Clustered regulatory interspaced short palindromic repeats(CRISPR)has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade.In the study of ...Clustered regulatory interspaced short palindromic repeats(CRISPR)has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade.In the study of cancer,the CRISPR/CRISPR-associated protein(Cas)system opens new avenues into issues that were once unknown in our knowledge of the non-coding genome,tumor heterogeneity,and precision medicines.CRISPR/Cas-based geneediting technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs(miRNAs).However,the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities.This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy.Furthermore,we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.展开更多
鼓虾噪声是声源级高、频带宽的冲激噪声,对浅海高频声呐和水下通信系统有很强干扰。本文针对实地测量鼓虾噪声声源级存在的多径传播和随机多声源问题,提出一种自动测量实际海域中鼓虾噪声声源级的方法。基于匹配场思想,在一个大孔径垂...鼓虾噪声是声源级高、频带宽的冲激噪声,对浅海高频声呐和水下通信系统有很强干扰。本文针对实地测量鼓虾噪声声源级存在的多径传播和随机多声源问题,提出一种自动测量实际海域中鼓虾噪声声源级的方法。基于匹配场思想,在一个大孔径垂直线阵上对近场的大量鼓虾噪声进行自动定位。利用鼓虾噪声的强冲激特性,使用阈值检测的方法获得鼓虾信号的到达时间,同时将其幅度进行归一化,解决了各声源幅度动态范围相差大的问题。利用射线理论计算近场直达波到达时间作为拷贝场,对数据进行球面波波束形成,解决近场多途多声源定位问题。通过定位结果将接收鼓虾信号的峰峰值声压换算到距离声源1 m处,计算峰峰值声源级。在东海测量的结果显示,该海域的鼓虾噪声峰峰值声源级平均值为173 dB re:1μPa@1 m,50%的测量值在168~175 dB re:1μPa@1 m之间。展开更多
We studied the driving force of the Kuroshio intrusion into the South China Sea （SCS） during the winter monsoon, using satellite-tracked drifters entering the Luzon Strait （LS） through the Balintany and Babuyan Ch...We studied the driving force of the Kuroshio intrusion into the South China Sea （SCS） during the winter monsoon, using satellite-tracked drifters entering the Luzon Strait （LS） through the Balintany and Babuyan Channels from the Philippine Sea. Most drifters passing through the Babuyan Channel in winter entered the interior SCS without a significant change in velocity. However, half of the drifters passing through the Balintany Channel entered the SCS at -30 cn/s, which was faster than when they entered the LS. The other half continued moving northwestward into the Kuroshio and returned to the North Pacific. Quantitative analyses, using surface climatological wind and sea surface height anomaly （SSHa） data explained both the difference in velocity of drifters between the two channels and their acceleration through the Balintany Channel. The results suggest that the positive meridional gradient of sea surface height in the Luzon Strait, caused by the pileup of seawater driven by the Northeast monsoon, as well as Ekman flow, contribute to the Kuroshio intrusion into the SCS through the Babuyan and Balintany Channels. The former may be the main driving force.展开更多
Objective:Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor.However,at present,there is no immune vaccine targeting these cells.Octamer-bindi...Objective:Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor.However,at present,there is no immune vaccine targeting these cells.Octamer-binding transcription factor 4(OCT4),a marker of embryonic stem cells and germ cells,often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development.Methods:To identify the optimal carrier and adjuvant combination,we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein,keyhole limpet hemocyanin(KLH),combined with Toll-like receptor 9 agonist(TLR9).Results:Immunization with OCT4-3+TLR9 produced the strongest immune response in mice.In prevention assays,significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3+TLR9(P<0.01).Importantly,the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9.Meanwhile,multiple cytokines[such as interferon(IFN)-γ(P<0.05),interleukin(IL)-12(P<0.05),IL-2(P<0.01),and IL-6(P<0.05)]promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3+TLR9.Moreover,we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines.Conclusions:Collectively,these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response,leading to the suppression of primary tumor growth in testis embryonic carcinoma.展开更多
The Izu-Bonin arc system is sediment-poor(~400 m thick with no accretionary prism)and,therefore,the influence of the altered oceanic crust(AOC)is most likely the source of the documented along-arc lava compositional v...The Izu-Bonin arc system is sediment-poor(~400 m thick with no accretionary prism)and,therefore,the influence of the altered oceanic crust(AOC)is most likely the source of the documented along-arc lava compositional variations,especially in Pb isotopes.Izu-Bonin arc lava geochemistry suggests an influx of subduction component from an Indian-type AOC.However,samples drilled from the western Pacific geochemical reference site at Integrated Ocean Drilling Program Site 1149 implies subduction of a Pacific-type AOC.To solve the apparent discrepancy of slab input versus arc output in this arc system,samples of the AOC were dredged from vertical fault scarps of the subducting Pacific Plate along a transect from 27.5°N to 34.50 N.Samples range from tholeiitic to mildly alkalic mid-ocean ridge basalts as well as trachybasalts,basaltic trachyandesites,tephrites,and phono-tephrites.Isotope ratios also exhibit a range of values(87Sr/86Sr=0.70282-0.70673,143 Nd/144 Nd=0.512552-0.513174,206Pb/204 Pb=18.43-20.00,207 Pb/204 Pb=15.40-15.67,208Pb/204Pb=37.75-39.55).Our results suggest that there is a geochemical variation in the AOC that is neither completely due to seawater or hydrothermal alteration,nor to petrogenetic processes.Rather,this variation is the result of the Pacific-Izanagi Ridge system tapping into a heterogeneous,plume-polluted mantle source during the Mid-Cretaceous volcanic event.The observed Pacific-type AOC is not responsible for the Indian-type Pb isotopic signature of Izu-Bonin arc lavas.This leads us to propose an alternative scenario where the Izu-Bonin arc lava Indian-type Pb isotopic signature originates from slab-derived fluids interacting and adsorbing Pb from an Indian-type mantle wedge through zone-refining.展开更多
Purpose: To assess retinal nerve fiber layer (RNFL) thickness in patients with human immunodeficiency virus (HIV) disease without cytomegalovirus retinitis (CMV). Design: A casecontrol study. Methods: The study includ...Purpose: To assess retinal nerve fiber layer (RNFL) thickness in patients with human immunodeficiency virus (HIV) disease without cytomegalovirus retinitis (CMV). Design: A casecontrol study. Methods: The study included 113 eyes of 65 patients in one center. Thickness of RNFL along a 3.4- mmdiameter circle centered on the optic nerve head was evaluated using third- generation optical coherence tomography. Patients in group A (39 eyes of 22 patients) were human immunode- ficiency virus- negative control subjects. Group B (36 eyes of 18 patients) was composed of HIV patients with no history of CMVretinitis and CD4 counts consistently above 100. Group C (38 eyes of 25 patients) comprised HIV patients with no history of CMV retinitis but a history of CD4 count less than 100 at some point lasting for at least 6 months. Results: The average RNFL thicknesses in groups A, B, and C were 103.33± 8.50 μ m, 103.30± 9.28 μ m, and 90.10± 12.50 μ m, respectively. Group C had significantly thinner overall RNFL than either of the groups A and B (Tukey- Kramer). This difference was most prominent in temporal, superior, and inferior retinal areas. No differencewas in nasal retinal area, nor between groups A and B in any of the areas. Conclusions: Significant RNFL thinning occurs in HIV patients without CMV retinitis and with low CD4 counts compared with the same subgroup of patients with CD4 count increased to above 100 and HIV- negative control subjects. Third- generation OCT may be useful in diagnosis of early subclinicalHIV- associated visual functional loss.展开更多
There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug develop...There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.展开更多
This paper reviews our present knowledge of the role of the one-carbon cycle in mood disorder and schizophrenia with particular attention to S-adenosyl methionine (SAM). After an historical introduction the clinical d...This paper reviews our present knowledge of the role of the one-carbon cycle in mood disorder and schizophrenia with particular attention to S-adenosyl methionine (SAM). After an historical introduction the clinical data is first reviewed of the anti-depressant action of SAM, in particular a survey of double blind placebo-controlled trials. Then follows an account of the biochemical parameters of the action of SAM, in particular the role of folic acid and 5-methyltetrahydrofolate (vitamin B9), polyamines, homocysteine, together with epigenetic studies. In schizophrenia the effect of oral l-methionine on worsening the symptoms of some chronic schizophrenics has been known since 1961. Recent epigenetic research covered has addressed the mechanism of this reaction. This includes the role of SAM in modulating DNA methyltransferase-1 mRNA activity, cytosine 5-methylation, spine numbers and the expression of mRNAs encoding for reelin and GAD67 in GABAergic neurons in the frontal cortex in schizophrenia. There is also evidence that marker D8S542 located within the methionine sulfoxide reductase (MSRA) gene may be involved in schizophrenia as well as 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. The possible roles of homocysteine and methionine S-adenosyl transferase kinetics are also discussed.展开更多
Study Objective: We studied the overall efficacy of fiberoptic aided intubation using three different supraglottic airways (SGA) as intubation conduits with a standard endotracheal tube (ETT) to determine which, if an...Study Objective: We studied the overall efficacy of fiberoptic aided intubation using three different supraglottic airways (SGA) as intubation conduits with a standard endotracheal tube (ETT) to determine which, if any, is superior as an intubation conduit. Design: After induction of general anesthesia, subjects were randomized to one of three groups: Air-Q ILATM, LMA Classic ExcelTM, and LMA UniqueTM. Subjects were intubated with a fiberoptic aided technique with continuous ventilation with FiO2 = 1.0 through one of these SGAs. The primary endpoint was the overall efficacy of the intubation procedure. In addition, the following data were collected: demographic data, intubation times, grade of view of the larynx, and a visual analog scale (VAS) score of difficulty as determined by the primary anesthesiologist performing the procedure. Data were analyzed using a Kruskal-Wallis one-way analysis of variance and Post hoc analysis was done using Dunn’s Multiple Comparison Test. Results: 126 total subjects were studied. Intubation success rates were 100%, 87.8%, and 95% with the Air-Q ILATM, LMA Classic ExcelTM, and LMA UniqueTM respectively. There was no significant difference among the three different SGAs when comparing the times to place the SGA (T1), the true intubating time (T2), the time to remove the SGA (T3), or the total time (T4). Data were also stratified by the grade of view of the larynx;all grade I views, grade II views, and grade III views were grouped together regardless of the type of the SGA used. The grade I view of the larynx group had significantly faster true intubation times (T2 = 75.1 sec, p = 0.01) and significantly lower VAS scores (VAS = 1.9, P = TM provides the best view of the larynx and is the easiest one to use as an intubation conduit.展开更多
We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian （ALE） hydrodynamics with Adaptive Mesh Refinement （AMR） to connect the continuum to the microstru...We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian （ALE） hydrodynamics with Adaptive Mesh Refinement （AMR） to connect the continuum to the microstructural regimes. The code is unique in its ability to model hot radiating plasmas and cold fragmenting solids. New numerical techniques were developed for many of the physics packages to work efficiently on a dynamically moving and adapting mesh. We use interface reconstruction based on volume fractions of the material components within mixed zones and reconstruct interfaces as needed. This interface reconstruction model is also used for void coalescence and fragmentation. A flexible strength/failure framework allows for pluggable material models, which may require material history arrays to determine the level of accumulated damage or the evolving yield stress in J2 plasticity models. For some applications laser rays are propagating through a virtual composite mesh consisting of the finest resolution representation of the modeled space. A new 2nd order accurate diffusion solver has been implemented for the thermal conduction and radiation transport packages. One application area is the modeling of laser/target effects including debris/shrapnel generation. Other application areas include warm dense matter, EUV lithography, and material wall interactions for fusion devices.展开更多
AIM:To validate the first third-person-rated measure assessing combat-related peritraumatic stress symptoms and evaluate its psychometric properties and war-zone applicability.METHODS:The valid assessment of peritraum...AIM:To validate the first third-person-rated measure assessing combat-related peritraumatic stress symptoms and evaluate its psychometric properties and war-zone applicability.METHODS:The valid assessment of peritraumatic symptoms in the theater of military operations represents a significant challenge in combat-related,mental health research,which mainly relies on retrospective,subjective self-report ratings.This longitudinal observational study used data from actively deployed troops to correlate third-person observer ratings of deployment peritraumatic behaviors[Peritraumatic Behavior Questionnaire-Observer Rated(PBQ-OR)]collected on a bimonthly basis with post-deployment(1-wk follow-up)ratings of the previously validated PBQ self-rate version(PBQ-SR),and(3-mo follow-up)clinician assessed and self-report posttraumatic stress disorder(PTSD)symptoms(Clinician Administered PTSD Scale,PTSD Checklist).Cronbach's alpha(α)and correlation coefficients were calculated to assess internal reliability and concurrent validity respectively.RESULTS:Eight hundred and sixty male Marines were included in this study after signing informed consents at pre-deployment(mean age 23.2±2.6 years).Although our findings were limited by an overall sparse return rate of PBQ-OR ratings,the main results indicate satisfactory psychometric properties with good internal consistency for the PBQ-OR(α=0.88)and high convergent and concurrent validity with 1-wk post-deployment PBQSR ratings and 3-mo posttraumatic stress symptoms.Overall,later PBQ-OR report date was associated with higher correlation between PBQ-OR and postdeployment measures.Kappa analysis between PBQOR and PBQ-SR single items,showed best agreement in questions relating of mortal peril,desire for revenge,and experience of intense physical reactions.Logistic regression demonstrated satisfactory predictive validity of PBQ-OR total score with respect to PTSD caseness(OR=1.0513;95%CI:1.011-1.093;P=0.02).CONCLUSION:Since no comparable tools have been developed,PBQ-OR could be valuable as real-time screening tool for earlier detection of Service Members at risk.展开更多
文摘Clustered regulatory interspaced short palindromic repeats(CRISPR)has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade.In the study of cancer,the CRISPR/CRISPR-associated protein(Cas)system opens new avenues into issues that were once unknown in our knowledge of the non-coding genome,tumor heterogeneity,and precision medicines.CRISPR/Cas-based geneediting technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs(miRNAs).However,the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities.This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy.Furthermore,we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.
文摘鼓虾噪声是声源级高、频带宽的冲激噪声,对浅海高频声呐和水下通信系统有很强干扰。本文针对实地测量鼓虾噪声声源级存在的多径传播和随机多声源问题,提出一种自动测量实际海域中鼓虾噪声声源级的方法。基于匹配场思想,在一个大孔径垂直线阵上对近场的大量鼓虾噪声进行自动定位。利用鼓虾噪声的强冲激特性,使用阈值检测的方法获得鼓虾信号的到达时间,同时将其幅度进行归一化,解决了各声源幅度动态范围相差大的问题。利用射线理论计算近场直达波到达时间作为拷贝场,对数据进行球面波波束形成,解决近场多途多声源定位问题。通过定位结果将接收鼓虾信号的峰峰值声压换算到距离声源1 m处,计算峰峰值声源级。在东海测量的结果显示,该海域的鼓虾噪声峰峰值声源级平均值为173 dB re:1μPa@1 m,50%的测量值在168~175 dB re:1μPa@1 m之间。
基金Supported by the National Basic Research Program of China (973 Program) (Nos. 2007CB816002, 2005CB422303)the National Natural Science Foundation of China (Nos. 40776018, 41176029)
文摘We studied the driving force of the Kuroshio intrusion into the South China Sea （SCS） during the winter monsoon, using satellite-tracked drifters entering the Luzon Strait （LS） through the Balintany and Babuyan Channels from the Philippine Sea. Most drifters passing through the Babuyan Channel in winter entered the interior SCS without a significant change in velocity. However, half of the drifters passing through the Balintany Channel entered the SCS at -30 cn/s, which was faster than when they entered the LS. The other half continued moving northwestward into the Kuroshio and returned to the North Pacific. Quantitative analyses, using surface climatological wind and sea surface height anomaly （SSHa） data explained both the difference in velocity of drifters between the two channels and their acceleration through the Balintany Channel. The results suggest that the positive meridional gradient of sea surface height in the Luzon Strait, caused by the pileup of seawater driven by the Northeast monsoon, as well as Ekman flow, contribute to the Kuroshio intrusion into the SCS through the Babuyan and Balintany Channels. The former may be the main driving force.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant Nos.81803081,81703050,and 21677102)Shenzhen Basic Research Project(Grant Nos.JCYJ20170303160906960,JCYJ20170307100703967,and JCYJ20160331114230843)+2 种基金the Shenzhen International Cooperation Research Project(Grant No.GJHZ20170313111237888)the Subject Layout Project of Shenzhen Science and Technology Creation Commission(Grant Nos.JCYJ20170818092553608 and JCYJ20160331114230843)the China Shenzhen Peacock Innovation Team Project(Grant No.KQTD20140630100658078)。
文摘Objective:Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor.However,at present,there is no immune vaccine targeting these cells.Octamer-binding transcription factor 4(OCT4),a marker of embryonic stem cells and germ cells,often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development.Methods:To identify the optimal carrier and adjuvant combination,we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein,keyhole limpet hemocyanin(KLH),combined with Toll-like receptor 9 agonist(TLR9).Results:Immunization with OCT4-3+TLR9 produced the strongest immune response in mice.In prevention assays,significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3+TLR9(P<0.01).Importantly,the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9.Meanwhile,multiple cytokines[such as interferon(IFN)-γ(P<0.05),interleukin(IL)-12(P<0.05),IL-2(P<0.01),and IL-6(P<0.05)]promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3+TLR9.Moreover,we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines.Conclusions:Collectively,these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response,leading to the suppression of primary tumor growth in testis embryonic carcinoma.
基金funded by the United States National Science Foundation grants(NSF-1333698)to P.Castillo(NSF-1333235)to S.Straub。
文摘The Izu-Bonin arc system is sediment-poor(~400 m thick with no accretionary prism)and,therefore,the influence of the altered oceanic crust(AOC)is most likely the source of the documented along-arc lava compositional variations,especially in Pb isotopes.Izu-Bonin arc lava geochemistry suggests an influx of subduction component from an Indian-type AOC.However,samples drilled from the western Pacific geochemical reference site at Integrated Ocean Drilling Program Site 1149 implies subduction of a Pacific-type AOC.To solve the apparent discrepancy of slab input versus arc output in this arc system,samples of the AOC were dredged from vertical fault scarps of the subducting Pacific Plate along a transect from 27.5°N to 34.50 N.Samples range from tholeiitic to mildly alkalic mid-ocean ridge basalts as well as trachybasalts,basaltic trachyandesites,tephrites,and phono-tephrites.Isotope ratios also exhibit a range of values(87Sr/86Sr=0.70282-0.70673,143 Nd/144 Nd=0.512552-0.513174,206Pb/204 Pb=18.43-20.00,207 Pb/204 Pb=15.40-15.67,208Pb/204Pb=37.75-39.55).Our results suggest that there is a geochemical variation in the AOC that is neither completely due to seawater or hydrothermal alteration,nor to petrogenetic processes.Rather,this variation is the result of the Pacific-Izanagi Ridge system tapping into a heterogeneous,plume-polluted mantle source during the Mid-Cretaceous volcanic event.The observed Pacific-type AOC is not responsible for the Indian-type Pb isotopic signature of Izu-Bonin arc lavas.This leads us to propose an alternative scenario where the Izu-Bonin arc lava Indian-type Pb isotopic signature originates from slab-derived fluids interacting and adsorbing Pb from an Indian-type mantle wedge through zone-refining.
文摘Purpose: To assess retinal nerve fiber layer (RNFL) thickness in patients with human immunodeficiency virus (HIV) disease without cytomegalovirus retinitis (CMV). Design: A casecontrol study. Methods: The study included 113 eyes of 65 patients in one center. Thickness of RNFL along a 3.4- mmdiameter circle centered on the optic nerve head was evaluated using third- generation optical coherence tomography. Patients in group A (39 eyes of 22 patients) were human immunode- ficiency virus- negative control subjects. Group B (36 eyes of 18 patients) was composed of HIV patients with no history of CMVretinitis and CD4 counts consistently above 100. Group C (38 eyes of 25 patients) comprised HIV patients with no history of CMV retinitis but a history of CD4 count less than 100 at some point lasting for at least 6 months. Results: The average RNFL thicknesses in groups A, B, and C were 103.33± 8.50 μ m, 103.30± 9.28 μ m, and 90.10± 12.50 μ m, respectively. Group C had significantly thinner overall RNFL than either of the groups A and B (Tukey- Kramer). This difference was most prominent in temporal, superior, and inferior retinal areas. No differencewas in nasal retinal area, nor between groups A and B in any of the areas. Conclusions: Significant RNFL thinning occurs in HIV patients without CMV retinitis and with low CD4 counts compared with the same subgroup of patients with CD4 count increased to above 100 and HIV- negative control subjects. Third- generation OCT may be useful in diagnosis of early subclinicalHIV- associated visual functional loss.
基金funding from National Institutes of Health(No.1UG3TR003148-01)the American Heart Association(No.442611-NU-80922)+1 种基金California Institute for Regenerative Medicine(No.DISC2COVID19-11838)COVID-19 research funding from David Geffen School of Medicine at UCLA.
文摘There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.
文摘This paper reviews our present knowledge of the role of the one-carbon cycle in mood disorder and schizophrenia with particular attention to S-adenosyl methionine (SAM). After an historical introduction the clinical data is first reviewed of the anti-depressant action of SAM, in particular a survey of double blind placebo-controlled trials. Then follows an account of the biochemical parameters of the action of SAM, in particular the role of folic acid and 5-methyltetrahydrofolate (vitamin B9), polyamines, homocysteine, together with epigenetic studies. In schizophrenia the effect of oral l-methionine on worsening the symptoms of some chronic schizophrenics has been known since 1961. Recent epigenetic research covered has addressed the mechanism of this reaction. This includes the role of SAM in modulating DNA methyltransferase-1 mRNA activity, cytosine 5-methylation, spine numbers and the expression of mRNAs encoding for reelin and GAD67 in GABAergic neurons in the frontal cortex in schizophrenia. There is also evidence that marker D8S542 located within the methionine sulfoxide reductase (MSRA) gene may be involved in schizophrenia as well as 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. The possible roles of homocysteine and methionine S-adenosyl transferase kinetics are also discussed.
文摘Study Objective: We studied the overall efficacy of fiberoptic aided intubation using three different supraglottic airways (SGA) as intubation conduits with a standard endotracheal tube (ETT) to determine which, if any, is superior as an intubation conduit. Design: After induction of general anesthesia, subjects were randomized to one of three groups: Air-Q ILATM, LMA Classic ExcelTM, and LMA UniqueTM. Subjects were intubated with a fiberoptic aided technique with continuous ventilation with FiO2 = 1.0 through one of these SGAs. The primary endpoint was the overall efficacy of the intubation procedure. In addition, the following data were collected: demographic data, intubation times, grade of view of the larynx, and a visual analog scale (VAS) score of difficulty as determined by the primary anesthesiologist performing the procedure. Data were analyzed using a Kruskal-Wallis one-way analysis of variance and Post hoc analysis was done using Dunn’s Multiple Comparison Test. Results: 126 total subjects were studied. Intubation success rates were 100%, 87.8%, and 95% with the Air-Q ILATM, LMA Classic ExcelTM, and LMA UniqueTM respectively. There was no significant difference among the three different SGAs when comparing the times to place the SGA (T1), the true intubating time (T2), the time to remove the SGA (T3), or the total time (T4). Data were also stratified by the grade of view of the larynx;all grade I views, grade II views, and grade III views were grouped together regardless of the type of the SGA used. The grade I view of the larynx group had significantly faster true intubation times (T2 = 75.1 sec, p = 0.01) and significantly lower VAS scores (VAS = 1.9, P = TM provides the best view of the larynx and is the easiest one to use as an intubation conduit.
基金the National Energy Research Scientific Computing Center,a DOE Office of Science User Facility supported by the Office of Science,U. S.Department of Energy under Contract No.DEAC02-05CH11231LBNL under DE-AC0205CH11231 was supported by the Director,Office of Science of the U.S.Department of Energy and the Petascale Initiative in Computational Science and Engineering+1 种基金LLNL was performed under the auspices of the U.S.Department of Energy by Lawrence Livermore National Security,LLC,Lawrence Livermore National Laboratory under Contract DE-AC5207NA27344UCLA and LLNL acknowledge UC Lab Fees Research Grant 09-LR-04-116741-BERA
文摘We have developed a new 3D multi-physics multi-material code, ALE-AMR, which combines Arbitrary Lagrangian Eulerian （ALE） hydrodynamics with Adaptive Mesh Refinement （AMR） to connect the continuum to the microstructural regimes. The code is unique in its ability to model hot radiating plasmas and cold fragmenting solids. New numerical techniques were developed for many of the physics packages to work efficiently on a dynamically moving and adapting mesh. We use interface reconstruction based on volume fractions of the material components within mixed zones and reconstruct interfaces as needed. This interface reconstruction model is also used for void coalescence and fragmentation. A flexible strength/failure framework allows for pluggable material models, which may require material history arrays to determine the level of accumulated damage or the evolving yield stress in J2 plasticity models. For some applications laser rays are propagating through a virtual composite mesh consisting of the finest resolution representation of the modeled space. A new 2nd order accurate diffusion solver has been implemented for the thermal conduction and radiation transport packages. One application area is the modeling of laser/target effects including debris/shrapnel generation. Other application areas include warm dense matter, EUV lithography, and material wall interactions for fusion devices.
基金Supported by The Congressionally Directed Medical Research Programs small(pilot)project mechanism,No.Contract W81XWH-10-1-0693(to Baker DG)It was linked to the MRS study,funded by VA’s Health Services Research and Development Service,No.RDIS 0024the Marine Corps and Navy BUMED,from which pre-and post-deployment data were drawn
文摘AIM:To validate the first third-person-rated measure assessing combat-related peritraumatic stress symptoms and evaluate its psychometric properties and war-zone applicability.METHODS:The valid assessment of peritraumatic symptoms in the theater of military operations represents a significant challenge in combat-related,mental health research,which mainly relies on retrospective,subjective self-report ratings.This longitudinal observational study used data from actively deployed troops to correlate third-person observer ratings of deployment peritraumatic behaviors[Peritraumatic Behavior Questionnaire-Observer Rated(PBQ-OR)]collected on a bimonthly basis with post-deployment(1-wk follow-up)ratings of the previously validated PBQ self-rate version(PBQ-SR),and(3-mo follow-up)clinician assessed and self-report posttraumatic stress disorder(PTSD)symptoms(Clinician Administered PTSD Scale,PTSD Checklist).Cronbach's alpha(α)and correlation coefficients were calculated to assess internal reliability and concurrent validity respectively.RESULTS:Eight hundred and sixty male Marines were included in this study after signing informed consents at pre-deployment(mean age 23.2±2.6 years).Although our findings were limited by an overall sparse return rate of PBQ-OR ratings,the main results indicate satisfactory psychometric properties with good internal consistency for the PBQ-OR(α=0.88)and high convergent and concurrent validity with 1-wk post-deployment PBQSR ratings and 3-mo posttraumatic stress symptoms.Overall,later PBQ-OR report date was associated with higher correlation between PBQ-OR and postdeployment measures.Kappa analysis between PBQOR and PBQ-SR single items,showed best agreement in questions relating of mortal peril,desire for revenge,and experience of intense physical reactions.Logistic regression demonstrated satisfactory predictive validity of PBQ-OR total score with respect to PTSD caseness(OR=1.0513;95%CI:1.011-1.093;P=0.02).CONCLUSION:Since no comparable tools have been developed,PBQ-OR could be valuable as real-time screening tool for earlier detection of Service Members at risk.
