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Purpose: This review discusses the molecular mechanism involved in the targeting and delivery of antibody-drug conjugates (ADCs), the new class of biopharmaceuticals mainly designed for targeted cancer therapy. Methods: this review goes over major progress in preclinical and clinical studies of ADCs, in the past 5 years. Results: The pharmacokinetics and pharmacodynamics of ADCs involve multiple mechanisms, including internalization of ADCs by target cells, intracellular trafficking, release of conjugated drugs, and payload. Conclusion: These mechanisms actually jointly determine the efficacy of ADCs. Therefore, the optimization of ADCs should take them as necessary rationales. © 2015 Springer Science+Business Media New York Source


Ganjei J.,Manager Inc.
2015 10th International Microsystems, Packaging, Assembly and Circuits Technology Conference, IMPACT 2015 - Proceedings | Year: 2015

The process of singulating IC packages such as Quad Flat Pack No-Lead (QFNs) by either a sawing or punching operation results in exposed copper on the sidewalls. This exposed copper surface can oxidize leading to poor or no solder wetting up the sidewall during the assembly operation. The consequence of this oxidized copper surface is either incomplete or no solder fillet formation during the PCB mounting operation resulting in solder joint reliability concerns. Currently, JEDEC and IPC assembly standards do not specify a toe fillet for assembly. However, several component manufacturers have requested a toe fillet solderability process which would improve current QFN reliability by ensuring toe fillet solder coverage. A process whereby tin is plated on the copper sidewall of the QFN after singulation has been developed to improve toe fillet solderability. Several assembly studies have been conducted which demonstrate improved QFN reliability due to the use of this toe fillet solderability process. The plating process, toe fillet inspection and improved QFN reliability after assembly due to the use of this toe fillet solderability is described. © 2015 IEEE. Source


Confer K.A.,Delphi Corporation | Kirwan J.,Delphi Corporation | Engineer N.,Manager Inc.
SAE Technical Papers | Year: 2013

Global fuel economy and CO2 reduction mandates are driving the need for a substantial increase in vehicle fuel efficiency over the next several years, with improvements coming from many sources. This paper describes a vehicle demonstration program to improve fuel economy by implementing a systems approach to reduce friction and parasitic losses. The work concentrated on nearer term technologies that can be quickly transferred to production vehicle programs. Major technologies demonstrated on the vehicle included gasoline direct injection (GDi) with cooled EGR, advanced valvetrain, rollerization of both crankshaft and camshaft, and stop-start engine operation. The work described in this paper comprises Phase I of a two phase program funded by DOE contract DE-EE0003258. It includes a hardware overview and a description of the system development activities. Results focus on vehicle fuel economy benefits compared to a production baseline vehicle. Copyright © 2013 SAE International. Source


Sen Bai P.E.,Tetra Tech Inc. | Li J.,Manager Inc.
Journal of Hydrologic Engineering | Year: 2013

Sediment wash-off from impervious land is believed to be related to various factors including sediment buildup, rainfall intensity, rainfall energy, runoff rate, sediment sizes, and land surface characteristics. Most previous studies have used controlled rainfall in small areas to investigate mechanisms of sediment wash-off. This paper presents sediment wash-off results from an impervious urban surface under actual accumulation and rainfall events. Two temporal scales were considered when the sediment wash-off processes were investigated. On the event scale, sediment wash-off is strongly correlated with runoff volume. On the instantaneous scale, sediment wash-off from eight rainfall events was investigated using first-order and zero-order wash-off equations. Source-limited and transport-limited wash-off processes were discussed. The wash-off process on October 10, 2002, was linearly dependent on runoff and can be described using a first-order exponential equation. The wash-off processes on May 15, 2003, and June 7, 2003, can be described using a zero-order equation. For the remaining storms, both first-order and zero-order wash-off equations can represent the wash-off processes. DOI: 10.1061/(ASCE)HE.1943-5584.0000654. © 2013 American Society of Civil Engineers. Source


A computer-implemented method for mortality tracking The method includes electronically receiving contact information of a beneficiary of a life insurance policy. The method also includes electronically receiving a unique identifier of the policyholder of the life insurance policy. The method further includes periodically electronically searching mortality database records to obtain a periodic mortality search result. Upon occurrence of an aperiodic triggering event, the method may further aperiodically electronically search the mortality database records for the unique identifier of the policyholder to obtain an aperiodic mortality search result. The method may include verifying the deceased status of the policyholder upon occurrence of an indication that the policyholder being deceased according to the periodic mortality search result. The method further includes transmitting a deceased status notification to the beneficiary of the life insurance policy based on the policyholder being deceased according to the periodic or the aperiodic mortality search result.

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