomaly over Central and Northern Europe, as well as a strong positive precipitation anomaly over southern Europe. However, there tends to be a strong negative temperature anomaly in the west(east) part of Europe when the center of the blocking action is shifted to the Eastern Atlantic and west Europe(east Europe). In particular, when the blocking action center is closer to the European continent, the fall in temperature becomes more evident over Central and south Europe than over other regions. Moreover, it was found that when the region where the blocking action center exists changes from the Eastern Atlantic and west Europe region to the east Europe region, the existing region of dominant positive precipitation anomalies varies from southwest Europe to southeast Europe and the Middle East.展开更多
We propose a scheme for realizing an unconventional three-qubit controlled-phase gate via the Rydberg blockade mechanism.The qubit is encoded by atomic ensembles that are trapped in optical traps and fixed on an atom ...We propose a scheme for realizing an unconventional three-qubit controlled-phase gate via the Rydberg blockade mechanism.The qubit is encoded by atomic ensembles that are trapped in optical traps and fixed on an atom chip.Because of the collective nature of the encoding and the Rydberg blockade mechanism,the scheme do not require separate addressing of individual atoms.The time needed for the gate operation is much shorter than that in a similar scheme.In addition,we show the gate can be used as a basic tool for effective generation of large-scale 2D cluster states.展开更多
A square graphene single electron transistor （SET） was defined with two side gates, and its transport was studied at low temperature at T = 2 K. At zero magnetic field, Coulomb blockade oscillations were clearly obs...A square graphene single electron transistor （SET） was defined with two side gates, and its transport was studied at low temperature at T = 2 K. At zero magnetic field, Coulomb blockade oscillations were clearly observed near the Dirac point of this device. At high magnetic field, in the quantum Hall regime, we observed ballistic tunneling of the carders through the graphene SET, contrary to the Coulomb blockades observed while approaching the vicinity of the Dirac point.展开更多
Antigen-specific CD8＋T cells play a critical role in eradicating transformed or virally infected cells. Upon recognition of cancerous or viral originated peptides, presented by antigen-presenting cells （APCs） in th...Antigen-specific CD8＋T cells play a critical role in eradicating transformed or virally infected cells. Upon recognition of cancerous or viral originated peptides, presented by antigen-presenting cells （APCs） in the form of peptide-MHC class I complex, CD8＋T cells become activated, rapidly and extensively proliferate and differentiate into functionally competent effector cells. Following successfully and timely clearing transformed or virally infected cells, the majority of effector CD8＋Tcells die of apoptosis. Concomitantly a small fraction （around 5%-10%） of effector CD8＋T cells survive and progressively differentiate into long-lived and self-renewable memory CD8＋T cells.展开更多
In the famous quantum communication scheme developed by Duan et al.[L.M.Duan,M.D.Lukin,J.I.Cirac,and P.Zoller,Nature(London) 414(2001) 413],the probability of successful generating a symmetric collective atomic state ...In the famous quantum communication scheme developed by Duan et al.[L.M.Duan,M.D.Lukin,J.I.Cirac,and P.Zoller,Nature(London) 414(2001) 413],the probability of successful generating a symmetric collective atomic state with a single-photon emitted have to be far smaller than 1 to obtain an acceptable entangled state.Based on strong dipole-dipole interaction between two Rydberg atoms,two simultaneous excitations in an atomic ensemble are greatly suppressed,which makes it possible to excite a mesoscopic cold atomic ensemble into a near-ideal singly-excited symmetric collective state accompanied by a signal-photon with near unity success probability.展开更多
文摘Cancer immunotherapy has greatly advanced in recent years,and PD-1/PD-L1 blocking therapy has become a major pillar of immunotherapy.Successful clinical trials of PD-1/PD-L1 blocking therapies in cancer treatments have benefited many patients,which promoted the Food and Drug Administration(FDA)approval of PD-1/PD-L1 blocking drugs.In this review,we provide a detailed introduction of five PD-1/PD-L1 blocking drugs,with indications and studies,as a valuable reference for doctors and medical investigators.Moreover,the characteristics of PD-1/PD-L1 blocking therapies,including their universality and sustainability,are discussed in this review.Furthermore,we also discuss and predict the possibility of PD-L1 as an indication marker of PD-1/PD-L1 blocking therapy for pan-cancer treatment,and the current status of combination therapies.
基金supported by National Institutes of Health (NIH/NCATS) grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination(OSC)the NIH/NCI grant 1 R01 CA182905-01+6 种基金a U54 grant-UPR/MDACC Partnership for Excellence in Cancer Research 2016 Pilot Projecta Team DOD (Grant No.CA160445P1) granta Ladies Leukemia League granta CLL Moonshot Flagship projecta SINF 2017 grantthe Estate of C.G.Johnson,Jr.supported by a POC grant, entitled "Clinical and economical impact of personalized targeted anti-microRNA therapies in reconverting lung cancer chemoresistance"-CANTEMIR, Competitively Operational Program, 2014-2020, Grant No.35/01.09.2016,My SMIS 103375
文摘The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro RNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.
基金Supported by the International Cooperation Program under Grant No.2007DFR80340the National Natural Science Foundation of China under Grant No.50779007
文摘Rigid blocking masses are located in the typical base structure of a power cabin based on the impedance mismatch principle.By combining the acoustic-structural coupling method and statistical energy analysis,the full-band vibration and sound radiation reduction effect of vibration isolation masses located in a base structure was researched.The influence of the blocking mass’ cross-section size and shape parameters and the layout location of the base isolation performance was discussed.Furthermore,the effectiveness of rigid vibration isolation design of the base structure was validated.The results show that the medium and high frequency vibration and sound radiation of a power cabin are effectively reduced by a blocking mass.Concerning weight increment and section requirement,suitably increasing the blocking mass size and section height and reducing section width can result in an efficiency-cost ratio.
基金supported by the National Natural Science Foundation of China (Grant No. 41375067)
文摘The impact on temperature and precipitation anomalies over the European continent of the different action centers of blocking events in the Euro-Atlantic sector was investigated. It was found that the position of the blocking action center in the Euro-Atlantic region seems to dominate European climates. When the center of the blocking action is in the Greenland region, there is a strong negative temperature anomaly over Central and Northern Europe, as well as a strong positive precipitation anomaly over southern Europe. However, there tends to be a strong negative temperature anomaly in the west(east) part of Europe when the center of the blocking action is shifted to the Eastern Atlantic and west Europe(east Europe). In particular, when the blocking action center is closer to the European continent, the fall in temperature becomes more evident over Central and south Europe than over other regions. Moreover, it was found that when the region where the blocking action center exists changes from the Eastern Atlantic and west Europe region to the east Europe region, the existing region of dominant positive precipitation anomalies varies from southwest Europe to southeast Europe and the Middle East.
基金supported by the National Natural Science Foundation of China (Grant Nos.61275215 and 11004033)the Natural Science Foundation of Fujian Province (Grant No.2010J01002)the National Fundamental Research Program of China (Grant No.2011CBA00203)
文摘We propose a scheme for realizing an unconventional three-qubit controlled-phase gate via the Rydberg blockade mechanism.The qubit is encoded by atomic ensembles that are trapped in optical traps and fixed on an atom chip.Because of the collective nature of the encoding and the Rydberg blockade mechanism,the scheme do not require separate addressing of individual atoms.The time needed for the gate operation is much shorter than that in a similar scheme.In addition,we show the gate can be used as a basic tool for effective generation of large-scale 2D cluster states.
基金supported by the National Natural Science Foundation of China (Grant No. 10874220)the Main Direction Program of Knowledge Innovation of Chinese Academy of Sciences (Grant No. KJCX2-YW- W30)the Natinal Basic Research Program of China from the MOST (Grant No. 2011CB932704)
文摘A square graphene single electron transistor （SET） was defined with two side gates, and its transport was studied at low temperature at T = 2 K. At zero magnetic field, Coulomb blockade oscillations were clearly observed near the Dirac point of this device. At high magnetic field, in the quantum Hall regime, we observed ballistic tunneling of the carders through the graphene SET, contrary to the Coulomb blockades observed while approaching the vicinity of the Dirac point.
文摘Antigen-specific CD8＋T cells play a critical role in eradicating transformed or virally infected cells. Upon recognition of cancerous or viral originated peptides, presented by antigen-presenting cells （APCs） in the form of peptide-MHC class I complex, CD8＋T cells become activated, rapidly and extensively proliferate and differentiate into functionally competent effector cells. Following successfully and timely clearing transformed or virally infected cells, the majority of effector CD8＋Tcells die of apoptosis. Concomitantly a small fraction （around 5%-10%） of effector CD8＋T cells survive and progressively differentiate into long-lived and self-renewable memory CD8＋T cells.
基金Supported by the National Natural Science Foundation of China under Grant Nos. 61076094,11072218,and 11272287Zhejiang Provincial Natural Science Foundation of China under Grant No. Y6110314Scientific Research Fund of Zhejiang Provincial Education Department under Grant No. Y200909693
文摘In the famous quantum communication scheme developed by Duan et al.[L.M.Duan,M.D.Lukin,J.I.Cirac,and P.Zoller,Nature(London) 414(2001) 413],the probability of successful generating a symmetric collective atomic state with a single-photon emitted have to be far smaller than 1 to obtain an acceptable entangled state.Based on strong dipole-dipole interaction between two Rydberg atoms,two simultaneous excitations in an atomic ensemble are greatly suppressed,which makes it possible to excite a mesoscopic cold atomic ensemble into a near-ideal singly-excited symmetric collective state accompanied by a signal-photon with near unity success probability.
