Megakaryocytic particles and microparticles for in vivo hematopoietic cell and gene therapies

    公开(公告)号:US11820968B2

    公开(公告)日:2023-11-21

    申请号:US16711396

    申请日:2019-12-11

    IPC分类号: A61K35/19 C12N5/078 A01N1/02

    摘要: Applications in transfusion medicine requiring platelets, and hematopoietic stem-cell transplantations require either platelets or enhancement of in vivo platelet biogenesis. Gene therapy applications of hematopoietic stem and progenitor cells (HSPCs) require effective and specific modification of HSPCs by DNA, RNA or other biological molecules. Here we disclose methods for the generation, and modification of megakaryocytic microparticles (MkMPs), proplatelets, preplatelets, platelet-like particles and megakaryocyte extracellular vesicles, that can be used in the aforementioned transfusion and transplantation medicine applications and in gene therapy applications involving hematopoietic stem cells. The biological effects of modified or unmodified MkMPs have never been previously disclosed and thus, this invention claims all biological applications of MkMPs in in vivo therapeutic applications to produce various cells and cell parts, modify various target cells or deliver molecules including drugs to HSPCs and related cells.

    MICRORNAS ENRICHED IN MEGAKARYOCYTIC EXTRACELLULAR VESICLES AND USES THEREOF

    公开(公告)号:US20220372441A1

    公开(公告)日:2022-11-24

    申请号:US17770433

    申请日:2020-10-21

    IPC分类号: C12N5/078 C12N15/113

    摘要: The present invention relates to a method for inducing megakaryocytic differentiation of hematopoietic stem/progenitor cells (HSPCs). The method comprises transferring into the HSPCs an effective amount of small RNAs. The HSPCs may differentiate into megakaryocytes in the absence of thrombopoietin (TPO) and/or without using megakaryocytic microparticles (MkMPs). The small RNAs may be micro RNAs (miRs) selected from the group consisting of miR-486, miR-22, miR-191, miR-181, miR-378, miR-26, let-7, miR-92, miR-126, miR-92, miR-21, miR-146, miR-181, and combinations thereof. For example, the small RNAs are miR-486 and miR-22. The small RNAs may be synthetic or isolated from cells. Also provided is a method for enhancing megakaryocytic differentiation of HSPCs cultured with megakaryocytic microparticles MkMPs in the presence of an effective amount of one or more exogenous small RNAs (e.g., miR-486).

    Megakaryocytic particles and microparticles for cell therapy & fate modification of stem and progenitor cells
    3.
    发明申请
    Megakaryocytic particles and microparticles for cell therapy & fate modification of stem and progenitor cells 审中-公开
    用于细胞治疗的巨核细胞颗粒和微粒以及干细胞和祖细胞的命运修饰

    公开(公告)号:US20170058262A1

    公开(公告)日:2017-03-02

    申请号:US15308221

    申请日:2015-05-18

    IPC分类号: C12N5/078 A61K35/19

    摘要: Applications in transfusion medicine requiring platelets, and hematopoietic stem-cell transplantations require either platelets or enhancement of in vivo platelet biogenesis. Gene therapy applications of hematopoietic stem and progenitor cells (HSPCs) require effective and specific modification of HSPCs by DNA, RNA or other biological molecules. Here we disclose methods for the generation, and modification of megakaryocytic microparticles (MkMPs) or microvesicles, that can be used in the aforementioned transfusion and transplantation medicine applications and in gene therapy applications involving hematopoietic stem cells. The biological effects of modified or unmodified MkMPs have never been previously disclosed and thus, this invention claims all biological applications of MkMPs in in vivo therapeutic applications or ex vivo applications to produce various cells and cell parts, modify various target cells or deliver molecules including drugs to HSPCs and related cells.

    摘要翻译: 在需要血小板的输血药物和造血干细胞移植中的应用需要血小板或增强体内血小板生物发生。 造血干细胞和祖细胞(HSPC)的基因治疗应用需要通过DNA,RNA或其他生物分子对HSPC进行有效和特异性的修饰。 在这里,我们公开了可用于上述输血和移植医学应用以及涉及造血干细胞的基因治疗应用中的巨核细胞微粒(MkMP)或微泡的产生和修饰的方法。 修饰或未经修饰的MkMPs的生物学效应从未在之前公开过,因此,本发明要求所有生物学应用MkMPs在体内治疗应用或离体应用中产生各种细胞和细胞部分,修饰各种靶细胞或递送分子包括药物 到HSPC和相关细胞。

    Method and structure in the manufacture of mask read only memory
    4.
    发明授权
    Method and structure in the manufacture of mask read only memory 有权
    掩膜只读存储器的制造方法和结构

    公开(公告)号:US07244653B2

    公开(公告)日:2007-07-17

    申请号:US10807795

    申请日:2004-03-23

    申请人: Lawrence Liu Yuan Kao

    发明人: Lawrence Liu Yuan Kao

    IPC分类号: H01L27/76

    CPC分类号: H01L27/112 H01L27/1126

    摘要: A method and structure of manufacture of mask ROM device is provided. Firstly, a semiconductor structure is provided that comprises a first dielectric layer, a plurality of buried bit lines and a plurality of code areas, wherein each of the code areas is placed between two buried bit lines. Next, a second dielectric layer having a plurality of contact plugs is formed on the semiconductor structure, wherein the contact plug comprises a second dielectric layer and a first glue layer, furthermore; the first glue layer is placed on the side-wall and bottom of the contact plugs. In addition, the contact plugs filled with the first metal layer. Then, a second glue layer, a second metal layer and a pad layer having an opening pattern are respectively formed on the second dielectric layer and contact plug. Thus, the processes of the present invention can improve the stability and accuracy in the electricity of the mask ROM device.

    摘要翻译: 提供了掩模ROM器件的制造方法和结构。 首先,提供半导体结构,其包括第一介电层,多个掩埋位线和多个代码区域,其中每个代码区域被放置在两个掩埋位线之间。 接下来,在半导体结构上形成具有多个接触插塞的第二电介质层,其中,所述接触插塞还包括第二电介质层和第一胶合层; 第一胶层位于接触塞的侧壁和底部。 另外,填充有第一金属层的接触塞子。 然后,在第二电介质层和接触插塞上分别形成具有开口图案的第二胶合层,第二金属层和垫层。 因此,本发明的方法可以提高掩模ROM装置的电力的稳定性和精度。

    Megakaryocytic particles and microparticles for cell therapy and fate modification of stem and progenitor cells

    公开(公告)号:US10538738B2

    公开(公告)日:2020-01-21

    申请号:US15308221

    申请日:2015-05-18

    IPC分类号: C12N5/078 A61K35/19

    摘要: Applications in transfusion medicine requiring platelets, and hematopoietic stem-cell transplantations require either platelets or enhancement of in vivo platelet biogenesis. Gene therapy applications of hematopoietic stem and progenitor cells (HSPCs) require effective and specific modification of HSPCs by DNA, RNA or other biological molecules. Here we disclose methods for the generation, and modification of megakaryocytic microparticles (MkMPs) or microvesicles, that can be used in the aforementioned transfusion and transplantation medicine applications and in gene therapy applications involving hematopoietic stem cells. The biological effects of modified or unmodified MkMPs have never been previously disclosed and thus, this invention claims all biological applications of MkMPs in in vivo therapeutic applications or ex vivo applications to produce various cells and cell parts, modify various target cells or deliver molecules including drugs to HSPCs and related cells.

    Synthesis of specifically labeled tetrodotoxin
    6.
    发明授权
    Synthesis of specifically labeled tetrodotoxin 失效
    特异性标记的河豚毒素的合成

    公开(公告)号:US5288870A

    公开(公告)日:1994-02-22

    申请号:US793597

    申请日:1991-11-18

    CPC分类号: C07D498/18

    摘要: The present invention relates to a process for the preparation of specifically labelled TTX of high specific activity. In the present process, TTX is oxidized by use of the Pfitzer-Moffat method or Fenton's reagent and the aldehyde obtained is hydrated. The hydrated aldehyde is reduced with alkali metal o alkaline earth metal borotritide. The radioactive TTX so obtained, quite surprisingly, has a specific activity many times greater than previously prepared radioactive TTX.

    摘要翻译: 本发明涉及制备高比活性的特异标记的TTX的方法。 在本方法中,TTX通过使用Pfitzer-Moffat法或Fenton试剂进行氧化,得到的醛水合。 水合醛用碱金属碱土金属硼硝酸盐还原。 如此获得的放射性TTX相当令人惊奇地具有比先前制备的放射性TTX多许多倍的比活度。

    Zoom lens array and switchable two and three dimensional display
    7.
    发明授权
    Zoom lens array and switchable two and three dimensional display 有权
    变焦镜头阵列和可切换二,三维显示

    公开(公告)号:US08520153B2

    公开(公告)日:2013-08-27

    申请号:US12630809

    申请日:2009-12-03

    IPC分类号: G02F1/1335 G02F1/13

    CPC分类号: G02B27/2214 G02B3/14

    摘要: A zoom lens array, including a liquid crystal layer, a first strip electrode, and a second strip electrode, is provided. The liquid crystal layer has a plurality of zoom regions. The first strip electrode is disposed on an upper side of the liquid crystal layer and located at the boundary between the zoom regions. The second strip electrode is disposed on a lower side of the liquid crystal layer and located at the boundary between the zoom regions. The first strip electrode and the second strip electrode are alternatively arranged. Moreover, a switchable two and three dimensional display with the above zoom lens array is also provided.

    摘要翻译: 提供了包括液晶层,第一带状电极和第二带状电极的变焦透镜阵列。 液晶层具有多个变焦区域。 第一条状电极设置在液晶层的上侧并且位于变焦区域之间的边界处。 第二带状电极设置在液晶层的下侧并位于变焦区域之间的边界处。 交替布置第一带状电极和第二带状电极。 此外,还提供了具有上述变焦透镜阵列的可切换二维和三维显示。

    Thin Object Holder Apparatus for Use with a Portable Device Patent
    8.
    发明申请
    Thin Object Holder Apparatus for Use with a Portable Device Patent 审中-公开
    用于便携式设备专利的薄物体保持器装置

    公开(公告)号:US20100224519A1

    公开(公告)日:2010-09-09

    申请号:US12396882

    申请日:2009-03-03

    申请人: Yuan Kao

    发明人: Yuan Kao

    IPC分类号: B65D85/00

    摘要: The disclosed is an apparatus for a portable device such as a mobile phone which includes a body defining cavities for receiving and holding thin objects, such as credit cards or business cards. The body also has other additional cavities that allow the users to access the thin objects the apparatus is holding. In conjunctions, these cavities provide added functions to the portable device users, in additional to protecting the portable device from scratches and accidental drop.

    摘要翻译: 所公开的是用于诸如移动电话的便携式设备的装置,其包括限定用于接收和保持薄物体(例如信用卡或名片)的腔的主体。 身体还具有其他额外的空腔,允许用户访问设备所保持的薄物体。 在连接中,除了保护便携式设备免受刮擦和意外跌落之外,这些空腔还为便携式设备用户提供附加功能。

    Layer-built body having hidden barcode and figures thereof
    9.
    发明申请
    Layer-built body having hidden barcode and figures thereof 审中-公开
    具有隐藏的条形码及其图形的层叠体

    公开(公告)号:US20080290175A1

    公开(公告)日:2008-11-27

    申请号:US12076816

    申请日:2008-03-24

    IPC分类号: G06K19/00

    CPC分类号: G06K19/16

    摘要: A layer-built body having hidden barcodes and figures thereof is disclosed in the invention, so as to allow barcode scanning devices to read the barcodes, the layer-built body comprising: a lenticular lens sheet divided into a first surface and a second surface, and the first surface has a plurality of convex lens-shaped optical structures disposed thereon; a patterned layer printed with trademarks or figures, and divided into a plurality of striped images; and at least a barcode layer printed with information about barcodes and divided into a plurality of striped images. The striped images of the barcode layer are alternated with the striped images of the patterned layer to make a synthesized image layer, and are combined with the second surface of the lenticular lens sheet; wherein when a viewer looks at the layer-built body from an ordinary angle, the optical structures of the lenticular lens sheet allows the viewer to see contents of the patterned layer completely, and when the layer-built body is tilted at specific angles, the optical structures of the lenticular lens sheet allows barcode scanning devices to read contents of the barcode layer. Therefore, information about barcodes and figures may be provided on a fixed surface area simultaneously.

    摘要翻译: 本发明公开了一种具有隐藏的条形码和图形的层叠体,为了允许条形码扫描装置读取条形码,该层叠体包括:分为第一表面和第二表面的双凸透镜片, 并且所述第一表面具有设置在其上的多个凸透镜形光学结构; 打印有商标或图形的图案层,并分成多个条纹图像; 以及至少一个印有条形码信息并分成多个条纹图像的条形码层。 条形码层的条纹图像与图案化层的条纹图像交替以形成合成图像层,并与双凸透镜片的第二表面组合; 其中,当观看者从普通角度观看层叠体时,双凸透镜片的光学结构允许观看者完全看到图案层的内容物,并且当层叠体以特定角度倾斜时, 双凸透镜片的光学结构允许条形码扫描装置读取条形码层的内容。 因此,可以在固定表面区域上同时提供关于条形码和图形的信息。

    Method and structure in the manufacture of mask read only memory
    10.
    发明申请
    Method and structure in the manufacture of mask read only memory 有权
    掩膜只读存储器的制造方法和结构

    公开(公告)号:US20050224892A1

    公开(公告)日:2005-10-13

    申请号:US10807795

    申请日:2004-03-23

    申请人: Lawrence Liu Yuan Kao

    发明人: Lawrence Liu Yuan Kao

    CPC分类号: H01L27/112 H01L27/1126

    摘要: A method and structure of manufacture of mask ROM device is provided. Firstly, a semiconductor structure is provided that comprises a first dielectric layer, a plurality of buried bit lines and a plurality of code areas, wherein each of the code areas is placed between two buried bit lines. Next, a second dielectric layer having a plurality of contact plugs is formed on the semiconductor structure, wherein the contact plug comprises a second dielectric layer and a first glue layer, furthermore; the first glue layer is placed on the side-wall and bottom of the contact plugs. In addition, the contact plugs filled with the first metal layer. Then, a second glue layer, a second metal layer and a pad layer having an opening pattern are respectively formed on the second dielectric layer and contact plug. Thus, the processes of the present invention can improve the stability and accuracy in the electricity of the mask ROM device.

    摘要翻译: 提供了掩模ROM器件的制造方法和结构。 首先,提供半导体结构,其包括第一介电层,多个掩埋位线和多个代码区域,其中每个代码区域被放置在两个掩埋位线之间。 接下来,在半导体结构上形成具有多个接触插塞的第二电介质层,其中,所述接触插塞还包括第二电介质层和第一胶合层; 第一胶层位于接触塞的侧壁和底部。 另外,填充有第一金属层的接触塞子。 然后,在第二电介质层和接触插塞上分别形成具有开口图案的第二胶合层,第二金属层和垫层。 因此,本发明的方法可以提高掩模ROM装置的电力的稳定性和精度。