公开(公告)号：US08143222B2

公开(公告)日：2012-03-27

申请号：US12255947

申请日：2008-10-22

申请人： Jonathan E. McDunn ,  William G. Hawkins ,  Robert H. Mach ,  Richard A. Hotchkiss

发明人： Jonathan E. McDunn ,  William G. Hawkins ,  Robert H. Mach ,  Richard A. Hotchkiss

IPC分类号： A61K38/02 ,  A61K38/16 ,  C07K2/00 ,  C07K14/00

CPC分类号： C07D221/22 ,  A61K47/54

摘要： Pharmaceutical compounds, pharmaceutical compositions and methods of treatment are disclosed, wherein a compound comprises a targeting moiety which, in free form, binds a cell receptor with a dissociation constant Kd of less than about 10−7 M, and a pharmaceutically active moiety, wherein the targeting moiety is other than an oligopeptide, a polypeptide, a peptidomimetic, a protein or a protein domain, and wherein the targeting moiety and the pharmaceutically active moiety are covalently attached. In some aspects, the targeting moiety binds a sigma-2 receptor with high affinity and high specificity, and the pharmaceutically active moiety is a pro-apoptotic peptide moiety. Methods of cancer treatment are disclosed comprising administering a disclosed pharmaceutical compound to a subject in need of thereof. The treatments selectively induce apoptosis in cancer cells. These methods can further comprise co-administration of radiation therapy and/or an additional chemotherapeutic agent.

摘要翻译： 公开了药物化合物，药物组合物和治疗方法，其中化合物包含以游离形式结合小于约10-7M的解离常数Kd的细胞受体的靶向部分和药学活性部分，其中 靶向部分不同于寡肽，多肽，肽模拟物，蛋白质或蛋白质结构域，并且其中靶向部分和药学活性部分共价连接。 在一些方面，靶向部分以高亲和力和高特异性结合σ-2受体，并且药物活性部分是促凋亡肽部分。 公开了癌症治疗方法，其包括将所公开的药物化合物施用于需要其的受试者。 治疗选择性诱导癌细胞凋亡。 这些方法还可以包括放射治疗和/或另外的化学治疗剂的共同给药。

公开(公告)号：US06310968B1

公开(公告)日：2001-10-30

申请号：US09198787

申请日：1998-11-24

申请人： William G. Hawkins ,  Daniel Gagnon

发明人： William G. Hawkins ,  Daniel Gagnon

IPC分类号： G06K900

CPC分类号： G01T1/1615 ,  A61B6/037 ,  G01T1/2985

摘要： 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. 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; and, (ii) a reprojection of the previous emission map which is carried out with the multi-dimensional projection model. In a preferred embodiment, with source-assisted reconstruction, the recalculation of the attenuation map is additionally based upon: (iii) measured transmission projection data; and, (iv) a reference or blank data set of measured transmission projection data taken without the subject present in the imaging apparatus (10).

摘要翻译： 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。 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; 和（ii）用多维投影模型进行的先前发射图的重新投射。 在优选实施例中，通过源辅助重建，衰减映射的重新计算另外基于：（iii）测量的传输投影数据; 以及（iv）在成像装置（10）中没有被摄体存在的测量的透射投影数据的参考或空白数据集。

公开(公告)号：US5767517A

公开(公告)日：1998-06-16

申请号：US733947

申请日：1996-10-21

申请人： William G. Hawkins

发明人： William G. Hawkins

IPC分类号： G01T1/164 ,  G01T1/166

CPC分类号： G01T1/1648

摘要： A method of resampling of a sinogram from a fan beam SPECT includes the steps of angular resampling of the sinogram using frequency modulation, and thence transfers resampling of the sinogram using linear interpolation. This permits the use of parallel geometry algorithms in quantitative work without the expected degradation of resolution or the introduction of artifacts.

摘要翻译： 从风扇光束SPECT重新采样正弦图的方法包括使用频率调制对正弦图进行角度重采样的步骤，并且然后使用线性插值来转移正弦图的重采样。 这允许在定量工作中使用并行几何算法，而不会导致预期的分辨率降低或引入伪影。

公开(公告)号：US5300968A

公开(公告)日：1994-04-05

申请号：US943822

申请日：1992-09-10

申请人： William G. Hawkins

发明人： William G. Hawkins

IPC分类号： B41J2/05 ,  B41J2/195

CPC分类号： B41J2/04541 ,  B41J2/04543 ,  B41J2/04563 ,  B41J2/0457 ,  B41J2/0458 ,  B41J2/04588 ,  B41J2/0459 ,  B41J2/04591 ,  B41J2/04598 ,  B41J2/195

摘要： A controller controls an ink jet printing apparatus that propels ink jet droplets on demand from a printhead having a plurality of drop ejectors. The printhead includes a plurality of heater elements which are responsive to electrical input signals, each input signal having an amplitude and time duration which produce a temporary vapor bubble and cause a quantity of ink to be ejected for creation of a mark on a copy sheet. The controller has power supply means and delay means that vary the amplitude and duration of the input signals in relation to the printhead temperature.

摘要翻译： 控制器控制从具有多个液滴喷射器的打印头按要求推动喷墨滴的喷墨打印设备。 打印头包括响应于电输入信号的多个加热器元件，每个输入信号具有产生暂时蒸汽气泡的振幅和持续时间，并且导致一定量的墨被喷射以在复印纸上产生标记。 控制器具有相对于打印头温度改变输入信号的幅度和持续时间的电源装置和延迟装置。

公开(公告)号：US5201987A

公开(公告)日：1993-04-13

申请号：US899597

申请日：1992-06-18

申请人： William G. Hawkins ,  Donald J. Drake ,  James F. O'Neill

发明人： William G. Hawkins ,  Donald J. Drake ,  James F. O'Neill

IPC分类号： H01L21/308

CPC分类号： H01L21/3081

摘要： A precision etched, three dimensional device is fabricated from a silicon wafer by etching from one side of the wafer. A chemical masking layer, such as silicon nitride, is first deposited on all sides of the wafer, followed by the deposition of a robust mechanical layer, such as polycrystalline silicon, over the masking layer on all sides of the wafer. The two layers are sequentially patterned on one side of the wafer and then the wafer is placed into an etchant bath which etches the exposed surface of the wafer and concurrently removes the protective layer, leaving a defect-free masking layer that prevents unintentional etching that would reduce yields of fabricated devices.

摘要翻译： 通过从晶片的一侧进行蚀刻从硅晶片制造精密蚀刻的三维器件。 首先在晶片的所有侧面上沉积诸如氮化硅的化学掩蔽层，然后在晶片的所有侧面上的掩模层上沉积坚固的机械层，例如多晶硅。 这两层在晶片的一侧依次构图，然后将晶片放入蚀刻液中，蚀刻晶片的暴露表面并同时去除保护层，留下无缺陷的掩模层，防止无意蚀刻， 降低制造装置的产量。

公开(公告)号：US5124717A

公开(公告)日：1992-06-23

申请号：US624390

申请日：1990-12-06

申请人： Michael R. Campanelli ,  William G. Hawkins ,  Donald J. Drake ,  James F. O'Neill

发明人： Michael R. Campanelli ,  William G. Hawkins ,  Donald J. Drake ,  James F. O'Neill

IPC分类号： B41J2/05 ,  B41J2/16

CPC分类号： B41J2/1604 ,  B41J2/1623 ,  B41J2/1628 ,  B41J2/1629 ,  B41J2/1631 ,  B41J2/1632 ,  B41J2/1635 ,  B41J2/1642 ,  B41J2002/14403

摘要： An ink jet printhead having an integral membrane filter fabricated over the surface of the printhead containing the ink inlet is disclosed. The individual printheads are obtained by a sectioning operation which cuts aligned and bonded channel and heater wafers. The mated wafers contain a plurality of printheads and must be separated. The integral membrane filter is formed on the channel wafer after it is anisotropically etched incorporating the etch resistant mask layer and prior to mating with the heater wafer. A patternable layer is deposited over the etch resistant masking layer and exposed, patterned and developed to establish the mesh filter. In one embodiment, the side of the channel wafer not patterned and etched is heavily doped to form an etch stop which increases the robustness of the membrane filter by ensuring that the masking layer remains intact during subsequent fabricating steps. This doped region beneath the patternable layer is then etched using the membrane filter as a mask to open the filter pores through the doped layer of the channel wafer, thereby increasing the filter thickness and its overall strength.

摘要翻译： 公开了一种在包含墨水入口的打印头的表面上制造的具有整体膜过滤器的喷墨打印头。 单个打印头通过切割对准和粘合的通道和加热器晶片的切片操作获得。 配对的晶片包含多个打印头，必须分开。 整体膜过滤器在其各向异性蚀刻之后形成在通道晶片上，其包含耐蚀刻掩模层并且在与加热器晶片配合之前。 将可图案层沉积在抗蚀刻掩模层上，并进行曝光，图案化和显影以建立网状过滤器。 在一个实施例中，未图案化和蚀刻的沟道晶片的侧面被重掺杂以形成蚀刻停止件，其通过确保掩模层在随后的制造步骤期间保持完整而增加了膜过滤器的鲁棒性。 然后使用膜过滤器作为掩模蚀刻可图案层下面的该掺杂区域，以通过通道晶片的掺杂层打开过滤器孔，从而增加过滤器厚度及其整体强度。

公开(公告)号：US5096535A

公开(公告)日：1992-03-17

申请号：US631519

申请日：1990-12-21

申请人： William G. Hawkins ,  James F. O'Neill ,  Roberto E. Proano

发明人： William G. Hawkins ,  James F. O'Neill ,  Roberto E. Proano

IPC分类号： B41J2/16 ,  H01L21/306

CPC分类号： B41J2/1635 ,  B41J2/1604 ,  B41J2/1628 ,  B41J2/1629 ,  B41J2/1631 ,  B41J2/1645 ,  H01L21/30608

摘要： In semiconductor technologies such as thermal ink jet printhead fabrication, there exists a need for the precise placement of channels in a substrate. Due to errors in plane alignment in semiconductor substrates, channel structures tend to widen dimensions, thus lowering precision. A one-step anisotropic etching process is disclosed for accurately making channel structures, as well as reservoir structures. Channel structures are formed by segmenting the channel, such that during the anisotropic etching, thin walls between the segments break down before the completion of the etch. Widening of channels is greatly reduced, thus increasing precision. During such a one-step process, larger structures, such as a reservoir, can be formed during the same step.

摘要翻译： 在诸如热喷墨打印头制造的半导体技术中，需要在衬底中精确地放置通道。 由于半导体衬底中的平面对准错误，通道结构趋向于扩大尺寸，从而降低精度。 公开了一步法各向异性蚀刻工艺，用于准确地制造通道结构以及储层结构。 通道结构是通过对通道进行分段而形成的，使得在各向异性蚀刻期间，段之间的薄壁在蚀刻完成之前分解。 渠道扩大大大减少，精度提高。 在这样的一步法中，可以在相同的步骤中形成更大的结构，例如储存器。

公开(公告)号：US4887098A

公开(公告)日：1989-12-12

申请号：US275991

申请日：1988-11-25

申请人： William G. Hawkins ,  Stephen F. Pond

发明人： William G. Hawkins ,  Stephen F. Pond

IPC分类号： B41J2/05

CPC分类号： B41J2/04548 ,  B41J2/04568 ,  B41J2/0457 ,  B41J2/0458 ,  B41J2002/14387 ,  B41J2202/13

摘要： A thermal ink jet printer utilizes a printhead whose electrical connections to the heating elements used to expel the ink droplets has been modified to reduce the effects of parasitic resistance of the common return when a number of resistors are simultaneously addressed. The common return, formed in the same substrate level as the resistor elements, has been modified by forming and interconnecting a second common return. The resistor is connected to an input source by a low resistance connection which is formed to cross-over, or under, the second common.

公开(公告)号：US20110300629A1

公开(公告)日：2011-12-08

申请号：US13155577

申请日：2011-06-08

申请人： William G. Hawkins ,  Dirk Spitzer ,  Richard S. Hotchkiss

发明人： William G. Hawkins ,  Dirk Spitzer ,  Richard S. Hotchkiss

IPC分类号： C12N5/09 ,  C07H21/00 ,  C07K19/00 ,  C12N15/63 ,  C07K14/52

CPC分类号： C07K14/4747 ,  C07K14/52

摘要： 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.

摘要翻译： 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。

公开(公告)号：US06339652B1

公开(公告)日：2002-01-15

申请号：US09437784

申请日：1999-11-10

申请人： William G. Hawkins ,  Daniel Gagnon

发明人： William G. Hawkins ,  Daniel Gagnon

IPC分类号： G06K900

CPC分类号： G01T1/1615 ,  A61B6/037 ,  G01T1/2985

摘要： 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.

摘要翻译： 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。