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    • 1. 发明申请
    • TRAIL trimers, methods and uses therefor
    • TRAIL三聚体,方法和用途
    • US20110300629A1
    • 2011-12-08
    • US13155577
    • 2011-06-08
    • William G. HawkinsDirk SpitzerRichard S. Hotchkiss
    • William G. HawkinsDirk SpitzerRichard S. Hotchkiss
    • C12N5/09C07H21/00C07K19/00C12N15/63C07K14/52
    • C07K14/4747C07K14/52
    • Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. In some configurations, a modification such as the addition of a functional domain can be stoichiometrically controlled. In some configurations, a modification can be inconsequential with regard to the bioactivity of TRAIL. In various embodiments, a TR3, including a modified TR3, can be a cancer-selective drug. In some configurations, a TR3 that comprises an additional biologically active moiety such as a functional domain of a protein can have fewer off-target toxicities compared to TRAIL alone. In some configurations, a TR3 that comprises an additional biologically active moiety such as a functional domain of a protein can have enhanced killing capacities compared to the moiety alone. In some aspects, TR3 activity can be targeted to an RBC membrane. The inventors disclose TR3-decorated RBCs that target cell killing in a model of pancreatic cancer.
    • 公开了TNF相关凋亡诱导配体(TRAIL)三聚体(TR3)和编码共价连接的TRAIL三聚体的核酸。 与天然TRAIL相比,TRAIL三聚体可以具有更高的稳定性,并且可以保留TRAIL的天然杀伤能力。 可通过用可溶性死亡受体5(DR5-Fc)阻断其活性来显示TR3的靶特异性。 还公开了修饰的TRAIL三聚体和编码它们的核酸。 这些修饰包括额外的功能域,例如抗体片段(scFv)。 包含附加功能域的TR3可以允许TR3的细胞特异性递送。 在一些配置中,可以化学计量地控制诸如添加功能域的修饰。 在一些配置中,关于TRAIL的生物活性,修饰可能是无关紧要的。 在各种实施方案中,包括修饰的TR3的TR3可以是癌症选择性药物。 在一些配置中,与单独的TRAIL相比,包含另外的生物活性部分如蛋白质的功能结构域的TR3可以具有较少的靶外毒性。 在一些构型中,与单独的部分相比,包含另外的生物活性部分如蛋白质的功能结构域的TR3可以具有增强的杀伤能力。 在一些方面,TR3活性可以靶向RBC膜。 本发明人公开了在胰腺癌模型中靶向细胞杀伤的TR3装饰的RBC。
    • 2. 发明授权
    • Source-assisted attenuation correction for emission computed tomography
    • 用于排放计算机断层扫描的源辅助衰减校正
    • US06339652B1
    • 2002-01-15
    • US09437784
    • 1999-11-10
    • William G. HawkinsDaniel Gagnon
    • William G. HawkinsDaniel Gagnon
    • G06K900
    • G01T1/1615A61B6/037G01T1/2985
    • A method of ML-EM image reconstruction is provided for use in connection with a diagnostic imaging apparatus (10) that generates projection data. The method includes collecting projection data, including measured emission projection data and measured transmission projection data. Optionally, the measured transmission projection data is truncated. An initial emission map and attenuation map are assumed. The emission map and the attenuation map are iteratively updated. With each iteration, the emission map is recalculated by taking a previous emission map and adjusting it based upon: (i) the measured emission projection data; (ii) a reprojection of the previous emission map which is carried out with a multi-dimensional projection model; and, (iii) a reprojection of the attenuation map. As well, with each iteration, the attenuation map is recalculated by taking a previous attenuation map and adjusting it based upon: (i) the measured emission projection data; (ii) a reprojection of the previous emission map which is carried out with the multi-dimensional projection model; and (iii) measured transmission projection data.
    • 提供了一种ML-EM图像重建方法,用于与产生投影数据的诊断成像设备(10)相结合。 该方法包括收集投影数据,包括测量的发射投影数据和测量的透射投影数据。 可选地,所测量的传输投影数据被截断。 假设初始发射图和衰减图。 发射图和衰减图迭代更新。 通过每次迭代,通过采取先前的发射图并根据以下进行调整来重新计算发射图:(i)测量的发射投影数据; (ii)用多维投影模型进行的先前发射图的重新投影; 和(iii)衰减图的重新投射。 同样地,通过每次迭代,通过采取先前的衰减图并且基于以下来调整衰减图来重新计算衰减图:(i)测量的发射投影数据; (ii)用多维投影模型进行的先前发射图的重新投影; 和(iii)测量的传输投影数据。
    • 4. 发明授权
    • Ink jet printhead with improved operation
    • 喷墨打印头具有改进的操作
    • US5850234A
    • 1998-12-15
    • US784632
    • 1997-01-21
    • Gary A. KneezelWilliam G. HawkinsPeter J. John
    • Gary A. KneezelWilliam G. HawkinsPeter J. John
    • B41J2/14B41J29/377B41J2/175
    • B41J2/1408B41J2/14072B41J2/14145B41J29/377B41J2002/14379B41J2002/14491B41J2202/20
    • An ink jet printhead is disclosed which has improved printhead cooling thereby improving operating efficiency. The printhead is constructed so that the manifold bringing ink from an ink reservoir into an ink inlet to the printer directly contacts the thermally conductive surface of the substrate in which the heater elements are formed- The cooler ink removes some of the accumulated heat from the heater substrate and is subsequently ejected. In one embodiment the printhead comprises an upper channel substrate which is bonded to a lower heater substrate which is formed with a ledge which extends past the rear face of the channel substrate. The channel substrate has an ink inlet formed into its rear face and adjacent to an extended portion of the heater silicon surface. An ink reservoir brings ink to the printhead via an ink manifold which is sealed against the exposed silicon surface and against the side of the ink inlet. In a second embodiment, the formation of an ink inlet at the rear face enables the construction of a compact multicolor sideshooting printhead with 2 rows of nozzles.
    • 公开了一种喷墨打印头,其具有改进的打印头冷却,从而提高了操作效率。 打印头被构造成使得将墨水从墨水储存器插入到打印机的墨水入口中的歧管直接接触形成加热器元件的基板的导热表面。较冷的墨水从加热器中去除一些积聚的热量 底物并随后喷射。 在一个实施例中,打印头包括上通道基板,其被接合到下加热器基板,下加热器基板形成有延伸经过通道基板的后表面的凸缘。 通道基板具有形成在其后表面中并与加热器硅表面的延伸部分相邻的墨入口。 墨水储存器通过经由暴露的硅表面和墨水入口的侧面密封的墨水歧管向打印头提供墨水。 在第二实施例中,在后面形成墨水入口使得能够构造具有2排喷嘴的紧凑型多色侧面打印头。
    • 5. 发明授权
    • Hybrid ink jet printer
    • 混合式喷墨打印机
    • US5710582A
    • 1998-01-20
    • US569034
    • 1995-12-07
    • William G. HawkinsIvan RezankaRoger G. MarkhamDale R. ImsDonald J. Drake
    • William G. HawkinsIvan RezankaRoger G. MarkhamDale R. ImsDonald J. Drake
    • B41J2/21B41J2/01B41J2/05B41J2/15B41J2/155B41J2/525B41J3/54
    • B41J3/543B41J2/15B41J2/155
    • An ink jet printer is configured in a hybrid architecture wherein a full width printbar is combined with a partial width color scanning assembly to provide the capability of selectively printing in black only or, alternately, of producing color prints by operating the color scan assembly exclusively. The cost of the hybrid system, when compared to a full width color system using four full width printbars, is greatly reduced. Throughput time is reduced by providing the control circuitry for distinguishing between black only and color operation and selectively controlling the printer mode of operation. The hybrid architecture is particularly useful in a LAN system since it provides a mechanism for balancing the relative color versus black page decomposition speed limitations. Also, the hybrid architecture enables a relatively simple implementation of a checkerboarding technique to suppress banding in output prints.
    • 喷墨打印机被配置为混合架构,其中全宽度打印条与部分宽度彩色扫描组合组合,以提供选择性地以黑色打印的能力,或者通过专门操作彩色扫描组件来产生彩色打印。 与使用四个全宽度打印棒的全幅彩色系统相比,混合系统的成本大大降低。 通过提供用于区分黑色和彩色操作的控制电路并选择性地控制打印机操作模式来减少吞吐时间。 混合架构在LAN系统中特别有用,因为它提供了用于平衡相对颜色与黑色页面分解速度限制的机制。 此外,混合架构使得能够相对简单地执行棋盘棋技术来抑制输出打印中的条带。
    • 7. 发明授权
    • Self-aligned features for accurate etched silicon transducer placement
    • 用于精确蚀刻硅转换器放置的自对准特征
    • US5565901A
    • 1996-10-15
    • US337495
    • 1994-11-08
    • William G. Hawkins
    • William G. Hawkins
    • B41J2/14B41J2/16B41J2/05
    • B41J2/1623B41J2/14024B41J2/1604B41J2/1626B41J2/1637
    • An ink jet module that can be accurately positioned on a carrier includes a channel die and a heater die. The channel die is rectangular and has a top surface, a bottom surface, a first pair of sides, and a second pair of sides. The bottom surface has a number of spaced parallel channels disposed within it. The channels are parallel to the first pair of sides and extend through one of the second pair of sides. The top surface of the heater die is attached to and aligned with the bottom surface of the channel die. At least one pair of alignment features is disposed within and adjacent a side of the bottom surface of the channel die. The alignment features are recessed areas disposed on opposite sides from each other. The alignment features are dimensioned to receive a retainer that secures the ink jet module to a carrier.
    • 可精确地定位在载体上的喷墨模块包括通道模和加热模。 通道模具是矩形的,并且具有顶表面,底表面,第一对侧面和第二对侧面。 底表面具有设置在其内的多个间隔开的平行通道。 通道平行于第一对侧面并延伸穿过第二对侧边之一。 加热器管芯的顶表面附接到通道管芯的底表面并与其对准。 至少一对对准特征设置在通道管芯的底表面的侧面内并与其相邻。 对准特征是彼此相对设置的凹陷区域。 对准特征的尺寸被设计成接收将喷墨模块固定到载体上的保持器。
    • 9. 发明授权
    • Integrated circuit fan-in for semiconductor transducer devices
    • 用于半导体传感器器件的集成电路引入
    • US5457311A
    • 1995-10-10
    • US092640
    • 1993-07-16
    • Donald J. DrakeWilliam G. HawkinsThomas A. Tellier
    • Donald J. DrakeWilliam G. HawkinsThomas A. Tellier
    • B41J2/45H01L27/146H01J40/14H01L27/14
    • B41J2/45H01L27/146
    • A wide semiconductor transducer device comprises a linear array of semiconductor chips. Each of the semiconductor chips has a plurality of transducer elements arranged on it along a front edge at a constant spacing, the constant spacing being maintained across the semiconductor chip boundaries. Each of the semiconductor chips also includes associated transducer circuits which are each connected one of the plurality of transducer elements formed on the semiconductor chip. While the requirement that the transducer elements maintain the constant spacing requires them to be located within a damage zone created during the dicing and/or thermally induced compression of the semiconductor chip, the associated transducer circuits can be located within an interior portion of the semiconductor chip. The interior portion of the semiconductor chip is located a sufficient distance from the edges of the semiconductor chip such that it does not encroach on the damage zone.
    • 宽的半导体传感器装置包括半导体芯片的线性阵列。 每个半导体芯片具有沿着前边缘以恒定间隔布置在其上的多个换能器元件,恒定间隔保持在半导体芯片边界两边。 每个半导体芯片还包括相关联的换能器电路,它们各自连接形成在半导体芯片上的多个换能器元件中的一个。 虽然传感器元件保持恒定间隔的要求要求它们位于在半导体芯片的切割和/或热诱导压缩期间产生的损伤区域内,但是相关联的换能器电路可以位于半导体芯片的内部部分内 。 半导体芯片的内部部分位于与半导体芯片的边缘足够的距离处,使得它不会侵入损伤区域。
    • 10. 发明授权
    • High voltage input pad protection circuitry
    • 高压输入焊盘保护电路
    • US5371395A
    • 1994-12-06
    • US879626
    • 1992-05-06
    • William G. Hawkins
    • William G. Hawkins
    • H01L27/04H01L21/822H01L27/02H01L23/62
    • H01L27/0259H01L27/0255H01L2924/0002
    • An electrostatic discharge (ESD) protection device for protecting a high voltage operating circuit having a high voltage input terminal is disclosed. The ESD protection circuit has a substrate, a first diffusion region formed in the substrate connected to the high voltage input terminal, a second diffusion region formed in the substrate connected to ground, a field oxide layer over the substrate having a thickened region extending into the substrate between the first and second diffusion regions, and a drift region formed in the substrate and located between the first diffusion region and the thickened field oxide layer. These regions are so arranged to move the point of avalanche breakdown away from the first diffusion/field oxide interface, so that the avalanche breakdown voltage is lower than that of the protected circuit while simultaneously preventing avalanche included bipolar feedback in the protection device.
    • 公开了一种用于保护具有高压输入端子的高电压工作电路的静电放电(ESD)保护装置。 ESD保护电路具有衬底,形成在与高压输入端子连接的衬底中的第一扩散区域,形成在与衬底连接的衬底中的第二扩散区域,衬底上的场氧化物层具有延伸到 第一扩散区和第二扩散区之间的衬底,以及形成在衬底中并位于第一扩散区和增厚场氧化物层之间的漂移区。 这些区域被布置为将雪崩击穿点移动离开第一扩散/场氧化物界面,使得雪崩击穿电压低于受保护电路的雪崩击穿电压,同时防止在保护装置中包括双极反馈的雪崩。