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    • 25. 发明授权
    • Deformable spindle end portion
    • 可变形主轴端部
    • US06688773B2
    • 2004-02-10
    • US10193542
    • 2002-07-11
    • Alan Charles WebbPeter HollandPeter StandringDouglas H. SmithLarry L. Bahney
    • Alan Charles WebbPeter HollandPeter StandringDouglas H. SmithLarry L. Bahney
    • F16C1938
    • B23P11/005B23P11/00B60B27/001B60B35/18B60B2310/208B60B2310/228B60B2310/306B60B2310/316B60B2360/10B60B2360/102B60B2380/14F16C19/386F16C35/063F16C41/007F16C2326/02G01P3/443G01P3/446
    • A hub (2) includes a spindle (14) which projects through a housing (4) and rotates relative to the housing (4) on a bearing (6) that is located between the spindle (14) and the housing (4). The bearing (6) has two sets of raceways (28,40) that are oblique to the axis x, and in addition rolling elements (36) arranged in two rows between the sets of raceways (28,40). The inner raceways (28) that fit around the spindle (14) and have back faces (32), with the back face (32) for one of the races (26) being against a shoulder (18) from which the spindle (14) projects. Initially, the end of the spindle (14) projects straight beyond the back face (32) of the outer race—indeed, so that the races (26) can be installed over the spindle (14). But once the housing (4) and races (26) are in a position around the spindle (14), the projecting end portion of the spindle (14) is deformed radially and axially in a rotary forming operation such that it transforms into a formed end (20) that lies behind back face (32) of the race (26). With the two races (26) between the formed end (20) and the shoulder (18). During the rotary forming operation the hub (26) rotates, and the end of its spindle (14) is forced against a rotating forming tool and the force is monitored. The housing (4) is restrained and the torque transferred from the rotating hub (2) to the housing (4) is monitored.
    • 轮毂(2)包括主轴(14),该主轴突出通过壳体(4)并且相对于壳体(4)在位于主轴(14)和壳体(4)之间的轴承(6)上旋转。 轴承(6)具有与轴线x倾斜的两组滚道(28,40),以及在滚道组(28,40)之间布置成两排的滚动元件(36)。 安装在主轴(14)周围并且具有后表面(32)的内滚道(28),其中一个座圈(26)的后表面(32)抵靠在肩部(18)上,主轴 )项目。 最初,主轴(14)的端部直接突出超过外圈的背面(32),实际上,使得座圈(26)可以安装在主轴(14)上。 但是,一旦壳体(4)和座圈(26)处于围绕心轴(14)的位置,则主轴(14)的突出端部在旋转成形操作中径向和轴向地变形,使得其转变成形成 端部(20)位于座圈(26)的背面(32)之后。 通过形成的端部(20)和肩部(18)之间的两个座圈(26)。 在旋转成形操作期间,毂(26)旋转,并且其主轴(14)的端部被迫抵抗旋转成形工具,并且该力被监测。 对壳体(4)进行限制,并且监测从旋转轮毂(2)传递到壳体(4)的扭矩。
    • 26. 发明授权
    • Multispecific chimeric receptors
    • 多特异性嵌合受体
    • US6103521A
    • 2000-08-15
    • US454098
    • 1995-05-30
    • Daniel J. CaponDouglas H. SmithHuan TianGenine A. WinslowMiriam Siekevitz
    • Daniel J. CaponDouglas H. SmithHuan TianGenine A. WinslowMiriam Siekevitz
    • A61K35/14A61K35/17A61K39/00C07K14/16C07K14/725C07K14/73C07K16/10C12N15/12C12N15/62C07K14/705
    • C07K14/005A61K35/17C07K14/7051C07K14/70514C07K16/1063A61K2039/505C07K2317/24C07K2317/31C07K2317/622C07K2319/00C07K2319/02C12N2740/10043C12N2740/16122
    • Novel multispecific chimeric receptor DNA sequences, expression cassettes and vectors containing these sequences as well as cells containing the chimeric DNA and novel chimeric receptor proteins expressed from the sequences are provided in the present invention. The novel multispecific chimeric receptor DNA and amino acid sequences comprise at least three domains that do not naturally exist together: (1) a multispecific binding domain comprising at least two extracellular inducer-responsive clustering domains which serves to bind at least one specific inducer molecule, (2) a transmembrane domain, which crosses the plasma membrane, and (3) either a proliferation signaling domain that signals the cell to divide, or an effector function signaling domain which directs a host cell to perform its specialized function. Optionally, all the multispecific chimeric receptors may contain one or more intracellular inducer-responsive clustering domains attached to one or more of the cytoplasmic signaling domains or the transmembrane domain. The present invention also relates to novel hybrid multispecific chimeric receptors comprising at least one proliferation signaling domain and at least one effector function signaling domain together on the multispecific receptor molecule. The present invention further relates to therapeutic methods and strategies that employ the cells expressing these novel chimeric receptors for the treatment of cancer, infectious disease and autoimmune disease which may have greater therapeutic benefit over a combination of drug therapies.
    • 在本发明中提供了新的多特异性嵌合受体DNA序列,表达盒和含有这些序列的载体以及含有嵌合DNA的细胞和由序列表达的新型嵌合受体蛋白。 新颖的多特异性嵌合受体DNA和氨基酸序列包含至少三个不天然存在的结构域:(1)多特异性结合结构域,其包含至少两个用于结合至少一个特异性诱导物分子的细胞外诱导物反应性聚簇结构域, (2)穿越质膜的跨膜结构域,和(3)信号细胞分裂的增殖信号转导域或引导宿主细胞执行其特异功能的效应子功能信号结构域。 任选地,所有多特异性嵌合受体可以含有连接至一个或多个胞质信号结构域或跨膜结构域的一个或多个细胞内诱导物反应性聚簇结构域。 本发明还涉及在多特异性受体分子上包含至少一个增殖信号结构域和至少一个效应子功能信号结构域的新型杂合多特异性嵌合受体。 本发明还涉及使用表达这些新型嵌合受体的细胞治疗癌症,感染性疾病和自身免疫疾病的治疗方法和策略,其可以比药物疗法的组合具有更大的治疗益处。
    • 27. 发明授权
    • DNA encoding an intracellular chimeric receptor comprising Janus kinase
    • 编码包含Janus激酶的细胞内嵌合受体的DNA
    • US6077947A
    • 2000-06-20
    • US485598
    • 1995-06-07
    • Daniel J. CaponHuan TianDouglas H. SmithGenine A. WinslowMiriam Siekevitz
    • Daniel J. CaponHuan TianDouglas H. SmithGenine A. WinslowMiriam Siekevitz
    • A61K38/00C07K14/705C07K14/715C07K14/73C12N9/12C12N15/12C12N15/62C12N5/10C12N15/52C12N15/63
    • C12N9/1205C07K14/705C07K14/70514C07K14/7155A61K38/00C07K2319/00
    • The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide. In yet a third category, a novel hybrid chimeric protein receptor is contemplated that contains an intracellular or extracellular inducer domain, a transmembrane domain, a proliferation signaling domain and an effector signaling domain in a single chain molecule. Whether the binding domain is intracellular or extracellular, the binding of inducer to these novel chimeric receptor proteins induces the clustering of the binding domains to each other and further signals the cell to proliferate, and optionally, signal an effector function. The present invention further relates to expression vectors containing the nucleic acids encoding the novel chimeric receptors, cells expressing the novel chimeric receptors and therapeutic methods of using cells expressing these novel receptors for the treatment of cancer, infectious disease and autoimmune diseases, for example.
    • 本发明涉及嵌合增殖受体蛋白和编码这些蛋白的DNA序列,其中嵌合蛋白的特征在于三个一般类别。 在一个类别中,新型嵌合蛋白质包含至少三个结构域,即能够结合将信号传递给增殖信号转导域的细胞外诱导物 - 响应性聚簇结构域,跨膜结构域和增殖信号转导域, 宿主细胞分裂。 在第二类中,新的嵌合蛋白包含至少两个结构域,即能够结合细胞内诱导物的细胞内诱导物 - 响应聚簇结构域和信号细胞分裂的增殖信号转导域。 在三分之一类别中,预期在单链分子中含有细胞内或细胞外诱导物结构域,跨膜结构域,增殖信号结构域和效应子信号结构域的新型杂合嵌合蛋白受体。 结合结构域是细胞内还是细胞外,诱导物与这些新型嵌合受体蛋白的结合诱导结合结构域彼此聚集,并进一步使细胞信号增殖,并且任选地发送效应子功能。 本发明还涉及含有编码新型嵌合受体的核酸,表达新型嵌合受体的细胞和使用表达这些新受体的细胞治疗癌症,感染性疾病和自身免疫疾病的治疗方法的表达载体。
    • 28. 发明授权
    • Cycle sequencing thermal profiles
    • US5998143A
    • 1999-12-07
    • US986176
    • 1997-12-05
    • Nicole M. EllisDeborah E. DodgeDouglas H. Smith
    • Nicole M. EllisDeborah E. DodgeDouglas H. Smith
    • C12M1/00B01L7/00C12M1/36C12Q1/68C07H21/02C07H21/04C12P19/34
    • C12Q1/6869
    • The present invention relates to improved methods of generating polynucleotide sequencing reaction products from cycle sequencing and relates to various instruments and reagents for use in the subject methods. The use of "step-down" thermal profiles in conjunction with cycle sequencing is described. Step-down thermal profiles are formed by combining several thermal cycle sets such that the annealing temperature of each thermal cycle set is less than the annealing temperature of the preceding thermal cycle set. One embodiment of the invention is a method of generating a plurality of polynucleotide sequencing reaction products in parallel by subjecting a plurality of sequencing solution preparations to a step-down thermal profile, i.e., exposure to repeated thermal cycle sets, each thermal cycle set having an annealing temperature that is lower than the annealing temperature of the annealing phases of the preceding thermal cycle set. Other embodiments of the invention include systems for generating a plurality of polynucleotide sequencing reaction products in parallel. The systems comprise (i) a programmable thermal cycler programmed to perform a step-down thermal profile and (ii) a plurality of polynucleotide sequencing preparations. Additional embodiments of the invention include sets of polynucleotide sequencing reaction preparations that may be used in the methods of the invention.Another aspect of the invention is a device for generating a plurality of polynucleotide sequencing reaction products. The devices of the invention include (i) a plurality of polynucleotide sequencing reaction preparation chambers, each chamber containing a sequencing primer, (ii) a common fluid entry port, and (iii) a fluid dispensing channel, the channel connecting each of the sequencing reaction preparation chambers to the common fluid entry port. At least two of the sequencing primers in the device have Tms different from one another by at least 2.degree. C.
    • 29. 发明授权
    • Combined bearing and sensor assembly
    • 组合轴承和传感器组件
    • US5893648A
    • 1999-04-13
    • US903125
    • 1997-07-30
    • Douglas H. Smith
    • Douglas H. Smith
    • F16C19/52G01P3/44F16C19/00
    • G01P3/443F16C19/34F16C33/7883F16C41/007F16C2326/02
    • A combined bearing and sensor assembly comprises a sensor unit 30 and a bearing unit 40. The sensor unit 30 includes a coupling ring 10 which has a radially inwardly directed lip 22 which engages with a groove 11 formed in the inner raceway 18 of the bearing unit 40. The coupling ring 10 also has an axially extending portion 5, the radially inwardly facing surface of which engages with a sensor unit mounting surface 8a such that the sensor unit's engagement to the mounting surface 8a is greater than its engagement to the bearing unit 40. In this way the combined bearing and sensor unit may be sold, transported and fitted as a single unit, but will separate to allow the sensor unit 30 to remain properly mounted when the bearing unit 40 is dismounted for general maintenance purposes.
    • 组合的轴承和传感器组件包括传感器单元30和轴承单元40.传感器单元30包括联接环10,其具有径向向内指向的唇缘22,其与形成在轴承单元的内滚道18中的凹槽11接合 联接环10还具有轴向延伸部分5,其径向向内的表面与传感器单元安装表面8a接合,使得传感器单元与安装表面8a的接合大于其与轴承单元40的接合 以这种方式,组合的轴承和传感器单元可以作为单个单元被出售,运输和安装,但是当轴承单元40被拆卸以用于一般维护目的时,将分离以允许传感器单元30保持正确地安装。
    • 30. 发明授权
    • Replicated-in-place internal viscous shear damper for machine structures
and components
    • 用于机器结构和部件的复制内部粘性剪切阻尼器
    • US5799924A
    • 1998-09-01
    • US406253
    • 1995-03-13
    • Alexander H. SlocumEric R. MarshDouglas H. Smith
    • Alexander H. SlocumEric R. MarshDouglas H. Smith
    • E04H9/02E04C3/29E04C3/36F16F9/30F16F13/04F16F15/023F16M7/00F16S3/00F16M13/00
    • F16F15/023E04C3/29E04C3/36F16F13/04F16F9/30
    • A novel means for providing an internal damping mechanism for a system with structural load supporting members that may be subject to time-varying loads, where the structure's structural members have rough holes formed in them, either by casting, drilling, or welding pipe, where the holes can be any shape, but the ideal shape and location maximizes the product of the perimeter of the shape and the distance from the neutral axes to the neutral axis of the structure, so a smooth surfaced shear member, with a diameter several millimeters smaller than the hole and a surface finish on the order of 0.5 micron R.sub.a, with its surfaced covered with a very viscous fluid, can be inserted into the hole so a replicant, such as epoxy or rubber, can be injected around the shear member, such that when the structure bends, shear strains occur between the structure and the shear members and this strain occurs across the viscous fluid interface which is very thin because of the use of the replicant, so therefore the energy dissipation rate will be high and bending and axial vibrations will be damped, said damping system being referred to as a replicated-in-place shear damper.
    • 一种用于为具有可能经受时变负载的结构负载支撑构件的系统提供内部阻尼机构的新型装置,其中结构的结构构件具有通过铸造,钻孔或焊接管形成的粗孔,其中, 孔可以是任何形状,但是理想的形状和位置最大化形状的周长和从中性轴到结构的中性轴线的距离的乘积,因此具有直径几个毫米的直径的光滑的表面剪切构件 并且其表面覆盖有非常粘稠的流体的0.5微米Ra的表面光洁度可以插入孔中,因此可以将复制物(例如环氧树脂或橡胶)注入到剪切构件周围,例如 当结构弯曲时,剪切应变发生在结构和剪切构件之间,并且这种应变发生在粘性流体界面上,因为使用复制物非常薄,因此, 再次,能量消耗速率将高,并且弯曲和轴向振动将被阻尼,所述阻尼系统被称为现场复制剪切阻尼器。